bluuebunny/crossref_metadata_2025 huggingface dataset:
What's new?: From gene to phenotype in Drosophila and other organisms
Authors: Kaiser Kim
Published: February 2005

The growing number of cloned eukaryotic genes lacking a defined or proven biological function poses a major challenge in ‘reverse genetics’. A method is described here that permits efficient screening for new lesions in, or close to, genes corresponding to cloned DNA sequences of interest. The technique involves transposon mutagenesis, followed by screening of DNA isolated from a population of mutagenised individuals (or their progeny) for evidence that the population contains at least one individual in which transposon insertion has occurred at the target locus. Detection of rare individuals within the population is facilitated by the use of the polymerase chain reaction (PCR). Once recognised, specific individuals (or their progeny) are isolated from the population by a process of sib‐selection. In cases where insertion of the transposon has occurred close to, but not within, the target locus, secondary events involving imprecise excision of the transposon will nonetheless allow the isolation of mutant individuals. Though the method was developed specifically for the transposon‐mutagenesis of Drosophila, extensions to other organisms and to other mutagenic strategies are feasible and some of the possibilities are discussed.
Expression of human plasma protein genes in ageing transgenic mice
Authors: Bowman Barbara H. , Yang Funmei , Adrian Gwendolyn S.
Published: February 2005

Introduction of human plasma protein genes into the mouse genome to produce transgenic mice furnishes an in vivo model for correlating chromosomal DNA sequences with developmental and tissue‐specific expression. The liver produces an array of plasma proteins that circulate throughout the body contributing to homeostasis. Non‐hepatic tissue sites of synthesis have been identified where a local provision of plasma proteins in needed. Analysis of expression of human plasma protein genes in ageing transgenic mice appears especialy promising in identifying DNA sequences that respond to environmental adversities such as inflammatory factors, hormonal changes and metal toxicity. The results indicate that human genes encoding and controlling liver plasma proteins serve as useful models for studying genetic regulation in the background of development and ageing.
Cellular and genetic responses to mesoderm induction in Xenopus
Authors: Hopwood N. D.
Published: February 2005

Mesodermal cell differentiation begins in response to an inductive interaction early in frog development. In parallel with the recent finding that certain peptide growth factors can induce mesoderm, early cellular and genetic responses to the induction have been discovered. I review here recent work on these responses, work that aims to understand how cells respond to inducers to form the complex pattern of the vertebrate mesoderm.
The endoplasmic reticulum and calcium storage
Authors: Koch Gordon L. E.
Published: February 2005

Calcium storage is one of the functions commonly attributed to the endoplasmic reticulum (ER) in non‐muscle cells. Several recent studies have added support to this concept. Analysis of reticuloplasm, the luminal ER content, has shown that it contains several proteins (reticuloplasmins) which are prospective calcium storage proteins. One of these, calreticulin, is also present in the sarcoplasmic reticulum (SR). In sea urchin eggs, a calsequestrin‐like protein has been clearly localised to the ER. The recent demonstration that the IP3 receptor, which has similarities with the calcium release channel in the SR is also localised in the ER membrane suggests that calcium stored in the ER is important for intracellular signalling. The alternative view, that the physiologically important calcium store is a specialised organelle, the calciosome, is not supported by these observations. Recent evidence also suggests that ER calcium might be important in ER structure and in the retention of the luminal ER proteins.
The cellular and molecular events of central nervous system remyelination
Authors: Dubois‐Dalcq Monique , Armstrong Regina
Published: February 2005

Central nervous system (CNS)

Abbreviations: CNS=central nervous system; PNS=peripheral nervous system; MS=multiple sclerosis; MBP=myelin basic protein; MHC=major histocompatibility complex; EAE=experimental allergic encephalomyelitis; O‐2A=oligodendrocyte‐type 2 astrocyte; GC=galactocerebroside; GFAP=glial fibrillary acidic protein; FGF=fibroblast growth factor; IGF1=insulin‐like growth factor.

regeneration is a subject of great interest, particularly in diseases causing a dramatic loss of neurons. However, some CNS diseases do not affect neurons but damage other cells, such as the myelin‐forming cells — called oligodendrocytes — which are also crucial to the harmonious function of the nervous system. Diseases in which oligodendrocytes and myelin are attacked can cause devastating neurological dysfunction which is sometimes followed by recovery and myelin repair or remyelination. The question of the regeneration potential of oligodendrocytes in experimental and human demyelinating diseases such as multiple sclerosis has been debated for a long time. Present evidence suggests that oligodendrocyte precursor cells persist in the adult CNS and that oligodendrocyte regeneration can occur but may be limited by ongoing disease processes. Here we will briefly review recent advances which have broadened our understanding of the cellular and molecular events of CNS remyelination.
Inhibition of tumor angiogenesis as a strategy to circumvent acquired resistance to anti‐cancer therapeutic agents
Authors: Kerbel Robert S.
Published: February 2005

Cancers have a formidable capacity to develop resistance to a large and diverse array of chemical, biologic, and physical anti‐neoplastic agents. This can be largely traced to the instability of the tumor cell genome, and the resultant ability of tumor cell populations to generate phenotypic variants rapidly. It is therefore argued that anti‐cancer strategies should be directed at eliminating those genetically stable normal diploid cells that are required for the progressive growth of tumors. Micro‐vascular endothelial cells comprising the tumor vasculature represent such a normal cell target. Moreover, specificity for tumor associated vasculature by anti‐cancer agents may be achieved by virtue of the fact that many of the endothelial cells that comprise these blood vessels are in an immature, cycling, and ‘activated’ state, in contrast to the endothelial cells associated with normal tissue and organ blood vessels.
The structure of the mammalian centromere
Authors: Rattner Jerome B.
Published: February 2005

The mammalian centromere is a multifunctional chromosomal domain with a complexity that is reflected in its higher order structure, DNA sequence organization and protein composition. The centromere plays a major role during cell division where it functions as the site for the integration of the chromosome with the mitotic spindle, the site of the mechanochemical motor responsible for the movement of chromosomes and the major and last point of interaction between sister chromatids. Recent studies have focused on characterizing the components of the centromere and establishing their relationship to its function. The following brief review summarizes some selected aspects of this recent work.
Drosophila chorion genes: Cracking the eggshell's secrets
Authors: Orr‐Weaver Terry L.
Published: February 2005

The chorion genes of Drosophila are amplified in response to developmental signals in the follicle cells of the ovary prior to their transcription. Their expression is regulated both temporally and spatially within this tissue. They thus serve as models both for the regulation of DNA replication and of developmental transcription. The regulatory elements for DNA amplification have been delineated. Their analysis reveals that amplification is mediated by several regulatory regions and initiates at defined origins within the chorion cluster. Proteins involved in amplification are being identified both by mutations affecting amplification and by DNA binding studies. Regulatory elements for temporal as well as spatial control of chorion gene, expression have been characterized, and two candidate transcription factor genes have been cloned.
The molecular genetics of α1 antitrypsin deficiency
Authors: Wu Ying , Foreman Richard C.
Published: February 2005

The human serum protein α1‐antitrypsin is the major source of antiprotease activity found in the blood. The protein is synthesised primarily by liver cells but, to a lesser extent, by at least one other cell type. Expression of the gene has provided a paradigm for studies on transcriptional regulation in liver and of tissue‐specific promoter activity. The pleiomorphic nature of the gene has given rise to a variety of α1‐antitrypsin variants some of which are clinically important. These abnormal variants may be poorly synthesised, rapidly degraded or inefficiently secreted; studies on the molecular mechanisms which underly these events are providing interesting insights into the general processes of protein transport and intracellular protein degradation.
Translational control during early development
Authors: Richter Joel D.
Published: February 2005

Early development in many animals is programmed by maternally inherited messenger RNAs. Many of these mRNAs are translationally dormant in immature oocytes, but are recruited onto polysomes during meiotic maturation, fertilization, or early embryogenesis. In contrast, other mRNAs that are translated in oocytes are released from polysomes during these later stages of development. Recent studies have begun to define the cis and trans elements that regulate both translational repression and translational induction of maternal mRNA. The inhibition of translation of some mRNAs during early development is controlled by discrete sequences residing in the 3′ and 5′ untranslated regions, respectively. The translation of other RNAs is due to polyadenylation which, at least in oocytes of the frog Xenopus laevis, is regulated by a U‐rich cytoplasmic polyadenylation element (CPE). Although similar, the CPE sequences of various mRNAs are sufficiently different to be bound by different proteins. Two of these proteins and their interactions are described here.
Growth cones: The mechanism of neurite advance
Authors: Gordon‐Weeks P. R.
Published: February 2005

Growth cones are the highly motile structures found at the tips of growing axons and dendrites (neurites), which extend from neurones, during the development of the nervous system. They function both as detectors and transducers of extrinsic guidance cues and as regions where the neurite cytoskeleton is assembled. Without concerted neurite assembly, advance cannot occur. Assembly of the neurite cytoskeleton in growing neurites chiefly involves microtubule assembly at the growth cone. Some of the factors that may influence microtubule assembly in growth cones are becoming apparent and include posttranslational modification of tubulin itself and microtubule associated proteins, particularly tau and MAP1B.
Fragile X‐linked mental retardation and the difficulties of reverse genetics
Authors: Jordan Bertrand R.
Published: February 2005

Fragile X‐linked mental retardation is an enigmatic inheritable syndrome in which severe mental retardation, a cytogenetically detectable fragile site at Xq27.3 (FraX) and a number of dysmorphic features are associated. Genetic analysis shows that the mode of inheritance is more complex than a straightforward X‐linked recessive trait and probably involves a two‐step process for which several models have been proposed. Early attempts ‘at cloning the fragile site’ provided several DNA segments lying in its general vicinity, and large scale DNA mapping methods were extensively applied in an effort to generate maps including this region. These efforts were complemented by more focussed methods such as microdissection; together these approaches have now provided a number of DNA segments within a 5cM interval around FraX, and with the help of these new probes the site is indeed being cloned. Unravelling the nature of the sequence(s) responsible for the mental retardation syndrome will probably take some time, however.
Why is mendelian segregation so exact?
Authors: Crow James F.
Published: February 2005

The precise 1:1 segregation of Mendelian heredity is ordinarily taken for granted, yet there are numerous examples of ‘cheating’ genes that perpetuate themselves in the population by biasing the Mendelian process in their favor. One example is the Segregation Distortion system of Drosophila melanogaster, in which the distorting gene causes its homologous chromosome to produce a nonfunctional sperm. This system depends on three closely linked components, whose molecular basis is beginning to be understood.

The system is characterized by numerous modifiers changing the degree of distortion. Mathematical theory shows that unlinked modifiers that change the degree of distortion in the direction of Mendelism always increase in the population. This provides a mechanism for removing cheaters and preserving the honesty of the Mendelian gene‐shuffle.
Parallels between development of embryonic and matrix‐induced endochondral bone
Authors: Carrington Jill L. , Reddi A. H.
Published: February 2005

Endochondral bone formation can take place in the embryo, during fracture healing, or in postnatal animals after induction by implanted demineralized bone matrix. This matrix‐induced bone formation recapitulates the embryonic sequence of bone formation morphologically and biochemically. The steps in bone formation in both systems include differentiation of cartilage from mesenchyme, cartilage maturation, invasion of the cartilage by blood vessels and marrow precursors, and formation of bone and bone marrow. Recently, bone inductive molecules from demineralized bone matrix have been purified, sequenced and produced as recombinant proteins. While there are similarities between bone development in the embryo and that after induction by these purified molecules, the molecules responsible for bone induction in the embryo have not yet been defined. Because of similarities between the two methods of bone formation, studies of Bone induction by demineralized bone matrix may help to elucidate mechanisms of embryonic bone induction.
Laminin binding proteins
Authors: Mercurio Arthur M. , Shaw Leslie M.
Published: February 2005

Cells express many proteins that bind to laminin, the major adhesive component of basement membranes. Some of these, specifically integrins, function as transmembrane receptors that ‘signal’ the presence of laminin on the cell surface to the cytoplasm. Lectins constitute a second class of laminin binding proteins that may augment integrin function by interacting with laminin carbohydrate. Caution must be used in ascribing functions to other laminin binding proteins, especially cytosolic proteins.
Intercommunication between mammalian oocytes and companion somatic cells
Authors: Eppig John J.
Published: February 2005

Cellular interactions in the mammalian ovarian follicle between its germ‐line and somatic cell components are crucial for its development and function. These interactions are mediated by both membrane gap junctions and paracrine factors. Somatic cell‐to‐oocyte communication is essential for oocyte growth and the regulation of meiotic maturation. In particular, granulosa cells provide nutrients and molecular signals that regulate oocyte development. Oocytes, on the other hand, promote the organization of the follicle, the proliferation of granulosa cells, and the differentiation and function of cumulus cells, a subset of granulosa cells. Determining the nature of the oocyte‐to‐granulosa cell signals remains a key challenge for future work.
Biological activities of oxygenated sterols: Physiological and pathological implications
Authors: Hwang Peter L.
Published: February 2005

Oxygenated derivatives of cholesterol (oxysterols) are widely distributed in nature, being found in the blood and tissues of animals and man as well as in foodstuff. They exhibit many biological activities which are of potential physiological, pathological or pharmacological importance. Many oxysterols have been found to be potent inhibitors of cholesterol biosynthesis and one or more oxysterols may play a role as the physiologic feedback regulator of cholesterol synthesis. Oxysterols also inhibit cell replication and have cytotoxic properties effects which suggest that these sterols may participate in the regulation of cell proliferation and may be potentially useful as therapeutic agents for cancer. Furthermore, there is considerable evidence that oxysterols may be involved in the pathogenesis of atherosclerosis. Although the mechanism of action of oxysterols in all these instances is not well understood, the existence of cytosolic and microsomal proteins which bind oxysterols with high affinity and specificity suggests that this group of compounds may represent a family of intracellular regulatory molecules.
Altered cellular responsiveness during ageing
Authors: Rattan Suresh I. S. , Derventzi Anastassia
Published: February 2005

The capacity of cells and organisms to respond to external stimuli and to maintain stability in order to survive decreases progressively during ageing. The mitogenic and stimulatory effects of growth factors, hormones and other agents are reduced significantly during cellular ageing. The sensitivity of ageing cells to toxic agents including antibiotics, phorbol esters, radiations and heat shock increases. This failure of homeostasis during cellular ageing does not appear to be due to any quantitative and qualitative defects in the receptor systems. Instead, metabolic defects in the pathways of macromolecular synthesis may be the basis of altered cellular responsiveness during ageing.
The role of DNA double strand breaks in lonizing radiation‐induced killing of eukaryotic cells
Authors: Lliakis George
Published: February 2005

A widely accepted assumption in radiobiology is that ionizing radiation kills cells by inducing forms of damage in DNA structures that lead to the formation of lethal chromosome aberrations. One goal of radiation biology research is the identification of these forms of DNA damage, the characterization of the mechanisms involved in their repair and the elucidation of the processes involved in their transformation to chromosome damage, In recent years, evidence has accumulated implicating DNA double stranded breaks as lesions relevant for cell killing. Here, the available information on this topic is reviewed together with the methods most commonly used to quantitate induction and repair of this type of lesion. The presentation concludes with an outline of present research directions and future goals.
Insect antibacterial proteins: Not just for insects and against bacteria
Authors: Kimbrell Deborah A.
Published: February 2005

In response to a bacterial infection, insects launch an array of countermeasures. Among these are the antibacterial proteins, which effectively lyse bacteria or are bacteriostatic. These proteins were generally assumed to be restricted to insects, yet recent information has shown some homologous counterparts in verte brates, including humans. Recent data have revealed that at least some of these proteins can also act against eukaryotic cells, including human infectious Parasites The latter activities have opened up new possibilities for disease control.
Auxin‐binding proteins and their possible roles in auxin‐mediated plant cell growth
Authors: Jones Alan M. , Prasad Paruchuri V.
Published: February 2005

Like several other classes of hormones, the class of plant hormones called auxins exert myriad effects on cell development. While auxins are most noted for inducing cell elongation, they are also involved in cell division, cell differentiation, cell and organ polarity, and wound responsiveness. Consistent with this pleiotropy, is the recent identification of several putative auxin receptors that in theory could represent the primary elements of more than one auxin signal pathway leading to distinct responses or leading in parallel to a single response. Our current working hypothesis is that some auxin‐mediated responses may be mediated by multiple receptors. We describe some of what is known about each of the new putative receptors and elaborate on the hypothesis using the example of cell elongation. Specifically for auxin‐induced elongation, we propose that two rapid events, specific gene transcription and cell wall acidification, are separately mediated by at least two receptors, acting in the nucleus and at the plasma membrane, respectively.
What the papers say: Compartmentalized transcription and the establishment of cell type during sporulation in Bacillus subtilis
Authors: Gober James W.
Published: February 2005

An early step in sporulation of the bacterium Bacillus subtilis, is the formation of two compartments in the developing sporangium: the mother cell and the forespore. These compartments differ in their programs of gene expression and developmental fate. The establishment of cell type within this simple developmental program, is accomplished by the compartmentalization of sigma subunits of RNA polymerase. The localization of these sigma factors results in compartment‐specific gene expression. Recent experiments have elucidated some of the early steps in the establishment of 3V cell type. After septum formation, the activity of the sigma factor, σF, is confined to the forespore compartment. This, in turn, results in the localized expression of another developmental sigma factor, σG. The forespore localization of these two sigma factors, establishes the forespore line of gene expression. σF and σG also regulate mother cell events. σF activity in the forespore regulates the proteolytic processing of σE within the mother cell compartment. The localization σE activity leads to mother cell expression of another sigma factor, pro‐σK The proteolytic processing of pro‐σK to mature σK is controlled by the forespore sigma factor, σG Mature σK then directs the transcription of mother cell specific genes. Therefore, the initial localization of σF activity to the forespore compartment, orchestrates the establishment of cell type in both forespore and mother cell compartments.
The homeodomain: A new face for the helix‐turn‐helix?
Authors: Treisman Jessica , Harris Esther , Wilson David , Desplan Claude
Published: February 2005

The discovery of conserved protein domains found in many Drosophila and mammalian developmental gene products suggests that fundamental developmental processes are conserved throughout evolution. Our understanding of development has been enhanced by the discovery of the widespread role of the homeodomain (HD). The action of HD‐containing proteins as transcriptional regulators is mediated through a helix‐turn‐helix motif which confers sequence specific DNA binding. Unexpectedly, the well conserved structural homology between the HD and the prokaryotic helix‐turn‐helix proteins contrasts with their divergent types of physical interaction with DNA. A C‐terminal extension of the HD recognition helix has assumed the role that the N‐terminus of the prokaryotic helix plays for specification of DNA binding preference. However, the HD appears also capable of recognizing DNA in an alternative way and its specificity in vivo may be modified by regions outside the helix‐turn‐helix motif. We propose that this intrinsic complexity of the HD, as well as its frequent association with other DNA binding domains, explains the functional specificity achieved by genes encoding highly related HDs.
Challenges: Observing development through evolutionary eyes: A practical approach
Authors: Dover Gabriel A.
Published: February 2005

An argument is made that only through a detailed comparison of mutational mechanisms underlying the evolution of the genetic systems governing development, can the 'logic' of individual development be fully comprehended. To do this, it is essential to choose two or more genes (or their products) that interact in the establishment of a given function, and to compare the molecular basis of that interaction in closely related species. The rationale to this approach arises from observations of molecular co‐evolution between interacting partners involved with given functions which have led to species specificity in the manner in which such functions are effected. Molecular coevolution reveals that divergence in sequence can be tolerated whilst biological functions are maintained, not because it is neutral and dispensable but because successful, compensatory changes can evolve in eukaryotic genomes that are in continuous states of flux.
Biological asymmetries and the fidelity of eukaryotic DNA replication
Authors: Kunkel Thomas A.
Published: February 2005

A diploid human genome contains approximately six billion nucleotides. This enormous amount of genetic information can be replicated with great accuracy in only a few hours. However, because DNA strands are oriented antiparallel while DNA polymerization only occurs in the 5′ → 3′ direction, semi‐conservative replication of double‐stranded DNA is an asymmetric process, i.e., there is a leading and a lagging strand. This provides a considerable opportunity for non‐random error rates, because the architecture of the two strands as well as the DNA polymerases that replicate them may be different. In addition, the proteins that start or finish chains may well be different from those that perform the bulk of chain elongation. Furthermore, while replication fidelity depends on the absolute and relative concentrations of the four deoxyribonucleotide precursors, these are not equal in vivo, not constant throughout the cell cycle, and not necessarily equivalent in all cell types. Finally, the fidelity of DNA synthesis is sequence‐dependent and the eukaryotic nuclear genome is a heterogeneous substrate. It contains repetitive and non‐repetitive sequences and can actually be considered as two subgenomes that differ in nucleotide composition and gene content and that replicate at different times. The effects that each of these asymmetries may have on error rates during replication of the eukaryotic genome are discussed.
Cutting, splicing, reordering, and elimination of DNA sequences in hypotrichous ciliates
Authors: Prescott David M.
Published: February 2005

Hypotrichous ciliates extensively process genomic DNA during their life cycle. Processing occurs after cell mating, beginning with multiple rounds of DNA replication to form polytene chromosomes. Thousands of transposonlike elements are then excised from the chromosomes and destroyed, and thousands of short, internal eliminated sequences (IESs) are excised from coding and noncoding parts of genes and destroyed. IES removal from a gene is accompanied by splicing of the remaining chromosomal DNA segments to form a transcriptionally competent gene. For some genes these DNA segments are in a scrambled order and are ligated into a genetically correct order at the time of IES removal. Next the polytene chromosomes are cut up band‐by‐band and all genes are excised from the chromosomes as short, linear molecules averaging 2.2 kbp (in Oxytricha nova). Gene excision is accompanied by destruction of all nongenic DNA, which, together with the transposonlike elements and IESs, accounts for ∼95% of the total sequence complexity of the genome in O. nova. Telomeric sequences are added to the excised gene‐sized DNA molecules. Finally, the gene‐sized molecules are replicated several times to form the macronucleus of the organism.
Molecular movements in oocyte patterning and pole cell differentiation
Authors: Lasko Paul F.
Published: February 2005

Central to the differentiation and patterning of the Drosophila oocyte is the asymmetric intracellular localization of numerous mRNA and protein molecules involved in developmental signalling. Recent advances have identified some of the molecules mediating oocyte differentiation, specification of the anterior pole of the embryo, and determination of the embryonic germ line. This work is considered in the context of the classical model of the germ plasm as a cytoplasmic determinant for germ cell formation.
Role of the interleukin 5 receptor system in hematopoiesis: Molecular basis for overlapping function of cytokines
Authors: Tominaga Akira , Takaki Satoshi , Hitoshi Yasumichi , Takatsu Kiyoshi
Published: February 2005

Interleukin 5 (IL‐5) is a kind of peptide hormone released from T lymphocytes of mammals infected with microorganisms or parasites. It is an acidic glycoprotein with a molecular mass of 40 to 50 kDa that consists of a homodimer of polypeptides. It controls hematopoiesis so that it increases natural immunity. In the mouse, IL‐5 acts on committed B cells to induce differentiation into Ig‐producing cells and on common progenitors for CD5+ pre‐B cells and CD5+ macrophages to support their survival. The antibodies secreted by CD5+ B cells seem to be responsible for the primary protection against the infection with microorganisms or parasites. It also supports the growth and/or differentiation of eosinophil precursor and mature eosinophils, which can be effective for the removal of parasites in combination with the antibodies against them. Murine IL‐5 receptor (IL‐5R) consists of two different polypeptide chains; αL chain and β chain. The IL‐5R α chain is 60 kDa protein that binds IL‐5 with low affinity. The IL‐5R β chain is a 130 kDa protein which does not bind IL‐5 by itself but is necessary to form the high affinity IL‐5R. The β chain was identified by using one of the anti‐IL‐5R mAb and anti‐IL‐3R mAb as the IL‐3R homologue. This β chain is also used as the β chain of GM‐CSF receptor. This fact suggests that there is a common signaling mechanism among these cytokines and efficient cooperation among them. At the same time, these findings may explain the overlapping role of these cytokines in the development of granulocytes.
Membrane protein insertion into the endoplasmic reticulum ‐ another channel tunnel?
Authors: High Stephen
Published: February 2005

The synthesis of biological membranes requires the insertion of proteins into a lipid bilayer. The rough endoplasmic reticulum of eukaryotic cells is a principal site of membrane biogenesis. The insertion of proteins into the membrane of the endoplasmic reticulum is mediated by a resident proteinaceous machinery. Over the last five years several different experimental approaches have provided information about the components of the machinery and how it may function.
Genes and Genomes: Genes, Genes and More Genes in the Human Major Histocompatibility Complex
Authors: Milner Caroline M. , Campbell R. Duncan
Published: February 2005

The human major histocompatibility complex (MHC), on the short arm of chromosome 6, represents one of the most extensively characterised regions of the human genome. This ∼4 Mb segment of DNA contains genes encoding the polymorphic MHC class I and class II molecules which are involved in antigen presentation during an immune response. Recently the whole of the MHC has been cloned in cosmids and/or yeast artificial chromosomes (YACs) and large portions have been characterised for the presence of novel genes. Many unrelated genes, both housekeeping and tissue specific, have been identified and the gene density in some regions is now approaching one gene every few kilobases. Some of the novel genes encode proteins involved in the intracellular processing and transport of antigens that are presented by MHC class I molecules. Others, however, have no obvious role in the immune response. The MHC is located in the chromosome band 6p21.3 which is a Giemsa (G)‐light band. The detection of such a large number of functional genes (at least 70) in this region is compatible with the idea that both housekeeping and tissue‐specific genes are localised predominantly in G‐light bands.
Problems and paradigms. All animals develop from a blastula: Consequences of an undervalued definition for thinking on development
Authors: De Loof Arnold
Published: February 2005

An early embryo becomes a blastula at the moment that its constituent cells become organised into a simple epithelium. Epithelial folding and compartmentation are essential elements of animal development. All the different cell types ‐ epithelial and other ones ‐ of which a differentiated organism consists differ in their plasmamembrane‐cytoskeletal complex but they are assumed to have an identical genome. The hypothesis is put forward that, perhaps, the basic mechanism underlying differentiation can be defined as the generation of cells which have an identical genome but which differ in their plasmamembrane‐cytoskeletal complex and which, because of these differences, can engage in differential protein synthesis‐physiology.
On the nature of origins of DNA replication in eukaryotes
Authors: Benbow Robert M. , Zhao Jiyong , Larson Drena D.
Published: February 2005

Chromosomal origins of DNA replication in higher eukaryotes differ significantly from those of E. coli (oriC) and the tumor virus, SV40 (ori sequence). Initiation events appear to occur throughout broad zones rather than at specific origin sequences. Analysis of four chromosomal origin regions reveals that they share common modular sequence elements. These include DNA unwinding elements, pyrimidine tracts that may serve as strong DNA polymerase‐primase start sites, scaffold associated regions, transcriptional regulatory sequences, and, possibly, initiator protein binding sites and inherently destabilized regions. Based on the novel organization of chromosomal origin regions, we propose a model for initiation of DNA replication in higher eukaryotes. Unwinding of duplex DNA during initiation may be uncoupled, both temporally and spatially, from DNA synthesis, resulting in transient single‐stranded intermediates that function in lieu of conventional replication forks during chromosomal DNA replication. DNA synthesis begins subsequently at multiple sites Within the unwound regions rather than at specific origin sequences.
The origin of P elements in Drosophila melanogaster
Authors: Engels William R.
Published: February 2005

The P family of transposable genetic elements is thought to be a recent addition to the Drosophila melanogaster genome. New evidence suggests that the elements came from another Drosophila species, possibly carried by parasitic mites. The transposition mechanism of P elements involves DNA gap repair which may have facilitated their rapid spread through D. melanogaster worldwide. These results provide new insight into the process of a transpo‐son's invasion into a new species and the potential risk of extinction such an invasion might entail.
My favourite molecule. Thy‐1, the enigmatic extrovert on the neuronal surface
Authors: Morris Roger
Published: February 2005

Thy‐1 is a small glycoprotein of 110 amino acids which, folded in the characteristic structure of an immunoglobulin variable domain1, are anchored to the plasma membrane via a glycophosphatidylinositol (GPI) tail(2,3) (Fig. 1). It is a major component of the surface of various cell types, including neurons, at certain stages of their development (4). These qualities doubtlessly appeal to certain cognoscenti, but it is not clear why they would raise Thy‐1 to the status of a favourite molecule. Indeed, few scientists readily admit to having a favourite. We study individual molecules because science is rooted in specific observations; but we do so in order to discover mechanisms of general importance. A molecule's appeal is dependent on its ability to reveal novel aspects of how nature works.

Thy‐1 has been unusual in this respect. It was the first lymphocyte surface antigen shown to be restricted to a functional subset of lymphocytes (T cells in the mouse), a finding crucial to the development of cellular immunology(5); it was one of the first cell surface molecules to be sequenced and indicated the importance of immunoglobulin domains and GPI anchors as structural motifs(1–3); it has been pivotal in studies demonstrating that GPI‐anchored molecules are able to signal across the membrane they do not span(6, 7). Thy‐1 has revealed this much, however, with the charm of an adroit stripper: it has always promised glimpses of things more exciting than that displayed. In particular, the function of this molecule has never emerged.

Our current work on Thy‐1 in the nervous system is, we believe, finally prizing this last secret into the open. It suggests that Thy‐1 on the neuronal surface interacts with one of the main glial types of adult brain, the astrocyte, to restrict axonal growth(8). There is no current consensus that astrocytes do regulate such growth, and this is the wider question we are addressing from the perspective of Thy‐1. At issue also is how to progress from knowing the nature of a molecule to defining its function. This task has already been achieved with molecules which were harder to characterise than Thy‐1. The problem is a classic Catch 22 situation: Thy‐1 has been readily characterised because it is small and abundant it is ten times more abundant than any other surface glycoprotein on rat thymocytes(9); but since there is so much of it, whatever it does it must do rather badly (or there would be no need to have so much of it!). Defining a function based on low activity or affinity is not trivial.

Here I describe two aspects of work on Thy‐1. One is long completed ‐ the research which led to Thy‐1 being isolated and characterised ‐ and included because it demonstrates features which are still applicable to much research using a antibodies today. The other is our ongoing work on the nervous system, which is at that exciting early stage where hypotheses are formed, but the answers are still coming in.
The selectin family of carbohydrate‐binding proteins: Structure and importance of carbohydrate ligands for cell adhesion
Authors: Cummings Richard D. , Smith David F.
Published: February 2005

Protein‐carbohydrate interactions have been found to be important in many steps in lymphocyte recirculation and inflammatory responses. A family of carbohydrate‐binding proteins or lectins, termed selectins, has been discovered and shown to be involved directly in these processes. The three known selectins, termed L‐, E‐ and P‐selectins, have domains homologous to other Ca2+‐dependent (C‐type) lectins. L‐selectin is expressed constitutively on lymphocytes, E‐selectin is expressed by activated endothelial cells, and P‐selectin is expressed by activated platelets and endothelial cells. Here, we review the nature of the carbohydrate determinants in tissues recognized by these selectins. The expression of specific sialylated, fucosylated and sulfated carbohydrates in activated endothelium and high endothelial venules promotes interactions with L‐selectin on leukocyte surfaces. In contrast, E‐ and P‐selectins recognize specific carbohydrate determinants related to sialyl Lex antigen on neutrophil and monocyte surfaces. The discovery of the selectins has generated excitemient among glycoconjugate researchers that other carbohydrate‐binding proteins and their cognate ligands will be found to function in regulating many types of cellular interactions.
What determines whether chromosomes segregate reductionally or equationally in meiosis?
Authors: Simchen Giora , Hugerat Yasser
Published: February 2005

Normal meiosis consists of a single round of DNA replication followed by two nuclear divisions. In the 1st division the chromosomes segregate reductionally whereas in the 2nd division they segregate equationally (as they do in mitosis). In certain yeast mutants, a single‐division meiosis takes place, in which some chromosomes segregate reductionally while others divide equationally. This autonomous segregation behaviour of individual chromosomes on a common spindle is determined by the centromeres they carry. The relationship between reductional segregation of a pair of chromosomes and their earlier recombinational history is also discussed.
RNA processing in prokaryotic cells
Authors: Apirion David , Miczak Andras
Published: February 2005

RNA processing in Escherichia coli and some of its phages is reviewed here, with primary emphasis on rRNA and tRNA processing. Three enzymes, RNase III, RNase E and RNase P are responsible for most of the primary endonucleolytic RNA processing events. The first two are proteins, while RNase P is a ribozyme. These three enzymes have unique functions and in their absence, the cleavage events they catalyze are not performed. On the other hand a relatively large number of exonucleases participate in the trimming of the 3′ ends of tRNA precursor molecules and they can substitute for each other. Primary processing is the first event that happens to the nascent RNA molecule, while in secondary RNA processing, the substrate is a product of a primary processing event. Although most RNA processing occurs in RNP particles, it seems that only in secondary RNA processing is the RNP particle required for the reaction. Bacteria and especially bacteriophages contain self‐splicing introns which in cases were probably acquired from other species.
Hypothesis: The telophase disc: Its possible role in mammalian cell cleavage
Authors: Margolis Robert L. , Andreassen Paul R.
Published: February 2005

The molecular signals that determine the
position and timing of the furrow that forms during mammalian cell
cytokinesis are presently unknown. It is apparent, however, that
these signals are generated by the mitotic spindle after the onset of
anaphase. Recently we have described a structure that bisects the
cell during telophase at the position of the cytokinetic furrow. This
structure, the telephase disc, appears to the templated by the motitc spindle during anaphase, and precedes the formation of the cytokinetic furrow. The relationship of the telephase disc to the myosin and actin based furrowing mechanism is discussed here. We propose that the telophase disc may determine the position and timing of cleavage by recruitment and alignment of myosin.
Mechanisms of neural crest cell migration
Authors: Bronner‐Fraser Marianne
Published: February 2005

Neural crest cells are remarkable in their extensive and stereotypic patterns of migration. The pathways of neural crest migration have been documented by cell marking techniques, including interspecific neural tube grafts, immunocytochemistry and Dil‐labelling. In the trunk, neural crest cells migrate dorsally under the skin or ventrally through the somites, where they move in a segmental fashion through the rostral half of each sclerotome. The segmental migration of neural crest cells appears to be prescribed by the somites, perhaps by an inhibitory cue from the caudal half. Within the rostral sclerotome, neural crest cells fill the available space except for a region around the notochord, suggesting the notochord may inhibit neural crest cells in its vicinity. In the cranial region, antibody perturbation experiments suggest that multiple cell‐matrix interactions are required for proper in vivo migration of neural crest cells. Neural crest cells utilize integrin receptors to bind to a number of extracellular matrix molecules. Substrate selective inhibition of neural crest cell attachment in vitro by integrin antibodies and antisense oligonucleotides has demonstrated that they possess at least three integrins, one being an α1β1 integrin which functions in the absence of divalent cations. Thus, neural crest cells utilize complex sets of interactions which may differ at different axial levels.
Gene expression during metamorphosis: An ideal model for post‐embryonic development
Authors: Tata Jamshed R.
Published: February 2005

The precocious induction in vivo and in culture of insect and amphibian metamorphosis by exogenous ecdysteroids and thyroid hormones, and its retardation or inhibition by juvenile hormone and prolactin, respectively, has allowed the analysis of such diverse processes of post‐embryonic development as morphogenesis, tissue remodelling, functional reorganization, and programmed cell death. Metamorphosis in vertebrates also shares many similarities with mammalian development in the late foetal and perinatal period. This review describes the regulation of expression of some of the ‘adult’ gene products during metamorphosis in invertebrates and vertebrates. Recent studies on metamorphosis have revealed the important role played by auto‐induction of hormone receptor genes, based on which a model will be presented to explain the activation of ‘downstream’ genes which give rise to the adult phenotype. It will also be argued that metamorphosis is an ideal model for analyzing some of the major mechanisms governing post‐embryonic development.
RNA as a catalyst: Natural and designed ribozymes
Authors: Von Ahsen Uwe , Schroeder Renée
Published: February 2005

RNA can catalyse chemical reactions through its ability to fold into complex three‐dimensional structures and to specifically bind small molecules and divalent metal ions. The 2′‐hydroxyl groups of the ribose moieties contribute to this exceptional reactivity of RNA, compared to DNA. RNA is not only able to catalyse phosphate ester transfer reactions in ribonucleic acids, but can also show aminoacyl esterase activity, and is probably able to promote peptide bond formation. Bearing its potential for functioning both as a genome and as a gene product, RNA is suitable for in vitro evolution experiments enabling the selection of molecules with new properties. The growing repertoire of RNA catalysed reactions will establish RNA as a primordial molecule in the evolution of life.
Integrins hold Drosophila together
Authors: Brown Nicholas H.
Published: February 2005

The Drosophila position‐specific (PS) integrins are members of the integrin family of cell surface receptors and are thought to be receptors for extracellular matrix components. Each PS integrin consists of an α subunit, αPS1 or αPS2, and a βPS subunit. Mutations in the βPS subunit and the αPS2 subunit have been characterised and reveal that the PS integrins have an essential role in the adhesion of different cell layers to each other. The PS integrins are especially required for the function of the cell‐matrix‐cell junctions, where the muscles attach to the epidermis and where one surface of the developing wing adheres to the other. These junctions are similar to vertebrate focal adhesions and hemidesmosomes, which also contain integrins. Integrin‐mediated cell to cell adhesion via the extracellular matrix provides a way for tissues to adhere to each other without intermingling of their cells.
Molecular mechanisms of segmental patterning in the vertebrate hindbrain and neural crest
Authors: Wilkinson David G.
Published: February 2005

Recent work has shown that segmentation underlies the patterning of the vertebrate hindbrain and its neural crest derivatives. Several genes have been identified with segment‐restricted expression, and evidence is now emerging regarding their function and regulatory relationships. The expression patterns of Hox genes and the phenotype of null mutants indicate roles in specifying segment identity. A zinc finger gene Krox‐20 is a segment‐specific regulator of Hox expression, and it seems probable that retinoic acid receptors also regulate Hox genes in the hindbrain. The receptor tyrosine kinase gene Sek may mediate cell‐cell interactions that lead to segmentation. These studies provide a starting point for understanding the molecular basis of segmental patterning in the hindbrain.