bluuebunny/crossref_metadata_2025_split huggingface dataset:
Untangling the role of DNA topoisomerase II in mitotic chromosome structure and function
Authors: Warburton Peter E. , Earnshaw William C. 
Published: February 2005

AbstractDNA topoisomerase II (topo II) is involved in chromosome structure and function, although its exact location and role in mitosis are somewhat controversial. This is due in part to the varied reports of its localization on mitotic chromosomes, which has been described at different times as uniformly distributed, axial on the chromosome arms and predominantly centromeric. These disparate results are probably due to several factors, including use of different preparation and fixation techniques, species differences and changes in distribution during the cell cycle. Recently, several papers have re‐investigated the distribution of topo II on chromosomes as a function of cell cycle and species(1–3). The new studies suggest that Topo II has a dynamic pattern of distribution on the chromosomes, in general becoming axial as chromosomes condense during prophase and then concentrating at centromeres during metaphase. These experiments suggest a novel role for topo II in centromere structure and function.
The Drosophila fusome, organelle biogenesis and germ cell differentiation: If you build it…
Authors: McKearin Dennis 
Published: February 2005

AbstractFrom stem cells to oocyte, Drosophila germ cells undergo a short, defined lineage. Molecular genetic analyses of a collection of female sterile mutations have indicated that a germ cell‐specific organelle called the fusome has a central role at several steps in this lineage. The fusome grows from a prominent spherical organelle to an elongated and branched structure that connects all mitotic sisters in a germ cell syncytium. The organelle is assembled from proteins normally found in the membrane skeleton and, additionally, contains an extensive membranous reticulum, the probable product of differentiation‐dependent vesicle trafficking. This review briefly summarizes a current view of the processes that drive germ cell differentiation, particularly the various roles that the fusome might play in regulating the developmental events. Future efforts will consider to what extent an organelle assembly‐dependent model for differentiation is heuristic and whether the Drosophila fusome represents a homolog of a similar organelle in vertebrate lymphocytes.
Good things in small packages: The tiny genomes of chlorarachniophyte endosymbionts
Authors: Gilson Paul R. , McFadden Geoffrey I. 
Published: February 2005

AbstractChlorarachniophytes are amoeboflagellate, marine protists that have acquired photosynthetic capacity by engulfing and retaining a green alga. These green algal endosymbionts are severely reduced, retaining only the chloroplast, nucleus, cytoplasm and plasma membrane. The vestigial nucleus of the endosymbiont, called the nucleomorph, contains only three small linear chromosomes and has a haploid genome size of just 380 kb ‐ the smallest eukaryotic genome known. Initial characterisation of nucleomorph DNA has revealed that all chromosomes are capped with inverted repeats comprising a telomere and a single ribosomal RNA operon. The nucleomorph genome is the quintessence of compactness; average space between genes is a mere 65 bp, some genes overlap, others are cotranscribed. Intense reductive pressures upon nucleomorph genes have apparently squeezed their spliceosomal‐type introns down to only 18, 19 or 20 bases in length. Studies to date indicate the nucleomorph ‐ essentially a stripped‐down eukaryotic genome ‐ encodes principally genetic housekeeping functions such as translation, transcription and splicing.
The mammalian acrosome reaction: Gateway to sperm fusion with the oocyte?
Authors: Allen Catherine A. , Green David P. L. 
Published: February 2005

AbstractMammalian sperm undergo discharge of a single, anterior secretory granule following their attachment to the zona pellucida surrounding the oocyte. This secretory discharge is known for historical reasons as the acrosome reaction. It fulfils a number of purposes and without it, sperm are unable to penetrate the zona pellucida and fuse with the oocyte. In this review, we focus on the role of the acrosome reaction in the development of fusion competence in sperm. Any naturally occurring membrane fusion has two major sequential steps: a docking or adhesion step, in which two membranes adhere, and a fusion step, in which their lipid bilayers are destabilized and merged and a cellular compartment is either created or destroyed. Recent evidence suggests that there is an important role for oocyte integrins and sperm‐bound disintegrins in mammalian sperm/oocyte adhesion and fusion. The fusion mechanism employed by sperm remains poorly understood, however, and circumstantial evidence suggests it is more complex than the interaction between a single protein species and its target. Sperm/oocyte fusion is probably the most accessible eukaryotic model for intercellular fusion currently available, partly because it is temporally separated from gene expression. Elucidation of the mechanism of sperm/oocyte fusion may throw light on the mechanism of other intercellular fusions such as myoblast fusion, and the evolutionary relationship of intercellular membrane fusion to intracellular membrane fusion.
Canalization: A molecular genetic perspective
Authors: Wilkins Adam S. 
Published: February 2005

AbstractThe phenomenon of ‘canalization’ ‐ the genetic capacity to buffer developmental pathways against mutational or environmental perturbations ‐ was first characterized in the late 1930s and early 1940s. Despite enormous subsequent progress in understanding the nature of the genetic material and the molecular basis of gene expression, there have been few attempts to interpret the classical work on canalization in molecular genetic terms. Some recent findings, however, bear on one form of canalization, ‘genetic canalization’, the stabilization of development against mutational effects. These data indicate that co‐expressed paralogous genes can function as mutual ‘back‐up’ elements in developmental processes. Paralogues, however, are far from the only basis of canalization: other genetic sources can be readily envisaged and some of these are described here. The evolutionary questions about genetic canalization and the mechanistic questions about developmental instability that still need to be addressed are also briefly discussed.
Left‐right asymmetry in vertebrate embryogenesis
Authors: Levin Michael 
Published: February 2005

AbstractEmbryonic development results in animals whose body plans exhibit a variety of symmetry types. While significant progress has been made in understanding the molecular events underlying the early specification of the antero‐posterior and dorso‐ventral axes, little information has been available regarding the basis for left‐right (LR) differences in animal morphogenesis. Recently however, important advances have been made in uncovering the molecular mechanisms responsible for LR patterning. A number of genes (including well‐known signaling molecules such as Sonic hedgehog and activin) are asymmetrically expressed in early chick embryos, well before the appearance of morphological asymmetries. One of these, nodal, is asymmetrically expressed in frogs and mice as well, and its expression is altered in mouse mutants exhibiting defects in laterality. In the chick, these genes regulate each other in a sequential cascade, which independently determines the situs of the heart and other organs.
Receptor tyrosine kinase‐dependent neural crest migration in response to differentially localized growth factors
Authors: Wehrle‐Haller Bernhard , Weston James A. 
Published: February 2005

AbstractHow different neural crest derivatives differentiate in distinct embryonic locations in the vertebrate embryo is an intriguing issue. Many attempts have been made to understand the underlying mechanism of specific pathway choices made by migrating neural crest cells. In this speculative review we suggest a new mechanism for the regulation of neural crest cell migration patterns in avian and mammalian embryos, based on recent progress in understanding the expression and activity of receptor tyrosine kinases during embryogenesis. Distinct subpopulations of crest‐derived cells express specific receptor tyrosine kinases while residing in a migration staging area. We postulate that the differential expression of receptor tyrosine kinases by specific subpopulations of neural crest cells allows them to respond to localized growth factor ligand activity in the embryo. Thus, the migration pathway taken by neural crest subpopulations is determined by their receptor tyrosine kinase response to the differential localization of their cognate ligand.
A novel signalling mechanism for generating ca2+ oscillations at fertilization in mammals
Authors: Swann Karl , Lai F. A. 
Published: February 2005

AbstractAt fertilization in mammals the sperm activates the egg by triggering a series of oscillations in the intracellular free Ca2+ concentration. The precise sequence of events that occur between sperm‐egg contact and the increases in intracellular Ca2+ remains unknown. Here, we discuss recent evidence supporting the hypothesis that a cytosolic sperm protein enters the egg after gamete membrane fusion and triggers Ca2+ oscillations from within the egg cytoplasm. Biochemical studies suggest that there exists a novel sperm protein, named oscillin, that specifically comigrates with Ca2+ oscillation‐inducing activity. Oscillin has been immunolocalised to the region of the sperm that first fuses with the egg. The concept of a specific protein that triggers Ca2+ oscillations may have wider physiological significance since sperm oscillin can induce Ca2+ oscillations in somatic cells, such as neurons and hepatocytes. Unravelling the novel signalling system involved in mammalian fertilization may help reveal some fundamental molecular mechanisms responsible for triggering cytoplasmic Ca2+ oscillations.
The role of phosphotyrosine phosphatases in haematopoietic cell signal transduction
Authors: Frearson Julie A. , Alexander Denis R. 
Published: February 2005

AbstractPhosphotyrosine phosphatases (PTPases) are the enzymes which remove phosphate groups from protein tyrosine residues. An enormous number of phosphatases have been cloned and sequenced during the past decade, many of which are expressed in haematopoietic cells. This review focuses on the biochemistry and cell biology of three phosphatases, the transmembrane CD45 and the cytosolic SH2‐domain‐containing PTPases SHP‐1 and SHP‐2, to illustrate the diverse ways in which PTPases regulate receptor signal transduction. The involvement of these and other PTPases has been demonstrated in haematopoietic cell development, apoptosis, activation and non‐responsiveness. A common theme in the actions of many haematopoietic cell PTPases is the way in which they modulate the thresholds for receptor signalling, thereby regulating critical events in the positive and negative selection of lymphocytes. There is growing interest in haematopoietic PTPases and their associated regulatory proteins as targets for pharmaceutical intervention and in the involvement of these enzymes in human disease.
Developmental phenotypic plasticity: Where ecology and evolution meet molecular biology
Authors: Callahan Hilary S. , Pigliucci Massimo , Schlichting Carl D. 
Published: February 2005

AbstractThe plastic response of phenotypic traits to environmental change is a common research focus in several disciplines ‐ from ecology and evolutionary biology to physiology and molecular genetics. The use of model systems such as the flowering plantArabidopsis thalianahas facilitated a dialogue between developmental biologists askinghowplasticity is controlled (proximate causes) and organismal biologists askingwhyplasticity exists (ultimate causes). Researchers studying ultimate causes and consequences are increasingly compelled to reject simplistic, ‘black box’ models, while those studying proximate causes and mechanisms are increasingly obliged to subject their interpretations to ecological ‘reality checks.’ We review the successful multidisciplinary efforts to understand the phytochrome‐mediated shade‐avoidance and light‐seeking responses of flowering plants as a pertinent example of convergence between evolutionary and molecular biology. In this example, the two‐way exchange between reductionist and holist camps has been essential to rapid and sustained progress. This should serve as a model for future collaborative efforts towards understanding the responses of organisms to their constantly changing environments.
Homeosis and polyposis: A tale from the mouse
Authors: He Tong‐Chuan , Da Costa Luis T. , Thiagalingam Sam 
Published: February 2005

AbstractHomeobox genes play essential roles in specifying the fates of different cell types during embryogenesis. In Drosophila, the homeotic gene caudal is important for the generation of posterior structures. In the mouse, the caudal homologue Cdx2 has been implicated in directing early processes in intestinal morphogenesis and in the maintenance of the differentiated phenotype. A recent study showed that Cdx2 null mutation was embryonically lethal, whereas Cdx2+/− mice developed multiple intestinal polyps in the proximal colon in addition to developmental defects(1). There are striking phenotypic similarities and differences between Cdx2+/− and other mice predisposed to intestinal neoplasia. The possible role of Cdx2 in human colorectal tumorigenesis is discussed.
Structural studies on myosin II: Communication between distant protein domains
Authors: Gulick Andrew M. , Rayment Ivan 
Published: February 2005

AbstractUnderstanding how chemical energy is converted into directed movement is a fundamental problem in biology. In higher organisms this is accomplished through the hydrolysis of ATP by three families of motor proteins: myosin, dynein and kinesin. The most abundant of these is myosin, which operates against actin and plays a central role in muscle contraction. As summarized here, great progress has been made towards understanding the molecular basis of movement through the determination of the three‐dimensional structures of myosin and actin and through the establishment of systems for site‐directed mutagenesis of this motor protein. It now appears that the generation of movement is coupled to ATP hydrolysis by a series of domain movements within myosin.
In pursuit of influenza: Fort monmouth to valhalla (and back)
Authors: Kilbourne Edwin D. 
Published: February 2005

AbstractIn reviewing 50 years of personal research on influenza, I have journeyed, literally and figuratively, from an army camp epidemic in Fort Monmouth NJ in 1947 to a (literal and figurative) Valhalla, where I now conduct my research. Having entered the field as a physician, I have always sought practical applications of my work, yet in every instance, such applications have led me to seek further answers in basic research as new questions arose. I entered the area of influenza virus genetics by the back door through an interest in the effects of corticosteroid hormones on viral replication, used the genetic approach in analyzing the morphological variation of the virus and, in so doing, exploited the finding of a linkage of high‐yield growth to spherical morphology. Today, all influenza vaccine viruses are high‐yield genetic reassortants. Subsequent study of reassortant viruses facilitated the identification and isolation of the two major antigens of the virus in antigenic hybrids and showed their differing functions in the induction of immunity. In turn, a new approach to influenza vaccination has been discovered and is presently under clinical investigation.
Spatial features of calcium‐regulated gene expression
Authors: Finkbeiner Steven , Greenberg Michael E. 
Published: February 2005

AbstractA key characteristic of an animal's nervous system is that it can respond to brief environmental stimuli with lasting changes in its structure and function. These changes are triggered by specific patterns of neuronal electrical activity and are manifested as changes in the strength and patterns of synaptic connectivity between activated neurons. The biochemical mechanisms that control these changes are unclear, but cytoplasmic rises in Ca2+ levels may play a critical role, especially in regulating neuronal gene expression for making activity‐induced synaptic changes permanent. Recently, two reports have explored the spatial features by which activity‐induced rises in Ca2+ levels activate transcription factors and gene expression(1,2). The reports suggest that Ca2+ influx acts both locally at the synapse and distantly within the nucleus to regulate transcription factors and gene expression. The results also show that regulatory elements within genes can respond differentially, depending on spatial differences in intracellular Ca2+ rises. These reports suggest new spatial mechanisms by which Ca2+‐dependent gene expression could contribute to activity‐dependent synaptic changes.
Epithelial differentiation in Drosophila
Authors: Tepass Ulrich 
Published: February 2005

AbstractOur understanding of epithelial development in Drosophila has been greatly improved in recent years. Two key regulators of epithelial polarity, Crumbs and DE‐cadherin, have been studied at the genetic and molecular levels and a number of additional genes are being analyzed that contribute to the differentiation of epithelial cell structure. Epithelial architecture has a profound influence on morphogenetic movements, patterning and cell‐type determination. The combination of embryological and genetic/molecular tools in Drosophila will help us to elucidate the complex events that determine epithelial cell structure and how they relate to morphogenesis and other developmental processes.
Challenges: Selective compartments for resistant microorganisms in antibiotic gradients
Authors: Baquero Fernando , Negri María‐Cristina 
Published: February 2005

AbstractThe development of bacterial resistance to antibiotics is one of the best documented examples of contemporary biological evolution. Variability in the mechanisms of resistance depends on the diversity of genotypes in the huge bacterial populations, and also on the diversity of selective pressures that are produced along the antibiotic concentration gradients formed in the highly compartmentalized human body during therapy. These antibiotic gradients can be conceived as comprising selective compartments, each one of them defined as the concentration able to select a particular genetic variant.In vitroexperimental models confirm that some antibiotic resistant variants are selected only at certain selective concentrations of antibiotics. The correspondence between selective compartments and selectable variants could offer a way of describing more accurately the antibiotic selective landscapes and for taking measures to prevent the development of a major threat to the future of modern medicine.
Pax genes and organogenesis
Authors: Dahl Edgar , Koseki Haruhiko , Balling Rudi 
Published: February 2005

AbstractPax genes are a family of development control genes that encode nuclear transcription factors. They are characterized by the presence of the paired domain, a conserved amino acid motif with DNA‐binding activity. Originally, paired‐box‐containing genes were detected in Drosophila malenogaster, where they exert multiple functions during embryogenesis. In vertebrates, Pax genes are also involved in embryogenesis. Mutations in four out of nine characterized Pax genes have been associated with either congenital human diseases such as Waardenburg syndrome (PAX3), Aniridia (PAX6), Peter's anomaly (PAX6), renal coloboma syndrome (PAX2), Small eye (Pax6), (Pax21Neu), which all show defects in development. Recently, analysis of spontaneous and transgenic mouse mutants has revealed that vertebrate Pax genes are key regulators during organogenesis of kidney, eye, ear, nose, limb muscles, vertebral column and brain. Like their Drosophila counterparts, vertebrate Pax genes are involved in pattern formation during embryogenesis, possibly by determiing the time and place of organ initiation of morphogenesis. For most tissues, however, the nature of the primary development action of Pax transcription factors remains to be elucidated. One predominant theme is signal transduction during tissue interactions, which may lead to a position‐specific regulation of cell proliferation.
Molecular events in neutrophil transepithelial migration
Authors: Parkos Charles A. 
Published: February 2005

AbstractNeutrophil transepithelial migration is a central component of many inflammatory diseases of the gastrointestinal, respiratory and urinary tracts, and correlates with disease symptoms. In vitro modeling with polarized intestinal epithelial monolayers has shown that neutrophil transepithelial migration can influence crucial epithelial functions, ranging from barrier maintenance to electrolyte secretion. Studies have also demonstrated a dynamic involvement of the epithelium in modulating neutrophil transepithelial migration. Characterization of the molecular interactions between neutrophils and epithelial cells has revealed that transepithelial migration is dependent on the neutrophil β2 integrin CD11b/CD18, and does not appear to involve adhesive interactions with the selectins or intercellular adhesion molecule‐1. Recent studies have implicated another transmembrane glycoprotein, CD47, as a crucial component of the transepithelial migration response. While the precise function of CD47 is not known, current evidence suggests that CD47‐dependent events occur after CD11b/CD18‐mediated neutrophil adhesion to the epithelium. This review will highlight key features of the current understanding of the molecular events important in neutrophil migration across epithelial surfaces.
Mammalian DNA ligases
Authors: Tomkinson Alan E. , Levin David S. 
Published: February 2005

AbstractDNA joining enzymes play an essential role in the maintenance of genomic integrity and stability. Three mammalian genes encoding DNA ligases, LIG1, LIG3 and LIG4, have been identified. Since DNA ligase II appears to be derived from DNA ligase III by a proteolytic mechanism, the three LIG genes can account for the four biochemically distinct DNA ligase activities, DNA ligases I, II, III and IV, that have been purified from mammalian cell extracts. It is probable that the specific cellular roles of these enzymes are determined by the proteins with which they interact. The specific involvement of DNA ligase I in DNA replication is mediated by the non‐catalytic amino‐terminal domain of this enzyme. Furthermore, DNA ligase I participates in DNA base excision repair as a component of a multiprotein complex. Two forms of DNA ligase III are produced by an alternative splicing mechanism. The ubiqitously expressed DNA ligase III‐α forms a complex with the DNA single‐strand break repair protein XRCC1. In contrast, DNA ligase III‐β, which does not interact with XRCC1, is only expressed in male meiotic germ cells, suggesting a role for this isoform in meiotic recombination. At present, there is very little information about the cellular functions of DNA ligase IV.
Insect societies and the molecular biology of social behavior
Authors: Robinson Gene E. , Fahrbach Susan E. , Winston Mark L. 
Published: February 2005

AbstractThis article outlines the rationale for a molecular genetic study of social behavior, and explains why social insects are good models. Summaries of research on brain and behavior in two species, honey bees and fire ants, are presented to illustrate the richness of the behavioral phenomena that can be addressed with social insects and to show how they are beginning to be used to study genes that influence social behavior. We conclude by considering the problems and potential of this emerging field.