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Background Diverse architectures of nervous systems (NSs) such as a plexus in cnidarians or a more centralized nervous system (CNS) in insects and vertebrates are present across Metazoa, but it is unclear what selection pressures drove evolution and diversification of NSs. One underlying aspect of this diversity lies in the cellular and molecular mechanisms driving neurogenesis, i.e. generation of neurons from neural precursor cells (NPCs). In cnidarians, vertebrates, and arthropods, homologs of SoxB and bHLH proneural genes control different steps of neurogenesis, suggesting that some neurogenic mechanisms may be conserved. However, data are lacking for spiralian taxa. Results To that end, we characterized NPCs and their daughters at different stages of neurogenesis in the spiralian annelid Capitella teleta. We assessed cellular division patterns in the neuroectoderm using static and pulse-chase labeling with thymidine analogs (EdU and BrdU), which enabled identification of NPCs that underwent multiple rounds of division. Actively-dividing brain NPCs were found to be apically-localized, whereas actively-dividing NPCs for the ventral nerve cord (VNC) were found apically, basally, and closer to the ventral midline. We used lineage tracing to characterize the changing boundary of the trunk neuroectoderm. Finally, to start to generate a genetic hierarchy, we performed double-fluorescent in-situ hybridization (FISH) and single-FISH plus EdU labeling for neurogenic gene homologs. In the brain and VNC, Ct-soxB1 and Ct-neurogenin were expressed in a large proportion of apically-localized, EdU+ NPCs. In contrast, Ct-ash1 was expressed in a small subset of apically-localized, EdU+ NPCs and subsurface, EdU− cells, but not in Ct-neuroD+ or Ct-elav1+ cells, which also were subsurface. Conclusions Our data suggest a putative genetic hierarchy with Ct-soxB1 and Ct-neurogenin at the top, followed by Ct-ash1, then Ct-neuroD, and finally Ct-elav1. Comparison of our data with that from Platynereis dumerilii revealed expression of neurogenin homologs in proliferating NPCs in annelids, which appears different than the expression of vertebrate neurogenin homologs in cells that are exiting the cell cycle. Furthermore, differences between neurogenesis in the head versus trunk of C. teleta suggest that these two tissues may be independent developmental modules, possibly with differing evolutionary trajectories.

B-ATF is a member of the ATF/AP-1 superfamily of basic leucine zipper (bZIP) transcription factors. The ZIP regions of these proteins facilitate the formation of stable homodimers or heterodimers which bind to consensus DNA sites through adjacent basic amino acid residues. The B-ATF cDNA encodes a 125-amino acid protein with a centrally located bZIP domain. Previously, we have shown that B-ATF forms heterodimers with Jun proteins, but not with Fos or with a number of other bZIP proteins including ATF-2, CREB, or NF-IL6. B-ATF/Jun heterodimers bind consensus ATF/AP-1 DNA sites and, in contrast to Fos/Jun heterodimers, B-ATF/Jun complexes interfere with the transcriptional activation of target genes (Echlin and Taparowsky, in preparation). This suggests that the major cellular function of B-ATF is as a negative regulator of ATF/AP-1 transcriptional events. Furthermore, the observation that EBV and HTLV-1 up-regulate the expression of B-ATF in cells implies that these viruses may influence cellular gene expression patterns through increased production of B-ATF. As a first step towards defining the cis-acting regulatory elements controlling transcription of the B-ATF gene in normal cells and in virus-infected cells, we determined the structure and organization of the human B-ATF genomic locus.

Listeria monocytogenes is a Gram-positive facultative intracellular pathogen capable of causing severe food born illness. Escape from the phagosome is essential for the intracellular life cycle of L. monocytogenes and has tremendous consequences on many biological processes including protective immunity and autophagy. Wild-type L. monocytogenes express the gene hly that results in the production of the cholesterol-dependent cytolysin listeriolysin O (LLO). Expression of LLO is required for phagosomal escape and for the induction of a cell-mediated immune response to L. monocytogenes. A mutant of L. monocytogenes that does not express LLO is avirulent, remains trapped in the phagosome, and is unable to induce cell-mediated immunity. The reason that L. monocytogenes mutants, lacking LLO, do not induce a cell-mediated immune response is not understood. Using a mixed inoculum of cytosolic and phagosome-trapped L. monocytogenes, we found that when L. monocytogenes was confined to the vacuole, it suppressed the immunizing capability of L. monocytogenes in the cytosol. Further, as we increased the concentration of the bacteria trapped in the phagosome with an inoculum containing an immunizing dose of cytosolic L. monocytogenes, a concomitant decrease in the expression of proinflammatory cytokines and L. monocytogenes-speciftc T cells was observed. Additionally, immunosuppressive cytokines, including IL-10, were made in response to bacteria trapped in the phagosome, and blockage of the IL-10R restored the immunizing capability of cytosolic L. monocytogenes even in the presence of phagosome-trapped bacteria. L. monocytogenes escape from the phagosome also induced autophagy. Autophagy is cellular bulk degradation pathway used to degrade long-lived proteins and organelles. We found L. monocytogenes mutants lacking LLO did not induce autophagy, whereas wild-type and other mutants induced relatively equal amounts of autophagy early in an infection of bone marrow-derived macrophages. Bacillus subtilis expressing LLO also induced autophagy, indicating that the induction was not specific to L. monocytogenes. Lastly, we found that liposomes containing LLO were sufficient to induce autophagy in the absence of infection. Thus, LLO was necessary and sufficient to induce autophagy in an L. monocytogenes infection. In summary, we found that LLO expression by L. monocytogenes was required for both the proper induction of the cell-mediated immune response to L. monocytogenes and was also required for the induction of autophagy in response to infection with L. monocytogenes.

Part of the problem is the emphasis put on cosmetic results rather than tackling underlying problems. So, for example, our local hospital is chronically short of beds for emergencies. This should inevitably feed, disadvantageously, into their \"trolley wait\" figures. The response by the managers is to make patients for emergency admission, arranged by GPs, wait at home until a bed becomes available, a system which is potentially dangerous and burdens the community services unnecessarily.

A candidate vaccine against smallpox, modified vaccinia Ankara, was studied in 440 participants. MVA elicited immune responses similar to those associated with the established vaccinia-based vaccine and attenuated vaccinia replication in a human challenge model.

Temporary rivers are increasingly common freshwater ecosystems, but there have been no global syntheses of their community patterns. In this study, we examined the responses of aquatic invertebrate communities to flow intermittence in 14 rivers from multiple biogeographic regions covering a wide range of flow intermittence and spatial arrangements of perennial and temporary reaches. Hydrological data were used to describe flow intermittence (FI, the proportion of the year without surface water) gradients. Linear mixed‐effects models were used to examine the relationships between FI and community structure and composition. We also tested if communities at the most temporary sites were nested subsets of communities at the least temporary and perennial sites. Taxon richness decreased as FI increased and invertebrate communities became dominated by ubiquitous taxa. The number of resilient taxa (with high dispersal capacities) decreased with increased FI, whereas the number of resistant taxa (with adaptations to desiccation) was not related to FI. River‐specific and river‐averaged model comparisons indicated most FI‐community relationships did not differ statistically among rivers. Community nestedness along FI gradients was detected in most rivers and there was little or no influence of the spatial arrangement of perennial and temporary reaches. These results indicate that FI is a primary driver of aquatic communities in temporary rivers, regardless of the biogeographic species pool. Community responses are largely due to resilience rather than resistance mechanisms. However, contrary to our expectations, resilience was not strongly influenced by spatial fragmentation patterns, suggesting that colonist sources other than adjacent perennial reaches were important.

Background The Human Cell Atlas is a large international collaborative effort to map all cell types of the human body. Single-cell RNA sequencing can generate high-quality data for the delivery of such an atlas. However, delays between fresh sample collection and processing may lead to poor data and difficulties in experimental design. Results This study assesses the effect of cold storage on fresh healthy spleen, esophagus, and lung from ≥ 5 donors over 72 h. We collect 240,000 high-quality single-cell transcriptomes with detailed cell type annotations and whole genome sequences of donors, enabling future eQTL studies. Our data provide a valuable resource for the study of these 3 organs and will allow cross-organ comparison of cell types. We see little effect of cold ischemic time on cell yield, total number of reads per cell, and other quality control metrics in any of the tissues within the first 24 h. However, we observe a decrease in the proportions of lung T cells at 72 h, higher percentage of mitochondrial reads, and increased contamination by background ambient RNA reads in the 72-h samples in the spleen, which is cell type specific. Conclusions In conclusion, we present robust protocols for tissue preservation for up to 24 h prior to scRNA-seq analysis. This greatly facilitates the logistics of sample collection for Human Cell Atlas or clinical studies since it increases the time frames for sample processing.