Vertical Stratification of Sediment Microbial Communities Along Geochemical Gradients of a Subterranean Estuary Located at the Gloucester Beach of Virginia, United States

Subterranean estuaries (STEs) have been recognized as important ecosystems for the exchange of materials between the land and sea, but the microbial players of biogeochemical processes have not been well examined. In this study, we investigated the bacterial and archaeal communities within 10 cm depth intervals of a permeable sediment core (100 cm in length) collected from a STE located at Gloucester Point (GP-STE), VA, United States. High throughput sequencing of 16S rRNA genes and subsequent bioinformatics analyses were conducted to examine the composition, diversity, and potential functions of the sediment communities. The community composition varied significantly from the surface to a depth of 100 cm with up to 13,000 operational taxonomic units (OTUs) based on 97% sequence identities. More than 95% of the sequences consisted of bacterial OTUs, while the relative abundances of archaea, dominated by Crenarchaea, gradually increased with sediment core depth. Along the redox gradients of GP-STE, differential distribution of ammonia-and methane-oxidizing, denitrifying, and sulfate reducing bacteria was observed as well as methanogenic archaea based on predicted microbial functions. The aerobic-anaerobic transition zone (AATZ) had the highest diversity and abundance of microorganisms, matching with the predicted functional diversity. This indicates the AATZ as a hotspot of biogeochemical processes of STEs. The physical and geochemical gradients in different depths have attributed to vertical stratification of microbial community composition and function in the GP-STE

A variational Bayesian approach for inverse problems with skew-t error distributions

In this work, we develop a novel robust Bayesian approach to inverse problems with data errors following a skew-t distribution. A hierarchical Bayesian model is developed in the inverse problem setup. The Bayesian approach contains a natural mechanism for regularization in the form of a prior distribution, and a LASSO type prior distribution is used to strongly induce sparseness. We propose a variational type algorithm by minimizing the Kullback-Leibler divergence between the true posterior distribution and a separable approximation. The proposed method is illustrated on several two-dimensional linear and nonlinear inverse problems, e.g. Cauchy problem and permeability estimation problem

Antigen spreading-induced CD8+T cells confer protection against the lethal challenge of wild-type malignant mesothelioma by eliminating myeloid-derived suppressor cells

published_or_final_versio

Preparation and characterization of in situ polymerized cyclic butylene terephthalate/graphene nanocomposites

Graphene reinforced cyclic butylene terephthalate (CBT) matrix nanocomposites were prepared and characterized by mechanical and thermal methods. These nanocomposites containing different amounts of graphene (up to 5 wt%) were prepared by melt mixing with CBT that was polymerized in situ during a subsequent hot pressing. The nanocomposites and the neat polymerized CBT (pCBT) as reference material were subjected to differential scanning calorimetry (DSC), dynamical mechanical analysis (DMA), thermogravimetrical analysis (TGA) and heat conductivity measurements. The dispersion of the grapheme nanoplatelets was characterized by transmission electron microscopy (TEM). It was established that the partly exfoliated graphene worked as nucleating agent for crystallization, acted as very efficient reinforcing agent (the storage modulus at room temperature was increased by 39 and 89% by incorporating 1 and 5 wt.% graphene, respectively). Graphene incorporation markedly enhanced the heat conductivity but did not influence the TGA behaviour due to the not proper exfoliation except the ash content

Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

Gastric cancer surgery: Billroth I or Billroth II for distal gastrectomy?

<p>Abstract</p> <p>Background</p> <p>The selection of an anastomosis method after a distal gastrectomy is a highly debatable topic; however, the available documentation lacks the necessary research based on a comparison of early postoperative complications. This study was conducted to investigate the difference of early postoperative complications between Billroth I and Billroth II types of anastomosis for distal gastrectomies.</p> <p>Methods</p> <p>A total of 809 patients who underwent distal gastrectomies for gastric cancer during four years were included in the study. The only study endpoint was analysis of in-patients' postoperative complications. The risk adjusted complication rate was compared by POSSUM (Physiological and operative severity score for enumeration of morbidity and mortality) and the severity of complications was compared by Rui Jin Hospital classification of complication.</p> <p>Results</p> <p>Complication rate of Billroth II type of anastomosis was almost double of that in Billroth I (P = 0.000). Similarly, the risk adjusted complication rate was also higher in Billroth II group. More severe complications were observed and the postoperative duration was significantly longer in Billroth II type (P = 0.000). Overall expenditure was significantly higher in Billroth II type (P = 0.000).</p> <p>Conclusion</p> <p>Billroth II method of anastomosis was associated with higher rate of early postoperative complications. Therefore, we conclude that the Billroth I method should be the first choice after a distal gastrectomy as long as the anatomic and oncological environment of an individual patient allows us to perform it. However more prospective studies should be designed to compare the overall surgical outcomes of both anastomosis methods.</p

Quantifying the impact of immunotherapy on RNA dynamics in cancer

BACKGROUND: Checkpoint inhibitor (CPI) immunotherapies have provided durable clinical responses across a range of solid tumor types for some patients with cancer. Nonetheless, response rates to CPI vary greatly between cancer types. Resolving intratumor transcriptomic changes induced by CPI may improve our understanding of the mechanisms of sensitivity and resistance. METHODS: We assembled a cohort of longitudinal pre-therapy and on-therapy samples from 174 patients treated with CPI across six cancer types by leveraging transcriptomic sequencing data from five studies. RESULTS: Meta-analyses of published RNA markers revealed an on-therapy pattern of immune reinvigoration in patients with breast cancer, which was not discernible pre-therapy, providing biological insight into the impact of CPI on the breast cancer immune microenvironment. We identified 98 breast cancer-specific correlates of CPI response, including 13 genes which are known IO targets, such as toll-like receptors TLR1, TLR4, and TLR8, that could hold potential as combination targets for patients with breast cancer receiving CPI treatment. Furthermore, we demonstrate that a subset of response genes identified in breast cancer are already highly expressed pre-therapy in melanoma, and additionally we establish divergent RNA dynamics between breast cancer and melanoma following CPI treatment, which may suggest distinct immune microenvironments between the two cancer types. CONCLUSIONS: Overall, delineating longitudinal RNA dynamics following CPI therapy sheds light on the mechanisms underlying diverging response trajectories, and identifies putative targets for combination therapy

A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus

Generally, the second messenger bis-(3’-5’)-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-diGMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be—at least partially—functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus