bluuebunny/crossref_metadata_2025_split huggingface dataset:
IFN-γ–Dependent Activation of Macrophages during Experimental Infections by Mycobacterium ulcerans Is Impaired by the Toxin Mycolactone
Authors: Torrado Egídio , Fraga Alexandra G. , Logarinho Elsa , Martins Teresa G. , Carmona Jenny A. , Gama José B. , Carvalho Maria A. , Proença Fernanda , Castro Antonio G. , Pedrosa Jorge 
Published: December 2009

Abstract
Buruli ulcer, caused by Mycobacterium ulcerans infections, is a necrotizing skin disease whose pathogenesis is associated with the exotoxin mycolactone. Despite the relevance of this emergent disease, little is known on the immune response against the pathogen. Following the recent demonstration of an intramacrophage growth phase for M. ulcerans, we investigated the biological relevance of IFN-γ and the antimycobacterial mechanisms activated by this cytokine in M. ulcerans-infected macrophages. Three M. ulcerans strains were tested: 5114 (mutant mycolactone-negative, avirulent strain); 94–1327 (intermediate virulence); and 98–912 (high virulence). We show in this study that IFN-γ is expressed in mouse-infected tissues and that IFN-γ–deficient mice display increased susceptibility to infection with strains 5114 and, to a lesser extent, 94–1327, but not with the highly virulent strain. Accordingly, IFN-γ–activated cultured macrophages controlled the proliferation of the avirulent and the intermediate virulent strains. Addition of mycolactone purified from strain 98–912 to cultures of IFN-γ–activated macrophages infected with the mycolactone-negative strain led to a dose-dependent inhibition of the IFN-γ–induced protective mechanisms, involving phagosome maturation/acidification and increased NO production, therefore resulting in increased bacterial burdens. Our findings suggest that the protection mediated by IFN-γ in M. ulcerans-infected macrophages is impaired by the local buildup of mycolactone.
Vitamin D Decreases Respiratory Syncytial Virus Induction of NF-κB–Linked Chemokines and Cytokines in Airway Epithelium While Maintaining the Antiviral State
Authors: Hansdottir Sif , Monick Martha M. , Lovan Nina , Powers Linda , Gerke Alicia , Hunninghake Gary W. 
Published: December 2009

Abstract
Epidemiological studies suggest that low vitamin D levels may increase the risk or severity of respiratory viral infections. In this study, we examined the effect of vitamin D on respiratory syncytial virus (RSV)-infected human airway epithelial cells. Airway epithelium converts 25-hydroxyvitamin D3 (storage form) to 1,25-dihydroxyvitamin D3 (active form). Active vitamin D, generated locally in tissues, is important for the nonskeletal actions of vitamin D, including its effects on immune responses. We found that vitamin D induces IκBα, an NF-κB inhibitor, in airway epithelium and decreases RSV induction of NF-κB–driven genes such as IFN-β and CXCL10. We also found that exposing airway epithelial cells to vitamin D reduced induction of IFN-stimulated proteins with important antiviral activity (e.g., myxovirus resistance A and IFN-stimulated protein of 15 kDa). In contrast to RSV-induced gene expression, vitamin D had no effect on IFN signaling, and isolated IFN induced gene expression. Inhibiting NF-κB with an adenovirus vector that expressed a nondegradable form of IκBα mimicked the effects of vitamin D. When the vitamin D receptor was silenced with small interfering RNA, the vitamin D effects were abolished. Most importantly we found that, despite inducing IκBα and dampening chemokines and IFN-β, there was no increase in viral mRNA or protein or in viral replication. We conclude that vitamin D decreases the inflammatory response to viral infections in airway epithelium without jeopardizing viral clearance. This suggests that adequate vitamin D levels would contribute to reduced inflammation and less severe disease in RSV-infected individuals.
Glycogen Synthase Kinase 3β Activation Is a Prerequisite Signal for Cytokine Production and Chemotaxis in Human Mast Cells
Authors: Rådinger Madeleine , Kuehn Hye Sun , Kim Mi-Sun , Metcalfe Dean D. , Gilfillan Alasdair M. 
Published: December 2009

Abstract
In addition to regulating mast cell homeostasis, the activation of KIT following ligation by stem cell factor promotes a diversity of mast cell responses, including cytokine production and chemotaxis. Although we have previously defined a role for the mammalian target of rapamycin complex 1 in these responses, it is clear that other signals are also required for maximal KIT-dependent cytokine production and chemotaxis. In this study, we provide evidence to support a role for glycogen synthase kinase 3β (GSK3β) in such regulation in human mast cells (HuMCs). GSK3β was observed to be constitutively activated in HuMCs. This activity was inhibited by knockdown of GSK3β protein following transduction of these cells with GSK3β-targeted shRNA. This resulted in a marked attenuation in the ability of KIT to promote chemotaxis and, in synergy with FcεRI-mediated signaling, cytokine production. GSK3β regulated KIT-dependent mast cell responses independently of mammalian target of rapamycin. However, evidence from the knockdown studies suggested that GSK3β was required for activation of the MAPKs, p38, and JNK and downstream phosphorylation of the transcription factors, Jun and activating transcription factor 2, in addition to activation of the transcription factor NF-κB. These studies provide evidence for a novel prerequisite priming mechanism for KIT-dependent responses regulated by GSK3β in HuMCs.
DNAM-1/CD155 Interactions Promote Cytokine and NK Cell-Mediated Suppression of Poorly Immunogenic Melanoma Metastases
Authors: Chan Christopher J. , Andrews Daniel M. , McLaughlin Nicole M. , Yagita Hideo , Gilfillan Susan , Colonna Marco , Smyth Mark J. 
Published: December 2009

Abstract
A role for NK cells in therapeutic intervention for hematologic malignancies, such as acute myeloid leukemia and multiple myeloma, and nonhematologic malignancies, such as melanoma, is becoming more apparent. DNAM-1 is an NK cell receptor whose importance in facilitating activation signals received by NK cells in natural and cytokine-driven responses to tumor metastases in vivo is poorly explored. In this study, we used matched tumor lines expressing a variety of relevant ligands, neutralizing monoclonal Abs, and DNAM-1 gene-targeted mice to determine the relative importance of DNAM-1–ligand interactions in controlling tumor metastases. Our results demonstrate that NK cells require DNAM-1 for natural or cytokine (IL-2, IL-12, or IL-21) suppression of tumor metastases or their variants expressing CD70 or CD80. In contrast, DNAM-1 was dispensable when tumor cells were targets of Ab-dependent cellular cytotoxicity or presented ligands for NKG2D. CD155 appeared to be a key ligand recognized by DNAM-1 in NK cell-mediated suppression of metastases, and DNAM-1-mediated suppression coincided with perforin activity. Overall, these data implied a general role for DNAM-1-CD155 interactions in NK cell-mediated killing of tumors, even in the presence of tumor CD70 or CD80 expression, and further defined the optimal efficacy requirements of cytokines that directly activate NK cells.
Morphometric analysis and classification of the facial phenotype associated with fetal alcohol syndrome in 5‐ and 12‐year‐old children
Authors: Mutsvangwa Tinashe E.M. , Meintjes Ernesta M. , Viljoen Dennis L. , Douglas Tania S. 
Published: December 2009

AbstractLandmark‐based morphometric analysis holds promise for quantitative assessment of craniofacial dysmorphology. We describe an application of facial shape analysis to characterize the facial anomalies associated with fetal alcohol syndrome (FAS) in a mixed ancestry population. Generalized Procrustes analysis, regression and discriminant function analysis were applied to stereo‐photogrammetrically derived 3D coordinates of landmarks taken from 34 subjects (n = 17 FAS and n = 17 normal controls). Four shape analyses were carried out, namely a comparison of the FAS and control facial shapes at age 5, and one at age 12; a comparison of the FAS facial shapes at ages 5 and 12; and a comparison of control facial shapes at ages 5 and 12. The first two analyses showed that the FAS face is characterized by small palpebral fissures, a thin upper lip, and midfacial hypoplasia. Classification of subjects as having FAS using leave‐one‐out cross‐validation showed that the 5‐year‐old group could be classified with 95.46% accuracy and the 12‐year‐olds with 80.13% accuracy. The third and fourth analyses revealed that the differences in facial shape between FAS individuals in different age groups were more pronounced than for control individuals, supporting the notion that FAS facial anomalies diminish with age. Geometric morphometric analysis of stereo‐photogrammetrically derived 3D facial landmarks allows visualization of the facial anomalies associated with FAS, as well as classification of facial shapes. © 2009 Wiley‐Liss, Inc.
Proceedings from the 2009 genetic syndromes of the Ras/MAPK pathway: From bedside to bench and back
Authors: Rauen Katherine A. , Schoyer Lisa , McCormick Frank , Lin Angela E. , Allanson Judith E. , Stevenson David A. , Gripp Karen W. , Neri Giovanni , Carey John C. , Legius Eric , Tartaglia Marco , Schubbert Suzanne , Roberts Amy E. , Gelb Bruce D. , Shannon Kevin , Gutmann David H. , McMahon Martin , Guerra Carmen , Fagin James A. , Yu Benjamin , Aoki Yoko , Neel Benjamin G. , Balmain Allan , Drake Richard R. , Nolan Garry P. , Zenker Martin , Bollag Gideon , Sebolt‐Leopold Judith , Gibbs Jackson B. , Silva Alcino J. , Patton E. Elizabeth , Viskochil David H. , Kieran Mark W. , Korf Bruce R. , Hagerman Randi J. , Packer Roger J. , Melese Teri 
Published: December 2009

AbstractThe RASopathies are a group of genetic syndromes caused by germline mutations in genes that encode components of the Ras/mitogen‐activated protein kinase (MAPK) pathway. Some of these syndromes are neurofibromatosis type 1, Noonan syndrome, Costello syndrome, cardio‐facio‐cutaneous syndrome, LEOPARD syndrome and Legius syndrome. Their common underlying pathogenetic mechanism brings about significant overlap in phenotypic features and includes craniofacial dysmorphology, cardiac, cutaneous, musculoskeletal, GI and ocular abnormalities, and a predisposition to cancer. The proceedings from the symposium “Genetic Syndromes of the Ras/MAPK Pathway: From Bedside to Bench and Back” chronicle the timely and typical research symposium which brought together clinicians, basic scientists, physician‐scientists, advocate leaders, trainees, students and individuals with Ras syndromes and their families. The goals, to discuss basic science and clinical issues, to set forth a solid framework for future research, to direct translational applications towards therapy and to set forth best practices for individuals with RASopathies were successfully meet with a commitment to begin to move towards clinical trials. © 2009 Wiley‐Liss, Inc.
Chemoselektivität und die eigentümlichen Reaktivitäten funktioneller Gruppen
Authors: Afagh Nicholas A. , Yudin Andrei K. 
Published: December 2009

AbstractMangelnde Chemoselektivität ist ein klassisches Problem der chemischen Synthese, und die Suche nach den richtigen Bedingungen, die unter oftmals vielfältigen Reaktionswegen den richtigen Mechanismus selektieren können, kennt jeder Praktiker als ein mühsames Unterfangen. Wir diskutieren in diesem Aufsatz verschiedene Aspekte der Chemoselektivität, die in den letzten rund zehn Jahren im Zusammenhang mit der Entwicklung diverser Synthesemethoden thematisiert worden sind. Unser Hauptaugenmerk gilt den Reaktionsmechanismen der zur Diskussion stehenden Prozesse, mit dem Versuch, diese zu kategorisieren und die Schlüsselkonzepte zu beleuchten, die aus diesen Studien hervorgegangen sind. Unsere Übersicht wird zeigen, dass erhebliche Fortschritte erzielt wurden, gleichzeitig aber noch große Herausforderungen vor uns liegen.
Relative clinical utility of three child symptom inventory‐4 scoring algorithms for differentiating children with autism spectrum disorder vs. attention‐deficit hyperactivity disorder
Authors: DeVincent Carla J. , Gadow Kenneth D. 
Published: December 2009

AbstractObjective: The present study compared three separate Child Symptom Inventory‐4 (CSI‐4) scoring algorithms for differentiating children with autism spectrum disorder (ASD) from youngsters with attention‐deficit/hyperactivity disorder (ADHD). Method: Parents/teachers completed the CSI‐4, a DSM‐IV‐referenced rating scale, for 6 to 12‐year‐old clinical referrals with ASD (N=186) and ADHD (N=251). Algorithms were based on either all CSI‐4 items (forward logistic regressions) or the 12 DSM‐IV symptoms of pervasive developmental disorder (PDD) included in the CSI‐4. Results: ROC analyses indicated generally good to excellent values for area under the curve, sensitivity, specificity, and positive predictive power. Algorithms for parent ratings were superior to teacher ratings. The algorithm based solely on PDD symptoms evidenced the greatest generalizability. Conclusion: Although algorithms generated from regression analyses produced greater clinical utility for specific samples, the PDD‐based algorithm resulted in greater stability across samples.
Dimensionierung von maschinellen Tunnelvortrieben mit Tübbingausbau im Fels
Authors: Schmitt Jürgen , Stahlmann Joachim 
Published: December 2009

AbstractIn diesem Aufsatz werden auf theoretischer Grundlage abgeleitete Berechnungsansätze vorgestellt, durch die es möglich ist, das Risiko der Verklemmung des Schildmantels bei einer Tunnelbohrmaschine mit Schild (TBM‐S) beurteilen und die Größe des erforderlichen planmäßigen Überschnitts bemessen zu können. Ebenso werden analytische Berechnungsansätze für den Gebirgsdruck aufgeführt, die zu einer wirtschaftlicheren Dimensionierung der Tübbingsicherung für die zuvor genannte Vortriebsart beitragen können.Dimensioning of shield tunnelling with segment lining in hard rock. In the available essay formulations based on theoretical elaborations are introduced, by which it is possible to estimate the risk of blocking of the shield skin of tunnel boring machine with shield (TBM‐S) and the size of the necessary regular overcut can calculated. Likewise analytic formulations for the ground pressure are specified, with which it is possible to design an economic segment lining for the kind of driving specified before.
Tragverhalten von horizontal belasteten Flügelpfählen
Authors: Dührkop Jan , Grabe Jürgen 
Published: December 2009

AbstractZur Verbesserung des horizontalen Last‐Verformungsverhaltens von Pfählen ist der Einsatz von Flügeln zur Aufweitung des Pfahlschafts im Pfahlkopfbereich eine sinnvolle Maßnahme. Der Bettungswiderstand wird im aufgeweiteten Bereich erhöht und die Verformung reduziert. In diesem Beitrag werden numerische Untersuchungen zur Verbesserung der Tragwirkung vorgestellt und ein Berechnungskonzept abgeleitet. Des Weiteren werden Feldversuche in Sand und Klei beschrieben, bei denen die Tragwirkung des Flügelpfahls messtechnisch dokumentiert wird. Es werden zudem Bemessungsdiagramme für Flügelpfähle in Sand vorgelegt.On the response of laterally loaded piles with wings. The use of wings attached to the pile shaft near ground surface is a simple but effective way to improve the lateral pile response. The mobilised soil resistance in this section is significantly higher and the lateral deformation decreases. This paper presents numerical analysis of winged piles and a design method is outlined. Small‐scale field trials in sand and organic clay clearly point out the benefit of winged piles and proved the validity of the design method. Furthermore, design charts for a pre‐design of winged piles in sand are included.
Ein Modell zur Abschätzung der Tausetzung und der Kompressionseigenschaften aufgetauter Böden
Authors: Unold Florian 
Published: December 2009

AbstractEs wird ein Berechnungsmodell zur quantitativen Bestimmung der Netto‐Tausetzung sowie der Druck‐Porenzahl‐Beziehung bei Weiterbelastung nach dem Auftauen feinkörniger Böden vorgestellt. Der Ansatz berücksichtigt die Inhomogenität der Veränderung des Bodengefüges infolge der Vereisung. Hierbei wird der Boden vereinfachend in zwei Bereiche unterteilt. Nach dem Modell wird ein Teil des Bodens mit einer rechnerischen Auflast, die der Summe der komprimierenden Vorgänge während der Bodenvereisung äquivalent ist, verdichtet. Für den übrigen Teil wird angenommen, dass er von der Vereisung unbeeinflusst bleibt. Die mit Hilfe des Modells ermittelten Berechnungsergebnisse stehen in sehr guter Übereinstimmung mit den Versuchsergebnissen. Der große Vorteil des Berechnungsansatzes liegt darin, dass eine zuverlässige Prognose der Kompressionseigenschaften des aufgetauten Bodens allein mit den Ergebnissen von Standard‐Laborversuchen möglich ist.A model for the estimation of the thaw‐settlements and the compressibility properties of thawed soils. A mathematical model is presented which allows the quantitative calculation of the net thaw‐settlement as well as of the pressure‐void ratio relation at continued loading of fine grained soils after thawing. The approach takes into account the inhomogeneity of the change of the soil fabric caused by freezing. For this purpose, the soil is being divided into two parts, which is a simplification of the real situation. In the model, one part of the soil is being compacted with a load that is equivalent to the sum of all compressing processes during ground freezing. For the rest of the soil, it is assumed that it remains unaffected by freezing. The calculation results obtained by the model show good agreement with the results of laboratory tests. The great advantage of the introduced approach is that the compression properties of thawed soil can be reliably predicted just based on the results of standard laboratory tests.
Zum Erddruck auf Lawinenschutzgalerien
Authors: Kolymbas Dimitrios , Kirsch Ansgar 
Published: December 2009

AbstractEine Fehleinschätzung des Erddrucks auf überschüttete Galerien kann zu Schadensfällen führen. Im vorliegenden Beitrag wird ein analytischer Ansatz zur Prognose des Erddrucks auf Galerien vorgestellt. Grundlegende Annahme ist dabei, dass sich die Böschung aus kohäsionslosem Boden, in der sich die Galerie befindet, in einem Rankine'schen Spannungszustand befindet. Unter der weiteren Annahme einer reibungsfreien Kontaktfuge zwischen Galerie und Boden ergibt sich eine ausgeprägte Spitze in der Erddruckverteilung. Die Ausprägung der prognostizierten Spitze der Erddruckverteilung kann mit Finite‐Element‐Berechnungen nachvollzogen werden.On the earth pressure on avalanche protection galleries. Structural damage of avalanche protection galleries is often attributed to misjudgement of the prevailing earth pressure. In this paper we present an analytical expression for the prediction of the earth pressure on avalanche protection galleries. The main assumption is that the soil surrounding the gallery is in a Rankine stress state. Under further assumption of a frictionless contact between soil and gallery, a distinct peak in the contact pressure on the gallery can be predicted. These findings are supported by a numerical parametric study with finite elements.
Einheit von Wissenschaft und Kunst im Brückenbau: Hellmut Homberg (1909–1990) – Sein Beitrag zur Theorie des Brückenbaus (Teil II)
Authors: Kurrer Karl‐Eugen , Pelke Eberhard , Stiglat Klaus 
Published: December 2009

AbstractAus dem baustatischen ŒuvreHombergs ragt sein Beitrag zur Theorie hochgradig statisch unbestimmter Trägerroste hervor, der im Folgenden im Zusammenhang mit der Entwicklung im Brückenbau und der Baustatik von den 1930‐er bis in die 1960‐er Jahre herausgearbeitet wird.Harmony between science and art in bridge‐building: Hellmut Homberg (1909–1990) – his contribution to the theory of bridges (part II).The one theory of Hellmut Homberg that stands out from the rest of his contributions to the theory of structures is that concerning grillages with a high degree of static indeterminacy. This is described below in conjunction with the development of bridge‐building and theory of structures from the 1930s to the 1960s.
Geschichte und Evolution der Lactose(in)toleranz. Das Erbe der frühen Viehzüchter
Authors: Höffeler Fritz 
Published: December 2009

AbstractDie Fähigkeit, auch im Erwachsenenalter noch Lactose verarbeiten zu können, basiert auf Punktmutationen in einem dem Lactase‐(LPH‐)Gen vorgelagerten Sequenzbereich, der Bindestellen für Regulatorproteine enthält. Die Ursache für die weltweit sehr uneinheitliche Verteilung der Lactase‐Persistenz liegt in der europäischen Menschheitsgeschichte: Im Verlauf des 8. vorchristlichen Jahrtausends entwickelte sich im Nahen Osten innerhalb einer größtenteils lactoseintoleranten Population eine Tradition der Milchviehzucht und des Milchverzehrs. Durch den starken Selektionsdruck auf die Lactosetoleranz verbreiteten sich die mutierten Allele sehr schnell. Während des 7. Jahrtausends v. Chr. begannen etliche dieser Populationen sukzessiv Europa zu besiedeln. Auch im nordöstlichen Afrika und auf der arabischen Halbinsel entstand eine Milchwirtschaft, die jedoch auf anderen Mutationen basiert.
Telomere: Ende gut, alles gut
Authors: Zacharias Helmut , Kronberg Inge 
Published: December 2009

AbstractDie Verleihung des Nobelpreises in Physiologie oder Medizin an Elizabeth H. Blackburn, Jack W. Szostak und Carol W. Greider am 10. Dezember 2009 in Stockholm war nicht das Ende, sondern der Höhepunkt eines märchenhaften Verlaufes der Telomer‐ und Telomeraseforschung. Die Aufklärung von Bau und Synthese der Telomere hat in den vergangenen Jahrzehnten wesentliche Impulse für Krebs‐, Stammzell‐ und Seneszenzforschung geliefert.
Springspinne Bagheera kiplingi: Vegetarier auf acht Beinen
Authors: Wendler Silke 
Published: December 2009

AbstractDie Forschergruppe um Christopher J. Meehan staunte nicht schlecht, als sie in Mexiko und Costa Rica eine Spinnenart entdeckten, die sich überwiegend vegetarisch ernährt. Die zu den Springspinnen gehörende Art Bagheera kiplingi “erbeutet” lieber Futterkörperchen von Akazienblättern, als Insekten nachzustellen.
Zur Einführung biowissenschaftlicher Bachelor‐ und Masterstudiengänge
Authors: Volke Beate , Gropengießer Harald 
Published: December 2009

AbstractWelche Folgen hat die Umstellung der Studiengänge auf das Bachelor‐/Master‐System für das Biologiestudium? Antworten darauf gibt eine Umfrage der Universität Hannover: Im Sommersemester 2008 wurden die Studiendekane beziehungsweise die Studiengangskoordinatoren an 53 deutschen Hochschulen, an denen biowissenschaftliche Studiengänge angeboten werden, schriftlich befragt. Der Fragebogen enthielt Fragen mit Antwortvorgaben, mit halboffener und offener Beantwortung. Eine Rücklaufquote von nahezu 76 % verspricht einen verlässlichen Eindruck der Lage in den biowissenschaftlichen Studiengängen.
Nachrichten des Verbandes Biologie, Biowissenschaften & Biomedizin in Deutschland
Authors: Tautz Diethard 
Published: December 2009

AbstractAus den FachgesellschaftenNachgefragt: Deutsche Botanische GesellschaftAusbildung und KarriereVBIO verleiht BIOTECHNICA StudienpreisBilingualer Biologieunterricht im AufwindTaxonomen: Wo sind sie geblieben?