bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA damage and cell cycle regulation of ribonucleotide reductase
Authors: Elledge Stephen J. , Zhou Zheng , Allen James B. , Navas Tony A. 
Published: February 2005

AbstractRibonucleotide reductase (RNR) catalyzes the rate limiting step in the production of deoxyribonucleotides needed for DNA synthesis. In addition to the well documented allosteric regulation, the synthesis of the enzyme is also tightly regulated at the level of transcription. mRNAs for both subunits are cell cycle regulated and inducible by DNA damage in all organisms examined, including E. coli, S. cerevisiae and H. sapiens. This DNA damage regulation is thought to provide a metabolic state that facilitates DNA replicational repair processes. S. cerevisiae also encodes a second large subunit gene, RNR3, that is expressed only in the presence of DNA damage. Genetic analysis of the DNA damage response in S. cerevisiae has shown that RNR expression is under both positive and negative control. Among mutants constitutive for RNR expression are the general transcriptional repression genes, SSN6 and TUP1. Mutations in POL1 and POL3 also activate RNR expression, indicating that the DNA damage sensory network may respond directly to blocks in DNA synthesis. A protein kinase, Dun1, has been identified that controls inducibility of RNR1, RNR2 and RNR3 in response to DNA damage and replication blocks. This result suggests that the RNR genes in S. cerevisiae form a regulon that is coordinately regulated by protein phosphorylation in response to DNA damage.
Endocytosis of growth factor receptors
Authors: Sorkin Alexander , Waters Christopher M. 
Published: February 2005

AbstractBinding of a growth factor (GF) to its specific receptor on the cell surface causes the initiation of a signal transduction cascade which eventually results in mitosis. GF:receptor complexes are removed from the cell surface via receptor‐mediated endocytosis, a process which involves clathrin‐coated pits. After internalization into the endosomal compartment, a significant pool of GFs and GF receptors escape recycling to the cell surface and are sorted to the degradation pathway. The ligandinduced internalization and lysosomal degradation of GF receptors result in the dramatic loss of surface receptors, a phenomenon termed receptor down‐regulation. In this review, we discuss relevant biochemical, morphological and kinetic studies of the mechanism of GF endocytosis, and the possible role of this process in mitogenic signaling by growth factor receptors.
Dynamic aspects of adhesion receptor function — integrins both twist and shout
Authors: Humphries Martin J. , Mould A. Paul , Tuckwell Danny S. 
Published: February 2005

AbstractThe recognition of extracellular molecules by cell surface receptors is the principal mechanism used by cells to sense their environment. Consequently, signals transduced as a result of these interactions make a major contribution to the regulation of cellular phenotype. Historically, particular emphasis has been placed on elucidating the intracellular consequences of growth factor and cytokine binding to cells. In addition to these interactions, however, cells are usually in intimate contact with a further source of complex structural and functional information, namely immobilised extracellular matrix and/or cell surface adhesion proteins. A key question in recent years has been whether cells use the myriad of adhesion protein‐receptor interactions purely for structural and migratory function, or whether these interactions also make a more varied contribution to cell phenotype. Here we review dynamic aspects of the function of one major class of adhesion receptor, the integrins. In particular, we focus on the evidence for shape changes in integrin molecules, the mechanisms responsible for regulating ligand binding, and the signals transduced following integrin occupancy.
Protein lateral mobility as a reflection of membrane microstructure
Authors: Zhang Fen , Lee Greta M. , Jacobson Ken 
Published: February 2005

AbstractThe lateral mobility of membrane lipids and proteins is presumed to play an important functional role in biomembranes. Photobleaching studies have shown that many proteins in the plasma membrane have diffusion coefficients at least an order of magnitude lower than those obtained when the same proteins are reconstituted in artificial bilayer membranes. Depending on the protein, it has been shown that either the cytoplasmic domain or the ectodomain is the key determinant of its lateral mobility. Single particle tracking microscopy, which allows the motions of single or small groups of membrane molecules to be followed, promises not only to reveal new features of membrane dynamics, but also to help explain longstanding puzzles presented by the photobleaching studies, particularly the so‐called immobile fraction. The combination of the two complementary technologies should measurably enhance our understanding of membrane microstructure.
Problems and paradigms: Altering sex ratios: The games microbes play
Authors: Hurst Gregory D. D. , Hurst Laurence D. , Majerus Michael E. N. 
Published: February 2005

AbstractThe male gametes of most organisms lack cytoplasm. Consequently, most cytoplasmic genetic elements are maternally inherited: they cannot be transmitted patrilinnearly. The evolutionary interests of cytoplasmic elements therefore lie in transmission through the female. These elements may thus be in evolutionary conflict with nuclear genes which are transmitted by both sexes. This conflict is manifested in observations of cytoplasmically induced biased sex‐ratios. Some cytoplasmic genes avoid this fate by biasing the primary sex ratio towards females, or by inducing parthenogenesis. Others kill male hosts, and either achieve transmission via dispersal, or benefit their clonal relatives in the dead male's female siblings. Still others cause the failure of zygotes resulting from pairings between males carrying specific microbes and females lacking them, causing an increase in the microbes through the sterilisation of non‐bearing females. Many, but not all, of these ‘ultra‐selfish’ microbes are closely related. Investigations of the significance of their phylogenetic affinities, or lack of them, their adaptability in terms of the methods by which they avoid, or ameliorate, the adverse effects of being in male hosts, and their importance as selective agents in the evolution of invertebrate sex determination systems, provide fertile spheres for future research.
Pure thoughts with impure proteins: Permeabilized cell models of organelle motility
Authors: Swanson Joel A. 
Published: February 2005

AbstractPermeabilized cell models provide an experimental middle ground wherein the in vitro properties of mechanochemical proteins can be reconciled with the physical and topological constraints of the intact cell. Several well‐studied examples of organelle motility are described here, including the actin‐based cytoplasmic streaming of Characean algae, the microtubule‐based aggregation and dispersion of pigment granules in chromatophores and the saltatory movements of vesicles along microtubules in fibroblasts and macrophages. The permeabilized models developed for these systems have helped to integrate observations in vivo with in vitro assays of motor proteins.
What's new: Ligation‐based DNA diagnostics
Authors: Landegren Ulf 
Published: February 2005

AbstractA number of novel gene detection techniques all revolve around the ligation of synthetic nucleic acid probes. In such ligase‐assisted gene detection reactions, specific DNA or RNA sequences are investigated by using them as guides for the covalent joining of pairs of probe molecules. The probes are designed to hybridize immediately next to each other on the target nucleic acid strand. Demonstration of ligated probes results in highly specific detection of and efficient distinction between similar sequence variants under standard reaction conditions. Accordingly, the principle has been applied in automated genetic screening procedures. Ligation reactions are also integral to a number of amplification procedures and they will be of value in an expanding range of genetic analyses.
Chemosensory regulation of development in C. elegans
Authors: Thomas James H. 
Published: February 2005

AbstractThe dauer larva is a specialized third‐larval stage of Caenorhabditis elegans that is long‐lived and resistant to environmental insult. The dauer larva is formed in response to a high external concentration of a constitu‐tively secreted pheromone. Response to the dauer‐inducing pheromone of C. elegans is a promising genetic model for metazoan chemosensory transduction. More than 20 genes have been identified that are required for normal pheromone response. The functions of these genes include production of the pheromone, exposure of sensory neuron endings to the environment, structural and functional integrity of those sensory endings, and the capacity of sensory neurons to make appropriate output. Genetic evidence suggests that two partially redundant sensory pathways act in concert to control dauer formation. At least two classes of chemosensory neurons, ADF and ASI, are implicated in the pheromone response. On the basis of on these findings, a speculative model for the pheromone response is proposed. In this model, the neurons ADF and ASI are pheromone sensors that repress dauer formation in the absence of pheromone and dere‐press dauer formation in response to pheromone. It is currently unclear whether or not the two genetically defined sensory pathways both act in ADF and ASI.
Neu and its ligands: From an oncogene to neural factors
Authors: Peles Elior , Yarden Yosef 
Published: February 2005

AbstractTransmembrane receptor tyrosine kinases that bind to peptide factors transmit essential growth and differentiation signals. A growing list of orphan receptors, of which some are oncogenic, holds the promise that many unknown ligands may be discovered by tracking the corresponding surface molecules. The neu gene (also called erbB‐2 and HER‐2) encodes such a receptor tyrosine kinase whose oncogenic potential is released in the developing rodent nervous system through a point mutation. Amplification and overexpression of neu are thought to contribute to malignancy of certain human adenocarcinomas. The search for soluble factors that interact with the Neu receptor led to the discovery of a 44 kDa glyco‐protein that induces phenotypic differentiation of cultured mammary tumor cells to growth‐arrested and milk‐producing cells. The Neu differentiation factor (NDF or heregulin), however, also acts as a mitogen for epithelial, Schwann and glial cells. Multiple forms of the factor are produced by alternative splicing and their expression is confined predominantly to the central and to the peripheral nervous systems. One identified neuronal function of this family of polypeptides is to control the formation of neuromuscular junctions, but their physiological role in secretory epithelia is still unknown. Other open questions relate to the transmembrane topology of various precursors, the identity of a putative co‐receptor, the possible existence of additional ligands of Neu and the functional significance of the interaction between Neu and at least three highly related receptor tyrosine kinases.
Genes and genomes: High‐frequency induction of chromosomal rearrangements in mouse germ cells by the chemotherapeutic agent chlorambucil
Authors: Rinchik Eugene M. , Flaherty Lorraine , Russell Liane B. 
Published: February 2005

AbstractRecent mutagenesis studies have demonstrated that the chemotherapeutic agent, chlorambucll (CHL), is highly mutagenic in male germ cells of the mouse. Post‐melotic germ cells, and especially early spermatids, are the most sensitive to the cytotoxic and mutagenic effects of this agent. Genetic, cytogenetic and molecular analyses of many induced mutations have shown that, in these germ‐cell stages, CHL induces predominantly chromosomal rearrangements (deletions and translocations), and mutation‐rate studies show that, in terms of tolerated doses, CHL is perhaps five to ten times more efficient in inducing rearrangements than is radiation exposure. Appropriate breeding protocols, along with knowledge of the advantages and limitations associated with the use of CHL, can be used to expand the current resource of chromosomal rearrangements in the mouse and to provide new phenotype‐associated mutations amenable to positional‐cloning techniques. The analysis of CHL‐induced mutations has also contributed to understanding the factors that affect the yield and nature of chemically induced germline mutations in mammals.
The molecular basis of retinotectal topography
Authors: Kaprielian Zaven , Patterson Paul H. 
Published: February 2005

AbstractOver 50 years have passed since Roger Sperry formulated a simple model of how visual space, as seen by the retina, can be projected onto the brain in a two‐dimensional, topographic map during development. Sperry posited a set of two orthogonal gradients in the retina that gives each cell a positional identity. He further suggested that these molecules could be used to match up with complementary gradients in the target field of the retinal projection, the tectum. While some investigators hold that the existence of such molecules may not be necessary to establish retinotectal maps, recent work has identified several cell surface proteins whose distributions are of the type predicted by Sperry. An unexpected twist comes from culture assays demonstrating that inhibitory activities on tectal membranes can guide the growth of processes from retinal neurons. Moreover, the expression patterns of several enzymes and three transcription factors suggest that these proteins are candidates for regulatory agents in the determination of cell position in the retina. In addition, results from perturbation experiments support the candidacy of two of the enzymes, and a new mutant screen has uncovered several as yet unidentified genes that are required for establishment of the proper retinotectal map. A number of these results were presented at a recent meeting on neurospecificity held in Cargese, Corsica and sponsored by NATO and NSF.
Atherosclerosis and glycation
Authors: Colaco Camilo A. L. S. , Roser Bruce J. 
Published: February 2005

AbstractAtherosclerosis is the major cause of death in the industrialised world. Though much work on the pathogenesis of atherosclerosis points to ‘oxidised’ low density lipoprotein (;LDL) as a key aeitological feature in the generation of the atherosclerotic plaque, the nature of this ‘oxidised’ LDL in vivo remains an enigma. We argue here that glycated LDL shows many of the characteristics attributed to ‘oxidised LDL’ and may be the source of the latter in vivo. These include the increased uptake and impaired degradation of glycated LDL by macrophages and the stimulation of transendothelial chemotaxis of monocytes, cytokine secretion and platelet aggregation. We hypothesise that the covalent binding of glycated LDL to the endothelial cell wall may result in the formation of the early atherosclerotic lesion of the fatty streak and that apolipoprotein E may mediate the physiological clearance of glycated moieties. The proposed role of glycation in the pathogenesis of atherosclerosis would explain its high incidence among diabetics and the contentious epidemiological and experimental correlations between dietary sugar and atherosclerosis.
Architectural variations of inducible eukaryotic promoters: Preset and remodeling chromatin structures
Authors: Wallrath Lori L. , Lu Quinn , Granok Howard , Elgin Sarah C. R. 
Published: February 2005

AbstractThe DNA in a eukaryotic nucleus is packaged into a nucleosome array, punctuated by variations in the regular pattern. The local chromatin structure of inducible genes appears to fall into two categories: preset and remodeling. Preset genes are those in which the binding sites for trans‐acting factors are accessible (;i.e. in a non‐nucleosomal, DNase I hypersensitive configuration) prior to activation. In response to the activation signal, positive factors bind to cis‐acting regulatory elements and trigger transcription with no major alterations in the chromatin structure of the promoter region. In contrast, remodeling genes are those in which some of the required cis‐acting regulatory elements are packaged into nucleosomes. The nucleosomes must be perturbed in response to an activation signal in order for the trans‐acting factors to gain access to cis‐acting elements; a chromatin remodeling process which forms DNase I hypersensitive sites must occur. In both cases, precise positioning of nucleosomes along the promoter region of a gene appears to be critical for appropriate regulation of expression.
Recent trends in rifamycin research
Authors: Lal Rup , Lal Sukanya 
Published: February 2005

AbstractRifamycin is a clinically useful macrolide antibiotic produced by the gram positive bacterium. Amycolatopsis mediterranei. This antibiotic is primarily used against Mycobacterium tuberculosis and Mycobacterium leprae, causative agents of tuberculosis and leprosy, respectively. In these bacteria, rifamycin treatment specifically inhibits the initiation of RNA synthesis by binding to β‐subunit of RNA polymerase. Apart from its activity against the bacteria, rifamycin has also been reported to inhibit reverse transcriptase (RT) of certain RNA viruses. Recently, rifamycin derivatives have been dis‐covered that are effective against Mycobacterium avium, which is associated with the AIDS complex. Consequently, the importance of and demand for rifamycin has increased tremendously, the world over. In this article, recent trends in rifamycin research and accessability of recombinant DNA techniques to increase rifamycin production are reviewed.
The RAD6 DNA repair pathway in Saccharomyces cerevisiae: What does it do, and how does it do it?
Authors: Lawrence Christopher 
Published: February 2005

AbstractThe RAD6 pathway of budding yeast, Saccharomyces cerevisiae, is responsible for a substantial fraction of this organism's resistance to DNA damage, and also for induced mutagenesis. The pathway appears to incorporate two different recovery processes, both regulated by RAD6. The error‐prone recovery prcess accounts for only a small amount of RAD6‐dependent resistance, but probably all induced mutagenesis. The underlying mechanism, for error‐prone recovery is very likely to be translesion synthesis. The error‐free recovery process accounts for most of RAD6‐dependent resistace, but its mechanism is less clear; it may entail error‐free bypass by template switching and/or DNA gap filling by recombination. RAD6 regulates these activities by ubiquitinateins, and the roles they play in error‐free and error‐prone recovery, have not yet been established.
Gross chromosome rearrangements mediated by transposable elements in Drosophila melanogaster
Authors: Lim Johng K. , Simmons Michael J. 
Published: February 2005

AbstractA combination of cytogenetic and molecular analyses has shown that several different transposable elements are involved in the restructuring of Drosophila chromosomes. Two kinds of elements, P and hobo, are especially prone to induce chromosome rearrangements. The mechanistic details of this process are unclear, but, at least some of the time, it seems to involve ectopic recombination between elements inserted at different chromosomal sites; the available data suggest that these ectopic recombination events are much more likely to occure between elements in the same chromosome than between elements in different chromosomes. Other Drosophila transposons also appear to mediate chromosome restructuring by ectopic recombination; these include the retrotransposons BEL, roo, Docand I and the foldback element FB. In addition, two retrotransposons, HeT‐A and TART, have been found to be associated specifically with the ends of Drosophila chromosomes. Very limited data indicate that transposon‐mediated chromosome restructuring is occurring in natural populations of Drosophila. This suggests that transposable elements may help to shape the structure of the Drosophila genome and implies that they may have a similar role in other organisms.
Alternative mRNA splicing of the FMRFamide gene and its role in neuropeptidergic signalling in a defined neural network
Authors: Benjamin Paul R. , Burke Julian F. 
Published: February 2005

AbstractNeuronal signalling involves multiple neuropeptides that are diverse in structure and function. Complex patterns of tissue‐specific expression arise from alternate RNA splicing of neuropeptide‐encoding gene transcripts. The pattern of expression and its role in cell signalling is diffecult to study at the level of single neurons in the complex vertebrate brain. However, in the model molluscan system, Lymnaea, it is possible to show that alternate mRNA expression of the FMRFamide gene is specific to single identified neurons. Two different transcripts are expressed in a mutually exclusive manner in different neurons. Post‐translational processing of the two precursor proteins leads to completely distinct sets of neuropeptide transmitters. The function of these transmitter cocktails, resulting from alternate mRNA splicing, was studied physiologically in identified neurons forming part of a behaviourally important network regulating heartbeat.
Hypothesis: Intermediate filament and related proteins: Potential activators of nucleosomes during transcription initiation and elongation?
Authors: Traub Peter , Shoeman Robert L. 
Published: February 2005

AbstractIntermediate filament (IF) protein tetramers contain two DNA‐ and core‐histone‐binding motifs in rotational symmetry in one and the same structural entity. We propose that IF protein oligomers might displace histone octamers from nucleosomes in the process of transcription initiation and elongation, to deposit them transiently on their α‐helical coiled‐coil domains. We further propose that structurally related proteins of the karyoskeleton, constructed from an α‐helical domain capable of coiled‐coil formation and a basic DNA‐binding region adjacent to it, may be similarly involved in nucleosome activation. These proteins would function as auxiliary factors that disrupt nucleosomal structure to permit transcription and other DNA‐dependent processes to proceed expiditiously.
My favourite cell: Tetrahymena: A model for growth, cell cycle and nutritional studies, with biotechnological potential
Authors: Wheatley Denys N. , Rasmussen Leif , Tiedtke Arno 
Published: February 2005

AbstractTetrahymena has been used as a model cell system in many studies of morphogenesis, conjugation, gene mapping, cell division and growth kinetics. In this article, we consider some advances which have resulted from the successful development of a chemically defined medium (CDM), and how subsequent work has extended the contribution that this organism has made to our understanding of different aspects of growth, nutrition, cell cycle control, cytokinesis and intercellular signalling. Finally, we discuss the considerable potential that has arisen for the biotechnological exploitation of this big and rapidly growing eukaryotic cell.