bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human UDP‐glucuronosyl transferases: Chemical defence, jaundice and gene therapy
Authors: Brierley Catherine H. , Burchell Brian 
Published: February 2005

AbstractHuman UDP‐glucuronosyltransferases (UDPGTs) are a family of enzymes which detoxify many hundreds of compounds by their conjugation to glucuronic acid, rendering them both harmless and more water soluble, hence, excretable. The level of expression of each UDPGT isoform in the body is the result of interplay between temporal, tissue‐specific and environmental regulators. This complexity contributes to the difficulty in predicting the metabolic fate of compounds.Genetic defects and polymorphisms affecting individual isoform activities have deleterious and potentially lethal effects, as exemplified by the severe hyperbilirubinaemia observed in Crigler‐Najjar Syndrome. Such severe genetic defects in bilirubin glucuronidation are obvious candidates for antenatal screening and gene therapy.
Protein tracking‐induced supercoiling of DNA: A tool to regulate DNA transactions in vivo?
Authors: Dröge Peter 
Published: February 2005

AbstractAn interplay between DNA‐dependent biological processes appears to be crucial for cell viability. At the molecular level, this interplay relies heavily on the communication between DNA‐bound proteins, which can be facilitated and controlled by the dynamic structure of double‐stranded DNA. Hence, DNA structural alterations are recognized as potential tools to transfer biological information over some distance within a genome. Until recently, however, direct evidence for DNA structural information as a mediator between cellular processes was lacking. This changed when the concept of transient waves of DNA supercoiling, induced by proteins tracking along the right‐handed DNA double helix, came into the limelight. Indeed, a number of observations now suggest that helix tracking‐induced DNA structural information might be exploited to participate in the regulation of a variety of DNA transactions in vivo.
α/β Barrel evolution and the modular assembly of enzymes: Emerging trends in the flavin oxidase/dehydrogenase family
Authors: Scrutton Nigel S. 
Published: February 2005

Abstractα/β barrels have an ill‐defined origin. Evidence exists which favours their divergent evolution from a common ancestral barrel and convergent evolution to a stable fold. However, recent sequence and structural information for the flavin oxidase/dehydrogenase family of barrel enzymes indicate that sub‐families of α/β barrels have evolved divergently. The modular fusion of barrel domains with core structures from other gene families has also contributed to the evolution of related but catalytically distinct enzyme molecules within each sub‐family of the flavin oxidases/dehydrogenases. An analysis of the structures and sequences of the flavin oxidases/dehydrogenases has now enabled studies focusing on the evolutionary origins and modular assembly of this important family of proteins to be initiated.
The chromosome periphery during mitosis
Authors: Hernandez‐Verdun Danièle , Gautier Thierry 
Published: February 2005

AbstractA complex structure, visible by electron microscopy, surrounds each chromosome during mitosis. The organization of this structure is distinct from that of the chromosomes and the cytoplasm. It forms a perichromosomal layer that can be isolated together with the chromosomes. This layer covers the chromosomes except in centromeric regions. The perichromosomal layer includes nuclear and nucleolar proteins as well as ribonucleoproteins (RNPs). The list of proteins and RNAs identified includes nuclear matrix proteins (perichromin, peripherin), nucleolar proteins (perichro‐monucleolin, Ki‐67 antigen, B23 protein, fibrillarin, p103, p52), ribosomal proteins (S1) and snRNAs (U3 RNAs). Only limited information is available about how and when the perichromosomal layer is formed. During early prophase, the proteins extend from the nucleoli towards the periphery of the nucleus. Thin cordon‐like structures reach the nuclear envelope delimiting areas in which chromosomes condense. At telophase, the proteins are associated with the part of the chromosomes remaining condensed and accumulate in newly formed nucleoli in regions where chromatin is already decondensed. The perichromosomal layer contains several different classes of proteins and RNPs and it has been attributed various roles: (1) in chromosome organization, (2) as a barrier around the chromosomes, (3) involvement in compartmentation of the cells in prophase and telophase and (4) a binding site for chromosomal passenger proteins necessary to the early process of nuclear assembly.
Reovirus protein σ1: From cell attachment to protein oligomerization and folding mechanisms
Authors: Lee Patrick W. K. , Leone Gustavo 
Published: February 2005

AbstractThe reovirus cell attachment protein σ1 is a lollipopshaped structure with the fibrous tail anchored to the virion. Since it interacts with the cell receptor, σ1 is a major determinant of reovirus infectivity and tissue tropism. Studies on its structure‐function relationships have been facilitated by the fact that protein σ1 produced in any expression system is capable of binding to cell receptors. The use of site‐specific and deletion mutants has led to the identification and characterization of its virion anchorage and receptor binding domains. Studies on the oligomeric status of σ1 have revealed that σ1 is a homotrimer and that two independent trimerization events at different loci (the N‐ and C‐terminal halves, respectively) of the protein, are involved in its generation. This also accounts for a clearly demonstrable dominant negative effect by a mutant subunit in a wild‐type/mutant σ1 heterotrimer. Current efforts are focused on the involvement of chaperones in the generation of σ1 and on events that take place upon σ1 binding to the cell receptor. Protein σ1 has therefore become an excellent model system for the study of both virus attachment and protein oligomerization and folding mechanisms.
Structural and functional properties of the evolutionarily ancient Y‐box family of nucleic acid binding proteins
Authors: Wolffe Alan P. 
Published: February 2005

AbstractThe Y‐box proteins are the most evolutionarily conserved nucleic acid binding proteins yet defined in bacteria, plants and animals. The central nucleic acid binding domain of the vertebrate proteins is 43% identical to a 70‐amino‐acid‐long protein (CS7.4) from E. coli. The structure of this domain consists of an antiparallel fivestranded β‐barrel that recognizes both DNA and RNA. The diverse biological roles of these Y‐box proteins range from the control of the E. coli cold‐shock stress response to the translational masking of messenger RNA in vertebrate gametes. This review discusses the organization of the prokaryotic and eukaryotic Y‐box proteins, how they interact with nucleic acids, and their biological roles, both proven and potential.
Genes and genomes: Sequencing 5‐methylcytosine residues in genomic DNA
Authors: Grigg Geoffrey , Clark Susan 
Published: February 2005

AbstractTo analyse the biological role of 5‐methylation of cytosine residues in DNA requires precise and efficient methods for detecting individual 5‐methylcytosines (5‐MeCs) in genomic DNA. The methods developed over the past decade rely on either differential enzymatic or chemical cleavage of DNA, or more recently on differential sensitivity to chemical conversion of one base to another. The most commonly used methods for studying the methylation profile of DNA, including the bisulphite base‐conversion method, are reviewed.
Mechanics of myosin motor: Force and step size
Authors: Jiang Ming Ya , Sheetz Michael P. 
Published: February 2005

AbstractHow motor proteins induce mechanical movement at the molecular level has been a focus of biophysicists for a long time. While the whole picture is yet to be completely revealed, recent developments in looking at nanometer‐scale movement with millisecond‐time resolution driven by single motors have revealed important new details about the moving step size and amount of force generated per molecule.
Salmonella: Now you see it, now you don't
Authors: Stein Murry A. , Mills Scott D. , Finlay B. Brett 
Published: February 2005

AbstractDiseases caused by Salmonella species are characterized by bacterial invasion of host cells. Salmonella invasion requires a genetic locus (inv) with homology to bacterial systems involved in specific protein export and organelle assembly. Until recently, the actual Salmonella invasion factors exported or assembled by the inv system remained unidentified. It now appears that Salmonella produces novel appendages upon contact with host cells. These appendages are transient, appearing and disappearing rapidly from the bacterial surface. Appendages are altered in strains unable to invade due to mutations within the inv/spa locus. Therefore, a role for the invasion locus has been identified, providing another example of bacterial pathogens responding to signals provided by the host cell surface.
Phosphatidylinositol 3‐kinase
Authors: Kapeller Rosana , Cantley Lewis C. 
Published: February 2005

AbstractCurrently, a central question in biology is how signals from the cell surface modulate intracellular processes. In recent years phosphoinositides have been shown to play a key role in signal transduction. Two phosphoinositide pathways have been characterized, to date. In the canonical phosphoinositide turnover pathway, activation of phosphatidylinositol‐specific phospholipase C results in the hydrolysis of phosphatidylinositol 4,5‐bisphospate and the generation of two second messengers, inositol 1,4,5‐trisphosphate and diacylglycerol. The 3‐phosphoinositide pathway involves protein‐tyrosine kinase‐mediated recruitment and activation of phosphatidylinositol 3‐kinase, resulting in the production of phosphatidylinositol 3,4‐bisphosphate and phosphatidylinositol 3,4,5‐trisphosphate. The 3‐phosphoinositides are not substrates of any known phospholipase C, are not components of the canonical phosphoinositide turnover pathway, and may themselves act as intracellular mediators. The 3‐phosphoinositide pathway has been implicated in growth factor‐dependent mitogenesis, membrane ruffling and glucose uptake. Furthermore the homology of the yeast vps34 with the mammalian phosphatidylinositol 3‐kinase has suggested a role for this pathway in vesicular trafficking.In this review the different mechanisms employed by protein‐tyrosine kinases to activate phosphatidylinositol 3‐kinase, and its involvement in the signaling cascade initiated by tyrosine phosphorylation, are examined.
Molecular biology of embryonic development: How far have we come in the last ten years?
Authors: Davidson Eric H. 
Published: February 2005

AbstractThe successes of molecular developmental biology over the last ten years have been particularly impressive in those directions favored by its major paradigms. New technologies have both guided and been guided by the progress of the field. I review briefly some of the major insights into embryonic development that have derived from research in four specific areas: early embryogenesis of various forms; “pattern formation”; evolutionary conservation of regulatory elements; and spatial mechanisms of gene regulation. There remain many major problem areas, some of which may require new orientations to solve.
Gene targeting in the mouse
Authors: Melton David W. 
Published: February 2005

AbstractMice with alterations to specific endogenous genes can be produced by gene targeting in embryonic stem cells. The field has developed rapidly over the past decade, so that large numbers of mice with different gene deficiencies have been generated. Knockout mice provide an ideal opportunity to analyse the function of individual mammalian genes and to model a range of human inherited disorders. This powerful approach has also identified numerous examples of gene redundancy and has highlighted the need to consider metabolic differences between man and mouse in disease modelling. More sophisticated gene‐targeting methods are now being used to introduce subtle gene alterations. In the future, more refined genetic analysis and genome, rather than individual gene, alterations will be achieved by incorporating site‐specific recombination into targeting strategies. Gene targeting could also make a contribution to improved protocols for gene therapy.
Tensin: A potential link between the cytoskeleton and signal transduction
Authors: Lo Su Hao , Weisberg Ellen , Chen Lan Bo 
Published: February 2005

AbstractCytoskeletal proteins provide the structural foundation that allows cells to exist in a highly organized manner. Recent evidence suggests that certain cytoskeletal proteins not only maintain structural integrity, but might also be associated with signal transduction and suppression of tumorigenesis. Since the time of the discovery of tensin, a fair amount of data has been gathered which supports the notion that tensin is one such protein possessing these characteristics. In this review, we discuss recent studies that: (1) elucidate a role for tensin in maintenance of cellular structure and signal transduction; (2) implicate tensin as the anchor for actin filaments at the focal adhesion; (3) describe the phosphorylation of tensin; (4) describe potential targets for its Src homology region 2 domain; (5) describe the association between tensin and the nuclear protein p130; and (6) demonstrate that increased tensin expression in a cell line appears to reduce its transformation potential.
DNA damage tolerance, mismatch repair and genome instability
Authors: Karran P. , Bignami M. 
Published: February 2005

AbstractDNA mismatch repair is an important pathway of mutation avoidance. It also contributes to the cytotoxic effects of some kinds of DNA damage, and cells defective in mismatch repair are resistant, or tolerant, to the presence of some normally cytotoxic base analogues in their DNA. The absence of a particular mismatch binding function from some mammalian cells confers resistance to the base analogues O6‐methylguanine and 6‐thioguanine in DNA. Cells also acquire a spontaneous mutator phenotype as a consequence of this defect. Impaired mismatch binding can cause an instability in DNA microsatellite regions that comprise repeated dinucleotides. Microsatellite DNA instability is common in familial and sporadic colon carcinomas as well as in a number of other tumours. Several independent lines of investigation have identified defects in mismatch repair proteins that are causally related to these cancers.
The tails of survival curves
Authors: Smith David W. E. 
Published: February 2005

AbstractThis article focuses on the occasional individuals of many species that live longer than is usual for their populations – here called longevity outliers. They appear to be exceptions to the usual patterns of mortality rates that increase with age. There is no model of survivorship that accommodates all of these individuals. They are less vulnerable to the usual causes of death than most in their populations. There are hints of genetically based mechanisms in the form of life‐prolonging genes in invertebrates and genetic resistance to fatal diseases in higher organisms. The reasons why longevity outliers ultimately die are not known. Based on well‐established trends, I predict that there will be many more humans reaching very old ages in the next century.
Nuclear/growth factors
Authors: Prochiantz A. , Théodore L. 
Published: February 2005

AbstractThe now classical model for cell‐cell communication espouses that information travels between cells in the form of molecules that bind specific cell‐surface receptors and trigger signal‐transducing mechanisms that eventually lead to transcriptional modifications. Here we gather the available information suggesting that some growth factors may also act by interfering directly with gene transcription, following their internalization and nuclear translocation. Among these factors are bona fide growth factors such as Fibroblast Growth Factor‐1 and ‐2 and Schwannoma Derived Growth Factor, for which internalization and nuclear translocation have been demonstrated. Conversely, we propose that some isoforms of nuclear factors of the homeoprotein family could pass from cell to cell. The implications of the model are presented in the context of the specificity of cellular interactions.
Illuminating plant development
Authors: Duckett Catherine M. , Gray John C. 
Published: February 2005

AbstractThroughout 1994 remarkable progress was made with molecular and genetic studies on signal transduction pathways of photomorphogenesis, the lightdependent development of plants. Analysis of Arabidopsis DET and COP genes suggests that they are involved in suppression of photomorphogenic development in the dark and that this is then reversed by light. Studies with COP1 indicate that this is achieved by redistribution of COP1 from the nucleus, in the dark, to the cytosol in the light(1). Overexpression of COP1 in the light, however, was able to partially suppress photomorphogenic development, confirming its role as a light‐inactivatable repressor(2). Evidence also suggests that some of the COP gene products may interact directly to form a large complex(3).
Surprising developments in the legume root nodule
Authors: Cook Douglas 
Published: February 2005

AbstractRoot nodule morphogenesis involves the induction of mitotic activity in otherwise quiescent root cortical cells, giving rise to the nodule primordium. One gene expressed during nodule initiation, ENOD40, has been implicated in nodule growth and/or differentiation(1,2). Interestingly, although the nucleotide sequence of ENOD40 genes from soybean(3,4) and Medicago(1,2) are highly homologous, they are unlikely to encode a similar protein product. In fact, a remarkable feature of these genes is their apparent lack of protein coding potential. Thus, ENOD40 is a member of the growing list of eukaryotic genes whose RNA product is implicated in control of cell growth and differentiation, the so called riboregulators(5).
The cryptic life style of adenoassociated virus
Authors: Berns Kenneth I. , Linden R. Michael 
Published: February 2005

AbstractAlthough 80–90% of adults are seropositive for antibodies against the human parvovirus adeno‐associated virus (AAV), infection has not been associated with either symptoms or disease. In cell culture, AAV infection is not productive unless there is a coinfection with a helper virus, either adenovirus or any type of herpes virus; in the absence of a helper virus coinfection the viral genome is integrated into the genome, usually at a specific site on chromosome 19q13.3‐qter. The integrated genome can be activated and rescued by subsequent super infection by a helper virus. The high frequency of site‐specific integration by AAV and the lack of associated disease have encouraged the use of AAV as a vector for gene therapy. This review will focus on the molecular mechanisms involved in the establishment of, and rescue from, the latent state and their relevance to use of AAV as a vector.
The initiation of senescence and its relationship to embryonic cell differentiation
Authors: Rosenberger Robert F. 
Published: February 2005

AbstractMouse embryonic stem cells have an unlimited lifespan in cultures if they are prevented from differentiating. After differentiating, they produce cells which divide only a limited number of times. These changes seen in cultures parallel events that occur in the developing embryo, where immortal embryonic cells differentiate and produce mortal somatic ones. The data strongly suggest that differentiation initiates senescence, but this view entails additional assumptions in order to explain how the highly differentiated sexual gametes manage to remain potentially immortal. Cells differentiate by blocking expression from large parts of their genome and it is suggested that losses or gains of genetic totipotency determine cellular lifespans. Cells destined to be somatic do not regain totipotency and senesce, while germ‐line cells regain complete genome expression and immortality after meiosis and gamete fusions. Losses of genetic totipotency could induce senescence by lowering the levels of repair and maintenance enzymes.
The origin and function of the mammalian Y chromosome and Y‐borne genes – an evolving understanding
Authors: Graves Jennifer A. Marshall 
Published: February 2005

AbstractMammals have an XX:XY system of chromosomal sex determination in which a small heterochromatic Y controls male development. The Y contains the testis determining factor SRY, as well as several genes important in spermatogenesis. Comparative studies show that the Y was once homologous with the X, but has been progressively degraded, and now consists largely of repeated sequences as well as degraded copies of X linked genes. The small original X and Y have been enlarged by cycles of autosomal addition to one partner, recombination onto the other and continuing attrition of the compound Y. This addition–attrition hypothesis predicts that the pseudoautosomal region of the human X is merely the last relic of the latest addition. Genes (including SRY) on the conserved or added region of the Y evolved functions in male sex determination and differentiation distinct from the general functions of their X‐linked partners. Although the gonadogenesis pathway is highly conserved in vertebrates, its control has probably changed radically and rapidly in vertebrate – even mammalian – evolution.
The channels model of nuclear matrix structure
Authors: Razin Sergey V. , Gromova Irina I. 
Published: February 2005

AbstractThe specificity of eukaryotic DNA organization into loops fixed to the nuclear matrix/chromosomal scaffold has been studied for more than fifteen years. The results and conclusions of different authors remain, however, controversial. Recently, we have elaborated a new approach to the study of chromosomal DNA loops. Instead of characterizing loop basements (nuclear matrix DNA), we have concentrated our efforts on the characterization of individual loops after their excision by DNA topoisomerase II‐mediated DNA cleavage at matrix attachment sites. In this review the results of applying this mapping approach are compared with the results and conclusions from studies of nuclear matrix DNA. An attempt is also made to reconsider all data about the specificity of DNA interactions with the nuclear matrix and to suggest a model of spatial organization of the eukaryotic genome which resolves apparent contradictions between these data.
Origins of G1 arrest in senescent human fibroblasts
Authors: Stein Gretchen H. , Dulić Vjekoslav 
Published: February 2005

AbstractHuman diploid fibroblasts have a finite proliferative lifespan in culture, at the end of which they are ararrested with G1 phase DNA contents. Upon serum stimulation, senescent cells are deficient in carrying out a subset of early signal transduction events such as activation of protein kinase C and induction of c‐fos. Later in G1, they uniformly fail to express late G1 genes whose products are required for DNA synthesis, implying that they are unable to pass the R point. Failure to pass the R point may occur because senescent cells are unable to phosphorylate the retinoblastoma protein, owing to the accumulation of inactive complexes of cyclin E/Cdk2 and possibly cyclin D/Cdk4. Senescent cells contain high amounts of p21, a potent cyclin‐dependent kinase inhibitor whose levels are also elevated in cells arrested in G1 following DNA damage, suggesting that both arrests might share a common mechanism. Cell aging is accompanied by a progressive shortening of chromosomal telomeres, which could be perceived by the cells as a form of DNA damage that gives rise to the signals that inactivate the cell cycle machinery.