STING-dependent recognition of cyclic di-AMP mediates type I interferon responses during Chlamydia trachomatis infection.

UnlabelledSTING (stimulator of interferon [IFN] genes) initiates type I IFN responses in mammalian cells through the detection of microbial nucleic acids. The membrane-bound obligate intracellular bacterium Chlamydia trachomatis induces a STING-dependent type I IFN response in infected cells, yet the IFN-inducing ligand remains unknown. In this report, we provide evidence that Chlamydia synthesizes cyclic di-AMP (c-di-AMP), a nucleic acid metabolite not previously identified in Gram-negative bacteria, and that this metabolite is a prominent ligand for STING-mediated activation of IFN responses during infection. We used primary mouse lung fibroblasts and HEK293T cells to compare IFN-β responses to Chlamydia infection, c-di-AMP, and other type I IFN-inducing stimuli. Chlamydia infection and c-di-AMP treatment induced type I IFN responses in cells expressing STING but not in cells expressing STING variants that cannot sense cyclic dinucleotides but still respond to cytoplasmic DNA. The failure to induce a type I IFN response to Chlamydia and c-di-AMP correlated with the inability of STING to relocalize from the endoplasmic reticulum to cytoplasmic punctate signaling complexes required for IFN activation. We conclude that Chlamydia induces STING-mediated IFN responses through the detection of c-di-AMP in the host cell cytosol and propose that c-di-AMP is the ligand predominantly responsible for inducing such a response in Chlamydia-infected cells.ImportanceThis study shows that the Gram-negative obligate pathogen Chlamydia trachomatis, a major cause of pelvic inflammatory disease and infertility, synthesizes cyclic di-AMP (c-di-AMP), a nucleic acid metabolite that thus far has been described only in Gram-positive bacteria. We further provide evidence that the host cell employs an endoplasmic reticulum (ER)-localized cytoplasmic sensor, STING (stimulator of interferon [IFN] genes), to detect c-di-AMP synthesized by Chlamydia and induce a protective IFN response. This detection occurs even though Chlamydia is confined to a membrane-bound vacuole. This raises the possibility that the ER, an organelle that innervates the entire cytoplasm, is equipped with pattern recognition receptors that can directly survey membrane-bound pathogen-containing vacuoles for leaking microbe-specific metabolites to mount type I IFN responses required to control microbial infections

Timing and causes of North African wet phases during the last glacial period and implications for modern human migration

We present the first speleothem-derived central North Africa rainfall record for the last glacial period. The record reveals three main wet periods at 65-61 ka, 52.5-50.5 ka and 37.5-33 ka that lead obliquity maxima and precession minima. We find additional minor wet episodes that are synchronous with Greenland interstadials. Our results demonstrate that sub-tropical hydrology is forced by both orbital cyclicity and North Atlantic moisture sources. The record shows that after the end of a Saharan wet phase around 70 ka ago, North Africa continued to intermittently receive substantially more rainfall than today, resulting in favourable environmental conditions for modern human expansion. The encounter and subsequent mixture of Neanderthals and modern humans – which, on genetic evidence, is considered to have occurred between 60 and 50 ka – occurred synchronously with the wet phase between 52.5 and 50.5 ka. Based on genetic evidence the dispersal of modern humans into Eurasia started less than 55 ka ago. This may have been initiated by dry conditions that prevailed in North Africa after 50.5 ka. The timing of a migration reversal of modern humans from Eurasia into North Africa is suggested to be coincident with the wet period between 37.5 and 33 ka

The Heavy Photon Search beamline and its performance

The Heavy Photon Search (HPS) is an experiment to search for a hidden sector photon, aka a heavy photon or dark photon, in fixed target electroproduction at the Thomas Jefferson National Accelerator Facility (JLab). The HPS experiment searches for the e$^+$e$^-$ decay of the heavy photon with bump hunt and detached vertex strategies using a compact, large acceptance forward spectrometer, consisting of a silicon microstrip detector (SVT) for tracking and vertexing, and a PbWO$_4$ electromagnetic calorimeter for energy measurement and fast triggering. To achieve large acceptance and good vertexing resolution, the first layer of silicon detectors is placed just 10 cm downstream of the target with the sensor edges only 500 $\mu$m above and below the beam. Placing the SVT in such close proximity to the beam puts stringent requirements on the beam profile and beam position stability. As part of an approved engineering run, HPS took data in 2015 and 2016 at 1.05 GeV and 2.3 GeV beam energies, respectively. This paper describes the beam line and its performance during that data taking

Pretransplant HLA typing revealed loss of heterozygosity in the major histocompatibility complex in a patient with acute myeloid leukemia

Introduction Chromosomal abnormalities are frequent events in hematological malignancies. The degree of HLA compatibility between donor and recipient in hematopoietic stem cell transplantation is critical. Purpose of the study In this report, we describe an acute myeloid leukemia case with loss of heterozygosity (LOH) encompassing the entire HLA. Materials and methods HLA molecular typing was performed on peripheral blood (PB) and buccal swabs (BS). Chromosomal microarray analysis (CMA) was performed using a whole genome platform. Results Typing results on PB sample collected during blast crisis demonstrated homozygosity at the -A, -B, -C, -DR, and -DQ loci. A BS sample demonstrated heterozygosity at all loci. A subsequent PB sample drawn after count recovery confirmed heterozygosity. The CMA performed on PB samples collected during and after blast crisis revealed a large terminal region of copy-neutral LOH involving chromosome region 6p25.3p21.31, spanning approximately 35.9 Mb. The results of the CMA assay on sample collected after count recovery did not demonstrate LOH. Conclusions LOH at the HLA gene locus may significantly influence the donor search resulting in mistakenly choosing homozygous donors. We recommend confirming the HLA typing of recipients with hematological malignancies when homozygosity is detected at any locus by using BS samples, or alternatively from PB when remission is achieved

Self-Assembling Ice Membranes on Europa: Brinicle Properties, Field Examples, and Possible Energetic Systems in Icy Ocean Worlds

Brinicles are self-assembling tubular ice membrane structures, centimeters to meters in length, found beneath sea ice in the polar regions of Earth. We discuss how the properties of brinicles make them of possible importance for chemistry in cold environments-including that of life's emergence-and we consider their formation in icy ocean world. We argue that the non-ice composition of the ice on Europa and Enceladus will vary spatially due to thermodynamic and mechanical properties that serve to separate and fractionate brines and solid materials. The specifics of the composition and dynamics of both the ice and the ocean in these worlds remain poorly constrained. We demonstrate through calculations using FREZCHEM that sulfate likely fractionates out of accreting ice in Europa and Enceladus, and thus that an exogenous origin of sulfate observed on Europa's surface need not preclude additional endogenous sulfate in Europa's ocean. We suggest that, like hydrothermal vents on Earth, brinicles in icy ocean worlds constitute ideal places where ecosystems of organisms might be found

Surface Emissions Modulate Indoor SVOC Concentrations through Volatility-Dependent Partitioning.

Measurements by semivolatile thermal desorption aerosol gas chromatography (SV-TAG) were used to investigate how semivolatile organic compounds (SVOCs) partition among indoor reservoirs in (1) a manufactured test house under controlled conditions (HOMEChem campaign) and (2) a single-family residence when vacant (H2 campaign). Data for phthalate diesters and siloxanes suggest that volatility-dependent partitioning processes modulate airborne SVOC concentrations through interactions with surface-laden condensed-phase reservoirs. Airborne concentrations of SVOCs with vapor pressures in the range of C13 to C23 alkanes were observed to be correlated with indoor air temperature. Observed temperature dependencies were quantitatively similar to theoretical predictions that assumed a surface-air boundary layer with equilibrium partitioning maintained at the air-surface interface. Airborne concentrations of SVOCs with vapor pressures corresponding to C25 to C31 alkanes correlated with airborne particle mass concentration. For SVOCs with higher vapor pressures, which are expected to be predominantly gaseous, correlations with particle mass concentration were weak or nonexistent. During primary particle emission events, enhanced gas-phase emissions from condensed-phase reservoirs partitioned to airborne particles, contributing substantially to organic particulate matter. An emission event related to oven-usage was inferred to deposit siloxanes in condensed-phase reservoirs throughout the house, leading to the possibility of reemission during subsequent periods with high particle loading

Baryon Number Fluctuation and the Quark-Gluon Plasma

We show that $\omega_B$ or $\omega_{\bar B}$, the squared baryon or antibaryon number fluctuation per baryon or antibaryon, is a possible signature for the quark-gluon plasma that is expected to be created in relativistic heavy ion collisions, as it is a factor of three smaller than in an equilibrated hadronic matter due to the fractional baryon number of quarks. Using kinetic equations with exact baryon number conservation, we find that their values in an equilibrated matter are half of those expected from a Poisson distribution. Effects due to finite acceptance and non-zero net baryon number are also studied.Comment: discussion and references added, version to appear in PR

The Heavy Photon Search Beamline and Its Performance

The Heavy Photon Search (HPS) is an experiment to search for a hidden sector photon, aka a heavy photon or dark photon, in fixed target electroproduction at the Thomas Jefferson National Accelerator Facility (JLab). The HPS experiment searches for the e+e- decay of the heavy photon with bump hunt and detached vertex strategies using a compact, large acceptance forward spectrometer, consisting of a silicon microstrip detector (SVT) for tracking and vertexing, and a PbWO4 electromagnetic calorimeter for energy measurement and fast triggering. To achieve large acceptance and good vertexing resolution, the first layer of silicon detectors is placed just 10cm downstream of the target with the sensor edges only 500 μm above and below the beam. Placing the SVT in such close proximity to the beam puts stringent requirements on the beam profile and beam position stability. As part of an approved engineering run, HPS took data in 2015 and 2016 at 1.05GeV and 2.3GeV beam energies, respectively. This paper describes the beam line and its performance during that data taking