bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unusual evolution of 11β‐ and 17β‐hydroxysteroid and retinol dehydrogenases
Authors: Baker Michael E. 
Published: February 2005

Abstract11β‐hydroxysteroid dehydrogenases regulate glucocorticoid concentrations and 17β‐hydroxysteroid dehydrogenases regulate estrogen and androgen concentrations in mammals. Phylogenetic analysis of the sequences from two 11β‐hydroxysteroid dehydrogenases and four mammalian 17β‐hydroxysteroid dehydrogenases indicates unusual evolution in these enzymes. Type 1 11β‐ and 17β‐hydroxysteroid dehydrogenases are on the same branch; Type 2 enzymes cluster on another branch with β‐hydroxybutyrate dehydrogenase, 11‐cis retinol dehydrogenase and retinol dehydrogenase; Type 3 17β‐hydroxysteroid dehydrogenase is on a third branch; while the pig dehydrogenase clusters with a yeast multifunctional enzyme on a fourth branch. Pig 17β‐hydroxysteroid dehydrogenase appears to have evolved independently from the other three 17β‐hydroxysteroid dehydrogenase dehydrogenases; in which case, the evolution of 17β‐hydroxysteroid dehydrogenase activity is an example of functional convergence. The phylogeny also suggests that independent evolution of specificity toward C11 substituents on glucocorticoids and C17 substituents on androgens and estrogens has occurred in Types 1 and 2 11β‐ and 17β‐hydroxysteroid dehydrogenases.
The role of thrombospondin‐1 in tumor progression and angiogenesis
Authors: Tuszynski George P. , Nicosia Roberto F. 
Published: February 2005

AbstractThrombospondin (TSP‐1) is a large glycoprotein secreted by platelets and synthesized by many cell types, including endothelial and tumor cells. Although controversy exists about the biological function of TSP‐1, the following observations suggest that TSP‐1 may potentiate tumor progression. (1) Tumor metastases in mice are promoted by TSP‐1 and inhibited by anti‐TSP‐1 antibodies. (2) TSP‐1 promotes tumor cell adhesion, migration and invasion. (3) TSP‐1 promotes angiogenesis in the rat aorta model. (4) TSP‐1 up‐regulates the plasminogen activator system through a mechanism involving the activation of TGF‐β1. (5) Human tumors express increased levels of the CSVTCG‐specific TSP‐1 receptor. (6) Tumor stroma is enriched in TSP‐1. (7) Cancer patients have high blood levels of TSP‐1. (8) Poor patient survival correlates with a higher expression of the CSVTCG‐specific TSP‐1 receptor on tumor cells. In this paper we discuss the evidence that TSP‐1 promotes tumor progression and present a hypothetical scheme for its mechanism of action.
STATs and MAPKs: Obligate or opportunistic partners in signaling
Authors: Ihle James N. 
Published: February 2005

AbstractLigand binding to cellular receptors initiates a series of signal transducing cascades that are essential to cellular responses. The Ras pathway is activated in response to a variety of ligands and has been extensively studied. More recently, a novel family of transcription factors (Stats) has been found to be activated in response to many ligands. Three recent publications(1–3) have presented evidence to suggest that these two pathways converge at the level of modulation of Stat function by phosphorylation by MAP kinases. However, each proposes radically different models that are not easily reconciled but invite further experimentation.
Supramolecular assembly of basement membranes
Authors: Timpl Rupert , Brown Judith C. 
Published: February 2005

AbstractBasement membranes are thin sheets of extracellular proteins situated in close contact with cells at various locations in the body. They have a great influence on tissue compartmentalization and cellular phenotypes from early embryonic development onwards. The major constituents of all basement membranes are collagen IV and laminin, which both exist as multiple isoforms and each form a huge irregular network by self assembly. These networks are connected by nidogen, which also binds to several other components (proteoglycans, fibulins). Basement membranes are connected to cells by several receptors of the integrin family, which bind preferentially to laminins and collagen IV, and via some lectin‐type interactions. The formation of basement membranes requires cooperation between different cell types since nidogen, for example, is usually synthesized by cells other than those exposed to the basement membranes. Thus many molecular interactions, of variable affinities, determine the final shape of basement membranes and their preferred subanatomical localization.
Myosin II function in non‐muscle cells
Authors: Maciver Sutherland K. 
Published: February 2005

AbstractAmongst the remarkable variety of motility that cells display, cytokinesis (cell division) is particularly striking. Dramatic changes in cell shape occur before, during and after cytokinesis. Myosin II is implicated in the ‘rounding up’ of cells prior to cytokinesis, and is essential in the formation of the contractile cleavage furrow during cytokinesis. Now it appears that myosin II plays a role in all stages of cytokinesis, as a recent report(1) suggests that myosin II drives post‐mitotic cell spreading. A similar type of motile mechanism operating in cell spreading may occur in other cell types in other situations.
Polarised membrane traffic in hepatocytes
Authors: Wilton Joanne C. , Matthews Glenn M. 
Published: February 2005

AbstractThe liver was used widely in early studies of polarised transport but has been largely overlooked in recent years, mostly because of the development of epithelial cell lines which provide more tractable experimental systems. The majority of membrane proteins and lipids reach the hepatocyte apical membrane by transcytosis and it remains unclear whether there is a direct route for apical targeting, although the pathways present have yet to be fully characterised. The recent development of systems that allow hepatocyte transport processes to be studied in culture and the observation that transcytosis can be significantly stimulated under physiological conditions suggest that hepatocytes have a role to play in future studies of polarised transport. This review discusses the known features of polarised membrane traffic in hepatocytes and contrasts them with the characteristics of vesicular transport in other epithelial cell types.
CAC – the neglected repeat
Authors: Sertedaki Amalia , Lindsay Susan 
Published: February 2005

AbstractIt is becoming increasingly clear that repetitive DNA is of biological significance as well as experimental importance. Here we review the information available about one type of repetitive DNA, the trinucleotide repeat (CAC)n, and briefly compare it with other trinucleotide repeats. Although much work has been done in analysing DNA fingerprinting patterns produced using the synthetic oligonucleotide (CAC)5 as a probe, there is relatively little information about individual (CAC)n‐containing sequences and their abundance, organisation and distribution in mammalian DNA. From the data that is available, it is clear that there are at least two areas that should repay further study: (1) the organisation and generation of long sequences that contain (CAC)n motifs as part of a larger repeating unit (minisatellites) and (2) the distribution of small (CAC)n sequences (microsatellites), in particular their relationship to genes.
Common ground plans in early brain development in mice and flies
Authors: Arendt Detlev , Nübler‐Jung Katharina 
Published: February 2005

AbstractComparing expression patterns of orthologous genes between insects and vertebrates, we have recently proposed that the ventral nerve cord in insects may correspond to the dorsal nerve cord in vertebrates. Here we show that the early development of the insect and vertebrate brain anlagen is indeed very similar. Insect and vertebrate brains express similar sets of genes in comparable areas with similar functions in the adult. In addition, early axogenesis establishes surprisingly similar patterns of axonal connectivity in both groups. We therefore propose that insect and vertebrate brains are built according to a common ground plan, and that specific areas of the insect and vertebrate brains be considered as homologous, meaning that these areas already existed, with their specific functions, in their common ancestor.
Antigenic variation in trypansosomes: Secrets surface slowly
Authors: Cross George A. M. 
Published: February 2005

AbstractAmong pathogenic micro‐organisms that evade the mammalian immune responses, Trypanosoma brucei has developed the most elaborate capacity for antigenic variation. Trypanosomes branched early during eukaryotic evolution. They are characterized by many aberrations, ranging from the unusual compartmentation of metabolic pathways to the heresy of RNA editing. The ubiquitous phenomenon of glycosylphosphatidylinositol‐anchoring of eukaryotic plasma membrane proteins and RNA trans‐splicing (trypanosome genes contain no introns), which adds an identical leader sequence to all trypanosome mRNAs, were first defined during studies of antigenic variation. Genetic transformation of trypanosomes and the high efficiency of gene targeting provide new opportunities to investigate the regulation of antigenic variation. There is every reason to expect trypanosomes to provide further surprises and insights into the evolution of genetic regulatory mechanisms.
Holding chromatids together to ensure they go their separate ways
Authors: Bickel Sharon E. , Orr‐Weaver Terry L. 
Published: February 2005

AbstractAssociation between sister chromatids is essential for their attachment and segregation to opposite poles of the spindle in mitosis and meiosis II. Sister‐chromatid cohesion is also likely to be involved in linking homologous chromosomes together in meiosis I. Cytological observations provide evidence that attachment between sister chromatids is different in meiosis and mitosis and suggest that cohesion between the chromatid arms may differ mechanistically from that at the centromere. The physical nature of cohesion is addressed, and proteins that are candidates for holding sister chromatids together are discussed. Dissolution of sister‐chromatid cohesion must be regulated precisely, and potential mechanisms to release cohesion are presented.
A case of convergent evolution of nucleic acid binding modules
Authors: Graumann Peter , Marahiel Moharned A. 
Published: February 2005

AbstractDivergent evolution can explain how many proteins containing structurally similar domains, which perform a variety of related functions, have evolved from a relatively small number of modules or protein domains. However, it cannot explain how protein domains with similar, but distinguishable, functions and similar, but distinguishable, structures have evolved. Examples of this are the RNA‐binding proteins containing the RNA‐binding domain (RBD), and a newly established protein group, the cold‐shock domain (CSD) protein family. Both protein domains contain conserved RNP motifs on similar single‐stranded nucleic acid‐binding surfaces. Apart from the RNP motifs, which have a similar function, the two families show little similarity in topology or amino acid sequence. This can be considered an interesting example of convergent evolution at the molecular level. Previously, a β‐sheet surface was found to interact with RNA in non‐homologous proteins from yeast, phage and man, revealing that this mode of RNA binding may be a widely recurring theme.
Developmental genetics and traditional homology
Authors: Bolker Jessica A. , Raff Rudolf A. 
Published: February 2005

AbstractThe concept of homology arose from classical studies of comprative morphology, and took on a new signficance with the advent of evolutionary theory. It is currentlyl undergoing antoher metamorphosis: many developmental geneticists now dfine homology as shared patterns of gene expression. However, this ne usage conflaes difinition with criteri, and fails to recognize the meaninful asignments of homology must speify a biologcal level. We argue the although developmental genetic data can help identify homologus structures. they are niether necessary nor sufficient, and do not in any case jutify a new definition of homology.
Molecular mechanisms of durg inhibition of DNA gyrase
Authors: Lewis Richard J. , Tsai Francis T. F. , Wigley Dale B. 
Published: February 2005

AbstractDNA gyrase, an enzyme unique to prokaryotes, has been implicated in almost all processes that involve DNA. Although efficient inhibitors of this protein have been known for more than 20 years, none of them have enjoyed prolonged pharmaceutical success. It is only recently that the mechanisms of inhibition for some of these classes of drugs have been established unequivocally by X‐ray crystallography. It is hoped that this detailed structural information will assist the design of novel, effective inhibitors of DNA gyrase.
Unraveling the late stages of recombinational repair: Metabolism of DNA junctions in Escherichia coli
Authors: Kuzminov Andrei 
Published: February 2005

AbstractDNA junctions are by‐products of recombinational repair, during which a damaged DNA sequence, assisted by RecA filament, invades an intact homologous DNA to form a joint molecule. The junctions are three‐strand or four‐strand depending on how many single DNA strands participate in joint molecules. In E. coli, at least two independent pathways to remove the junctions are proposed to operate. One is via RuvAB‐promoted migration of four‐strand junctions with their subsequent resolution by RuvC. In vivo, RuvAB and RuvC enzymes might work in a single complex, a resolvasome, to clean DNA from used RecA filaments and to resolve four‐strand junctions. An alternative pathway for junction removal could be via RecG‐promoted branch migration of three‐strand junctions, provided that an as yet uncharacterized endonuclease activity incises one of the strands in the joint molecules.
recA mutants of E. coli K12: A personal turning point
Authors: Clark Alvin J. 
Published: February 2005

AbstractA first year graduate student, Ann Dee Margulies, changed my research career in 1962 by challenging me to direct her in the isolation of recombination‐deficient mutants of Escherichia coli K‐12. She succeeded in isolating two mutants, which conjugated with donor strains and received the donor DNA, but could not recombine that DNA with their own chromosomes. Ann Dee showed that both mutants were much more sensitive to UV radiation than was the wild type. Furthermore, she showed that one of these mutants carried a single mutation affecting both recombination and resistance. This work, published in 1965, was the first demonstration of the recA gene of E. coli. Subsequent work led to the discovery of many more recombination genes, the phenomenon of post replication‐recombination repair, the invention of the SOS hypothesis and the discovery of genes encoding proteins with similar primary structure and function in all major groups of organisms. This article honors the memory of Ann Dee.
PKC ‐ A pivotal regulator of early development
Authors: Gallicano G. Ian , Yousef Martin C. , Capco David G. 
Published: February 2005

AbstractOocytes, eggs and blastomeres of the embryo are special cells that undergo rapid changes in structure and function at developmental transitions. These changes are frequently regulated by cytoplasmic signaling events, particularly at the developmental transition of fertilization, because the genome is largely inactivated at this time. Protein kinase C (PKC) is a signaling agent that acts after the sperm‐induced rise in calcium and has a central role in the remodeling of the structure of the egg into the zygote in many species. PKC also acts during other developmental transitions. This kinase serves as a chronometer, which can choreograph the cell's remodeling events in both space and time. Several technical advancements discussed in this review have permitted a better understanding of the actions of PKC.
Peroxisome biogenesis
Authors: Waterham Hans R. , Cregg James M. 
Published: February 2005

AbstractPeroxisomes are eukaryotic organelles that are the subcellular location of important metabolic reactions. In humans, defects in the organelle's function are often lethal. Yet, relative to other organelles, little is known about how cells maintain and propagate peroxisomes or how they direct specific sets of newly synthesized proteins to these organelles (peroxisome biogenesis/assembly). In recent years, substantial progress has been made in elucidating aspects of peroxisome biogenesis and in identifying PEX genes whose products, peroxins, are essential for one or more of these processes. The most progress has been made in understanding the mechanism by which peroxisome matrix proteins are imported into the organelles. Signal sequences responsible for targeting proteins to the organelle have been defined. Potential signal receptor proteins, a receptor docking protein and other components of the import machinery have been identified, along with insights into how they operate. These studies indicate that multiple peroxisomal protein‐import mechanisms exist and that these mechanisms are novel, not simply variations of those described for other organelles.
Wnt signalling goes nuclear
Authors: Kühl Michael , Wedlich Doris 
Published: February 2005

AbstractThe Wnt signalling cascade is a highly conserved signalling pathway throughout the animal kingdom. In Xenopus, Wnt signalling functions in mesodermal dorsoventral patterning. Earlier work on deciphering the components of the wnt signalling cascade left a gap between cytosolic β‐catenin, the final member of the cascade, and the nuclear target genes. Several recent papers now reveal how the Wnt signal is transmitted into the nucleus. Surprisingly, β‐catenin directly interacts with the transcription factor LEF‐1/XTCF‐3, and thereby is not only translocated into the nucleus but also modulates the properties of LEF‐1/XTCF‐3 as a transcription factor(1–5).
Signaling through focal adhesion kinase
Authors: Hanks Steven K. , Polte Thomas R. 
Published: February 2005

AbstractFocal adhesion kinase (FAK) is a nonreceptor protein‐tyrosine kinase implicated in controlling cellular responses to the engagement of cell‐surface integrins, including cell spreading and migration, survival and proliferation. Aberrant FAK signaling may contribute to the process of cell transformation by certain oncoproteins, including v‐Src. Progress toward elucidating the events leading to FAK activation following integrin‐mediated cell adhesion, as well as events downstream of FAK, has come through the identification of FAK phosphorylation sites and interacting proteins. A signaling partnership is formed between FAK and Src‐family kinases, leading to tyrosine phosphorylation of FAK and associated ‘docking’ proteins Cas and paxillin. Subsequent recruitment of proteins containing Src homology 2 domains, including Grb2 and c‐Crk, to the complex is likely to trigger adhesion‐induced cellular responses, including changes to the actin cytoskeleton and activation of the Ras‐MAP kinase pathway.
Mechanism of gene expression by the glucocorticoid receptor: Role of protein‐protein interactions
Authors: McEwan Iain J. , Wright Anthony P. H. , Gustafsson Jan‐Åke 
Published: February 2005

AbstractThe glucocorticoid receptor belongs to an important class of transcription factors that alter the expression of target genes in response to a specific hormone signal. The glucocorticoid receptor can function at least at three levels: (1) recruitment of the general transcription machinery; (2) modulation of transcription factor action, independent of DNA binding, through direct protein‐protein interactions; and (3) modulation of chromatin structure to allow the assembly of other gene regulatory proteins and/or the general transcription machinery on the DNA. This review will focus on the multifaceted nature of protein‐protein interactions involving the glucocorticoid receptor and basal transcription factors, coactivators and other transcription factors, occurring at these different levels of regulation.
On the functions of lithium: The mood stabilizer
Authors: Shastry Barkur S. 
Published: February 2005

AbstractLithium, despite its simple structure, has numerous biological effects. It also has a remarkable therapeutic effect in the prophylactic treatment of manic depression, and is finding a role in controlling aggressive and self‐mutilating behavior. The special feature of lithium is that it only acts on overactive systems to bring them back to normal, without affecting the stable system. The mechanisms of action of this simple cation are still largely unknown although the inositol depletion theory is the most widely accepted model. A recent paper(1) described a different molecular mechanism for its effect on development, which may also explain its action in manic depression.
Variable peroxisomal and mitochondrial targeting of alanine: Glyoxylate aminotransferase in mammalian evolution and disease
Authors: Danpure Christopher J. 
Published: February 2005

AbstractUnder the putative influence of dietary selection pressure, the subcellular distribution of alanine:glyoxylate aminotransferase 1 (AGT) has changed on many occasions during the evolution of mammals. Depending on the particular species, AGT can be found either in peroxisomes or mitochondria, or in both peroxisomes and mitochondria. This variable localization depends on the differential expression of N‐terminal mitochondrial and C‐terminal peroxisomal targeting sequences by the use of alternative transcription and translation initiation sites. AGT is peroxisomal in most humans, but it is mistargeted to the mitochondria in a subset of patients suffering from the rare herediatry disease primary hyperoxaluria type 1. Mistargeting is due to the unlikely combination of a normally occurring polymorphism that generates a functionally weak mitochondrial targeting sequence and a disease‐specific mutation which, in combination with the polymorphism, inhibits AGT dimerization. The mechanisms by which AGT can be targeted differentially to peroxisomes and/or mitochondria highlight the different molecular requirements for protein import into these two organelles.
Genetics of phototaxis in a model eukaryote, Dictyostelium discoideum
Authors: Fisher Paul R. 
Published: February 2005

AbstractThe life cycle of Dictyostelium discoideum offers a unique opportunity to study signal transduction in eukaryotic cells at both the unicellular and multicellular levels of organization. Adding to the already extensive knowledge of the unicellular stages, classical and molecular genetics have begun to unravel transduction of signals controlling morphogenesis and behaviour (phototaxis and thermotaxis) in the multicellular ‘slug’ stage of the life cycle. Distributed over all seven genetic linkage groups are probably about 20, but possibly as many as 55, genes of importance for slug behaviour. The encoded proteins appear from pharmacological studies and mutant phenotypes to govern transduction pathways involving the intracellular second messengers cyclic AMP, cyclic GMP, IP3 and Ca2+. Pathways from the photo‐ and thermoreceptors converge first with each other and thence, at the level of the second messengers, with those from extracellular tip activation (cyclic AMP) and inhibition (Slug Turning Factor and/or ammonia and/or adenosine) signals that control slug movement and morphogenesis.