bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic dissection of Ca2+‐dependent ion channel function in Paramecium
Authors: Preston Robin R. 
Published: February 2005

AbstractThe ciliated protozoan, Paramecium, broadcasts the activity of its individual ion channel classes through its swimming behaviour. This fact has made it possible to isolate mutants with defective ion currents, simply by selecting individuals with abnormal swimming patterns. At least four of Paramecium's ion currents are activated by rising intracellular calcium concentration, including two K+ currents and a Na+ current. A variety of cell lines with defects in these Ca2+‐dependent currents have been isolated: in several cases, the defects have been traced to mutations in the structural gene for calmodulin. Sequence analysis of calmodulins from these and other Ca2+ ‐dependent ion‐current mutants may enable a detailed mapping of putative channel interaction domains on the surface of the calmodulin molecule.
The functional importance of multiple actin isoforms
Authors: Rubenstein Peter A. 
Published: February 2005

AbstractActin is a protein that plays an important role in cell structure, cell motility, and the generation of contractile force in both muscle and nonmuscle cells. In many organisms, multiple forms of actin, or isoactins, are found. These are products of different genes and have different, although very similar, amino acid sequences. Furthermore, these isoactins are expressed in a tissue specific fashion that is conserved across species, suggesting that their presence is functionally important and their behavior can be distinguished quantitatively from one another in vitro. In muscle cells, they are differentially distributed within the cell and some are specifically associated with structures such as costameres, mitochondria, and neuromuscular junctions. There is also good evidence for specific isoactin function in microvascular pericytes and in the intestinal brush border. However, the necessity of specific isoactins for various functions has not yet been conclusively demonstrated.
Perspectives on methylmalonic acidemia resulting from molecular cloning of methylmalonyl CoA mutase
Authors: Ledley Fred D. 
Published: February 2005

AbstractMethylmalonyl CoA mutase deficiency (methylmalonic acidemia) has been a paradigm for biochemical and somatic cell genetic approaches to human disease. Recently, genes encoding this enzyme have been cloned from several species. These studies have provided information about the primary structure and evolution of this enzyme, the mutations which underlie its deficiency state, and the structure‐function determinants which are required for its activity. Gene transfer studies now permit restitution of this enzyme to genetically deficient cells and may enable somatic gene therapy to be undertaken. Molecular genetic studies not only provide more detailed information about this enzyme, but introduce new perspectives on the molecular mechanisms and dynamics of its function and raise new questions about the dyshomeostatic consequences of its deficiency.
At the crossroads of developmental genetics: The cloning of the classical mouse T locus
Authors: Silver Lee M. 
Published: February 2005

AbstractThe discovery, more than 60 years ago, of a mutant mouse with a short tail led to the birth of the new field of developmental genetics. Over the years since, numerous investigators have probed the biology of the original short‐tail mutation at the T locus, as well the naturally‐occurring t haplotypes that were uncovered as a result of their interaction with this mutation. Although the T locus ranks among the best characterized developmental loci in the mouse, it was not among the first to be cloned. This situation has now been rectified with two recent reports from Herrmann, Lehrach and their colleagues. While the T locus is expressed uniquely in the embryonic tissues predicted from the mutant phenotype, the gene itself, as well as the predicted amino acid sequence of the T product, show no strong homology to any known sequence. For the moment, at least, the mystery behind the function of the T locus still awaits definitive resolution.
S100 protein and down syndrome
Authors: Marks Alexander , Allore Robert 
Published: February 2005

AbstractS100 protein is a low molecular weight calcium‐binding protein widely distributed in the central nervous system of vertebrates. Recent evidence suggests that S100 protein may play a role in the regulation of glial proliferation and neuronal differentiation. The gene for S100 protein has been mapped to the 21q22 region, a chromosomal locus whose duplication has been implicated in the generation of Down Syndrome (DS). This raises the possibility that abnormalities in S100 protein gene dosage at a critical period during development may be responsible for some of the neurologic abnormalities associated with DS.
Traction and the formation of mesenchymal condensations in vivo
Authors: Bard Jonathan B. L. 
Published: February 2005

AbstractAlthough the segregation of mesenchyme into distinct aggregates is the first step in the development of a range of tissues that includes bones, somites, feathers and nephrons, we still know very little about the mechanisms by which this happens. There are two obvious types of explanation: first, that there are global pre‐patterns within the mesenchyme whose molecular expression leads to tissue fragmentation and, second, that the condensations arise spontaneously through the local morphogenetic abilities of the cells. The only known mechanism for the latter possibility is cell traction and this paper suggests that current studies are compatible with traction playing a primary role in the formation of nephrogenic condensations in the developing kidney and the separation of somites, but not for the generation of feather rudiments where there is evidence of a prepattern of adhesivity.
From the structure to the function of villin, an actin‐binding protein of the brush border
Authors: Friederich Evelync , Pringault Eric , Arpin Monique , Louvard Daniel 
Published: February 2005

AbstractVillin, a calcium‐regulated actin‐binding protein, modulates the structure and assembly of actin filaments in vitro. It is organized into three domains, the first two of which are homologous. Villin is mainly produced in epithelial cells that develop a brush border and which are responsible for nutrient uptake. Expression of the villin structural gene is precisely regulated during mouse embryogenesis and is restricted in adults, to certain epithelia of the gastrointestinal and urogenital tracts. The function of villin has been assessed by transfecting CV1 cells with a human cDNA encoding wild‐type villin or mutant villin. Synthesis of large amounts of villin in cells which do not normally produce this protein induces the growth of microvilli on the cell surface and the redistribution of F‐actin, concomitant with the disappearance of stress fibers. The complete villin sequence is required for the morphogenic effect. These results suggest that villin plays a key role in the morphogenesis of microvilli.
X‐linked gene expression and sex determination in Caenorhabditis elegans
Authors: Meneely Philip M. 
Published: February 2005

AbstractThe signal for sex determination in the nematode Caenorhabditis elegans is the ratio between the number of × chromosomes and the number of sets of autosomes (the X/A ratio). Animals with an X/A ratio of 0.67 (a triploid with two × chromosomes) or less are males. Animals with an X/A ratio of 0.75 or more are hermaphrodites. Thus, diploid males have one × chromosome and diploid hermaphrodites have two × chromosomes. However, the difference in X‐chromosome number between the sexes is not reflected in general levels of X‐linked gene expression because of the phenomenon of dosage compensation. In dosage compensation, X‐linked gene expression appears to be ‘turned down’ in 2X animals to the 1X level of expression. An intriguing and unexplained finding is that mutations and X‐chromosome duplications that elevate X‐linked gene expression also feminize triploid males. One way that this relationship between sex determination and X‐linked gene expression may be operating is discussed.
The role of recombinational hotspots in genome instability in mammalian cells
Authors: Murnane John P. 
Published: February 2005

AbstractGenome instability has been associated with progression of transformed cells to high tumorigenicity. Although genome instability may result from a variety of factors, some studies suggest that DNA in the region of a chromosome rearrangement can subsequently have much higher rates of DNA deletions or gene amplification. One approach to studying the factors that produce these high rates of DNA rearrangement is by analysis of unstable integration sites for DNA transfected into mammalian cells. Integrated sequences commonly show a temporary instability, and at rare locations this instability is continuous and can be observed even after multiple subclonings. These continuously unstable locations undergo DNA amplification of both the integrated sequences and the surrounding cell DNA, and it can occur either at the original site or on episomes after looping out from the chromosome. Because the adjacent cell DNA plays a role in this instability, and the region can be shown to be stable before integration, the results indicate that these recombinational hotspots can be formed de novo by the process of integration. Current studies are attempting to determine which sequences are responsible for the high rates of recombination and whether similar types of event are involved in the instability associated with endogenous cellular genes in cancer cells.
Cells and cell‐interactions that guide motor axons in the developing chick embryo
Authors: Tonsey Karthryn W. 
Published: February 2005

AbstractA considerable challenge confronts, any developing neuron. Before it can establish a functional and specific connection, it must extend an axon over tens and sometimes hundreds of microns through a complex and mutable environment to reach one out of many possible destinations. The field of axonal guidance concerns the control of this navigation process. To satisfactorily identify the cell interactions and molecular mechanisms that mediate axonal guidance, it is essential to first identify the pertinent cell populations. Embryonic surgeries have provided solid information on which tissues are critical and which are irrelevant to the navigation of motor axons within the chick embryo. The gross anatomical nerve pattern is established as axons respond to both positive (path) and negative (barrier) tissue environments. Analysis of the interactions of motoneurons with these tissues reveals that several cellular interactions – chemotaxis, substratum preference, and perhaps contact paralysis – are important to the common patterns of motor axon advance. Axons simultaneously interact with population‐specific cues that have begun to be identified on the tissue level.
Titin, a huge, elastic sarcomeric protein with a probable role in morphogenesis
Authors: Fulton Alice B. , Isaacs William B. 
Published: February 2005

AbstractTitin, the largest protein identified to date (over 1 μm long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere. In the mature myofibril, titin molecules span from M line to Z line, forming a third filament system which provides sarcomeric alignment and elastic recoil. In the developing sarcomere, accumulating evidence from studies both in vivo and in vitro implicates titin as part of a morphogenetic scaffolding, upon which critical events in myofibrillogenesis are coordinated in a time‐ and spacedependent manner.
Transport across the nuclear envelope: Enigmas and explanations
Authors: Dingwall Colin 
Published: February 2005

AbstractThe transport of molecules across the nuclear envelope plays a central role in the metabolism of the cell. Significant advances hi three major areas highlight the limits of our current knowledge and point to the prospect of exciting future developments. Firstly, findings that ions and small proteins do not diffuse freely into the nucleus call into question the current views of nuclear envelope permeability. Secondly, indications that nuclear protein import can be regulated in conjunction with the cell cycle and development have been confirmed by the clear demonstration of regulated nuclear entry of specific transcription factors and morphogens. Thirdly, identification and characterisation of candidate receptor proteins indicates that the recognition of the nuclear targeting sequence occurs in the cytoplasm, suggesting that a different recognition event occurs at the nuclear pore.
C‐CAM (cell‐CAM 105) – a member of the growing immunoglobulin superfamily of cell adhesion proteins
Authors: Öbrink Björn 
Published: February 2005

AbstractCell recognition and adhesion, being of prime importance for the formation and integrity of tissues, are mediated by cell adhesion molecules, which can be divided into several distinct protein superfamilies. The cell adhesion molecule C‐CAM (cell‐CAM 105) belongs to the immunoglobulin superfamily, and more specifically is a member of the carcinoembryonic antigen (CEA) gene family. C‐CAM can mediate adhesion between hepatocytes in vitro in a homophilic, calcium‐independent binding reaction. The molecule, which occurs in various isoforms, is expressed in liver, several epithelia, vessel endothelia, platelets and granulocytes and its expression is dynamically regulated under various physiological and pathological conditions. It is proposed that C‐CAM in different cells and tissues plays different functional roles, where the common denominator is membrane‐membrane binding.
How do plant virus nucleic acids move through intercellular connections?
Authors: Citovsky Vitaly , Zambryski Particia 
Published: February 2005

AbstractIn addition to their function in transport of water, ions, small metabolites, and growth factors in normal plant tissue, the plasmodesmata presumably serve as routes for cell‐to‐cell movement of plant viruses in infected tissue. Virus cell‐to‐cell spread through plasmodesmata is an active process mediated by specialized virus encoded movement proteins; however, the mechanism by which these proteins operate is not clear. We incorporate recent information on the biochemical properties of plant virus movement proteins and their interaction with plasmodesmata in a model for transport of nucleic acids through plasmodesmatal channels. We propose that only single stranded (ss) nucleic acids can be transported efficiently through plasmodesmata, and that movement proteins function as molecular chaperones for ss nucleic acids to form unfolded movement protein‐ss nucleic acid complexes. These complexes are targeted to plasmodesmata. Plasmodesmatal permeability is then increased following interaction with movement protein and the entire movement complex or its nucleic acid component is translocated across the plasmodesmatal channel.
DNA excision repair in mammalian cell extracts
Authors: Wood Richard D. , Coverley Dawn 
Published: February 2005

AbstractThe many genetic complementation groups of DNA excision‐repair defective mammalian cells indicate the considerable complexity of the excision repair process. The cloning of several repair genes is taking the field a step closer to mechanistic studies of the actions and interactions of repair proteins. Early biochemical studies of mammalian DNA repair in vitro are now at hand. Repair synthesis in damaged DNA can be monitored by following the incorporation of radiolabelled nucleotides. Synthesis is carried out by mammalian cell extracts and is defective in extracts from cell lines derived from individuals with the excisionrepair disorder xeroderma pigmentosum. Biochemical complementation of the defective extracts can be used to purify repair proteins. Repair of damage caused by agents including ultraviolet irradiation, psoralens, and platinating compounds has been observed. Neutralising antibodies against the human single‐stranded DNA binding protein (HSSB) have demonstrated a requirement for this protein in DNA excision repair as well as in DNA replication.
Poly(ADP‐ribose) polymerase: Molecular biological aspects
Authors: De Murcia Gilbert , Ménissier‐De Murcia Josiane , Schreiber Valérie 
Published: February 2005

AbstractA number of roles have been ascribed to poly(ADP‐ribose) polymerase* including involvement in DNA repair, cell proliferation, differentiation and transformation. Cloning of the gene has allowed the development of molecular biological approaches to elucidate the structure and the function(s) of this highly conserved enzyme. This article will review the recent results obtained in this field.
Na+‐coupled alternative to H+‐coupled primary transport systems in bacteria
Authors: Dimroth Peter 
Published: February 2005

AbstractProtons are the most common coupling ions in bacterial energy conversions. However, while many organisms, such as the alkaliphilic Bacilli, employ H+‐bioenergetics for electron transport phosphorylation, they use Na+ as the coupling ion for transport and flagellar movement. The Na+ gradient required for these bioenergetic functions is established by the secondary Na+/H+ antiporter. In contrast, Vibrio alginolyticus and methanogenic bacteria have primary pumps for both H+ and Na+. They use the proton gradient for ATP synthesis while other, less energy‐consuming membrane reactions are powered by the Na+ gradient. In a third mode, some anaerobic bacteria possess decarboxylases acting as primary Na+ pumps. For instance, in Klebsiella pneumoniae, the Na+ gradient established by oxaloacetate decarboxylase is used for the uptake of the growth substrate citrate, and Propionigenium modestum consumes the energy of the Na+ gradient formed by methylmalonyl‐CoA decarboxylase directly for ATP synthesis.
The interactions of transcription factors and their adaptors, coactivators and accessory proteins
Authors: Martin Katherine J. 
Published: February 2005

AbstractConsistent with the complexity of the temporally regulated processes that must occur for growth and development of higher eukaryotes, it is now apparent that transcription is regulated by the formation of multi‐component complexes that assemble on the promoters of genes. These complexes can include (in addition to the five or more general transcription factors and RNA polymerase II) DNA‐binding proteins, transcriptional activators, coactivators, adaptors and various accessory proteins. The best studied example of a complex that includes a transcriptional adaptor, accessory proteins and a DNA‐binding protein is that involving the herpes simplex virus VP16 protein. Evidence suggests that the adenovirus E1a protein and the cellular Sp1 and CTF/NF1 transcription factors also function through adaptors or coactivators. Each additional component of the transcription complex provides the cell with another point at which to exert control of gene expression.
Control of eukaryotic DNA replication at the chromosomal level
Authors: Wanka Friedrich 
Published: February 2005

AbstractA hypothesis for the control of eukaryotic DNA replication at the chromosomal level is proposed. The specific regulatory problem arises from the subdivision of the genome into thousands of individually replicating units, each of which must be duplicated a single time during S‐phase. The hypothesis is based on the finding of direct repeats at replication origins. Such repeats can adopt, beyond the full‐length double helical structure, another configuration exposing two single‐stranded loops that provide suitable templates for the initiation of DNA replication. Any further initiation at the same origin is excluded as the single strandedness is eliminated by the replication process. Restoration of the initiable loop structure is proposed to occur by DNA‐protein rearrangements involved in chromosome condensation and duplication of the chromosomal protein backbone during mitosis. A possible role of the maturation promoting factor (MPF) is suggested.
Bristle patterning in Drosophila
Authors: Held Lewis I. 
Published: February 2005

AbstractThe 5000 bristles that protrude from the cuticle of a Drosophila adult function as either mechanosensors or chemosensors, and they are arranged in surprisingly intricate patterns. Development of the patterns appears to involve five stages: (1) establishment of a coordinate system of ‘positional information’; (2) partitioning of the epidermis into areas where bristles either can or cannot originate; (3) selection of one or more bristle mother cells within each permissible area; (4) suppression of bristle development in the neighborhood of each mother cell; and (5) differentiation of the mother cell to produce four or more descendant cells, each of which forms part of the bristle apparatus. Some of the genes that control these events participate in more than one stage, and others play key roles in roles in seemingly unrelated developmental pathways, including embryonic neurogenesis, body segmentation, and sex determination.
Protein translocation across mitochondrial membranes
Authors: Wienhues Ulla , Neupert Walter 
Published: February 2005

AbstractProtein translocation across biological membranes is of fundamental importance for the biogenesis of organelles and in protein secretion. We will give an overview of the recent achievements in the understanding of protein translocation across mitochondrial membranes(1‐5). In particular we will focus on recently identified components of the mitochondrial import apparatus.
High blood pressure: Hunting the genes
Authors: Leckie Brenda J. 
Published: February 2005

AbstractHigh blood pressure is a disease of unknown cause. Family history of the disease indicates higher risk, but it is not known which genes are involved or how they interact with environmental influences to produce the disorder. Molecular biology offers an approach to problems that have not so far been solved by classical physiology or biochemistry. By analysing polymorphic variation in chromosome markers such as minisatellite sequences, or by restriction fragment polymorphism analysis of candidate genes, attempts are being made to link genetic variations with hypertension. In genetically hypertensive rats, hypertension is associated with a polymorphism of the renin gene and with other loci on chromosomes 10 and 18. The role of these loci in human hypertension remains to be determined. Other genes such as sodium‐lithium countertransport may be involved. Environmental factors such as stress or salt intake could influence the rate or timing of expression of certain genes and thus result in hypertension.
Regulatory mechanisms for ras proteins
Authors: Downward Julian 
Published: February 2005

AbstractThe proteins encoded by the ras proto‐oncogenes play critical roles in normal cellular growth, differentiation and development in addition to their potential for malignant transformation. Several proteins that are involved in the control of the activity of p21ras have now been characterised. p120GAP stimulates the GTPase activity of p21ras and hence acts as a negative regulator of ras proteins. It may be controlled by tyrosine phosphorylation or association with tyrosine phosphorylated proteins. The neurofibromatosis type 1 (NF 1) gene also encodes a potential GTPase activating protein which is likely to be subject to a different control mechanism. Guanosine nucleotide exchange factors for p21ras have now been identified: these may be positive regulators of ras protein function. It appears that p21ras is subject to rapid regulation by several distinct mechanisms which are likely to vary in different cell types; the ras proteins are thereby able to act as very sensitive cellular monitors of the extracellular environment.