Functional conservation of the Drosophila hybrid incompatibility gene Lhr

<p>Abstract</p> <p>Background</p> <p>Hybrid incompatibilities such as sterility and lethality are commonly modeled as being caused by interactions between two genes, each of which has diverged separately in one of the hybridizing lineages. The gene <it>Lethal hybrid rescue </it>(<it>Lhr</it>) encodes a rapidly evolving heterochromatin protein that causes lethality of hybrid males in crosses between <it>Drosophila melanogaster </it>females and <it>D. simulans </it>males. Previous genetic analyses showed that hybrid lethality is caused by <it>D. simulans Lhr </it>but not by <it>D. melanogaster Lhr</it>, confirming a critical prediction of asymmetry in the evolution of a hybrid incompatibility gene.</p> <p>Results</p> <p>Here we have examined the functional properties of <it>Lhr </it>orthologs from multiple Drosophila species, including interactions with other heterochromatin proteins, localization to heterochromatin, and ability to complement hybrid rescue in <it>D. melanogaster</it>/<it>D. simulans </it>hybrids. We find that these properties are conserved among most <it>Lhr </it>orthologs, including <it>Lhr </it>from <it>D. melanogaster</it>, <it>D. simulans </it>and the outgroup species <it>D. yakuba</it>.</p> <p>Conclusions</p> <p>We conclude that evolution of the hybrid lethality properties of <it>Lhr </it>between <it>D. melanogaster </it>and <it>D. simulans </it>did not involve extensive loss or gain of functions associated with protein interactions or localization to heterochromatin.</p

Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection

The antiviral immune response to SARS-CoV-2 infection can limit viral spread and prevent development of pneumonic COVID-19. However, the protective immunological response associated with successful viral containment in the upper airways remains unclear. Here, we combine a multi-omics approach with longitudinal sampling to reveal temporally resolved protective immune signatures in non-pneumonic and ambulatory SARS-CoV-2 infected patients and associate specific immune trajectories with upper airway viral containment. We see a distinct systemic rather than local immune state associated with viral containment, characterized by interferon stimulated gene (ISG) upregulation across circulating immune cell subsets in non-pneumonic SARS-CoV2 infection. We report reduced cytotoxic potential of Natural Killer (NK) and T cells, and an immune-modulatory monocyte phenotype associated with protective immunity in COVID-19. Together, we show protective immune trajectories in SARS-CoV2 infection, which have important implications for patient prognosis and the development of immunomodulatory therapies

Welthandel mit Steinkohle Preisentwicklung fuer Kesselkohlenimporte in die Bundesrepublik Deutschland bis 2010

Im Jahr 1993 wurden im Seeverkehr 360 Mio. t Steinkohle gehandelt. Davon waren 200 Mio. t fuer Kernkraftwerke bestimmte Kesselkohle. Ihr Preis erreicht mit rund 70 DM/t Steinkohleneinheit (SKE) den niedrigsten Stand seit 20 Jahren. Eine im August 1994 veroeffentlichte Studie der Rheinbraun AG, die die Preisentwicklung fuer Kesselkohleimport nach Deutschland bis zum Jahre 2010 untersucht, wagt die Prognose, dass die Talsohle in der Preisentwicklung nunmehr erreicht ist und es in den kommenden 15 Jahren zu einem kontinuierlichen Preisanstieg kommen wird. Dieser aber werde keinesfalls bewirken, dass sich die Wettbewerbsfaehigkeit der Importkesselkohle gegenueber Oel und Gas verschlechtere. Im Gegenteil. Die vier Autoren der Studie analysieren zunaechst die Ausgangslage in den wichtigsten kohleexportierenden Staaten. Es folgen Thesen zum Transport, zur Nachfrage- und Preisentwicklung weltweit. (HS)In 1993, 360 million tons of black coal were shipped overseas. 200 million tons of this were steam coal for power plants. Their price, appr. 70 DM/t hard coal unit (SKE), is on its lowest level of 20 years. An investigation by Rheinbraun AG published in August 1994 discussed the development of the price level has now reached its minimum and there will be a continuous price rise over the next 15 years. This, however, is not expected to weaken the competitive strength of imported steam coal as compared with petroleum and gas. The four authors of the investigation first analyse the starting situation in the most important coal-exporting countries. This is followed by theses on transport, demand and price development world-wide. (HS)SIGLEAvailable from TIB Hannover / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

A catabolic block does not sufficiently explain how 2-deoxy-D-glucose inhibits cell growth

The glucose analogue 2-deoxy-d-glucose (2-DG) restrains growth of normal and malignant cells, prolongs the lifespan of C. elegans, and is widely used as a glycolytic inhibitor to study metabolic activity with regard to cancer, neurodegeneration, calorie restriction, and aging. Here, we report that separating glycolysis and the pentose phosphate pathway highly increases cellular tolerance to 2-DG. This finding indicates that 2-DG does not block cell growth solely by preventing glucose catabolism. In addition, 2-DG provoked similar concentration changes of sugar-phosphate intermediates in wild-type and 2-DG-resistant yeast strains and in human primary fibroblasts. Finally, a genome-wide analysis revealed 19 2-DG-resistant yeast knockouts of genes implicated in carbohydrate metabolism and mitochondrial homeostasis, as well as ribosome biogenesis, mRNA decay, transcriptional regulation, and cell cycle. Thus, processes beyond the metabolic block are essential for the biological properties of 2-DG

Cell-free production of personalized therapeutic phages targeting multidrug-resistant bacteria.

Bacteriophages are potent therapeutics against biohazardous bacteria, which rapidly develop multidrug resistance. However, routine administration of phage therapy is hampered by a lack of rapid production, safe bioengineering, and detailed characterization of phages. Thus, we demonstrate a comprehensive cell-free platform for personalized production, transient engineering, and proteomic characterization of a broad spectrum of phages. Using mass spectrometry, we validated hypothetical and non-structural proteins and could also monitor the protein expression during phage assembly. Notably, a few microliters of a one-pot reaction produced effective doses of phages against enteroaggregative Escherichia coli (EAEC), Yersinia pestis, and Klebsiella pneumoniae. By co-expressing suitable host factors, we could extend the range of cell-free production to phages targeting gram-positive bacteria. We further introduce a non-genomic phage engineering method, which adds functionalities for only one replication cycle. In summary, we expect this cell-free methodology to foster reverse and forward phage engineering and customized production of clinical-grade bacteriophages