bluuebunny/crossref_metadata_2025 huggingface dataset:
The making of a feather: Homeoproteins, retinoids and adhesion molecules
Authors: Chuong Cheng‐Ming
Published: February 2005

We have been using feather development as a model for understanding the molecular basis of pattern formation and to explore the roles of homeoproteins, retinoids and adhesion molecules in this process. Two kinds of homeobox (Hox) protein gradients in the skin have been identified: a ‘microgradient’ within a single feather bud and a ‘macrogradient’ across the feather tract. The asynchronous alignment of different Hox macrogradients establishes a unique repertoire of Hox expression patterns in skin appendages within the integument, designated here as the ‘Hox codes of skin appendages’. It is hypothesized that these Hox codes contribute to the phenotypic determination of skin appendages. High doses of retinoic acid cause a morphological transformation between feather and scale, while low doses of retinoic acid cause an alteration of the axial orientation of skin appendages. We have tested the ability of molecules directly involved in the feather formation process to mediate the action of the Hox codes, and surmise that adhesion molecules are potential candidates. Using specific Fabs to suppress the activity of adhesion molecules, we have found that L‐CAM is involved in the formation of the hexagonal pattern, N‐CAM is involved in mediating dermal condensations, tenascin is involved in feather bud growth and elongation, and integrin β‐1 is essential for epithelial‐mesenchymal interactions. More work is in progress to fully understand the molecular pathways regulating the feather formation process.
A signature for the HMG‐1 box DNA‐binding proteins
Authors: Landsman David , Bustin Michael
Published: February 2005

A diverse group of DNA‐binding regulatory proteins share a common structural domain which is homologous to the sequence of a highly conserved and abundant chromosomal protein, HMG‐1. Proteins containing this HMG‐1 box regulate various cellular functions involving DNA binding, suggesting that the target DNA sequences share a common structural element. Members of this protein family exhibit a dual DNA‐binding specificity: each recognizes a unique sequence as well as a common DNA conformation. The highly conserved HMG‐1/‐2 proteins may modulate the binding of other HMG‐1 box proteins to bent DNA. We examine the structural and functional relationships between the proteins, identify their signature† and describe common features of their target DNA elements.
Assembly of intermediate filaments
Authors: Shoeman Robert L. , Traub Peter
Published: February 2005

The assembly of intermediate filaments is a fundamental property of the central rod domain of the individual subunit proteins. This rod domain, with its high propensity for α‐helix formation, is the common and identifying feature of this family of proteins. Assembly occurs in vitro in the absence of other proteins or exogenous sources of energy; in vivo, it appears as if other factors, as yet poorly understood, modulate the assembly of intermediate filaments. Parallel, in‐register dimers form via coiled‐coil interactions of the rod domain. Tetramers may form from staggered arrays of parallel or antiparallel arrangements of dimers. Higher‐order polymerization, which occurs spontaneously if the ionic strength of a mixture of dimers and tetramers is raised, proceeds rapidly through poorly described intermediates to the final 10 nm filament. This process is dependent on and modulated by the non‐α‐helical end domains, as well as those amino acids present at the very beginning and end of the rod domain. The interactions governing tetramer formation are most probably the same ones that are responsible for the lateral and longitudinal associations within intermediate filaments.
Problems and Paradigms: Relating biochemistry to biology: How the recombinational repair function of RecA protein is manifested in its molecular properties
Authors: Cox Michael M.
Published: February 2005

The multiple activities of the RecA protein in DNA metabolism have inspired over a decade of research in dozens of laboratories around the world. This effort has nevertheless failed to yield an understanding of the mechanism of several RecA protein‐mediated processes, the DNA strand exchange reactions prominent among them. The major factors impeding progress are the invalid constraints placed upon the problem by attempting to understand RecA protein‐mediated DNA strand exchange within the context of an inappropriate biological paradigm – namely, homologous genetic recombination as a mechanism for generating genetic diversity. In this essay I summarize genetic and biochemical data demonstrating that RecA protein evolved as the central component of a recombinational DNA repair system, with the generation of genetic diversity being a sometimes useful byproduct, and review the major in vitro activities of RecA protein from a repair perspective. While models proposed for both recombination and recombinational repair often make use of DNA strand cleavage and transfer steps that appear to be quite similar, the molecular and thermodynamic requirements of the two processes are very different. The recombinational repair function provides a much more logical and informative framework for thinking about the biochemical properties of RecA and the strand exchange reactions it facilitates.
The molecular biology of taste transduction
Authors: Margolskee Robert F.
Published: February 2005

Taste cells respond to a wide variety of chemical stimuli: certain ions are perceived as salty (Na+) or sour (H+); other small molecules are perceived as sweet (sugars) and bitter (alkaloids). Taste has evolutionary value allowing animals to respond positively (to sweet carhohydrates and salty NaCl) or aversively (to bitter poisons and corrosive acids). Recently, some of the proteins involved in taste transduction have been cloned. Several different G proteins have been identified and cloned from taste tissue: gustducin is a taste cell specific G protein closely related to the transducins. Work is under way to clone additional components of the taste transduction pathways. The combination of electrophysiology, biochemistry and molecular biology is being used to characterize taste receptor cells and their sensory transduction mechanisms.
Protein splicing: Excision of intervening sequences at the protein level
Authors: Cooper Antony A. , Stevens To M. H.
Published: February 2005

Protein splicing is an extraordinary post‐translational reaction that removes an intact central “spacer” domain (Sp) from precursor proteins (N‐Sp‐C) while splicing together the N‐ and C‐domains of the precursor, via a peptide bond, to produce a new protein (N‐C). All of the available data on protein splicing fit a model in which these intervening sequences excise at the protein level via a self‐splicing mechanism. Several proteins have recently been discovered that undergo protein splicing, and in two such cases, the excised spacer protein is an endonuclease. Such endonucleases are capable of conferring genetic mobility upon the intervening sequences that encodes them. These intervening sequences define a new family of mobile genetic elements that are translated yet remain phenotypically silent by excising at the protein rather than the RNA level.
Movement of virus and photoassimilate in the phloem: A comparative analysis
Authors: Leisner Scott M. , Turgeon Robert
Published: February 2005

Recent progress in the study of short‐distance (cell‐to‐cell) movement of plant virus, facilitated by ‘movement proteins’, has led to a resurgence of interest in long‐distance virus transport in the phloem. Relatively little is known about phloem‐specific barriers to virus movement or about the form in which virus enters, travels within and exits this tissue. Progress in understanding virus and photoassimilate transport is limited by a paucity of information on the substructure and properties of plasmodesmata at specific interfaces. The direction of virus movement, once it has entered the phloem, can be understood by following photoassimilate translocation, a complex and dynamic process influenced by plant growth, development and vascular topology.
Feedback controls and G2 checkpoints: Fission yeast as a model system
Authors: Sheldrick Katherine S. , Carr Antony M.
Published: February 2005

Dependency relationships within the cell cycle allow cells to arrest the cycle reversibly in response to agents or conditions that interfere with specific aspects of its normal progression. In addition, overlapping pathways exist which also arrest the cell cycle in response to DNA damage. Collectively, these control mechanisms have become known as checkpoints. Analysis of checkpoints is facilitated by the fact that dependency relationships within the cell cycle, such as the dependency of mitosis on the completion of DNA synthesis, and the DNA damage checkpoint can be separated genetically. In fission yeast, Schizosaccharomyces pombe, the dependency of mitosis on prior completion of DNA synthesis is mediated through tyrosine‐15 phosphorylation of the ubiquitous mitotic regulator p34cdc2. In contrast, the arrest of mitosis caused by DNA damage acts through a separate mechanism that appears to be independent of tyrosine‐15 phosphorylation. Despite these distinct interactions with the mitotic machinery, the majority of fission yeast mutants that are deficient in mitotic arrest after DNA damage are also unable to respond to inhibition of DNA synthesis. In this essay we survey the current knowledge concerning feedback controls and checkpoints within fission yeast and relate this to information derived from other systems.
DNA helicases: Enzymes with essential roles in all aspects of DNA metabolism
Authors: Matson Steven W. , Bean Daniel W. , George James W.
Published: February 2005

DNA helicases catalyze the disruption of the hydrogen bonds that hold the two strands of double‐stranded DNA together. This energy‐requiring unwinding reaction results in the formation of the single‐stranded DNA required as a template or reaction intermediate in DNA replication, repair and recombination. A combination of biochemical and genetic studies have been used to probe and define the roles of the multiple DNA helicases found in E. coli. This work and similar efforts in eukaryotic cells, although far from complete, have established that DNA helicases are essential components of the machinery that interacts with the DNA molecule.
Convergence and divergence in the evolution of transport proteins
Authors: Saier Milton H.
Published: February 2005

Different families of transport proteins catalyze transmembrane solute translocation, employing different mechanisms and energy sources. Several of these functionally dissimilar proteins nevertheless exhibit similar strutural units, consisting of six tightly packed α‐helices which may comprise all or part of a transmembrane channel. It is now recognized that some of these families arose independently of each other by convergence, while others arose from common precursors by divergence. The former families apparently arose at different times in evolutionary history, in different groups of organisms, employing different routes.
Why do plants have phosphoinositides?
Authors: Coté Gary G. , Crain Richard C.
Published: February 2005

Phosphoinositides are inositol‐containing phospholipids whose hydrolysis is a key step in the rapid responses of animal cells to extracellular signals. Whether they play similar roles in plant cells has not been established, and some have suggested alternative roles as direct modulators of specific proteins. Nonetheless, evidence is accumulating that phosphoinositide hydrolysis mediates transduction of some signal in plants. The evidence is strongest for a role in triggering the shedding of flagella by the unicellular alga Chlamydomonas reinhardtii under acid stress. Rapid kinetic analysis indicates that phosphoinositide hydrolysis occures within half a second and could trigger the rapid loss of flagella. Plant responses to pathogens and osmotic stress, as well as the regulation of turgor changes which underlie stomatal opening and closing and the movement of leaves and flower parts, may also be mediated by phosphoinositide hydrolysis. The evidence thus indicates that at least one reason plants have phosphoinositides is to mediate transduction of environmental signals.
Unusual DNA structures, chromatin and transcription
Authors: van Holde Kensal , Zlatanova Jordanka
Published: February 2005

Extensive studies of DNA secondary structure during the past decade have shown that DNA is a dynamic molecule, whose structure depends on the underlying nucleotide sequence and is influenced by the environment and the overall DNA topology. Three major non‐B‐DNA structures have been described (Z‐DNA, triplex DNA and cruciform DNA) which are stabilized by unconstrained negative supercoiling and can be formed under physiological conditions. In this essay we summarize the DNA primary structure features that are pertinent to the formation of these conformers and present data concerning the occurrence of these sequences in the eukaryotic genome. The evidence in favor of the existence of these unusual DNA structures in vivo is discussed. The effect of alternative non‐B‐DNA structures on the way DNA is organized in chromatin is considered, and this is followed by evaluation of the data relating these structures to eukaryotic transcription. Some possible mechanisms by which the effect of non‐B structures on transcription might be exerted are proposed.
Spatial cues play a role in the development of Myxococcus xanthus
Authors: Crawford Eugene W. , Shimkets Lawrence J.
Published: February 2005

Intercellular signaling plays an important role in spatially regulated developmental processes. Myxococcus xanthus C signal transmission during fruiting body formation requires motile, densely packed, well aligned cells. tThe fruiting body consists of two domains: an outer domain which has densely packed, well aligned, motile cells: and an inner domain of more loosely packed, non‐motile, sporulating cells. The two domains are characterized by different patterns of C‐dependent gene expression, which begins in the outer domain where C‐signaling is most efficient, and reaches its maximum in the inner domain. These domains may be maintained by a dynamic mechanism which relies on passive transport of the sporulating cells from the outer domain, where sporulation is initiated, to the inner domain by the motile cells in the outer domain.
Neutrophil chemoattractant receptors and the membrane skeleton
Authors: Klotz Karl‐Norbert , Jesaitis Algirdas J.
Published: February 2005

Signal transduction via receptors for N‐formylmethionyl peptide chemoattractants (FPR) on human neutrophils is a highly regulated process which involves participation of cytoskeletal elements. Evidence exists suggesting that the cytoskeleton and/or the membrane skeleton controls the distribution of FPR in the plane of the plasma membrane, thus controlling the accessibility of FPR to different proteins in functionally distinct domains. In desensitized cells, FPR are restricted to domains which are depleted of G proteins but enriched in cytoskeletal proteins such as actin and fodrin. Thus, the G protein signal transduction partners of FPR become inaccessible to the agonist‐occupied receptor, preventing cell activation. The mechanism of interaction of FPR with the membrane skeleton is poorly understood but evidence is accumulating that suggests a direct binding of FPR (and other receptors) to cytoskeletal proteins such as actin.
Hypothesis: RNA polymerase: Structural determinat of the chromatin loop and the chromosome
Authors: Cook Peter R.
Published: February 2005

Current models for RNA synthesis involve an RNA polymerase that tracks along a static template. However, research on chromatin loops suggests that the template slides past a stationary polymerase; individual polymerases tie the chromatin fibre into loops and clusters of polymerases determine the basic structure of the interphase and metaphase chromosome. RNA polymerase is then both a player and a manager of the chromosome loop.
Cysteine strings, calcium channels and synaptic transmission
Authors: Ganetzky Barry
Published: February 2005

Multidisciplinary studies have led to the discovery and characterization of cysteine string proteins (csps) in both Drosophila and Torpedo. Phenotypic analysis of csp mutants in Drosophila demonstrates a crucial role for csp in synaptic transmission. Expression studies of Torpedo csp (Tcsp) in Xenopus oocytes suggests that the protein has some role in the function of presynaptic Ca2+ channels. However, biochemical purification of Tcsp indicates that is associated with synaptic vesicles rather than with the plasma membrane of presynaptic terminals where Ca2+ channels reside. These results suggest a model in which csps serve as a link by which docked synaptic vesicles could modulate the activity of presynaptic Ca2+ channels.
Borrowing thy neighbour's genetics: Neural induction and a Brachyury mutant in Xenopus
Authors: Green JeremyB. A.
Published: February 2005

A recent article by Rao(1) exemplifies a number of new trends in developmental biology, both of technical strategy and approach to the problem of neural induction. Rao introduced into frog embryos a mutant form of a mesodermal gene, Brachyury, and caused ectopic neural differentiation. This essay traces the route from the original Brachyury mutation in mouse to the most likely conclusion of Rao's experiments — suggested previously(2) — that neural fate is a default pathway.
Butterfly wings: Colour patterns and now gene expression patterns
Authors: French Vernon , Monteiro Antonia
Published: February 2005

The particular fascination of butterfly wings for developmental biologists (and others) lies in their spectacular array of colour patterns. The evolutionary and developmental relationships between these patterns have been analysed and we know something of the cell interactions involved in their formation(1). Now butterfly homologues of Drosophila wing‐patterning genes have been identified, and their expression patterns offer the first clues to the molecular mechanisms which specify wing colour patterns(2).
Mapping in the realm of polyploidy: The wheat model
Authors: Gill Kulvinder S. , Gill Bikram S.
Published: February 2005

Wheat is an allopolyploid containing three distinct but genetically related (homoeologous) genomes, A, B and D. Because of polyploid inheritance and large genome size (16×1012bp), the wheat genome is thought to be intractable to map‐based cloning of agronomic and other genes of interest. We propose a targeted geneti mapping strategy that combines linkage and physical mapping and may facilitate map‐based cloning. High‐density linkage maps are either generated in wheat or in diploidTriticum tauschii, the donor of the D genome to wheat. Molecular marker‐based chromosome maps are constructed, using an array of deletion lines in wheat. The conventional genetic linkage maps are aligned with chromosome maps to construct cytogenetic ladder maps (CLMs). The CLMs allow region‐specific mapping and convert genetic distances into physical distances. The information from CLMs suggests that many genes in wheat are present in clusters that are highly recombiogenic, small, and may be amenable to cloning by chromosome walking. Therefore, the effective genome size of wheat is relatively small in comparison to the whole genome. The utility of using the smaller genome of rice for mapping and homologous gene cloning is discussed.
TKO'ed: Lox, stock and barrel
Authors: Chambers Cynthia A.
Published: February 2005

The generation of panels of mutant mice by homologous recombination has greatly increased the ability to assess the function of particular gene products in vivo. The ability to control the developmental stage, the tissue and the nature of the mutation would be an important innovation. A recent report(1) demonstrates that the conservative site‐specific recombination of bacteriophage P1, namely Cre‐lox, can be used successfuly in combination with homologous recombination to generate temporal‐and cell‐restricted mutations in vivo. The technical advance allows a greater flexibility in gene targeting and will have a significant impact on how complex gene functions are studied in vivo.
Morphogens in vertebrate development: How do they work?
Authors: Cooke Jonathan
Published: February 2005

The idea that concentration gradients of crucial substances might control the pattern of development, even in the embryos of complex organisms, has been around for a long time, but mostly in obscure forms. Twenty five years ago clear, experimentally testable ideas about how such gradients might work were enunciated, and more recently the morphogen gradient principle was shown to underlie the beginnings of patterning in Drosophila. Is it also central to vertebrate development? Four recent papers raise experimentation to a new level(1–4), while showing how difficult it might be to pin down the precise form of the mechanism.
Cell‐cell signalling, microtubule organization and RNA localization: Is PKA a link?
Authors: Lasko Paul
Published: February 2005

Specification of the anterior‐posterior axis of the Drosophila embryo is brought about by the asymmetric localization of specific maternally expressed RNAs and proteins within the oocyte. While many of these localized molecules have been identified and progress has been made towards understanding their functions, how the localization process is instigated remains unclear. A recent paper reports that protein kinase A (PKA) activity is essential for many of these RNA localizations and for the correct polarization of the microtubule cytoskeleton(1). These and other results support a model for anterior‐posterior axis establishment which involves intercellular signalling between the oocyte and certain neighbouring somatic cells.
Phagocytosis
Authors: Brown Eric J.
Published: February 2005

Phagocytosis is the process of recognition and engulfment of microorganisms or tissue debris that accumulate during infection, inflammation or wound repair. This ingestion, which is performed most efficiently by migrating, bone marrow‐derived cells called ‘professional phagocytes’, is essential for successful host defense. Ingestion results when an invading microorganism is recognized by specific receptors on the phagocyte surface and requires multiple, successive interactions between the phagocyte and the target. Each of these interactions results in a signal transduction event, which is confined to the membrane and cytoskeleton around the ligated receptor and which is required for successful phagocytosis. Many molecules found at sites of inflammation or infection stimulate phagocytosis, so that efficient ingestion is confined to the site of infection or inflammation, which in turn limits the proinflammatory and tissue‐destructive processes that accompany phagocytosis. This review summarizes current understanding of this critical component of host defense and of its regulation.
Root gravitropism
Authors: Masson Patrick H.
Published: February 2005

When a plant root is reoriented within the gravity field, it responds by initiating a curvature which eventually results in vertical growth. Gravity sensing occurs primarily in the root tip. It may involve amyloplast sedimentation in the columella cells of the root cap, or the detection of forces exerted by the mass of the protoplast on opposite sides of its cell wall. Gravisensing activates a signal transduction cascade which results in the asymmetric redistribution of auxin and apoplastic Ca2+across the root tip, with accumulation at the bottom side. The resulting lateral asymmetry in Ca2+and auxin concentration is probably transmitted to the elongation zone where differential cellular elongation occurs until the tip resumes vertical growth. The Cholodny‐Went theory proposes that gravity‐induced auxin redistribution across a gravistimulated plant organ is responsible for the gravitropic response. However, recent data indicate that the gravity‐induced reorientation is more complex, involving both auxin gradient‐dependent and auxin gradient‐independent events.
Genetic control of intrachromosomal recombination
Authors: Klein Hannah L.
Published: February 2005

Intrachromosomal recombination between direct repeats can occur either as gene conversion events, which maintain exactly the number of repeat units, or as deletions, which reduce the number of repeat units. Gene conversions are classical recombination events that utilize the standard chromosome recombination machinery. Spontaneous deletions between direct repeats are generally recA‐independent in E. coli and RAD52‐independent in S. cerevisiae. This independence from the major recombination genes does not mean that deletions form through a nonrecombinational process. Deletions have been suggested to result from sister chromatid exchange at the replication fork in a recA‐independent process. The same type of exchange is proposed to be RAD52‐independent in Saccharomyces cerevisiae. RAD52‐dependent events encompass all events that involve the initial steps of a recombination reaction, which include strand invasion to form a heteroduplex intermediate.
Synaptic vesicle recycling intermediates revealed
Authors: Vijayraghavan K.
Published: February 2005

Neurotransmitter release takes place by the exocytosis of loaded synaptic vesicles. The vesicles then fuse to the presynaptic membrane and are recycled by an endocytotic mechanism. A quantitative optical assay that detects uptake and release of a fluorescent dye during presynaptic activity was recently developed and used on the frog neauromuscular junction. I discuss a report(1) that demonstrates the effective application of this method to a Drosophila preparation. The authors use the shibire mutation and a spider venom to identify two intermediates in vesicle recycling. Their report, along with other recent studies, demonstrates the power and promise of the genetic approach for the understanding of mechanisms of synapse function and development.
Compartments and appendage development in Drosophila
Authors: Blair Seth S.
Published: February 2005

The appendages of Drosophila develop from the imaginal discs. During the extensive growth of these discs cell lineages are for the most part unfixed, suggesting a strong role for cell‐cell interactions in controlling the final pattern of differentiation. However, during early and middle stages of development, discs are subdivided by strict lineage restrictions into a small number of spatially distinct compartments. These compartments appear to be maintained by stably inheriting states of gene expression; the compartmentspecific expression of two such ‘selector’ ‐ like genes, engrailed and apterous, are critical for anterior‐posterior and dorso‐ventral compartmentalization, respectively. Recent work suggests that one purpose of compartmentalization is to establish regions of specialized cells near compartment boundaries via intercompartmental induction, using molecules like the hedgehog protein. Thus, compartments can act as organizing centers for patterning within compartments. Evidence for non‐compartmental patterning mechanisms will also be discussed.
Does Flo flow? Cell layer interactions during floral development
Authors: Szymkowiak Eugene J.
Published: February 2005

Higher plant shoot meristems are multicellular structures that are the site of postembryonic organogenesis. Analysis of chimeric plants has indicated that cells in different regions of the meristem can interact with each other so that their activities are coordinated during developmental processes. Correlations have not been demonstrated between events at a molecular level and the interactions observed at a phenotypic level in chimeras. Two recent papers(1,2) address this problem by reporting that expression of the floricaula gene in one region of chimeric snapdragon meristems is sufficient to promote the transition from inflorescence to floral development and to induce the expression of the downstream organ identity genes deficiens and plena throughout the meristem.
A radical approach to enzyme catalysis
Authors: Marsh E. Neil G.
Published: February 2005

Free radicals are generally perceived as highly reactive species which are harmful to biological systems. There are, however, a number of enzymes that use carbon‐based radicals to catalyse a variety of important and unusual reactions. The most prominent example is ribonucleotide reductase, an enzyme which is crucial for the synthesis of DNA. In general, radicals are used to remove hydrogen from unreactive positions in the substrate, and in this way the substrate is activated to undergo chemical transformations that would otherwise be difficult to achieve. Several different mechanisms have evolved which allow enzymes to generate and maintain radicals in increasingly aerobic enviroments. An unexpected finding is the existance of stable protein‐based radicals, residing on a variety of amino‐acid side chains, which serve to link the radical‐generating and catalytic sites and to store the radical between turnovers.
Model systems in developmental biology
Authors: Bolker Jessica A.
Published: February 2005

The practical criteria by which developmental biologists choose their model systems have evolutionary correlates. The result is a sample that is not merely small, but biased in particular ways, for example towards species with rapid, highly canalized development. These biases influence both data collection and interpretation, and our views of how development works and which aspects of it are important.
Overview of controls in the Escherichia coli cell cycle
Authors: Vinella Daniel , D'Ari Richard
Published: February 2005

The harmonious growth and cell‐to‐cell uniformity of steady‐state bacterial populations indicate the existence of a well‐regulated cell cycle, responding to a set of internal signals. In Escherichia coli, the key events of this cycle are the initiation of DNA replication, nucleoid segregation and the initiation of cell division. The replication initiator is the DnaA protein. In nucleoid segregation, the MukB protein, required for proper partitioning, may be a member of the myosin‐kinesin superfamily of mechanoenzymes. In cell division, the FtsZ protein has a tubulin motif, is a GTPase and polymerizes in a ring around midcell during septation; the FtsA protein has an actin‐like structure. The nature of the internal signals triggering these events is not known but candidates include cell mass, the superhelical density of the chromosome and the concentration of two regulatory nucleotides, cyclic AMP and ppGpp. The involvement of cytoskeletal‐like proteins in key cycle events encourages the notion of a fundamental biological unity in cell cycle regulation in all organisms.
Cell death suffers a TKO
Authors: Osborne Barbara A. , Schwartz Lawrence M.
Published: February 2005

The cytokine interferon‐γ (IFN‐γ), initiates both cell cycle arrest and cell death in certain cell lines. Through a novel strategy of cell transfection with episomal vectors expressing antisense cDNAs, Deiss et al.(1.2) have demonstrated that it is possible to isolate genes that are required for the initiation of cell death by the cytokine IFN‐γ. This approach, referred to as TKO, for Technical Knock Out, has identified several genes whose activity appears to be essential for the induction of apoptosis by IFN‐γ in HeLa cells. Interestingly, these genes appear to mediate IFN‐γ‐induced apoptosis in HeLa cells, but their inhibition by antisense does not ameliorate the anti‐proliferative effects of IFN‐γ in these cells. The clever strategy employed by these authors holds promise for others who wish to isolate genes required for other differentiative processes in cultured cell lines.
Alkylation of DNA and its aftermath
Authors: Lawley P. D.
Published: February 2005

Current pharmacopoeias invariably refer to a category of ‘alkylating drugs’, still among the most widely used in cancer chemotherapy. They are described as acting through their ability to damage DNA, thus interfering with cell replication. Unfortunately, this mode of action implicates these drugs as carcinogens. Thus the early studies recalled in this essay proved to be relevant to our understanding of both the main problems with which cancer research concerns itself: the causation of cancer and possible methods of treatment of this group of diseases.
The significances of bacterial colony patterns
Authors: Shapiro James A.
Published: February 2005

Bacteria do many things as organized populations. We have recently learned much about the molecular basis of intercellular communication among prokaryotes. Colonies display bacterial capacities for multicellular coordination which can be useful in nature where bacteria predominantly grow as films, chains, mats and colonies. E. coli colonies are organized into differentiated non‐clonal populations and undergo complex morphogenesis. Multicellularity regulates many aspects of bacterial physiology, including DNA rearrangement systems. In some bacterial species, colony development involves swarming (active migration of cell groups). Swarm colony development displays precise geometrical controls and periodic phenomena. Motile E. coli cells in semi‐solid media form organized patterns due to chemotactic autoaggregation. On poor media, B. subtilis forms branched colonies using group motility and longrange chemical signalling. The significances of bacterial colony patterns thus reside in a deeper understanding of prokaryotic biology and evolution and in experimental systems for studying self‐organization and morphogenesis.
Transcriptional silencing of homeotic genes in drosophila
Authors: Bienz Mariann , Müller Jürg
Published: February 2005

Homeotic genes are subject to transcriptional silencing, which prevents their expression in inappropriate body regions. Here, we shall focus on Drosophila, as little is known about this process in other organisms. Evidence is accumulating that silencing of Drosophila homeotic genes is conferred by two types of cis‐regulatory sequences: initiation (SIL‐I) and maintenance (SIL‐M) elements. The former contain target sites for transient repressors with a highly localised distribution in the early embryo and the latter for constitutive repressors that are likely to be present in all cells. We discuss how SIL‐I elements may cooperate with SIL‐M elements to promote formation of a silencing complex. We propose that this complex consists of specific non‐histone proteins, the so‐called Polycomb group proteins, and that it is anchored at SIL‐M elements and at the promoter.
The genetics of lantibiotic biosynthesis
Authors: Jack Ralph , Bierbaum Gabriele , Heidrich Christoph , Sahl Hans‐Georg
Published: February 2005

The lantibiotics are a rapidly expanding group of biologically active peptides produced by a variety of Gram‐positive bacteria, and are so‐called because of their content of the thioether amino acids lanthionine and β‐methyllanthionine. These amino acids, and indeed a number of other unusual amino acids found in the lantibiotics, arise following post‐translational modification of a ribosomally synthesised precursor peptide. A number of genes involved in the biosynthesis of these highly modified peptides have been identified, including genes encoding the precursor peptide, enzymes responsible for specific amino acid modifications, proteases able to remove the leader peptide, ABC‐superfamily transport proteins involved in lantibiotic translocation, regulatory proteins controlling lantibiotic biosynthesis and proteins that protect the producing strain from the action of its own lantibiotic. Analysis of these genes and their products is allowing greater understanding of the complex mechanism(s) of the biosynthesis of these unique peptides.
Dual mechanisms of lymphocytemediated cytotoxicity serve to control and deliver the immune response
Authors: Smyth Mark J.
Published: February 2005

Cytotoxic lymphocytes play a central role in immune inflammatory responses against tumour cells, viruses and cells transplanted or infected with intracellular bacteria. The pivotal importance of lymphocytes in each of these immune responses has justified our continued interest in their cytotoxic function. Recent studies of cytotoxic lymphocytes have involved the characterisation of recognition structures on cytotoxic lymphocytes and the definition of two mechanisms of cytotoxicity. In contrast to normal cell death, which occurs during embryonic development and the formation and death of hematopoietic cell lineages, lymphocyte‐mediated cytotoxicity occurs in the context of an inflammatory response and the dying cells are lysed into the surroundings rather than phagocytosed. The roles of the two different forms of lymphocyte‐mediated cytotoxicity are quite distinct; however they both involve induction of an endogenous pathway of apoptosis in the targeted cell, and they do share features with all other forms of physiological cell death.
Transparent things: Cell fates and cell movements during early embryogenesis of zebrafish
Authors: Solnica‐Krezel Lilianna , Stemple Derek L. , Driever Wolfgang
Published: February 2005

Development of an animal embryo involves the coordination of cell divisions, a variety of inductive interactions and extensive cellular rearrangements. One of the biggest challenges in developmental biology is to explain the relationships between these processes and the mechanisms that regulate them. Teleost embryos provide an ideal subject for the study of these issues. Their optical lucidity combined with modern techniques for the marking and observation of individual living cells allow high resolution investigations of specific morphogenetic movements and the construction of detailed fate maps. In this review we describe the patterns of cell divisions, cellular movements and other morphogenetic events during zebrafish early development and discuss how these events relate to the formation of restricted lineages.
The macrophage
Authors: Gordon Siamon
Published: February 2005

The macrophage plays an important role in host development and physiology, and in pathogenesis of many infectious, immunologic and degenerative disease processes. It displays marked heterogeneity of phenotype in different tissues, reflecting local interactions with other cell types, and contributes to host homeostasis through a varied repertoire of plasma membrane and secretory molecules. Upon isolation from the body it continues to express special, as well as general, features of cellular organisation and function, which make it a delight to study in cell culture.
DNA packaging and cutting by phage terminases: Control in phage T4 by a synaptic mechanism
Authors: Black Lindsay W.
Published: February 2005

Phage DNA packaging occurs by DNA translocation into a prohead. Terminases are enzymes which initiate DNA packaging by cutting the DNA concatemer, and they are closely fitted structurally to the portal vertex of the prohead to form a ‘packasome’. Analysis among a number of phages supports an active role of the terminases in coupling ATP hydrolysis to DNA translocation through the portal. In phage T4 the small terminase subunit promotes a sequence‐specific terminase gene amplification within the chromosome. This link between recombination and packaging suggests a DNA synapsis mechanism by the terminase to control packaging initiation, formally homologous to eukaryotic chromosome segregation.
Developmental regulation of αβ T cell antigen receptor assembly in immature CD4+CD8+ thymocytes
Authors: Kearse Kelly P. , Roberts Joseph P. , Wiest David L. , Singer Alfred
Published: February 2005

Most lymphocytes of the T cell lineage develop along the CD4/CD8 pathway and express antigen receptors on their surfaces consisting of clonotypic αβ chains associated with invariant CD3‐γδε components and ζ chains, collectively referred to as the T cell antigen receptor complex (TCR). Expression of the TCR complex is dynamically regulated during T cell development, with immature CD4+CD8+ thymocytes expressing only 10% of the number of αβ TCR complexes on their surfaces expressed by mature CD4+ and CD8+ T cells. Recent evidence demonstrates that low surface TCR density on CD4+CD8+ thymocytes results from the limited survival of a single TCR component within the ER, the TCRα chain, which has a half life of only 15 minutes in immature thymocytes, compared to >75 minutes in mature T cells. Instability of TCRα proteins in immature CD4+CD8+ thymocytes represents a novel mechanism by which expression of the multisubunit TCR complex is quantitatively regulated during T cell development. In the current review we discuss our recent findings concerning the assembly, intracellular transport, and expression of αβ TCR complexes in CD4+CD8+ thymocytes and comment on the functional significance of TCRα instability during T cell development.
The pleckstrin homology domain: An intriguing multifunctional protein module
Authors: Shaw Gerry
Published: February 2005

Pleckstrin homology (PH) domains are a family of compact protein modules defined by sequences of roughly 100 amino acids. These domains are common in vertebrate, Drosophila, C. elegans and yeast proteins, suggesting an early origin and fundamental importance to eukaryotic biology. Many enzymes which have important regulatory functions contain PH domains, and mutant forms of several such proteins are implicated in oncogenesis and developmental disorders. Numerous recent studies show that PH domains bind various proteins and inositolphosphates. Here I discuss PH domains in detail and conclude that they form a versatile family of membrane binding and protein localization modules.
Drosophila Sgs genes: Stage and tissue specificity of hormone responsiveness
Authors: Lehmann Michael
Published: February 2005

The up‐ and down‐regulation of the salivary gland secretion protein (Sgs) genes during the third larval instar of Drosophila melanogaster are controlled by fluctuations of the titre of the steroid hormone 20‐hydroxyecdysone (20E). Induction of these genes by a low hormone titre is a secondary response to 20E mediated by products of 20E‐induced ‘early’ genes. Surprisingly, in the case of the Sgs‐4 gene this response also requires a direct contribution of the 20E‐receptor complex. A model is presented which proposes that the Sgs genes, and other 20E‐regulated genes with similar temporal expression profiles, are regulated by complex hormone response units. The hormonal signal is effectively transmitted by these response units only after binding of additional factors, e.g. secretion enhancer binding proteins, which act together in a synergistic manner with the 20E receptor and early gene products to establish a stage‐ and tissuespecific expression pattern.
Unusual evolution of 11β‐ and 17β‐hydroxysteroid and retinol dehydrogenases
Authors: Baker Michael E.
Published: February 2005

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

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

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

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

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