bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic aspects of adhesion receptor function — integrins both twist and shout
Authors: Humphries Martin J. , Mould A. Paul , Tuckwell Danny S.
Published: February 2005

The recognition of extracellular molecules by cell surface receptors is the principal mechanism used by cells to sense their environment. Consequently, signals transduced as a result of these interactions make a major contribution to the regulation of cellular phenotype. Historically, particular emphasis has been placed on elucidating the intracellular consequences of growth factor and cytokine binding to cells. In addition to these interactions, however, cells are usually in intimate contact with a further source of complex structural and functional information, namely immobilised extracellular matrix and/or cell surface adhesion proteins. A key question in recent years has been whether cells use the myriad of adhesion protein‐receptor interactions purely for structural and migratory function, or whether these interactions also make a more varied contribution to cell phenotype. Here we review dynamic aspects of the function of one major class of adhesion receptor, the integrins. In particular, we focus on the evidence for shape changes in integrin molecules, the mechanisms responsible for regulating ligand binding, and the signals transduced following integrin occupancy.
Protein lateral mobility as a reflection of membrane microstructure
Authors: Zhang Fen , Lee Greta M. , Jacobson Ken
Published: February 2005

The lateral mobility of membrane lipids and proteins is presumed to play an important functional role in biomembranes. Photobleaching studies have shown that many proteins in the plasma membrane have diffusion coefficients at least an order of magnitude lower than those obtained when the same proteins are reconstituted in artificial bilayer membranes. Depending on the protein, it has been shown that either the cytoplasmic domain or the ectodomain is the key determinant of its lateral mobility. Single particle tracking microscopy, which allows the motions of single or small groups of membrane molecules to be followed, promises not only to reveal new features of membrane dynamics, but also to help explain longstanding puzzles presented by the photobleaching studies, particularly the so‐called immobile fraction. The combination of the two complementary technologies should measurably enhance our understanding of membrane microstructure.
Problems and paradigms: Altering sex ratios: The games microbes play
Authors: Hurst Gregory D. D. , Hurst Laurence D. , Majerus Michael E. N.
Published: February 2005

The male gametes of most organisms lack cytoplasm. Consequently, most cytoplasmic genetic elements are maternally inherited: they cannot be transmitted patrilinnearly. The evolutionary interests of cytoplasmic elements therefore lie in transmission through the female. These elements may thus be in evolutionary conflict with nuclear genes which are transmitted by both sexes. This conflict is manifested in observations of cytoplasmically induced biased sex‐ratios. Some cytoplasmic genes avoid this fate by biasing the primary sex ratio towards females, or by inducing parthenogenesis. Others kill male hosts, and either achieve transmission via dispersal, or benefit their clonal relatives in the dead male's female siblings. Still others cause the failure of zygotes resulting from pairings between males carrying specific microbes and females lacking them, causing an increase in the microbes through the sterilisation of non‐bearing females. Many, but not all, of these ‘ultra‐selfish’ microbes are closely related. Investigations of the significance of their phylogenetic affinities, or lack of them, their adaptability in terms of the methods by which they avoid, or ameliorate, the adverse effects of being in male hosts, and their importance as selective agents in the evolution of invertebrate sex determination systems, provide fertile spheres for future research.
Pure thoughts with impure proteins: Permeabilized cell models of organelle motility
Authors: Swanson Joel A.
Published: February 2005

Permeabilized cell models provide an experimental middle ground wherein the in vitro properties of mechanochemical proteins can be reconciled with the physical and topological constraints of the intact cell. Several well‐studied examples of organelle motility are described here, including the actin‐based cytoplasmic streaming of Characean algae, the microtubule‐based aggregation and dispersion of pigment granules in chromatophores and the saltatory movements of vesicles along microtubules in fibroblasts and macrophages. The permeabilized models developed for these systems have helped to integrate observations in vivo with in vitro assays of motor proteins.
What's new: Ligation‐based DNA diagnostics
Authors: Landegren Ulf
Published: February 2005

A number of novel gene detection techniques all revolve around the ligation of synthetic nucleic acid probes. In such ligase‐assisted gene detection reactions, specific DNA or RNA sequences are investigated by using them as guides for the covalent joining of pairs of probe molecules. The probes are designed to hybridize immediately next to each other on the target nucleic acid strand. Demonstration of ligated probes results in highly specific detection of and efficient distinction between similar sequence variants under standard reaction conditions. Accordingly, the principle has been applied in automated genetic screening procedures. Ligation reactions are also integral to a number of amplification procedures and they will be of value in an expanding range of genetic analyses.
Chemosensory regulation of development in C. elegans
Authors: Thomas James H.
Published: February 2005

The dauer larva is a specialized third‐larval stage of Caenorhabditis elegans that is long‐lived and resistant to environmental insult. The dauer larva is formed in response to a high external concentration of a constitu‐tively secreted pheromone. Response to the dauer‐inducing pheromone of C. elegans is a promising genetic model for metazoan chemosensory transduction. More than 20 genes have been identified that are required for normal pheromone response. The functions of these genes include production of the pheromone, exposure of sensory neuron endings to the environment, structural and functional integrity of those sensory endings, and the capacity of sensory neurons to make appropriate output. Genetic evidence suggests that two partially redundant sensory pathways act in concert to control dauer formation. At least two classes of chemosensory neurons, ADF and ASI, are implicated in the pheromone response. On the basis of on these findings, a speculative model for the pheromone response is proposed. In this model, the neurons ADF and ASI are pheromone sensors that repress dauer formation in the absence of pheromone and dere‐press dauer formation in response to pheromone. It is currently unclear whether or not the two genetically defined sensory pathways both act in ADF and ASI.
Neu and its ligands: From an oncogene to neural factors
Authors: Peles Elior , Yarden Yosef
Published: February 2005

Transmembrane receptor tyrosine kinases that bind to peptide factors transmit essential growth and differentiation signals. A growing list of orphan receptors, of which some are oncogenic, holds the promise that many unknown ligands may be discovered by tracking the corresponding surface molecules. The neu gene (also called erbB‐2 and HER‐2) encodes such a receptor tyrosine kinase whose oncogenic potential is released in the developing rodent nervous system through a point mutation. Amplification and overexpression of neu are thought to contribute to malignancy of certain human adenocarcinomas. The search for soluble factors that interact with the Neu receptor led to the discovery of a 44 kDa glyco‐protein that induces phenotypic differentiation of cultured mammary tumor cells to growth‐arrested and milk‐producing cells. The Neu differentiation factor (NDF or heregulin), however, also acts as a mitogen for epithelial, Schwann and glial cells. Multiple forms of the factor are produced by alternative splicing and their expression is confined predominantly to the central and to the peripheral nervous systems. One identified neuronal function of this family of polypeptides is to control the formation of neuromuscular junctions, but their physiological role in secretory epithelia is still unknown. Other open questions relate to the transmembrane topology of various precursors, the identity of a putative co‐receptor, the possible existence of additional ligands of Neu and the functional significance of the interaction between Neu and at least three highly related receptor tyrosine kinases.
Genes and genomes: High‐frequency induction of chromosomal rearrangements in mouse germ cells by the chemotherapeutic agent chlorambucil
Authors: Rinchik Eugene M. , Flaherty Lorraine , Russell Liane B.
Published: February 2005

Recent mutagenesis studies have demonstrated that the chemotherapeutic agent, chlorambucll (CHL), is highly mutagenic in male germ cells of the mouse. Post‐melotic germ cells, and especially early spermatids, are the most sensitive to the cytotoxic and mutagenic effects of this agent. Genetic, cytogenetic and molecular analyses of many induced mutations have shown that, in these germ‐cell stages, CHL induces predominantly chromosomal rearrangements (deletions and translocations), and mutation‐rate studies show that, in terms of tolerated doses, CHL is perhaps five to ten times more efficient in inducing rearrangements than is radiation exposure. Appropriate breeding protocols, along with knowledge of the advantages and limitations associated with the use of CHL, can be used to expand the current resource of chromosomal rearrangements in the mouse and to provide new phenotype‐associated mutations amenable to positional‐cloning techniques. The analysis of CHL‐induced mutations has also contributed to understanding the factors that affect the yield and nature of chemically induced germline mutations in mammals.
The molecular basis of retinotectal topography
Authors: Kaprielian Zaven , Patterson Paul H.
Published: February 2005

Over 50 years have passed since Roger Sperry formulated a simple model of how visual space, as seen by the retina, can be projected onto the brain in a two‐dimensional, topographic map during development. Sperry posited a set of two orthogonal gradients in the retina that gives each cell a positional identity. He further suggested that these molecules could be used to match up with complementary gradients in the target field of the retinal projection, the tectum. While some investigators hold that the existence of such molecules may not be necessary to establish retinotectal maps, recent work has identified several cell surface proteins whose distributions are of the type predicted by Sperry. An unexpected twist comes from culture assays demonstrating that inhibitory activities on tectal membranes can guide the growth of processes from retinal neurons. Moreover, the expression patterns of several enzymes and three transcription factors suggest that these proteins are candidates for regulatory agents in the determination of cell position in the retina. In addition, results from perturbation experiments support the candidacy of two of the enzymes, and a new mutant screen has uncovered several as yet unidentified genes that are required for establishment of the proper retinotectal map. A number of these results were presented at a recent meeting on neurospecificity held in Cargese, Corsica and sponsored by NATO and NSF.
Atherosclerosis and glycation
Authors: Colaco Camilo A. L. S. , Roser Bruce J.
Published: February 2005

Atherosclerosis is the major cause of death in the industrialised world. Though much work on the pathogenesis of atherosclerosis points to ‘oxidised’ low density lipoprotein (;LDL) as a key aeitological feature in the generation of the atherosclerotic plaque, the nature of this ‘oxidised’ LDL in vivo remains an enigma. We argue here that glycated LDL shows many of the characteristics attributed to ‘oxidised LDL’ and may be the source of the latter in vivo. These include the increased uptake and impaired degradation of glycated LDL by macrophages and the stimulation of transendothelial chemotaxis of monocytes, cytokine secretion and platelet aggregation. We hypothesise that the covalent binding of glycated LDL to the endothelial cell wall may result in the formation of the early atherosclerotic lesion of the fatty streak and that apolipoprotein E may mediate the physiological clearance of glycated moieties. The proposed role of glycation in the pathogenesis of atherosclerosis would explain its high incidence among diabetics and the contentious epidemiological and experimental correlations between dietary sugar and atherosclerosis.
Architectural variations of inducible eukaryotic promoters: Preset and remodeling chromatin structures
Authors: Wallrath Lori L. , Lu Quinn , Granok Howard , Elgin Sarah C. R.
Published: February 2005

The DNA in a eukaryotic nucleus is packaged into a nucleosome array, punctuated by variations in the regular pattern. The local chromatin structure of inducible genes appears to fall into two categories: preset and remodeling. Preset genes are those in which the binding sites for trans‐acting factors are accessible (;i.e. in a non‐nucleosomal, DNase I hypersensitive configuration) prior to activation. In response to the activation signal, positive factors bind to cis‐acting regulatory elements and trigger transcription with no major alterations in the chromatin structure of the promoter region. In contrast, remodeling genes are those in which some of the required cis‐acting regulatory elements are packaged into nucleosomes. The nucleosomes must be perturbed in response to an activation signal in order for the trans‐acting factors to gain access to cis‐acting elements; a chromatin remodeling process which forms DNase I hypersensitive sites must occur. In both cases, precise positioning of nucleosomes along the promoter region of a gene appears to be critical for appropriate regulation of expression.
Recent trends in rifamycin research
Authors: Lal Rup , Lal Sukanya
Published: February 2005

Rifamycin is a clinically useful macrolide antibiotic produced by the gram positive bacterium. Amycolatopsis mediterranei. This antibiotic is primarily used against Mycobacterium tuberculosis and Mycobacterium leprae, causative agents of tuberculosis and leprosy, respectively. In these bacteria, rifamycin treatment specifically inhibits the initiation of RNA synthesis by binding to β‐subunit of RNA polymerase. Apart from its activity against the bacteria, rifamycin has also been reported to inhibit reverse transcriptase (RT) of certain RNA viruses. Recently, rifamycin derivatives have been dis‐covered that are effective against Mycobacterium avium, which is associated with the AIDS complex. Consequently, the importance of and demand for rifamycin has increased tremendously, the world over. In this article, recent trends in rifamycin research and accessability of recombinant DNA techniques to increase rifamycin production are reviewed.
The RAD6 DNA repair pathway in Saccharomyces cerevisiae: What does it do, and how does it do it?
Authors: Lawrence Christopher
Published: February 2005

The RAD6 pathway of budding yeast, Saccharomyces cerevisiae, is responsible for a substantial fraction of this organism's resistance to DNA damage, and also for induced mutagenesis. The pathway appears to incorporate two different recovery processes, both regulated by RAD6. The error‐prone recovery prcess accounts for only a small amount of RAD6‐dependent resistance, but probably all induced mutagenesis. The underlying mechanism, for error‐prone recovery is very likely to be translesion synthesis. The error‐free recovery process accounts for most of RAD6‐dependent resistace, but its mechanism is less clear; it may entail error‐free bypass by template switching and/or DNA gap filling by recombination. RAD6 regulates these activities by ubiquitinateins, and the roles they play in error‐free and error‐prone recovery, have not yet been established.
Gross chromosome rearrangements mediated by transposable elements in Drosophila melanogaster
Authors: Lim Johng K. , Simmons Michael J.
Published: February 2005

A combination of cytogenetic and molecular analyses has shown that several different transposable elements are involved in the restructuring of Drosophila chromosomes. Two kinds of elements, P and hobo, are especially prone to induce chromosome rearrangements. The mechanistic details of this process are unclear, but, at least some of the time, it seems to involve ectopic recombination between elements inserted at different chromosomal sites; the available data suggest that these ectopic recombination events are much more likely to occure between elements in the same chromosome than between elements in different chromosomes. Other Drosophila transposons also appear to mediate chromosome restructuring by ectopic recombination; these include the retrotransposons BEL, roo, Docand I and the foldback element FB. In addition, two retrotransposons, HeT‐A and TART, have been found to be associated specifically with the ends of Drosophila chromosomes. Very limited data indicate that transposon‐mediated chromosome restructuring is occurring in natural populations of Drosophila. This suggests that transposable elements may help to shape the structure of the Drosophila genome and implies that they may have a similar role in other organisms.
Alternative mRNA splicing of the FMRFamide gene and its role in neuropeptidergic signalling in a defined neural network
Authors: Benjamin Paul R. , Burke Julian F.
Published: February 2005

Neuronal signalling involves multiple neuropeptides that are diverse in structure and function. Complex patterns of tissue‐specific expression arise from alternate RNA splicing of neuropeptide‐encoding gene transcripts. The pattern of expression and its role in cell signalling is diffecult to study at the level of single neurons in the complex vertebrate brain. However, in the model molluscan system, Lymnaea, it is possible to show that alternate mRNA expression of the FMRFamide gene is specific to single identified neurons. Two different transcripts are expressed in a mutually exclusive manner in different neurons. Post‐translational processing of the two precursor proteins leads to completely distinct sets of neuropeptide transmitters. The function of these transmitter cocktails, resulting from alternate mRNA splicing, was studied physiologically in identified neurons forming part of a behaviourally important network regulating heartbeat.
Hypothesis: Intermediate filament and related proteins: Potential activators of nucleosomes during transcription initiation and elongation?
Authors: Traub Peter , Shoeman Robert L.
Published: February 2005

Intermediate filament (IF) protein tetramers contain two DNA‐ and core‐histone‐binding motifs in rotational symmetry in one and the same structural entity. We propose that IF protein oligomers might displace histone octamers from nucleosomes in the process of transcription initiation and elongation, to deposit them transiently on their α‐helical coiled‐coil domains. We further propose that structurally related proteins of the karyoskeleton, constructed from an α‐helical domain capable of coiled‐coil formation and a basic DNA‐binding region adjacent to it, may be similarly involved in nucleosome activation. These proteins would function as auxiliary factors that disrupt nucleosomal structure to permit transcription and other DNA‐dependent processes to proceed expiditiously.
My favourite cell: Tetrahymena: A model for growth, cell cycle and nutritional studies, with biotechnological potential
Authors: Wheatley Denys N. , Rasmussen Leif , Tiedtke Arno
Published: February 2005

Tetrahymena has been used as a model cell system in many studies of morphogenesis, conjugation, gene mapping, cell division and growth kinetics. In this article, we consider some advances which have resulted from the successful development of a chemically defined medium (CDM), and how subsequent work has extended the contribution that this organism has made to our understanding of different aspects of growth, nutrition, cell cycle control, cytokinesis and intercellular signalling. Finally, we discuss the considerable potential that has arisen for the biotechnological exploitation of this big and rapidly growing eukaryotic cell.
Drosophila wingless: A paradigm for the function and mechanism of Wnt signaling
Authors: Siegfried Esther , Perrimon Norbert
Published: February 2005

The 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

The 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

The 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

Mammalian 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

The 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

The 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

Intercellular 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

The 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

The 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

Classically, 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

Arabidopsis 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

A 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

Long 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

Endothelial 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

The 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

Diffuse‐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

Stimulation 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

The 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

Gene 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

One 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

β1,4‐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

Analysis 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

The 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

The 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

The 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.
Out‐of body experiences: Cell‐free cell death
Authors: Hengartner Michael O.
Published: February 2005

Apoptosis (programmed cell death) is an evolutionarily conserved cellular process, important for development and homeostasis(1). Most apoptotic cells share a common set of morphological and physiological characteristics that distinguish them from necrotic deaths(2). While genetic studies have indicated that these characteristic changes result from the activation of an endogenous ‘suicide program’(3), little is known about the nature of this program and the molecular events underlying these changes. Two recent papers(4,5) describing cell‐free extracts that reproduce several of the characteristic changes observed in apoptotic cells promise to make these phenomena accessible to biochemical analysis.
Steps towards a mouse model of Alzheimer's disease
Authors: Crowther R. Anthony
Published: February 2005

Alzheimer's disease, a form of senile dementia, is characterised by two kinds of pathological deposits in the brain, called plaques and tangles. The molecular nature of the deposits has been identified but there is as yet little understanding of the underlying biochemistry and cell biology that lead to their formation. Progress in this area would be greatly aided by a realistic animal model. Two recent papers describe the production of transgenic mice that develop significant aspects of Alzheimer‐like pathology. The mice produced by Games et al.(1) develop plaques while those produced by Götz et al.(2) display the early stages of tangle pathology.
Rapid detection of selected aneuploidies by quantitative fluorescent PCR
Authors: Adinolfi Matteo , Sherlock Jon , Pertl Barbara
Published: February 2005

Selected aneuploidies can be rapidly diagnosed by the analysis of fluorescent polymerase chain reaction (PCR) products of chromosome‐specific and highly polymorphic small tandem repeats (STRs). The quantitative STR patterns obtained from samples of normal individuals are markedly different from those seen when patients with aneuploidies involving chromosome X, or trisomies of chromosomes 21 and 18, are tested. For example, while samples from normal subjects – tested with a chromosome 21‐derived STR (D21S11) – show two fluorescent PCR peaks with similar activities in a 1:1 ratio, the analysis of samples from patients with trisomy 21 reveals the presence of either three peaks (ratio 1:1:1), or two peaks with a ratio of 2:1. The use of an internal non‐polymorphic marker allows identification of trisomic samples with three copies of the same allele. This rapid approach (24 hours) is particularly valuable when applied to prenatal diagnosis of chromosomal abnormalities since it reduces the time of anxiety of the parents waiting for the results of the conventional cytogenetic tests, which require several weeks.
Ubiquitin in homeostasis, development and disease
Authors: Muller Sylviane , Schwartz Lawrence M.
Published: February 2005

Ubiquitin is the most phylogenetically conserved protein known. This 8,500 Da polypeptide can be covalently attached to cellular proteins as a posttranslational modification. In most cases, the addition of multiple ubiquitin adducts to a protein targets it for rapid degradation by a multisubunit protease known as the 26S proteasome. While the ubiquitin/26S proteasome pathway is responsible for the degradation of the bulk of cellular proteins during homeostasis, it may also be responsible for the rapid loss of protein during the programmed death of certain cells, such as skeletal muscle during insect metamorphosis. In addition, alterations in the expression and regulation of ubiquitin may play significant roles in pathological disorders. For example, dramatic increases in ubiquitin and ubiquitin‐protein conjugates are observed in a wide variety of neurodegenerative disorders, including Alzheimer's disease. Patients suffering from the autoimmune disease systemic lupus erythematosus generate antibodies reacting with ubiquitin and ubiquitinated histones. At present, it is not known whether these changes in ubiquitin expression and regulation initiate pathological changes in these diseases or if they are altered as a consequence of these disorders.