The alarmones pppGpp and ppGpp mediate starvation response and maintain purine homeostasis to protect bacteria. In the bacterial phyla Firmicutes and Bacteroidetes, xanthine phosphoribosyltransferase ...(XPRT) is a purine salvage enzyme that produces the nucleotide XMP from PRPP and xanthine. Combining structural, biochemical, and genetic analyses, we show that pppGpp and ppGpp, as well as a third newly identified alarmone pGpp, all directly interact with XPRT from the Gram-positive bacterium Bacillus subtilis and inhibit XPRT activity by competing with its substrate PRPP. Structural analysis reveals that ppGpp binds the PRPP binding motif within the XPRT active site. This motif is present in another (p)ppGpp target, the purine salvage enzyme HPRT, suggesting evolutionary conservation in different enzymes. However, XPRT oligomeric interaction is distinct from HPRT in that XPRT forms a symmetric dimer with two (p)ppGpp binding sites at the dimer interface. (p)ppGpp's interaction with an XPRT bridging loop across the interface results in XPRT cooperatively binding (p)ppGpp. Also, XPRT displays differential regulation by the alarmones as it is potently inhibited by both ppGpp and pGpp, but only modestly by pppGpp. Lastly, we demonstrate that the alarmones are necessary for protecting GTP homeostasis against excess environmental xanthine in B. subtilis, suggesting that regulation of XPRT is key for regulating the purine salvage pathway.
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•The purine salvage enzyme XPRT uses xanthine and PRPP for efficient GTP synthesis.•The alarmones pppGpp, ppGpp, and pGpp bind XPRT's PRPP binding motif.•XPRT is potently inhibited by pGpp and ppGpp and moderately inhibited by pppGpp.•XPRT dimers cooperatively bind (p)ppGpp using bridging loops between two monomers.•Regulation of XPRT protects cell viability during growth with environmental xanthine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Secure sustainable seafood from developing countries Sampson, Gabriel S; Sanchirico, James N; Roheim, Cathy A ...
Science (American Association for the Advancement of Science),
05/2015, Volume:
348, Issue:
6234
Journal Article
Peer reviewed
Demand for sustainably certified wild-caught fish and crustaceans is increasingly shaping global seafood markets. Retailers such as Walmart in the United States, Sainsbury's in the United Kingdom, ...and Carrefour in France, and processors such as Canadianbased High Liner Foods, have promised to source all fresh, frozen, farmed, and wild seafood from sustainable sources by 2015 (1, 2). Credible arbiters of certifications, such as the Marine Stewardship Council (MSC), require detailed environmental and traceability standards. Although these standards have been met in many commercial fisheries throughout the developed world (3), developing country fisheries (DCFs) represent only 7% of ~220 total MSC-certified fisheries (4, 5). With the United Nations Food and Agriculture Organization reporting that developing countries account for ~50% of seafood entering international trade, this presents a fundamental challenge for marketers of sustainable seafood (see the photo).
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The Magnetospheric Multiscale (MMS) spacecraft obtained unprecedented high‐time resolution multipoint particle and field measurements of an interplanetary shock event on 8 January 2018. The ...spacecraft encountered the supercritical forward shock of a forward/reverse shock pair in the pristine solar wind upstream of the bow shock near the subsolar point as they neared apogee at ~25 RE. The high‐time resolution measurements from the four spacecraft, separated by only ~20 km, allowed direct measurement of particle distributions revealing evidence of electron heating and near specularly reflected ions. The cross‐shock potential is calculated directly from 3‐D electric field measurements. This is the first reported direct high temporal resolution (<1 s) observation at an interplanetary shock of near specularly reflected ions. Calculation of the cross‐shock potential yields a potential jump significant enough to reflect at least some of the protons from the incident solar wind beam. The cross‐shock potential calculated here is consistent with previous estimations based on particle measurements and numerical/analytical simulations. The ambipolar contribution to the cross‐shock potential calculated from the four‐spacecraft divergence of the electron pressure tensor is somewhat higher than that inferred form the Liouville‐mapped electron energy gain across the shock. Furthermore, the high‐time‐resolution 3‐D electric field measurements reported here reveal small‐scale nonlinear structures embedded in the shock layer that contribute to the nonmonotonic shock transition.
Key Points
MMS observed a supercritical IP shock in the upstream pristine solar wind, directly resolving near specularly reflected ions
The cross‐shock potential jump calculated from 3‐D E‐field measurements is consistent with the observed electron heating and ion reflection
The high‐temporal‐resolution 3‐D electric field measurements revealed small‐scale nonlinear structures embedded within the shock front
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
There is growing recognition that fisheries should be managed for all three pillars of sustainability: economic, social and environmental sustainability. Limited quantitative evidence exists on ...factors supporting social sustainability, much less factors that contribute to multiple dimensions of sustainability. To develop a broader understanding of the factors that influence the performance of fishery management systems in environmental, economic and social pillars, we examine 11 input factors conjectured to contribute to successful fisheries using a global dataset of 145 fisheries case studies. The analysis indicates that management approaches are cross‐cutting and contribute to multiple dimensions of sustainability to varying extents. Importantly, factors exogenous to fisheries management can be as important as fisheries management, suggesting collaboration of fisheries institutions with other public and private institutions is important for sustainable fisheries development.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Summary
CXCR4WHIM somatic mutations are distinctive to Waldenström Macroglobulinaemia (WM), and impact disease presentation and treatment outcome. The clonal architecture of CXCR4WHIM mutations ...remains to be delineated. We developed highly sensitive allele‐specific polymerase chain reaction (AS‐PCR) assays for detecting the most common CXCR4WHIM mutations (CXCR4S338X C>A and C>G) in WM. The AS‐PCR assays detected CXCR4S338X mutations in WM and IgM monoclonal gammopathy of unknown significance (MGUS) patients not revealed by Sanger sequencing. By combined AS‐PCR and Sanger sequencing, CXCR4WHIM mutations were identified in 44/102 (43%), 21/62 (34%), 2/12 (17%) and 1/20 (5%) untreated WM, previously treated WM, IgM MGUS and marginal zone lymphoma patients, respectively, but no chronic lymphocytic leukaemia, multiple myeloma, non‐IgM MGUS patients or healthy donors. Cancer cell fraction analysis in WM and IgM MGUS patients showed CXCR4S338X mutations were primarily subclonal, with highly variable clonal distribution (median 35·1%, range 1·2–97·5%). Combined AS‐PCR and Sanger sequencing revealed multiple CXCR4WHIM mutations in many individual WM patients, including homozygous and compound heterozygous mutations validated by deep RNA sequencing. The findings show that CXCR4WHIM mutations are more common in WM than previously revealed, and are primarily subclonal, supporting their acquisition after MYD88L265P in WM oncogenesis. The presence of multiple CXCR4WHIM mutations within individual WM patients may be indicative of targeted CXCR4 genomic instability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Aquaculture is a rapidly growing food production technology, but there are significant concerns related to its environmental impact and adverse social effects. We examine aquaculture ...outcomes in a three pillars of sustainability framework by analyzing data collected using the Aquaculture Performance Indicators. Using this approach, comparable data has been collected for 57 aquaculture systems worldwide on 88 metrics that measure social, economic, or environmental outcomes. We first examine the relationships among the three pillars of sustainability and then analyze performance in the three pillars by technology and species. The results show that economic, social, and environmental outcomes are, on average, mutually reinforced in global aquaculture systems. However, the analysis also shows significant variation in the degree of sustainability in different aquaculture systems, and weak performance of some production systems in some dimensions provides opportunity for innovative policy measures and investment to further align sustainability objectives.
We present characteristics of current layers in the off‐equatorial near‐Earth plasma sheet boundary observed with high time‐resolution measurements from the Magnetospheric Multiscale mission during ...an intense substorm associated with multiple dipolarizations. The four Magnetospheric Multiscale spacecraft, separated by distances of about 50 km, were located in the southern hemisphere in the dusk portion of a substorm current wedge. They observed fast flow disturbances (up to about 500 km/s), most intense in the dawn‐dusk direction. Field‐aligned currents were observed initially within the expanding plasma sheet, where the flow and field disturbances showed the distinct pattern expected in the braking region of localized flows. Subsequently, intense thin field‐aligned current layers were detected at the inner boundary of equatorward moving flux tubes together with Earthward streaming hot ions. Intense Hall current layers were found adjacent to the field‐aligned currents. In particular, we found a Hall current structure in the vicinity of the Earthward streaming ion jet that consisted of mixed ion components, that is, hot unmagnetized ions, cold E × B drifting ions, and magnetized electrons. Our observations show that both the near‐Earth plasma jet diversion and the thin Hall current layers formed around the reconnection jet boundary are the sites where diversion of the perpendicular currents take place that contribute to the observed field‐aligned current pattern as predicted by simulations of reconnection jets. Hence, multiscale structure of flow braking is preserved in the field‐aligned currents in the off‐equatorial plasma sheet and is also translated to ionosphere to become a part of the substorm field‐aligned current system.
Key Points
Multiscale field‐aligned currents in the boundary of the expanding plasma sheet during plasma jet braking intervals are resolved
Intense Hall current layers are found at the inner boundary of the hot Earthward streaming ion jets and flow shear regions
Both plasma jet diversion and Hall effects from reconnection region contribute to the structure of the substorm wedge currents
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•Fate of current-use pesticides in an agricultural estuary is documented.•Pesticide application corresponded to maximum in-stream pesticide concentrations.•Relationship in bed sediment pesticide ...concentrations and distance from source.•Fish and crabs accumulate current-use pesticides, including fungicides.•First report on the occurrence and accumulation of fungicides in tissue.
The current study documents the fate of current-use pesticides in an agriculturally-dominated central California coastal estuary by focusing on the occurrence in water, sediment and tissue of resident aquatic organisms. Three fungicides (azoxystrobin, boscalid, and pyraclostrobin), one herbicide (propyzamide) and two organophosphate insecticides (chlorpyrifos and diazinon) were detected frequently. Dissolved pesticide concentrations in the estuary corresponded to the timing of application while bed sediment pesticide concentrations correlated with the distance from potential sources. Fungicides and insecticides were detected frequently in fish and invertebrates collected near the mouth of the estuary and the contaminant profiles differed from the sediment and water collected. This is the first study to document the occurrence of many current-use pesticides, including fungicides, in tissue. Limited information is available on the uptake, accumulation and effects of current-use pesticides on non-target organisms. Additional data are needed to understand the impacts of pesticides, especially in small agriculturally-dominated estuaries.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Tumor cells can induce certain cytokines and soluble receptors that have a suppressive effect on the immune system. In this study, we showed that an extracellular portion of a membrane-bound ligand ...of CD40 (soluble CD40 ligand; sCD40L) was significantly elevated in the serum of cancer patients compared with healthy donors. In addition, PBMCs from cancer patients had a relatively larger population of myeloid-derived suppressor cells (MDSCs), defined as CD33+HLA-DR− cells, and these cells expressed higher levels of CD40. T-cell proliferation and IFN-γ production decreased when stimulated T cells were cocultured with an increased amount of autologous MDSCs. The addition of recombinant monomeric sCD40L enriched MDSCs and had an additive inhibitory effect on T-cell proliferation. PBMCs cultured in vitro with sCD40L also showed an expansion of regulatory T cells (CD4+CD25highFoxp3+), as well as induction of cytokines, such as IL-10 and IL-6. Moreover, sCD40L-induced enrichment of programmed death-1–expressing T cells was greater in cancer patients than in healthy donors. Preexisting sCD40L also inhibited IL-12 production from monocytes on activation. These data suggest that the higher levels of sCD40L seen in cancer patients may have an immunosuppressive effect. These studies were registered at www.clinicaltrials.gov as NCT00060528, NCT00019695, NCT00179309, NCT00514072, NCT00081848, and NCT00436956.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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