bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vav: A potential link between tyrosine kinases and Ras‐like GTPases in hematopoietic cell signaling
Authors: Hu Patrick , Margolis Ben , Schlessinger Joseph 
Published: February 2005

AbstractThe vav proto‐oncogene encodes a 95 kDa protein which is expressed exclusively in hematopoietic cells. Analysis of the deduced amino acid sequence has revealed the presence of a src‐homology 2 (SH2) domain, 2 SH3 domains, a cysteine‐rich region with similarity to protein kinase C, and a region highly similar to proteins with guanine nucleotide exchange activity on ras‐like GTPases. Recent work has shown that vav is tyrosine phosphorylated in response to stimulation of surface membrane receptors in a variety of hematopoietic cell lines. Vav may play a role in hematopoietic cell signaling by coupling tyrosine kinase pathways to ras‐like GTPases through the regulation of guanine nucleotide exchange.
Mechanisms of transactivation by retinoic acid receptors
Authors: Stunnenberg Hendrik G. 
Published: February 2005

AbstractRetinoids play an important role in development and differentiation(1,2). Their effect is mediated through nuclear receptors, RAR (α, β and γ) and RXR (α, β and γ),Abbreviations. RAR: retinoic acid receptor; RXR: retinoid X receptor; T3:thyroid hormone receptor; VD3R: vitamin D3 receptor; PPAR: peroxisome proliferator activated receptor; EcR ecdycsone receptor; USP, ultraspiracle; NGFI‐B: also referred to as nur77a; ELP: embryonal long terminal repeat‐binding protein; FTZ‐F1: positive regulator of the fushi tarazu gene in blastodermstage embryos of Drosophila melanogaster; GR: glucocorticoid receptor; ER: estrogen receptor; RARE, retinoic acid response element; PR: progesterone receptor; DR+x: direct repeat with a spacing of x nucleotides; DBD: DNA‐binding domain; CRABP I and II: cellular retinoic acid binding protein type I and II, respectively; MoMLV: Moloney Murine Leukemia Virus; TBP: TATA‐binding protein; TAF: TBP associated factor.
which are members of a distinct subclass (hereafter referred to as type II) of the nuclear receptor superfamily that includes the thyroid hormone receptor (T3R), the vitamin D3 receptor (VD3R) and the peroxisome proliferator activated receptor (PPAR). Type II receptors transactivate through binding sites composed of closely related half‐sites (consensus sequence AGG/T TCA) arranged as direct repeats and, with the possible exception of RXR, do not bind to their cognate binding sites as homodimers but require RXR for high affinity binding. RXR thus provides a link between biologically distinct ligand induced pathways and is a potential target for cross‐regulation. In addition, RAR can utilize alternative routes to enhance transcription initiation mediated through transcriptional co‐activators which are expressed in a cell‐type specific manner.
Protein targeting to dense‐core secretory granules
Authors: Chidgey Martyn A. J. 
Published: February 2005

AbstractRegulated secretory proteins are stored within specialized vesicles known as secretory granules. It is not known how proteins are sorted into these organelles. Regulated proteins may possess targeting signals which interact with specific sorting receptors in the lumen of the trans‐Golgi network (TGN) prior to their aggregation to form the characteristic dense‐core of the granule. Alternatively, sorting may occur as the result of specific aggregation of regulated proteins in the TGN. Aggregates may be directed to secretory granules by interaction of a targeting signal on the surface with a sorting receptor. Novel targeting signals which confer on regulated proteins a tendency to aggregate under certain conditions, and in so doing cause them to be incorporated into secretory granules, have been implicated. Specific targeting signals may also play a role in directing membrane proteins to secretory granules.
Problems and paradigms: Dystrophin as a mechanochemical transducer in skeletal muscle
Authors: Brown Susan C. , Lucy Jack A. 
Published: February 2005

AbstractThis review is primarily concerned with two key issues in research on dystrophin: (1) how the protein interacts with the plasma membrane of skeletal muscle fibres and (2) how an absence of dystrophin gives rise to Duchenne muscular dystrophy. In relation to the first point, we suggest that the post‐translational acylation of dystrophin may contribute to its interaction with the plasma membrane. Regarding the second point, it is generally considered that an absence of dystrophin makes the plasma membrane susceptible to damage by contraction/relaxation cycles. In this connection, we propose that the progressive nature of Duchenne dystrophy, and the phenotypic characteristics of mdx mice, are more consistent with dystrophin functioning as a mechanical transducer that transmits growth stimuli from the enlarging skeleton to the muscle. On the basis of this hypothesis, dystrophin‐deficient muscles would be unable to grow at the same rate as the skeleton.
Multiple bacterial topoisomerases: Specialization or redundancy?
Authors: Schmid Molly B. , Sawitzke James A. 
Published: February 2005

AbstractIn the past few years, two new DNA topoisomerases have been discovered in bacteria, bringing the total number of DNA topoisomerases in E. coli to four. Two classes of topoisomerases, type 1 and type 2, are distinguishable by their amino acid homology and their apparent reaction mechanism. Of the four E. coli topoisomerases, there are two type 1 and two type 2 enzymes. In eukaryotes, the existence of multiple type 1 and type 2 enzymes has also become apparent. The existence of these multiple enzymes provokes a question whose answer has both evolutionary and physiological implications: are these topoisomerases functionally redundant, or have they acquired sufficient specialization that they now perform unique biological reactions? In bacteria, there is evidence for both specialization and redundancy in the functions of topoisomerases.
Gene delivery to neurons: Is herpes simplex virus the right tool for the job?
Authors: Leib David A. , Olivo Paul D. 
Published: February 2005

AbstractHerpes simplex virus (HSV)‐derived vectors are currently being developed for the introduction of foreign DNA into neurons. HSV vectors can facilitate a range of molecular studies on postmitotic neurons and may ultimately be used for somatic cell gene therapy for certain neurologic diseases. In this article, the salient features of the pathogenesis and molecular biology of HSV relevant to its use as a vector are described, along with an overview of the methods used to derive these vectors. The accomplishments which have been made to date using the HSV vector system are discussed, with emphasis on the issues of this technology which remain to be addressed. HSV has the potential to be a most useful tool for neuronal cell transgenesis and it is likely that important neurobiological questions will be answered using this vector system.
The Spliceosome
Authors: Lamond Angus I. 
Published: February 2005

AbstractThe spliceosome is a large RNA‐protein complex that catalyses the removal of introns from nuclear pre‐mRNA. A wide range of biochemical and genetical studies shows that the spliceosome comprises three major RNA‐protein subunits, the U1, U2 and [U4/U6.U5] small nuclear ribonucleoprotein particles (snRNPs), and an additional group of non‐snRNP protein splicing factors. Rapid progress is being made in unravelling the interactions which take place between these factors during the splicing reaction. The emerging picture of the spliceosome reveals a highly dynamic structure that assembles on pre‐mRNA transcripts in a stepwise pathway and is organised, at least in part, by complex RNA base‐pairing interactions between the small nuclear RNAs (snRNAs) and the intron substrate. Many of these interactions can be detected both in mammalian and yeast spliceosomes, suggesting that the basic splicing mechanism is an ancient one that has been highly conserved during evolution.
γ‐Tubulin: The hub of cellular microtubule assemblies
Authors: Joshi Harish C. 
Published: February 2005

AbstractIn eukaryotic cells a specialized organelle called the microtubule organizing center (MTOC) is responsible for disposition of microtubules in a radial, polarized array in interphase cells and in the spindle in mitotic cells. Eukaryotic cells across different species, and different cell types within single species, have morphologically diverse MTOCs, but these share a common function of organizing microtubule arrays. MTOCs effect microtubule organization by initiating microtubule assembly and anchoring microtubules by their slowly growing minus ends, thus ensuring that the rapidly growing plus ends extend distally in each microtubule array. The goal is to define molecular components of the MTOC responsible for regulating microtubule assembly. One approach to defining the molecules responsible for MTOC function is to look for molecules common to all MTOCs. A newly discovered centrosomal protein, γ‐tubulin, is found in MTOCs in cells from many different organisms, and has several properties which make it a candidate for both initiation of microtubule assembly and anchorage. The hypothesis that γ‐tubulin plays a role in MTOCs in microtubule initiation and anchorage is currently being tested by a variety of experimental approaches.
Common mechanisms for the control of eukaryotic transcriptional elongation
Authors: Krumm Anton , Meulia Tea , Groudine Mark 
Published: February 2005

AbstractRegulation of transcriptional elongation is emerging as an important control mechanism for eukaryotic gene expression. In this essay, we review the basis of the current view of the regulation of elongation in the human c‐myc gene and discuss similarities in elongation control among the c‐myc, Drosophila hsp70 and the HIV‐1 genes. Based upon these similarities, we propose a model for control of expression of these genes at the elongation phase of transcription. This model suggests that distinct promoter elements direct the assembly of RNA polymerase II transcription complexes which differ in their elongation efficiency.
The aminoacyl‐tRNA synthetase family: Modules at work
Authors: Delarue M. , Moras D. 
Published: February 2005

AbstractThe combined use of molecular and structural biology techniques has proved very efficient in elucidating structure‐function relationships in aminoacyl‐tRNA synthetases. Our present understanding of this family of enzymes is based on two main unifying principles: (i) division into two different classes, corresponding to two different modes of ATP binding and attachment of the activated amino acid to the last nucleotide of tRNA (either 2′OH or 3′OH of the ribose) by two different catalytic mechanisms and two structural domains with completely different folding, and (ii) the modular organization into separate and additional domains that we are just beginning to understand. Sequence analysis complements very nicely existing structural, biochemical and genetic results and makes them more general, leading to verifiable predictions.
Discerning the function of p53 by examining its molecular interactions
Authors: Oliner Jonathan D. 
Published: February 2005

AbstractOf the many genes mutated on the road to tumor formation, few have received as much attention as p53. The gene has come to occupy center stage for the simple reason that it is more frequently altered in human tumors than any other known gene, undergoing mutation at a significant rate in almost every tumor type in which it has been studied. This association between p53 mutation and tumorigenesis has spurred a flurry of research attempting to delineate the normal function of p53 and, by extension, the role of p53 mutation in tumor formation. At the cellular level, p53 has been shown to suppress growth. Recent efforts to further discern the function of p53 have centered on the underlying molecular basis for this growth suppression. In particular, research has focused on the identification of cellular molecules (specifically DNA and proteins) with which the p53 protein associates. p53 has now been shown to bind DNA in a sequence‐specific manner, and mounting evidence suggests that p53 acts as a transcription factor, perhaps regulating the expression levels of genes involved in the inhibition of cell growth. The logical next step in understanding p53 function involves the resolution of two questions: (1) what are the physiological transcriptional targets of p53, and (2) what cellular proteins regulate or mediate the ability of p53 to modulate transcription? Some initial clues to these puzzles are now emerging, and these form the subject of this review.
The ascidian embryo as a prototype of vertebrate neurogenesis
Authors: Okamura Yasushi , Okado Haruo , Takahashi Kunitaro 
Published: February 2005

AbstractAscidian tadpole larvae, composed of only about 2500 cells, have a primitive nervous system which is derived from the neural plate. The stereotyped cell cleavage pattern and well characterized cell lineage in these animals allow the isolation and culture of identified blastomeres in variable combinations. Ascidian embryos express cell‐type‐specific markers corresponding to their cell fates, even when cultured under cleavage‐arrest by cytochalasin B. This system provides us with a unique opportunity to study the roles of cell lineage and cell contact in early neuronal differentiation in the absence of events associated with complex morphogenesis. In addition, the isolated, cleavage‐arrested blastomeres are ideally suited to electrical recording, permitting the use of ionic channels as specific markers for differentiation. In the cleavage‐arrested embryos, suppression of one type of K+ channel, and induction of two types of Na+ channels, occur following cell contact with the vegetal blastomere. The combination of molecular and electrophysiological analyses on this simple animal system may provide insights into the nature of the cell interactions important in early neurogenesis, both in ascidians and in vertebrates.
Immunosuppressants: Tools to investigate the physiological role of cytokines
Authors: Quesniaux Valerie F. J. 
Published: February 2005

AbstractThe cyclic opeptide Cyclosporinee A (CsA) is best known as the immunosuppressive drug which has revoulutionized organ transplantation. It selectively suppresses T cell activation by blocking the transcription of cytokine genes such as IL‐2 at the level of transxcription factor modulation. The structurally unrelated immuniusuppressant FK 506 acts on the same pathway and blocks cytokine gene expression . In contrast, rapamycin, a structural analoguwe of FK 506, interferes with the immune response at a different level, by blocking the response induced by ctytokines such as IL‐2.Although these drugs have been most studied for their immunosuppressive activities, it is clear that their effects on cytokine pathways extend far beyond the scole IL‐2.‐mediated responses involved in the immune response. IFor instance, CsA and FK 506 inhibit the transcription of IL‐3, IL‐4, IFNγ, TNFα or GM‐CSF by activated T cells, and rapamycin has been shown to blcock the response to various growth factors such as IL‐3, IL‐4 or IL‐6.Here, we receap what is known about the effects of CsA, FK 506 and rapamycin on hematopoiesis in vitro and in vivo and extrapolate on what these drugs can teach us aboput the physiological role of cytokines for hematopoiesis.
Dogs, distemper and Paget's disease
Authors: Mee Andrew P. , Sharpe Paul T. 
Published: February 2005

AbstractThe cause of Paget's disease is still unknown, despite many years of intensive study. During this time, evidence has sporadically emerged to suggest that the disease may result from a slow viral infection by one or more of the Paramyxoviruses. More recently, epidemiologic and molecular studies have suggested that the canine paramyxovirus, canine distemper virus, is the virus responsible for the disease. If true, then along with rabies, this would be a further example of a canine virus causing human disease. Studies in the natural host have now supported these findings. Further investigations have proposed that the bony abnormalities seen in Paget's disease are due to the effects of the virus on osteoclastic interleukin‐6 and c‐FOS production, possibly via the transcription factor NF‐kB.
Radical solutions and cultural problems: Could free oxygen radicals be responsible for the impaired development of preimplantation mammalian embryos in vitro?
Authors: Johnson Martin H. , Nasresfahani Mohammad H. 
Published: February 2005

AbstractA major obstacel to the study of mammalian development, and to the practical application of knowledge gained from it in the clinic during therapeutic in vitro fertilisation and embryo transfer (IVF‐ET), is the propensity of embryos to become retarded or arrested during their culture in vitro. The precise developmental cell cycle in which embryos arrest or delay is characteristic for the species and coincides with the earliest period of embryonic gene expression. Much evidence reviewed here implicates free oxygen radicals (FORs) in the process of arrest. Thus, studies on the development of mouse preimplantation embryos in vitro have shown that (i) FORs are elevated in vitro, but not in vivo, at the time at which embryos become arrested or delayed, (ii) systems for removing reactive oxygen species to limit the formation of hydroxy radicals are present, although they have not yet been assessed quantitatively and may differ qualitatively from those in adult cells, (iii) metabolic and possibly genetic adaptations to oxidative damage are evident, (iv) published procedures for overcoming in vitro arrest are explicable in terms of FOR‐mediated damage or responses and (v) the arrest or delay of most embryos in vitro can be reduced or prevented experimentally by addition of metal chelators to limit hydroxy radical formation and lipid hydroperoxidation.
Growth factors as survival factors: Regulation of apoptosis
Authors: Collins Mary K. L. , Perkins Gordon R. , Rodriguez‐Tarduchy Gemma , Nieto Maria Angela , López‐Rivas Abelardo 
Published: February 2005

AbstractApoptosis is now widely recognized as a common form of cell death and represents a mechanism of cell clearance in many physiological situations where deletion of cells is required. Peptide growth factors, initially characterised as stimulators of cell proliferation, have now been shown to inhibit death in many cell types. Deprivation of growth factors leads to the induction of apoptosis, i.e. condensation of chromatin and degradation in oligonucleosomesized fragments, formation of plasma and nuclear membrane blebs and cell fragmentation into apoptotic bodies which can be taken up by neighbouring cells. Here we discuss the mechanism(;s) by which growth factors may inhibit apoptosis.
The cuticle of the nematode Caenorhabditis elegans: A complex collagen structure
Authors: Johnstone Iain L. 
Published: February 2005

AbstractThe cuticle of the nematode Caenorhabditis elegans forms the barrier between the animal and its environment. In addition to being a protective layer, it is an exoskeleton which is important in maintaining and defining the normal shape of the nematode. The cuticle is an extracellular matrix consisting predominantly of small collagen‐like proteins that are extensively crosslinked. Although it also contains other protein and non‐protein compounds that undoubtedly play a significant part in its function, the specific role of collagen in cuticle structure and morphology is considered here. The C. elegans genome contains between 50 and 150 collagen genes, most of which are believed to encode cuticular collagens. Mutations that result in cuticular defects and grossly altered body form have been identified in more than 40 genes. Six of these genes are now known to encode cuticular collagens, a finding that confirms the importance of this group of structural proteins to the formation of the cuticle and the role of the cuticle as an exoskeleton in shaping the worm. It is likely that many more of the genes identified by mutations giving altered body form, will be collagen genes. Mutations in the cuticular collagen genes provide a powerful tool for investigating the mechanisms by which this group of proteins interact to form the nematode cuticle.
Cytokine signal transduction and the JAK family of protein tyrosine kinases
Authors: Wilks Andrew F. , Harpur Ailsa G. 
Published: February 2005

AbstractCytokine receptors fall into two basic classes: those with their own intrinsic protein tyrosine kinase (PTK) domain, and those lacking a PTK domain. Nonetheless, PTK activity plays a fundamental role in the signal transduction processes lying downstream of both classes of receptor. It now seems likely that many of those cytokine receptors that lack their own PTK domain use members of the JAK family of PTKs to propagate their intracellular signals. Moreover, the involvement of the JAK kinases in a newly defined pathway which links membrane receptors directly to the activation of nuclear genes, via latent cytoplasmic transcription factors known as STATs (for Signal Transducers and Activators of Transcription), appears to be a theme common to cytokine receptors of both classes.
Uncontrolled growth associated with novel somatic recombination in the fungus Schizophyllum
Authors: Leonard Thomas J. , Dick Stanley 
Published: February 2005

AbstractIn the bracket mushroom, Schizophyllum commune, a recessive genetic alteration, mnd, causes abnormally hyperplastic three‐dimensional mounds of hyphae to rise from the surface of both haploid and dikaryotic mycelia. mnd, although not a genetic block in the fruiting body developmental pathway, is at least partially epistatic to fruiting. Within dikaryons containing both mutant and wild‐type nuclei, [mnd + mnd+], a nonreciprocal somatic recombination event can lead to stable conversion of the mnd+ region of the wild‐type nucleus to mnd. This transformation to the homoallelic [mnd + mnd] condition involves no genomic areas other than the mnd region and permanently prevents any further fruiting. Studies relating to the recombination mechanism have ruled out a diploid intermediate state and other concomitants of orthodox somatic recombination, as well as whole chromosome transfer. Instead, a novel form of internuclear genetic transfer is postulated whereby a nearby locus, mob+, controls the mobilization of the mnd chromosomal region alone from one nucleus to the other within the binucleate cells of dikaryotic mycelia.