bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel 3‐Arylamino‐ and 3‐Cycloalkylamino‐5, 6‐diphenyl‐pyridazines Active as ACAT Inhibitors
Authors: Toma Lucio , Giovannoni Maria Paola , Vergelli Claudia , Dal Piaz Vittorio , Kwon Byoung‐Mog , Kim Young‐Kook , Gelain Arianna , Barlocco Daniela 
Published: February 2003

AbstractA new series of pyridazine derivatives, structurally related to the previously reported ACAT inhibitors 3‐(cyclo)alkylamino‐5, 6‐diphenyl‐pyridazines, were synthesized and tested for their inhibitory properties. Substitution of the 3‐alkylamino chain with a phenylamino group maintains activity. In contrast, the presence of either substituents on the phenylamino group or aliphatic rings having more or less than six carbon atoms lowers it.
Statistical bioinformatic methods in microbial genome analysis
Authors: Liò Pietro 
Published: February 2003

AbstractIt is probable that, increasingly, genome investigations are going to be based on statistical formalization. This review summarizes the state of art and potentiality of using statistics in microbial genome analysis. First, I focus on recent advances in functional genomics, such as finding genes and operons, identifying gene conversion events, detecting DNA replication origins and analysing regulatory sites. Then I describe how to use phylogenetic methods in genome analysis and methods for genome‐wide scanning for positively selected amino acids. I conclude with speculations on the future course of genome statistical modeling. BioEssays 25:266–273, 2003. © 2003 Wiley Periodicals, Inc.
Cytogenetics in reproductive medicine: The contribution of comparative genomic hybridization (CGH)
Authors: Wells Dagan , Levy Brynn 
Published: February 2003

AbstractCytogenetic research has had a major impact on the field of reproductive medicine, providing an insight into the frequency of chromosomal abnormalities that occur during gametogenesis, embryonic development and pregnancy. In humans, aneuploidy has been found to be relatively common during fetal life, necessitating prenatal screening of high‐risk pregnancies. Aneuploidy rates are higher still during the preimplantation stage of development. An increasing number of IVF laboratories have attempted to improve pregnancy rates by using preimplantation genetic diagnosis (PGD) to ensure that the embryos transferred to the mother are chromosomally normal. This paper reviews some of the techniques that are key to the detection of aneuploidy in reproductive samples including comparative genomic hybridization (CGH). CGH has provided an unparalleled insight into the nature of chromosome imbalance in human embryos and polar bodies. The clinical application of CGH for the purposes of PGD and the future extensions of the methodology, including DNA microarrays, are discussed. BioEssays 25:289–300, 2003. © 2003 Wiley Periodicals, Inc.
Nonculturable bacteria: programmed survival forms or cells at death's door?
Authors: Nyström Thomas 
Published: February 2003

AbstractUpon starvation and growth arrest, Escherichia coli cells gradually lose their ability to reproduce. These apparently sterile/nonculturable cells initially remain intact and metabolically active and the underlying molecular mechanism behind this sterility is something of an enigma in bacteriology. Three different models have been proposed to explain this phenomenon. The first theory suggests that starving cells become nonculturable due to cellular deterioration, are moribund, and show some of the same signs of senescence as aging organisms. The two other theories suggest that genetically programmed pathways, rather than stochastic deterioration, trigger nonculturability. One “program” theory suggests that nonculturability is the culmination of an adaptive pathway generating dormant survival forms, similar to spore formation in differentiating bacteria. The other “program” theory states that starved cells lose viability due to activation of genetic modules mediating programmed cell death. The different models will be reviewed and evaluated in light of recent data on the physiology and molecular biology of growth‐arrested E. coli cells. BioEssays 25:204–211, 2003. © 2003 Wiley Periodicals, Inc.
On the mechanism ofWolbachia‐induced cytoplasmic incompatibility: Confronting the models with the facts
Authors: Poinsot Denis , Charlat Sylvain , Merçot Hervé 
Published: February 2003

AbstractThe endocellular bacteriumWolbachiamanipulates the reproduction of its arthropod hosts for its own benefit by various means, the most widespread being cytoplasmic incompatibility (CI). To date, the molecular mechanism involved in CI has not been elucidated. We examine here three different CI models described in previous literature, namely, the “lock‐and‐key”, “titration–restitution” and “slow‐motion” models. We confront them with the full range of CI patterns discovered so far, including the most complex ones such as multiple infections, asymmetrical and partial compatibility relationships and the existence ofWolbachiavariants that can rescue the host from CI but not induce it. We conclude that the lock‐and‐key model is the most parsimonious of the models and fits the observations best. The two other models cannot be categorically invalidated, but they encounter some difficulties that make additional hypotheses necessary. BioEssays 25:259–265, 2003. © 2003 Wiley Periodicals, Inc.
Alzheimer vaccine: amyloid‐β on trial
Authors: Robinson Stephen R. , Bishop Glenda M. , Münch Gerald 
Published: February 2003

AbstractA new therapeutic approach is being developed for the treatment of Alzheimer's disease (AD). This approach involves the deliberate induction of an autoimmune response to amyloid‐β (Aβ) peptide, the constituent of neuritic plaques that is thought to cause the neurodegeneration and dementia in AD. If this approach is to be effective, antibodies must be produced that can selectively target the toxic forms of Aβ, while leaving the functionally‐relevant forms of Aβ and its precursor protein untouched. Furthermore, an approach needs to be found that avoids provoking an acute neuroinflammatory response. The situation is made even more challenging by uncertainty regarding which isoforms of Aβ contribute to the pathogenesis of AD. BioEssays 25:283–288, 2003. © 2003 Wiley Periodicals, Inc.
AraC protein: A love–hate relationship
Authors: Schleif Robert 
Published: February 2003

AbstractIn the bacterium Escherichia coli, the AraC protein positively and negatively regulates expression of the proteins required for the uptake and catabolism of the sugar L‐arabinose. This essay describes how work from my laboratory on this system spanning more than thirty years has aided our understanding of positive regulation, revealed DNA looping (a mechanism that explains many action‐at‐a‐distance phenomena) and, more recently, has uncovered the mechanism by which arabinose shifts AraC from a state where it prefers to bind to two well‐separated DNA half‐sites and form a DNA loop to a state where it binds to two adjacent half‐sites and activates transcription. This work required learning how to assay, purify, and work with a protein possessing highly uncooperative biochemical properties. Present work is focussed on understanding arabinose‐responsive mechanism in atomic detail and is also directed towards understanding protein structure and function well enough to be able to engineer the allosteric mechanism seen in AraC onto other proteins. BioEssays 25:274–282, 2003. © 2003 Wiley Periodicals, Inc.
Sex‐determination gene and pathway evolution in nematodes
Authors: Stothard Paul , Pilgrim Dave 
Published: February 2003

AbstractThe pathway that controls sexual fate in the nematode Caenorhabditis elegans has been well characterized at the molecular level. By identifying differences between the sex‐determination mechanisms in C. elegans and other nematode species, it should be possible to understand how complex sex‐determining pathways evolve. Towards this goal, orthologues of many of the C. elegans sex regulators have been isolated from other members of the genus Caenorhabditis. Rapid sequence evolution is observed in every case, but several of the orthologues appear to have conserved sex‐determining roles. Thus extensive sequence divergence does not necessarily coincide with changes in pathway structure, although the same forces may contribute to both. This review summarizes recent findings and, with reference to results from other animals, offers explanations for why sex‐determining genes and pathways appear to be evolving rapidly. Experimental strategies that hold promise for illuminating pathway differences between nematodes are also discussed. BioEssays 25: 221–231, 2003. © 2003 Wiley Periodicals, Inc.
Kidney development and the fetal programming of adult disease
Authors: Moritz Karen M. , Dodic Miodrag , Wintour E. Marelyn 
Published: February 2003

AbstractRecent evidence, from both epidemiological and animal experimental studies, suggest that the very first environment, the intrauterine, is extremely important in determining the future health of the individual. Genetic and ‘lifestyle’ factors impinge on, and can exacerbate, a ‘programming’ effect of an adverse fetal environment. In this review, we present compelling evidence to suggest that one of the major organs affected by an unfavourable prenatal environment is the kidney. Many of the factors that can affect fetal renal development (i.e. exposure to excess glucocorticoids, insufficient vitamin A, protein/calorie malnutrition (in rats) and alterations in the intrarenal renin angiotensinogen system), also produce hypertension in the adult animal. When nephron number is compromised during kidney development, maladaptive functional changes occur and can lead, eventually, to hypertension and/or renal disease. Surprisingly, it is during the very earliest stages of kidney development that the vulnerability to these effects occurs. BioEssays 25:212–220, 2003. © 2003 Wiley Periodicals, Inc.
Does cholesterol use the mitochondrial contact site as a conduit to the steroidogenic pathway?
Authors: Thomson Murray 
Published: February 2003

AbstractThe first and rate‐limiting step of steroidogenesis is the transfer of cholesterol from the outer mitochondrial membrane to the inner membrane where it is converted to pregnenolone by cytochrome P450 side‐chain cleavage (P450scc). This reaction is modulated in the gonads and adrenals by the steroidogenic acute regulatory protein (StAR), however, the mechanism used by StAR is not understood. The outer and inner mitochondrial membranes are joined at contact sites that are thought to be held in place by protein complexes that bridge the two membranes. While it is generally accepted that proteins are imported into the mitochondrion via contact sites, it is not clear whether cholesterol takes the same conduit to the inner membrane. Strategies to combat diseases caused by interrupted cholesterol transfer will rely on a full understanding of the steroidogenic mechanism. The challenge for the future is to determine whether StAR relies on the molecular architecture that spans the mitochondrial intermembrane space to deliver its cargo. BioEssays 25:252–258, 2003. © 2003 Wiley Periodicals, Inc.
Phylogenomics of type II DNA topoisomerases
Authors: Gadelle Danièle , Filée Jonathan , Buhler Cyril , Forterre Patrick 
Published: February 2003

AbstractType II DNA topoisomerases (Topo II) are essential enzymes implicated in key nuclear processes. The recent discovery of a novel kind of Topo II (DNA topoisomerase VI) in Archaea led to a division of these enzymes into two non‐homologous families, (Topo IIA and Topo IIB) and to the identification of the eukaryotic protein that initiates meiotic recombination, Spo11. In the present report, we have updated the distribution of all Topo II in the three domains of life by a phylogenomic approach. Both families exhibit an atypical distribution by comparison with other informational proteins, with predominance of Topo IIA in Bacteria, Eukarya and viruses, and Topo IIB in Archaea. However, plants and some Archaea contain Topo II from both families. We confront this atypical distribution with current hypotheses on the evolution of the three domains of life and origin of DNA genomes. BioEssays 25:232–242, 2003. © 2003 Wiley Periodicals, Inc.
Molecular architecture of intermediate filaments
Authors: Strelkov Sergei V. , Herrmann Harald , Aebi Ueli 
Published: February 2003

AbstractTogether with microtubules and actin microfilaments, ∼11 nm wide intermediate filaments (IFs) constitute the integrated, dynamic filament network present in the cytoplasm of metazoan cells. This network is critically involved in division, motility and other cellular processes. While the structures of microtubules and microfilaments are known in atomic detail, IF architecture is presently much less understood. The elementary ‘building block’ of IFs is a highly elongated, rod‐like dimer based on an α‐helical coiled‐coil structure. Assembly of cytoplasmic IF proteins, such as vimentin, begins with a lateral association of dimers into tetramers and gradually into the so‐called unit‐length filaments (ULFs). Subsequently ULFs start to anneal longitudinally, ultimately yielding mature IFs after a compaction step. For nuclear lamins, however, assembly starts with a head‐to‐tail association of dimers. Recently, X‐ray crystallographic data were obtained for several fragments of the vimentin dimer. Based on the dimer structure, molecular models of the tetramer and the entire filament are now a possibility. BioEssays 25:243–251, 2003. © 2003 Wiley Periodicals, Inc.
Sex steroids, ANGELS and osteoporosis
Authors: Moggs Jonathan G. , Deavall Damian G. , Orphanides George 
Published: February 2003

AbstractOsteoporosis is characterized by reduced bone density and strength. Bone mass peaks between age 30 and 40 and then declines. This can be accelerated by factors including menopause and insufficient dietary calcium. Hormone replacement therapy (HRT) is currently the standard treatment for osteoporosis. However, growing concern over potential side effects of HRT has driven a search for alternative therapies. A recent report1 reveals a potential alternative to HRT: a gender‐neutral synthetic steroid that increases bone mass and strength without affecting reproductive organs. This compound acts via a novel extranuclear sex steroid receptor signaling mechanism that has important implications for nuclear receptor biology and human health. BioEssays 25:195–199, 2003. © 2003 Wiley Periodicals, Inc.
A Hes1‐based oscillator in cultured cells and its potential implications for the segmentation clock
Authors: Dale J. Kim , Maroto Miguel 
Published: February 2003

AbstractDuring somitogenesis an oscillatory mechanism termed the “segmentation” clock generates periodic waves of gene expression, which translate into the periodic spatial pattern manifest as somites. The dynamic expression of the clock genes shares the same periodicity as somitogenesis. Notch signaling is believed to play a role in the segmentation clock mechanism. The paper by Hirata et al.(1) identifies a biological clock in cultured cells that is dependent upon the Notch target gene Hes1, and which shows a periodicity similar to that of the segmentation clock. This finding opens the possibility that the same oscillator mechanism might also operate in other tissues or cell types. BioEssays 25:200–203, 2003. © 2003 Wiley Periodicals, Inc.
Ballungszentrum Muschelbank: Biodiversität und nachhaltige Nutzung
Authors: Buschbaum Christian , Saier Bettina 
Published: February 2003

AbstractAuf den Sedimentflächen des Wattenmeeres verspinnen sich Miesmuscheln (Mytilus edulis) zu großflächigen Muschelbänken. Diese sind im vergleichsweise artenarmen Wattenmeer Inseln hoher Biodiversität. Etwa 100 festsitzende Algen‐ und Tierarten nutzen die Muschelschalen als Hartsubstrat, und viele mobile Organismen finden in den Nischen zwischen den einzelnen Muscheln einen geeigneten Lebensraum. Sowohl die Artenzusammensetzung, die Dichte als auch die Wechselwirkungen zwischen den Organismen hängen von der Position der Muschelbank im Gezeitenbereich ab. Vor allem die Muschelbänke im dauerüberfluteten Bereich des Wattenmeeres weisen eine hohe Artenvielfalt auf. Sie unterliegen einer intensiven fischereilichen Nutzung, so dass einer der vielfältigsten Lebensräume im Wattenmeer gefährdet ist. Um einen weiteren Verlust an Arten zu verhindern, stellen wir ein nachhaltiges Nutzungskonzept für die Muschelfischerei vor.
Das Devon: Quastenflosser und Nacktpflanzen
Authors: Rothe Peter 
Published: February 2003

AbstractWährend des Devons wurden die Voraussetzungen für das Variskische Gebirgssystem geschaffen, das heute große Teile Europas geologisch bestimmt. Ein durch Rotsedimente geprägter Festlandsbereich im Norden ging in ein südliches Meer über, dessen wechselvolle Entwicklung Flach‐ und Tiefseeareale kennzeichnen, deren vielfältige Fossilienwelt durch die unterschiedlichen Wassertiefen gesteuert scheint. Riffe wuchsen am Schelfrand und auf untermeerischen Vulkanschwellen und produzierten große Mengen von Kalk. Das entsprechend warme Klima war durch die plattentektonische Konfiguration bedingt, der devonische Äquator verlief durch Europa und Nordamerika. Die fortschreitende Eroberung des Landes durch Pflanzen und Wirbeltiere macht das Devon zu einem der wesentlichsten geologischen Systeme in der Geschichte der Erde.
Völlig losgelöst: Schüler forschen unter Weltraumbedingungen
Authors: Schwertner Jürgen , Wiedemann Meike , Hanke Wolfgang 
Published: February 2003

AbstractDie Untersuchung der Schwerkraftabhängigkeit biologischer Systeme ist Ausgangsbasis eines gemeinsamen aufwendigen Projektes der Universität Hohenheim und des Wilhelms‐Gymnasiums in Stuttgart, das auf einer Tagung des DLR von Wissenschaftlern unter anderem zur Popularisierung der Raumforschung unter Jugendlichen angeregt wurde. Auch die interessierte Öffentlichkeit soll mit diesem Projekt erreicht werden, und es soll gezeigt werden, dass solche Projekte für alle Beteiligten profitabel sein können.
Naturwunder in Gefahr: Rift‐Valley‐Seen Kenias
Authors: Krienitz Lothar , Ballot Andreas , Kotut Kiplagat , Wiegand Claudia , Codd Geoff. A. , Pflugmacher Stephan 
Published: February 2003

AbstractAn fünf Rift‐Valley‐Seen in Kenia wird gezeigt, welchen Gefahren diese einmaligen Habitate ausgesetzt sind. Als Parameter zur Gewässerbewertung wurde die Biodiversität des Phytoplanktons herangezogen. Besonders die Cyanobakterienpopulationen haben erheblichen Einfluss auf das ökologische Gleichgewicht der Seen und die Nutzbarkeit des Wassers. Die Untersuchungsgewässer repräsentieren hochinteressante Biodiversitäts‐ und Salinitätsgradienten. Der Baringosee ist starken Verlandungs‐ und zunehmend auch Versalzungsproblemen ausgesetzt, darüber hinaus wurden Microcystine nachgewiesen. An den alkalinen Seen Bogoria und Nakuru ist seit zwei Jahrzehnten eine erhöhte Sterberate des Kleinen Flamingos beobachtet worden. Bisherige Befunde weisen auf verschiedene Ursachen hin: Pestizide, Schwermetalle, bakterielle Krankheiten sowie Leber‐ und Nervengifte aus der Gruppe der Cyanotoxine. Der Naivashasee als Süßwasser leidet unter erheblicher Übernutzung und Degradation, was sich auch an seiner ehemaligen Bucht, dem Oloidiensee, durch einen deutlichen Anstieg des Salzgehaltes und einer Verarmung des Phytoplanktons zeigt.
Stephen Jay Gould
Authors: Benedetter‐Herramhof Andrea 
Published: February 2003

AbstractWie nur wenige andere verstand es der amerikanische Paläontologe Stephen Jay Gould, seine Leserschaft für die Evolutionsforschung zu begeistern. In Fachkreisen waren seine unkonventionellen Ansätze und Interpretationen nicht unumstritten: Während er für seine Anhänger der maßgebliche Verfechter der modernen Evolutionstheorie war, wurde er für seine Gegner zur Zielscheibe heftiger Kritik. Doch ungeachtet dessen, ob man Goulds neuen Entwürfen der Evolutionstheorie in allem folgen mag oder nicht, werden seine Ideen die Forschung noch für Jahre und Jahrzehnte bereichern.
Maus‐Genom entziffert
Authors: Zimmer Andreas 
Published: February 2003

AbstractWie viele Gene braucht eine Maus? Der Beantwortung dieser Frage, ein zentrales Anliegen der molekularen Genetik und der Genomprojekte, sind wir nun mit der gleichzeitigen Sequenzierung des Mausgenoms durch das International Mouse Genome Sequencing Consortium und des Transkriptoms durch das internationale FANTOM (Functional Annotation of the Mouse) Consortium ein ganzes Stück näher gekommen. Zum ersten Mal verfügen wir damit über die genomische Sequenz eines Säugetiers und die experimentell abgesicherte Analyse der darin kodierten Transkripte.
Fossiler Gleitflieger mit vier Flügeln
Authors: Kronberg Inge 
Published: February 2003

AbstractEs ist unstrittig, dass die Vögel Nachkommen der Dinosaurier sind. Innerhalb der Dinosaurier sind die Dromaeosaurier wohl die engsten Vogelverwandten. Nach wie vor wird aber diskutiert, wie die Vögel den Luftraum erschlossen: Lösten sie sich flatternd vom Boden oder ließen sie sich gleitend von Bäumen fallen? Die Entdeckung eines Dinosaurierfossils mit vier Flügeln und langen Federn erregte daher Aufsehen.
Neue Fledermausarten in Europa
Authors: Kiefer Andreas , Seitz Alfred , Veith Michael 
Published: February 2003

AbstractMolekulare Methoden haben in den vergangenen Jahren die Biologie verändert. Ob in der Physiologie, Ethologie, Ökologie oder Systematik — überall haben insbesondere die Techniken der Polymerase‐Kettenreaktion (PCR) und die automatisierte DNA‐Sequenzierung zu revolutionären Fortschritten geführt. Als direkte Folge dieser technischen Revolution nimmt die Zahl der bekannten Tier‐ und Pflanzenarten selbst in einem gut untersuchten Raum wie Europa rapide zu.Sogar innerhalb der europäischen Säugetiere wurden mittels molekularer Verfahren bislang unerkannt gebliebene, so genannte kryptische Arten entdeckt wie beispielsweise die Langohrfledermäuse Plecotus alpinus und Plecotus sardus.
Partnerwahl mit Schalleffekt
Authors: Wendler Silke 
Published: February 2003

AbstractIm Flachlandregenwald von Borneo lebt der etwa 2, 5 Zentimeter große Frosch Metaphrynella sundana. Zur Paarungszeit versuchen die Männchen, durch nächtliche Rufe die Weibchen auf sich aufmerksam zu machen — und schrecken dabei auch vor technischen Tricks nicht zurück.
Folgen des Klimawandels
Authors: Irsch Wilhelm 
Published: February 2003

AbstractEine Gruppe von US‐amerikanischen Wissenschaftlern hat durch Auswertung von Langzeitstudien ein weiteres Mosaiksteinchen zu dem sich langsam abzeichnenden Bild von den Auswirkungen einer globalen Erderwärmung hinzugefügt.
Transportproteine für Bor identifiziert
Authors: Brennicke Axel 
Published: February 2003

AbstractÜber das Element Bor macht man sich normalerweise keine Gedanken, obwohl es lebensnotwendig ist. Bewussten Kontakt mit Bor haben wir höchstens in Form von „Borwasser”︁ zur Augenspülung. Wenn aber nicht genügend Bor im Boden verfügbar ist, wachsen Pflanzen nicht richtig und kümmern vor sich hin. Jetzt gelang es einer japanischen Arbeitsgruppe zum ersten Mal, die Moleküle in Pflanzen zu identifizieren, die das Element Bor transportieren und seine Konzentration regulieren. Ähnliche Moleküle sind in den menschlichen Nieren am Transport von Carbonat beteiligt.
Das Trauma‐Gedächtnis: Biologie der Angst
Authors: Rüegg Johann Caspar 
Published: February 2003

AbstractOpfer von schweren Verkehrsunfällen und anderen lebensbedrohlichen Ereignissen bekommen oft noch Wochen oder Monate nach dem Trauma posttraumatische Belastungsstörungen. Sie reagieren dann beispielsweise mit Angst und Panik, wenn sie — etwa beim Quietschen von Autoreifen — wieder an das traumatische Geschehen erinnert werden, das im Traumagedächtnis gespeichert ist. Experimente an furchtkonditionierten Ratten haben jetzt aufgedeckt, welche biochemischen und neurophysiologischen Vorgänge beim Erwerb eines solchen Gedächtnisses für Angst ablaufen können: Konditionierte Reaktionen der Furcht entstehen letztlich dadurch, dass traumatische Erfahrungen (durch Lernprozesse) die Genexpression bestimmter neuronaler Proteine und damit die Struktur neuronaler Netzwerke des Gehirns (vor allem in der Amygdala) krankmachend verändern und damit eine Spur im Traumagedächtnis hinterlassen.