bluuebunny/crossref_metadata_2025_split huggingface dataset:
New strategies for treating AIDS
Authors: Sandstrom Paul A. , Folks Thomas M. 
Published: February 2005

AbstractTo date, the effective management of HIV‐1 infection by anti‐retroviral drugs has proved remarkably difficult to achieve. This is primarily due to the ease with which HIV‐1 becomes resistant to drugs which initially may be very effective at blocking viral replication. In a recent issue of Science, two promising new AIDS treatments were reported. The first described the use of retroviral‐type zinc finger structures found in the HIV‐1 nucleocapsid protein as targets for anti‐retroviral drugs(1). The second demonstrated the feasibility of the reverse transcriptase inhibitor (R)‐9‐(2‐phosphonylmethoxypropyl) adenine as a postexposure prophylaxis in blocking HIV‐1 infection(2).
Do imprinted genes have few and small introns?
Authors: Haig David 
Published: February 2005

AbstractA gene is described as imprinted if its pattern of expression depends on whether it passed the previous generation in a male or female germ line. A recent paper(1) reports that imprinted genes have fewer and smaller introns than a control set of genes. The differences are striking but their interpretation is unclear. The loss of introns after a gene becomes imprinted is not sufficient to explain why imprinted genes have fewer introns than average, because related unimprinted genes also have few introns. Similarly, small introns appear to be a property of chromosomal region rather than of imprinting status itself, because neighboring unimprinted genes also have small introns.
Intracellular trafficking of lysosomal membrane proteins
Authors: Hunziker Walter , Geuze Hans J. 
Published: February 2005

AbstractLysosomes are the site of degradation of obsolete intracellular material during autophagy and of extracellular macromolecules following endocytosis and phagocytosis. The membrane of lysosomes and late endosomes is enriched in highly glycosylated transmembrane proteins of largely unknown function. Significant progress has been made in recent years towards elucidating the pathways by which these lysosomal membrane proteins are delivered to late endosomes and lysosomes. While some lysosomal membrane proteins follow the constitutive secretory pathway and reach lysosomes indirectly via the cell surface and endocytosis, others exit the trans‐Golgi network in clathrin‐coated vesicles for direct delivery to endosomes and lysosomes. Sorting from the Golgi or the plasma membrane into the endosomal system is mediated by signals encoded by the short cytosolic domain of these proteins. This review will discuss the role of lysosomal membrane proteins in the biogenesis of the late endosomal and lysosomal membranes, with particular emphasis on the structural features and molecular mechanisms underlying the intracellular trafficking of these proteins.
Dosage‐dependent modification of position‐effect variegation in Drosophla
Authors: Henikoff Steven 
Published: February 2005

AbstractMany loci in Drosophila exhibit dosage effects on single phenotypes. In the case of modifiers of position‐effect variegation, increases and decreases in dosage can have opposite effects on variegating phenotypes. This is seemingly paradoxical: if each locus encodes a limiting gene product sensitive to dosage decreases, then increasing the dosage of any one should have no effect, because the others should remain limiting. An earlier model put forward to resolve this paradox suggested that dosage‐dependent modifiers encode protein subunits of a macromolecular complex that is sensitive to mass action equilibrium conditions. Because chemical equilibria are dynamic, however, such hypothetical complexes will be unstable to an extent that is inconsistent with the known properties of molecules that make up chromatin. An alternative model accounts for the dosage effects in terms of interactions between structural proteins that bind at multiple linked sites. These might include indirect interactions occurring between regulatory proteins and genes for structural proteins or their protein products. The large number of direct and inverse regulatory genes which are known to exist in Drosophila could account for the apparent genetic complexity that is seen for modifiers of position‐effect variegation and for other systems of phenotypic modification.
Dynamic property of intermediate filaments: Regulation by phosphorylation
Authors: Inagaki Masaki , Matsuoka Yoichiro , Tsujimura Kunio , Ando Shoji , Tokui Toshiya , Takahashi Toshitada , Inagaki Naoyuki 
Published: February 2005

AbstractSite‐specific phosphorylation of intermediate filament (IF) proteins on serine and threonine residues leads to alteration of the filament structure, in vitro and in vivo. Protein kinases involved in cell signaling and those activated in mitosis dynamically control spatial and temporal organization of intracellular IF phosphorylation. Thus, IF phosphorylation appears to be one of the most predominant strategies in coordinating intracellular organization of the IF network.
Adherens junctions in the Drosophila embryo: The role of E‐cadherin in their establishment and morphogenetic function
Authors: Knust Elisabeth , Leptin Maria 
Published: February 2005

AbstractThe integrity of epithelia depends largely on specialised adhesive structures, the adherens junctions. Several of the components required for building these structures are highly conserved between vertebrates and insects (e.g. E‐cadherin and α‐ and β‐catenin), while others have so far been found only in invertebrates (e.g. crumbs). Two recent papers(1,2) show that the Drosophila E‐cadherin is encoded by the gene shotgun. Phenotypic analyses of shotgun as well as armadillo (β‐catenin) and crumbs mutants provide new insights into the mechanisms by which adherens junctions are built and, further, show that the requirement for E‐cadherin largely depends on the morphogenetic activity of an epithelium.
DNA elements responsive to auxin
Authors: Abel Steffen , Ballas Nurit , Wong Lu‐Min , Theologis Athanasios 
Published: February 2005

AbstractGenes induced by the plant hormone auxin are probably involved in the execution of vital cellular functions and developmental processes. Experimental approaches designed to elucidate the molecular mechanisms of auxin action have focused on auxin perception, genetic dissection of the signaling apparatus and specific gene activation. Auxin‐responsive promoter elements of early genes provide molecular tools for probing auxin signaling in reverse. Functional analysis of several auxin‐specific promoters of unrelated early genes suggests combinatorial utilization of both conserved and variable elements. These elements are arranged into autonomous domains and the combination of such modules generates uniquely composed promoters. Modular promoters allow for auxin‐mediated transcriptional responses to be revealed in a tissue‐ and development‐specific manner.
The neutral theory is dead. The current significance and standing of neutral and nearly neutral theories
Authors: Ohta Tomoko 
Published: February 2005

AbstractComparative studies of DNA sequences provide opportunities for testing the neutral and the selection theories of molecular evolution. In particular, the separate estimation of the numbers of synonymous and nonsynonymous substitutions is a powerful tool for detecting selection of the latter. The difference in the patterns of these two types of substitutions of mammalian genes turned out to be in accord with the slightly deleterious or nearly neutral mutation theory for nonsynonymous changes. Interaction systems at the amino acid level were suggested to be responsible for such nearly neutral, or very weak, selection. Synonymous substitutions are not strictly neutral, but because of their minute effect, random drift predominates such that the rate of substitution is only slightly less than the completely neutral prediction. It was concluded that the strictly neutral theory has not held up as well as the nearly neutral theory, yet remains invaluable as a null hypothesis for detecting selection. On the other hand, the main difference between the nearly neutral and the traditional selection theories is that the former predicts rapid evolution in small populations, whereas the latter predicts rapid evolution in large populations.
Connexins in mammalian heart function
Authors: Gros Daniel B. , Jongsma Habo J. 
Published: February 2005

AbstractIn heart, the propagation of electrical activity is mediated by intercellular channels, referred to as junctional channels, aggregated into gap junctions and localised between myocytes. These channels consist of structurally related transmembrane proteins, the connexins, three of which (CX43, CX40 and CX45) have been shown to be associated with the myocytes of mammalian heart; a fourth, CX37, was detected exclusively in endothelial cells. In this paper, we review the recent data dealing with the topographical heterogeneity of expression of these connexins in the different cardiac tissues and the unique conductance properties of the channels they form, and attempt to assess the role played by each connexin and the consequences of their multiplicity in the propagation of action potentials.
Signaling mechanisms mediating synapse formation
Authors: Wallace Bruce G. 
Published: February 2005

AbstractRecent experiments have begun to decipher the molecular dialog that mediates differentiation at sites of synaptic between neurons and their targets. It had been hypothesized that the protein agrin is released by axon terminals at embryonic neuromuscular junctions and binds to a receptor on the myofiber surface to trigger postsynaptic differentiation. Now a genetic ‘Knockout’ experiment has confirmed the essential role of agrin in signaling between developing nerve and muscle(1). A second ‘knockout’ has shown that the muscle‐specific receptor tyrosine kinase MuSK is a critical element in the agrin‐induced signaling cascade(2). Additional results suggest that MuSK may comprise a portion of the agrin receptor(3).
Cell proliferation control in Drosophila: Flies are not worms
Authors: Bryant Peter J. 
Published: February 2005

AbstractThe development of organs during animal development requires the allocation of appropriate numbers of cells to each part of the structure. Yet in Drosophila the patterns of cell proliferation can be quite different from one individual to the next, and in fact can be altered experimentally without altering final morphology. The developing pattern seems to control proliferation, rather than the other way around. Even though the pattern of proliferation is variable, there is some order to it. A recent paper(1) shows that small clusters of cells in developing cell populations are in mitotic synchrony, but that the synchrony is transient. What is the significance of this mitotic synchrony?
Invertebrate gerontology: The age mutations of Caenorhabditis elegans
Authors: Lithgow Gordon J. 
Published: February 2005

AbstractAgeing is a complex phenomenon which remains a major challenge to modern biology. Although the evolutionary biology of ageing is well understood, the mechanisms that limit lifespan are unknown. The isolation and analysis of single‐gene mutations which extend lifespan (Age mutations) is likely to reveal processes which influence ageing. Caenorhabditis elegans is the only metazoan in which Age mutations have been identified. The Age mutations not only prolong life, but also confer a complex array of other phenotypes. Some of these phenotypes provide clues to the evolutionary origins of these genes while others allude to mechanisms of lifespan‐extension. Many of the Age genes interact and share a second common phenotype, that of stress resistance. Rather than invertebrate ageing being determined by a ‘clock mechanism’, a picture is emerging of ageing as a non‐adaptive process determined, in part, by resistance to intrinsic stress mediated by stress‐response genes.
Striving for atomic resolution in biomolecular topography: The scanning force microscope (SFM)
Authors: Schaper Achim , Jovin Thomas M. 
Published: February 2005

AbstractThe invention in 1986 of scanning force microscopy (SFM) provided a new and powerful tool for the investigation of biological structures. SFM yields a three‐dimensional view at nanometer resolution of the surface topography associated with biological objects. The potential for imaging either macromolecules or biomolecules and cells under native (physiological) conditions is currently being exploited to obtain functional information at the molecular level. In addition, the forces involved in individual bimolecular interactions are being assessed under static and dynamic conditions. In this report we focus on the imaging capability of the SFM. The rather broad spectrum of applications represented is intended to orient the prospective user of biological SFM.
DNA rearrangements and mating‐type determination in Paramecium tetraurelia
Authors: Forney James 
Published: February 2005

AbstractCiliated protozoa have separate germline and somatic nuclei, yet unlike larger organisms, both nuclei reside in the same cytoplasm. The micronuclei contain the germline and the macronucleus is the somatic nucleus. Thousands of DNA elements are normally removed from the micronuclear genome as it forms a new macronucleus during each sexual cycle. A recent study directly links the excision of these internal eliminated sequences (IESs) to mating type determination by showing that a pleiotropic mutation affecting mating type also prevents the excision of an IES from a surface protein gene(1). Remarkably, once the IES is present in the old macronucleus it prevents excision of that specific IES during formation of the next macronucleus.
What does mos do in oocytes and somatic cells?
Authors: Sagata Noriyuki 
Published: February 2005

AbstractMos, a protein kinase, is specifically expressed and functions during meiotic maturation (or G2/M progression) of vertebrate oocytes. When expressed ectopically, however, it can also readily induce oncogenic transformation (or uncontrolled G1/S transitions) in somatic cells. In both of these cell types, Mos activates mitogen‐activated protein kinase (MAPK), which seems largely to mediate its different functions in both oocyte maturation and cellular transformation. In oocyte maturation, the Mos‐MAPK pathway probably serves to activate and stabilize M‐phase promoting factor (MPF) (possibly by inhibiting some negative regulator(s) of this factor), while in cellular transformation, it seems to stabilize and activate the nuclear oncoprotein c‐Fos as well as to induce transcription of its gene. Thus, the different functions of Mos in oocytes and somatic cells may arise chiefly from its different MAPK‐mediated targets in the respective cell types. This review discusses the cellular basis that may enable Mos to act differently in oocytes and somatic cells.
Histone acetylation: A possible mechanism for the inheritance of cell memory at mitosis
Authors: Jeppesen Peter 
Published: February 2005

AbstractImmunofluorescent labelling demonstrates that human metaphase chromosomes contain hyperacetylated histone H4. With the exception of the inactive X chromosome in female cells, where the bulk of histone H4 is under‐acetylated, H4 hyperacetylation is non‐uniformly distributed along the chromosomes and clustered in cytologically resolvable chromatin domains that correspond, in general, with the R‐bands of conventional staining. The strongest immunolabelling is often found in T‐bands, the subset of intense R‐bands having the highest GC content. The majority of mapped genes also occurs in R‐band regions, with the highest gene density in T‐bands. These observations are consistent with a model in which hyperacetylation of histone H4 marks the position of potentially active gene sequences on metaphase chromosomes. Since acetylation is maintained during mitosis, progeny cells receive an imprint of the histone H4 acetylation pattern that was present on the parental chromosomes before cell division. Histone acetylation could provide a mechanism for propagating cell memory, defined as the maintenance of committed states of gene expression through cell lineages.
Axis specification in animal development
Authors: Goldstein Bob , Freeman Gary 
Published: February 2005

AbstractAxis specification is the first step in defining specific regions of the developing embryo. Embryos exploit asymmetries, either pre‐existing in the egg or triggered by external cues, to establish embryonic axes. The axial information is then used to generate regional differences within the embryo. In this review, we discuss experiments in animals which address three questions: whether the unfertilized egg is constructed with pre‐determined axes, what cues are used to specify the embryonic axes, and how these cues are interpreted to generate the initial regional differences within the embryo. Based on mapping the data onto an animal phylogeny, we then propose a scenario for how this primary developmental decision occurred in ancestral metazoans.
Genetic depletion reveals an essential role for an SR protein splicing factor in vertebrate cells
Authors: Mount Stephen M. 
Published: February 2005

AbstractSR proteins are essential for the splicing of messenger RNA precursors in vitro, where they also alter splice site selection in a concentration‐dependent manner. Although experiments involving overexpression or dominant mutations have confirmed that these proteins can influence RNA processing decisions in vivo, similar results with loss‐of‐function mutations have been lacking. Now, a system for genetic depletion of the chicken B cell line DT40 has revealed that the SR protein ASF/SF2 (alternative splicing factor/splicing factor 2) is essential for viability in these cells(1). This study opens the way for a complete functional dissection of this protein, and other SR proteins, in vivo.
Developmental control of cell division in leech embryos
Authors: Bissen Shirley T. 
Published: February 2005

AbstractDuring embryogenesis, cell division must be spatially and temporally regulated with respect to other developmental processes. Leech embryos undergo a series of unequal and asynchronous cleavages to produce individually recognizable cells whose lineages, developmental fates and cell cycle properties have been characterized. Thus, leech embryos provide an opportunity to examine the regulation of cell division at the level of individual well‐characterized cells within a community of different types of cells. Isolation of leech homologues of some of the highly conserved regulators of the cell division cycle, and characterization of their patterns of maternal and zygotic expression, indicate that the cell divisions of early leech embryos are regulated by cell type‐specific mechanisms. These studies with leech embryos contribute to the emerging appreciation of the diverse mechanisms by which animals regulate cell division during early development.
Evolution and development — the nematode vulva as a case study
Authors: Sommer Ralf J. 
Published: February 2005

AbstractTo understand how morphological characters change during evolution, we need insight into the evolution of developmental processes. Comparative developmental approaches that make use of our fundamental understanding of development in certain model organisms have been initiated for different animal systems and flowering plants. Nematodes provide a useful experimental system with which to investigate the genetic and molecular alterations underlying evolutionary changes of cell fate specification in development, by comparing different species to the genetic model system Caenorhabditis elegans. In this review, I will first discuss the different types of evolutionary alterations seen at the cellular level by focusing mainly on the analysis of vulva development in different species. The observed alterations involve changes in cell lineage, cell migration and cell death, as well as induction and cell competence. I then describe a genetic approach in the nematode Pristionchus pacificus that might identify those genetic and molecular processes that cause evolutionary changes of cell fate specification.
What do linker histones do in chromatin?
Authors: Wolffe Alan P. , Khochbin Saadi , Dimitrov Stefan 
Published: February 2005

AbstractKnockout experiments in Tetrahymena show that linker histone H1 is not essential for nuclear assembly or cell viability. These results, together with a series of biochemical and cell biological observations, challenge the existing paradigm that requires linker histones to be a key organizing component of higher‐order chromatin structure. The H1 Knockouts also reveal a much more subtle role for H1. Instead of acting as a general transcriptional repressor, H1 is found to regulate a limited number of specific genes. Surprisingly, H1 can both activate and repress transcription. We discuss how this architectural protein might accomplish this important regulatory role.
Illuminating flowers: CONSTANS induces LEAFY expression
Authors: Blázquez Miguel A. 
Published: February 2005

AbstractHigher plants must undergo a major developmental switch, the transition to flowering, if they are to successfully complete their life cycle. In many plants, the crucial decision of when to begin to produce flowers is primarily controlled by environmental signals. The process of floral induction involves the integration of the activities of two types of genes: those that control flowering time as a response to the environment as well as an endogenous clock, and those that determine the floral identity of the cells. The first direct link between these two classes of genes has now been demonstrated(1). Forced expression of CONSTANS, a flowering‐time gene, promotes flowering through the transcriptional activation of LEAFY, a flower‐meristem‐identity gene.
Fish are like flies are like frogs: Conservation of dorsal‐ventral patterning mechanisms
Authors: Holley Scott A. , Ferguson Edwin L. 
Published: February 2005

AbstractGenetic analysis of Drosophila has shown that a morphogenetic gradient of the Transforming Growth Factor‐β family member dpp patterns the embryonic dorsalventral axis. Molecular and embryological evidence from Xenopus has strongly suggested a similar role for Bmp‐4, the dpp homolog, in patterning the dorsalventral axis of chordates. A recent report has now identified mutations in two genes, dino and swirl, that disrupt dorsal‐ventral patterning in the zebrafish Danio rerio(1). Characterization of these mutations parallels findings from Drosophila, thus establishing a genetic framework for the analysis of dorsalventral patterning in a vertebrate.
Dynamic organisation of intermediate filaments and associated proteins during the cell cycle
Authors: Foisner Roland 
Published: February 2005

AbstractIntermediate filaments, which form the structural framework of both the cytoskeleton and the nuclear lamina in most eukaryotic cells, have been found to be highly dynamic structures. A continuous exchange of subunit proteins at the filament surface and a stabilisation of soluble subunits by chaperone‐type proteins may modulate filament structure and plasticity. Recent studies on the cell cycle‐dependent interaction of intermediate filaments with associated proteins, and a detailed analysis of intermediate filament phosphorylation in defined subcellular locations at various stages of mitosis, have brought new insights into the molecular mechanisms involved in the mitotic reorganisation of intermediate filaments. Some of these studies have allowed new speculations about the possible cellular functions of cytoplasmic intermediate filaments, and increased our understanding of the specific functions of the lamins and the lamina‐associated membrane proteins in the post‐mitotic reassembly of the nucleus.