University of Marburg

About: University of Marburg is a education organization based out in Marburg, Germany. It is known for research contribution in the topics: Population & Virus. The organization has 23195 authors who have published 42907 publications receiving 1506069 citations. The organization is also known as: Philipps University of Marburg & Philipps-Universität.

The Ebola Virus VP35 Protein Inhibits Activation of Interferon Regulatory Factor 3

Abstract: The Ebola virus VP35 protein was previously found to act as an interferon (IFN) antagonist which could complement growth of influenza delNS1 virus, a mutant influenza virus lacking the influenza virus IFN antagonist protein, NS1. The Ebola virus VP35 could also prevent the virus- or double-stranded RNA-mediated transcriptional activation of both the beta IFN (IFN-β) promoter and the IFN-stimulated ISG54 promoter (C. Basler et al., Proc. Natl. Acad. Sci. USA 97:12289-12294, 2000). We now show that VP35 inhibits virus infection-induced transcriptional activation of IFN regulatory factor 3 (IRF-3)-responsive mammalian promoters and that VP35 does not block signaling from the IFN-α/β receptor. The ability of VP35 to inhibit this virus-induced transcription correlates with its ability to block activation of IRF-3, a cellular transcription factor of central importance in initiating the host cell IFN response. We demonstrate that VP35 blocks the Sendai virus-induced activation of two promoters which can be directly activated by IRF-3, namely, the ISG54 promoter and the ISG56 promoter. Further, expression of VP35 prevents the IRF-3-dependent activation of the IFN-α4 promoter in response to viral infection. The inhibition of IRF-3 appears to occur through an inhibition of IRF-3 phosphorylation. VP35 blocks virus-induced IRF-3 phosphorylation and subsequent IRF-3 dimerization and nuclear translocation. Consistent with these observations, Ebola virus infection of Vero cells activated neither transcription from the ISG54 promoter nor nuclear accumulation of IRF-3. These data suggest that in Ebola virus-infected cells, VP35 inhibits the induction of antiviral genes, including the IFN-β gene, by blocking IRF-3 activation.

Baseline Biomarkers for Outcome of Melanoma Patients Treated with Pembrolizumab.

Abstract: Purpose: Biomarkers for outcome after immune-checkpoint blockade are strongly needed as these may influence individual treatment selection or sequence. We aimed to identify baseline factors associated with overall survival (OS) following pembrolizumab treatment in melanoma patients. Experimental design: Serum lactate dehydrogenase (LDH), routine blood count parameters, and clinical characteristics were investigated in 616 patients. Endpoints were OS and best overall response following pembrolizumab. Kaplan-Meier analysis and Cox regression were applied for survival analysis. Results: Relative eosinophil count (REC) {greater than or equal to}1.5%, relative lymphocyte count (RLC) {greater than or equal to}17.5%, {less than or equal to}2.5-fold elevation of LDH, and the absence of metastasis other than soft-tissue/lung were associated with favorable OS in the discovery (n=177) and the confirmation (n=182) cohort and had independent positive impact (all P<0.001). Their independent role was subsequently confirmed in the validation cohort (n=257; all P<0.01). The number of favorable factors was strongly associated with prognosis. One-year-OS probabilities of 83.9% vs 14.7% and response rates of 58.3% vs 3.3% were observed in patients with four out of four compared to those with none out of four favorable baseline factors present, respectively. Conclusions: High REC and RLC, low LDH, and absence of metastasis other than soft-tissue/lung are independent baseline characteristics associated with favorable OS of patients with melanoma treated with pembrolizumab. Presence of four favorable factors in combination identifies a subgroup with excellent prognosis. In contrast, patients with no favorable factors present have a poor prognosis, despite pembrolizumab, and additional treatment advances are still needed. A potential predictive impact needs to be further investigated.

Explaining Radical Group Behavior: Developing Emotion and Efficacy Routes to Normative and Nonnormative Collective Action

Abstract: A recent model of collective action distinguishes 2 distinct pathways: an emotional pathway whereby anger in response to injustice motivates action and an efficacy pathway where the belief that issues can be solved collectively increases the likelihood that group members take action (van Zomeren, Spears, Fischer, & Leach, 2004). Research supporting this model has, however, focused entirely on relatively normative actions such as participating in demonstrations. We argue that the relations between emotions, efficacy, and action differ for more extreme, nonnormative actions and propose (a) that nonnormative actions are often driven by a sense of low efficacy and (b) that contempt, which, unlike anger, entails psychological distancing and a lack of reconciliatory intentions, predicts nonnormative action. These ideas were tested in 3 survey studies examining student protests against tuition fees in Germany (N = 332), Indian Muslims' action support in relation to ingroup disadvantage (N = 156), and British Muslims' responses to British foreign policy (N = 466). Results were generally supportive of predictions and indicated that (a) anger was strongly related to normative action but overall unrelated or less strongly related to nonnormative action, (b) contempt was either unrelated or negatively related to normative action but significantly positively predicted nonnormative action, and (c) efficacy was positively related to normative action and negatively related to nonnormative action. The implications of these findings for understanding and dealing with extreme intergroup phenomena such as terrorism are discussed.

Synthesis and Characterization of a Neutral Tricoordinate Organoboron Isoelectronic with Amines

Abstract: Amines and boranes are the archetypical Lewis bases and acids, respectively. The former can readily undergo one-electron oxidation to give radical cations, whereas the latter are easily reduced to afford radical anions. Here, we report the synthesis of a neutral tricoordinate boron derivative, which acts as a Lewis base and undergoes one-electron oxidation into the corresponding radical cation. These compounds can be regarded as the parent borylene (H-B:) and borinylium (H-B(+.)), respectively, stabilized by two cyclic (alkyl)(amino)carbenes. Ab initio calculations show that the highest occupied molecular orbital of the borane as well as the singly occupied molecular orbital of the radical cation are essentially a pair and a single electron, respectively, in the p(π) orbital of boron.

Identification of the differentiation-associated Na+/PI transporter as a novel vesicular glutamate transporter expressed in a distinct set of glutamatergic synapses.

Abstract: Glutamate transport into synaptic vesicles is a prerequisite for its regulated neurosecretion. Here we functionally identify a second isoform of the vesicular glutamate transporter (VGLUT2) that was previously identified as a plasma membrane Na + -dependent inorganic phosphate transporter (differentiation-associated Na + /P I transporter). Studies using intracellular vesicles from transiently transfected PC12 cells indicate that uptake by VGLUT2 is highly selective for glutamate, is H + dependent, and requires Cl − ion. Both the vesicular membrane potential (Δψ) and the proton gradient (ΔpH) are important driving forces for vesicular glutamate accumulation under physiological Cl − concentrations. Using an antibody specific for VGLUT2, we also find that this protein is enriched on synaptic vesicles and selective for a distinct class of glutamatergic nerve terminals. The pathway-specific, complementary expression of two different vesicular glutamate transporters suggests functional diversity in the regulation of vesicular release at excitatory synapses. Together, the two isoforms may account for the uptake of glutamate by synaptic vesicles from all central glutamatergic neurons.