bluuebunny/crossref_metadata_2025_split huggingface dataset:
The enigmatic oxygen‐avid hemoglobin of Ascaris
Authors: Goldberg Daniel E. 
Published: February 2005

AbstractThe parasitic nematode Ascaris lives in the low‐oxygen intestinal folds of over one billion people world‐wwide. The worm has an octameric hemoglobin that binds oxygen four orders of magnitude more tightly than does human hemogobin. Our studies have focused on elucidating the molecular mechanism of oxygen avidity, the basis of multimerization and the function of this remarkable molecule. We now believe that we understand a fair amount about the molecular interactions that result in enhanced avidity, have some preliminary ideas on octamer formation, and have some hypotheses about possible function. Along the way we have stumbled into the disciplines of intron evolution, sterol biosynthesis and oxygen‐regulated gene expression.
Retinoic acid and the differentiation of lymphohaemopoietic stem cells
Authors: Göttgens Bertholdm , Green Anthony R. 
Published: February 2005

AbstractThe study of haemopoiesis enables us to address one of the central questions of developmental biology, concerning the molecular mechanisms by which a multipotent cell develops into distinct differentiated progeny. Recent work(1) suggests specific roles for retinoic acid receptors at two distinct stages of haemopoiesis. Continuous cell lines of lymphohaemopoietic progenitors were established by infection with a retrovirus containing a dominant negative retinoic acid receptor. The cell lines depend on stem cell factor for their proliferation and can be induced to diffentiate into B‐lymphocytes, erythrocytes, neutrophils, monocytes, mast cells and megakaryocytes. Since lymphohaemopoietic progenitors represent less than 0.01% of nucleated marrow cells, immortalised progenitors provide a valuable system with which to study haemopoiesis on a molecular level.
Epigenetic regulation of the maize Spm transposon
Authors: Fedoroff Nina , Schläppi Michael , Raina Ramesh 
Published: February 2005

AbstractExpression and transposition of the Suppressor‐mutator (Spm) transposon of maize are controlled by interacting epigenetic and autoregulatory mechanisms. Methylation of critical element sequences prevents both transcription and transposition, heritably inactivating the element. The promoter, comprising the terminal 0.2 kb of the element, and a 0.35‐kb, highly GC‐rich, downstream sequence are the methylation target sequences. The element encodes two proteins necessary for transposition, TnpA and TnpD. There are multiple TnpA binding sites, both in the 5′ terminal promoter region and at the element's 3′ end. In addition to its role in transposition, TnpA is both a positive and a negative regulator of transcription. TnpA represses the element's promoter when it is not methylated. When the element is inactive and its promoter methylated, TnpA activates the methylated promoter and facilitates both its transient and heritable demethylation.
Precursor cell types in the germinal zone of the cerebral cortex
Authors: Williams Brenda P. 
Published: February 2005

AbstractRetroviral lineage tracing experiments suggest that the cortical ventricular zone is composed of a mixture of precursor cell types. The majority generate a single cell type (neurones, astrocytes or oligodendrocytes) and the remainder generate neurones and a single type of glial cell. Pluripotential precursor cells, that have the ability to generate all three cell types, are not observed. A recent paper, however, reports that when single ventricular zone cells are cultured in isolation, a small percentage of these cells are pluripotential(1). This review will discuss what this knowledge tells us about cortical development.
Determinants of blastomere identity in the early C. elegans embryo
Authors: Bowerman Bruce 
Published: February 2005

AbstractGenetic and molecular studies of development in Caenorhabiditis elegans have identified regulators that appear to control pattern formation in the cellularized nematode embryo. Two genes, skn‐1 and pie‐1, are required for specifying the different identities of two sister blastomeres in a 4‐cell embryo, called P2 and EMS. The skn‐1 gene encodes a DNA binding protein that may control blastomere development by regulating transcription in EMS and its descendants. ABa and ABp, the other two sisters in a 4‐cell embryo, are influenced to develop differently by cell signaling events that require the two genes apx‐1 and glp‐1. In this review, I summarize evidence that some or all of these genes may encode embryonic determinants of blastomere identity.
A model for repair of radiation‐induced DNA double‐strand breaks in the extreme radiophile Deinococcus radiodurans
Authors: Minton Kenneth W. , Daly Michael J. 
Published: February 2005

AbstractThe bacterium Deinococcus (formerly Micrococcus) radiodurans and other members of the eubacterial family Deinococaceae are extremely resistant to ionizing radiation and many other agents that damage DNA. Stationary phase D. radiodurans exposed to 1.0‐1.5 Mrad γ‐irradiation sustains >120 DNA double‐strand breaks (dsbs) per chromosome; these dsbs are mended over a period of hours with 100% survival and virtually no mutagenesis. This contrasts with nearly all other organisms in which just a few ionizing radiation induced‐dsbs per chromosome are lethal. In this article we present an hypothesis that resistance of D. radiodurans to ionizing radiation and its ability to mend radiation‐induced dsbs are due to a special form of redundancy wherein chromosomes exist in pairs, linked to each other by thousands of four‐stranded (Holliday) junctions. Thus, a dsb is not a lethal event because the identical undamaged duplex is nearby, providing an accurate repair template. As addressed in this article, much of what is known about D. radiodurans suggests that it is particularly suited for this proposed novel form of DNA repair.
Calcium signalling and cell proliferation
Authors: Berridge Michael J. 
Published: February 2005

AbstractThe orderly sequence of events that constitutes the cell cycle is carefully regulated. A part of this regulation depends upon the ubiquitous calcium signalling system. Many growth factors utilize the messenger inositol trisphosphate (InsP3) to set up prolonged calcium signals, often organized in an oscillatory pattern. These repetitive calcium spikes require both the entry of external calcium and its release from internal stores. One function of this calcium signal is to activate the immediate early genes responsible for inducing resting cells (G0) to re‐enter the cell cycle. It may also promote the initiation of DNA synthesis at the G1/S transition. Finally, calcium contributes to the completion of the cell cycle by stimulating events at mitosis. The role of calcium in cell proliferation is highlighted by the increasing number of anticancer therapies and immunosuppressant drugs directed towards this calcium signalling pathway.
A 200‐amino acid ATPase module in search of a basic function
Authors: Confalonieri Fabrice , Duguet Michel 
Published: February 2005

AbstractA fast growing family of ATPases has recently been highlighted. It was named the AAA family, for ATPases Associated to a variety of cellular Activities. The key feature of the family is a highly conserved module of 230 amino acids present in one or two copies in each protein. Despite extensive sequence conservation, the members of the family fulfil a large diversity of cellular functions: cell cycle regulation, gene expression in yeast and HIV, vesicle‐mediated transport, peroxisome assembly, 26S protease function etc. In addition, several members of this family can be found in the same organism (up to 17 in S. cerevisiae). The contrast between functional diversity and structural conservation of the module, from archaebacteria to mammals, suggests that it plays an essential, but as yet unknown, role at key points of the cellular machinery. Two (non‐exclusive) such possibilities are: (1) ATP‐dependent proteasome function and (2) ATP‐dependent anchorage of proteins. Finally, the basic biochemical activity of the AAA module is still a matter of speculation, and we propose that it acts as an ATP‐dependent protein clamp.
Disease lesion mimics of maize: A model for cell death in plants
Authors: Johal Gurmukh S. , Hulbert Scot H. , Briggs Steven P. 
Published: February 2005

AbstractA class of maize mutants, collectively known as disease lesion mimics, display discrete disease‐like symptoms in the absence of pathogens. It is intriguing that a majority of these lesion mimics behave as dominant gain‐of‐function mutations. The production of lesions is strongly influenced by light, temperature, developmental state and genetic background. Presently, the biological significance of this lesion mimicry is not clear, although suggestions have been made that they may represent defects in the plants' recognition of, or response to, pathogens. One feature that is common to all lesion mimics is their association with cell death. In plants, as in animals, a number of developmental and pathological processes exist where controlled cell death, whether programmed or triggered in response to physiological or environmental stimuli, constitutes the normal aspect of life. Might disease lesion mimic mutations represent variants where regulation of desirable cell death has gone awry? In this paper we argue that this might be the case, and further conjecture that these mutants offer a unique opportunity for studying the genetic and cellular mechanisms of cell death in plants.
Mhox and vertebrate skeletogenesis: The long and the short of it
Authors: Brickell Paul M. 
Published: February 2005

AbstractThe development of the vertebrate skeleton is under complex genetic control, and good progress is being made towards identifying the genes responsible. A recent paper(1) contributes to this progress by describing transgenic mice in which the homeobox‐containing MHox gene has been disrupted. MHox(−/−) mice have a range of skeletal defects, involving loss or shortening of structures in the skull, face and limb. Puzzling features of the MHox(−/−) mutation, which has similar effects on bones with very different embryological origins and yet spares other bones completely, may hold clues to the mechanisms that shape the skeleton. MHox(−/−) mice, used in conjunction with other skeletal mutants, will be important tools for exploring these mechanisms further.
DNA topoisomerase II mutations and resistance to anti‐tumor drugs
Authors: Vassetzky Yegor S. , Alghisi Gian‐Carlo , Gasser Susan M. 
Published: February 2005

AbstractMutations in DNA topoisomerase II are often correlated with drug‐resistance in tumor cell lines. Studies of topoisomerase II‐mediated drug‐resistance in various model systems, as well as the sequencing of such mutations from drug‐resistant tumors, have shed light on the functional domains of topoisomerase II, on how it interacts with inhibitors, and on the different mechanisms by which cells avoid the toxic effects of many clinically important anti‐tumor drugs.
Structure‐function relationships in smooth muscle: The missing links
Authors: Small J. Victor 
Published: February 2005

AbstractSmooth muscle cells have developed a contractile machinery that allows them to exert tension on the surrounding extracellular matrix over their entire length. This has been achieved by coupling obliquely organized contractile filaments to a more‐or‐less longitudinal framework of cytoskeletal elements. Earlier structural data suggested that the cytoskeleton was composed primarily of intermediate filaments and played only a passive role. More recent findings highlight the segregation of actin isotypes and of actin‐associated proteins between the contractile and cytoskeletal domains and raise the possibility that the cytoskeleton performs a more active function. Current efforts focus on defining the relative contributions of myosin cross‐bridge cycling and actin‐associated protein interactions to the maintenance of tension in smooth muscle tissue.
Sex determination in hymenoptera: A need for genetic and molecular studies
Authors: Beukeboom Leo W. 
Published: February 2005

AbstractSex‐determining mechanisms appear to be very diverse in invertebrates. Haplodiploidy is a widespread mode of reproduction in insects: males are haploid and females are diploid. Several models have been proposed for the genetic mechanisms of sex determination in haplodiploid Hymenoptera. Although a one‐locus multi‐allele model is valid for several species, sex determination in other species cannot be explained by any of the existing models. Evidence for and predictions of two recently proposed models are discussed. Some genetic and molecular approaches are proposed to study sex determination in Hymenoptera.
Keeping the beat: Form meets function in the Chlamydomonas flagellum
Authors: Johnson Karl A. 
Published: February 2005

AbstractRecent studies in the green alga Chlamydomonas and other flagellated cells have revealed new insights into the relationships between the structure and function of the eukaryotic flagellum. These advances provide a basis from which a unified view can be constructed of how a flagellum operates. In addition, investigations of flagellar assembly offer new perspectives revealing the mechanisms used by cells to create these nanoscale structures. New developments in the molecular biology of Chlamydomonas provide powerful tools for the continued exploration of flagellar biology in this cell. These studies are of interest not only within the field of biology, but also in physics and materials science; the problems of fabrication, assembly, function and regulation of nanoscale machines have been elegantly solved during the evolution of biological systems, providing models from which much remains to be learned.
The complexity in regulating the expression of tenascins
Authors: Chiquet‐Ehrismann Ruth , Hagios Carmen , Schenk Susanne 
Published: February 2005

AbstractThe tenascins are a growing family of extracellular matrix proteins of typical multidomain structure. The prototype to be discovered was tenascin‐C. It shows a highly regulated expression pattern during embryonic development and is often transiently associated with morphogenetic tissue interactions during organogenesis. In the adult organism reexpression of tenascin‐C occurs in tumors and many other pathological conditions. Tenascin‐C expression can be regulated by many different growth factors and hormones. Furthermore, mechanical strain exerted by fibroblasts seems to induce the expression of tenascin‐C. This could represent a mechanism of translating mechanical forces into protein patterns, a step of potential relevance in the organization of embryogenesis. Tenascin‐C as well as tenascin‐R are believed to counteract the cell adhesion and spreading activity of fibronectin, thereby facilitating cell movement.
A unique role for enhancers is revealed during early mouse development
Authors: Majumder Sadhan , Depamphilis Melvin L. 
Published: February 2005

AbstractTranscription and replication of genes in mammalian cells always requires a promoter or replication origin, respectively, but the ability of enhancers to stimulate these regulatory elements and the interactions that mediate this stimulation are developmentally acquired. The primary function of enhancers is to prevent repression, which appears to result from particular components of chromatin structure. Factors responsible for this repression are present in the maternal nucleus of oocytes and its descendant, the maternal pronucleus of mouse 1‐cell embryos and in mouse 2‐cell embryos, but are absent in the paternal pronucleus. Thus, enhancers are not needed to achieve efficient transcription and replication in paternal pronuclei. However, enhancers, even in the presence of their specific activation protein, are inactive prior to formation of a 2‐cell embryo, suggesting that a coactivator essential for enhancer function is not available until zygotic gene expression begins. Furthermore, enhancer stimulation of transcription appears to be mediated through a promoter transcription factor, but this interaction can change as cells undergo differentiation, switching from a TATA‐box independent to a TATA‐box dependent mode.
Stress signaling in yeast
Authors: Ruis Helmut , Schüller Christoph 
Published: February 2005

AbstractIn the yeast Saccharomyces cerevisiae three positive transcriptional control elements are activated by stress conditions: heat shock elements (HSEs), stress response elements (STREs) and AP‐1 responsive elements (AREs). HSEs bind heat shock transcription factor (HSF), which is activated by stress conditions causing accumulation of abnormal proteins. STREs mediate transcriptional activation by multiple stress conditions. They are controlled by high osmolarity via the HOG signal pathway, which comprises a MAP kinase module and a two‐component system homologous to prokaryotic signal transducers. AREs bind the transcription factor Yap1p. The three types of control elements seem to have overlapping, but distinct functions. Some stress proteins encoded by HSE‐regulated genes are necessary for growth of yeast under moderate stress, products of STRE‐activated genes appear to be important for survival under severe stress and ARE‐controlled genes may mainly function during oxidative stress and in the response to toxic conditions, such as caused by heavy metal ions.
Does replication‐induced transcription regulate synthesis of the myriad low copy number proteins of Escherichia coli?
Authors: Guptasarma Purnananda 
Published: February 2005

AbstractOver 80% of the genes in the E. coli chromosome express fewer than a hundred copies each of their protein products per cell. It is argued here that transcription of these genes is neither constitutive nor regulated by protein factors, but rather, induced by the act of replication. The utility of such replication‐induced (RI) transcription to the temporal regulation of synthesis of determinate quantities of low copy number (LCN) proteins is described. It is suggested that RI transcription may be necessitated, as well as facilitated, by the folding of the bacterial chromosome into a compact nucleoid. Mechanistic aspects of the induction of transcription by replication are discussed with respect to the modulation of transcriptional initiation by negative supercoiling effects, promoter methylation status and derepression. It is shown that RI transcription offers plausible explanations for the constancy of the C period of the E. coli cell cycle and the remarkable conservation of gene order in the chromosomes of enteric bacteria. Some experimental tests of the hypothesis are proposed.
Microsatellite instability and a TGFβ receptor: Clues to A growth control pathway
Authors: Benson John R. , Wells K. 
Published: February 2005

AbstractDefects of growth inhibitory pathways have an important role in disorders of cell growth and differentiation. The discovery of a mutation in one of the principle components of the transforming growth factor β (TGFβ) receptor system which is linked to a DNA repair defect(1) represents one possible mechanism of escape from negative regulatory influences acting upon cells. TGFβ is a pre‐eminent negative growth factor and this article discusses (1) the role of TGFβ in maintaining epithelial homeostasis; (2) how breakdown of inhibitory pathways can promote neoplastic development; (3) the significance of a receptor defect in a negative signalling pathway; and (4) the potential therapeutic sequelae resulting from restoration of cellular responsiveness to TGFβ.
The therapeutic potential of antisense oligonucleotides
Authors: Sharma Harsh W. , Narayanan Ramaswamy 
Published: February 2005

AbstractSpecific inhibition of gene expression by antisense agents provides the basis for rational drug discovery based on molecular targets. Due to the specificity of Watson‐Crick base‐pair hybridization, antisense oligodeoxynucleotides have been used extensively in attempts to inhibit gene expression in both in vitro and in vivo models. Analogues modified from normal phosphodiester oligodeoxynucleotides have entered clinical trials against diseases including AIDS and cancer. Although the precise mechanism of action of these drugs has not been clarified, these oligodeoxynucleotides offer considerable promise as novel molecular therapeutics. We review the recent attempts to harness the therapeutic potential of these oligodeoxynucleotides and appraise the near‐term prospects for antisense technology.
Transformations in null mutants of hox genes: Do they represent intercalary regenerates?
Authors: Crawford Michael 
Published: February 2005

AbstractIn the minds of many, Hox gene null mutant phenotypes have confirmed the direct role that these genes play in specifying the pattern of vertebrate embryos. The genes are envisaged as defining discrete spatial domains and, subsequently, conferring specific segmental identities on cells undergoing differentiation along the antero‐posterior axis. However, several aspects of the observed mutant phenotypes are inconsistent with this view. These include: the appearance of other, unexpected transformations along the dorsal axis; the occurrence of mirror‐image duplications; and the development of anomalies outside the established domains of normal Hox gene expression. In this paper, Hox gene disruptions are shown to elicit regeneration‐like responses in tissues confronted with discontinuities in axial identity. The polarities and orientations of transformed segments which emerge as a consequence of this response obey the rules of distal transformation and intercalary regeneration. In addition, the incidence of periodic anomalies suggests that the initial steps of Hox‐mediated patterning occurs in Hensen's node. As gastrulation proceeds, mesoderm cell cycle kinetics impose constraints upon subsequent cellular differentiation. This results in the delayed manifestation of transformations along the antero‐posterior axis. Finally, a paradigm is sketched in which temporal, rather than spatial axial determinants direct differentiation. Specific, testable predictions are made about the role of Hox genes in the establishment of segmental identity.
The small nuclear GTPase Ran: How much does it run?
Authors: Rush Mark G. , Drivas George , D'eustachio Peter 
Published: February 2005

AbstractRan is one of the most abundant and best conserved of the small GTP binding and hydrolyzing proteins of eukaryotes. It is located predominantly in cell nuclei. Ran is a member of the Ras family of GTPases, which includes the Ras and Ras‐like proteins that regulate cell growth and division, the Rho and Rac proteins that regulate cytoskeletal organization and the Rab proteins that regulate vesicular sorting. Ran differs most obviously from other members of the Ras family in both its nuclear localization, and its lack of sites required for post‐translational lipid modification. Ran is, however, similar to other Ras family members in requiring a specific guanine nucleotide exchange factor (GEF) and a specific GTPase activating protein (GAP) as stimulators of overall GTPase activity. In this review, the multiple cellular functions of Ran are evaluated with respect to its known biochemistry and molecular interactions.
Expanded glutamines and neurodegeneration – a gain of insight
Authors: Bates Gillian 
Published: February 2005

AbstractGlutamine repeat expansion has been established as the mutation underlying five inherited neurodegenerative diseases. The mechanism by which this apparently universal mutation, in ubiquitously expressed proteins, causes highly selective neurodegeneration is unknown. The proteins containing the glutamine expansions are otherwise unrelated and likely to have different functions. Two recently published papers(1,2) provide evidence of a conformational change occurring in polyglutamine expansions, which may allow novel interactions and is consistent with a toxic gain‐of‐function hypothesis. HAP1, a protein that interacts with huntingtin (Huntington's disease protein), has an expression profile that intriguingly mirrors the selective neurodegeneration seen in Huntington's disease(2).