The influence of a changing bacterial community on trace metal scavenging in a deep-sea particle plume

An extensive set of particle samples was collected from the extended (nonbuoyant) hydrothermal plume, the distal remnant plume, and the adjacent waters in a transect across the Southern Juan de Fuca Ridge. Bacterial capsules comprised the primary species of particulate Mn. However, the data also showed significant shifts in the relative abundance of distinctive subpopulations of this bacterial community, as expressed by several consistently recurring capsule morphologies. The data are discussed with respect to distance from plume origins (relative plume age), total bacterial numbers, experimentally determined scavenging rate constants and total particulate and dissolved Mn. The relative distribution of one morph (Fibrous) corresponded (r = .825, p \u3c 0.001) to that of the scavenging rate constant, k1 (Cowen et al., 1990) for dissolved Mn onto particles. The greatest Mn deposits (by a factor of over 10×) were associated with this same morph, which was also the numerically dominant capsule morph at the off-axis stations where total particulate Mn plume values were highest. The disequilibrium in the particle population and the geochemical cycle of Mn in an evolving hydrothermal vent plume is reflected in the distribution coefficients for Mn (KD), which increase with distance from vent origins. The potential influence that changing subpopulations of bacteria may exert on the overall scavenging behavior of Mn in this evolving natural particle population is emphasized

Enhanced nitrogen and phosphorus flows in a mixed land use basin: drivers and consequences

Rapid increase in accumulation of phosphorus (P) relative to nitrogen (N) has been observed in human-impacted regions, but the reasons are largely unknown. We developed an Integrated Nutrient Flow Analysis (INFA) model in order to assess the changes in nutrient flows of the Chaohu Lake basin from 1978 to 2015. Results show that the increase in total N input is slower than that of P (3.5-fold versus 4.2-fold) during 1978–2015, while total N loss increases much faster than that of P (3.1-fold versus 2.3-fold). We found a decline trend in the N:P ratio of nutrient input and accumulation since the mid-1990s. The decline in N:P ratio of nutrient loss to waterbodies in the basin is correlated (p < 0.05) with TN:TP of water concentration in Chaohu Lake, which may be related to the frequent algal blooms in the P-limited lake by supplying more P than N. Using an extended STIRPAT model, we found that nutrient use efficiency, urban rate, diet choice and population are key factors driving the change in nutrient flows, which contribute over 90% to the total change. This study confirms that human activities decrease N:P in regional environment and demonstrates the importance of P management to balance nutrient for improving water quality. The method in this study has a wide application for many other mixed land use regions to address nutrient flows imbalance problems and to explore nutrient management options

Identification and analysis of seven H2O2-responsive miRNAs and 32 new miRNAs in the seedlings of rice (Oryza sativa L. ssp. indica)

Plant microRNAs (miRNAs) have been shown to play critical roles in regulating gene expression at the post-transcriptional level. In this study, we employed high throughput sequencing combined with computational analysis to survey miRNAomes from the seedlings of rice under normal conditions and treatments of H2O2 that result in oxidative stress. Comparison of the miRNAomes and subsequent northern blot analysis identified seven miRNA families differentially expressed under H2O2 stress. Predicted and experimentally validated targets of these H2O2-responsive miRNAs are involved in different cellular responses and metabolic processes including transcriptional regulation, nutrient transport, auxin homeostasis, cell proliferation and programmed cell death. This indicates that diverse miRNAs form a complex regulatory network to coordinate plants’ responses under oxidative stress. In addition, we also discovered 32 new miRNAs in the seedlings of rice. Interestingly, of these new miRNAs, miR3981 was originally found to be a putative exonic miRNA located in the exon of AK106348, suggesting that plants may also use some exons as an miRNA source. This study is the first genome-wide investigation of H2O2-regulated miRNAs in plants and broadens our perspectives on the important regulatory roles of miRNAs in plant oxidative stress and physiological adaption

Initiation of T cell signaling by CD45 segregation at 'close contacts'.

It has been proposed that the local segregation of kinases and the tyrosine phosphatase CD45 underpins T cell antigen receptor (TCR) triggering, but how such segregation occurs and whether it can initiate signaling is unclear. Using structural and biophysical analysis, we show that the extracellular region of CD45 is rigid and extends beyond the distance spanned by TCR-ligand complexes, implying that sites of TCR-ligand engagement would sterically exclude CD45. We also show that the formation of 'close contacts', new structures characterized by spontaneous CD45 and kinase segregation at the submicron-scale, initiates signaling even when TCR ligands are absent. Our work reveals the structural basis for, and the potent signaling effects of, local CD45 and kinase segregation. TCR ligands have the potential to heighten signaling simply by holding receptors in close contacts.The authors thank R.A. Cornall, M.L. Dustin and P.A. van der Merwe for comments on the manuscript and S. Ikemizu for useful discussions about the structure. We also thank W. Lu and T. Walter for technical support with protein expression and crystallization, the staff at Diamond Light Source beamlines I02, I03 and I04-1 (proposal mx10627) and European Synchrotron Radiation Facility beamlines ID23EH1 and ID23EH2 for assistance at the synchrotrons, G. Sutton for assistance with MALS experiments, and M. Fritzsche for advice on the calcium analysis. This work was funded by the Wellcome Trust (098274/Z/12/Z to S.J.D.; 090532/Z/09/Z to R.J.C.G.; 090708/Z/09/Z to D.K.), the UK Medical Research Council (G0700232 to A.R.A.), the Royal Society (UF120277 to S.F.L.) and Cancer Research UK (C20724/A14414 to C.S.; C375/A10976 to E.Y.J.). The Oxford Division of Structural Biology is part of the Wellcome Trust Centre for Human Genetics, Wellcome Trust Core Award Grant Number 090532/Z/09/Z. We acknowledge financial support from Instruct, an ESFRI Landmark Project. The OPIC electron microscopy facility was funded by a Wellcome Trust JIF award (060208/Z/00/Z).This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/ni.339

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

One-step solid-oil-water emulsion for sustained bioactive ranibizumab release

Background: The advent of therapeutic proteins highlights the need for delivery systems that protect and extend the duration of its action. Ranibizumab-VEGF is one such drug used for treating wet AMD. This paper describes a facile method to sustain bioactive ranibizumab release from PLGA-based particles. Methods: Two emulsion techniques were explored namely: water-in-oil-in-water (WOW) and solid-in-oil-in-water (SOW) emulsion. The bioactivity of ranibizumab was evaluated by comparing its binding capability to VEGF, measured with ELISA to total protein measured by microBCA. Results: During the emulsion process, contact of ranibizumab with the water-oil interface is the main destabilizing factor and this can be prevented with the use of amphiphilic PVA and solid-state protein in WOW and SOW emulsion respectively. In vitro release of the ranibizumab-loaded particles indicated that a 15-day release could be achieved with SOW particles while the WOW particles generally suffered from a burst release. Released ranibizumab was capable of inhibiting endothelial cell growth indicating its retention of bioactivity. The suppression of burst release from the SOW particles was attributed to the relatively smooth surface morphology of the SOW microparticles. Conclusions: The use of SOW encapsulation in modulating ranibizumab release while maintaining their bioactivity has been highlighted.MOE (Min. of Education, S’pore

Increased Risk of Herpes Zoster in Diabetic Patients Comorbid with Coronary Artery Disease and Microvascular Disorders: A Population-Based Study in Taiwan.

We investigated the association between the risk of herpes zoster (HZ) and diabetes-related macrovascular comorbidities and microvascular disorders in diabetic patients. This retrospective study included 25,345 patients with newly identified HZ and age- and gender-matched controls retrieved from the National Health Insurance Research Database in Taiwan during the period of 2005 to 2011. Multivariate logistic regression analyses were used to calculate the odds ratios (OR) and to assess the risk factors for HZ in diabetic patients with associated macrovascular or microvascular disorders. Risk factors for HZ were significantly increased in cases of diabetes mellitus (DM) compared with those in cases of non-DM controls (20.2% vs. 17.0%, OR = 1.24, p<0.001). Results of age- and gender-adjusted analyses demonstrated a significantly higher risk of HZ in DM patients with accompanying coronary artery disease (CAD) (adjusted OR = 1.21, p<0.001) and microvascular disorders (aOR = 1.32, p<0.001) than in DM patients with other comorbidities but no microvascular disorders. Patients who took thiazolidinedione, alpha-glucosidase inhibitors and insulin had a higher HZ risk than those taking metformin or sulphonylureas alone (aOR = 1.11, 1.14 and 1.18, p<0.001, respectively). Patients who took insulin alone or in combination with other antidiabetic agents had a significantly higher risk of HZ (aOR = 1.25, p<0.001) than those who received monotherapy. Diabetic patients comorbid with coronary artery disease and associated microvascular disorders had an increased risk of HZ occurrence

Inhibitory effects of propofol on Th17 cell differentiation

<p>Propofol (2,6-diisopropylphenol) is probably the most widely used intravenous anesthetic agent in daily practice. It has been reported to show immunomodulatory activity. However, the effect of propofol on the differention of T cells remains unclear. In this study, we demonstrated for the first time that propofol inhibited both interleukin (IL)-6 plus transforming growth factor-β (TGF-β)-induced Th17 cell differentiation <i>in vitro</i> and in LPS-challenged mice. Propofol also suppressed the IL-6-induced phosphorylation of Janus kinase-2 (JAK2)/signal transducer and activator of transcription (STAT3) pathway, a cytokine-activated essential transcription factor in Th17 cell development, which occurred concomitantly with the enhancement of suppressor of cytokine signaling-3 (SOCS3) expression involved in the downregulation of STAT3 phosphorylation. These data extend our knowledge of the immunosuppressive effects of propofol and their underlying mechanism.</p