bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anoxia, wound healing, VL30 elements, and the molecular basis of malignant conversion
Authors: Anderson Garth R. , Stoler Daniel L. 
Published: February 2005

AbstractAlthough VL30 retrotransposable elements have been associated with certain cancers for nearly twenty years, because of their expression in rodent malignancies and recombination into murine sarcoma viruses, their causative role, if any, in cancer has been uncertain and enigmatic. Recent findings suggest loss of normal transcriptional control of specific VL30 element expression may make a critical contribution to tumor progression at a step associated with malignant conversion, by bringing into play a cellular program normally involved in wound healing. This program, the fibroblast anoxic response system, includes an adaptation to glycolytic metabolism, secretion of metalloproteinases, and activation of an endonuclease. While appropriate for facilitating debris removal during wound healing, loss of control of this program in a cell which has already progressed to the benign neoplastic state has the potential to simultaneously produce the invasiveness and genomic instability charateristic of malignancy. Examination of tumors and tumor derived cell lines has confirmed that key aspects of this system are in fact activated in cancer.
Hypothesis: An apparent dimerization motif in the third domain of alphafetoprotein: Molecular mimicry of the steroid/thyroid nuclear receptor superfamily
Authors: Mizejewski G. J. 
Published: February 2005

AbstractAlpha‐fetoprotein (AFP)AFP, alpha‐fetoprotein; T3R, thyroid hormone (triiodothyronine) receptor; RAR, retionic acid receptor; erbA, putative thyroid hormone receptor proto‐oncogene products; VDR, vitamin D receptor; MR, mineralocorticoid receptor; GR, glucocorticoid receptor; PR, progesterone receptor; AR, androgen receptor; HRE, hormone response element on DNA; RXR, retionic‐X‐receptor; RAP, receptor auxiliary (accessory) proteins; E, estrogen.
is a tumor‐associated fetal marker, associated both with tumor growth and with birth defects. AFP, whose precise function is unknown, has been classified as belonging to a protein superfamily together with albumin and vitamin D‐binding (Gc) protein. AFP has been shown to bind various ligands in vitro including fatty acids, estrogens, thyroid hormones and retinoic acids. The steroid/thyroid nuclear receptor superfamily of proteins has recently become a major focus of biomedical investigation regarding regulation of gene expression. These receptors are thought to bind to DNA‐hormone response elements (HRE) that affect growth, development, differentiation, reproduction and homeostasis. The HREs are known to share DNA sequences with the various members of the nuclear receptor superfamily. In the present report, the possibility of a leucine‐zipper dimerization (heptad) motif in the carboxy‐terminal third domain of both rodent and human AFP is postulated. The presence of nine such hydrophobic repeats in the third domain of the AFP molecule mimics the heptad dimerization repeats found in the retinoic acid, thyroid, e‐erbA and other members of the nuclear receptor superfamily. Computer analysis revealed that the most conservative matching occurred between AFP and the retinoic acid class of receptors. However, other superfamily members displayed 40–60% homology with 5 of 9 AFP heptads. These findings could provide a possible mechanism for explaining the growth‐regulatory properties (both inhibition and enhancement) that have been ascribed to AFP in the last decade.
Structure and function of the homeotic gene complex (HOM‐C) in the beetle, Tribolium castaneum
Authors: Beeman Richard W. , Stuart Jeffrey J. , Brown Susan J. , Denell Robin E. 
Published: February 2005

AbstractThe powerful combination of genetic, developmental and molecular approaches possible with the fruit fly, Drosophila melanogaster, has led to a profound understanding of the genetic control of early developmental events. However, Drosophila is a highly specialized long germ insect, and the mechanisms controlling its early development may not be typical of insects or Arthropods in general. The beetle, Tribolium castaneum, offers a similar opportunity to integrate high resolution genetic analysis with the developmental/molecular approaches currently used in other organisms. Early results document significant differences between insect orders in the functions of genes responsible for establishing developmental commitments.
The centromere of budding yeast
Authors: Hegemann Johannes H. , Fleig Ursula N. 
Published: February 2005

AbstractStable maintenance of genetic information during meiosis and mitosis is dependent on accurate chromosome transmission. The centromere is a key component of the segregational machinery that couples chromosomes with the spindle apparatus. Most of what is known about the structure and function of the centromeres has been derived from studies on yeast cells. In Saccharomyces cerevisiae, the centromere DNA requirements for mitotic centromere function have been defined and some of the proteins required for an active complex have been identified. Centromere DNA and the centromere proteins form a complex that has been studied extensively at the chromatin level. Finally, recent findings suggest that assembly and activation of the centromere are integrated in tethe cell cycle.
The crystal δ‐endotoxins of Bacillus thuringiensis: Models for their mechanism of action on the insect gut
Authors: Knowles Barbara H. , Dow Julian A. T. 
Published: February 2005

AbstractThe crystal δ‐endotoxins of Bacillus thuringiensis (Bt) are a family of insecticidal proteins which have been known for some time to kill insects by lysing their gut epithelial cells, but the precise molecular mechanism of toxicity has remained elusive. The recent publication of the crystal structure of a Bt δ‐endotoxin has made it possible for us to model the molecular events that occur as the toxin binds to its receptor and inserts into the membrane to form a pore. Using our knowledge of insect gut physiology, we can also predict the effect on the insect of the formation of a toxic pore. We present a new model to explain the events that occur in the insect gut during toxin action.
Intracellular pH regulation in the early embryo
Authors: Baltz Jay M. 
Published: February 2005

AbstractIntracellular pH (pHi) regulation is a homeostatic function of all cells. Additionally, the plasma membrane‐based transporters controlling pHi are involved in growth factor activation, cell proliferation and salt transport – all processes active in early embryos. pHi regulation in the early embryos of many species exhibits unique features: in mouse preimplantation embryos, mechanisms for correcting excess acid apparently are inactive, while excess base is removed by the mechanism common in differentiated cells. Additionally, unlike differentiated cells, mouse preimplantation embryos are highly permeable to H+ until the blastocyst stage, where the epithelial cells surrounding the embryo are impermeable. In several non‐mammalian species, of which the best‐studied is sea urchin, cytoplasmic alkalinization at fertilization is necessary for development of the embryo, and elevated pHi must be maintained during early development. Thus, pHi regulatory mechanisms appear to be important for early embryo development in many species.
Localized RNAs and their functions
Authors: Ding Dali , Lipshitz Howard D. 
Published: February 2005

AbstractThe eukaryotic cell is partitioned by membranes into spatially and functionally discrete subcellular organelles. In addition, the cytoplasm itself is partitioned into discrete subregions that carry out specific functions. Such compartmentation can be achieved by localizing proteins and RNAs to different subcellular regions. This review will focus on localized RNAs, with a particular emphasis on RNA localization mechanisms and on the possible biological functions of localization of these RNAs. In recent years, an increasing number of localized RNAs have been identified in a variety of cell types among many animal species. Emphasis here will be on localized RNAs in the most intensively studied systems – Drosophila and Xenopus eggs and early embryos.
Molecular perspectives of chromosome pairing at meiosis
Authors: Moens Peter B. 
Published: February 2005

AbstractIdeas about the mechanisms that regulate chromosome pairing, recombination, and segregation during meiosis have gained in molecular detail over the last few years. The purpose of this article is to survey briefly the shifts in paradigms and experiments that have generated new perspectives. It has never been very clear what it is that brings together the homologous chromosomes at meiotic prophase. For a while it appeared that the synaptonemal complex might be the nuclear organelle responsible for synapsis, but the supporting evidence has not been entirely convincing. Whatever the mechanism, it has always been assumed that homologous synapsis creates the opportunity for homologous DNA sequences to initiate recombination. At present, alternative ideas are developing. Attractive is the concept that double strand DNA repair mechanisms, that find and use the undamaged homologue for repair, have evolved into a meiotic mechanism for the recognition and pairing of homologous sequences. Subsequent intimate synapsis of homologous chromosomes in the context of the synaptonemal complex may serve later functions in the regulation of interference and segregation at first anaphase. A number of areas that are being tested at present and some that may be investigated in the future are discussed at the end of the review.
Ras regulatory interactions: Novel targets for anti‐cancer intervention?
Authors: Prendergast George C. , Gibbs Jackson B. 
Published: February 2005

AbstractAdvances in the understanding of Ras oncoprotein function suggest novel points for anti‐tumor intervention. First, upstream‐acting guanine nucleotide exchange factors and SH2/SH3 domain‐containing adaptor proteins that link Ras with growth factor receptor tyrosine kinases have recently been characterized. Second, work on downstream‐acting Ras effector functions including the Ras GTPase‐activating protein (p120GAP) and the Raf kinase has revealed direct biochemical interactions that are functionally required for oncogenic Ras signalling. We summarize progress in these areas and discuss the potential for novel applications to anti‐cancer chemotherapy.
The chaperonin cycle and protein folding
Authors: Lund Peter 
Published: February 2005

AbstractThe process of protein folding in the cell is now known to depend on the action of other proteins. These proteins include molecular chaperones, Which interact non‐covalently with proteins as they fold and improve the final yields of active protein in the cell. The precise mechanism by which molecular chaperones act is obscure. Experiments reported recently(1) show that for one molecular chaperone (Cpn60, typified by the E. coli protein GroEL), the folding reaction is driven by cycles of binding and release of the co‐chaperone Cpn10 (known as GroES in E. coli). These alternate with binding and release of the unfolded protein substrate. These cycles come about because of the opposite effects of Cpn10 and unfolded protein on the Cpn60 complex: the former stabilises the ADP‐bound state of Cpn60, whereas the latter stimulates ADP‐ATP exchange. This model proposes that the substrate protein goes through multiple cycles of binding and release, and is released into the cavity of the Cpn60 complex where it can undergo folding without interacting with other nearby folding intermediates. This is consistent with the ability of Cpn60 proteins to enhance folding by blocking pathways to aggregation.
Reactive oxygen species generation and human spermatozoa: The balance of benefit and risk
Authors: Aitken John , Fisher Helen 
Published: February 2005

AbstractAlthough the generation of reactive oxygen species is an activity normally associated with phagocytic leucocytes, mammalian spermatozoa were, in fact, the first cell type in which this activity was described. In recent years it has become apparent that spermatozoa are not the only nonphagocytic cells to exhibit a capacity for reactive oxygen species production, because this activity has been detected in a wide variety of different cells including fibroblasts, mesangial cells, oocytes, Leyding cells endothelial cells, thryroid cells, adipocytes, tumour cell and platelets. Since the capacity to generate reactive oxygen species is apparently so widespread, the risk‐benefit equation for these potentially pernicious molecules becomes a matter of intese interest. In the case of human spermatozoa, the risk of manufacturing reactive oxygen metabolites is considerable because these cells are particularly vulnerable to lipid peroxidation. Indeed, there is now good evidence to indicate that oxygen radicals are involved in the initiation of peroxidative damage to the sperm plasma membrane, seen in many cases of male infertility. This risk is off‐set by recent data suggesting that superoxide anions and hydrogen peroxide also participate in the induction of key biological events such as hyperactiavated motility and the acrosome reaction. Thus, human spermatozoa appear to use reactive oxygen species for a physiological purpose and have the difficult task of ensuring the balanced generation of these potentially harmful, but biologically important, modulators of cellular function.
A good eye for arthropod evolution
Authors: Osorio D. , Bacon J. P. 
Published: February 2005

AbstractInsect and crustacean lineages diverged over 500 Myr ago, and there are continuing uncertaintles about whether they evolved from a common arthropod ancestor or, alternatively, they evolved independently from annelid worms. Despite the diversity of their limbs and lifestyles, the nervous systems of insects and crustaeeans share many common features both in development and in function. Cellular and molecular embryology techniques reveal good evidence for homologies in the developing segmental ganglia. In the visual system, this seemingly common programme of insect and crustacean CNS development culminates in common adult neural function. Comparisons of the cellular anatomy and physiology of animals as diverse as flies and crayfishes indicate that the neural circuits in the lamina of their optic lobe have been inherited largely unchanged from a common ancestor with good compound eyes.
The regulation of the yolk protein genes, a family of sex differentiation genes in Drosophila melanogaster
Authors: Bownes Mary 
Published: February 2005

AbstractThere are many obvious morphological and behavioural differences between male and female Drosophila, whose differing phenotypes are produced by a hierarchy of sex determination genes. These genes have been well characterised at the genetic and molecular level. Similarly, a number of sex‐specific differentiation genes have been characterised, such as the chorion and vitelline membrane genes in females and the sex peptide and other accessory gland proteins in males. Despite the depth of these parallel studies, there is only one example of a direct link between the sex determination pathway and the downstream sex differentiation genes, namely the regulation of the female‐specific yolk protein genes. The yolk proteins are synthesised in the fat body and ovarian follicle cells of the adult female and are subsequently transported to the oocyte where they are stored for utilization during embrygenesis. The expression of the yolk protein genes is not entirely controlled by the sex determination hierarchy, as several different regulatory pathways must interact to direct their correct sexual, temporal and spatial regulation during development.
Endo‐exonucleases: Enzymes involved in DNA repair and cell death?
Authors: Fraser Murray J. 
Published: February 2005

AbstractEndo‐exonucleases from E. coli to man, although very different proteins, are multifunctional enzymes with similar enzymatic activities. They probably have two common but opposing biological roles. On the one hand, they promote survival of the organism by acting in recombination and recombinational DNA repair to diversify and help preserve the genome intact. On the other hand, they degrade the genomic DNA when it is damaged beyond repair. This ensures elimination of heavily mutagenized cells from the population.
The return of copy‐choice in DNA recombination
Authors: Tang Roderick S. 
Published: February 2005

AbstractIn a recent publication, d'Alençon et al.(1) presented evidence that a form of non‐homologous DNA recombination involving direct repeats is dependent upon the replication of the DNA. In addition, density‐labeling experiments showed that after recombination was stimulated, progenies were present only in molecules that had undergone complete replication. These observations are consistent with a replicative and not a breakage‐and‐rejoining model for the DNA recombination events. These two models had of course been contrasted many years ago in mechanistic studies of homologous DNA recombination. It is therefore interesting to place the latest findings of d'Alençon et al. in this historical context.
Mitogenesis and protein synthesis: A role for ribosomal protein S6 phosphorylation?
Authors: Stewart Mary J. , Thomas George 
Published: February 2005

AbstractIt has been known for 20 years that the ribosomal protein S6 is rapidly phosphorylated when cells are stimulated to grow or divide. Furthermore, numerous studies have documented that there is a strong correlation between increases in S6 phosphorylation and protein synthesis, leading to the idea that S6 phosphorylation is involved in up‐regulating translation. In an attempt to define a mechanism by which S6 phosphorylation exerts translational control, other studies have focused on characterizing the sites of phosphorylation of this protein and its location within the ribosome. Recent data show that S6 is a protein which may have diverse cellular functions and is essential for normal development, and that it may be involved in the translational regulation of a specific class of messages.
A role for Y‐box proteins in cell proliferation
Authors: Ladomery Michael , Sommerville John 
Published: February 2005

AbstractMembers of the Y‐box (YB) family of transcription factors are expressed in a wide range of cell types and are implicated in the regulation of a rapidly increasing number of genes. Although the biological activities of YB proteins appear to be varied, distinct patterns, relating to the timing of their expression and the identity of their target genes, are beginning to emerge. A recent report by Ito et al.(1) focusses attention on cell proliferation and adds support to earlier suggestions(2, 3) that a primary function of YB proteins is to help activate growth‐associated genes.
How many receptors does it take?
Authors: Wharton Kristi A. 
Published: February 2005

AbstractThree recent reports (1–3) identify two genes, thick veins (tkv) and saxophone (sax), which encode serine/threonine transmembrane proteins that act as receptors for mediating different aspects of the Drosophila TGF‐β‐related signal, dpp. tkv is required for patterning the entire embryonic dorsal region, while sax is required for patterning only amnioserosa, the dorsalmost cell fates. dpp signaling in other developmental processes again requires both tkv and sax, but to differing degrees. tkv and sax, encode type I receptors, which appear to directly bind ligand, unlike what has been observed for other type I receptors.
Regulation of vertebrate muscle differentiation by thyroid hormone: The role of the myoD gene family
Authors: Muscat George E. O. , Downes Michael , Dowhan Dennis H. 
Published: February 2005

AbstractSkeletal myoblasts have their origin early in embryogenesis within specific somites. Determined myoblasts are committed to a myogenic fate; however, they only differentiate and express a muscle‐specific phenotype after they have received the appropriate environmental signals. Once proliferating myoblasts enter the differentiation programme they withdraw from the cell cycle and form post‐mitotic multinucleated myofibres (myogenesis); this transformation is accompanied by muscle‐specific gene expression. Muscle development is associated with complex and diverse protein isoform transitions, generated by differential gene expression and mRNA splicing. The myofibres are in a state of dynamic adaptation in response to hormones, mechanical activity and motor innervation, which modulate differential gene expression and splicing during this functional acclimatisation. This review will focus on the profound effects of thyroid hormone on skeletal muscle, which produce alterations in gene and isoform expression, biochemical properties and morphological features that precipitate in modified contractile/mechanical characteristics. Insight into the molecular events that control these events was provided by the recent characterisation of the MyoD gene family, which encodes helix‐loop‐helix proteins; these activate muscle‐specific transcription and serve as targets for a variety of physiological stimuli. The current hypothesis on hormonal regulation of myogenesis is that thyroid hormones (1) directly regulate the myoD and contractile protein gene families, and (2) induce thyroid hormone receptor‐transcription factor interactions critical to gene expression.
The cnidarian cnidocyte, a hightech cellular weaponry
Authors: Tardent Pierre 
Published: February 2005

AbstractThe members of the phylum Cnidaria (corals, sea anemones, medusae) are all equipped with stinging cells (cnidocytes, nematocytes), which serve mainly in prey capture and defense. The secretory product of these cells is a most complicated extrusome consisting of a cyst containing a tubule and a liquid matrix. Mechanical stimulation of the cell's cnidocil apparatus by a prey or an offender leads via bioelectrical signal transduction to the explosive discharge of the cnidocyst. In stenoteles of Hydra this process, during which the tubule is everted out of the cyst, takes less than 3 msec. The forces involved are partly due to spring‐like tensions stored in the collagenous structural compartment, and partly to an osmotically generated intracapsular pressure, which can amount to 150 bar (1.5 × 107 Pa). The osmotic machinery depends on the presence in the cyst's matrix of inorganic cations (either K+, Mg2+ or Ca2+) and rare polyanions (poly‐γ‐L‐glutamates), which, so far, have not been reported from recently evolved eukaryotes. The discharging cyst acts like a self‐reloading syringe, injecting poison and other components into the target. Since the cnidocytes are incapable of regenerating their exocytosed cysts, they have to be replaced by new cells derived by differentiation from pluripotent stem cells (interstitial cells).
Specifying the target identity of motoneurons
Authors: Tosney Kathryn W. , Hotary Kevin B. , Lance‐Jones Cynthia 
Published: February 2005

AbstractIn the vertebrate spinal cord, motoneurons are clustered into longitudinal columns in agreement with the targets they innervate. Motoneurons within each column acquire properties early in development that ensure their axons navigate to appropriate targets, but how this target identity is specified is unknown. Recently, Tsuchida et al.(1) described the expression of putative regulatory genes within motor columns in the chicken spinal cord. Combinations of LIM‐family homeobox genes differentially mark columns that project to distinct target groups. Expression precedes column formation and axon outgrowth, making these genes candidates for specifying the target identity of motoneuron groups.