bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear lamin proteins and the structure of the nuclear envelope: Where is the function?
Authors: McKeon Frank D.
Published: February 2005

The nuclear envelope has recently become the object of intense scrutiny because it is the site of nuclear transport and is possibly involved in the organization of the interphase genome, thereby affecting gene expression. The major structural support for the nuclear envelope is the nuclear lamina, composed of the nuclear lamin proteins. They lie on the surface of the inner nuclear membrane and are in direct contact with the chromatin at the edge of the nucleus. The structure of the nuclear lamin proteins has recently been deduced from their cDNAs and shown to have remarkable homologies to the family of cytoplasmic intermediate filaments. However, the lamin proteins have been found to depolymerize in response to metaphase‐specific phosphorylation events, and reassemble around daughter chromosomes at the completion of cell division. Little is known of the mechanisms of these dynamics, nor of other post‐translational modifications evident in these proteins. In addition, we have as yet no concrete idea of the function of these highly conserved proteins in the cell. This review will summarize our present knowledge of nuclear lamin structure and the new experimental approaches designed to elucidate their function.
Calpactins: Calcium‐regulated membrane‐skeletal proteins
Authors: Glenney John R.
Published: February 2005

The calpactins are a novel group of proteins associated with the membrane skeleton. The two main forms, calpactin I and II, have been shown to bind to the cytoskeletal proteins actin and spectrin, as well as to anionic phospholipids, which may imply some sort of bridging role. By raising monoclonal antibodies to the heavy and light chains of calpactin I, and to calpactin II, the protein subunits were shown to be coordinately expressed, and the existence of separate calpactin pools hypothesized. Calcium‐binding studies suggest that the calpactins may translate Ca2+ signals into cellular responses at the membrane. Structural studies have revealed two distinct domains and are beginning to throw light on heavy‐‐light chain interaction and cytoskeletal attachment.
The vacuolar proton‐ATPase of eukaryotic cells
Authors: Nelson Nathan
Published: February 2005

A novel class of proton‐ATPase has been identified in the vacuolar system of eukaryotic cells. The properties of these enzymes and their relation to other proton‐ATPases is discussed.
Permease on parade: Application of site‐directed mutagenesis to ion‐gradient driven active transport
Authors: Kaback H. Ronald
Published: February 2005

Oligonucleotide‐directed, site‐specific mutagenesis is being applied to the problem of ion‐gradient driven active transport with the lac permease as a model system. It has been shown that Arg‐302, His‐322 and Glu‐325, neighboring residues in putative transmembrane helices IX and X, play an important role in lactose‐coupled H+ translocation, possibly as components of a catalytic triad similar to that found in the serine proteases. In addition, Cys residues, long thought to be involved in the mechanism of the permease, are not directly involved in either substrate binding or H+ translocation. Finally, a variety of mutations have no effect on permease activity indicating that single amino acid changes do not lead indiscriminately to long‐range conformational alterations.
Gap junctions: Towards a molecular structure
Authors: Evans W. Howard
Published: February 2005

Gap junctions are ubiquitous plasma membrane specializations that allow cells to exchange small molecules and ions directly. The isolation, biochemical characterization and molecular cloning of the major protein of rat liver gap junctions lead to a clearer view of these membrane zones that allow cells to ‘talk’ to each other and co‐ordinate their activities in tissues and organs.
The pivotal role of ferritin in cellular iron homeostasis
Authors: Mattia Elena , van Renswoude Jos
Published: February 2005

Iron delivered by transferrin to the interior of the cell is in part utilized in biosynthetic processes and in part incorporated into ferritin, the major iron storage protein. The intracellular ferritin concentration is directly correlated to and determined by the extent of iron supply to the cell. Intracellular partitioning of iron to ferritin is suggested as forming the basis of cellular iron homeostasis.
Megabase methods: A quantum jump in recombinant DNA techniques
Authors: Jordan Bertrand R.
Published: February 2005

Until quite recently, recombinant DNA technology was not able to deal with DNA molecules larger than 20–40 kb. This is a serious limitation for the study of mammalian, and in particular human genomes whose total length is approx. 3 × 106 kb, since the best resolution of genetic and chromosomal analysis is usually the rough equivalent of 1000–5000 kb. Three recently developed methods promise to bridge this gap: pulsed field gel electrophoresis, which can analyze megabase‐sized DNA fragments; cloning in yeast, which can clone and propagate DNA fragments of several hundred kb; and jumping libraries, which allow ‘jumping’ over large distances along the chromosome. This review presents the current status of these very promising technologies.
DNA topoisomerases and DNA repair
Authors: Downes C. S. , Johnson R. T.
Published: February 2005

DNA topoisomerases are enzymes that can modify, and may regulate, the topological state of DNA through concerted breaking and rejoining of the DNA strands. They have been believed to be directly involved in DNA excision repair, and perhaps to be required for the control of repair as well. The vicissitudes of this hypothesis provide a noteworthy example of the dangers of interpreting cellular phenomena without genetic information and vice versa.
Molecular and cellular biology of malaria
Authors: Braun Richard
Published: February 2005

Thanks to the extensive use of recombinant DNA technology and immunological methods, much insight into cellular functions of the human malaria parasite Plasmodium falciparum has been gained since it was learnt ten years ago how to grow this organism in culture. The amino acid sequence of over a dozen surface proteins of the parasite and of several proteins the parasite excretes into its most important host cell, the erythrocyte, have been determined. Interestingly many of these proteins show blocks of repeated amino acids. Several proteins have been shown to be involved in specific aspects of the complex hostparasite interaction, such as penetration of host cells or increased stickiness of infected red blood cells in the blood vessels. Some of the proteins described here may be protective antigens and may become important in vaccine development.
A new interleukin with pleiotropic activities
Authors: Kishimoto Tadamitsu , Hirano Toshio
Published: February 2005

Human B cell stimulatory factor 2 (originally designated BSF2) was initially characterized and isolated as a T cell‐derived factor that caused the terminal maturation of activated B cells to immunoglobulin producing cells. Molecular cloning of the cDNA has revealed that BSF2 is identical with 26 kD protein, interferon β2, plasmacytoma growth factor and hepatocyte stimulating factor and the designation “IL‐6” has been proposed for this molecule. It is now known that BSF2/IL‐6 has a wide variety of biological functions and that abnormal regulation of BSF2/IL‐6 expression may be related to the pathogenesis of certain autoimmune diseases such as rheumatoid arthritis and multiple myeloma.
Chromatin assembly in vitro and in vivo
Authors: Dilworth Stephen M. , Dingwall Colin
Published: February 2005

The assembly of nucleosomes and higher‐order chromatin structures has been extensively studied in vitro. Provided that non‐specific charge interactions are controlled, all the information for correct assembly is found to be inherent in the macromolecular components. Cellular extracts which can assemble chromatin in vitro with nucleosomes correctly spaced on the DNA have been studied in detail and also used to investigate the role of chromatin structure in transcription. However, the mechanisms of chromatin assembly in vivo are still controversial.
X chromosome inactivation: A hypothesis
Authors: McBurney Michael W.
Published: February 2005

X‐chromosome inactivation refers to the coordinate regulation of almost all genes on the mammalian × chromosome. Most models for × chromosome inactivation suppose a role for methylation of × chromosome DNA sequences and/or the heterochromatinization of large «domains» of the × chromosome containing many genes.1 Some recent work concerning the expression of X‐linked transgenes, and parallels between regulated expression of sex‐linked genes in invertebrates and mammals, suggest that × chromosome inactivation may be a gene‐by‐gene event mediated by the interaction between regulatory sequences common to all X‐linked genes and soluble activators and repressors.
Biochemistry and physiology of nitrogen fixation
Authors: Haaker H.
Published: February 2005

Biological dinitrogen fixation, the reduction of N2 to NH3, requires the enzyme nitrogenase, MgATP, a strongly reducing electron donor and an anaerobic environment. Reducing power for nitrogen fixation is generated by two particular mechanisms, while the mechanisms for protecting nitrogen fixation from oxygen show a greater diversity. Both the reduction and the protection aspects of nitrogen fixation, especially those of the legume root nodule, will be discussed.
Research opportunities in typhoid fever: Epidemiology and molecular biology
Authors: Calva Edmundo , Puente Jose Luis , Calva Juan José
Published: February 2005

It is estimated that typhoid fever (TF) annually affects more than 12 million persons, worldwide. TF is the result of a generalized infection by the enterobacterium Salmonella typhi. Patients with TF, most of whom live in developing countries have impaired activity for several weeks resulting in an important loss in productivity and welfare. Death may occur, with the single most frequent cause being intestinal perforation. While the first priority must be to develop better methods of disease prevention, there is also an urgent need to devise easy, accurate, and inexpensive diagnostic assays that will allow early routine distinction of TF from other febrile illnesses. Research on TF offers the opportunity to explore many aspects of pathogenesis and the host immune response, as well as to contribute toward the development of new vaccines and diagnostic laboratory tests.
Human endogenous retroviruses
Authors: Cohen Maurice , Larsson Erik
Published: February 2005

Several studies have revealed the presence in human DNA of thousands of endogenous retrovirus genomes, or HERVs. Many HERVs are related to extant retroviruses that infect other vertebrates and some have been present in the germ line of primates for millions of years. Although the HERVs that have been isolated are defective and thus do not encode infectious retroviruses, there may be HERVs that are capable of infection. In addition, because HERVs are so ancient in the human lineage, evolution of the human genome may have included the acquisition of some HERV genes for strictly cellular functions.
Selectivity in solute transport: Binding sites and channel structure in maltoporin and other bacterial sugar transport proteins
Authors: Ferenci Thomas
Published: February 2005

A stereospecific binding site is not the only determinant governing the selectivity of transport proteins. An understanding of transport across cellular membranes requires a description of the different compartments within a transmembrane channel; evidence for the existence of these compartments comes from the selectivity properties of genetically modified maltoporin. Such compartments may also be of significance in determining the specificity of other transport proteins.
Atrial natriuretic peptides: Receptors and second messengers
Authors: Waldman Scott A. , Murad Ferid
Published: February 2005

Atrial natriuretic peptides appear to elicit their actions in some target tissues by binding to a novel cell‐surface transmembrane protein which possesses both peptide binding and guanylate cyclase activities. Ligand binding stimulates enzyme activity to produce increased intracellular concentrations of cyclic GMP which, in turn, mediates the cell's physiological response.
The chemical kinetics of molecular evolution
Authors: Woolley Paul
Published: February 2005

This article describes a current view of the events that initiated the transition from the rich organic and inorganic chemistry of the primitive Earth to the earliest forms of life. It is a personal condensation of the basic ideas developed in the so‐called Göttingen school. Most of these will be found in the seminal paper of Eigen1 and the other sources cited. A detailed exposition is given by Küppers2.
The acetylcholine receptor: Its molecular biology and biotechnological prospects
Authors: Changeux Jean‐Pierre
Published: February 2005

The structure and behaviour of the acetylcholine receptor (AChR) is described, and the evidence that it is an allosteric protein is discussed. The genes for the AChR subunits are subject to a complex set of spatio‐temporal transcriptional controls during development of the motor endplate, and these findings are reviewed here. Finally, the biotechnological prospects suggested by the new data are noted.
The structural and functional interrelationships of muscarinic acetylcholine receptor subtypes
Authors: Ramachandran J. , Peralta E. G. , Ashkenazi A. , Winslow J. W. , Capon D. J.
Published: February 2005

Molecular cloning of the genes encoding the muscarinic acetylcholine receptors has shwon that receptor subtypes classified on the basis of pharmacological properties are related polypeptides encoded by distinct genes. These studies have laso revealed the existence of novel muscarinic receptor subtypes. Functional analysis of each of the subtypes expressed in mammalian cells indicates that the different subtypes activate distinct biochemical pathways, a finding that explains the tissue‐specific physiological response elicited by the neurotransmitter, acetylcholine.
The polyprotein nature of substance P precursors
Authors: Krause James E. , Macdonald Margaret R. , Takeda Yasuo
Published: February 2005

Substance P and related tachykinin peptides probably act as neurotransmitters or modulators of neurotransmission, and regulate biological processes as diverse as salivary secretion and transmission of pain signals. Substance P peptide sequences are expressed in three distinct mRNAs that are generated from one gene by differential RNA splicing. In addition to substance P, as many as three other tachykinin peptides can be generated from the polyprotein precursors by differential posttranslational processing. Three tachykinin receptor subtypes have been extensively characterized which differentially interact with the naturally occurring tachykinin peptides. Therefore, the generation of diversity of tachykinin peptides results from differential precursor RNA splicing and differential posttranslational processing. The specificity of peptide responses is the result of selective receptor subtype expression.
The genetic analysis of mitosis in Aspergillus nidulans
Authors: Ronald Morris N. , Doonan John H. , Osmani Stephen A. , Engle Dorothy B.
Published: February 2005

We describe here recent work on the molecular genetics of mitosis in the filamentous fungus Aspergillus nidulans. Aspergillus is one of three simple eukaryotes with powerful genetic systems that have been used to analyze mitosis. The modern molecular biological techniques available with this organism have made it possible to use mutations to identify genes and proteins that play an important role in mitosis. Three Aspergillus genes that affect mitosis are described. One gene, nimA, is specifically expressed late in the cell cycle and codes for a putative protein kinase that induces mitosis, even in cells blocked in S‐phase. The second gene, bimG, codes for a putative phosphatase that interacts functionally with the nimA kinase. The third gene, bimE, codes for a protein that suppresses mitosis during interphase, apparently by keeping nimA turned off. None of these genes appear to be similar to any of the genes affecting mitosis that have been characterized in other eukaryotes, but rather appear to be elements of a system that prevents mitosis from occurring during interphase.
The mechanism of anaphase spindle elongation
Authors: Cande W. Z. , Hogan C. J.
Published: February 2005

At anaphase chromosomes move to the spindle poles (anaphase A) and the spindle poles move apart (anaphase B). In vitro studies using isolated diatom spindles demonstrate that the primary mechano‐chemical event responsible for spindle elongation is the sliding apart of half‐spindle microtubules. Further, these forces are generated within the zone of microtubule overlap in the spindle midzone.
Regulation of meiosis: From DNA binding protein to protein kinase
Authors: McLeod Maureen
Published: February 2005

The transition from mitotic cell division to meiosis in yeast is governed by both the mating‐type genes and signals from the environment. Analysis of mutants that are unable to regulate entry into meiosis has identified many genes that function in this process and in some cases, the biochemical activity of their protein products has been described. At least two of the the mating‐type genes of Saccharomyces cerevisiae encode DNA binding proteins that regulate transcription of unlinked genes required for entry into meiosis. Meiotic development of the distantly related yeast, Schizosaccharomyces pombe, is also controlled by the mating‐type genes but in this yeast, their role is to regulate expression of a protein that acts as an inhibitor of a protein kinase. The ability to use the powerful tool of genetics in yeast has provided us with many new insights into the problem of meiotic development.
Smooth operators. The molecular mechanics of smooth muscle contraction
Authors: Cross Robert A.
Published: February 2005

Smooth muscle cells squeeze the blood back to your heart, raise the hackles on your neck and change the F‐stop of your eyes. The past year has provided penetrating new insights into their mechanism of contraction.
Mitosis at st andrews: Pulling the treads together
Authors: Brooks R. F.
Published: February 2005

The following is a report of a meeting of the British Society for Cell Biology on ‘The Cell Cycle’, at St Andrews University, 4‐6 April, 1989.
Molecular genetics of drosophila vision
Authors: Montell Craig
Published: February 2005

The fruitfly,Drosophila melanogaster, is an excellent organism for dissecting the components of vision genetically. Many mutations have been generated that affect a diversity of processes important in vision. Through a combined application of molecular and genetic approaches many of the genes important in Drosophila vision are now being identified.
Insect baculoviruses: Powerful gene expression vectors
Authors: Miller Lois K.
Published: February 2005

Baculovirus vectors have proven useful in producing high levels of biologically active eukaryotic proteins and providing cellular fractions which are enriched in the protein of interest. Expression occurs in infected insect cells which also provide a suitable environment for posttranslational modification and folding of the protein product. Stable baculovirus vectors can be constructed rapidly with a minimum of viral manipulation.
How does a key fit a flexible lock? Structure and dynamics in receptor function
Authors: Neubig Richard R. , Thomsen William J.
Published: February 2005

The preceding five years have brought remarkable advances in our understanding of the primary structure of drug receptors. The roles of certain amino acid residues in binding drugs and effecting receptor function have been proposed. As even more detailed structures become available, the goal of rational design of drug molecules based on predicted fits between the drug and its receptor will be near at hand. Although none of the classical receptors has yet yielded to X‐ray crystallographic analysis, the methods of molecular biology facilitate the production of the large amounts of these rare proteins necessary for crystallization. Receptor proteins share one fundamental characteristic with allosterically regulated enzymes. Both have the structural flexibility that allows information to be transmitted to distant parts of the molecule. We will discuss recent observations about receptor structure and the dynamic nature of drug receptors, and pose questions about the significance of receptor dynamics for drug design.
Regulation of pituitary peptides by the immune system
Authors: Hall Nicholas R. S. , O'Grady Maureen P.
Published: February 2005

It has long been thought that the central nervous system is able to influence the progression of disease. Furthermore, there is now overwhelming evidence that the communication pathways are bidirectional. A variety of immune system peptides are now known to be capable of transmitting information from the immune system to the central nervous system. These immunotransmitters include interleukins, interferons and thymosine peptides which have the capability of modulating slow‐wave sleep as well as the release of neuro‐ and pituitary peptides. In some instances, release of these peptides during early development may have long lasting, if not permanent effects upon the normal development of neuro‐endocrine circuits. Collectively these various brain mediated events appear to contribute in various and diverse ways to defense against pathogens. It is becoming more and more apparent that certain abnormalities within the immune system may be the consequence of a neurological abnormality. The converse is also true.
Trichothiodystrophy and the relationship between DNA repair and cancer
Authors: Lehmann A. R.
Published: February 2005

The identification of cellular deficiences in the ability to repair damage in DNA in individuals with several cancer‐prone genetic disorders, has led to the idea that defective DNA repair results in cancer. In patients with trichothiodystrophy, however, a recently discovered defect in the repair of ultraviolet damage in DNA is not associated with cancer‐proneness. Thus our previous ideas about the connections between DNA repair capacity and cancer susceptibility need to be reevaluated.
Proto‐oncogenes in cell differentiation
Authors: Zelenka Peggy S.
Published: February 2005

Proto‐oncogene products may be multi‐functional proteins with various roles in cell differentiation as well as cell proliferation. The molecular biology of the gene products of three well characterized proto‐oncogenes (c‐fos, c‐myc and c‐src) are described, and the roles of three other proto‐oncogene products, involved in hormone and growth factor reception, are reviewed.
Problems and paradigms: On the clonal origin of tumours – lessons from studies of intestinal epithelium
Authors: Schmidt Günter H. , Mead Roger
Published: February 2005

Clonal studies of adult chimaeric mouse epithelium have demonstrated the monoclonal composition of crypts of Lieberkühn(1). In neonatal life, however, polyclonal crypts have been found, indicating that crypts are of polyclonal origin(2). We here relate these findings to studies of mosaic tissues which have addressed the question whether solid tumours are of monoclonal or polyclonal origin (ref. 3 for review, 4). The issues has so far remained unresolved because the expected frequencies of polyclonal tumours, given polyclonal origins, have not previously been estimated. A general approach for the calculation of such expected values is suggested. The consistent reports of tumours with polyclonal components suggest that autocrine or paracrine mechanisms play an important role during tumorigenesis.
The emerging structure of the Agrobacterium T‐DNA transfer complex
Authors: Howard Elizabeth , Citovsky Vitaly
Published: February 2005

Single‐stranded DNA‐protein complex (T‐complex) is proposed to mediate T‐DNA transfer from Agrobacterium to plant cells. A novel model for transfer is presented which incorporates features of both bacterial conjugation and viral infection. Specific protein components of the T‐complex, its ultrastructure and possible functions in the plant cell are discussed.
Growth‐related protein kinases
Authors: Ralph Ray K. , Darkin‐Rattray Sandra , Schofield Phillip
Published: February 2005

A protein kinase cascade is involved in the action of some mitogens. The cascade begins with receptor tyrosine kinase activation by growth factors. The resulting signal is transmitted into cells via phospholipid metabolism which produces a variety of second messengers and by intracellular protein kinase activation. The signal is then propagated and disseminated via a network of other proteln kinases and protein phosphatases. Recent research suggests that ribosomal protein S6 kinase and casein kinase II are two important elements in the kinase cascade that leads to the initiation of growth. The nature and some properties of these hitherto lesser known enzymes is considered.
Eukaryotic transcription factors
Authors: Polyanovsky Oleg L. , Stepchenko Alexander G.
Published: February 2005

Many nuclear proteins have been found recently to interact with short conserved sequences which are involved in regulating the transcription of various genes. Nuclear transcription factors may be arbitrarily subdivided into two groups, ubiquitous and tissue‐specific. The transcription of one gene is usually regulated by several factors which interact with different sequences located either in the promoter region of the gene or outside it. The appearance or disappearance of transcription factors for some genes corresponds to certain phases of cell differentiation or dedifferentiation and even to individual stages of the cell cycle.
Genetic dissection of Ca2+‐dependent ion channel function in Paramecium
Authors: Preston Robin R.
Published: February 2005

The ciliated protozoan, Paramecium, broadcasts the activity of its individual ion channel classes through its swimming behaviour. This fact has made it possible to isolate mutants with defective ion currents, simply by selecting individuals with abnormal swimming patterns. At least four of Paramecium's ion currents are activated by rising intracellular calcium concentration, including two K+ currents and a Na+ current. A variety of cell lines with defects in these Ca2+‐dependent currents have been isolated: in several cases, the defects have been traced to mutations in the structural gene for calmodulin. Sequence analysis of calmodulins from these and other Ca2+ ‐dependent ion‐current mutants may enable a detailed mapping of putative channel interaction domains on the surface of the calmodulin molecule.
The functional importance of multiple actin isoforms
Authors: Rubenstein Peter A.
Published: February 2005

Actin is a protein that plays an important role in cell structure, cell motility, and the generation of contractile force in both muscle and nonmuscle cells. In many organisms, multiple forms of actin, or isoactins, are found. These are products of different genes and have different, although very similar, amino acid sequences. Furthermore, these isoactins are expressed in a tissue specific fashion that is conserved across species, suggesting that their presence is functionally important and their behavior can be distinguished quantitatively from one another in vitro. In muscle cells, they are differentially distributed within the cell and some are specifically associated with structures such as costameres, mitochondria, and neuromuscular junctions. There is also good evidence for specific isoactin function in microvascular pericytes and in the intestinal brush border. However, the necessity of specific isoactins for various functions has not yet been conclusively demonstrated.
Perspectives on methylmalonic acidemia resulting from molecular cloning of methylmalonyl CoA mutase
Authors: Ledley Fred D.
Published: February 2005

Methylmalonyl CoA mutase deficiency (methylmalonic acidemia) has been a paradigm for biochemical and somatic cell genetic approaches to human disease. Recently, genes encoding this enzyme have been cloned from several species. These studies have provided information about the primary structure and evolution of this enzyme, the mutations which underlie its deficiency state, and the structure‐function determinants which are required for its activity. Gene transfer studies now permit restitution of this enzyme to genetically deficient cells and may enable somatic gene therapy to be undertaken. Molecular genetic studies not only provide more detailed information about this enzyme, but introduce new perspectives on the molecular mechanisms and dynamics of its function and raise new questions about the dyshomeostatic consequences of its deficiency.
At the crossroads of developmental genetics: The cloning of the classical mouse T locus
Authors: Silver Lee M.
Published: February 2005

The discovery, more than 60 years ago, of a mutant mouse with a short tail led to the birth of the new field of developmental genetics. Over the years since, numerous investigators have probed the biology of the original short‐tail mutation at the T locus, as well the naturally‐occurring t haplotypes that were uncovered as a result of their interaction with this mutation. Although the T locus ranks among the best characterized developmental loci in the mouse, it was not among the first to be cloned. This situation has now been rectified with two recent reports from Herrmann, Lehrach and their colleagues. While the T locus is expressed uniquely in the embryonic tissues predicted from the mutant phenotype, the gene itself, as well as the predicted amino acid sequence of the T product, show no strong homology to any known sequence. For the moment, at least, the mystery behind the function of the T locus still awaits definitive resolution.
S100 protein and down syndrome
Authors: Marks Alexander , Allore Robert
Published: February 2005

S100 protein is a low molecular weight calcium‐binding protein widely distributed in the central nervous system of vertebrates. Recent evidence suggests that S100 protein may play a role in the regulation of glial proliferation and neuronal differentiation. The gene for S100 protein has been mapped to the 21q22 region, a chromosomal locus whose duplication has been implicated in the generation of Down Syndrome (DS). This raises the possibility that abnormalities in S100 protein gene dosage at a critical period during development may be responsible for some of the neurologic abnormalities associated with DS.
Traction and the formation of mesenchymal condensations in vivo
Authors: Bard Jonathan B. L.
Published: February 2005

Although the segregation of mesenchyme into distinct aggregates is the first step in the development of a range of tissues that includes bones, somites, feathers and nephrons, we still know very little about the mechanisms by which this happens. There are two obvious types of explanation: first, that there are global pre‐patterns within the mesenchyme whose molecular expression leads to tissue fragmentation and, second, that the condensations arise spontaneously through the local morphogenetic abilities of the cells. The only known mechanism for the latter possibility is cell traction and this paper suggests that current studies are compatible with traction playing a primary role in the formation of nephrogenic condensations in the developing kidney and the separation of somites, but not for the generation of feather rudiments where there is evidence of a prepattern of adhesivity.
From the structure to the function of villin, an actin‐binding protein of the brush border
Authors: Friederich Evelync , Pringault Eric , Arpin Monique , Louvard Daniel
Published: February 2005

Villin, a calcium‐regulated actin‐binding protein, modulates the structure and assembly of actin filaments in vitro. It is organized into three domains, the first two of which are homologous. Villin is mainly produced in epithelial cells that develop a brush border and which are responsible for nutrient uptake. Expression of the villin structural gene is precisely regulated during mouse embryogenesis and is restricted in adults, to certain epithelia of the gastrointestinal and urogenital tracts. The function of villin has been assessed by transfecting CV1 cells with a human cDNA encoding wild‐type villin or mutant villin. Synthesis of large amounts of villin in cells which do not normally produce this protein induces the growth of microvilli on the cell surface and the redistribution of F‐actin, concomitant with the disappearance of stress fibers. The complete villin sequence is required for the morphogenic effect. These results suggest that villin plays a key role in the morphogenesis of microvilli.
X‐linked gene expression and sex determination in Caenorhabditis elegans
Authors: Meneely Philip M.
Published: February 2005

The signal for sex determination in the nematode Caenorhabditis elegans is the ratio between the number of × chromosomes and the number of sets of autosomes (the X/A ratio). Animals with an X/A ratio of 0.67 (a triploid with two × chromosomes) or less are males. Animals with an X/A ratio of 0.75 or more are hermaphrodites. Thus, diploid males have one × chromosome and diploid hermaphrodites have two × chromosomes. However, the difference in X‐chromosome number between the sexes is not reflected in general levels of X‐linked gene expression because of the phenomenon of dosage compensation. In dosage compensation, X‐linked gene expression appears to be ‘turned down’ in 2X animals to the 1X level of expression. An intriguing and unexplained finding is that mutations and X‐chromosome duplications that elevate X‐linked gene expression also feminize triploid males. One way that this relationship between sex determination and X‐linked gene expression may be operating is discussed.
The role of recombinational hotspots in genome instability in mammalian cells
Authors: Murnane John P.
Published: February 2005

Genome instability has been associated with progression of transformed cells to high tumorigenicity. Although genome instability may result from a variety of factors, some studies suggest that DNA in the region of a chromosome rearrangement can subsequently have much higher rates of DNA deletions or gene amplification. One approach to studying the factors that produce these high rates of DNA rearrangement is by analysis of unstable integration sites for DNA transfected into mammalian cells. Integrated sequences commonly show a temporary instability, and at rare locations this instability is continuous and can be observed even after multiple subclonings. These continuously unstable locations undergo DNA amplification of both the integrated sequences and the surrounding cell DNA, and it can occur either at the original site or on episomes after looping out from the chromosome. Because the adjacent cell DNA plays a role in this instability, and the region can be shown to be stable before integration, the results indicate that these recombinational hotspots can be formed de novo by the process of integration. Current studies are attempting to determine which sequences are responsible for the high rates of recombination and whether similar types of event are involved in the instability associated with endogenous cellular genes in cancer cells.
Cells and cell‐interactions that guide motor axons in the developing chick embryo
Authors: Tonsey Karthryn W.
Published: February 2005

A considerable challenge confronts, any developing neuron. Before it can establish a functional and specific connection, it must extend an axon over tens and sometimes hundreds of microns through a complex and mutable environment to reach one out of many possible destinations. The field of axonal guidance concerns the control of this navigation process. To satisfactorily identify the cell interactions and molecular mechanisms that mediate axonal guidance, it is essential to first identify the pertinent cell populations. Embryonic surgeries have provided solid information on which tissues are critical and which are irrelevant to the navigation of motor axons within the chick embryo. The gross anatomical nerve pattern is established as axons respond to both positive (path) and negative (barrier) tissue environments. Analysis of the interactions of motoneurons with these tissues reveals that several cellular interactions – chemotaxis, substratum preference, and perhaps contact paralysis – are important to the common patterns of motor axon advance. Axons simultaneously interact with population‐specific cues that have begun to be identified on the tissue level.
Titin, a huge, elastic sarcomeric protein with a probable role in morphogenesis
Authors: Fulton Alice B. , Isaacs William B.
Published: February 2005

Titin, the largest protein identified to date (over 1 μm long, almost 3 million daltons in mass) is the third most abundant component of the sarcomere. In the mature myofibril, titin molecules span from M line to Z line, forming a third filament system which provides sarcomeric alignment and elastic recoil. In the developing sarcomere, accumulating evidence from studies both in vivo and in vitro implicates titin as part of a morphogenetic scaffolding, upon which critical events in myofibrillogenesis are coordinated in a time‐ and spacedependent manner.
Transport across the nuclear envelope: Enigmas and explanations
Authors: Dingwall Colin
Published: February 2005

The transport of molecules across the nuclear envelope plays a central role in the metabolism of the cell. Significant advances hi three major areas highlight the limits of our current knowledge and point to the prospect of exciting future developments. Firstly, findings that ions and small proteins do not diffuse freely into the nucleus call into question the current views of nuclear envelope permeability. Secondly, indications that nuclear protein import can be regulated in conjunction with the cell cycle and development have been confirmed by the clear demonstration of regulated nuclear entry of specific transcription factors and morphogens. Thirdly, identification and characterisation of candidate receptor proteins indicates that the recognition of the nuclear targeting sequence occurs in the cytoplasm, suggesting that a different recognition event occurs at the nuclear pore.
C‐CAM (cell‐CAM 105) – a member of the growing immunoglobulin superfamily of cell adhesion proteins
Authors: Öbrink Björn
Published: February 2005

Cell recognition and adhesion, being of prime importance for the formation and integrity of tissues, are mediated by cell adhesion molecules, which can be divided into several distinct protein superfamilies. The cell adhesion molecule C‐CAM (cell‐CAM 105) belongs to the immunoglobulin superfamily, and more specifically is a member of the carcinoembryonic antigen (CEA) gene family. C‐CAM can mediate adhesion between hepatocytes in vitro in a homophilic, calcium‐independent binding reaction. The molecule, which occurs in various isoforms, is expressed in liver, several epithelia, vessel endothelia, platelets and granulocytes and its expression is dynamically regulated under various physiological and pathological conditions. It is proposed that C‐CAM in different cells and tissues plays different functional roles, where the common denominator is membrane‐membrane binding.
How do plant virus nucleic acids move through intercellular connections?
Authors: Citovsky Vitaly , Zambryski Particia
Published: February 2005

In addition to their function in transport of water, ions, small metabolites, and growth factors in normal plant tissue, the plasmodesmata presumably serve as routes for cell‐to‐cell movement of plant viruses in infected tissue. Virus cell‐to‐cell spread through plasmodesmata is an active process mediated by specialized virus encoded movement proteins; however, the mechanism by which these proteins operate is not clear. We incorporate recent information on the biochemical properties of plant virus movement proteins and their interaction with plasmodesmata in a model for transport of nucleic acids through plasmodesmatal channels. We propose that only single stranded (ss) nucleic acids can be transported efficiently through plasmodesmata, and that movement proteins function as molecular chaperones for ss nucleic acids to form unfolded movement protein‐ss nucleic acid complexes. These complexes are targeted to plasmodesmata. Plasmodesmatal permeability is then increased following interaction with movement protein and the entire movement complex or its nucleic acid component is translocated across the plasmodesmatal channel.
DNA excision repair in mammalian cell extracts
Authors: Wood Richard D. , Coverley Dawn
Published: February 2005

The many genetic complementation groups of DNA excision‐repair defective mammalian cells indicate the considerable complexity of the excision repair process. The cloning of several repair genes is taking the field a step closer to mechanistic studies of the actions and interactions of repair proteins. Early biochemical studies of mammalian DNA repair in vitro are now at hand. Repair synthesis in damaged DNA can be monitored by following the incorporation of radiolabelled nucleotides. Synthesis is carried out by mammalian cell extracts and is defective in extracts from cell lines derived from individuals with the excisionrepair disorder xeroderma pigmentosum. Biochemical complementation of the defective extracts can be used to purify repair proteins. Repair of damage caused by agents including ultraviolet irradiation, psoralens, and platinating compounds has been observed. Neutralising antibodies against the human single‐stranded DNA binding protein (HSSB) have demonstrated a requirement for this protein in DNA excision repair as well as in DNA replication.
Poly(ADP‐ribose) polymerase: Molecular biological aspects
Authors: De Murcia Gilbert , Ménissier‐De Murcia Josiane , Schreiber Valérie
Published: February 2005

A number of roles have been ascribed to poly(ADP‐ribose) polymerase* including involvement in DNA repair, cell proliferation, differentiation and transformation. Cloning of the gene has allowed the development of molecular biological approaches to elucidate the structure and the function(s) of this highly conserved enzyme. This article will review the recent results obtained in this field.
Na+‐coupled alternative to H+‐coupled primary transport systems in bacteria
Authors: Dimroth Peter
Published: February 2005

Protons are the most common coupling ions in bacterial energy conversions. However, while many organisms, such as the alkaliphilic Bacilli, employ H+‐bioenergetics for electron transport phosphorylation, they use Na+ as the coupling ion for transport and flagellar movement. The Na+ gradient required for these bioenergetic functions is established by the secondary Na+/H+ antiporter. In contrast, Vibrio alginolyticus and methanogenic bacteria have primary pumps for both H+ and Na+. They use the proton gradient for ATP synthesis while other, less energy‐consuming membrane reactions are powered by the Na+ gradient. In a third mode, some anaerobic bacteria possess decarboxylases acting as primary Na+ pumps. For instance, in Klebsiella pneumoniae, the Na+ gradient established by oxaloacetate decarboxylase is used for the uptake of the growth substrate citrate, and Propionigenium modestum consumes the energy of the Na+ gradient formed by methylmalonyl‐CoA decarboxylase directly for ATP synthesis.
The interactions of transcription factors and their adaptors, coactivators and accessory proteins
Authors: Martin Katherine J.
Published: February 2005

Consistent with the complexity of the temporally regulated processes that must occur for growth and development of higher eukaryotes, it is now apparent that transcription is regulated by the formation of multi‐component complexes that assemble on the promoters of genes. These complexes can include (in addition to the five or more general transcription factors and RNA polymerase II) DNA‐binding proteins, transcriptional activators, coactivators, adaptors and various accessory proteins. The best studied example of a complex that includes a transcriptional adaptor, accessory proteins and a DNA‐binding protein is that involving the herpes simplex virus VP16 protein. Evidence suggests that the adenovirus E1a protein and the cellular Sp1 and CTF/NF1 transcription factors also function through adaptors or coactivators. Each additional component of the transcription complex provides the cell with another point at which to exert control of gene expression.
Control of eukaryotic DNA replication at the chromosomal level
Authors: Wanka Friedrich
Published: February 2005

A hypothesis for the control of eukaryotic DNA replication at the chromosomal level is proposed. The specific regulatory problem arises from the subdivision of the genome into thousands of individually replicating units, each of which must be duplicated a single time during S‐phase. The hypothesis is based on the finding of direct repeats at replication origins. Such repeats can adopt, beyond the full‐length double helical structure, another configuration exposing two single‐stranded loops that provide suitable templates for the initiation of DNA replication. Any further initiation at the same origin is excluded as the single strandedness is eliminated by the replication process. Restoration of the initiable loop structure is proposed to occur by DNA‐protein rearrangements involved in chromosome condensation and duplication of the chromosomal protein backbone during mitosis. A possible role of the maturation promoting factor (MPF) is suggested.
Bristle patterning in Drosophila
Authors: Held Lewis I.
Published: February 2005

The 5000 bristles that protrude from the cuticle of a Drosophila adult function as either mechanosensors or chemosensors, and they are arranged in surprisingly intricate patterns. Development of the patterns appears to involve five stages: (1) establishment of a coordinate system of ‘positional information’; (2) partitioning of the epidermis into areas where bristles either can or cannot originate; (3) selection of one or more bristle mother cells within each permissible area; (4) suppression of bristle development in the neighborhood of each mother cell; and (5) differentiation of the mother cell to produce four or more descendant cells, each of which forms part of the bristle apparatus. Some of the genes that control these events participate in more than one stage, and others play key roles in roles in seemingly unrelated developmental pathways, including embryonic neurogenesis, body segmentation, and sex determination.
Protein translocation across mitochondrial membranes
Authors: Wienhues Ulla , Neupert Walter
Published: February 2005

Protein translocation across biological membranes is of fundamental importance for the biogenesis of organelles and in protein secretion. We will give an overview of the recent achievements in the understanding of protein translocation across mitochondrial membranes(1‐5). In particular we will focus on recently identified components of the mitochondrial import apparatus.
High blood pressure: Hunting the genes
Authors: Leckie Brenda J.
Published: February 2005

High blood pressure is a disease of unknown cause. Family history of the disease indicates higher risk, but it is not known which genes are involved or how they interact with environmental influences to produce the disorder. Molecular biology offers an approach to problems that have not so far been solved by classical physiology or biochemistry. By analysing polymorphic variation in chromosome markers such as minisatellite sequences, or by restriction fragment polymorphism analysis of candidate genes, attempts are being made to link genetic variations with hypertension. In genetically hypertensive rats, hypertension is associated with a polymorphism of the renin gene and with other loci on chromosomes 10 and 18. The role of these loci in human hypertension remains to be determined. Other genes such as sodium‐lithium countertransport may be involved. Environmental factors such as stress or salt intake could influence the rate or timing of expression of certain genes and thus result in hypertension.