Description: Author(s): A. König, R. Schuster, M. Knupfer, B. Büchner, and H. Berger Inelastic electron scattering is applied to investigate the impact of potassium intercalation on the charge-carrier plasmon energy and dispersion in the charge-density wave (CDW) bearing compound 2 H -TaSe 2 . We observe an unususal doping dependence of the plasmon dispersion, which even changes sign on... [Phys. Rev. B 87, 195119] Published Wed May 15, 2013

Description: IL-17–producing Th17 cells mediate immune responses against a variety of fungal and bacterial infections. Signaling via NF-B has been linked to the development and maintenance of Th17 cells. We analyzed the role of the unusual inhibitor of NF-B, IB NS , in the proliferation and effector cytokine production of murine Th17 cells. Our study demonstrates that nuclear IB NS is crucial for murine Th17 cell generation. IB NS is highly expressed in Th17 cells; in the absence of IB NS , the frequencies of IL-17A–producing cells are drastically reduced. This was measured in vitro under Th17-polarizing conditions and confirmed in two colitis models. Mechanistically, murine IB NS –/– Th17 cells were less proliferative and expressed markedly reduced levels of IL-2, IL-10, MIP-1α, and GM-CSF. Citrobacter rodentium was used as a Th17-inducing infection model, in which IB NS –/– mice displayed an increased bacterial burden and diminished tissue damage. These results demonstrate the important function of Th17 cells in pathogen clearance, as well as in inflammation-associated pathology. We identified IB NS to be crucial for the generation and function of murine Th17 cells upon inflammation and infection. Our findings may have implications for the therapy of autoimmune conditions, such as inflammatory bowel disease, and for the treatment of gut-tropic infections.

Description: Objective Despite widespread use of antibiotics for the treatment of life-threatening infections and for research on the role of commensal microbiota, our understanding of their effects on the host is still very limited. Design Using a popular mouse model of microbiota depletion by a cocktail of antibiotics, we analysed the effects of antibiotics by combining intestinal transcriptome together with metagenomic analysis of the gut microbiota. In order to identify specific microbes and microbial genes that influence the host phenotype in antibiotic-treated mice, we developed and applied analysis of the transkingdom network. Results We found that most antibiotic-induced alterations in the gut can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues and the effects of remaining antibiotic-resistant microbes. Normal microbiota depletion mostly led to downregulation of different aspects of immunity. The two other factors (antibiotic direct effects on host tissues and antibiotic-resistant microbes) primarily inhibited mitochondrial gene expression and amounts of active mitochondria, increasing epithelial cell death. By reconstructing and analysing the transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria, a finding further validated using in vitro experiments. Conclusions In addition to revealing mechanisms of antibiotic-induced alterations, this study also describes a new bioinformatics approach that predicts microbial components that regulate host functions and establishes a comprehensive resource on what, why and how antibiotics affect the gut in a widely used mouse model of microbiota depletion by antibiotics.

Description: In this issue, Paul and colleagues' meta-analysis examines the risk for HBV reactivation with and without antiviral prophylaxis and its effectiveness in adults with solid tumors and chronic or resolved HBV infection. The editorialists discuss the findings and their implications for pretreatment HBV screening and prophylaxis.

Description: Lakes are major depositional systems for which the related depositional processes have long been considered relatively simple. Breaking this statement, this study presents a detailed analysis of deposits in Lake Saint-Jean, the third largest natural lake in Québec. In addition to postglacial deltaic and coastal depositional systems fringing the lake, current-controlled features such as a large subaqueous prograding wedge and three sediment drifts have been identified in its central portion based on two-dimensional (2-D) acoustic high-resolution subbottom profiles. The large subaqueous prograding wedge is a 4-km-long and up to 15-m-thick heterolithic shelf-like construction in the southeastern part of the lake. The three sediment drifts are 0.1–0.5-km-long and 2–5-m-thick mud mounds distributed on the lake floor in the central portion of the lake. Diatom analyses and radiocarbon dating show that the development of these current-controlled features occurred during the lacustrine phase, after the disconnection with the postglacial marine Laflamme Gulf at 8.5 cal. k.y. B.P. Depositional facies show evidence of recurrent bottom-current activity. Related deposits alternate with pelagic sedimentation stages characterized by the settling of mud and biogenic accumulations. We investigated the origin of bottom currents using a numerical simulation (SYMPHONIE, an oceanographic model), with the aim of modeling wind-induced lake-scale water circulation. Simulations suggest that the subaqueous prograding wedge and the three sediment drifts result from wind-induced bottom currents generated by storm events having wind speed greater than 10 m s –1 . Such strong winds are able to significantly affect sedimentation in the central portion of Lake Saint-Jean. The resulting wind-induced sedimentary features were integrated into a refined lacustrine depositional model that summarizes the evolution of a group of water bodies referred to as "wind-driven water bodies." This study applies a new tool for lake strata characterization and highlights the potential difficulty in differentiating them from marine deposits in the geological record.

Description: The multifaceted functions of C/EBPα in normal and malignant haematopoiesis Leukemia 30, 767 (April 2016). doi:10.1038/leu.2015.324 Authors: E Ohlsson, M B Schuster, M Hasemann & B T Porse

Description: The stem cell protein SALL4 plays a critical role in hematopoiesis by regulating the cell fate. In primitive hematopoietic precursors, it activates or represses important genes via recruitment of various epigenetic factors such as DNA methyltransferases, and histone deacylases. Here, we demonstrate that LSD1, a histone lysine demethylase, also participates in the trans-repressive effects of SALL4. Based on luciferase assays, the amine oxidase domain of LSD1 is important in suppressing SALL4-mediated reporter transcription. In freshly isolated adult mouse bone marrows, both SALL4 and LSD1 proteins are preferentially expressed in undifferentiated progenitor cells and co-localize in the nuclei. Further sequential chromatin immunoprecipitation assay confirmed that these two factors share the same binding sites at the promoter regions of important hematopoietic regulatory genes including EBF1, GATA1, and TNF. In addition, studies from both gain- and loss-of-function models revealed that SALL4 dynamically controls the binding levels of LSD1, which is accompanied by a reversely changed histone 3 dimethylated lysine 4 at the same promoter regions. Finally, shRNA-mediated knockdown of LSD1 in hematopoietic precursor cells resulted in altered SALL4 downstream gene expression and increased cellular activity. Thus, our data revealed that histone demethylase LSD1 may negatively regulate SALL4-mediated transcription, and the dynamic regulation of SALL4-associated epigenetic factors cooperatively modulates early hematopoietic precursor proliferation.