1,315 research outputs found

    Hydraulic Geometry of Illinois Streams

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    published or submitted for publicationis peer reviewedOpe

    Mechanisms of Gasdermin Family Members in Inflammasome Signaling and Cell Death

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    The Gasdermin (GSDM) family consists of Gasdermin A (GSDMA), Gasdermin B (GSDMB), Gasdermin C (GSDMC), Gasdermin D (GSDMD), Gasdermin E (GSDME) and Pejvakin (PJVK). GSDMD is activated by inflammasome-associated inflammatory caspases. Cleavage of GSDMD by human or mouse caspase-1, human caspase-4, human caspase-5, and mouse caspase-11 liberates the N-terminal effector domain from the C-terminal inhibitory domain. The N-terminal domain oligomerizes in the cell membrane and forms a pore of 10-16 nm in diameter, through which substrates of a smaller diameter, such as interleukin-1β and interleukin-18, are secreted. The increasing abundance of membrane pores ultimately leads to membrane rupture and pyroptosis, releasing the entire cellular content. Other than GSDMD, the N-terminal domain of all GSDMs, with the exception of PJVK, have the ability to form pores. There is evidence to suggest that GSDMB and GSDME are cleaved by apoptotic caspases. Here, we review the mechanistic functions of GSDM proteins with respect to their expression and signaling profile in the cell, with more focused discussions on inflammasome activation and cell death.S.F. was supported by a scholarship from the China Scholarship Council. S.M.M. is supported by the Australian National University, The Gretel and Gordon Bootes Medical Research Foundation and the National Health and Medical Research Council of Australia under Project grants (APP1141504 and APP1146864) and the R.G. Menzies Early Career Fellowship (APP1091544)

    Bacillus cereus non-haemolytic enterotoxin activates the NLRP3 inflammasome

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    Inflammasomes are important for host defence against pathogens and homeostasis with commensal microbes. Here, we show non-haemolytic enterotoxin (NHE) from the neglected human foodborne pathogen Bacillus cereus is an activator of the NLRP3 inflammasome and pyroptosis. NHE is a non-redundant toxin to haemolysin BL (HBL) despite having a similar mechanism of action. Via a putative transmembrane region, subunit C of NHE initiates binding to the plasma membrane, leading to the recruitment of subunit B and subunit A, thus forming a tripartite lytic pore that is permissive to efflux of potassium. NHE mediates killing of cells from multiple lineages and hosts, highlighting a versatile functional repertoire in different host species. These data indicate that NHE and HBL operate synergistically to induce inflammation and show that multiple virulence factors from the same pathogen with conserved function and mechanism of action can be exploited for sensing by a single inflammasome

    A Novel Sparse Graphical Approach for Multimodal Brain Connectivity Inference

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    International audienceDespite the clear potential benefits of combining fMRI and diffusion MRI in learning the neural pathways that underlie brain functions, little methodological progress has been made in this direction. In this paper, we propose a novel multimodal integration approach based on sparse Gaussian graphical model for estimating brain connectivity. Casting functional connectivity estimation as a sparse inverse covariance learning problem, we adapt the level of sparse penalization on each connection based on its anatomical capacity for functional interactions. Functional connections with little anatomical support are thus more heavily penalized. For validation, we showed on real data collected from a cohort of 60 subjects that additionally modeling anatomical capacity significantly increases subject consistency in the detected connection patterns. Moreover, we demonstrated that incorporating a connectivity prior learned with our multimodal connectivity estimation approach improves activation detection

    Spring migration patterns, habitat use, and stopover site protection status for two declining waterfowl species wintering in China as revealed by satellite tracking

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    East Asian migratory waterfowl have greatly declined since the 1950s, especially the populations that winter in China. Conservation is severely hampered by the lack of primary information about migration patterns and stopover sites. This study utilizes satellite tracking techniques and advanced spatial analyses to investigate spring migration of the greater white‐fronted goose (Anser albifrons) and tundra bean goose (Anser serrirostris) wintering along the Yangtze River Floodplain. Based on 24 tracks obtained from 21 individuals during the spring of 2015 and 2016, we found that the Northeast China Plain is far‐out the most intensively used stopover site during migration, with geese staying for over 1 month. This region has also been intensely developed for agriculture, suggesting a causal link to the decline in East Asian waterfowl wintering in China. The protection of waterbodies used as roosting area, especially those surrounded by intensive foraging land, is critical for waterfowl survival. Over 90% of the core area used during spring migration is not protected. We suggest that future ground surveys should target these areas to confirm their relevance for migratory waterfowl at the population level, and core roosting area at critical spring‐staging sites should be integrated in the network of protected areas along the flyway. Moreover, the potential bird–human conflict in core stopover area needs to be further studied. Our study illustrates how satellite tracking combined with spatial analyses can provide crucial insights necessary to improve the conservation of declining Migratory species

    The changing environment of conservation conflict: geese and farming in Scotland

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    Conflict between conservation objectives and human livelihoods is ubiquitous and can be highly damaging, but the processes generating it are poorly understood. Ecological elements are central to conservation conflict, and changes in their dynamics — for instance due to anthropogenic environmental change — are likely to influence the emergence of serious human–wildlife impacts and, consequently, social conflict.  We used mixed-effects models to examine the drivers of historic spatio-temporal dynamics in numbers of Greenland barnacle geese (Branta leucopsis) on the Scottish island of Islay to identify the ecological processes that have shaped the environment in which conflict between goose conservation and agriculture has been triggered.  Barnacle goose numbers on Islay increased from 20,000 to 43,000 between 1987 and 2016. Over the same period, the area of improved grassland increased, the number of sheep decreased and the climate warmed.  Goose population growth was strongly linked to the increasing area of improved grassland, which provided geese with more high quality forage. Changing climatic conditions, particularly warming temperatures on Islay and breeding grounds in Greenland, have also boosted goose numbers.  As the goose population has grown, farms have supported geese more frequently and in larger numbers, with subsequent damaging effects on grassland. The creation of high-quality grassland appears to have largely driven the problem of serious economic damage by geese. Our analysis also reveals the drivers of spatial variation in goose impacts: geese were more likely to occur on farms closer to roosts and those with more improved grassland. However, as geese numbers have increased they have spread to previously less favoured farms.  Synthesis and applications. Our study demonstrates the primary role of habitat modification in the emergence of conflict between goose conservation and agriculture, alongside a secondary role of climate change. Our research illustrates the value of exploring socio-ecological history to understand the processes leading to conservation conflict. In doing so, we identify those elements that are more controllable, such as local habitat management, and less controllable, such as climate change, but which both need to be taken into account when managing conservation conflict

    An effective placental cotyledons proteins extraction method for 2D gel electrophoresis

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    Effective protein extraction is essential especially in producing a well-resolved proteome on 2D gels. A well-resolved placental cotyledon proteome, with good reproducibility, have allowed researchers to study the proteins underlying the physiology and pathophysiology of pregnancy. The aim of this study is to determine the best protein extraction protocol for the extraction of protein from placental cotyledons tissues for a two-dimensional gel electrophoresis (2D-GE). Based on widely used protein extraction strategies, 12 different extraction methodologies were carefully selected, which included one chemical extraction, two mechanical extraction coupled protein precipitations, and nine chemical extraction coupled protein precipitations. Extracted proteins were resolved in a one-dimensional gel electrophoresis and 2D-GE; then, it was compared with set criteria: extraction efficacy, protein resolution, reproducibility, and recovery efficiency. Our results revealed that a better profile was obtained by chemical extraction in comparison to mechanical extraction. We further compared chemical extraction coupled protein precipitation methodologies, where the DNase/lithium chloride-dense sucrose homogenization coupled dichloromethane-methanol precipitation (DNase/LiCl-DSH-D/MPE) method showed good protein extraction efficiency. This, however, was carried out with the best protein resolution and proteome reproducibility on 2D-gels. DNase/LiCl-DSH-D/MPE was efficient in the extraction of proteins from placental cotyledons tissues. In addition, this methodology could hypothetically allow the protein extraction of any tissue that contains highly abundant lipid and glycogen

    Helicobacter species are associated with possible increase in risk of biliary lithiasis and benign biliary diseases

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    <p>Abstract</p> <p>Background</p> <p>Hepato-biliary tract lithiasis is common and present either as pain or as asymptomatic on abdominal ultrasonography for other causes. Although the DNA of <it>Helicobacter </it>species are identified in the gallbladder bile, tissue or stones analyzed from these cases, still a causal relationship could not be established due to different results from different geographical parts.</p> <p>Methods</p> <p>A detailed search of pubmed and pubmedcentral was carried out with key words <it>Helicobacter </it>and gallbladder, gallstones, hepaticolithiasis, cholelithiasis and choledocholithiasis, benign biliary diseases, liver diseases. The data was entered in a data base and meta analysis was carried out. The analysis was carried out using odds ratio and a fixed effect model, 95% confidence intervals for odds ratio was calculated. Chi square test for heterogeneity was employed. The overall effect was calculated using Z test.</p> <p>Results</p> <p>A total of 12 articles were identified. One study used IgG for diagnosis while others used the PCR for Ure A gene, 16 S RNA or Cag A genes. A couple of studies used culture or histopathology besides the PCR. The cumulative results show a higher association of <it>Helicobacter </it>with chronic liver diseases (30.48%), and stone diseases (42.96%)(OR 1.77 95% CI 1.2–2.58; Z = 2.94, p = 0.003), the effect of each could not be identified as it was difficult to isolate the effect of helicobacter due to mixing of cases in each study.</p> <p>Conclusion</p> <p>The results of present meta analysis shows that there is a slight higher risk of cholelithiasis and benign liver disease (OR 1.77), however due to inherent inability to isolate the effect of stone disease from that of other benign lesions it is not possible to say for sure that <it>Helicobacter </it>has a casual relationship with benign biliary disease or stone disease or both.</p

    Pathogenic Intestinal Bacteria Enhance Prostate Cancer Development via Systemic Activation of Immune Cells in Mice

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    A role for microbes has been suspected in prostate cancer but difficult to confirm in human patients. We show here that a gastrointestinal (GI) tract bacterial infection is sufficient to enhance prostate intraepithelial neoplasia (PIN) and microinvasive carcinoma in a mouse model. We found that animals with a genetic predilection for dysregulation of wnt signaling, Apc[superscript Min/+] mutant mice, were significantly susceptible to prostate cancer in an inflammation-dependent manner following infection with Helicobacter hepaticus. Further, early neoplasia observed in infected Apc[superscript Min/+] mice was transmissible to uninfected mice by intraperitoneal injection of mesenteric lymph node (MLN) cells alone from H. hepaticus-infected mutant mice. Transmissibility of neoplasia was preventable by prior neutralization of inflammation using anti-TNF-α antibody in infected MLN donor mice. Taken together, these data confirm that systemic inflammation triggered by GI tract bacteria plays a pivotal role in tumorigenesis of the prostate gland.RO1CA108854National Institute of Environmental Health Sciences (Massachusetts Institute of Technology. Center for Environmental Health Sciences Pilot Project Award P30-ES002109

    Neutrino Mass, Sneutrino Dark Matter and Signals of Lepton Flavor Violation in the MRSSM

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    We study the phenomenology of mixed-sneutrino dark matter in the Minimal R-Symmetric Supersymmetric Standard Model (MRSSM). Mixed sneutrinos fit naturally within the MRSSM, as the smallness (or absence) of neutrino Yukawa couplings singles out sneutrino A-terms as the only ones not automatically forbidden by R-symmetry. We perform a study of randomly generated sneutrino mass matrices and find that (i) the measured value of ΩDM\Omega_{DM} is well within the range of typical values obtained for the relic abundance of the lightest sneutrino, (ii) with small lepton-number-violating mass terms mnn2n~n~m_{nn}^{2} {\tilde n} {\tilde n} for the right-handed sneutrinos, random matrices satisfying the ΩDM\Omega_{DM} constraint have a decent probability of satisfying direct detection constraints, and much of the remaining parameter space will be probed by upcoming experiments, (iii) the mnn2n~n~m_{nn}^{2} {\tilde n} {\tilde n} terms radiatively generate appropriately small Majorana neutrino masses, with neutrino oscillation data favoring a mostly sterile lightest sneutrino with a dominantly mu/tau-flavored active component, and (iv) a sneutrino LSP with a significant mu component can lead to striking signals of e-mu flavor violation in dilepton invariant-mass distributions at the LHC.Comment: Revised collider analysis in Sec. 5 after fixing error in particle spectrum, References adde
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