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Mate choice in many species is sensitive to social cues from neighboring individuals; for example, animals can copy mate choice decisions. If males copy other males’ choices, sperm of two or more males can compete for fertilization of the female’s ova. In the internally fertilizing fish Poecilia mexicana, males respond to the presence of rivals with reduced expression of mating preferences (audience effect), thereby lowering the risk of by-standing rivals copying their mate choice. Also, males interact initially more with a non-preferred female when observed by a rival, which has been interpreted in previous studies as a strategy to mislead rivals, again reducing sperm competition risk (SCR). Using a comparative approach, we tested the hypothesis that SCR is indeed a driving force explaining the occurrence of audience-induced changes in poeciliid male mate choice behavior. If this were true, then males of species with higher overall sexual activity — and, thus, higher potential for multiple mating — should show stronger audience effects. We investigated ten poeciliid species (in two cases including multiple populations) and found support for our hypothesis as mean sexual activity correlated positively with the occurrence of potentially deceptive behavior. An alternative explanation for audience effects would be that males attempt to avoid aggressive encounters, which would predict stronger audience effects in more aggressive species, and so we also characterized the examined species for aggressiveness using staged contests of size-matched males. We demonstrate a positive correlation between mean aggressiveness and sexual activity (suggesting a hormonal link as a mechanistic explanation), but we detected no correlation between aggressiveness and audience effects. Suites of correlated behavioral tendencies are termed behavioral syndromes, and our present study provides correlational evidence for the evolutionary significance of SCR in shaping a behavioral syndrome at the species level across poeciliid taxa.
Male reproductive biology can by characterized through competition over mates as well as mate choice. Multiple mating and male mate choice copying, especially in internally fertilizing species, set the stage for increased sperm competition, i.e., sperm of two or more males can compete for fertilization of the female’s ova. In the internally fertilizing fish Poecilia mexicana, males respond to the presence of rivals with reduced expression of mating preferences (audience effect), thereby lowering the risk of by-standing rivals copying their mate choice. Also, males interact initially more with a non-preferred female when observed by a rival, which has been interpreted in previous studies as a strategy to mislead rivals, again reducing sperm competition risk (SCR). Nevertheless, species might differ consistently in their expression of aggressive and reproductive behaviors, possibly due to varying levels of SCR. In the current study, we present a unique data set comprising ten poeciliid species (in two cases including multiple populations) and ask whether species can be characterized through consistent differences in the expression of aggression, sexual activity and changes in mate choice under increased SCR. We found consistent species-specific differences in aggressive behavior, sexual activity as well as in the level of misleading behavior, while decreased preference expression under increased SCR was a general feature of all but one species examined. Furthermore, mean sexual activity correlated positively with the occurrence of potentially misleading behavior. An alternative explanation for audience effects would be that males attempt to avoid aggressive encounters, which would predict stronger audience effects in more aggressive species. We demonstrate a positive correlation between mean aggressiveness and sexual activity (suggesting a hormonal link as a mechanistic explanation), but did not detect a correlation between aggressiveness and audience effects. Suites of correlated behavioral tendencies are termed behavioral syndromes, and our present study provides correlational evidence for the evolutionary significance of SCR in shaping a behavioral syndrome at the species level across poeciliid taxa.
Background: The underlying axiom in applying generic drugs is the equivalence of their active ingredient with the (usually more expensive) innovator product, an all-embracing statement with the insidious result that physicians assume that the generic products have been subjected to the same rigorous testing regimens as the brand-name products. The present paper presents novel experimental data on an investigator-blinded comparison between the innovator imipenem antibiotic, and a number of its generics.
Methods: Particulate matter contamination of each group was visualized by means of a membrane filter method. Functional studies in an animal model–the dorsal skinfold chamber technique in mice-designed to simulate the state of microcirculatory dysfunction in intensive care patients was performed, in order to assess the influence of the particulate matter of each group on the functional capillary density of the striated skin muscle, after their intravenous injection.
Results: The results showed massive particulate contamination of the generics, in a size range relevant for impacting the microcirculation. The particulate contamination contributed in some generic groups to a significant shutdown of tissue perfusion.
Conclusion: The presented data underscore the need to raise the regulatory barriers for the entry of generics to the market, well beyond the simplistic proof of “bioequivalence”, which in no measure deals with the essential questions of quality and patient safety. If generics are used, they should be tested by a filter technique and optical microscopy, to ensure the absence especially of small particulate contaminants and their purity.
Sustained HIV suppression depends on a number of factors including therapy adherence, management of side effects, viral resistance and individual characteristics of patients and therapeutic settings. Treatment response rates range up to 90% in therapy naïve patients but decline to approximately 50% in patients who received several antiretrovirals during treatment history. Furthermore, HIV protease inhibitors (PI) and non nucleoside reverse transcriptase inhibitors (NNRTI) plasma concentrations display high inter- and intra individual variability and the therapeutic window is comparably narrow. In this therapeutic setting the personalization of dosing regimens has been suggested in many cases to tailor the ARV plasma concentrations with the intention to maximize therapy success and minimize side effects in the individual. However, personalizing therapy by modifying the dosing regimen bears the danger of losing therapeutic efficacy, increasing side effects or causing viral resistance.
This topical review identifies pharmacokinetic and pharmacodynamic models of antiretroviral therapy appraising the potential application to HIV therapy and discusses its future in the light of new drug classes and fix-dose combinations.
Gene homologs of GlnK PII regulators and AmtB-type ammonium transporters are often paired on prokaryotic genomes, suggesting these proteins share an ancient functional relationship. Here, we demonstrate for the first time in Archaea that GlnK associates with AmtB in membrane fractions after ammonium shock, thus, providing a further insight into GlnK-AmtB as an ancient nitrogen sensor pair. For this work, Haloferax mediterranei was advanced for study through the generation of a pyrE2-based counterselection system that was used for targeted gene deletion and expression of Flag-tagged proteins from their native promoters. AmtB1-Flag was detected in membrane fractions of cells grown on nitrate and was found to coimmunoprecipitate with GlnK after ammonium shock. Thus, in analogy to bacteria, the archaeal GlnK PII may block the AmtB1 ammonium transporter under nitrogen-rich conditions. In addition to this regulated protein–protein interaction, the archaeal amtB-glnK gene pairs were found to be highly regulated by nitrogen availability with transcript levels high under conditions of nitrogen limitation and low during nitrogen excess. While transcript levels of glnK-amtB are similarly regulated by nitrogen availability in bacteria, transcriptional regulators of the bacterial glnK promoter including activation by the two-component signal transduction proteins NtrC (GlnG, NRI) and NtrB (GlnL, NRII) and sigma factor σN (σ54) are not conserved in archaea suggesting a novel mechanism of transcriptional control.
Diese Arbeit entstand im Rahmen eines größeren Forschungsprojektes zum Thema Bewältigung von Lebensenttäuschungen, initiiert von Prof. Dr. Siegfried Preiser am Institut für Psychologie der Universität Frankfurt am Main. In diesem Kontext wurde die vorliegende Studie entwickelt.
Ausgehend von interpersonalem Engagement wurden mögliche Verknüpfungen von Einflussfaktoren im Umgang mit unterschiedlichen kritischen Lebenssituationen und der sich daraus ergebenden Konsequenzen auf psychische und physische Gesundheit, d.h. persönliches Wohlbefinden untersucht. Das Konstrukt Wohlbefinden wurde in dieser Studie als eine latente Variable gebildet, die sich aus einer Konstellation von bereichsspezifischen und allgemeinen Lebenszufriedenheitsfaktoren, dem seelischen Gesundheitsempfinden und – mit negativem Gewicht - dem aktuellen Belastungsempfinden zusammensetzt.
Außer der Erfassung der Partizipation an sozialen Gemeinschaften bzw. des sozialen Engagements wurden intrapsychische, motivationale, biographische und soziale Faktoren erfasst sowie religiöse Aspekte einbezogen. Zielgruppen der Untersuchung waren Gruppierungen vorwiegend aus dem Selbsthilfebereich.
Zur Beachtung der Zeitperspektive war die Befragung als Längsschnittstudie in Form einer Zweifachmessung konzipiert.
Erhoben und untersucht wurden im einzelnen Belastungs-, Persönlichkeits-, Gesundheits- und Zufriedenheitsfaktoren, des Weiteren die Aspekte des sozialen Kontextes mit Differenzierung der Ebenen von sozialer Unterstützung sowie religiöse Aspekte als angenommene Einflussfaktoren auf Lebenszufriedenheit und persönliches Wohlbefinden.
Zusammenfassend hatten die Persönlichkeitsfaktoren Flexibilität und Selbstwirksamkeit den größten positiven Einfluss auf Wohlbefinden. Bzgl. des sozialen Engagements zeigte sich dagegen kein signifikanter Einfluss.
Neben den Variablen Flexibilität und Selbstwirksamkeit stellte sich die wahrgenommene Unterstützung als bedeutsamster Einflussfaktor auf das Wohlbefinden heraus.
Religiöse Vorstellungen konnten nach ihrer persönlichen positiven oder negativen Grundhaltung gegenüber Gott bzw. einer höheren Wirklichkeit differenziert werden. Eine positive religiöse Grundhaltung ist geprägt von der Vorstellung eines schützenden, fürsorglichen und hilfreichen Gottes. Ein negatives Gottesbild beinhaltet die Vorstellung eines bedrohlichen und strafenden Gottes. Nur für diese Betrachtungsweise konnten eindeutige - und zwar negative - Einflüsse auf das Wohlbefinden ermittelt werden
Inhaltlich gliedert sich die Arbeit in vier Blöcke:
In Kapitel 1 werden theoretische Grundlagen und untersuchungsrelevante Konzepte näher erläutert und daraus die konkreten Fragestellungen einschließlich der Hypothesen entwickelt.
In Kapitel 2 schließt sich der methodische Teil mit den Beschreibungen der Stichprobe, der Erhebungsinstrumente und des Untersuchungsverlaufes an.
Kapitel 3 enthält die Ergebnisse und deren Diskussion. Kapitel 4 beinhaltet ein Resümee und Ausblick. In Kapitel 5 befindet sich die für diese Arbeit verwendete Literatur, woran sich der Anhang anschließt. Der Anhang besteht zum einen aus weitergehenden Informationen und Erläuterungen, die Durchführung und Auswertung betreffend (Anhang I). Anhang II, der der Druckversion als CD beiliegt, listet zum anderen die Originalantworten der Probanden in strukturierter Form auf.
Transcription factors play a crucial role in regulating differentiation processes during human life and are important in disease. The basic helix-loop-helix transcription factors Tal1 and Lyl1 play a major role in the regulation of gene expression in the hematopoietic system and are involved in human leukemia. Tal2, which belongs to the same family of transcription factors as Tal1 and Lyl1, is also involved in human leukaemia. However, little is known regarding the expression and regulation of Tal2 in hematopoietic cells. Here we show that Tal2 is expressed in hematopoietic cells of the myeloid lineage. Interestingly, we found that usage of the Tal2 promoter is different in human and mouse cells. Two promoters, hP1 and hP2 drive Tal2 expression in human erythroleukemia K562 cells, however in mouse RAW cells only the mP1 promoter is used. Furthermore, we found that Tal2 expression is upregulated during oesteoclastogenesis. We show that Tal2 is a direct target gene of the myeloid transcription factor PU.1, which is a key transcription factor for osteoclast gene expression. Strikingly, PU.1 binding to the P1 promoter is conserved between mouse and human, but PU.1 binding to P2 was only detected in human K562 cells. Additionally, we provide evidence that Tal2 influences the expression of the osteoclastic differentiation gene TRACP. These findings provide novel insight into the expression control of Tal2 in hematopoietic cells and reveal a function of Tal2 as a regulator of gene expression during osteoclast differentiation.
Delayed wound repair in sepsis is associated with reduced local pro-inflammatory cytokine expression
(2013)
Sepsis is one of the main causes for morbidity and mortality in hospitalized patients. Moreover, sepsis associated complications involving impaired wound healing are common. Septic patients often require surgical interventions that in-turn may lead to further complications caused by impaired wound healing. We established a mouse model to the study delayed wound healing during sepsis distant to the septic focus point. For this reason cecal ligation and puncture (CLP) was combined with the creation of a superficial wound on the mouse ear. Control animals received the same procedure without CPL. Epithelialization was measured every second day by direct microscopic visualization up to complete closure of the wound. As interplay of TNF-α, TGF-β, matrix metalloproteinases (MMP), and tissue inhibitors of metalloproteinases (TIMP) is important in wound healing in general, TNF-α, TGF-β, MMP7, and TIMP1 were assessed immunohistochemical in samples of wounded ears harvested on days 2, 6, 10 and 16 after wounding. After induction of sepsis, animals showed a significant delay in wound epithelialization from day 2 to 12 compared to control animals. Complete wound healing was attained after mean 12.2± standard deviation (SD) 3.0 days in septic animals compared to 8.7± SD 1.7 days in the control group. Septic animals showed a significant reduction in local pro-inflammatory cytokine level of TNF-α on day 2 and day 6 as well as a reduced expression of TGF-β on day 2 in wounds. A significant lower expression of MMP7 as well as TIMP1 was also observed on day 2 after wounding. The induction of sepsis impairs wound healing distant to the septic focus point. We could demonstrate that expression of important cytokines for wound repair is deregulated after induction of sepsis. Thus restoring normal cytokine response locally in wounds could be a good strategy to enhance wound repair in sepsis.
Als Exilfilme im engeren Sinne werden Filme bezeichnet, die in den Jahren 1933 bis 1945 überwiegend von exilierten deutschen Filmschaffenden im jeweiligen Fluchtland produziert wurden, wobei nur in wenigen dieser Exilfilme das Exil selbst zum Gegenstand wird. Anlässlich einer Filmreihe, die die Walter A. Berendsohn Forschungsstelle für deutsche Exilliteratur zusammen mit dem Research Center for Media and Communication (Universität Hamburg) und der Hamburger Kinemathek e.V. veranstaltete, wurde im Januar 2013 eine kleine Auswahl von Exilfilmen (aus Hollywood) im Metropolis Kino gezeigt. [...] Das Heft versammelt mit den Artikeln von Matthias Koch zu "Casablanca" und Sebastian Schirrmeister zu "So Ends Our Night" einige der kontextualisierenden Einführungen, die anlässlich der Filmreihe im Metropolis Kino vor der Vorführung des jeweiligen Films gegeben wurden. Die Beiträge von Andreas Stuhlmann zu "Hitler’s Madman", von Christoph Hesse zu "Professor Mamlock" und von Alexander Zons über den Hollywood-Agenten Paul Kohner sind Ergebnisse eines sich an die Filmreihe anschließenden Workshops. Ziel der Veranstaltung war es, gemeinsam mit den teilnehmenden Wissenschaftlerinnen und Wissenschaftlern, mit Mitgliedern der Kinemathek, Studierenden und Filminteressierten Exilfilm und Filmexil als Forschungsfelder zu sondieren, um dann an Filmbeispielen verschiedene Zugänge zum Exilfilm bzw. unterschiedliche Analysekategorien zu erproben.