bluuebunny/crossref_metadata_2025_split huggingface dataset:
The neuronal growth cone as a specialized transduction system
Authors: Strittmatter Stephen M. , Fishman Mark C. 
Published: February 2005

AbstractNeuronal growth and remodelling are guided by both intracellular gene programs and extracellular stimuli. The growth cone is one site where the effects of these extrinsic and intrinsic factors converge upon the mechanical determinants of cell shape. We review the growth cone as a transduction device, converting extracellular signals into mechanical forces. A variety of soluble, extracellular matrix and membrane bound molecules control growth cone behavior. In addition, GAP‐43 is discussed as a possible component of the Intraneuronal gene program which modulates growth cone activity. The GTP‐binding protein, Go, is a major growth cone membrane protein that may transduce signals not only from outside the cell, but from within as well. This may provide a molecular site in the growth cone for the coordination of a genetic growth program with environmental signals.
Development of the mammalian gonad: The fate of the supporting cell lineage
Authors: McLaren Anne 
Published: February 2005

AbstractSex determination in mammals is mediated via the supporting cell lineage in the fetal gonad. In the very early stages of gonadal development, the fate of the supporting cell population is critically dependent on the expression of the male‐determining gene on the Y chromosome. If this gene is absent or fails to be expressed, or is expressed too late or in too small a number of supporting cells, all supporting cells (XX or XY) differentiate as pre‐follicle cells and development proceeds along the female pathway. Supporting cells in which the male‐determining gene is expressed in a timely manner differentiate as pre‐Sertoli cells; given sufficient such cells, testis cords form and development proceeds in a male direction. If XX supporting cells are also present, a few may be recruited into the pre‐Sertoli population and participate in testis cord formation. The subsequent fate of pre‐follicle cells depends critically on interaction with the germ cell population in the developing gonad: absence of germ cells may lead to partial masculinization of the gonad, and/or to disappearance of the supporting cell component.
Gap genes and gradients – The logic behind the gaps
Authors: Hülskamp Martin , Tautz Diathard 
Published: February 2005

AbstractGap genes stand at the top of the zygotic segmentation hierarchy in Drosophila. Their expression domains are set up by a combination of maternal regulatory signals and interactions among themselves. In addition, these regulatory pathways are partially redundantly specified by the maternal and zygotic genomes, or by multiple zygotic gene products. The gap genes code for transcription factors which exert their function by foming short‐range morphogenetic gradients; differential concentrations of these transcription factors can either act as activators or as repressors for the expression domains of neighbouring genes. It is possible to view the gap genes as a system of genes that subdivides the embryo by forming an activation‐repression cascade proceeding from anterior towards posterior.
Catalytic function of DNA topoisomerase II
Authors: Osheroff Neil , Zechiedrich E. Lynn , Gale Kevin C. 
Published: February 2005

AbstractAlthough the genetic code is defined by a linear array of nucleotides, it is the three‐dimensional structure of the double helix that regulates most of its cellular functions. Over the past two decades, it has become increasingly clear that aspects of this three‐dimensionality which reflect topological relationships within the double helix (i.e., superhelical twisting, knotting, or tangling) influence virtually every facet of nucleic acid physiology. In vivo, DNA topology is modulated by ubiquitous enzymes known as topoisomerases. The type II enzyme essential to the eukaryotic cell and is required for unlinking daughter chromosomes and maintaining chromosome structure. Moreover, topoisomerase II also has been identified as the primary cellular target for several widely used antineoplastic drugs. Before the physiological functions of topoisomerase II can be effectively dissected or its drug interactions fully exploited, it is imperative to understand the mechanism by which this important enzyme arries out its catalytic cycle.
Mapping replication origins in yeast chromosomes
Authors: Brewer Bonita J. , Fangman Walton L. 
Published: February 2005

AbstractThe replicon hypothesis, first proposed in 1963 by Jacob and Brenner(1), states that DNA replication is controlled at sites called origins. Replication origins have been well studied in prokaryotes. However, the study of eukaryotic chromosomal origins has lagged behind, because until recently there has been no method for reliably determining the identity and location of origins from eukaryotic chromosomes. Here, we review a technique we developed with the yeast Saccharomyces cerevisiae that allows both the mapping of replication origins and an assessment of their activity. Two‐dimensional agarose gel electrophoresis and Southern hybridization with total genomic DNA are used to determine whether a particular restriction fragment acquires the branched structure diagnostic of replication initiation. The technique has been used to localize origins in yeast chromosomes and assess their initiation efficiency. In some cases, origin activation is dependent upon the surrounding context. The technique is also being applied to a variety of eukaryotic organisms.
Calcium channels and signal transduction in plant cells
Authors: Johannes Eva , Brosnan James M. , Sanders Dale 
Published: February 2005

AbstractAn increasing number of studies indicate that changes in cytosolic free Ca2+ ([Ca2+]c) mediate specific types of signal transduction in plant cells. Modulation of [Ca2+]c is likely to be achieved through changes in the activity of Ca2+ channels, which catalyse passive influx of Ca2+ to the cytosol from extracellular and intracellular compartments. Voltage‐sensitive Ca2+ channels have been detected in the plasma membranes of algae, where they control membrane electrical properties and cell turgor. These channels are sensitive to 1,4‐dihydropyridines, which in animal cells specifically affect one class of voltage‐regulated plasma membrane Ca2+ channel. Ca2+‐permeable channels with different pharmacological properties have been found in the plasma membrane of higher plants. Recent evidence suggests the existence of two discrete classes of Ca2+ channel co‐resident in the vacuolar membrane (tonoplast) of higher plants. The first is gated by inositol 1,4,5‐trisphosphate, and bears a number of similarities to its animal counterpart which is located in the endoplasmic reticulum (ER). The second tonoplast Ca2+ channel is voltage‐operated. However, the specific roles of these tonoplast channels in signal transduction have yet to be elucidated.
Multidrug resistant transgenic mice as a novel pharmacologic tool
Authors: Mickisch Gerald H. , Pastan Ira , Gottesman Michael M. 
Published: February 2005

AbstractMultidrug resistance resulting from expression of an energy‐dependent drug efflux pump encoded by the human MDR1 gene is a major impediment to effective cancer therapy. Pharmacologic intervention aimed at inhibiting this multidrug transporter should improve existing chemotherapy of human cancer, but drug development has been delayed by the difficulty and expense of developing valid animal models. Using recombinant DNA technology, a transgenic mouse has been engineered whose bone marrow is protected from the toxic effects of chemotherapy by expression of the MDR1 gene. This animal system allows the rapid screening of drugs which inhibit the multidrug transporter and heralds a new era of using transgenic animals for pharmacologic screening.
The role of cell death genes during development
Authors: Schwartz Lawrence M. 
Published: February 2005

AbstractDuring development, large numbers of cells die by a process known as programmed cell death. This loss of cells plays a number of important roles, including the sculpting of the body form and the removal of vestigial tissues. Data obtained from a variety of organisms has suggested that a cell's ‘decision’ to die is a differentiative event, requiring the activation of specific sets of genes. Several putative ‘cell death’ genes have recently been cloned, and one has been identified as the product of the polyubiquitin gene. Accumulation of ubiquitin has been observed not only during programmed cell death, but also in several neurodegenerative disorders, including Alzheimer's Disease.
New enzymes for old: Redesigning the coenzyme and substrate specificities of glutathione reductase
Authors: Perham Richard N. , Scrutton Nigel S. , Berry Alan 
Published: February 2005

AbstractA set of amino acid side chains that confer specificity for the coenzyme NADPH and the substrate glutathione in the flavoprotein disulphide oxidoreductase, glutathione reductase, has been identified. Systematic replacement of these amino acid residues in the coenzyme‐binding site switches the specificity of the enzyme from its natural strong preference for NADPH to a marked preference For NADH. The amino acids replaced all lie in a structural motif within the dinucleotide‐binding domain of the protein. Since this domain is a feature common to most dehydrogenases (reductases) that use nicotinamide coenzymes, it may be that the coenzyme specificities of all such enzymes can be manipulated in this way. Similarly, amino acid residues involved in the selective recognition of trypanothione by trypanothione reductase, an enzyme related to glutathione reductase and exclusive to trypanosomatids, were identified. Suitable mutation of the corresponding residues in E. coli glutathione reductase switched its substrate specificity towards trypanothione. A better understanding of the substrate specificity of these enzymes could open up a route to the chemotherapy of trypanosomal infections.
Transfer of yeast artificial chromosomes from yeast to mammalian cells
Authors: Huxley Clare , Gnirke Andreas 
Published: February 2005

AbstractHuman DNA can be cloned as yeast artificial chromosomes (YACs), each of which contains several hundred kilobases of human DNA. This DNA can be manipulated in the yeast host using homologous recombination and yeast selectable markers. In relatively few steps it is possible to make virtually any change in the cloned human DNA from single base pair changes to deletions and insertions. In order to study the function of the cloned DNA and the effects of the changes made in the yeast, the human DNA must be transferred back into mammalian cells. Recent experiments indicate that large genes can be transferred from the yeast host to mammalian cells in tissue culture and that the genes are transferred intact and are expressed. Using the same methods it may soon be possible to transfer YAC DNA into the mouse germ line so that the expression and function of genes cloned in YACs can be studied in developing and adult mammalian animals.
Lethal chromosomal deletions in the mouse, a model system for the study of development and regulation of postnatal gene expression
Authors: Gluecksohn‐Waelsch Salome , Defranco Donald 
Published: February 2005

AbstractMechanisms involved in the regulation of development and its genetic control are receiving ever‐increasing attention in studies of mammalian developmental genetics. The potential success of such studies is strongly enhanced by the availability of suitable systems of analysis. Such a system was identified in a series of radiation‐induced chromosomal deletions at and around the albino (c) locus of the mouse associated with cell type‐specific effects on liver differentiation. Their detailed study has aided the analysis of possible machanisms of cell type‐specific gene expression. As summarized in this review, the experimental results strongly suggest that specific trans‐acting developmental regulatory genes are concerned with the differentiation of hormone‐inducible expression of a cluster of hepatocyte specific structural genes mapping in different parts of the genome.
Mitosis‐specific phosphorylation of caldesmon: Possible molecular mechanism of cell rounding during mitosis
Authors: Yamashiro Shigeko , Matsumura Fumio 
Published: February 2005

AbstractOne of the profound changes in cellular morphology during mitosis is a massive alteration in the organization of microfilament cytoskeleton. It has been recently discovered that nonmuscle caldesmon, an actin and calmodulin binding microfilament‐associated protein of relative molecular mass Mr = 83000, is dissociated from microfilaments during mitosis, apparently as a consequence of mitosis‐specific phosphorylation. cdc2 kinase, which is a catalytic subunit of MPF (maturation or mitosis promoting factor), is found to be responsible for the mitosis‐specific phosphorylation of caldesmon. Because caldesmon is implicated in the regulation of actin myosin interactions and/or microfilament organization, these results suggest that cdc2 kinase directly affects microfilament re‐organization during mitosis.
Transduction of plant signal molecules by the Rhizobium NodD proteins
Authors: Györgypal Zoltan , Kiss György Botond , Kondorosi Adam 
Published: February 2005

AbstractThe regulatory NodD proteins of Rhizobium bacteria mediate the activation of a gene set responsible for symbiotic nodule formation by plant signal molecules. Here we discuss the signal recognition and gene activation properties of NodD and present a model summarizing the current knowledge on NodD action.
Gene targeting and gene trap screens using embryonic stem cells: New approaches to mammalian development
Authors: Joyner Alexandra L. 
Published: February 2005

AbstractMouse embryonic stem cell lines offer an attractive route for introducing rare genetic alternations into the gene pool since the cells can be pre‐screened in culture and the mutations then transmitted into the germline through chimera production. Two applications of this technique seem ideally suited for a genetic analysis of development are enhancer and gene trap screens for loci expressed during gastrulation and production of targeted mutations using homologous recombination. These approaches should greatly increase the number of mouse developmental mutants available and help to elucidate the genetic hierarchy controlling embryogenesis.
The kinetics of mammalian gene expression
Authors: Hargrove James L. , Hulsey Martin G. , Beale Elmus G. 
Published: February 2005

AbstractWhen rates of transcription from specific genes change, delays of variable length intervene before the corresponding mRNAs and proteins attain new levels. For most mammalian genes, the time required to complete transcription, processing, and transport of mRNA is much shorter than the period needed to achieve a new, steady‐state level of protein. Studies of inducible genes have shown that the period required to attain new levels of individual mRNAs and proteins is related to their unique half‐lives. The basis for this is a physical principle that predicts rates of accumulation of particles in compartmental systems. The minimum period required to achieve a new level is directly proportional to product half‐lives because rates of decay control the ratio between the rate of synthesis and the concentration of gene products at steady state. This kinetic model suggests that sensitivity of gene products to degradation by ribonucleases and proteinases is an important determinant of the time scale of gene expression.
Reversible histone modification and the chromosome cell cycle
Authors: Morton Bradbury E. 
Published: February 2005

AbstractDuring the eukaryotic cell cycle, chromosomes undergo large structural transitions and spatial rearrangements that are associated with the major cell functions of genome replication, transcription and chromosome condensation to metaphase chromosomes. Eukaryotic cells have evolved cell cycle dependent processes that modulate histone:DNA interactions in chromosomes. These are; (i) acetylations of lysines; (ii) phosphorylations of serines and threonines and (iii) ubiquitinations of lysines. All of these reversible modifications are contained in the well‐defined very basic N‐ and C‐ terminal domains of histones. Acetylations and phosphorylations markedly affect the charge densities of these domains whereas ubiquitination adds a bulky globular protein, ubiquitin, to lysines in the C‐terminal tails of H2A and H2B. Histone acetylations are strictly associated with genome replication and transcription; histone H1 and H3 phosphorylations correlate with the process of chromosome condensation. The subunits of histone H1 kinase have now been shown to be cyclins and the p34CDC2 kinase product of the cell cycle control gene CDC2. It is probable that all of the processes that control chromosome structure:function relationships are also involved in the control of the cell cycle.
Methylation, mutation and cancer
Authors: Jones Peter A. , Rideout William M. , Shen Jiang‐Cheng , Spruck Charles H. , Tsai Yvonne C. 
Published: February 2005

AbstractThe fifth base in human DNA, 5‐methylcytosine, is inherently mutagenic. This has led to marked changes in the distribution of the CpG methyl acceptor site and an 80% depletion in its frequency of occurrence in vertebrate DNA. The coding regions of many genes contain CpGs which are methylated in sperm and serve as hot spots for mutation in human genetic diseases. Fully 30–40% of all human germline point mutations are thought to be methylation induced even though the CpG dinucleotide is under‐represented and efficient cellular repair systems exist. Importantly, tumor suppressor genes such as p53 also contain methylated CpGs and these serve as hot spots for mutations in some, but not all, human cancers. Comparison of the spectrum of mutations present in this gene in different human cancers allows for predictions to be made on the molecular mechanisms of tumorigenesis.
The rel family of proteins
Authors: Rushlow Chris , Warrior Rahul 
Published: February 2005

AbstractThe rel family of proteins can be defined as a group of proteins that share sequence homology over a 300 amino acid region termed the rel domain. The rel family comprises important regulatory proteins from a wide variety of species and includes the Drosophila morphogen dorsal, the mammalian transcription factor NF‐kB, the avian oncogene v‐rel, and the cellular proto‐oncogene c‐rel. Over the last two years it has become apparent that these proteins function as DNA‐binding transcription factors, and that their activity is regulated at the level of subcellular localization.
Accessory protein function in the DNA polymerase III holoenzyme from E. coli
Authors: O'Donnell Mike 
Published: February 2005

AbstractDNA polymerases which duplicate cellular chromosomes are multiprotein complexes. The individual functions of the many proteins required to duplicate a chromosome are not fully understood. The multiprotein complex which duplicates the Escherichia coli chromosome, DNA polymerase III holoenzyme (holoenzyme), contains a DNA polymerase subunit and nine accessory proteins. This report summarizes our current understanding of the individual functions of the accessory proteins within the holoenzyme, lending insight into why a chromosomal replicase needs such a complex structure.
Transgenic animal studies on the evolution of genetic regulatory circuitries
Authors: Cavener Douglas R. 
Published: February 2005

AbstractThe ability to transfer genes from one species to another provides a powerful method to study genetic regulatory differences between species in a homogeneous genetic background. A survey of several transgenic animal experiments indicates that the vast majority of regulatory differences observed between species are due to differences in the cis‐acting elements associated with the genes under study. A corollary is that in almost all cases the host species provides the necessary regulatory proteins for expression of the transgenes in specific tissues in which the endogenous homolog is not expressed. Although the details of the cis‐acting differences are unknown for most cases, it appears that these differences may consist of the acquisition or loss of unique elements or subtle variation of conserved elements. It is unknown whether much of this variation is directly related to adaptive evolution. The identification of the promoter enhancer elements responsible for these differences is an important first step in examining the functional significance of this variation.
Cancer predisposition in bloom's syndrome
Authors: Sullivan Neil F. , Willis Anne E. 
Published: February 2005

AbstractThis article focusses upon defining those factors which may contribute to the pathogenesis of cancer. The molecular basis of tumour etiology is discussed with reference to cancer predisposing syndromes, and in particular to the human inherited disease, Bloom's sysdrome. In Bloom's syndrome, patients are predisposed to a wide variety of malignant disease. We propose a model in which overexpression of the ubiquitous c‐myc proto‐oncogene contributes to this process.
Problems and paradigms: Induction mechanism of a single gene molecule: Stochastic or deterministic?
Authors: Ko Minoru S. H. 
Published: February 2005

AbstractA new field of gene expression regulation research is emerging that has previously been overlooked. This new area is concerned with distinguishing the expression of a single gene from the averaged expression of many gene copies within the cell population. This paper reviews research focused on individual genes in inducible gene expression systems. The main experimental strategy is to measure the gene expression level of a single cell containing a single reporter gene molecule. In contrast to the commonly held belief, gene induction is found to be stochastic under certain conditions. The possible mechanisms and implications are discussed.
Genes and genomes: Carrier detection of deletions in female relatives of X‐linked disorders by non‐isotopic in situ hybridisation
Authors: Adinolfi M. , Stone S. , Moralli D. 
Published: February 2005

AbstractRecent studies suggest that a non‐isotopic in situ hybridisation (NISH) approach can be successfully employed to investigate the carrier status of female relatives in families of selected patients with Duchenne muscular dystrophy (DMD) or Hunter syndrome, whose diseases are due to a specific X chromosome deletion.Whilst the majority of metaphase spreads from normal females show specific hybridisation signals on both X chromosomes when tested with either dystrophin or Hunter gene‐derived probes, only one X chromosome in each metaphase spread will show the relevant hybridisation complex in female carriers of deletions involving the dystrophin or Hunter gene.Thus, the NISH method can be a valuable diagnostic tool for the detection of the carrier status of female relatives of patients with X chromosome deletions.
Position effect variegation and chromatin proteins
Authors: Reute Gunter , Spierer Pierre 
Published: February 2005

AbstractVariegated phenotypes often result from chromosomal rearrangements that place euchromatic genes next to heterochromatin. In such rearrangements, the condensed structure of heterochromatin can spread into euchromatic regions, which then assume the morphology of heterochromatin and become transcriptionally inactive. In position‐effect variegation (PEV) therefore, gene inactivation results from a change in chromatin structure. PEV has been intensively investigated in the fruitfly Drosophila, where the phenomenon allows a genetic dissection of chromatin components. Consequently, many genes have been identified which, when mutated, act as dominant modifiers (suppressors or enhancers) of PEV. Data available already demonstrate that genetic, molecular and developmental analysis of these genes provides an avenue to the identification of regulatory and structural chromatin components, and hence to fundamental aspects of chromosome structure and function.