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Draft Genome Assembly of the Entomopathogenic Bacterium Photorhabdus luminescens subsp. sonorensis CaborcaPhotorhabdus luminescens subsp. sonorensis strain Caborca is an entomopathogenic bacterium with a dual lifestyle, namely, as a mutualist of the Heterorhabditis sonorensis nematode and a pathogen to a wide range of insect species. The genome assembly, in 231 contigs, is 5.2 Mbp long and includes 25 putative gene clusters for secondary metabolism.
Explaining the ANITA anomaly with inelastic boosted dark matterWe propose a new physics scenario in which the decay of a very heavy dark-matter candidate which does not interact with the neutrino sector could explain the two anomalous events recently reported by the Antarctic Impulsive Transient Antenna Collaboration. The model is composed of two components of dark matter, an unstable dark-sector state and a massive dark gauge boson. We assume that the heavier dark-matter particle of an EeV-range mass is distributed over the Galactic halo and disintegrates into a pair of lighter-highly boosted-dark-matter states in the present Universe which reach and penetrate the Earth. The latter scatters inelastically off a nucleon and produces a heavier dark-sector unstable state which subsequently decays back to the lighter dark matter along with hadrons, which induce extensive air showers, via on /off shell dark gauge boson. Depending on the mass hierarchy within the dark sector, either the dark gauge boson or the unstable dark-sector particle can be long-lived, hence transmitted significantly through the Earth. We study the angular distribution of the signal and show that our model favors emergence angles in the range similar to 25 degrees-35 degrees if the associated parameter choices bear the situation where the mean free path of the boosted incident particle is much larger than the Earth diameter, while its long-lived decay product has a decay length of dimensions comparable to the Earth radius. Our model, in particular, avoids any constraints from complementary neutrino searches such as IceCube or the Auger observatory.
Defective Transcriptional Programming of Effector CD8 T Cells in Aged Mice Is Cell-Extrinsic and Can Be Corrected by Administration of IL-12 and IL-18In response to infection with intracellular microorganisms, old mice mobilize decreased numbers of antigen-specific CD8T cells with reduced expression of effector molecules and impaired cytolytic activity. Molecular mechanisms behind these defects and the cell-intrinsic (affecting naive CD8 T cells themselves) vs. extrinsic, microenvironmental origin of such defects remain unclear. Using reciprocal transfer experiments of highly purified naive T cells from adult and old transgenic OT-1 mice, we decisively show that the dominant effect is cell-extrinsic. Naive adult OT-1 T cells failed to expand and terminally differentiate in the old organism infected with Listeria-OVA. This defect was preceded by blunted expression of the master transcription factor T-bet and impaired glycolytic switch when T cells are primed in the old organism. However, both old and adult naive CD8T cells proliferated and produced effector molecules to a similar extent when stimulated in vitro with polyclonal stimuli, as well as when transferred into adult recipients. Multiple inflammatory cytokines with direct effects on T cell effector differentiation were decreased in spleens of old animals, particularly IL-12 and IL-18. Of note, in vivo treatment of mice with IL-12 and IL-18 on days 4-6 of Listeria infection reconstituted cytotoxic T cell response of aged mice to the level of adult. Therefore, critical cytokine signals which are underproduced in the old priming environment can restore proper transcriptional programming of old naive CD8T cells and improve immune defense against intracellular microorganisms.
Targeting the Non-catalytic RVxF Site of Protein Phosphatase-1 With Small Molecules for Ebola Virus InhibitionEbola virus (EBOV) is a non-segmented negative-sense RNA virus that causes a severe human disease. The ongoing EBOV outbreak in the Eastern part of Democratic Republic of the Congo has resulted to date in over 2500 confirmed cases including over 1500 deaths. Difficulties with vaccine administration indicate the necessity for development of new general drugs and therapeutic strategies against EBOV. Host Ser/Thr protein phosphatases, particularly PP1 and PP2A, facilitate EBOV transcription by dephosphorylating the EBOV VP30 protein and switching activity of the polymerase complex toward replication. Previously, we developed small molecule 1E7-03 that targeted host protein phosphatase-1 (PP1) and induces phosphorylation of EBOV VP30 protein thus shifting transcription-replication balance and inhibiting EBOV replication. Here, we developed a new EBOV inhibitor, 1E7-07, that potently inhibits EBOV replication and displays significantly improved metabolic stability when compared to previously described 1E7-03. Proteome analysis of VP30 shows that 1E7-07 increases its phosphorylation on Thr-119 and Ser-124 over 3-fold with p < 0.001, which likely contributes to EBOV inhibition. We analyzed 1E7-07 binding to PP1 using a mass spectrometry-based protein painting approach. Combined with computational docking, protein painting shows that 1E7-07 binds to several PP1 sites including the RVxF site, C-terminal groove and NIPP1-helix binding pocket. Further analysis using surface plasmon resonance and a split NanoBiT system demonstrates that 1E7-07 binds primarily to the RVxF site. Together, detailed analysis of 1E7-07 binding to PP1 and identification of the RVxF site as the main binding site opens up an opportunity for future development of PP1-targeting EBOV inhibitors.
Drivers of C cycling in three arctic-alpine plant communitiesRecent vegetation changes in arctic-alpine tundra ecosystems may affect several ecosystem processes that regulate microbe and soil functions. Such changes can alter ecosystem carbon (C) cycling with positive feedback to the atmosphere if plant C uptake is less than the amount of soil C released. Here, we examine how differences in plant functional traits, microbial activity, and soil processes within and across Salix-dominated shrub, dwarf shrub-dominated heath, and herb- and cryptogam-dominated meadow communities influence C cycling. We develop a hypothesized framework based on a priori model selection of variation in daytime growing season gross ecosystem photosynthesis (GEP) and above-and belowground respiration. The fluxes were standardized to light and temperature. Gross ecosystem photosynthesis was primarily related to soil moisture and secondarily to plant functional traits and aboveground biomass, and belowground respiration was dependent on the community weighted mean of specific leaf area (SLA(CWM)). Similarly, microbial activity was linked with SLA(CWM) and was highest in meadows, and carbon-degrading microbial activity decreased with vegetation woodiness. These results suggest that shrub expansion may influence summer C cycling differently depending on plant community, as belowground respiration might increase in the heath and decrease in the meadow communities.