bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drosophila wingless: A paradigm for the function and mechanism of Wnt signaling
Authors: Siegfried Esther , Perrimon Norbert 
Published: February 2005

AbstractThe link between oncogenesis and normal development is well illustrated by the study of the Wnt family of proteins. The first Wnt gene (int‐1) was identified over a decade ago as a proto‐oncogene, activated in response to proviral insertion of a mouse mammary tumor virus. Subsequently, the discovery that Drosophila wingless, a developmentally important gene, is homologous to int‐1 supported the notion that int‐1 may have a role in normal development. In the last few years it has been recognized that int‐1 and Wingless belong to a large family of related glyco‐proteins found in vertebrates and invertebrates. In recognition of this, members of this family have been renamed Wnts, an amalgam of int and Wingless. Investigation of Wnt genes in Xenopus and mouse indicates that Wnts have a role in cell proliferation, differentiation and body axis formation. Further analysis in Drosophila has revealed that Wingless function is required in several developmental processes in the embryo and imaginal discs. In addition, a genetic approach has identified some of the molecules required for the transmission and reception of the Wingless signal. We will review recent data which have contributed to our growing understanding of the function and mechanism of Drosophila Wingless signaling in cell fate determination, growth and specification of pattern.
The beaded intermediate filaments and their potential functions in eye lens
Authors: Georgatos Spyros D. , Gounari Fotini , Remington Susann 
Published: February 2005

AbstractThe elongated fiber cells of the eye lens contain a unique cytoskeletal system, the beaded chain filaments (BFs). The BFs had been morphologically identified more than two decades ago, but the precise identity of their subunit molecules remained unknown. Recently, use of recombinant DNA approaches, refined morphological and immunochemical studies and experiments with mutant mice have allowed the molecular dissection of these structures and provided clues about their potential functins. The BFs represent a highly specialized network of intermediate filaments (IFs) juxtaposed to the plasma membrane. They are obligate heteropolymers composed of two lens‐specific polypeptides, filensin and phakinin. In this review we discuss the properties, molecular interactions and in situ arrangement of these two proteins, and comment on their potential roles during lens development.
Oxygen and the control of gene expression
Authors: Pahl Heike L. , Baeuerle Patrick A. 
Published: February 2005

AbstractThe respiration of oxygen, while essential to aerobic organisms for the generation of energy, leads to the formation of reactive oxygen intermediates (ROIs) as harmful byproducts. ROIs damage nucleic acids, lipids and proteins. Therefore, protective mechanisms against elevated intracellular ROI levels, referred to as oxidative stress, have evolved. These include the activation of transcription factors which elevate the expression of protective enzymes. Eukaryotic cells have also evolved the ability to specifically generate ROIs are used as second messengers to activate gene expression. Here we will discuss both prokaryotic and eukaryotic transcription factors that respond to ROIs. In addition, transcription factors will be described that are activated by either exposure to antioxidants, which reduce the intracellular ROI concentration, or by hypoxia, the absence of oxygen.
Hypothesis: Galactosyl and N‐acetylgalactosaminyl homeostasis: A function for mammalian asialoglycoprotein receptors
Authors: Weigel Paul H. 
Published: February 2005

AbstractMammalian livers express endocytic cell surface receptors that specifically bind natural or synthetic molecules containing terminal galactosyl or N‐acetylgalactosaminyl sugars. One of these hepatocyte receptors is the asialogly‐coprotein receptor, which mediates the endocytosis and subsequent lysosomal degradation of these glyco‐molecules. Although the receptor was discovered almost 30 years ago, the physiological reason why mammals have this receptor is still unknown. At the cellular level, the basic molecular function of the receptor is to mediate the uptake and ultimate degradation of galactosyl/N‐acetylgalactosaminyl‐containing molecules (ligands). At the organism level, however, the physiological function is uncertain. The identity of the natural ligands and the reasons for this elaborate receptor system to remove these ligands are both unknown. This article proposes an explanation for the purpose of this asialoglycoprotein receptor and its role in regulating the dynamic flux of galactosyl/N‐acetylgalactosaminyl glycoconjugates in mammals.
Unmasking the role of the 3′ UTR in the cytoplasmic polyadenylation and translational regulation of maternal mRNAs
Authors: Wormington Michael 
Published: February 2005

AbstractThe poly(A)‐dependent translational regulation of maternal mRNAs is an important mechanism to execute stage‐specific programs of protein synthesis during early development. This control underlies many crucial developmental events including the meiotic maturation of oocytes and activation of the mitotic cell cycle at fertilization. A recent report(1) demonstrates that the 3′ untranslated region of the cyclin A1, B1, B2 and c‐mos mRNAs determines the timing and extent of their cytoplasmic polyadenylation and translational activation during Xenopus oocyte maturation. These studies further establish that protein synthesis can be temporally and quantitatively controlled by developmentally regulated changes in the polyadenylation of maternal mRNAs.
The establishment of active promoters in chromatin
Authors: Becker Peter B. 
Published: February 2005

AbstractThe organization of eukaryotic genomes as chromatin provides the framework within which regulated transcription occurs in the nucleus. The association of DNA with chromatin proteins required to package the genome into the nucleus is, in general, inhibitory to transcription, and therefore provides opportunities for regulated transcriptional activation. Granting access to the cis‐acting elements in DNA, a prerequisite for any further action of the trans‐acting factors involved, requires the establishment of local heterogeneity of chromatin and, in some cases, extensive remodeling of nucleosomal structures. Challenging problems relate to the establishment of this heterogeneity at the level of the single nucleosome and to the mechanisms that operate when nucleosomal arrays are reorganized. Recent developments indicate that chromatin reconstitution in cell‐free systems allows the biochemical analysis of the interplay between transcription factors and chromatin components that brings about regulated transcription.
Combinatorial signaling in development
Authors: Cornell Robert A. , Kimelman David 
Published: February 2005

AbstractIntercellular signaling plays a major role in the development of vertebrate and invertebrate embryos. In several cases, including the induction of mesoderm and neural ectoderm induction in Xenopus and the induction of the vulva in C. elegans, multiple intercellular signals are utilized. This review examines a number of examples of signaling in development wherein two signals combine to affect the fate of a cell. The examples are placed in distinct categories, based on whether the signals synergize with or antagonize one another, and on the inductive potential of the individual signals. These types of combinatorial signaling events are suggested to be a general feature of embryonic development.
Molecular chaperones in cellular protein folding
Authors: Martin Jörg , Hartl F.‐Ulrich 
Published: February 2005

AbstractThe discovery of “molecular chaperones” has dramatically changed our concept of cellular protein folding. Rather than folding spontaneously, most newly synthesized polypeptide chains seem to acquire their native conformation in a reaction mediated by these versatile helper proteins. Understanding the structure and function of molecular chaperones is likely to yield useful applications for medicine and biotechnology in the future.
Molecular evolution: Codes, clocks, genes and genomes
Authors: Maclntyre Ross J. 
Published: February 2005

AbstractThe discoveries, advancements and continuing controversies in the field of molecular evolution are reviewed. Topics summarized are (1) the evolution of the genetic code, (2) gene evolution including the demonstration of homology, estimation of sequence divergence, phylogenetic trees, the molecular clock and the origin of genes and gene families by various genetic mechanisms, and (3) eukaryotic genome evolution, including the highly repeated satellite sequences, the interspersed and potentially mobile repeated sequences and the unique sequence fraction of the genome.
Position effect variegation in yeast
Authors: Tartof Kenneth D. 
Published: February 2005

AbstractClassically, position effect variegation has been studied in Drosophila and results when a euchromatic gene is placed adjacent to either centromeric heterochromatin or to a telomeric domain. In such a circumstance expression of the locus variegates, being active in some cells and silent in others. Over the last few years a comparable phenomenon in yeast has been discovered. This system promises to tell us much about this curious behaviour. Indeed, experiments reported recently(1) indicate that the variegation of a yeast telomeric gene is cell‐cycle regulated. The results suggest the following model. During DNA replication there is a disassembly of chromatin that allows a competition between silencing factors and trans‐activators to take place. Thus, reassembly of the domain may result in either the repression or the expression of the affected gene and, hence, produce a variegating phenotype.
Arabidopsis thaliana, a plant Drosophila
Authors: Langridge J. 
Published: February 2005

AbstractArabidopsis thaliana is a small cruciferous weed which grows naturally, mainly in Europe. Because of its qualities of small size, rapid growth, low chromosome number and self‐fertilisation, I adapted it to aseptic growth in purified agar in sterile test‐tubes. I found that it secreted various substances into the medium, but not in type or amount likely to interfere with the expression of biosynthetic mutants. Following X‐irradiation of seed, I obtained a number of mutants, including several lethals. One lethal mutant I discovered to be deficient in thiamine synthesis. It was the first biosynthetic mutant to be found in flowering plants.
Pollen maturation: Where ubiquitin is not required?
Authors: Worrall Dawn , Twell David 
Published: February 2005

AbstractA recent paper(1) describing the stage‐specific loss of ubiquitin (UBQ) and ubiquitinated proteins (UBQ‐Ps) during pollen development has raised some interesting questions regarding our understanding of the regulation of protein turnover during cellular differentiation and the specialized development of the pollen grain. The authors, Callis and Bedinger(1), describe experiments in which the profiles of free and protein‐conjugated ubiquitin were examined during pollen development. UBQ and UBQ‐Ps were immunologically detected in extracts of microspores and maturing pollen of maize at six developmental stages. Their results remarkably demonstrate that UBQ and UBQ‐Ps decline to barely detectable levels during the final stages of pollen development.
Long DNA palindromes, cruciform structures, genetic instability and secondary structure repair
Authors: Leach David R. F. 
Published: February 2005

AbstractLong DNA palindromes pose a threat to genome stability. This instability is primarily mediated by slippage on the lagging strand of the replication fork between short directly repeated sequences close to the ends of the palindrome. The role of the palindrome is likely to be the juxtaposition of the directly repeated sequences by intrastrand base‐pairing. This intra‐strand base‐pairing, if present on both strands, results in a cruciform structure. In bacteria, cruciform structures have proved difficult to detect in vivo, suggesting that if they form, they are either not replicated or are destroyed. SbcCD, a recently discovered exonuclease of Escherichia coli, is responsible for preventing the replication of long palindromes. These observations lead to the proposal that cells may have evolved a post‐replicative mechanism for the elimination and/or repair of large DNA secondary structures.
Differentiation of endothelial cells: Analysis of the constitutive and activated endothelial cell phenotypes
Authors: Augustin Hellmut G. , Kozian Detlef H. , Johnson Robert C. 
Published: February 2005

AbstractEndothelial cells line the inside of all blood vessels, forming a structurally and functionally heterogenous population of cells. Their complexity and diversity has long been recognized, yet very little is known about the molecules and regulatory mechanisms that mediate the heterogeneity of different endothelial cell populations. The constitutive organ‐ and microenvironment‐specific phenotype of endothelial cells controls internal body compartmentation, regulating the trafficking of circulating cells to distinct vascular beds. In contrast, surface molecules associated with the activated cytokine‐inducible endothelial phenotype play a critical role in pathological conditions including inflammation, tumor angiogenesis, and wound healing. Differentiation of the endothelial cell phenotypes appears to follow similar mechanisms to the differentiation of hematopoietic cells, with the exception that endothelial cells maintain transdifferentiating competence. The present review offers a scheme of endothelial cell differentially expressed endothelial cell molecules as targets for directed therapeutic intervention.
Nm23/nucleoside diphosphate kinase: Toward a structural and biochemical understanding of its biological functions
Authors: De La Rosa Abel , Steeg Patricia S. , Williams Roger L. 
Published: February 2005

AbstractThe nm23 gene, a putative metastasis suppressor gene, was originally identified by its reduced expression in highly metastatic K‐1735 murine melanoma cell lines, as compared to related, low metastatic melanoma cell lines. Transfection of nm23 cDNA has been reported to suppress malignant progression in Drosophila and mammalian cells. Highly conserved homologues of nm23 have been found in organisms ranging from the prokaryote Myxococcus xanthus to Drosophila, where the gene is involved in normal development and differentiation. The product of the nm23 gene exhibits a nucleoside diphosphate kinase activity, yet the nucleoside diphosphate kinase activity of Nm23 does not correlate with its apparent biological functions. We review recent cellular, genetic, biochemical and X‐ray crystallographic data to formulate and evaluate hypotheses concerning the molecular mechanism of nm23 action.
E‐cadherin as a tumor (invasion) suppressor gene
Authors: Birchmeier Walter 
Published: February 2005

AbstractDiffuse‐type gastric carcinomas show diminished cell‐cell adhesion. A recent paper(1) reports that 50% of these carcinomas contain mutations in the E‐cadherin gene, resulting in the destruction of the calcium‐binding sites of E‐cadherin, and providing strong in vivo evidence that alterations in E‐cadherin play a major role in the development of this particular type of cancer and the short survival of the patients.
Signaling, mitogenesis and the cytoskeleton: Where the action is
Authors: Carraway Kermit L. , Carraway Coralie A. Carothers 
Published: February 2005

AbstractStimulation of mitogenesis by the epidermal growth factor (EGF) operates through a pathway involving the receptor, the small G‐protein Ras and protein kinases of the MAP kinase cascade. It is proposed that two of the critical steps of that pathway utilize localization of components to the plasma membrane where Ras is located: recruitment of the nucleotide exchange protein Sos to the phosphorylated EGF receptor via a complex with the SH2/SH3‐containing protein Grb2 and recruitment of the protein kinase Raf to activated Ras. Moreover, it is then proposed that Raf associates with the cytoskeleton at the membrane as it is being activated. Other signaling elements, including class I receptor kinases, nonreceptor tyrosine kinases and tyrosine phosphatases, are known to function at specific cellular sites. These observations have led us to propose that localization of signaling components, and particularly sites at membrane‐microfilament interfaces, play critical roles in cellular regulation.
Singling out the tip cell of the Malpighian tubules ‐ lessons from neurogenesis
Authors: Wilkins Adam S. 
Published: February 2005

AbstractThe development of each of the four Malpighian tubules of Drosophila during embryogenesis requires a special cell, the tip cell, to achieve full growth. A central question concerns how the tip cell acquires its unique properties within the tubule primordium. In a recent report(1), a sequence of key gene expression events in both the tip cell and its cellular neighbours is described. The results show that there are some significant parallels between tip cell selection and the mechanisms that help select neuroblasts within the developing neuroectoderm. Beyond these similarities between neural development and tip cell selection, the later differentiation of the tip cell shows some intriguing elements of neural cell differentiation.
The MyoD family of transcription factors and skeletal myogenesis
Authors: Rudnicki Michael A. , Jaenisch Rudolf 
Published: February 2005

AbstractGene targeting has allowed the dissection of complex biological processes at the genetic level. Our understanding of the nuances of skeletal muscle development has been greatly increased by the analysis of mice carrying targeted null mutations in the Myf‐5, MyoD and myogenin genes, encoding members of the myogenic regulatory factor (MRF) family. These experiments have elucidated the hierarchical relationships existing between the MRFs, and established that functional redundancy is a feature of the MRF regulatory network. Either MyoD or Myf‐5 is sufficient for the formation or survival of skeletal myoblasts. Myogenin acts later in development and plays an essential in vivo role in the terminal differentiation of myotubes.
MyoD and myogenesis in C. elegans
Authors: Krause Michael 
Published: February 2005

AbstractOne of the goals in developmental biology is the identification of key regulatory genes that govern the transition of embryonic cells from a pluripotent potential to a specific, committed cell fate. During vertebrate skeletal myogenesis, this transition is regulated by the MyoD family of genes. C. elegans has muscle analogous to vertebrate skeletal muscle and has a gene(hlh‐1) related to the MyoD family. The molecular and genetic characterization of hlh‐1 shows that it is very similar to the vertebrate MyoD family in many respects, including its expression pattern and DNA binding activity. The hlh‐1 product is required for proper myogenesis, but it is not required for myogenic commitment during embryogenesis in the nematode. The role of this MyoD‐related gene in nematode myogenesis is discussed and compared to those of the vertebrate MyoD family.
Biological consequences of targeting β1,4‐galactosyltransferase to two different subcellular compartments
Authors: Evans Susan C. , Youakim Adel , Shur Barry D. 
Published: February 2005

Abstractβ1,4‐galactosyltransferase is unusual among the glycosyltransferases in that it is found in two subcellular compartments where it performs two distinct functions. In the trans‐Golgi complex, galactosyltransferase participates in oligosaccharide biosynthesis, as do the other glycosyltransferases. On the cell surface, however, galactosyltransferase associates with the cytoskeleton and functions as a receptor for extracellular oligosaccharide ligands. Although we now know much regarding galactosyltransferase function in these two compartments, little is known about how it is targeted to these different sites. By cloning the galactosyltransferase gene products, certain features of the protein have been identified that may be critical for its expression on the cell surface or retention within the Golgi complex. This article discusses recent studies which suggest that a cytoplasmic sequence unique to one galactosyltransferase isoform is required for targeting a portion of this protein to the plasma membrane, enabling it to function as a cell adhesion molecule. These findings allow one to manipulate surface galactosyltransferase expression, either positively or negatively, and perturb galactosyltransferase‐dependent cellular interactions during fertilization and development.
The dynamics of cytosolic calcium in photoreceptor cells
Authors: Williams David S. 
Published: February 2005

AbstractAnalysis of the light‐induced changes of cytosolic Ca2+ ([Ca2+]i) in photoreceptor cells has been taken a step further with two recently published studies(1,2). In one, changes in [Ca2+]i were measured in single detached rod outer segments from Gecko in response to various light intensities. The advances of the other(2) are embodied in its employment of transgenic Drosophila, whose photoreceptors express a visual pigment that is insensitive to the wavelength of light used in the fluorescence imaging of [Ca2+]i. These studies provide a better basis for understanding the regulation of Ca2+‐mediated events in photoreceptor cells.
Regulation of plant form: Identification of a molecule controlling cell expansion
Authors: Torii Keiko U. , Deng Xing‐Wang 
Published: February 2005

AbstractThe form of higher plants is largely dependent upon cell division and expansion patterns. Taking a genetic approach, Takahashi et al.(1) have identified a regulatory molecule in Arabidopsis thaliana called DIMINUTO (DIM), which is involved in determining the degree and direction of plant cell expansion. Their extensive characterization of a dim mutant suggested a direct involvement of the DIM gene in regulating cell elongation, perhaps by modulating the expression of structural genes which determine the orientation and elasticity of the cell wall.
Seminalplasmin
Authors: Sitaram N. , Nagaraj R. 
Published: February 2005

AbstractThe importance of seminal plasma in fertilization was appreciated as early as 1677 and would thus hardly seem a source for the search of antibacterial agents. The observation that seminal plasma had the ability to inhibit the growth of microorganisms in 1940 led to a systematic search for molecules possessing antimicrobial activity in addition to factors that might have a role in reproductive physiology. Extensive investigations led to the discovery in bovine seminal fluid of a 47‐residue peptide, possessing potent antimicrobial activity as well as calcium transport modulatory properties in bovine sperm. We describe in this article the two, apparently unrelated, biological activities of this peptide.
Stopped for repairs
Authors: Sanchez Yolanda , Elledge Stephen J. 
Published: February 2005

AbstractThe tumor suppressor protein p53 is intimately involved in the cellular response to DNA damage, controlling cell cycle arrest, apoptosis and the transcriptional induction of DNA damage inducible genes. A transcriptional target of p53, Gadd45, was recently found to bind to PCNA, a component of DNA replication/repair complexes, thereby implicating Gadd45 in DNA metabolism(1). Using biochemical assays, a role for Gadd45 in excision repair in vitro has been demonstrated(1). Antisense experiments have also indicated an in vivo role for the GADD45 gene in UV‐irradiation survival. These discoveries establish a link between p53 and DNA repair through Gadd45.