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Segmentation (biology)

Segmentation (biology)

Morphogenesis (from the Greek morphê shape and genesis creation) is one of three fundamental aspects of developmental biology along with the control of cell growth and cellular differentiation. Morphogenesis is concerned with the shapes of tissues, organs and entire organisms and the positions of the various specialized cell types. Cell growth and differentiation can take place in cell culture or inside of tumor cell masses without the normal morphogenesis that is seen in an intact organism. The study of morphogenesis involves an attempt to understand the processes that control the organized spatial distribution of cells that arises during the embryonic development of an organism and which give rise to the characteristic forms of tissues, organs and overall body anatomy. In the human embryo, the change from a cluster of nearly identical cells at the blastula stage to a post-gastrulation embryo with structured tissues and organs is controlled by the genetic "program" and can be modified by environmental factors. Some of the earliest ideas on how physical and mathematical processes and constraints affect biological growth were written by D'Arcy Wentworth Thompson and Alan Turing. These works postulated the presence of chemical signals and physico-chemical processes such as diffusion, activation and deactivation in cellular and organismic growth. The fuller understanding of the mechanisms involved in actual organisms required the discovery of DNA and the development of molecular biology and biochemistry. Several types of molecules are particularly important during morphogenesis. Morphogens are soluble molecules that can diffuse and carry signals that control cell differentiation decisions in a concentration-dependent fashion. Morphogens typically act through binding to specific protein receptors. An important class of molecules involved in morphogenesis are transcription factor proteins that determine the fate of cells by interacting with DNA. These can be coded for by master regulatory genes and either activate or deactivate the transcription of other genes and, in turn, these secondary gene products can regulate the expression of still other genes in a regulatory cascade. Another class of molecules involved in morphogenesis are molecules that control cell adhesion. For example, during gastrulation clumps of stem cells switch off their cell-to-cell adhesion, become migratory, and take up new positions with an embryo where they again activate specific cell adhesion proteins and form new tissues and organs. Several examples that illustrate the roles of morphogens, transcription factors and cell adhesion molecules in morphogenesis are discussed below.

Anterior-posterior axis patterning in Drosophila

Morphogenesis of the fruit fly Drosophila melanogaster starts with the construction of asymmetries within the oocyte and proceeds to pattern formation along the embryonic axes. The development of Drosophila is particularly well studied, and it is representative of one major class of insects. Other multicellular organisms sometimes use similar mechanisms for axis formation, although the relative importance of signal transfer between the earliest cells of many developing organisms is greater than in the example described here.

Maternal effect genes

oocyte A Drosophila oocyte is a polarized cell. The future anterior-posterior axis of the fly is established by mRNA molecules that are differentially localized within the oocyte. The genes that code for these differentially localized oocyte mRNAs are called maternal effect genes. They have profound effects on the development of a fertilized egg, but they are expressed by cells within the maternal ovary. Bicoid and hunchback are the maternal effect genes that are most important for patterning of anterior parts (head and thorax) of the Drosophila embryo. Nanos and Caudal are maternal effect genes that are important in the formation of more posterior abdominal segments of the Drosophila embryo. Cytoskeletal elements such as microtubules are polarized within the oocyte and can be used to allow the localization of mRNA molecules to specific parts of the cell. Maternally synthesized bicoid mRNAs attach to microtubules and are concentrated at the anterior ends of forming Drosophila eggs. Nanos mRNAs also attach to the egg cytoskeleton but they concentrate at the posterior ends of the eggs. Hunchback and caudal mRNAs lack special location control systems and are fairly evenly spread throughout the interior of egg cells. microtubule When the mRNAs from the maternal effect genes are translated into proteins a Bicoid protein gradient forms at the anterior end of the egg. Nanos protein forms a gradient at the posterior end. The Bicoid protein blocks translation of caudal mRNA so Caudal protein is made only in the posterior part the cell. Nanos protein binds to the hunchback mRNA and blocks its translation in the posterior end of Drosophila embryos. The Bicoid, Hunchback, and Caudal proteins are transcription factors. Bicoid has a DNA-binding homeodomain that binds both DNA and the nanos mRNA. Bicoid binds a specific RNA sequence in the 3' untranslated region of caudal mRNA and blocks translation. Hunchback protein levels in the early embryo are significantly augmented by new hunchback gene transcription and translation of the resulting zygotically produced mRNA. During early Drosophila embryogenesis there are nuclear divisions without cell division. The many nuclei that are produced distribute themselves around the periphery of the cell cytoplasm. Gene expression in these nuclei is regulated by the Bicoid, Hunchback, and Caudal proteins. For example, Bicoid acts as a transcriptional activator of hunchback gene transcription. zygotically zygotically

Gap genes

The other important function of the gradients of Bicoid, Hunchback, and Caudal proteins is in the transcriptional regulation of other zygotically expressed proteins. Many of these are the protein products derived from members of the "gap" family of developmental control genes. Hunchback, krüppel, giant, tailless and knirps are all gap genes. Their expression patterns in the early embryo are determined by the maternal effect gene products and shown in the diagrams on the left side of this page. The gap genes are part of a larger family called the segmentation genes. These genes establish the segmented body plan of the embryo along the anterior-posterior axis. The segmentation genes specify 14 "parasegments" that are closely related to the final anatomical segments. The gap genes are the first layer of a hierarchical cascade of the segmentation control genes. Proteins such as Bicoid can be described as morphogens that act within the syncytial blastoderm of the early Drosophila embryo. These intracellular morphogens enter the nuclei and act as transcription factors to control expression of the gap genes. In the blastoderm stage of Drosophila morphogenesis four types of nuclear specification can be distinguished:
- Anterior (head and thorax)
- Posterior (abdomen)
- Dorso-ventral
- Terminal (special structures at the unsegmented ends of the embryo)

Additional segmentation genes

ventral Two additional classes of segmentation genes are expressed after the gap gene products. The pair-rule genes are expressed in striped patterns of seven bands perpendicular to the anterior-posterior axis (see the example, even-skipped). These patterns of expression are established within the syncytial blastoderm. After these initial patterning events, cell membranes form around the nuclei of the syncytial blastoderm converting it to a cellular blastoderm. ventral The expression patterns of the final class of segmentation genes, the segment polarity genes, are then fine-tuned by interactions between the cells of adjacent parasegments (see the example, engrailed, to the right). The Engrailed protein is a transcription factor (yellow in figure to left) that is expressed in one row of cells at the edge of each parasegment. This expression pattern is initiated by the pair-rule genes (like even-skipped) that code for transcription factors that regulate the engrailed gene's transcription in the syncytial blastoderm. Cells that make Engrailed can make the cell-to-cell signaling protein Hedgehog (green in the figure to the left). Hedgehog is not free to move very far and activates a thin stripe of cells adjacent to the Engrailed-expressing cells. Only cells to one side of the Engrailed-expressing cells are competent to respond to Hedgehog because they express the receptor protein Patched (blue in figure to left). Cells with activated Patch receptor make the Wingless protein (red in the figure). Wingless protein acts as an extracelluar morphogen and patterns the adjacent rows of cells by activated its cell surface receptor, Frizzled in a concentration-dependent fashion. Wingless also acts on Engrailed-expressing cells to stabilize Engrailed expression after the cellular blastoderm forms. The reciprocal signaling by Hedgehog and Wingless stabilizes the boundary between each segment. The Wingless protein is called "wingless" because of the phenotype of some wingless mutants. Wingless also functioned during metamorphosis to coordinate wing formation. The transcription factors that are coded for by segmentation genes regulate yet another family of developmental control genes, the homeotic selector genes. These genes exist in two ordered groups on Drosophila chromosome 3. The order of the genes on the chromosome reflects the order that they are expressed along the anterior-posterior axis of the developing embryo. The Antennapedia group of homeotic selector genes includes labial, antennapedia, sex combs reduced, deformed, and proboscipedia. Labial and Deformed proteins are expressed in head segments where they activate the genes that define head features. Sex-combs-reduced and Antennapedia specify the properties of thoracic segments. The bithorax group of homeotic selector genes control the specializations of the third thoracic segment and the abdominal segments. In 1995, the Nobel Prize for Physiology or Medicine was awarded for studies concerning the genetic control of early embryonic development to Christiane Nüsslein-Volhard, Edward B. Lewis and Eric Wieschaus. Their researches on genetic screening for embryo patterning mutants revealed the role played in early embryologic development by Hox genes like bicoid. An example of a homeotic mutation is the so-called antennapedia mutation. In Drosophila, antennae and legs are created by the same basic "program", they only differ in a single transcription factor. If this transcription factor is damaged, the fly grows legs on its head instead of antennae. See images of this "antennapedia" mutant and others, at [http://flybase.bio.indiana.edu FlyBase]. The term morphogenesis can also be used to describe the development of unicellular life forms that do not have an embryonic stage in their life cycle, or to refer to the evolution of a body structure within a taxonomic group. Morphogenetic responses may be induced in organisms by hormones, or by environmental chemicals ranging from substances produced by other organisms to toxic chemicals or radionuclides released as pollutants.

Greek language

Greek (Greek Ελληνικά, IPA – "Hellenic") is an Indo-European language with a documented history of 3,500 years. Today, it is spoken by 15 million people in Greece, Cyprus, the former Yugoslavia, particularly The Former Yugoslav Republic of Macedonia, Bulgaria, Albania and Turkey. There are also many Greek emigrant communities around the world, such as those in Melbourne, Australia which is the third-largest Greek-populated city in the world, after Athens and Thessaloniki. Greek has been written in the Greek alphabet, the first true alphabet, since the 9th century B.C. and before that, in Linear B and the Cypriot syllabaries. Greek literature has a long and rich tradition.

History

This article does not cover the reconstructed history of Greek prior to the use of writing. For more information, see main article on Proto-Greek language. Greek has been spoken in the Balkan Peninsula since the 2nd millennium BC. The earliest evidence of this is found in the Linear B tablets dating from 1500 BC. The later Greek alphabet (q.v.) is unrelated to Linear B, and was derived from the Phoenician alphabet (abjad); with minor modifications, it is still used today. Greek is conventionally divided into the following periods:
- Mycenean Greek: the language of the Mycenean civilisation. It is recorded in the Linear B script on tablets dating from the 16th century BC onwards.
- Classical Greek (also known as Ancient Greek): In its various dialects was the language of the Archaic and Classical periods of Greek civilisation. It was widely known throughout the Roman empire. Classical Greek fell into disuse in western Europe in the Middle Ages, but remained known in the Byzantine world, and was reintroduced to the rest of Europe with the Fall of Constantinople and Greek migration to Italy.
- Hellenistic Greek (also known as Koine Greek): The fusion of various ancient Greek dialects with Attic (the dialect of Athens) resulted in the creation of the first common Greek dialect, which gradually turned into one of the world's first international languages. Koine Greek can be initially traced within the armies and conquered territories of Alexander the Great, but after the Hellenistic colonisation of the known world, it was spoken from Egypt to the fringes of India. After the Roman conquest of Greece, an unofficial diglossy of Greek and Latin was established in the city of Rome and Koine Greek became a first or second language in the Roman Empire. Through Koine Greek it is also traced the origin of Christianity, as the Apostles used it to preach in Greece and the Greek-speaking world. It is also known as the Alexandrian dialect, Post-Classical Greek or even New Testament Greek (after its most famous work of literature).
- Medieval Greek: The continuation of Hellenistic Greek during medieval Greek history as the official and vernacular (if not the literary nor the ecclesiastic) language of the Byzantine Empire, and continued to be used until, and after the fall of that Empire in the 15th century. Also known as Byzantine Greek.
- Modern Greek: Stemming independently from Koine Greek, Modern Greek usages can be traced in the late Byzantine period (as early as 11th century). Two main forms of the language have been in use since the end of the medieval Greek period: Dhimotikí (Δημοτική), the Demotic (vernacular) language, and Katharévousa (Καθαρεύουσα), an imitation of classical Greek, which was used for literary, juridic, and scientific purposes during the 19th and early 20th centuries. Demotic Greek is now the official language of the modern Greek state, and the most widely spoken by Greeks today. It has been claimed that an "educated" speaker of the modern language can understand an ancient text, but this is surely as much a function of education as of the similarity of the languages. Still, Koinē , the version of Greek used to write the New Testament and the Septuagint, is relatively easy to understand for modern speakers. Greek words have been widely borrowed into the European languages: astronomy, democracy, philosophy, thespian, etc. Moreover, Greek words and word elements continue to be productive as a basis for coinages: anthropology, photography, isomer, biomechanics etc. and form, with Latin words, the foundation of international scientific and technical vocabulary. See English words of Greek origin, and List of Greek words with English derivatives.

Classification

Greek is an independent branch of the Indo-European language family. The ancient languages which were probably most closely related to it, Ancient Macedonian language (which may be regarded as a dialect of Greek) and Phrygian, are not well enough documented to permit detailed comparison. Among living languages, Armenian seems to be the most closely related to it.

Geographic distribution

Modern Greek is spoken by about 15 million people mainly in Greece and Cyprus. There are also Greek-speaking populations in Georgia, Ukraine, Egypt, Turkey, Albania, Former Yugoslav Republic of Macedonia and Southern Italy. The language is spoken also in many other countries where Greeks have settled, including Armenia, Australia, Austria, Belgium, Bulgaria, Canada, Denmark, France, Germany, Netherlands, Sweden, United Kingdom, and the United States.

Official status

Greek is the official language of Greece where it is spoken by about 99.5% of the population. It is also, alongside Turkish, the official language of Cyprus. Due to the membership of Greece and Cyprus, Greek is one of the 20 official languages of the European Union.

Phonology

This section generally describes the post-Classic phonology of the Greek language. :All phonetic transcriptions in this section use the International Phonetic Alphabet

Vowel sounds

Greek has 5 vowel sounds, all phonemic:

Cell growth

The term cell growth is used in two different ways in biology. When used in the context of reproduction of living cells the phrase "cell growth" is shorthand for the idea of "growth in cell numbers by means of cell reproduction." During cell reproduction one cell (the "parental" cell) divides to produce daughter cells. In other contexts, "cell growth" refers to increases in cell size.

Cell size

Many cells never have a large increase in size after they are first formed from a parental cell. Typical stem cells reproduce, double in size, then reproduce again. Most Cytosolic contents such as the endomembrane system and the cytoplasm easily scale to larger sizes in larger cells. If a cell becomes too large, the normal cellular amount of DNA may not be adequate to keep the cell supplied with RNA. Large cells often replicate their chromosomes to an abnormally high copy number or become multinucleated. Large cells that are primarily for nutrient storage can have a smooth surface membrane, but metabolically active large cells often have some sort of folding of the cell surface membrane in order to increase the surface area available for transport functions.

Yeast cell size regulation

The relationship between cell size and cell division has been extensively studied in yeast. For some cells, there is a mechanism by which cell division is not initiated until a cell has reached a certain size. If the nutrient supply is restricted (after time t = 2 in the diagram, below) and the rate of increase in cell size is slowed, the time period between cell divisions is increased. Yeast cell size mutants were isolated that begin cell division before reaching the normal size (wee mutants). The Wee1 protein is a tyrosine kinase. It normally phosphorylates the Cdc2 cell cycle regulatory protein on a tyrosine residue. This covalent modification of the molecular structure of Cdc2 inhibits the enzymatic activity of Cdc2 and prevents cell division. In Wee1 mutants, there is less Wee1 activity and Cdc2 becomes active in smaller cells, causing cell division before the yeast cells reach their normal size. Cell division may be regulated in part by dilution of Wee1 protein in cells as they grow larger. Cell cycle and growth

Cell size regulation in mammals

The protein mTOR is a serine/threonine kinase that regulates translation and cell division. Nutrient availability influences mTOR so that when cells are not able to grow to normal size they will not undergo cell division. The details of the molecular mechanisms of mammalian cell size control are currently being investigated. The size of post-mitotic neurons depends on the size of the cell body, axon and dendrites. In vertebrates, neuron size is often a reflection of the number of synaptic contacts onto the neuron or from a neuron onto other cells. For example, the size of motoneurons usually reflects the size of the motor unit that is controlled by the motoneuron. Invertebrates often have giant neurons and axons that provide special functions such as rapid action potential propagation. Mammals also use this trick for increasing the speed of signals in the nervous system, but they can also use myelin to accomplish this, so most human neurons are releatively small.

Other experimental systems for the study of cell size regulation

One common means to produce very large cells is by cell fusion to form syncytia. For example, very long (several inches) skeletal muscle cells are formed by fusion of thousands of myocytes. Genetic studies of the fruit fly Drosophila have revealed several genes that are required for the formation of multinucleated muscle cells by fusion of myocyes. Some of the key proteins are important for cell adhesion between myocytes and some are involved in adhesion-dependent cell-to-cell signaling that allows for a cascade of cell fusion events. Oocytes can be unusually large cells in species for which embryonic development takes place away from the mother's body. Their large size can be achieved either by pumping in cytosolic components from adjacent cells through cytoplasmic bridges (Drosophila) or by internalization of nutrient storage granules (yolk granules) by endocytosis (frogs). Increases in the size of plant cells is complicated by the fact that almost all plant cells are inside of a solid cell wall. Under the influence of certain plant hormones the cell wall can be remodeled, allowing for increases in cell size that are important for the growth of some plant tissues. Most unicellular organisms are microscopic in size, but there are some giant bacteria and protozoa that are visible to the naked eye. See: [http://wikibooks.org/wiki/Biology_Cell_biology_Introduction_Cell_size Table of cell sizes] - [http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10205058 Dense populations of a giant sulfur bacterium in Namibian shelf sediments] - [http://www.bms.ed.ac.uk/research/others/smaciver/chaos.htm Large protists of the genus Chaos, closely related to the genus Amoeba]

Cell reproduction

The process of cell reproduction has three major parts. The first part of cell reproduction involves the replication of the parental cell's DNA. The second major issue is the separation of the duplicated DNA into two equally sized groups of chromosomess. The third major aspect of cell reproduction is the physical division of entire cells, usually called cytokinesis. Cell reproduction is more complex in eukaryotes than in other organisms. Non-eukaryotic cells such as bacterial cells reproduce by binary fission, a process that includes DNA replication, chromosome segregation, and cytokinesis. Eukaryotic cell reproduction either involves mitosis or a more complex process called meiosis. Mitosis and meiosis are sometimes called the two "nuclear division" processes. Binary fission is similar to eukaryotic cell reproduction that involves mitosis. Both lead to the production of two daughter cells with the same number of chromosomes as the parental cell. Meiosis is used for a special cell reproduction process of diploid organisms. It produces four special daughter cells (gametes) which have half the normal cellular amount of DNA. A male and a female gamete can then combine to produce a zygote, a cell which again has the normal amount of chromosomes. For details see the individual articles on DNA replication, binary fission, mitosis, meiosis, and cytokinesis. The rest of this article is a comparison of the main features of the three types of cell reproduction that either involve binary fission, mitosis, or meiosis. The diagram below depicts the similarities and differences of these three types of cell reproduction. cytokinesis

Comparison of the three types of cell reproduction

The DNA content of a cell is duplicated at the start of the cell reproduction process. Prior to DNA replication, the DNA content of a cell can be represented as the amount Z (the cell has Z chromosomes). After the DNA replication process, the amount of DNA in the cell is 2Z (multiplication: 2 x Z = 2Z). During Binary fission and mitosis the duplicated DNA content of the reproducing parental cell is separated into two equal halves that are destined to end up in the two daughter cells. The final part of the cell reproduction process is cell division, when daughter cells physically split apart from a parental cell. During meiosis, there are two cell division steps that together produce the four daughter cells. After the completion of binary fission or cell reproduction involving mitosis, each daughter cell has the same amount of DNA (Z) as what the parental cell had before it replicated its DNA. These two types of cell reproduction produced two daughter cells that have the same number of chromosomes as the parental cell. After meiotic cell reproduction the four daughter cells have half the number of chromosomes that the parental cell originally had. This is the haploid amount of DNA, often symbolized as N. Meiosis is used by diploid organisms to produce haploid gametes. In a diploid organism such as the human organism, most cells of the body have the haploid amount of DNA, 2N. Using this notation for counting chromosomes we say that human somatic cells have 46 chromosomes (2N = 46) while human sperm and eggs have 23 chromosomes (N = 23). Humans have 23 distinct types of chromosomes, the 22 autosomes and the special category of sex chromosomes. There are two distinct sex chromosomes, the X chromosome and the Y chromosome. A diploid human cell has 23 chromosomes from that person's father and 23 from the mother. That is, your body has two copies of human chromosome number 2, one from each of your parents.

Chromosomes

Immediately after DNA replication a human cell will have 46 "double chromosomes". In each double chromosome there are two copies of that chromosome's DNA molecule. During mitosis the double chromosomes are split to produce 92 "single chromosomes", half of which go into each daughter cell. During meiosis, there are two chromosome separation steps which assure that each of the four daughter cells gets one copy of each of the 23 types of chromosome (see meiosis for details).

Why we have sex

Main article: Evolution of sex If the type of cell reproduction that uses mitosis can reproduce our cells, why do we bother with the more complicated process of meiosis? You may think you know why you have sex, but you probably do not know the real reason; the reason why meiosis confers a selective advantage. Notice that when meiosis starts, the two copies of chromosome number 2 are adjacent to each other. During this time, there can be genetic recombination events. Parts of the chromosome 2 DNA that you got from your mother (red) will swap over to the chromosome 2 DNA molecule that you got from your father (green). Notice that in mitosis the two copies of chromosome number 2 do not interact. It is these new combinations of parts of chromosomes that provide the major advantage for sexually reproducing organisms by allowing for new combinations of genes and more efficient evolution. However, in organisms with more than one set of chromosomes at the main life cycle stage, sex may also provide an advantage because, under random mating, it produces homozygotes and heterozygotes according to the Hardy-Weinberg ratio.

Developmental biology

Developmental biology is the study of the process by which organisms grow and develop. Modern developmental biology studies the genetic control of cell growth, differentiation and "morphogenesis," which is the process that gives rise to tissues, organs and anatomy. Embryology is a subfield, the study of organisms between the one-cell stage (generally, the zygote) and the end of the embryonic stage, which is not necessarily the beginning of free living. Embryology was originally a more descriptive science until the 20th century. Embryology and developmental biology today deal with the various steps necessary for the correct and complete formation of the body of a living organism. The related field of evolutionary developmental biology was formed largely in the 1990s and is a synthesis of findings from molecular developmental biology and evolutionary biology which considers the diversity of organismal form in an evolutionary context. The findings of developmental biology can help to understand developmental malfunctions such as chromosomal aberrations, for example, Down syndrome. An understanding of the specialization of cells during embryogenesis may shield information on how to specialize stem cells to specific tissues and organs, which could lead to the specific cloning of organs for medical purposes. Another biologically important process that occurs during development is apoptosis - cell "suicide". For this reason, many developmental models are used to elucidate the physiology and molecular basis of this cellular process.

Molecular mechanisms of development

During the second half of the 20th century the types of molecules involved in embryonic development were identified. Transcription factors are the key regulators of which genes are expressed in cells. Transcriptional control in the various differentiated cell types allows each type of cell (epithelial, muscle, neuron, etc) to express different amounts of the possible proteins. The transcription factors are regulated by signal transduction pathways that relay signals from outside of cells to the cell nucleus. Signal transduction pathways often involve receptors, receptor ligands and enzymes such as protein kinases. One key class of genes that are differentially regulated by transcription factors in different cell types are genes for cell adhesion proteins. Cell adhesion proteins are among the key regulators of morphogenesis. :Concepts in developmental biology :allantois, amnion, blastocyst, blastomere, blastula, blastulation, chorion, chrysalis, cleavage, ectoderm, embryo, embryogenesis, embryogeny, embryology, endoderm, extra-embryonic membrane, fetus (or foetus), gastrula, gastrulation, germ layer, germ plasm, germination, induction, juvenile, larva, maternal effect, mesoderm, metamorphosis, genome, morphogenesis, morula, neoteny, neural development, nymph, ontogeny, oosperm, ovism, paedogenesis, pangenesis, phylogeny, primordium, pupa, rudiment, seed, teratology, zygote

Developmental model organisms

Often used model organisms in developmental biology include the following:
- Chordates
- Lancelet Branchiostoma lanceolatum
- Zebrafish Danio rerio
- Medakafish Oryzias latipes
- Fugu Takifugu rubripes
- Frogs Xenopus laevis
- Chicken Gallus gallus
- Mouse Mus musculus (Mammalian embryogenesis)
- Invertebrates
- Sea urchin
- Round worm Caenorhabditis elegans
- Fruit fly Drosophila melanogaster (Drosophila embryogenesis)
- Plants (Plant embryogenesis)
- Arabidopsis thaliana
- Maize
- Snapdragon

Developmental systems biology

Computer simulation of multicellular development is a research methodology to understand the function of the very complex processes involved in the development of organisms. This includes simulation of cell signaling, multicell interactions and regulatory genomic networks in development of multicellular structures and processes. Minimal genomes for minimal multicellular organisms may pave the way to understand such complex processes in vivo (see Genomes#Minimal genomes).

Sources

- [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?call=bv.View..ShowTOC&rid=dbio.TOC&depth=2 Developmental Biology] by Scott Gilbert. (online textbook)
- [http://www.sdbonline.org/Other/VL_DB.html Virtual Library - Developmental Biology] Category:Developmental biology ja:発生生物学 simple:Developmental biology

Biological tissue

Biological tissue is a substance made up of cells that perform a similar function. The study of tissues is known as histology, or, in connection with disease, histopathology. The classical tools for studying the tissues are the wax block, the tissue stain, and the optical microscope, though developments in electron microscopy, immunofluorescence, and frozen sections have all added to the sum of knowledge in the last couple of decades. With these tools, the classical appearances of the tissues can be examined in health and disease, enabling considerable refinement of clinical diagnosis and prognosis.

Animal Tissues

There are four basic types of tissue in the body of all animals, including the human body and lowar multicellular organisms such as insects. These compose all the organs, structures and other contents.
- Epithelium - Tissues composed of layers of cells that cover organ surfaces such as surface of the skin and inner lining of digestive tract. The tissues serve for protection, secretion, and absorption.
- Connective tissue - As the name suggests, connective tissue holds everything together. Blood is considered a connective tissue.
- Muscle tissue - Muscle cells contain contractile filaments that move past each other and change the size of the cell.
- Nervous tissue - Cells forming the brain, spinal cord and peripheral nervous system.

Plant Tissues

Examples of tissue in other multicellular organisms are vascular tissue in plants, such as xylem and phloem. Plant tissues are categorized broadly into three tissue systems: the epidermis, the ground tissue, and the vascular tissue.
- Epidermis - Cells forming the outer surface of the leaves and of the young plant body.
- Vascular tissue - The primary components of vascular tissue are the xylem and phloem. These two tissues transport fluid and nutrients internally.
- Ground tissue - Ground tissue is less differentiated than other tissues. Ground tissue manufactures nutrients by photosynthesis and stores reserve nutrients.

References

- Raven, Peter H., Evert, Ray F., & Eichhorn, Susan E. (1986). Biology of Plants (4th ed.). New York: Worth Publishers. ISBN 0-87901-315-X. Category:Anatomy Category:Tissues ms:Tisu biologi ja:組織 (生物学) simple:Tissue (biological)

Anatomy

Anatomy (from the Greek anatomia, from anatemnein, to cut up, cut open), is the branch of biology that deals with the structure and organization of living things. It can be divided into animal anatomy (zootomy) and plant anatomy (phytonomy). Major branches of anatomy include comparative anatomy, histology, and human anatomy. Animal anatomy may include the study of the structure of different animals, when it is called comparative anatomy or animal morphology, or it may be limited to one animal only, in which case it is spoken of as special anatomy. From a utilitarian point of view the study of humans is the most important division of special anatomy, and this human anatomy may be approached from different points of view. From that of Medicine it consists of a knowledge of the exact form, position, size and relationship of the various structures of the healthy human body, and to this study the term descriptive or topographical human anatomy is given, though it is often, less happily, spoken of as anthropotomy. So intricate is the human body that only a small number of professional human anatomists, after years of patient observation, are complete masters of all its details; most of them specialize on certain parts, such as the brain or viscera, contenting themselves with a good working knowledge of the rest. Topographical anatomy must be learned by repeated dissection and inspection of dead human bodies. It is no more a science than a pilot's knowledge is, and, like that knowledge, must be exact and available in moments of emergency. From the morphological point of view, however, human anatomy is a scientific and fascinating study, having for its object the discovery of the causes which have brought about the existing structure of humans, and needing a knowledge of the allied sciences of embryology or developmental biology, phylogeny, and histology. Pathological anatomy (or morbid anatomy) is the study of diseased organs, while sections of normal anatomy, applied to various purposes, receive special names such as medical, surgical, gynaecological, artistic and superficial anatomy. The comparison of the anatomy of different races of humans is part of the science of physical anthropology or anthropological anatomy. In the present edition of this work the subject of anatomy is treated systematically rather than topographically. Each anatomical article contains first a description of the structures of an organ or system (such as nerves, arteries, heart, and so forth), as it is found in humans; this is followed by an account of the development (embryology) and comparative anatomy (morphology), as far as vertebrate animals are concerned; but only those parts of the lower animals which are of interest in explaining human body structure are here dealt with. The articles have a twofold purpose; first, to give enough details of structure to make the articles on physiology, surgery, medicine and pathology intelligible; and, secondly, to give the non-expert inquirer, or the worker in some other branch of science, the chief theories on which the modern scientific groundwork of anatomy is built.
- Major body systems:
- Integumentary system
- Muscular system
- Nervous system
- Reproductive system
- Respiratory system
- Excretory system
- Circulatory system
- Lymphatic system
- Skeletal system (Human skeleton)
- Endocrine system
- Digestive system
- Immune system
- Organs:
- Anus
- Appendix
- Brain
- Breast
- Colon or large intestine
- Diaphragm
- Ear
- Eye
- Heart
- Kidney
- Labia
- Larynx
- Liver
- Lung
- Nose
- Ovary
- Pharynx
- Pancreas
- Penis
- Placenta
- Rectum
- Skin
- Small intestine
- Spleen
- Stomach
- Tongue
- Uterus
- Bones in the human skeleton:
- Collar bone (clavicle)
- Thigh bone (femur)
- Humerus
- Mandible
- Patella
- Radius
- Skull
- Tibia
- Ulna
- Rib
- Vertebrae
- Pelvis
- Sternum
- Glands:
- Ductless gland
- Mammary gland
- Salivary gland
- Thyroid gland
- Parathyroid gland
- Adrenal gland
- Pituitary gland
- Pineal gland
- Tissues:
- Connective tissue
- Endothelial tissue
- Epithelial tissue
- Glandular tissue
- Lymphoid tissue
- Externally visible parts of the human body:
- Abdomen
- Arm
- Back
- Buttock
- Chest
- Ear
- Eye
- Face
- Genitals
- Head
- Joint
- Leg
- Mouth
- Neck
- Scalp
- Skin
- Teeth
- Tongue
- Other anatomic terms (not classified):
- Artery
- Coelom
- Diaphragm
- Gastrointestinal tract
- Hair
- Exoskeleton
- Lip
- Nerve
- Peritoneum
- Serous membrane
- Skeleton
- Skull
- Spinal cord
- Vein

External links

- [http://brainmaps.org High-Resolution Cytoarchitectural Primate Brain Atlases]
- [http://www.innerbody.com/htm/body.html Free online anatomy atlas]
- [http://www.npac.syr.edu/projects/vishuman/VisibleHuman.html The NPAC Visible Human Viewer]
- [http://cancerweb.ncl.ac.uk/omd/index.html On-Line Medical Dictionary]
- [http://www.bartleby.com/107/ Anatomy of the Human Body by Henry Gray]
- [http://www.rtstudents.com/ Online Radiology Anatomy Resources]
- [http://www.wikimd.org/index.php?title=Gray%27s_Anatomy Gray's Anatomy wiki]
- http://immunity-info.net Category:Anatomy ko:해부학 ja:解剖学 simple:Anatomy th:กายวิภาคศาสตร์

Stem cell

nic stem cells. [http://www.news.wisc.edu/packages/stemcells/labphotos.html More lab photos] ]] Stem cells are primal undifferentiated cells which retain the ability to differentiate into other cell types. This ability allows them to act as a repair system for the body, replenishing other cells as long as the organism is alive. Medical researchers believe stem cell research has the potential to change the face of human disease by being used to repair specific tissues or to grow organs. Still, as government reports point out, "significant technical hurdles remain that will only be overcome through years of intensive research." The study of stem cells is attributed as beginning in the 1960s after research by Canadian scientists Ernest A. McCulloch and James E. Till.

Types

Stem cells are categorized by potency which describes the specificity of that cell.
- Totipotent stem cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg cell are also totipotent. These cells can grow into any type of cell without exception.
- Pluripotent stem cells are the descendants of totipotent cells and can grow into any cell type except for totipotent stem cells.
- Multipotent stem cells can produce only cells of a closely related family of cells (e.g. blood cells such as red blood cells, white blood cells and platelets).
- Progenitor (sometimes called unipotent) cells can produce only one cell type, but have the property of self-renewal which distinguishes them from non-stem cells. Stem cells are also categorized according to their source, as either adult or embryonic. :Adult stem cells are undifferentiated cells found among differentiated cells of a specific tissue and are mostly multipotent cells. They are already being used in treatments for over one hundred diseases and conditions. They are more accurately called somatic (Greek σωμα sōma = body) stem cells, because they need not come from adults but can also come from children or umbilical cords. Particularly interesting are adult stem cells termed "spore-like cells". They are present in all tissues (Vacanti, M. P., A. Roy, J. Cortiella, L. Bonassar, and C. A. Vacanti. 2001. Identification and initial characterization of spore-like cells in adult mammals. J Cell Biochem 80:455-60.)and seem to survive long time periods and harsh conditions. :Embryonic stem cells are cultured cells obtained from the undifferentiated inner mass cells of a blastocyst, an early stage embryo that is 50 to 150 cells. Embryonic stem cell research is "thought to have much greater developmental potential than adult stem cells," according to the National Institutes of Health. However, embryonic stem cell research is still in the basic research phase, as these stem cells were first isolated in 1998 (at least for humans), whereas adult stem cells have been studied since the 1960s. Research with embryonic stem cells derived from humans is controversial because, in order to start a stem cell 'line' or lineage, it requires the destruction of a blastocyst, which many believe is tantamount to the destruction of a human being. (See below: embryonic stem cell ethical debate)

Sources of stem cells

Cord blood stem cells

Blood from the placenta and umbilical cord that are left over after birth is one source of adult stem cells. Since 1988 these cord blood stem cells have been used to treat Gunther's disease, Hunter syndrome, Hurler syndrome, Acute lymphocytic leukemia and many more problems occurring mostly in children. Umbilical cord blood use has become so common that there are now umbilical cord blood banks that accept donations from parents. It is collected by removing the umbilical cord, cleansing it and withdrawing blood from the umbilical vein. This blood is then immediately analyzed for infectious agents and the tissue-type is determined. The cord blood is processed and depleted of red blood cells before being stored in liquid nitrogen for later use, at which point it is thawed, washed of the cryoprotectant, and injected through a vein of the patient. This kind of treatment, where the stem cells are collected from another donor, is called allogeneic treatment. When the cells are collected from the same patient on whom they will be used, it is called autologous and when collected from identical individuals, it is referred to as syngeneic. Xenogeneic transfer of cells (between different species) is very underdeveloped and is said to have little research potential. Researchers in South Korea announced in November 2004 that they had successfully used multipotent cord blood (adult) stem cell treatments to enable a paralyzed woman to walk with the aid of a walker. This was achieved by isolating the stem cells from the umbilical cord blood and injecting the cells into the damaged part of the woman's spinal cord. Work was done by Chosun University professor Song Chang-hun, Seoul National University professor Kang Kyung-susn, and the [http://www.seoulcord.co.kr/bin/main.asp Seoul Cord Blood Bank].[http://times.hankooki.com/lpage/200411/kt2004112617575710440.htm] [http://www.cordblood.com/cord_blood_news/stem_cell_news/a_paralyzed.asp] [http://www.connected.telegraph.co.uk/news/main.jhtml?xml=/news/2004/11/30/wcells30.xml] [http://www.wpherald.com/storyview.php?StoryID=20041127-121143-6745r] While exciting, many more studies are required to establish that such treatments are effective.

Adult stem cells

Stem cells can be found in all adults and young adults. Adult stem cells are undifferentiated cells that reproduce daily to provide certain specialized cells—for example 200 billion red blood cells are created each day in the body from hemopoietic stem cells. Until recently it was thought that each of these cells could produce just one particular type of cell—this is called differentiation (see Morphogenesis). However in the past few years, evidence has been gathered of stem cells that can transform into several different forms. Bone marrow stromal stem cells are thought to be able to transform into liver, nerve, muscle, hair follicle and kidney cells. Although there is some evidence that this type of transdifferentiation can occur, many scientists are skeptical of these claims and we are still learning about such transdifferentiated cells. Adult stem cells may be even more versatile than this. Researchers at the New York University School of Medicine have extracted stem cells from the bone-marrow of mice which they say are pluripotent. Turning one type of stem cell into another is called transdifferentiation. In fact, useful sources of adult stem cells are being found in organs all over the body. Researchers at McGill University in Montreal have extracted stem cells from skin that are able to differentiate into many types of tissue, including neurons, smooth muscle cells and fat-cells. These were found in the dermis, the inner layer of the skin. These stem cells play a pivotal role in healing small cuts. Blood vessels, the dental pulp, the digestive epithelium, the retina, liver and even the brain are all said to contain stem cells. The [http://www.som.tulane.edu/gene_therapy/ Tulane University Center for Gene Therapy] is the first U.S. government-funded center to produce and distribute well-characterized adult stem cells to researchers around the globe. These standardized cells are critical to ensuring comparability and reproducibility of world-wide research. Adipose derived adult stem (ADAS) cells have also been isolated from fat, e.g. from liposuction. This source of cells seems to be similar in many ways to Mesenchymal stem cells (MSCs) derived from bone marrow, except that it is possible to isolate many more cells from fat. These cells have been shown to differentiate into bone, fat, muscle, cartilage, and neurons. These cells have been recently used to successfully repair a large cranial defect in a human patient [http://www.msnbc.msn.com/id/6727466/]. Olfactory adult stem cells have been successfully grown by Prof. Alan Mackay-Sim,[http://www.gu.edu.au/school/bbs/content_mackay.html] deputy director of Griffith University’s new Institute for Cellular and Molecular Therapies in Brisbane, Queensland, Australia. He was awarded Queenslander of the Year in 2003 for his work. His team successfully grew adult stem cells harvested from the human nose, and was published in the journal Developmental Dynamics. The Courier-Mail cited him as follows (22 March 2005, p. 4): :Adult stem cells isolated from the olfactory mucosa (cells lining the inside of the nose involved in the sense of smell) have the ability to develop into many different cell types if they are given the right chemical environment. :These adult olfactory stem cells appear to have the same ability as embryonic stem cells in giving rise to many different cell types but have the advantage that they can be obtained from all individuals, even older people who might be most in need to stem cell therapies. ... :Adult olfactory stem cells are readily obtained from the nose and relatively easy to grow and multiply in the lab. In a few weeks we can make plenty of cells for transplantation. An advantage of adult stem cells is that, since they can be harvested from the patient, potential ethical issues and immunogenic rejection are averted. Although many different kinds of multipotent stem cells have been identified, adult stem cells that could give rise to all cell and tissue types have not yet been found. Adult stem cells are often present in only minute quantities and can therefore be difficult to isolate and purify. There is also limited evidence that they may not have the same capacity to multiply as embryonic stem cells do. Finally, adult stem cells may contain more DNA abnormalities—caused by sunlight, toxins, and errors in making more DNA copies during the course of a lifetime. However, there are a number of clinically proven adult stem cell successes. Adult stem cells do appear in "minute quantities" however, these minute in-vivo quantities can be multiplied in-vitro to therapeutic numbers. For example, many patients have received treatment for heart disease using adult stem cells originating in bone marrow. In 2005, technology has become available[http://www.theravitae.com] whereby stem cells can be harvested, differentiated and multiplied from about ½ pint of one’s own blood.” Several types of heart diseases have been treated in clinical trials and also is available commercially. Patients such as Jeannine Lewis[http://www.timesleader.com/mld/timesleader/living/health/12111058.htm], have traveled to Thailand to receive stem cell therapy for their heart disease. Dr. Amit Patel of the University of Pittsburgh McGowen Institute for Regenerative Medicine[http://www.mirm.pitt.edu/people/bios/Patel1.htm] has been one of the leaders in stem cell therapy for heart disease.

Spore-Like Cells

Spore-like cells were described first by Vacanti et al. in 2001 (Vacanti, M. P., A. Roy, J. Cortiella, L. Bonassar, and C. A. Vacanti. 2001. Identification and initial characterization of spore-like cells in adult mammals. J Cell Biochem 80:455-60.)They are extremely small (i.e. <5 micrometer). They appear to lie dormant and to be dispersed throughout the parenchyma of virtually every tissue in the body. Being dormant, they survive in extremely low oxygen environments and other hostile conditions, known to be detrimental to mammalian cells, including extremes of temperatures. Spore-like cells remain viable in unprepaired tissue, frozen at -86°C (using no special preservation techniques) and then thawed, or heated to 85°C for more than 30 min. This has led researchers to try to revitalize spore-like cells from tissue samples of frozen carcasses deposited in permafrost for decades (frozen walrus meat >100 years old)(mammoth and bison, Alaska 50,000 years old). In vitro, these structures have the capacity to enlarge, develop, and differentiate into cell types expressing characteristics appropriate to the tissue environment from which they were initially isolated. Vacanti et al. believed that these unique cells lie dormant until activated by injury or disease, and that they have the potential to regenerate tissues lost to disease or damage. Because the cell-size of less than 5 micrometers seems rather small as to contain the entire human germ-line genome the authors speculate on the "concept of a minimal genome" for these cells.

Embryonic stem cells

Embryonic stem cells are stem cells derived from the undifferentiated inner mass cells of a blastocyst, an early stage embryo consisting of 50-150 cells. They are pluripotent, meaning they are able to grow into each of the more than 200 cell types in the body as long as they are specified to do so. They are also, technically immortal, which means that they can replicate indefinitely although the moment there is no room for more replication then they start to differentiate. Embryonic stem cells can be obtained from a cloned blastocyst, created by fusing a denucleated egg cell with a patient's cell. The blastocyst produced is allowed to grow to the size of a few tens of cells, and stem cells are then extracted. Because they are obtained from a clone, they are genetically compatible with the patient. More commonly, they are obtained for research purposes from uncloned blastocysts, such as those discarded from in vitro fertilization clinics. Such cells might be rejected if transplanted into a patient. A possible solution for this is to derive multiple well-characterized embryonic stem cell lines from different genetic and ethnic backgrounds; treatment can then be tailored to the patient, minimizing the risk of rejection. The breakthrough in embryonic stem cell research came in November 1998 when a group led by James Thomson at the University of Wisconsin-Madison first developed a technique to isolate and grow the cells. Embryonic stem cell researchers are currently attempting to grow the cells beyond the first stages of cell development, to overcome difficulties in host rejection of implanted stem cells, and to control the multiplying of implanted embryonic stem cells, which otherwise multiply uncontrollably, producing a tumor. A major development in research came in May 2003, when researchers announced that they had successfully used embryonic stem cells to produce human egg cells. These egg cells could potentially be used in turn to produce new stem cells. If research and testing proves that artificially created egg cells could be a viable source for embryonic stem cells, they noted, then this would remove the necessity of starting a new embryonic stem cell line with the destruction of a blastocyst. Thus, the controversy over donating human egg cells and blastocysts could potentially be resolved, though a blastocyst would still be required to start each cycle. The online edition of Nature Medicine published a study on January 23, 2005 which stated that the human embryonic stem cells available for federally funded research are contaminated with nonhuman molecules from the culture medium used to grow the cells, for example, mouse cells and other animal cells. The nonhuman cell-surface sialic acid can compromise the potential uses of the embryonic stem cells in humans, according to scientists at the University of California, San Diego[http://www.nature.com/nm/journal/vaop/ncurrent/pdf/nm1181.pdf]. A study was published in the online edition of Lancet Medical Journal on March 8, 2005 that detailed information about a new stem-cell line which was derived from human embryos under completely cell- and serum-free conditions. This event is significant because exposure of existing human embryonic stem-cell lines to live animal cells and serum risks contamination with pathogens that could lead to human health risks. After more than 6 months of undifferentiated proliferation, these cells retained the potential to form derivatives of all three embryonic germ layers both in vitro and in teratomas. These properties were also successfully maintained (for more than 30 passages) with the established stem-cell lines. [http://www.thelancet.com/journals/lancet/article/PIIS0140673605664732/fulltext (Lancet Medical Journal)]

Treatments

Current treatments

For over 30 years, bone marrow (adult) stem cells have been used to treat cancer patients with conditions such as leukemia and lymphoma. During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents not only kill the leukemia or neoplastic cells, but also those which release the stem cells from the bone-marrow. These are therefore removed before chemotherapy, and are re-injected afterwards.

Potential treatments

Cancer

Research injecting neural (adult) stem cells into the brains of rats can be very successful in treating cancerous tumors. With traditional techniques brain cancer is almost impossible to treat because it spreads so rapidly. Researchers at the Harvard Medical School injected adult stem cells genetically engineered to convert a separately injected non-toxic substance into a cancer-killing agent. Within days the adult stem cells had migrated into the cancerous area and the injected substance was able to reduce tumor mass by 80 percent.

Stem cell injection restores ability to walk

A team of Korean researchers reported on November 25, 2004, that they had transplanted multipotent adult stem cells from umbilical cord blood to a patient suffering from a spinal cord injury and she can now walk on her own, without difficulty. The patient had not even been able stand up for the last 19 years. The team was co-headed by researchers at Chosun University, Seoul National University and the [http://www.seoulcord.co.kr/bin/main.asp Seoul Cord Blood Bank] (SCB). For the unprecedented clinical test, the scientists isolated adult stem cells from umbilical cord blood and then injected them into the damaged part of the spinal cord. Using stem cells, the tests were able to avoid triggering a negative bodily reaction, which are common in other transplantations, according to [http://www.histostem.co.kr/english/english_4.htm Hoon Han], one of the researchers. "We don’t need a strict match between cord blood stem cell type and the immune system of a patient because the latter accepts the former pretty well thanks to its immaturity," Han said. [http://times.hankooki.com/lpage/200411/kt2004112617575710440.htm] [http://www.cordblood.com/cord_blood_news/stem_cell_news/a_paralyzed.asp] [http://www.connected.telegraph.co.uk/news/main.jhtml?xml=/news/2004/11/30/wcells30.xml] [http://www.wpherald.com/storyview.php?StoryID=20041127-121143-6745r] The Korean researchers have followed up on their original work. The original treatment was conducted in November 2004. On April 18, 2005, the researchers announced that they will be conducting a second treatment on the woman. [http://times.hankooki.com/lpage/tech/200504/kt2005041818233411800.htm] The researchers have followed up with a case study write-up on their work. It is located in the journal [http://taylorandfrancis.metapress.com/(4ozazs45mhxqid20qghurzfi)/app/home/contribution.asp?referrer=parent&backto=issue,8,9;journal,2,41;linkingpublicationresults,1:107693,1 Cytotherapy]. [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16162459&query_hl=1]

Spinal cord injury

According to the October 7, 2005 issue of The Week, University of California researchers injected stem cells from aborted human fetuses into paralyzed mice, which resulted in the mice regaining the ability to move and walk four months later. The researchers discovered upon dissecting the mice that the stem cells regenerated not only the neurons, but also the cells of the myelin sheath, a layer of cells with which nerve fibers communicate with the brain (damage to which is often the cause of neurological injury in humans). [http://img227.imageshack.us/img227/7954/stemcellbreakthru052wl.jpg]

Blastocyst stem cells switched to neurons

In January 2005, researchers at the University of Wisconsin-Madison differentiated human blastocyst stem cells into neural stem cells, then into the beginnings of motor neurons, and finally into spinal motor neuron cells, the cell type that, in the human body, transmits messages from the brain to the spinal cord. The newly generated motor neurons exhibited electrical activity, the signature action of neurons. Lead researcher [http://www.waisman.wisc.edu/faculty/zhang.html Su-Chun Zhang] described the process as "you need to teach the blastocyst stem cells to change step by step, where each step has different conditions and a strict window of time." Transforming blastocyst stem cells into motor neurons had eluded researchers for decades. The next step will be to test if the newly generated neurons can communicate with other cells when transplanted into a living animal; the first test will be in chicken embryos. Su-Chun said their trial-and-error study helped them learn how motor neuron cells, which are key to the nervous system, develop in the first place. The new cells could be used to treat diseases like Lou Gehrig's disease, muscular dystrophy, and spinal cord injuries.

Muscle damage

Adult stem cells are also apparently able to repair muscle damaged after heart attacks. Heart attacks are due to the coronary artery being blocked, starving tissue of oxygen and nutrients. Days after the attack is over, the cells try to remodel themselves in order to become able to pump harder. However, because of the decreased blood flow this attempt is futile and results in even more muscle cells weakening and dying. Researchers at Columbia-Presbyterian found that injecting bone-marrow stem cells, a form of adult stem cells, into mice which had had heart attacks induced resulted in an improvement of 33 percent in the functioning of the heart. The damaged tissue had regrown by 68 percent.

Heart damage

Using the patient's own bone marrow derived stem cells, Dr. [http://www.ctsnet.org/home/anpatel Amit Patel] at the University of Pittsburgh, [http://www.mirm.pitt.edu McGowan Institute of Regenerative Medicine] has shown a dramatic increase in ejection fraction for patients with congestive heart failure. He works with many other countries such as Argentina, Uruguay, Ecuador, Greece, Japan, and Thailand where he has taught minimally invasive techniques for the treatment of non-ischemic (idiopathic) and ischemic heart failure. The treatment has been

Low blood supply

In December 2004, a team of researchers led by Dr. Luc Douay at the University of Paris developed a method to produce large numbers of red blood cells. The Nature Biotechnology paper, entitled [http://www.nature.com/nbt/journal/v23/n1/abs/nbt1047.html Ex vivo generation of fully mature human red blood cells], describes the process: precursor red blood cells, called hematopoietic stem cells, are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red blood cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells. Further research into this technique will have potential benefits to gene therapy, blood transfusion, and topical medicine.

Baldness

Hair follicles also contain stem cells, and some researchers predict research on these follicle stem cells may lead to successes in treating baldness through "hair multiplication," also known as "hair cloning," as early as 2007. This treatment is expected to work through taking stem cells from existing follicles, multiplying them in cultures, and implanting the new follicles into the scalp. Later treatments may be able to simply signal follicle stem cells to give off chemical signals to nearby follicle cells which have shrunk during the aging process, which in turn respond to these signales by regenerating and once again making healthy hair. [http://my.webmd.com/content/article/96/103836.htm?z=3734_00000_1000_qd_01 Hair Cloning Nears Reality as Baldness Cure] (WebMD Nov. 2004)

Missing teeth

In 2004, scientists at King's College discovered a way to cultivate a complete tooth in mice [http://www.telegraph.co.uk/connected/main.jhtml?view=DETAILS&grid=P8&targetRule=10&xml=%2Fconnected%2F2004%2F02%2F17%2Fecntee15.xml] and were able to grow them stand-alone in the laboratory. Researchers are confident that this technology can be used to grow live teeth in human patients. In theory, a small ball of adult stem cells implanted in the gums will give rise to the tooth, which is expected to take two months to grow. It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth. Its estimated that it may take until 2009 before the technology is widely available to the general public, but the genetic research scientist behind the technique, Professor Paul Sharpe of King's College, estimates the method could be ready to test on patients by 2007 [http://www.sciencedaily.com/releases/2004/05/040504063535.htm]. His startup company, Odontis, fully expects to offer tooth replacement therapy by the end of the decade.

Blindness

Since 2003, researchers have successfully transplanted corneal and limbal stem cells into damaged eyes to restore vision. Using cultured stems cells from aborted fetuses, scientists are able to grow a thin sheet of totipotent stem cells in the laboratory. When these sheets are transplanted over the eye, the stem cells stimulate renewed repair, eventually restoring vision [http://www.medicalnewstoday.com/medicalnews.php?newsid=15535]. The latest development was in June of 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Dr. Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing [http://news.bbc.co.uk/1/hi/england/southern_counties/4495419.stm]. As more research yields increasingly precise techniques, stem cell transplantation to restore vision may become viable on a large scale. However, the success rate of the procedure is still low, from 20 to 70 percent [http://www.theuniversityhospital.com/healthlink/archives/articles/limbalstem.html], and further clinical research is intensely required before any credible claim can be made.

Embryonic stem cell ethical debate

The controversy over stem cell research arises from how they are created. Some are the by-product of in-vitro fertilization attempts by couples trying to have children. Unused ones, rather than being discarded, are harvested. Others are deliberately created specifically for this research.

Blastocysts

in-vitro fertilization] A blastocyst is a stage of development of an embryo when it is around six days old and made up of about 120 cells. A blastocyst at the stage at which embryonic stem cells would be extracted is still young enough to be able to divide into two embryos, making identical twins, or in rare cases, merge with another blastocyst, even one of the opposite sex[1], to create a chimera, an individual comprised of populations of cells with two different sets of DNA. From the biological point of view, these points mean the blastocyst is not yet an individual. Blastocysts are an early developmental stage far from possessing a nervous system (or any other organs), and thus biologically speaking do not have feelings. This view raises other issues, as the blastocysts involved in the research are left over from in vitro fertility therapy, and when not used in additional therapy or in embryonic stem cell research are destroyed or frozen indefinitely by the thousands[http://www.time.com/time/magazine/article/0,9171,1101040531-641157,00.html]. To some, this does not address the concern that using doomed blastocysts in embryonic stem cell research is viewed as instrumentalizing a developing human being. In the U.S., the leaders of many Christian groups (such as Catholics, Eastern Orthodox and Fundamentalists) as well as other unaffiliated and non-religious groups, believe that a human blastocyst is a human being, with the according human rights, and therefore oppose embryonic stem cell research because the start of each cell line involves the destruction of a blastocyst. Catholics view embryonic stem cell research - not adult stem cell research though - as intrinsically evil and never to be supported since it requires the death of an innocent human life created by God. Others do not view a blastocyst as a human being, and may instead see opposition of stem cell research as unfounded due to the suffering that new medical technologies could prevent. Many Jews,Hindus, Muslims, Humanists, Mormons, and Unitarian Universalists, liberal members of the Church of Christ, as well as a significant number of mainstream Christians are supportive of embryonic stem cell research. Another area in embryonic stem cells that can be of ethical concern is the use of therapeutic cloning. This involves using a blastocyst cloned from the patient so that the resulting stem cells are a genetic match. Some see this as being in a category of unnaturalness shared with reproductive human cloning, in which cloned blastocysts would be allowed to grow into embryos and eventually infants. [http://news.bbc.co.uk/2/hi/health/4245267.stm]

Policy debate in the U.S.

Origins of debate

In 1995, Congress passed the Dickey Amendment, prohibiting federal funding of research that involves the use of a human embryo. Privately funded research led to the breakthrough that made embryonic stem cell research possible in 1998, prompting the Clinton Administration to develop federal regulations for its funding. Preparations for this funding were completed in 2001. President George W. Bush announced, on August 9, 2001 that federal funds could be used to support research on the newly developed field of human embryonic stem cells, but that funding would be limited to "existing (embryonic) stem cell lines where the 'life-and-death decision' has already been made" [http://www.whitehouse.gov/news/releases/2001/08/20010809-2.html]. This limitation does not apply to research involving stem cells from other sources, such as umbilical cord blood, placentas, and adult and animal tissues. Some conservative religious groups felt the restrictions should have been stronger, while some scientists felt frustrated with the restrictions. In 2002, President Bush appointed the Council on Bioethics, an advisory group composed of 18 doctors, legal and ethical scholars, scientists and a journalist [http://www.bioethics.gov/about/whpress.html]. In February 2004, Bush removed from the council two advocates of embryonic stem cell research, professor of ethics William May and biologist Elizabeth Blackburn [http://www.washingtonpost.com/ac2/wp-dyn?pagename=article&contentId=A13606-2004Feb27¬Found=true]. In their place, he appointed pediatric neurosurgeon Dr. Benjamin Carson, political scientist Dr. Diana Schaub, and professor of government Dr. Peter Lawler, all of whom have a more cautious point of view toward embryonic stem cell research. All of the Council members support adult stem cell research. Some scientists are concerned that embryonic stem cell research has become a politicized issue instead of a scientific issue in the national mindset, and feel that the politicization distorts representation of the scientific issues.

Private funding

The Bush administration's decision does not prohibit private embryonic stem cell research. Pharmaceutical companies and biotechnology companies initially expressed little interest because they consider therapies based on cells, which might have to be tailored to each patient, to be less profitable than one-size-fits-all drugs. However, there are start-up biotechs entering the field. They include StemCells Inc. and Aastrom Biosciences. Others are reluctant to enter the market because they fear government restrictions preventing them from capitalizing on the research. However, private research groups (such as pharmaceutical and biotechnology companies) are now financing individual medical treatments, including all of those mentioned in this article.

Congressional response

In April 2004, 206 members of Congress, including many moderate Republicans, signed a letter urging President Bush to expand federal funding of embryonic stem cell research beyond what Bush had already supported. In May 2005, the House of Representatives voted 238-194 to loosen the limitations on embryonic stem-cell research — by allowing surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donors — despite Bush's promise to veto the bill if passed. [http://www.wired.com/news/medtech/0,1286,67627,00.html] Similar measures are pending in the Senate. On July 29, 2005, Senate Majority Leader William H. Frist (R-TN), announced that he too favored loosening restrictions on federal funding of embryonic stem-cell research, making passage of an embryonic stem-cell funding bill in the Senate more likely. [http://www.washingtonpost.com/wp-dyn/content/article/2005/07/29/AR2005072900158.html]

Polls regarding embryonic stem cell research

Republican voters are divided on embryonic stem cell research, according to a survey of 800 conducted by pollster David Winston, who also conducts surveys for the Republican leadership in the House and Senate. 25% of Republicans said they wanted no government funding of the research, 33% favored the limited funding Bush offers, and 36% wanted expanded funding to cover research on leftover embryos at fertility clinics. The Winston poll was sponsored by a group of centrist Republicans, The Republican Main Street Partnership.[http://www.centredaily.com/mld/centredaily/news/politics/11608151.htm][http://www.medicalnewstoday.com/medicalnews.php?newsid=24197][http://www.txamr.org/poll042405.htm] A June 2004 poll conducted by Opinion Research Corp. on behalf of the Civil Society Institute found that three-quarters of 1,017 adults respondents--including 6 in 10 conservatives--supported former First Lady Nancy Reagan's call for fewer restrictions on the research. Therapeutic cloning was supported by 59% of respondents in a July 2005 poll of 1,000 adults. Remaining a world leader in medical research was considered important by 95% of respondents. The poll was conducted by Research!America and sponsored by a non-profit organization composed of universities, patient groups and biotech and pharmaceutical companies. [http://www.washtimes.com/upi/20050707-020433-9429r.htm]

Emerging U.S. state-by-state approach

California voters in November 2004 approved Proposition 71, creating a US$3 billion state taxpayer-funded institute for stem cell research, the California Institute for Regenerative Medicine. Providing $300 million a year, the institute is thought to be the world's largest single backer of research in stem cells, and is expected to substantially increase the pace of embryonic stem cell research. Several states, in some cases wary of a national migration of biotech researchers to California [http://www.chron.com/cs/CDA/ssistory.mpl/nation/3201670], have shown interest in providing their own funding support of embryonic and adult stem cell research. These states include Connecticut [http://wireservice.wired.com/wired/story.asp?section=Breaking&storyId=1042210&tw=wn_wire_story], Florida, Illinois, Massachusetts [http://wireservice.wired.com/wired/story.asp?section=RelatedStories&pitem=AP%2DMassachusetts+Stem+Cells&rev=20050531&pub_tag=APONLINE&relatedTo=1042210&from=relatedstory&rsNum=1], New Hampshire, New Jersey, New York, Pennsylvania, Texas [http://www.dallasnews.com/sharedcontent/dws/news/city/irving/stories/010705dnmetscienceaward.6f9a4.html][http://www.chron.com/cs/CDA/ssistory.mpl/metropolitan/3014287], Washington, and Wisconsin. Other states have, or have shown interest in, additional restrictions or even complete bans on embryonic stem cell research. These states include Arkansas, Iowa, Kansas, Louisiana, Michigan, Missouri, Nebraska, North Dakota, South Dakota, and Virginia. ([http://www.usatoday.com/news/nation/2004-12-16-stem-cells-usat_x.htm States play catch-up on stem cells], USA Today, December 2004)

Policy debate outside the U.S.

Due to the controversy surrounding embryonic stem cells, many nations around the world have passed legislation regulating research. In the United Kingdom, the law states that a license may be issued to enable embryos to be created or used for research for the following purposes: # promoting advances in the treatment of infertility, # increasing knowledge about the causes of congenital disease, # increasing knowledge about the causes of miscarriages, # developing more effective techniques of contraception, or # developing methods for detecting the presence of gene or chromosome abnormalities in embryos before implantation, # increasing knowledge about the development of embryos; # increasing knowledge about serious disease, or # enabling any such knowledge to be applied in developing treatments for serious disease. :(Human Fertilisation and Embryology Act 1990 as amended by the Human Fertilisation and Embryology (Research Purposes) Regulations 2001). As a result of the federal funding restrictions imposed by Congress in the United States, South Korea and other countries lead the U.S. in the area of embryonic stem cell research. The UK created the world's first embryonic stem cell bank in May 2004. Because other countries have moved forward with their embryonic stem cell research programs, some in the U.S. have questioned the practicality of the Congressional funding restrictions. The nations conducting research programs on stem cell research include: [http://www.biomedcentral.com/news/20050125/01/] the UK, South Korea, China, Australia, Israel, Singapore, Argentina, Uruguay, and Sweden. European nations that permit stem cell research also include Switzerland, Finland, Greece and the Netherlands. The UK allows the creation of human embryos for stem cell procurement. Countries with regulations allowing cloning for medical research include the UK, Belgium, Singapore and Japan. Recently Brazil has approved a law allowing the use of stem cells in research. See also:
- [http://www.mbbnet.umn.edu/scmap.html World Stem Cell Policy Map]
- [http://www.mbbnet.umn.edu/scmap/scresearchmap.html World map of stem cell research centers]

External links

Ethics

- [http://www.ethicsweb.ca/papers/BioScan-cm.pdf Stem cells: a pluripotent challenge] - Chris MacDonald, Ph.D., an ethicist at Dalhousie University's Department of Bioethics.
- [http://www.illinoisrighttolife.org/Issues.htm#StemCell Illinois Right to Life: Stem Cell Research]

Epigenetics

- [http://www.epigenome-noe.net/ Epigenome Network of Excellence]

Guides

- [http://www.newdrugs.com/Stem_Cell_Research.htm Stem Cell Research: From Start To Infinite Possibility] 70 Pages Detailing Stem Cell Research
- [http://www.stemcellresearchfoundation.org/ Stem Cell Research Foundation: The Promise of Stem Cells in Medical Research]
- [http://www.adultstemcells.info Information on Adult Stem Cells] N. Stute, M.D.
- PNAS supplement: [http://www.pnas.org/content/vol100/suppl_1/ "Regenerative medicine"].
- [http://www.fas.org/spp/civil/crs/RL31015.pdf Johnson, Judith A. & Erin Williams, Stem Cell Research] Congressional Research Service, The Library of Congress, Order Code RL31015, (13 August 2004).
- [http://my.webmd.com/content/pages/5/1728_86999?z=1626_00000_5022_pe_02 WebMd's Stem Cells Q & A].
- [http://www.zoolgi.com Zoolgi - Stem Cell Therapy Map].
- [http://www.genomenewsnetwork.org/resources/policiesandplayers/ Stem Cells: Policies and Players].
- [http://nakedscientists.com/HTML/Columnists/katarneycolumn3.htm Turning your Brain into Blood — How stem cells work].
- [http://www.answersingenesis.org/tj/v15/i3/stem_cells.asp Stem cells and Genesis] (Christian perspective, includes definitions, opposes ESCR, list of adult stem cell successes).
- [http://www.cord-blood.org Cord-Blood.org Information on cord blood banking].
- [http://www.parentsguidecordblood.com General information on Umbilical cord blood banking].
- [http://www.stemcellresearch.org Do No Harm Web site]
- [http://gslc.genetics.utah.edu/units/stemcells/whatissc/ What is a Stem Cell?] - A cartoon tour from University of Utah
- [http://usliberals.about.com/od/stemcellresearch/i/StemCell1.htm About.com Pros & Cons of Embryonic Stem Cell Research]
- http://www.stemcells.nih.gov/index.aspNational Institutes of Health Guide

News

- [http://www.biologynews.net/archives/stem_cell_research/ Stem cell Research - Biology News Net].
- [http://www.newdrugs.com/stemcells/ Stem Cell Research Blog - updated daily with latest stem cell news].
- [http://www.whatsnextnetwork.com/health/index.php?cat=60 Latest Advances In Stem Cell Research].
- [http://www.newscientist.com/hottopics/cloning/cloning.jsp New Scientist's list of stem-cell and cloning related articles it has covered].
- [http://www.HavenWorks.com/health/stem-cell Stem Cell News].
- [http://www.celltherapy.co.uk Latest cell therapy progress].
- [http://nakedscientists.com/HTML/Columnists/chrissmithcolumn2.htm A new way to grow stem cells outside the body].
- [http://www.napoli.msnbc.com/id/3077125/ Human hearts repaired using patient's own stem cells (Reuters' article)].
- [http://abcnews.go.com/Business/Technology/story?id=273177&page=1 Stem-Cell Industry, Research Evolving] (Nov. 23 2004, ABC News).
- [http://times.hankooki.com/lpage/200411/kt2004112617575710440.htm Tae-gyu, Kim, Korean Scientists Succeed in Stem Cell Therapy], Korea Times (26 November 2004).
- [http://www.wpherald.com/storyview.php?StoryID=20041127-121143-6745r Umbilical Cord Blood Used to Treat Paralysis], United Press International (27 November 2004).
- [http://www.cordblood.com/cord_blood_news/stem_cell_news/a_paralyzed.asp Paralyzed Woman Walks Again After Stem Cell Therapy], Agence France Presse (28 November 2004).
- [http://www.msnbc.msn.com/id/5832265 New jaw bone grown in man's back muscle] using stem cells in his bone marrow, MSNBC (26 August 2004).
- [http://www.connected.telegraph.co.uk/news/main.jhtml?xml=/news/2004/11/30/wcells30.xml Highfield, Roger, Umbilical cord cells "allow paralysed woman to walk"], London Telegraph (30 November 2004).
- [http://www.thelancet.com/journal/vol365/iss9463/abs/llan.365.9463.early_online_publication.32515.1 Human embryonic stem cells derived without feeder cells (Lancet Medical Journal)].
- [http://health.dailynewscentral.com/content/view/0001354/31//stem_cell_cure_heart_attack.html Stem Cell Study May Point To Cure For Heart Attacks] health.dailynewscentral.com (26 July 2005).
- [http://www.voanews.com/english/2005-08-22-voa40.cfm Scientists Change Adult Cells Back to Embryonic Stem Cells] Voice of America (22 August 2005).
- [http://www.boston.com/news/science/stemcell/ The Stem Cell Debate] - The Boston Globe

References

# National Institutes of Health, "[http://stemcells.nih.gov/info/basics/basics6.asp Stem Cell Basics]," July 19, 2004. # National Institutes of Health, [http://stemcells.nih.gov/info/faqs.asp Stem Cell FAQ], April 13, 2005. # Graham, Judith and Schodolski, Vincent J., "[http://www.resultsforamerica.org/calendar/files/Son%20of%20former%20President%20Reagan%20enters%20the%20fray%20with%20a%20speech%20at%20the.pdf Son of former President Reagan] enters the fray with a speech at the Democratic convention." Chicago Tribune, July 27, 2004. # Wild8754au, Gabriel, "Conservatives echoed Drudge's doctored quotation of Edwards on stem cell research." Media Matters for America, October 13, 2004. # Kang KS, Kim SW, Oh YH, Yu JW, Kim KY, Park HK, Song CH, Han H. "A 37-year-old spinal cord-injured female patient, transplanted of multipotent stem cells from human UC blood, with improved sensory perception and mobility, both functionally and morphologically: a case study." Cytotherapy 2005;7(4):368-73. Category:Cell biology Category:Developmental biology Category:Cloning Category:Issue in the Culture Wars ko:줄기 세포 ja:幹細胞

Gastrulation

.]] Gastrulation is a phase early in the development of animal embryos, during which the morphology of the embryo is dramatically restructured by cell migration. Gastrulation varies in different phyla; the following description concerns the gastrulation of the echinoderms, representative of the triploblasts, or animals with three embryonic germ layers. At the beginning of gastrulation, the embryo is hollow ball of cells, with an animal pole and a vegetal pole. The vegetal pole begins to flatten and then invaginates into the interior, replacing the blastocoelic cavity and thereby forming a new cavity, the archenteron (literally: primitive gut). Some of the cells of the vegetal pole detach and become mesenchyme cells. The mesenchyme cells divide rapidly, migrate to different parts of the blastocoel, and form filopodia, strands that help to pull the tip of the archenteron towards the animal pole. Once the archenteron reaches the animal pole, a perforation forms, and the archenteron becomes a digestive tract passing all the way through the embryo. The three embryonic germ layers have now formed. The endoderm, consisting of the archenteron, will develop into the digestive tract. The ectoderm, consisting of the cells on the outside of the gastrula that played little part in gastrulation, will develop into the skin and the central nervous system. The mesoderm, consisting of the mesenchyme cells that have proliferated in the blastocoel, will become all the other internal organs. Gastrulation is followed by the organogenesis, during which the individual organ anlagen of the embryo are set up within the newly formed germ layers. Part of the organogenesis is the Neurulation. Category:Developmental biology

Organ (anatomy)

In biology, an organ (Latin: organum, "instrument, tool") is a group of tissues, which perform a specific function or group of functions. Common animal organs include the heart, lungs, brain, eye, stomach, spleen, pancreas, kidneys, liver, intestines, skin, uterus, bladder, bone, etc. A group of related organs is an organ system. Organelles are analogous sub-cellular structures.

Organ systems

Organ system – a system composed of organs working together to carry out a function.
- Circulatory system
- Digestive system
- Endocrine system
- Immune system
- Integumentary system
- Lymphatic system
- Muscular system
- Nervous system
- Reproductive system
- Respiratory system
- Skeletal system
- Urinary system Category:Anatomy
- ko:기관 (생물) ja:器官

Alan Turing

Alan Mathison Turing (June 23, 1912 – June 7, 1954) was a British mathematician, logician, and cryptographer. Turing is often considered to be a father of modern computer science. With the Turing Test, he made a significant and characteristically provocative contribution to the debate regarding artificial intelligence: whether it will ever be possible to say that a machine is conscious and can think. He provided an influential formalisation of the concept of algorithm and computation with the Turing machine, formulating the now widely accepted "Turing" version of the Church-Turing thesis, namely that any practical computing model has either the equivalent or a subset of the capabilities of a Turing machine. During World War II, Turing worked at Bletchley Park, Britain's codebreaking centre and was for a time head of Hut 8, the section responsible for German Naval cryptanalysis. He devised a number of techniques for breaking German ciphers, including the method of the bombe, an electromechanical machine which could find settings for the Enigma machine. After the war, he worked at the National Physical Laboratory, creating one of the first designs for a stored program computer, although it was never actually built. In 1947 he moved to the University of Manchester to work, largely on software, on the Manchester Mark I then emerging as one of the world's earliest true computers. In 1952, Turing was convicted of acts of gross indecency after admitting having a sexual relationship with a man in Manchester. He was placed on probation and required to undergo hormone therapy. Turing died in 1954; the inquest found that he had committed suicide by eating an apple laced with cyanide.

Childhood and youth

Turing was conceived in 1911 in Chatrapur, India. His father, Julius Mathison Turing, was a member of the Indian civil service. Julius and wife Ethel (née Stoney) wanted Alan to be brought up in Britain, so they returned to Paddington, London. His father's civil service commission was still active, and during Turing's childhood years his parents travelled between Guildford, England and India, leaving their two sons to stay with friends in England, rather than risk their health in the British colony. Very early in life, Turing showed signs of the genius he was to display more prominently later. He is said to have taught himself to read in three weeks, and to have shown an early affinity for numbers and puzzles. His parents enrolled him at St. Michael's, a day school, at six years of age. The headmistress recognized his genius early on, as did many of his subsequent educators. In 1926, at the age of 14, he went on to Sherborne School in Dorset. His first day of term coincided with a general strike in England, and so determined was he to attend his first day that he rode his bike unaccompanied over sixty miles from Southampton to school, stopping overnight at an inn — a feat reported in the local press. Turing's natural inclination toward mathematics and science did not earn him respect with the teachers at Sherborne, a famous and expensive public school (a British private school with charitable status), whose definition of education placed more emphasis on the classics. His headmaster wrote to his parents: "I hope he will not fall between two schools. If he is to stay at Public School, he must aim at becoming educated. If he is to be solely a Scientific Specialist, he is wasting his time at a Public School," (, p26). But despite this, Turing continued to show remarkable ability in the studies he loved, solving advanced problems in 1927 without having even studied elementary calculus. In 1928, aged sixteen, Turing encountered Albert Einstein's work; not only did he grasp it, but he extrapolated Einstein's questioning of Newton's laws of motion from a text in which this was never made explicit. Newton's laws of motion Turing's hopes and ambitions at school were raised by his strong feelings for his friend Christopher Morcom, with whom he fell in love, though the feeling was not reciprocated. Morcom died only a few weeks into their last term at Sherborne, from complications of bovine tuberculosis, contracted after drinking infected cow's milk as a boy. Turing was heart-broken.

College and his work on computability

Due to his unwillingness to work as hard on his classical studies as on science and mathematics, Turing failed to win a scholarship to Trinity College, Cambridge, and went on to the college of his second choice, King's College, Cambridge. He was an undergraduate from 1931 to 1934, graduating with a distinguished degree, and in 1935 was elected a Fellow at King's on the strength of a dissertation on the Gaussian error function. error function In his momentous paper "On Computable Numbers, with an Application to the Entscheidungsproblem" (submitted on May 28, 1936), Turing reformulated Kurt Gödel's 1931 results on the limits of proof and computation, substituting Gödel's universal arithmetics-based formal language by what are now called Turing machines, formal and simple devices. He proved that such a machine would be capable of performing any conceivable mathematical problem if it were representable as an algorithm, even if no actual Turing machine would be likely to have practical applications, being much slower than alternatives. Turing machines are to this day the central object of study in theory of computation. He went on to prove that there was no solution to the Entscheidungsproblem by first showing that the halting problem for Turing machines is uncomputable: it is not possible to algorithmically decide whether a given Turing machine will ever halt. While his proof was published subsequent to Alonzo Church's equivalent proof in respect to his lambda calculus, Turing's work is considerably more accessible and intuitive. It was also novel in its notion of a "Universal (Turing) Machine," the idea that such a machine could perform the tasks of any other machine. The paper also introduces the notion of definable numbers. Most of 1937 and 1938 he spent at Princeton University, studying under Alonzo Church. In 1938 he obtained his Ph.D. from Princeton; his dissertation introduced the notion of hypercomputation where Turing machines are augmented with so-called oracles, allowing a study of problems that cannot be solved algorithmically. Back in Cambridge in 1939, he attended lectures by Ludwig Wittgenstein about the foundations of mathematics. The two argued and disagreed vehemently, with Turing defending formalism and Wittgenstein arguing that mathematics is overvalued and does not discover any absolute truths (Wittgenstein 1932/1976).

Cryptanalysis

foundations of mathematics During World War II, Turing was a major participant in the efforts at Bletchley Park to break German ciphers. Turing's codebreaking work was kept secret until the 1970s; not even his close friends knew about it. He contributed several mathematical insights into breaking both the Enigma machine and the Lorenz SZ 40/42 (a teletype cipher attachment codenamed "Tunny" by the British), and was, for a time, head of Hut 8, the section responsible for reading German Naval signals. Lorenz SZ 40/42 until he moved to Hut 8.]] Since September 1938, Turing had been recruited to work part-time for the Government Code and Cypher School. Turing reported to Bletchley Park when war was declared in September 1939. To break Enigma, Turing devised an electromechanical machine which searched for the correct settings of the Enigma rotors. The machine was called the bombe, named after the Polish-designed bomba. Using a bombe, it was possible to ignore the effect of the Enigma plugboard and consider the settings of its rotors alone, and eliminate most of them from consideration. For each possible setting, a chain of logical deductions was implemented electrically, and it was possible to detect when a contradiction had occurred and rule out that setting. Turing's bombe was first installed on 18 March 1940, and, with an enhancement suggested by mathematician Gordon Welchman, was the primary tool used to read Enigma traffic. Over 200 bombes were in operation by the end of the war. In December 1940, Turing solved the naval Enigma indicator system, which was more complex than the indicator systems used by the other services. Turing also invented a Bayesian statistical technique termed "Banburismus" to assist in breaking Naval Enigma. Banburismus could rule out certain orders of the Enigma rotors, reducing time needed to test settings on the bombes. Against the Lorenz cipher, Turing devised a technique termed Turingismus or Turingery, although other methods were also used. In the spring of 1941, Turing proposed marriage to fellow Hut 8 co-worker Joan Clarke, although the engagement was broken off by mutual agreement in the summer. In late November 1942, Turing visited the US to work on secure speech devices and Naval Enigma, returning in March 1943. During his absence, Hugh Alexander had assumed the position of head of Hut 8, although Alexander had been de facto head for some time, Turing having little interest in the day-to-day running of the section. Turing became a general consultant for cryptanalysis at Bletchley Park. In the later part of the war, Turing undertook (assisted with engineer Donald Bayley) the design of a portable machine codenamed Delilah to allow secure voice communications, teaching himself electronics at the same time. Intended for different applications, Delilah lacked the ability to be used over long-distance radio transmissions, and Delilah was completed too late to be used in the war. While Turing demonstrated it to officials by encoding/decoding a recording of a Winston Churchill speech, it was not adopted for use.

Work on early computers and the Turing Test

Winston Churchill.]] From 1945 to 1947 he was at the National Physical Laboratory, where he worked on the design of ACE (Automatic Computing Engine). He presented a paper on February 19, 1946, which was the first complete design of a stored-program computer. Although he succeeded in designing the ACE, there were delays in starting the project and he became disillusioned. In late 1947 he returned to Cambridge for a 'sabbatical' year. While he was at Cambridge work on building the ACE stopped before it was ever begun. In 1949 he became deputy director of the computing laboratory at the University of Manchester, and worked on software for one of the earliest true computers — the Manchester Mark I. During this time he continued to do more abstract work, and in "Computing machinery and intelligence" (Mind, October 1950), Turing addressed the problem of artificial intelligence, and proposed an experiment now known as the Turing test, an attempt to define a standard for a machine to be called "sentient". In 1948, Turing, working with his former undergraduate colleague, D.G. Champernowne, began writing a chess program for a computer that did not yet exist. In 1952, lacking a computer powerful enough to execute the program, Turing played a game in which he simulated the computer, taking about half an hour per move. [http://www.chessgames.com/perl/chessgame?gid=1356927 The game] was recorded; the program lost to a colleague of Turing, Alick Glennie, however, it is said that the program won a game against Champernowne's wife.

Work on pattern formation and mathematical biology

Turing worked from 1952 until his death in 1954 on mathematical biology, specifically morphogenesis. He published one paper on the subject called "The Chemical Basis of Morphogenesis" in 1952. His central interest in the field was understanding Fibonacci phyllotaxis, the existence of Fibonacci numbers in plant structures. He used reaction-diffusion equations which are now central to the field of pattern formation. Later papers went unpublished until 1992 when Collected Works of A.M. Turing was published.

Prosecution for homosexuality and Turing's death

Turing was a homosexual man during a period when homosexuality was illegal. In 1952, his lover, Arnold Murray, helped an accomplice to break into Turing's house, and Turing went to the police to report the crime. As a result of the police investigation, Turing acknowledged a sexual relationship with Murray, and they were charged with gross indecency under Section 11 of the Criminal Law Amendment Act of 1885. Turing was unrepentant and was convicted. Although he could have been sent to prison, he was placed on probation, conditional on him undergoing hormonal treatment designed to reduce libido. He accepted the oestrogen hormone injections, which lasted for a year, with side effects including the development of breasts. His conviction led to a removal of his security clearance and prevented him from continuing consultancy for GCHQ on cryptographic matters. In 1954, he died of cyanide poisoning, apparently from a cyanide-laced apple he left half-eaten. The apple itself was never tested for contamination with cyanide, and cyanide poisoning as a cause of death was established by a post-mortem. Most believe that his death was intentional, and the death was ruled a suicide. It is rumoured that this method of self-poisoning was in tribute to Turing's beloved film Snow White and the Seven Dwarfs. His mother, however, strenuously argued that the ingestion was accidental due to his careless storage of laboratory chemicals. Friends of his have said that Turing may have killed himself in this ambiguous way quite deliberately, to give his mother some plausible deniability. The possibility of assassination has also been suggested, owing to Turing's involvement in the secret service and the perception of Turing as a security risk due to his homosexuality. In the book, Zeroes and Ones, author Sadie Plant speculates that the rainbow Apple logo with a bite taken out of it was a homage to Turing. This seems to be an urban legend as the Apple logo was designed in 1976, two years before Gilbert Baker's rainbow pride flag. :See also: Sodomy law, :Category:LGBT civil rights

Recognition

Since 1966, the Turing Award has given by the Association for Computing Machinery to a person for technical contributions to the computing community. It is widely considered to be the equivalent of the Nobel Prize in the computing world. In 1994 a stretch of the Manchester city ring road was named Alan Turing Way. On 23 June 1998, on what would have been Turing's 86th birthday, Andrew Hodges, his biographer, unveiled an official English Heritage Blue Plaque on his childhood home in Warrington Crescent, London, now the Colonnade hotel [http://www.turing.org.uk/bio/oration.html], [http://www.blueplaque.com/detail.php?plaque_id=348]. London A statue of Turing was unveiled in Manchester on June 23 2001. It is in Sackville Park, between the University of Manchester building on Whitworth Street and the Canal Street gay village. To mark the 50th anniversary of his death, a memorial plaque was unveiled at his former residence, Hollymeade, in Wilmslow on June 7 2004. 2004 The Alan Turing Institute was initiated by UMIST and University of Manchester in Summer 2004. A celebration of Turing's life and achievements was held at the University of Manchester on 5 June 2004; it was arranged by the British Logic Colloquium and the British Society for the History of Mathematics. On October 28 2004 a bronze statue of Alan Turing sculpted by John W. Mills was unveiled at the University of Surrey [http://portal.surrey.ac.uk/press/oct2004/281004a/]. The statue marks the 50th anniversary of Turing's death. It portrays Turing carrying his books across the campus. Holtsoft produces a programming language named for Turing. The language is designed for beginner programmers and has no direct access to the hardware.

Turing biographies

- Andrew Hodges wrote a definitive biography Alan Turing: The Enigma in 1983 (see references below).
- The play Breaking the Code by Hugh Whitemore is about the life and death of Turing. In the original West End and Broadway runs, the role of Turing was played by Derek Jacobi, who also played Turing in a 1995 television adaptation of the play.

Turing in fiction

- Turing appears as a character in Neal Stephenson's Cryptonomicon.
- In another one of Stephenson's books, The Diamond Age, there is a very good explanation of Turing's work put into the format of a child's book.
- "Turing Police" (Artificial Intelligence law enforcers) appear in William Gibson's Neuromancer.
- In White Wolf Game Studio's World of Darkness role-playing universe, Turing was a leading member of the mage faction known as the Virtual Adepts.
- An FBI agent named Alan Turing made an appearance in the webcomic Questionable Content as a homage to Turing.
- Appears in Enigma by Robert Harris
- A young Alan Turing introduces the title character to Gödel's first incompleteness theorem in Apostolos Doxiadis's novel Uncle Petros and Goldbach's Conjecture.
- In the 1989 Doctor Who serial The Curse of Fenric, the character of Dr. Judson is based on Turing. Turing himself is the narrator of the Doctor Who spin-off novel The Turing Test by Paul Leonard.
- Greg Egan's novella, [http://gregegan.customer.netspace.net.au/MISC/ORACLE/Oracle.html Oracle], is about an alternate universe version of Turing

References

- Copeland, B. Jack (2004) "Colossus: Its Origins and Originators". IEEE Annals of the History of Computing, 26(4):38–45.
- Copeland, B. Jack (editor, 2004) [http://www.oup.co.uk/isbn/0-19-825079-7 The Essential Turing]. Oxford University Press, ISBN 0-19-825079-7 (hardback) and ISBN 0-19-825080-0 (paperback).
- Copeland, B. Jack (editor, 2005), [http://www.oup.co.uk/isbn/0-19-856593-3 Alan Turing's Automatic Computing Engine]. Oxford University Press, ISBN 0-19-856593-3.
- Hodges, Andrew (1983/2000). Alan Turing: The Enigma. Simon & Schuster, 1983, ISBN 0-671-49207-1. Also: Walker Publishing Company, 2000.
- Christof Teuscher (editor 2004), Alan Turing: Life and Legacy of a Great Thinker. Springer-Verlag, ISBN 3540200207.
- Yates, David M. (1997) Turing's Legacy: A history of computing at the National Physical Laboratory 1945—1995. London: Science Museum, ISBN 0-901805-94-7.
- Ludwig Wittgenstein (1932/1976) Wittgenstein's Lectures on the Foundations of Mathematics (1932-1935). Edited by Cora Diamond. Cornell University Press.

External links

-
- [http://www.turing.org.uk/turing/ Alan Turing Home Page] by Andrew Hodges including a [http://www.turing.org.uk/bio/part1.html short biography]
- [http://www.alanturing.net/ AlanTuring.net Turing Archive for the History of Computing] by Jack Copeland
- [http://www.idsia.ch/~juergen/turing.html A short biography]
- [http://www.systemtoolbox.com/article.php?history_id=3 Alan Turing – Towards a Digital Mind: Part 1]
- [http://www.loebner.net/Prizef/TuringArticle.html Computing machinery and intelligence] — full text of article.
- [http://www.skyscraper.org.uk Skyscraper song inspired by Alan Turing]
- [http://www.5xm.com/turing/ Hollymeade unveiling of memorial plaque marking 50th anniversary of Turing's untimely death]
- [http://www.swintons.net/jonathan/turing.htm Alan Turing and morphogenesis]
- [http://www.turingarchive.org The Turing Archive]
- [http://www.teuscher.ch/turingday Turing Day 2002]
- [http://www.maths.man.ac.uk/logic/turing2004/ Turing 2004: A celebration of his life and achievements]
- [http://plato.stanford.edu/entries/turing/ Stanford Encyclopedia of Philosophy entry]
- [http://www.adeptis.ru/vinci/m_part1_2.html Photos] Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan Turing, Alan ko:앨런 튜링 ja:アラン・チューリング simple:Alan Turing th:แอลัน ทัวริง

DNA

:For other uses, see DNA (disambiguation). DNA (disambiguation) Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life (and most viruses). DNA is a long polymer of nucleotides and encodes the sequence of the amino acid residues in proteins using the genetic code, a triplet code of nucleotides. In complex cells (eukaryotes), such as those from plants, animals, fungi and protists, most of the DNA is located in the cell nucleus. By contrast, in simpler cells called prokaryotes (the eubacteria and archaea), DNA is not separated from the cytoplasm by a nuclear envelope. The cellular organelles known as chloroplasts and mitochondria also carry DNA. DNA is often referred to as the molecule of heredity as it is responsible for the genetic propagation of most inherited traits. These traits can range from hair colour to disease susceptibility. During cell division, DNA is replicated and can be transmitted to offspring during reproduction. Lineage studies can be done based on the facts that the DNA in mitochondria (mitochondrial DNA) only comes from the mother, and the male "Y" chromosome only comes from the father. Every person's DNA, their genome, is inherited from both parents. The mother's mitochondrial DNA together with twenty-three chromosomes from each parent combine to form the genome of a fertilized egg. As a result, with certain exceptions such as red blood cells, most human cells contain 23 pairs of chromosomes, together with mitochondrial DNA inherited from the mother.

DNA Overview

red blood cell This section presents an introductory and therefore incomplete overview of DNA.
- Genes can be loosely viewed as the organism's "cookbook" or "blueprint";
- A strand of DNA contains genes, areas that regulate genes, and areas that either have no function, or a function we do not (yet) know (also see last bullet point in this section for the difference between DNA and RNA);
- DNA is organized as two complementary strands, head-to-toe, with bonds between them that can be "unzipped" like a zipper, separating the strands;
- DNA is a chain of chemical "building blocks", called "bases", of which there are four types: these can be abbreviated A, T, C, and G. Each base can only "pair up" with one single predetermined other base: A+T, T+A, C+G and G+C are the only possible combinations; that is, an "A" on one strand of double-stranded DNA will "mate" properly only with a "T" on the other, complementary strand;
- N.B.: U occasionally replaces T, notably in PBS1 phage DNA; you can thus substitute "U" for "T" throughout this section.
- Because each strand of DNA has a directionality, the sequence order does matter: A+T is not the same as T+A, just as C+G is not the same as G+C;
- For each given base, there is just one possible complementary base, so naming the bases on the conventionally chosen side of the strand is enough to describe the entire double-strand sequence;
- The genetic information contained in a strand of DNA is determined by the sequence of bases along its length;
- The cell begins DNA replication by forcibly unzipping the DNA double strand down the middle, and then recreates the "other half" of each new single strand by drowning each half in a "soup" made of the four bases. An enzyme makes a new strand by finding the correct "base" in the soup and pairing it with the original strand. In this way, the base on the old strand dictates which base will be on the new strand, and the cell ends up with an extra copy of its DNA.
- Mutations are simply chemical imperfections in this process: a base is accidentally skipped, inserted, or incorrectly copied, or the chain is trimmed, or added to; many basic mutations can be described as combinations of these accidental "operations". Mutations can also occur through chemical damage (through mutagens), light (UV damage), or through other more complicated gene swapping events.
- DNA (for DeoxyriboNucleic Acid) differs from RNA (for RiboNucleic Acid) by having the sugar 2-deoxyribose instead of ribose in its backbone (ribose contains one extra oxygen atom compared to deoxyribose -- in other words, DNA contains deoxygenated ribose, whereas RNA contains "plain" ribose.) This is the basic chemical distinction between RNA and DNA.

DNA in practice

DNA in crime

Forensic scientists can use DNA located in blood, semen, skin, saliva, or hair left at the scene of a crime to identify a possible suspect, a process called genetic fingerprinting or DNA profiling. In DNA profiling the relative lengths of sections of repetitive DNA, such as short tandem repeats and minisatellites, are compared. DNA profiling was developed in 1984 by English geneticist Alec Jeffreys, and was first used in 1986 in the Enderby murders case in Leicestershire, England. Many jurisdictions require convicts of certain types of crimes to provide a sample of DNA for inclusion in a computerized database. This has helped investigators solve old cases where the perpetrator was unknown and only a DNA sample was obtained from the scene (particularly in rape cases between strangers). This method is one of the most reliable techniques for identifying a criminal, but is not always perfect, for example if no DNA can be retrieved, or if the scene is contaminated with the DNA of several possible suspects.

DNA in computation

Despite its biological origins, DNA plays an important role in computer science, both as a motivating research problem and as a method of computation in itself, called DNA computing. As a simple example, research on string searching algorithms, which find an occurrence of a sequence of letters inside a larger sequence of letters, was motivated by DNA research, where it is used to find specific sequences of nucleotides in a large sequence. In other applications like text editors, even simple algorithms for this problem usually suffice, but DNA sequences cause these algorithms to exhibit near-worst-case behavior due to their small number of distinct characters. Databases have also been strongly motivated by DNA research, which requires special tools for storing and manipulating DNA sequences. Databases specialized for this purpose are called genomic databases, and have a number of unique technical challenges associated with the operations of approximate matching, sequence comparison, finding repeating patterns, and homology searching. In 1994, Leonard Adleman of the University of Southern California made headlines when he discovered a way of solving the directed Hamiltonian path problem, an NP-complete problem, using tools from molecular biology, in particular DNA. The new approach, dubbed DNA computing, has practical advantages over traditional computers in power use, space use, and efficiency, due to its ability to highly parallelize the computation (see parallel computing)(there is labor worth mention involved in retrieving answers computed these computational DNA techniques.). A number of other problems, including simulation of various abstract machines, the boolean satisfiability problem, and the bounded version of the Post correspondence problem, have since been analyzed using DNA computing. Due to its compactness, DNA also has an important role in cryptography, where in particular it allows unbreakable one-time pads to be efficiently constructed and used.[http://citeseer.ist.psu.edu/gehani99dnabased.html]

Overview of molecular structure

one-time pad Although sometimes called "the molecule of heredity", pieces of DNA as people typically think of them are not single molecules. Rather, they are pairs of molecules, which entwine like vines to form a double helix (see the illustration at the right). Each vine-like molecule is a strand of DNA: a chemically linked chain of nucleotides, each of which consists of a sugar, a phosphate and one of five kinds of nucleobases ("bases"). Because DNA strands are composed of these nucleotide subunits, they are polymers. The diversity of the bases means that there are five kinds of nucleotides, which are commonly referred to by the identity of their bases. These are adenine (A), thymine (T), uracil (U), cytosine (C), and guanine (G). U is rarely found in DNA except as a result of chemical degradation of C, but in some viruses, notably PBS1 phage DNA, U completely replaces the usual T in its DNA. Similarly, RNA usually contains U in place of T, but in certain RNAs such as transfer RNA, T is always found in some positions. Thus, the only true difference between DNA and RNA is the sugar, 2-deoxyribose in DNA and ribose in RNA. In a DNA double helix, two polynucleotide strands can associate through the hydrophobic effect and pi stacking. Specificity of which strands stay associated is determined by complementary pairing. Each base forms hydrogen bonds readily to only one other -- A to T and C to G -- so that the identity of the base on one strand dictates the strength of the association; the more complementary bases exist, the stronger and longer-lasting the association. The cell's machinery is capable of melting or disassociating a DNA double helix, and using each DNA strand as a template for synthesizing a new strand which is nearly identical to the previous strand. Errors that occur in the synthesis are known as mutations. The process known as PCR (polymerase chain reaction) mimics this process in vitro in a nonliving system. Because pairing causes the nucleotide bases to face the helical axis, the sugar and phosphate groups of the nucleotides run along the outside; the two chains they form are sometimes called the "backbones" of the helix. In fact, it is chemical bonds between the phosphates and the sugars that link one nucleotide to the next in the DNA strand.

The role of the sequence

Within a gene, the sequence of nucleotides along a DNA strand defines a messenger RNA sequence which then defines a protein, that an organism is liable to manufacture or "express" at one or several points in its life using the information of the sequence. The relationship between the nucleotide sequence and the amino-acid sequence of the protein is determined by simple cellular rules of translation, known collectively as the genetic code. The genetic code is made up of three-letter 'words' (termed a codon) formed from a sequence of three nucleotides (e.g. ACT, CAG, TTT). These codons can then be translated with messenger RNA and then transfer RNA, with a codon corresponding to a particular amino acid. There are 64 possible codons (4 bases in 3 places

4^3

) that encode 20 amino acids. Most amino acids, therefore, have more than one possible codon. There are also three 'stop' or 'nonsense' codons signifying the end of the coding region, namely the UAA, UGA and UAG codons. In many species, only a small fraction of the total sequence of the genome appears to encode protein. For example, only about 1.5% of the human genome consists of protein-coding exons. The function of the rest is a matter of speculation. It is known that certain nucleotide sequences specify affinity for DNA binding proteins, which play a wide variety of vital roles, in particular through control of replication and transcription. These sequences are frequently called regulatory sequences, and researchers assume that so far they have identified only a tiny fraction of the total that exist. "Junk DNA" represents sequences that do not yet appear to contain genes or to have a function. The reasons for the presence of so much non-coding DNA in eukaryotic genomes and the extraordinary differences in genome size ("C-value") among species represent a long-standing puzzle in DNA research known as the "C-value enigma". Some DNA sequences play structural roles in chromosomes. Telomers and centromeres typically contain few (if any) protein-coding genes, but are important for the function and stability of chromosomes. Some genes code for "RNA genes" (see tRNA and rRNA). Some RNA genes code for transcripts that function as regulatory RNAs (see siRNA) that influence the function of other RNA molecules. The intron-exon structure of some genes (such as immunoglobin and protocadeherin genes) is important for allowing alternative splicing of pre-mRNA which allows several different proteins to be made from the same gene. Some non-coding DNA represents pseudogenes that can be used as raw material for the creation of new genes with new functions. Some non-coding DNA provided hot-spots for duplication of short DNA regions; such sequence duplication has been the major form of genetic change in the human lineage (see evidence from the Chimpanzee Genome Project). Exons interspersed with introns allows for "exon shuffling" and the creation of modified genes that might have new adaptive functions. Large amounts of non-coding DNA is probably adaptive in that it provides chromosomal regions where recombination between homologous portions of chromosomes can take place without disrupting the function of genes. Some biologists such as Stuart Kauffman have speculated that there must be mechanisms by which the rate of evolution of a species can be increased or decreased. Non-coding DNA provides mechanisms for gene creation, modification and recombination it is probably important for control of the rate of human evolution. Sequence also determines a DNA segment's susceptibility to cleavage by restriction enzymes, the quintessential tools of genetic engineering. The position of cleavage sites throughout an individual's genome determines one kind of an individual's "DNA fingerprint".

DNA replication

Main article: DNA replication DNA replication DNA replication or DNA synthesis is the process of copying the double-stranded DNA prior to cell division. The two resulting double strands are generally almost perfectly identical, but occasionally errors in replication can result in a less than perfect copy (see mutation), and each of them consists of one original and one newly synthesized strand. This is called semiconservative replication. The process of replication consists of three steps: initiation, replication and termination.

Mechanical properties relevant to biology

Main article: Mechanical properties of DNA.

Strands association and dissociation

The hydrogen bonds between the strands of the double helix are weak enough that they can be easily separated by enzymes. Enzymes known as helicases unwind the strands to facilitate the advance of sequence-reading enzymes such as DNA polymerase. The unwinding requires that helicases chemically cleave the phosphate backbone of one of the strands so that it can swivel around the other. The strands can also be separated by gentle heating, as used in PCR, provided they have fewer than about 10,000 base pairs (10 kilobase pairs, or 10 kbp). The intertwining of the DNA strands makes long segments difficult to separate.

Circular DNA

When the ends of a piece of double-helical DNA are joined so that it forms a circle, as in plasmid DNA, the strands are topologically knotted. This means they cannot be separated by gentle heating or by any process that does not involve breaking a strand. The task of unknotting topologically linked strands of DNA falls to enzymes known as topoisomerases. Some of these enzymes unknot circular DNA by cleaving two strands so that another double:stranded segment can pass through. Unknotting is required for the replication of circular DNA as well as for various types of recombination in linear DNA.

Great length versus tiny breadth

The narrow breadth of the double helix makes it impossible to detect by conventional electron microscopy, except by heavy staining. At the same time, the DNA found in many cells can be macroscopic in length -- approximately 5 centimetres long for strands in a human chromosome. Consequently, cells must compact or "package" DNA to carry it within them. This is one of the functions of the chromosomes, which contain spool-like proteins known as histones, around which DNA winds.

Entropic stretching behavior

When DNA is in solution, it undergoes conformational fluctuations due to the energy available in the thermal bath. For entropic reasons, more floppy states are thermally accessible than stretched out states; for this reason, a single molecule of DNA stretches similarly to a rubber band. Using optical tweezers, the entropic stretching behavior of DNA has been studied and analyzed from a polymer physics perspective, and it has been found that DNA behaves like the Kratky-Porod worm-like chain model with a persistence length of about 53 nm. Furthermore, DNA undergoes a stretching phase transition at a force of 65 pN; above this force, DNA is thought to take the form that Linus Pauling originally hypothesized, with the phosphates in the middle and bases splayed outward. This proposed structure for overstretched DNA has been called "P-form DNA," in honor of Pauling.

Different helix geometries

The DNA helix can assume one of three slightly different geometries, of which the "B" form described by James D. Watson and Francis Crick is believed to predominate in cells. It is 2 nanometres wide and extends 3.4 nanometres per 10 bp of sequence. This is also the approximate length of sequence in which the double helix makes one complete turn about its axis. This frequency of twist (known as the helical pitch) depends largely on stacking forces that each base exerts on its neighbors in the chain.

Supercoiled DNA

The B form of the DNA helix twists 360° per 10.6 bp in the absence of strain. But many molecular biological processes can induce strain. A DNA segment with excess or insufficient helical twisting is referred to, respectively, as positively or negatively "supercoiled". DNA in vivo is typically negatively supercoiled, which facilitates the unwinding of the double-helix required for RNA transcription.

Sugar pucker

There are four conformations that the ribofuranose rings in nucleotides can acquire: # C-2' endo # C-2' exo # C-3' endo # C-3' exo Ribose is usually in C-3'endo, while deoxyribose is usually in the C-2' endo sugar pucker conformation. The A and B forms differ mainly in their sugar pucker. In the A form, the C3' configuration is above the sugar ring, whilst the C2' configuration is below it. Thus, the A form is described as "C3'-endo." Likewise, in the B form, the C2' configuration is above the sugar ring, whilst C3' is below; this is called "C2'-endo." Altered sugar puckering in A-DNA results in shortening the distance between adjacent phosphates by around one angstrom. This gives 11 to 12 base pairs to each helix in the DNA strand, instead of 10.5 in B-DNA. Sugar pucker gives uniform ribbon shape to DNA, a cylindrical open core, and also a deep major groove more narrow and pronounced that grooves found in B-DNA.

Conditions for formation of A and Z helices

The two other known double-helical forms of DNA, called A and Z, differ modestly in their geometry and dimensions. The A form appears likely to occur only in dehydrated samples of DNA, such as those used in crystallographic experiments, and possibly in hybrid pairings of DNA and RNA strands. Segments of DNA that cells have methylated for regulatory purposes may adopt the Z geometry, in which the strands turn about the helical axis like a mirror image of the B form.

Table of comparison of the properties of different helical forms

Non-helical forms

Other, including non-helical, forms of DNA have been described, for example a side-by-side (SBS) configuration. Indeed, it is far from certain that the B-form double helix is the dominant form in living cells.

Direction of DNA strands

The asymmetric shape and linkage of nucleotides means that a DNA strand always has a discernible orientation or directionality. Because of this directionality, close inspection of a double helix reveals that nucleotides are heading one way along one strand (the "ascending strand"), and the other way along the other strand (the "descending strand"). This arrangement of the strands is called antiparallel.

Chemical nomenclature (5' and 3')

For reasons of chemical nomenclature, people who work with DNA refer to the asymmetric ends of ("five prime" and "three prime"). Biologists and the DNA enzymes they use, predominantly read nucleotide sequences in the "5' to 3' direction". However, because chemically produced DNA is synthesized and manipulated in the opposite or in non-directional manners, the orientation should not be assumed. In a vertically oriented double helix, the 3' strand is said to be ascending while the 5' strand is said to be descending.

Sense and antisense

As a result of their antiparallel arrangement and the sequence-reading preferences of enzymes, even if both strands carried identical instead of complementary sequences, cells could properly translate only one of them. The other strand a cell can only read backwards. Molecular biologists call a sequence "sense" if it is translated or translatable, and they call its complement "antisense". It follows then, somewhat paradoxically, that the template for transcription is the antisense strand. The resulting transcript is an RNA replica of the sense strand and is itself sense.

Distinction between sense and antisense strands

A small proportion of genes in prokaryotes, and more in plasmids and viruses, blur the distinction made above between sense and antisense strands. Certain sequences of their genomes do double duty, encoding one protein when read 5' to 3' along one strand, and a second protein when read in the opposite direction (still 5' to 3') along the other strand. As a result, the genomes of these viruses are unusually compact for the number of genes they contain, which biologists view as an adaptation. This merely confirms that there is no biological distinction between the two strands of the double helix. Indeed, typically each strand of a DNA double helix will act as sense and antisense in different regions.

As viewed by topologists

Topologists like to note that the juxtaposition of the 3′ end of one DNA strand beside the 5′ end of the other at both ends of a double-helical segment makes the arrangement a "crab canon".

Single-stranded DNA (ssDNA) and repair of mutations

In some viruses DNA appears in a non-helical, single-stranded form. Because many of the DNA repair mechanisms of cells work only on paired bases, viruses that carry single-stranded DNA genomes mutate more frequently than they would otherwise. As a result, such species may adapt more rapidly to avoid extinction. The result would not be so favorable in more complicated and more slowly replicating organisms, however, which may explain why only viruses carry single-stranded DNA. These viruses presumably also benefit from the lower cost of replicating one strand versus two.

The history of DNA research

mutate at the University of Cambridge]] The discovery that DNA was the carrier of genetic information was a process that required many earlier discoveries. The existence of DNA was discovered in the mid 19th century. However, it was only in the early 20th century that researchers began suggesting that it might store genetic information. This was only accepted after the structure of DNA was elucidated by Watson and Crick in their 1953 Nature publication. Watson and Crick proposed the central dogma of molecular biology in 1957, describing the process whereby proteins are produced from nucleic DNA.

First isolation of DNA

Working in the 19th century, biochemists initially isolated DNA and RNA (mixed together) from cell nuclei. They were relatively quick to appreciate the polymeric nature of their "nucleic acid" isolates, but realized only later that nucleotides were of two types--one containing ribose and the other deoxyribose. It was this subsequent discovery that led to the identification and naming of DNA as a substance distinct from RNA. Friedrich Miescher (1844-1895) discovered a substance he called "nuclein" in 1869. Somewhat later, he isolated a pure sample of the material now known as DNA from the sperm of salmon, and in 1889 his pupil, Richard Altmann, named it "nucleic acid". This substance was found to exist only in the chromosomes. In 1929 Phoebus Levene at the Rockefeller Institute identified the components (the four bases, the sugar and the phosphate chain) and he showed that the components of DNA were linked in the order phosphate-sugar-base. He called each of these units a nucleotide and suggested the DNA molecule consisted of a string of nucleotide units linked together through the phosphate groups, which are the 'backbone' of the molecule. However Levene thought the chain was short and that the bases repeated in the same fixed order. Torbjorn Caspersson and Einar Hammersten showed that DNA was a polymer.

Establishing a link between heritable traits and chromosomes

Max Delbrück, Nikolai V. Timofeeff-Ressovsky, and Karl G. Zimmer published results in 1935 suggesting that chromosomes are very large molecules the structure of which can be changed by treatment with X-rays, and that by so changing their structure it was possible to change the heritable characteristics governed by those chromosomes. In 1937 William Astbury produced the first X-ray diffraction patterns from DNA. He was not able to propose the correct structure but the patterns showed that DNA had a regular structure and therefore it might be possible to deduce what this structure was. In 1943, Oswald Theodore Avery discovered that traits proper to the "smooth" form of the Pneumococcus could be transferred to the "rough" form of the same bacteria merely by making the killed "smooth" (S) form available to the live "rough" (R) form. Quite unexpectedly, the living R Pneumococcus bacteria were transformed into a new strain of the S form, and the transferred S characteristics turned out to be heritable. Avery called the medium of transfer of traits the transforming principle; he identified DNA as the transforming principle, and not protein as previously thought. In 1953, Alfred Hershey and Martha Chase did an experiment (Hershey-Chase experiment) that showed, in T2 phage, that DNA is the genetic material (Hershey shared the Nobel prize with Luria). genetic material double-helix pattern]] In 1944, the renowned physicist, Erwin Schrödinger, published a brief book entitled What is Life?, where he maintained that chromosomes contained what he called the "hereditary code-script" of life. He added: "But the term code-script is, of course, too narrow. The chromosome structures are at the same time instrumental in bringing about the development they foreshadow. They are law-code and executive power -- or, to use another simile, they are architect's plan and builder's craft -- in one." He conceived of these dual functional elements as being woven into the molecular structure of chromosomes. By understanding the exact molecular structure of the chromosomes one could hope to understand both the "architect's plan" and also how that plan was carried out through the "builder's craft." Three groups took up Schrödinger's challenge to work out the structure of the chromosomes and the question of how the segments of the chromosomes that were conceived to relate to specific traits could possibly do their jobs. Just how the presence of specific features in the molecular structure of chromosomes could produce traits and behaviors in living organisms was unimaginable at the time. Because chemical dissection of DNA samples always yielded the same four nucleotides, the chemical composition of DNA appeared simple, perhaps even uniform. Organisms, on the other hand, are fantastically complex individually and widely diverse collectively. Geneticists did not speak of genes as conveyors of "information" in such words, but if they had, they would not have hesitated to quantify the amount of information that genes need to convey as vast. The idea that information might reside in a chemical in the same way that it exists in text--as a finite alphabet of letters arranged in a sequence of unlimited length--had not yet been conceived. It would emerge upon the discovery of DNA's structure, but few researchers imagined that DNA's structure had much to say about genetics.

Discovery of the structure of DNA

In the 1950s, three groups made it their goal to determine the structure of DNA. The first group to start was at King's College London and was led Maurice Wilkins and was later joined by Rosalind Franklin. Another group consisting of Francis Crick and James D. Watson was at Cambridge. A third group was at CalTech and was led by Linus Pauling. Crick and Watson built physical models using metal rods and balls, in which they incorporated the known chemical structures of the nucleotides, as well as the known position of the linkages joining one nucleotide to the next along the polymer. At King's College Maurice Wilkins and Rosalind Franklin examined X-ray diffraction patterns of DNA fibers. Of the three groups, only the London group was able to produce good quality diffraction patterns and thus produce sufficient quantitative data about the structure X-ray diffraction

Discovery that DNA is helical

In 1948 Pauling discovered that many proteins included helical (see alpha helix) shapes. Pauling had deduced this structure from X-ray patterns. (Pauling was also later to suggest an incorrect three chain helical structure based on Astbury's data.) Even in the initial diffraction data from DNA by Maurice Wilkins, it was evident that the structure involved helices. But this insight was only a beginning. There remained the questions of how many strands came together, whether this number was the same for every helix, whether the bases pointed toward the helical axis or away, and ultimately what were the explicit angles and coordinates of all the bonds and atoms. Such questions motivated the modeling efforts of Watson and Crick.

Discovery that complementary nucleotides occur in equal proportions

In their modeling, Watson and Crick restricted themselves to what they saw as chemically and biologically reasonable. Still, the breadth of possibilities was very wide. A breakthrough occurred in 1952, when Erwin Chargaff visited Cambridge and inspired Crick with a description of experiments Chargaff had published in 1947. Chargaff had observed that the proportions of the four nucleotides vary between one DNA sample and the next, but that for particular pairs of nucleotides -- adenine and thymine, guanine and cytosine -- the two nucleotides are always present in equal proportions.

Watson and Crick's model

1947 Watson and Crick had begun to contemplate double helical arrangements, but they lacked information about the amount of twist (pitch) and the distance between the two strands. Rosalind Franklin had to disclose some of her findings for the Medical Research Council and Crick saw this material through Max Perutz's links to the MRC. Franklin's work confirmed a double helix that was on the outside of the molecule and also gave an insight into its symmetry, in particular that the two helical strands ran in opposite directions. Watson and Crick were again greatly assisted by more of Franklin's data. This is controversial because Franklin's critical X-ray pattern was shown to Watson and Crick without Franklin's knowledge or permission. Wilkins showed the famous Photo 51 to Watson at his lab immediately after Watson had been unsuccessful in asking Franklin to collaborate to beat Pauling in finding the structure. From the data in photograph 51 Watson and Crick were able to discern that not only was the distance between the two strands was constant, but also to measure its exact value of 2 nanometres. The same photograph also gave them the 3.4 nanometre-per-10 bp "pitch" of the helix. The final insight came when Crick and Watson saw that a complementary pairing of the bases could provide an explanation for Chargaff's puzzling finding. However the structure of the bases had been incorrectly guessed in the textbooks as the enol tautomer when they were more likely to be in the keto form. When Jerry Donohue pointed this fallacy out to Watson, Watson quickly realised that the pairs of adenine and thymine, and guanine and cytosine were almost identical in shape and so would provide equally sized 'rungs' between the two strands. With the base-pairing, the Watson and Crick quickly converged upon a model, which they announced before Franklin herself had published any of her work. Franklin was two steps away from the solution. She had not guessed the base-pairing and had not appreciated the implications of the symmetry that she had described. However she had been working almost alone and did not have regular contact with a partner like Crick and Watson, and with other experts such as Jerry Donohoe. Her notebooks show that she was aware both of Jerry Donohue's work concerning tautomeric forms of bases (she used the keto forms for three of the bases) and of Chargaff's work. The disclosure of Franklin's data to Watson has angered some people who believe Franklin did not receive due credit at the time and that she might have discovered the structure on her own before Crick and Watson. In Crick and Watson's famous paper in Nature in 1953, they said that their work had been stimulated by the work of Wilkins and Franklin, whereas it had been the basis of their work. However they had agreed with Wilkins and Franklin that they all should publish papers in the same issue of Nature in support of the proposed structure.

Publishing of the "Central Dogma"

Watson and Crick's model attracted great interest immediately upon its presentation. Arriving at their conclusion on February 21 1953, Watson and Crick made their first announcement on February 28. Their paper [http://www.nature.com/genomics/human/watson-crick/ 'A Structure for Deoxyribose Nucleic Acid'] was published on April 25. In an influential presentation in 1957, Crick laid out the "Central Dogma", which foretold the relationship between DNA, RNA, and proteins, and articulated the "sequence hypothesis." A critical confirmation of the replication mechanism that was implied by the double-helical structure followed in 1958 in the form of the Meselson-Stahl experiment. Work by Crick and coworkers showed that the genetic code was based on non-overlapping triplets of codons, and Har Gobind Khorana and others deciphered the genetic code not long afterward. These findings represent the birth of molecular biology. Watson, Crick, and Wilkins were awarded the 1962 Nobel Prize for Physiology or Medicine for discovering the molecular structure of DNA, by which time Franklin had died. Nobel prizes are not awarded posthumously; had she lived, the difficult decision over whom to jointly award the prize would have been complicated as the prize can only be shared between two or three. The process of the actual nomination is covered in Graeme Hunter's biography of Sir Lawrence Bragg, "Light is a Messenger" (pub. 2004)

Bibliography

- DNA: The Secret of Life, by James D. Watson. ISBN 0-375-41546-7
- The Double Helix: A Personal Account of the Discovery of the Structure of DNA (Norton Critical Editions), by James D. Watson. ISBN 0393950751

External links

- Extensive online guide to the life and work of Francis Crick, O.M. compiled by Martin Packer, Birmingham (England): http://www.packer34.freeserve.co.uk/rememberingfranciscrickacelebration.htm martin@packer34.freeserve.co.uk; recollections of Francis Crick (for publication) for the forthcoming biography would be very much appreciated as soon as possible.
- Listen to Francis Crick and James Watson talking on the BBC in 1962, 1972, and 1974: http://www.bbc.co.uk/bbcfour/audiointerviews/profilepages/crickwatson1.shtml
- [http://news.bbc.co.uk/1/hi/sci/tech/2949629.stm 17 April, 2003, BBC News: Most ancient DNA ever?]
- [http://www.whatsnextnetwork.com/health/index.php?cat=61 Latest Advances In Gene Research]
- [http://www.dnai.org DNA Interactive] (requires Macromedia Flash)
- [http://3dscience.com/3d_dna_models.asp Free 3d DNA model Images]
- [http://nist.rcsb.org/pdb/molecules/pdb23_1.html DNA: PDB molecule of the month]
- [http://www.fidelitysystems.com/Unlinked_DNA.html DNA under electron microscope]
- [http://www.myfirstbookaboutdna.com My First Book About DNA] Designed for children to learn more about DNA.
-
- [http://www.rotten.com/library/medicine/dna/ Rotten Library] articles on DNA
- Watson, James, and Francis Crick, "[http://biocrs.biomed.brown.edu/Books/Chapters/Ch%208/DH-Paper.html Molecular structure of nucleic acids], A structure for Deoxyribose Nucleic Acid". April 2, 1953. (paper on the structure of DNA) Category:Nucleic acids Category:Genetics
- ko:DNA ms:DNA ja:デオキシリボ核酸 simple:DNA th:ดีเอ็นเอ

Morphogen

A morphogen is a substance that governs morphogenesis by emanating from a localized source to form a concentration gradient during embryonic development, metamorphosis, or regeneration. The morphogen provides spatial information by reaching a higher concentration, or occasionally by persisting for a longer time, in tissue near to the source. Some of the best-studied morphogens are transcription factors that diffuse within early Drosophila (fruit fly) embryos. Drosophila is an unusual developmental system, in which the first thirteen cell divisions of the embryo occur within a syncytium prior to [http://flymove.uni-muenster.de/Stages/Stage05/Stg5page.html?http&&&flymove.uni-muenster.de/Stages/Stage05/Stg5txt.html cellularization]. Essentially the embryo remains a single cell with over 8000 nuclei evenly spaced near the membrane until the fourteenth cell division, when independent membranes furrow between each nucleus making it an independent cell. As a result, in fly embryos transcription factors such as Bicoid or Hunchback can act as morphogens, because they are free to diffuse between nuclei to produce smooth gradients of concentration without relying on specialized intracellular signalling mechanisms. Although there is some [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8144628&query_hl=18 evidence] that homeobox transcription factors can pass directly through cell membranes, this mechanism is not generally believed to contribute greatly to morphogenesis in cellularized systems. In most developmental systems, such as human embryos or later Drosophila development, syncytia occur only rarely (such as in skeletal muscle), and morphogens are generally secreted signalling proteins. These proteins bind to the extracellular domains of transmembrane receptor proteins, which use an elaborate process of signal transduction to communicate the level of morphogen to the nucleus. A few homologous sets of proteins are well-known morphogens in many species, such as Decapentaplegic, Hedgehog, Wingless, Notch, epidermal growth factor, and fibroblast growth factor. Morphogens are defined conceptually, not chemically, so simple chemicals such as retinoic acid also sometimes act as morphogens. Excellent resources for further study of this topic include [http://www.flybase.org/allied-data/lk/interactive-fly/aimain/1aahome.htm Interactive Fly] and other [http://www.flybase.org Flybase] references, and the [http://www.ncbi.nlm.nih.gov NCBI] resources OMIM and PubMed. ja:モルフォゲン

DNA

DNA Overview

DNA in practice

DNA in crime

DNA in computation

Overview of molecular structure

The role of the sequence

4^3

DNA replication

Mechanical properties relevant to biology

Main article: Mechanical properties of DNA.

Strands association and dissociation

Circular DNA

Great length versus tiny breadth

Entropic stretching behavior

Different helix geometries

Supercoiled DNA

Sugar pucker

Conditions for formation of A and Z helices

Table of comparison of the properties of different helical forms

Non-helical forms

Direction of DNA strands

Chemical nomenclature (5' and 3')

Sense and antisense

Distinction between sense and antisense strands

As viewed by topologists

Topologists like to note that the juxtaposition of the 3′ end of one DNA strand beside the 5′ end of the other at both ends of a double-helical segment makes the arrangement a "crab canon".

Single-stranded DNA (ssDNA) and repair of mutations

The history of DNA research

First isolation of DNA

Establishing a link between heritable traits and chromosomes

Discovery of the structure of DNA

Discovery that DNA is helical

Discovery that complementary nucleotides occur in equal proportions

Watson and Crick's model

Publishing of the "Central Dogma"

Bibliography

External links

Gene

:For the musical band, see Gene (band) Gene (band) (right). Introns are regions often found in eukaryote genes which are removed in the splicing process: only the exons encode the protein. This diagram labels a region of only 40 or so bases as a gene. In reality many genes are much larger.]] Genes are regions of the DNA that parents pass to offspring during reproduction as chromosomes in nuclei of gametes. These entities encode information essential for the construction and regulation of proteins (such as enzymes) and other molecules that determine the growth and functioning of the organism. The word "gene" comes from the Greek genos ("origin") and is shared by many disciplines, including classical genetics, molecular genetics, evolutionary biology and population genetics. Because each discipline models the biology of life differently, the usage of the word gene varies between disciplines. It may refer to either material or conceptual entities. Following the discovery that DNA is the genetic material, and with the growth of biotechnology and the project to sequence the human genome, the common usage of the word "gene" has increasingly reflected its meaning in molecular biology. In the molecular-biological sense, genes are the segments of DNA which cells transcribe into RNA and translate, at least in part, into proteins. The [http://song.sourceforge.net/ Sequence Ontology] project defines a gene as: "A locatable region of genomic sequence, corresponding to a unit of inheritance, which is associated with regulatory regions, transcribed regions and/or other functional sequence regions". In common speech, "gene" is often used to refer to the hereditary cause of a trait, disease or condition—as in "the gene for obesity." Speaking more precisely, a biologist might refer to an allele or a mutation that has been implicated in or is associated with obesity. This is because biologists know that many factors other than genes decide whether a person is obese or not: eating habits, exercise, prenatal environment, upbringing, culture and the availability of food, for example. Moreover, it is very unlikely that variations within a single gene—or single genetic locus—fully determine one's genetic predisposition for obesity. These aspects of inheritance—the interplay between genes and environment, the influence of many genes—appear to be the norm with regard to many and perhaps most ("complex" or "multi-factoral") traits. The term phenotype refers to the characteristics that result from this interplay (see genotype-phenotype distinction).

Overview

Properties of genes

In molecular biology, the DNA of a gene encodes the chemical structure of a protein. The genetic code determines the sequence of the amino acids that make up a protein. The coding of a three nucleotide DNA sequence to a specific amino acid is essentially the same for all known life, from bacteria to humans. Through the proteins they encode, genes govern the cells in which they reside. In multicellular organisms they control the development of the individual from the fertilized egg and the day-to-day functions of the cells that make up tissues and organs. The instrumental roles of their protein products range from mechanical support of the cell structure to the transportation and manufacture of other molecules and to the regulation of other proteins' activities. The genes that exist today are those that have reproduced successfully in the past. Often, many individual organisms share a gene; thus, the death of an individual need not mean the extinction of the gene. Indeed, if the sacrifice of one individual enhances the survivability of other individuals with the same gene, the death of an individual may enhance the overall survival of the gene. This is the basis of the selfish gene view, popularized by Richard Dawkins. He points out in his book, The Selfish Gene, that to be successful genes need have no other "purpose" than to propagate themselves, even at the expense of their host organism's welfare. A human that behaved in such a way would be described as "selfish," although ironically a selfish gene may promote altruistic behaviours. According to Dawkins, the possibly disappointing answer to the question "what is the meaning of life?" may be "the survival and perpetuation of ribonucleic acids and their associated proteins".

Types of genes

Due to rare, spontaneous errors (e.g. in DNA replication) mutations in the sequence of a gene may arise. Once propagated to the next generation, this mutation may lead to variations within a species' population. Variants of a single gene are known as alleles, and differences in alleles may give rise to differences in traits, for example eye colour. A gene's most common allele is called the wild type allele, and rare alleles are called mutants. Normally, RNA is an intermediate product in the translation of a molecular gene into a protein. However, for some gene sequences, RNA molecules are actually the functional products. For example, RNAs known as ribozymes are capable of enzymatic function, or small interfering RNAs have a regulatory role. The DNA sequences from which such RNAs are transcribed are known as non-coding RNA, or RNA genes. All living organisms carry their genes and transmit them to offspring as DNA, but some viruses carry only RNA. Because they use RNA, their cellular hosts may synthesize their proteins as soon as they are infected and without the delay in waiting for transcription. On the other hand, RNA retroviruses, such as AIDS, require the reverse transcription of their genome from RNA into DNA before their proteins can be synthesized.

Human gene nomenclature

For each known human gene the HUGO Gene Nomenclature Committee (HGNC) approve a gene name and symbol (short-form abbreviation). All approved symbols are stored in the [http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl HGNC Database]. Each symbol is unique and each gene is only given one approved gene symbol. It is necessary to provide a unique symbol for each gene so that people can talk about them. This also facilitates electronic data retrieval from publications. In preference each symbol maintains parallel construction in different members of a gene family and can be used in other species, especially the mouse.

Typical numbers of genes in an organism

The following table gives typical numbers of genes and genome size for some organisms. Estimates of the number of genes in an organism are somewhat controversial because they depend on the discovery of genes, and no techniques currently exist to prove that a DNA sequence contains no gene. (In early genetics, genes could be identified only if there were mutations, or alleles.) Nonetheless, estimates are made based on current knowledge.

Chemistry and function of genes

Chemical structure of a gene

Four kinds of sequentially linked nucleotides compose a DNA molecule or strand (more at DNA). These four nucleotides constitute the genetic alphabet. A sequence of three consecutive nucleotides, called a codon, is the protein-coding vocabulary. The sequence of codons in a gene specifies the amino-acid sequence of the protein it encodes. In most eukaryotic species, very little of the DNA in the genome encodes proteins, and the genes may be separated by vast sequences of so-called junk DNA. Moreover, the genes are often fragmented internally by non-coding sequences called introns, which can be many times longer than the genes themselves. Introns are removed on the heels of transcription by splicing. In the primary molecular sense, they represent parts of a gene, however. All the genes and intervening DNA together make up the genome of an organism, which in many species is divided among several chromosomes and typically present in two or more copies. The location (or locus) of a gene and the chromosome on which it is situated is in a sense arbitrary. Genes that appear together on the chromosomes of one species, such as humans, may appear on separate chromosomes in another species, such as mice. Two genes positioned near one another on a chromosome may encode proteins that figure in the same cellular process or in completely unrelated processes. As an example of the former, many of the genes involved in spermatogenesis reside together on the Y chromosome. Many species carry more than one copy of their genome within each of their somatic cells. These organisms are called diploid if they have two copies or polyploid if they have more than two copies. In such organisms, the copies are practically never identical. With respect to each gene, the copies that an individual possesses are liable to be distinct alleles, which may act synergistically or antagonistically to generate a trait or phenotype. The ways that gene copies interact are explained by chemical dominance relationships (more at genetics, allele).

Expression of molecular genes

For various reasons, the relationship between DNA strand and a phenotype trait is not direct. The same DNA strand in 2 different individuals may result in different traits because of the effect of other DNA strands or the environment.
- The DNA strand is expressed into a trait only if it is transcribed to RNA. Because the transcription starts from a specific base-pair sequence (a promoter) and stops at another (a terminator), our DNA strand needs to be correctly placed between the two. If not, it is considered as junk DNA, and is not expressed.
- Cells regulate the activity of genes in part by increasing or decreasing their rate of transcription. Over the short term, this regulation occurs through the binding or unbinding of proteins, known as transcription factors, to specific non-coding DNA sequences called regulatory elements. Therefore, to be expressed, our DNA strand needs to be properly regulated by other DNA strands.
- The DNA strand may also be silenced through DNA methylation or by chemical changes to the protein components of chromosomes (see histone). This is a permanent form of regulation of the transcription.
- The RNA is often edited before its translation into a protein. Eukaryotic cells splice the transcripts of a gene, by keeping the exons and removing the introns. Therefore, the DNA strand needs to be in an exon to be expressed. Because of the complexity of the splicing process, one transcribed RNA may be spliced in alternate ways to produce not one but a variety of proteins (alternative splicing) from one pre-mRNA. Prokaryotes produce a similar effect by shifting reading frames during translation.
- The translation of RNA into a protein also starts with a specific start and stop sequence.
- Once produced, the protein interacts with the many other proteins in the cell, according to the cell metabolism. This interaction finally produces the trait. This complex process helps explain the different meanings of "gene":
- a nucleotide sequence in a DNA strand;
- or the transcribed RNA, prior to splicing;
- or the transcribed RNA after splicing, i.e. without the introns The latter meaning of gene is the result of more "material entity" than the first one.

Mutations and evolution

Just as there are many factors influencing the expression of a particular DNA strand, there are many ways to have genetic mutations. For example, natural variations within regulatory sequences appear to underlie many of the heritable characteristics seen in organisms. The influence of such variations on the trajectory of evolution through natural selection may be as large as or larger than variation in sequences that encode proteins. Thus, though regulatory elements are often distinguished from genes in molecular biology, in effect they satisfy the shared and historical sense of the word. Indeed, a breeder or geneticist, in following the inheritance pattern of a trait, has no immediate way to know whether this pattern arises from coding sequences or regulatory sequences. Typically, he or she will simply attribute it to variations within a gene. Errors during DNA replication may lead to the duplication of a gene, which may diverge over time. Though the two sequences may remain the same, or be only slightly altered, they are typically regarded as separate genes (i.e. not as alleles of the same gene). The same is true when duplicate sequences appear in different species. Yet, though the alleles of a gene differ in sequence, nevertheless they are regarded as a single gene (occupying a single locus).

History

The existence of genes was first suggested by Gregor Mendel, who, in the 1860s, studied inheritance in pea plants and hypothesized a factor that conveys traits from parent to offspring. Although he did not use the term gene, he explained his results in terms of inherited characteristics. Mendel was also the first to hypothesize independent assortment, the distinction between dominant and recessive traits, the distinction between a heterozygote and homozygote, and the difference between what would later be described as genotype and phenotype. Mendel's concept was finally named when Wilhelm Johannsen coined the word gene in 1909. In the early 1900s, Mendel's work received renewed attention from scientists. In 1910, Thomas Hunt Morgan showed that genes reside on specific chromosomes. He later showed that genes occupy specific locations on the chromosome. With this knowledge, Morgan and his students began the first chromosomal map of the fruit fly Drosophila. In 1928, Frederick Griffith showed that genes could be transferred. In what is now known as Griffith's experiment, injections into a mouse of a deadly strain of bacteria that had been heat-killed transferred genetic information to a safe strain of the same bacteria, killing the mouse. In 1941, George Wells Beadle and Edward Lawrie Tatum showed that mutations in genes caused errors in certain steps in metabolic pathways. This showed that specific genes code for specific proteins, leading to the "one gene, one enzyme" hypothesis. Oswald Avery, Collin Macleod, and Maclyn McCarty showed in 1944 that DNA holds the gene's information. In 1953, James D. Watson and Francis Crick demonstrated the molecular structure of DNA. Together, these discoveries established the central dogma of molecular biology, which states that proteins are translated from RNA which is transcribed from DNA. This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses.

Evolutionary concept of gene

George C. Williams first explicitly advocated the gene-centered view of evolution in his book Adaptation and Natural Selection. Also, he proposed an evolutionary concept of gene to be used when we are talking about natural selection favoring some gene. The definition is: ""that which segregates and recombines with appreciable frequency." Acording to this definition, even an asexual genome could be considered a gene, insofar it have an appreciable permanency through many generations. The difference is: the molecular gene transcribes as a unit, and the evolutionary gene inherits as a unit. Richard Dawkins' The Selfish Gene and The Extended Phenotype defended that the gene is the only replicator in livings systems. This means that only genes transmit their structure largely intact and are potentially immortal in the form of copies. So, genes should be the unit of selection.

References

[http://print.google.com/print?id=WkHO9HI7koEC Google print]

External links

- [http://www.gene.ucl.ac.uk/nomenclature HUGO Gene Nomenclature Committee, HGNC]
- [http://www.gene.ucl.ac.uk/cgi-bin/nomenclature/searchgenes.pl the HGNC Database]
- [http://www.gene.ucl.ac.uk/hugo/ Human Genome Organisation, HUGO]
- [http://www.newscientist.com/news/news.jsp?id=ns99996561 Recount slashes number of human genes] (from New Scientist magazine)
- [http://www.genome.gov/12513430 National Human Genome Research Institute — News Release]
- [http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v431/n7011/full/nature03001_fs.html Nature - 21 October 2004 — Finishing the euchromatic sequence of the human genome]
- [http://www.ncbi.nlm.nih.gov/mapview/stats/BuildStats.cgi?taxid=10116&build=3&ver=1#contigs Rat Genome]
- [http://plato.stanford.edu/entries/gene/ Stanford Encyclopedia of Philosophy entry]
- [http://www.ihop-net.org/UniPub/iHOP/ iHOP - Information Hyperlinked over Proteins]
- [http://www.pir.uniprot.org/ UniProt] Category:Cloning Category:Genetics Category:Molecular biology ko:유전자 ja:遺伝子 simple:Gene th:หน่วยพันธุกรรม

Cell adhesion

The study of cell adhesion is part of cell biology. Cells are often not found in isolation, rather they tend to stick to other cells or non-cellular components of their environment. A fundamental question is: what makes cells sticky? Cell adhesion generally involves protein molecules at the surface of cells, so the study of cell adhesion involves cell adhesion proteins and the molecules that they bind to.

Cell adhesion proteins (or Cell adhesion molecules, CAMs)

:see main article on Cell adhesion molecules Cell adhesion proteins are often transmembrane receptors. Transmembrane cell adhesion proteins extend across the cell surface membrane and typically have domains that extend into both the extracellular space and the intracellular space. The extracellular domain of a cell adhesion protein can bind to other molecules that might be either on the surface of an adjacent cell (cell-to-cell adhesion) or part of the extracellular matrix (cell-to-ECM adhesion). The molecule that a cell adhesion protein binds to is called its ligand. There are families of cell adhesion proteins that can be characterized in terms of the structure of the adhesion proteins and their ligands. Adhesion between two copies of the same adhesion protein is called "homophilic" binding. Adhesion between an adhesion protein and some other molecule is "heterophilic" binding.

Cytoskeletal interactions

For a cell adhesion protein like the one shown in the diagram, the intracellular domain binds to protein components of the cell's cytoskeleton. This allows for very tight adhesion. Without attachment to the cytoskeleton, a cell adhesion protein that is tightly bound to a ligand would be in danger of being ripped out of the fragile cell membrane. Often the connection between the cell adhesion proteins and the cytoskeleton is not as direct as shown in the diagram. For example, cadherin cell adhesion proteins are typically coupled to the cytoskeleton by way of special linking proteins called "catenins".

Importance of cell adhesion

Cell adhesion proteins are important for the normal functioning of living organisms. Cell adhesion proteins hold together the components of solid tissues. They are also important for the function of migratory cells like white blood cells. Regulation of cell adhesion proteins is important during embryonic development for the process of morphogenesis. Some people have "blistering diseases" that result from inherited molecular defects in genes for adhesion proteins. Some cancers involve mutations in genes for adhesion proteins that result in abnormal cell-to-cell interactions and tumor growth. Cell adhesion proteins are also important for interactions that allow viruses and bacteria to cause damage to humans. Cell adhesion proteins hold synapses together and the regulation of synaptic adhesion is involved in learning and memory. In Alzheimer's disease there is abnormal regulation of synaptic cell adhesion.

External links

- [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?call=bv.View..ShowSection&rid=cooper.section.2058 The Cell] by G. Cooper (online textbook)
- [http://www.ncbi.nlm.nih.gov:80/books/bv.fcgi?call=bv.View..ShowSection&rid=mcb.chapter.6480 Molecular Cell Biology] by Lodish et al (online textbook)
- [http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=adhesion+AND+cell%5Bbook%5D+AND+cell%5Bbook%5D+AND+cell%5Bbook%5D+AND+8192%5Buid%5D&rid=cell.section.5121 Molecular Biology of the Cell] by Alberts et al (online textbook)
- [http://www.biochemweb.org/adhesion_ecm.shtml Cell Adhesion and Extracellular Matrix - The Virtual Library of Biochemistry and Cell Biology] Category:Cell biology ja:細胞接着

Stem cell

Types

Sources of stem cells

Cord blood stem cells

Adult stem cells

Spore-Like Cells

Embryonic stem cells

Treatments

Current treatments

Potential treatments

Cancer

Stem cell injection restores ability to walk

Spinal cord injury

Blastocyst stem cells switched to neurons

Muscle damage

Heart damage

Low blood supply

Baldness

Missing teeth

Blindness

Embryonic stem cell ethical debate

Blastocysts

Policy debate in the U.S.

Origins of debate

Private funding

Congressional response

Polls regarding embryonic stem cell research

Emerging U.S. state-by-state approach

Policy debate outside the U.S.

External links

Ethics

Epigenetics

- [http://www.epigenome-noe.net/ Epigenome Network of Excellence]

Guides

News

References

Drosophila melanogaster

Drosophila melanogaster Meigen , 1830 (Black-bellied Dew-lover) a dipteran (two-winged) insect, is the species of fruit fly that is commonly used in genetic experiments; it is among the most important model organisms. In modern biological literature, it is often simply called Drosophila or (common) fruit fly.

Physical appearance

model organism The flies have red eyes, a yellow-brown color, with transversal black rings across their abdomen. They exhibit sexual dimorphism: females are about 2.5 millimetres long; males are slightly smaller and the back of their bodies is darker. For a neophyte trying to tell the difference between the sexes under a dissecting microscope, perhaps the easiest distinguishing mark is the cluster of spiky hairs surrounding the anus and genitals of the male. There are extensive images at flybase (see link below).

Life cycle

The life cycle of Drosophila melanogaster at 25 °C takes only 2 weeks; everything takes about twice as long at 18 °C. Females lay some 400 eggs (embryos) into rotting fruit or other organic material. The eggs, which are about 0.5 millimetres long, eclose after 24 h. The resulting larvae grow for 5 days while molting twice, at about 24 and 48 h after eclosion. During this time, they feed on the microorganisms that decompose the fruit, as well as on the sugar of the fruit themselves. Then the larvae encapsulate in the puparium and undergo a five-day-long metamorphosis, after which the adults emerge. metamorphosis Females first mate about 12 hours after emergence. The females store sperm from previous males they mated with for later use. For this reason geneticists must collect the female fly before her first mating, that is, a virgin female, and ensure that she mates only with the particular male needed for the experiment. Inseminated females can be "re-virginized" by prolonged incubation at -10 °C, which kills the sperm, according to Michael Ashburner's "red book".

Model organism in genetics

Drosophila melanogaster is one of the most studied organisms in biological research, particularly genetics and developmental biology. There are several reasons:
- It is small and easy to grow in the laboratory
- It has a short generation time (about 2 weeks) and high productivity (females can lay 500 eggs in 10 days)
- The mature larvae show giant chromosomes in the salivary glands.
- It has only 4 pairs of chromosomes: 3 autosomal, and 1 sex.
- Males do not show recombination, facilitating genetic studies.
- Genetic transformation techniques have been available since 1987.
- Its compact genome was sequenced in 1998. Charles W. Woodworth is credited with being the first to breed Drosophila in quantity and for suggesting to W. E. Castle that they might be used for genetic research during his time at Harvard University. Beginning in 1910, fruit flies helped Thomas Hunt Morgan accomplish his studies on heredity. "Thomas Hunt Morgan and colleagues extended Mendel's work by describing X-linked inheritance and by showing that genes located on the same chromosome do not show independent assortment. Studies of X-linked traits helped confirm that genes are found on chromosomes, while studies of linked traits led to the first maps showing the locations of genetic loci on chromosomes" (Freman 214). The first maps of Drosophila chromosomes were completed by Alfred Sturtevant. Alfred Sturtevant

The Drosophila genome

The genome of Drosophila contains 4 pairs of chromosomes: an X/Y pair, and three autosomes labeled 2, 3, and 4. The fourth chromosome is so tiny that it is often ignored. The genome contains about 132 million bases and approximately 13,767 genes. The genome has been sequenced and has been annotated. genome

Similarity to humans

Genetically speaking, people and fruit flies are similar. About 61% of known human disease genes have a recognizable match in the genetic code of fruit flies, and 50% of fly protein sequences have mammalian analogues. Drosophila is being used as a genetic model for several human diseases including the neurodegenerative disorders Parkinson's, Huntington's, and Alzheimer's disease. The fly is also being used to study mechanisms underlying immunity, Diabetes, and cancer, as well as drug abuse.1

Genetic nomenclature

Genes named after recessive alleles begin with a lowercase letter, while dominant alleles begin with a uppercase letter. Genes named after a protein product begin with an uppercase letter. Genes are typically written in italics. The convention for writing out genotypes is X/Y; 2nd/2nd; 3rd/3rd.² In the molecular biology community, Drosophila geneticists are known for their relatively whimsical naming of discovered gene mutations. Compared to the stodgy (but perhaps more practical) "cdc4", "cdk4", etc. names in the yeast genome, Drosophila sports such favorites as "cheap date" (a mutation leading to increased sensitivity to ethanol intoxication) and "snafu" (a mutation leading to grotesque anatomical abnormalities).

Development and embryogenesis

Main article: Drosophila embryogenesis Embryogenesis in Drosophila has been extensively studied, the small size, short generation time, and large brood size makes it ideal for genetic studies. It is also unique among model organisms in that cleavage occurs in a syncytium. syncytium] During oogenesis, cytoplasmic bridges connect the forming oocyte to nurse cells. Nutrients and developmental control molecules move from the nurse cells into the oocyte. In the figure to the left, the forming oocyte can be seen to be covered by follicular support cells. About 5000 nuclei accumulate in the unseparated cytoplasm of the oocyte before they migrate to the surface and are encompassed by plasma membranes to form cells surrounding the yolk sac. Early on, the germ line segregates from the somatic cells through the formation of pole cells at the posterior end of the embryo. Cell division in the early Drosophila embryo happens so quickly there are no proper checkpoints so mistakes may be made in division of the DNA. To get around this problem the nuclei which have made a mistake detatch from their centrosomes and fall into the centre of the embryo which will not form part of the fly.

Behavioral genetics and neuroscience

In 1971 Ron Konopka and Seymour Benzer published a paper titled "Clock mutants of Drosophila melanogaster" in which they described the first mutations that affected an animal's behavior. Wild-type flies show an activity rhythm of with a frequency of about a day (24 hours). They found mutants with faster and slower rhythms as well as broken rhythms - flies that move and rest in random spurts. Work over the next 30 years has shown that these mutations (and others like them) affect a group of genes and their products that comprise a biochemical or molecular clock. This clock is found in a wide range of fly cells, but the clock-bearing cells that control activity are several dozen neurons in the fly's central brain. Since then Benzer, his students and many other have used behavioral screens to isolate genes involved in vision, olfaction, audition, learning/memory, courtship, pain and other processes such as longevity.

Vision in Drosophila

centrosome The compound eye of the fruit fly contains 800 unit eyes or ommatidia, and are one of the most advanced among insects. Each ommatidium contains 8 photoreceptor cells (R1-8), support cells, pigment cells, and a cornea. Wild-type flies have reddish pigment cells, which serve to absorb excess blue light so the fly isn't blinded by ambient light. Each photoreceptor cell consists of two main sections, the cell body and the rhabdomere. The cell body contains the nucleus while the rhabdomere is made up of toothbrush-like stacks of membrane called microvilli. Each microvillus is 1 mm to 1.5 mm in length and 50 nm in diameter. The membrane of the rhabdomere is packed with about 100 million rhodopsin molecules, the visual protein that absorbs light. The rest of the visual proteins are also tightly packed into the microvillar space, leaving little room for cytoplasm. The photoreceptors in Drosophila express a variety of rhodopsin isoforms. The R1-R6 photoreceptor cells express Rhodopsin1 (Rh1) which absorbs blue light (480 nm). The R7 and R8 cells express a combination of either Rh3 or Rh4 which absorb UV light (345 nm and 375 nm), and Rh5 or Rh6 which absorb blue (437 nm) and green (508 nm) light respectively. Each rhodopsin molecule consists of an opsin protein covalently linked to a carotenoid chromophore, 11-cis-3-hydroxyretinal.³ As in vertebrate vision, visual transduction in invertebrates occurs via a G protein-coupled pathway. However, in vertebrates the G protein is transducin, while the G protein in invertebrates is Gq (dgq in Drosophila). When rhodopsin (Rh) absorbs a photon of light its chromophore, 11-cis-3-hydroxyretinal, is isomerized to all-trans-3-hydroxyretinal. Rh undergoes a conformational change into its active form, metarhodopsin. Metarhodopsin activates Gq, which in turn activates a phospholipase Cβ (PLCβ) known as NorpA. phospholipase PLCβ hydrolyzes phosphoinositol-4,5-bisphosphate (PIP₂), a phospholipid found in the cell membrane, into soluble inositol triphosphate (IP₃) and diacylgycerol (DAG), which stays in the cell membrane. DAG or a derivative of DAG causes a calcium selective ion channel known as TRP (transient receptor potential) to open and calcium and sodium flows into the cell. IP₃ is thought to bind to IP₃ receptors in the subrhabdomeric cisternae, an extension of the endoplasmic reticulum, and cause release of calcium, but this process doesn't seem to be essential for normal vision.⁴ Calcium binds to proteins such as calmodulin (CaM) and an eye-specific protein kinase C (PKC) known as InaC. These proteins interact with other proteins and have been shown to be necessary for shut off of the light response. In addition, proteins called arrestins bind metarhodopsin and prevent it from activating more Gq. A potassium-dependent sodium/calcium exchanger known as NCKX30C pumps the calcium out of the cell. It uses the inward sodium gradient and the outward potassium gradient to extrude calcium at a stoichiometry of 4 Na⁺/ 1 Ca⁺⁺, 1 K⁺.⁵ TRP, InaC, and PLC form a signaling complex by binding a scaffolding protein called InaD. InaD contains five binding domains called PDZ domains which specifically bind the C termini of target proteins. Disruption of the complex by mutations in either the PDZ domains or the target proteins reduces the efficiency of signaling. For example, disruption of the interaction between InaC, the protein kinase C, and InaD results in a delay in inactivation of the light response. Unlike vertebrate metarhodopsin, invertebrate metarhodopsin can be converted back into rhodopsin by absorbing a photon of orange light (580 nm). Approximately two-thirds of the Drosophila brain (about 200,000 neurons total) is dedicated to visual processing. Although the spatial resolution of their vision is significantly worse than that of humans, their temporal resolution is approximately ten times better.

Drosophila flight

The wings of a fly are capable of beating at up to 250 times per second. Flies fly via straight sequences of movement interspersed by rapid turns called saccades. During these turns, a fly is able to rotate 90 degrees in less than 50 milliseconds. Drosophila, and probably many other flies, have optic nerves which lead directly to the wing muscles (while in other insects they always lead to the brain first), making it possible for them to react even more quickly. It was long thought that the characteristics of Drosophila flight were dominated by the viscosity of the air, rather than the inertia of the fly body. However, recent research by Michael Dickinson and Rosalyn Sayaman has indicated that flies perform banked turns, where the fly accelerates, slows down while turning, and accelerates again at the end of the turn. This indicates that inertia is the dominant force, as is the case with larger flying animals.

External links

- [http://ceolas.org/VL/fly/intro.html A quick and simple introduction to Drosophila melanogaster]
- [http://www.flybase.org/ FlyBase]
- [http://www.ceolas.org/VL/fly/ The WWW Virtual Library: Drosophila]
- [http://www.fruitfly.org/ The Berkeley Drosophila Genome Project]
- [http://www.easyinsects.co.uk/livefood/fruitflies/ Keeping and Breeding Fruit Flies]
- [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10731132&dopt=Abstract Abstract of the papers describing the genome of Drosophila melanogaster]
- [http://flymove.uni-muenster.de/ FlyMove]
- [http://www.sdbonline.org/fly/aimain/1aahome.htm The Interactive Fly - A guide to Drosophila genes and their roles in development]
- [http://www.flynome.com/index.html Drosophila Nomenclature - naming of genes]

Cytoskeleton

The cytoskeleton is a cellular "scaffolding" or "skeleton" contained, as all other organelles, within the cytoplasm. It is contained in all cells, including plant and animal cells as well as prokaryotic and eukaryotic cells. It is a dynamic structure that maintains cell shape, enables some cell motion (using structures such as flagella and cilia), and plays important roles in both intra-cellular transport (the movement of vesicles and organelles, for example) and cellular division. vesicle vesicle

The eukaryotic cytoskeleton

Eukaryotic cells contain three kinds of cytoskeletal filaments.

Actin filaments

Main article: microfilaments. Around 7 nm. in diameter, this filament is composed of two actin chains oriented in an helicoidal shape. They are mostly concentrated just beneath the plasma membrane, as they keep cellular shape, form cytoplasmatic protuberances (like pseudopodia and microvilli), and participate in some cell-to-cell or cell-to-matrix junctions and in the transduction of signals. They are also important for cytokinesis and, along with myosin, muscular contraction.

Intermediate filaments

Main article: intermediate filaments These 8 to 11 nanometers in diameter filaments are the more stable (strongly bound) and heterogeneous constitutents of the cytoskeleton. They organize the internal tridimensional structure of the cell (they are structural components of the nuclear envelope or the sarcomeres for example). They also participate in some cell-cell and cell-matrix junctions. Different intermediate filaments are:
- made of vimentins, being the common structural support of many cells.
- made of keratin, found in skin cells, hair and nails.
- neurofilaments of neural cells.
- made of lamin, giving structural support to the nuclear envelope.

Microtubules

Main article: microtubules They are hollow cylinders of about 25 nm., formed by 13 protofilaments which, in turn, are polymers of alpha and beta tubulin. They have a very dynamic behaviour, binding GTP for polymerization. They are organized by the centrosome. They play key roles in:
- intracellular transport (associated with dyneins and kinesins they transport organelles like mitochondria or vesicles).
- the axoneme of cilia and flagella.
- the mitotic spindle.
- synthesis of the cell wall in plants.

Microtrabeculae

They are very small, and ribosomes are found at their intersections. They play key roles in:
- interconnection of organelles.
- keeping cell shape and organelles stationary.

The prokaryotic cytoskeleton

The cytoskeleton was previously considered to be a feature only of eukaryotic cells, but recent research has revealed that homologues to all the major proteins of the eukaryotic cytoskeleton can also be found in prokaryotes. Although the evolutionary relationships are so distant that they are not obvious from protein sequence comparisons alone, the similarity of their three-dimensional structures provides strong evidence that the eukaryotic and prokaryotic cytoskeletons are truly homologous.

FtsZ

FtsZ, a relative of the eukaryotic tubulin, was the first protein of the prokaryotic cytoskeleton to be identified. Like tubulin, FtsZ forms filaments in the presence of GTP, but these filaments do not group into tubules. During cell division, FtsZ is the first protein to move to the division site, and is essential for recruiting other proteins that produce a new cell wall between the dividing cells.

MreB and ParM

Prokaryotic actin-like proteins, such as MreB, are involved in the maintenance of cell shape. All non-spherical bacteria have genes encoding actin-like proteins, and these proteins form a helical network beneath the cell membrane that guides the proteins involved in cell wall biosynthesis. Some plasmids encode a partitioning system that involves an actin-like protein ParM. Filaments of ParM exhibit dynamic instability, and may partition plasmid DNA into the dividing daughter cells by a mechanism analogous to that used by microtubules during eukaryotic mitosis.

Crescentin

The bacterium Caulobacter crescentus contains a third protein, crescentin, that is related to the intermediate filaments of eukaryotic cells. Crescentin is also involved in maintaining cell shape, but the mechanism by which it does this is currently unclear.

External links

- [http://www.biochemweb.org/cytoskeleton.shtml Cytoskeleton, Cell Motility and Motors - The Virtual Library of Biochemistry and Cell Biology] [http://www.namffocsmetahI.com/trick/ ---- Category:Organelles ja:細胞骨格

Homeobox

A homeobox is a stretch of DNA sequence found in genes involved in the regulation of the development (morphogenesis) of animals, fungi and plants. Genes that have a homeobox are called homeobox genes and form the homeobox gene family. A homeobox is about 180 base pairs long; it encodes a protein domain (the homeodomain) which can bind DNA. Homeobox genes encode transcription factors which typically switch on cascades of other genes, for instance all the ones needed to make a leg. The homeodomain binds DNA in a specific manner. However, the specificity of a single homeodomain protein is usually not enough to recognize only its desired target genes. Most of the time, homeodomain proteins act in the promoter region of their target genes as complexes with other transcription factors, often also homeodomain proteins. Such complexes have a much higher target specificity than a single homeodomain protein. A particular subgroup of homeobox genes are the Hox genes, which are found in a special gene cluster, the Hox cluster (also called Hox complex). Hox genes function in patterning the body axis. Thus, by providing the identity of particular body regions, Hox genes determine where limbs and other body segments will grow in a developing fetus or larva. Mutations in any one of these genes can lead to the growth of extra, typically non-functional body parts in invertebrates, for example aristapaedia complex in Drosophila, which results in a leg growing from the head in place of an antenna and is due to a defect in a single gene (this mutation is also known as Antennapedia). Mutation in vertebrate Hox genes usually results in spontaneous abortion. abortion The homeobox genes were first found in the fruit fly Drosophila melanogaster and have subsequently been identified in many other species, from insects to reptiles and mammals. The diagram to the right is a structural model of the Rattus norvegicus Pit-1 homeobox-containing protein (purple) bound to DNA. Pit-1 is a regulator of growth hormone gene transcription. Pit-1 is a member of the POU DNA-binding domain family of transcription factors so it can bind to DNA using both the POU domain and the homeodomain. Homeobox genes have even been found in fungi, for example the one-cellular yeasts, and plants. This suggests that this gene family evolved very early and that the basic mechanisms of morphogenesis are the same for many organisms. Mutations to homeobox genes can produce easily visible phenotypic changes. Two examples of homeobox mutations in the above-mentioned fruit fly are legs where the antennae should be, and a second pair of wings. Duplication of homeobox genes can produce new body segments, and such duplications are likely to have been important in the evolution of segmented animals. In a loose analogy to computing, one can think of a homeobox gene like a call to a subroutine. It switches on the production of a whole subsystem, the code for which must already be present elsewhere in the DNA.

Reference

External links

- [http://www.homeobox.cjb.net/ Homeodomain Resources provided by Thomas R. Bürglin] Category:Genes Category:Developmental biology ja:ホメオボックス

Zygote

A zygote (Greek: ζυγωτόν) is a cell that is the result of fertilization. That is, two haploid cells—usually (but not always) an ovum from a female and a sperm cell from a male—merge into a single diploid cell called the/a zygote (or zygocyte). Animal zygotes undergo mitotic cell divisions to become an embryo. Other organisms may undergo meiotic cell division at this time (for more information refer to biological life cycles). Twins and multiple births can be monozygotic (identical) or dizygotic (fraternal).

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