11,866 research outputs found
The interferon-stimulated gene IFITM3 restricts West Nile virus infection and pathogenesis
The interferon-induced transmembrane protein (IFITM) family of proteins inhibit infection of several different enveloped viruses in cell culture by virtue of their ability to restrict entry and fusion from late endosomes. As few studies have evaluated the importance of Ifitm3 in vivo in restricting viral pathogenesis, we investigated its significance as an antiviral gene against West Nile virus (WNV), an encephalitic flavivirus, in cells and mice. Ifitm3(−/−) mice were more vulnerable to lethal WNV infection, and this was associated with greater virus accumulation in peripheral organs and central nervous system tissues. As no difference in viral burden in the brain or spinal cord was observed after direct intracranial inoculation, Ifitm3 likely functions as an antiviral protein in nonneuronal cells. Consistent with this, Ifitm3(−/−) fibroblasts but not dendritic cells resulted in higher yields of WNV in multistep growth analyses. Moreover, transcomplementation experiments showed that Ifitm3 inhibited WNV infection independently of Ifitm1, Ifitm2, Ifitm5, and Ifitm6. Beyond a direct effect on viral infection in cells, analysis of the immune response in WNV-infected Ifitm3(−/−) mice showed decreases in the total number of B cells, CD4(+) T cells, and antigen-specific CD8(+) T cells. Finally, bone marrow chimera experiments demonstrated that Ifitm3 functioned in both radioresistant and radiosensitive cells, as higher levels of WNV were observed in the brain only when Ifitm3 was absent from both compartments. Our analyses suggest that Ifitm3 restricts WNV pathogenesis likely through multiple mechanisms, including the direct control of infection in subsets of cells. IMPORTANCE As part of the mammalian host response to viral infections, hundreds of interferon-stimulated genes (ISGs) are induced. The inhibitory activity of individual ISGs varies depending on the specific cell type and viral pathogen. Among ISGs, the genes encoding interferon-induced transmembrane protein (IFITM) have been reported to inhibit multiple families of viruses in cell culture. However, few reports have evaluated the impact of IFITM genes on viral pathogenesis in vivo. In this study, we characterized the antiviral activity of Ifitm3 against West Nile virus (WNV), an encephalitic flavivirus, using mice with a targeted gene deletion of Ifitm3. Based on extensive virological and immunological analyses, we determined that Ifitm3 protects mice from WNV-induced mortality by restricting virus accumulation in peripheral organs and, subsequently, in central nervous system tissues. Our data suggest that Ifitm3 restricts WNV pathogenesis by multiple mechanisms and functions in part by controlling infection in different cell types
Warmblood fragile foal syndrome type 1 mutation (PLOD1 c.2032G>A) is not associated with catastrophic breakdown and has a low allele frequency in the Thoroughbred breed.
BackgroundCatastrophic fractures are among the most common cause of fatalities in racehorses. Several factors, including genetics, likely contribute to increased risk for fatal injuries. A variant in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase1 gene (PLOD1 c.2032G>A) was shown to cause Warmblood fragile foal syndrome type 1 (WFFS), a fatal recessive defect of the connective tissue. Screening of multiple horse breeds identified the presence of the WFFS allele in the Thoroughbred. PLOD1 is involved in cross-linking of collagen fibrils and thus could potentially increase the risk of catastrophic breakdown.ObjectivesEstimate the frequency of the WFFS allele (PLOD1 c.2032G>A) and determine if it is a risk factor for catastrophic breakdown in the Thoroughbred.Study designCase-control genetic study.MethodsGenomic DNA from hair and/or tissue samples was genotyped for the WFFS allele. Fisher's Exact tests were performed to compare allele and carrier frequencies between the case cohort (catastrophic breakdown, n = 22) and several cohorts with no record of injury (n = 138 raced/trained at same track and season and n = 185 older than 7 years and raced during same season), nonracers (n = 92), and a random sample without consideration for racing history (n = 279).ResultsThe frequency of the PLOD1 c.2032G>A variant in the Thoroughbred breed is low (1.2%). Seventeen of 716 Thoroughbreds tested were carriers (2.4%) and no WFFS homozygotes were detected. Only one catastrophic breakdown case carried the WFFS allele. No statistically significant difference in allele or carrier frequency was identified between case and control cohorts (P>0.05 in all comparisons performed).Main limitationsThis study evaluated cases from one single track.ConclusionsThis study demonstrated that the PLOD1 c.2032G>A associated with WFFS is present at very low frequency in Thoroughbreds and is not a genetic risk factor for catastrophic breakdown
Fabric analysis of allende matrix using EBSD
Accepted versio
Applicability of an integrated moving sponge biocarrier-osmotic membrane bioreactor MD system for saline wastewater treatment using highly salt-tolerant microorganisms
© 2017 Elsevier B.V. Osmotic membrane bioreactors (OsMBRs) are a recent breakthrough technology designed to treat wastewater. Nevertheless, their application in high-salinity wastewater treatment is not widespread because of the effects of saline conditions on microbial community activity. In response, this study developed an integrated sponge biocarrier-OsMBR system using highly salt-tolerant microorganisms for treating saline wastewater. Results showed that the sponge biocarrier-OsMBR obtained an average water flux of 2 L/m2 h during a 92-day operation when 1 M MgCl2 was used as the draw solution. The efficiency in removing dissolved organic compounds from the proposed system was more than 99%, and nutrient rejection was close to 100%, indicating excellent performance in simultaneous nitrification and denitrification processes in the biofilm layer on the carriers. Moreover, salt-tolerant microorganisms in the sponge biocarrier-OsMBR system worked efficiently in salt concentrations of 2.4%. A polytetrafluoroethylene MD membrane (pores = 0.45 μm) served to regenerate the diluted draw solution in the closed-loop system and produce high-quality water. The moving sponge biocarrier-OsMBR/MD hybrid system demonstrated its potential to treat salinity wastewater treatment, with 100% nutrient removal and 99.9% conductivity rejection
Anatomy of a mixed-influence shelf edge delta, Karoo Basin, South Africa
The position and process regime of paralic systems relative to the shelf edge rollover is a major control on sediment transfer into deep water. The depositional strike and dip variability of an exhumed Permian shelf edge succession has been studied in the Paardeberg Ridge, Karoo Basin. Siltstone-rich slope turbidites are overlain by 25–75 m-thick prodelta parasequences. These are truncated by a 30 m-thick sandstone-prone unit of tabular or convex-topped sandstones, interpreted as wave-modified mouth bars, cut by multiple irregular concave-upwards erosive surfaces overlain by sandstones, interpreted as distributary channels. The stratigraphic context, lithofacies and architecture are consistent with a mixed-influence shelf edge delta; the erosional base to the unit marks a basinwards shift in facies, consistent with a sequence boundary. Channels become thicker, wider, more erosive and incise into deeper-water facies downdip and correlate with sandstone-rich upper slope turbidites, all of which support the bypass of sand across the rollover. The overall progradational stacking pattern results in a stratigraphic decrease in channel dimensions. The results of this study suggest a predictable relationship between channel geometry, facies and position on the shelf-to-slope profile under a mixed wave and fluvial process regime
The structure of the infinite models in integer programming
The infinite models in integer programming can be described as the convex
hull of some points or as the intersection of halfspaces derived from valid
functions. In this paper we study the relationships between these two
descriptions. Our results have implications for corner polyhedra. One
consequence is that nonnegative, continuous valid functions suffice to describe
corner polyhedra (with or without rational data)
Impact of Novel Sorghum Bran Diets on DSS-Induced Colitis.
We have demonstrated that polyphenol-rich sorghum bran diets alter fecal microbiota; however, little is known regarding their effect on colon inflammation. Our aim was to characterize the effect of sorghum bran diets on intestinal homeostasis during dextran sodium sulfate (DSS)-induced colitis. Male Sprague-Dawley rats (N = 20/diet) were provided diets containing 6% fiber from cellulose, or Black (3-deoxyanthocyanins), Sumac (condensed tannins) or Hi Tannin Black (both) sorghum bran. Colitis was induced (N = 10/diet) with three separate 48-h exposures to 3% DSS, and feces were collected. On Day 82, animals were euthanized and the colon resected. Only discrete mucosal lesions, with no diarrhea or bloody stools, were observed in DSS rats. Only bran diets upregulated proliferation and Tff3, Tgfβ and short chain fatty acids (SCFA) transporter expression after a DSS challenge. DSS did not significantly affect fecal SCFA concentrations. Bran diets alone upregulated repair mechanisms and SCFA transporter expression, which suggests these polyphenol-rich sorghum brans may suppress some consequences of colitis
Malaria control-two years' use of insecticide treated bednets compared with insecticide house spraying in KwaZulu-Natal
Objectives. The objective of this study was to produce data indicating whether insecticide-treated bednets should replaced insecticide house spraying as a malaria control method in South Africa. We report 2 years of preliminary data on malaria incidence comparing areas receiving insecticidetreated bednets and those subjected to house spraying in northern KwaZulu-Natal.Design, setting and subjects. In order to measure significant reductions in malaria incidence between the two interventions, a geographical information system (GIS) was used to identify and create seven pairs of geographical blocks (areas) in the malaria high-risk areas of Ndumu and Makanis in Ingwavuma magisterial district, KwaZulu-Natal. Individual blocks were then randomly allocated to either insecticide-treated bednets or house spraying with deltamethrin. Malaria cases were either routinely recorded by surveillance agents at home or were reported to the nearest health facility.Results and conclusions. The results show that 2 years' use of insecticide-treated bednets by communities in Ndumu and Makanis, KwaZulu-Natal, significantly reduced the malaria incidence both in 1997 (rate ratio (RR) = 0.879, 95% confidence interval (CI) 0.80- 0.95, P = 0.04) and in 1998 (RR = 0.667, CI 0.61 - 0.72, P= 0.0001). Using a t-test, these significant reductions were further confirmed by an assessment of the rate of change between 1996 and 1998, showing a 16% reduction in malaria incidence in blocks using treated bednets and an increase of 45% in sprayed areas (t =2.534, P = 0.026 (12 df)). In order to decide whether bednets should replace house spraying in South Africa, we need more data on the efficacy of treated bednets, their long-term acceptability and the cost of the two interventions
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