775 research outputs found

    Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation

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    Ischemia reperfusion injury results from tissue damage during ischemia and ongoing inflammation and injury during reperfusion. Liver reperfusion injury is reduced by lymphocyte depletion or activation of adenosine A2A receptors (A2ARs) with the selective agonist 4- {3-[6-amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]- prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester (ATL146e). We show that NKT cells are stimulated to produce interferon (IFN)-Îł by 2 h after the initiation of reperfusion, and the use of antibodies to deplete NK1.1-positive cells (NK and NKT) or to block CD1d-mediated glycolipid presentation to NKT cells replicates, but is not additive to, the protection afforded by ATL146e, as assessed by serum alanine aminotransferase elevation, histological necrosis, neutrophil accumulation, and serum IFN-Îł elevation. Reduced reperfusion injury observed in RAG-1 knockout (KO) mice is restored to the wild-type (WT) level by adoptive transfer of NKT cells purified from WT or A2AR KO mice but not IFN-Îł KO mice. Additionally, animals with transferred A2AR−/− NKT cells are not protected from hepatic reperfusion injury by ATL146e. In vitro, ATL146e potently inhibits both anti-CD3 and α-galactosylceramide–triggered production of IFN-Îł by NKT cells. These findings suggest that hepatic reperfusion injury is initiated by the CD1d-dependent activation of NKT cells, and the activation of these cells is inhibited by A2AR activation

    Exploring variations in childhood stunting in Nigeria using league table, control chart and spatial analysis

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    Background: Stunting, linear growth retardation is the best measure of child health inequalities as it captures multiple dimensions of children’s health, development and environment where they live. The developmental priorities and socially acceptable health norms and practices in various regions and states within Nigeria remains disaggregated and with this, comes the challenge of being able to ascertain which of the regions and states identifies with either high or low childhood stunting to further investigate the risk factors and make recommendations for action oriented policy decisions. Methods: We used data from the birth histories included in the 2008 Nigeria Demographic and Health Survey (DHS) to estimate childhood stunting. Stunting was defined as height for age below minus two standard deviations from the median height for age of the standard World Health Organization reference population. We plotted control charts of the proportion of childhood stunting for the 37 states (including federal capital, Abuja) in Nigeria. The Local Indicators of Spatial Association (LISA) were used as a measure of the overall clustering and is assessed by a test of a null hypothesis. Results: Childhood stunting is high in Nigeria with an average of about 39%. The percentage of children with stunting ranged from 11.5% in Anambra state to as high as 60% in Kebbi State. Ranking of states with respect to childhood stunting is as follows: Anambra and Lagos states had the least numbers with 11.5% and 16.8% respectively while Yobe, Zamfara, Katsina, Plateau and Kebbi had the highest (with more than 50% of their underfives having stunted growth). Conclusions: Childhood stunting is high in Nigeria and varied significantly across the states. The northern states have a higher proportion than the southern states. There is an urgent need for studies to explore factors that may be responsible for these special cause variations in childhood stunting in Nigeria

    Characterization of small RNA populations in non-transgenic andaflatoxin-reducing-transformed peanut

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    Aflatoxin contamination is a major constraint in food production worldwide. In peanut (Arachis hypogaea L.), these toxic and carcinogenic aflatoxins are mainly produced by Aspergillus flavus Link and A. parasiticus Speare. The use of RNA interference (RNAi) is a promising method to reduce or prevent the accumula-tion of aflatoxin in peanut seed. In this study, we performed high-throughput sequencing of small RNApopulations in a control line and in two transformed peanut lines that expressed an inverted repeattargeting five genes involved in the aflatoxin-biosynthesis pathway and that showed up to 100% less aflatoxin B1 than the controls. The objective was to determine the putative involvement of the smallRNA populations in aflatoxin reduction. In total, 41 known microRNA (miRNA) families and many novel miRNAs were identified. Among those, 89 known and 10 novel miRNAs were differentially expressed in the transformed lines. We furthermore found two small interfering RNAs derived from the inverted repeat, and 39 sRNAs that mapped without mismatches to the genome of A. flavus and were present only in the transformed lines. This information will increase our understanding of the effectiveness of RNAi and enable the possible improvement of the RNAi technology for the control of aflatoxins

    Study of the genetic diversity of the aflatoxin biosynthesis cluster in \u3ci\u3eAspergillus\u3c/i\u3e section \u3ci\u3eFlavi\u3c/i\u3e using insertion/deletion markers in peanut seeds from Georgia, USA

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    Aflatoxins are among themost powerful carcinogens in nature. The major aflatoxin-producing fungi are Aspergillus flavus and A. parasiticus. Numerous crops, including peanut, are susceptible to aflatoxin contamination by these fungi. There has been an increased use of RNA interference (RNAi) technology to control phytopathogenic fungi in recent years. In order to develop molecular tools targeting specific genes of these fungi for the control of aflatoxins, it is necessary to obtain their genome sequences. Although high-throughput sequencing is readily available, it is still impractical to sequence the genome of every isolate. Thus, in this work, the authors proposed a workflow that allowed prescreening of 238 Aspergillus section Flavi isolates from peanut seeds from Georgia, USA. The aflatoxin biosynthesis cluster (ABC) of the isolates was fingerprinted at 25 InDel (insertion/deletion) loci using capillary electrophoresis. All isolates were tested for aflatoxins using ultra-high-performance liquid chromatography. The neighbor- joining, three-dimension (3D) principal coordinate, and Structure analyses revealed that the Aspergillus isolates sampled consisted of three main groups determined by their capability to produce aflatoxins. Group I comprised 10 non-aflatoxigenic A. flavus; Group II included A. parasiticus; and Group III includedmostly aflatoxigenic A. flavus and the three non-aflatoxigenic A. caelatus.Whole genomes of 10 representative isolates from different groups were sequenced. Although InDels in Aspergillus have been used by other research groups, this is the first time that the cluster analysis resulting from fingerprinting was followed by whole-genome sequencing of representative isolates. In our study, cluster analysis of ABC sequences validated the results obtained with fingerprinting. This shows that InDels used here can predict similarities at the genome level. Our results also revealed a relationship between groups and their capability to produce aflatoxins. The database generated of Aspergillus spp. can be used to select target genes and assess the effectiveness of RNAi technology to reduce aflatoxin contamination in peanut. Supplementary file folder attached below

    GW150914: First search for the electromagnetic counterpart of a gravitational-wave event by the TOROS collaboration

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    We present the results of the optical follow-up conducted by the TOROS collaboration of the first gravitational-wave event GW150914. We conducted unfiltered CCD observations (0.35-1 micron) with the 1.5-m telescope at Bosque Alegre starting ~2.5 days after the alarm. Given our limited field of view (~100 square arcmin), we targeted 14 nearby galaxies that were observable from the site and were located within the area of higher localization probability. We analyzed the observations using two independent implementations of difference-imaging algorithms, followed by a Random-Forest-based algorithm to discriminate between real and bogus transients. We did not find any bona fide transient event in the surveyed area down to a 5-sigma limiting magnitude of r=21.7 mag (AB). Our result is consistent with the LIGO detection of a binary black hole merger, for which no electromagnetic counterparts are expected, and with the expected rates of other astrophysical transients.Comment: ApJ Letters, in pres

    A qualitative study of professional and carer perceptions of the threats to safe hospital discharge for stroke and hip fracture patients in the English National Health Service

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    Background: Hospital discharge is a vulnerable transitional stage in patient care. This qualitative study investigated the views of healthcare professionals and patients about the threats to safe hospital discharge with aim of identifying contributory and latent factors. The study was undertaken in two regional health and social care systems in the English National Health Service, each comprising three acute hospitals, community and primary care providers and municipal social care services. The study focused on the threats to safe discharge for hip fracture and stroke patients as exemplars of complex care transitions. Methods: A qualitative study involving narrative interviews with 213 representative stakeholders and professionals involved in discharge planning and care transition activities. Narratives were analysed in line with ‘systems’ thinking to identify proximal (active) and distal (latent) factors, and the relationships between them. Results: Three linked categories of commonly and consistently identified threat to safe discharge were identified:(1) ‘direct’ patient harms comprising falls, infection, sores and ulceration, medicines-related issues, and relapse; (2) proximal ‘contributing’ factors including completion of tests, assessment of patient, management of equipment and medicines, care plan, follow-up care and patient education; and distal ‘latent’ factors including discharge planning, referral processes, discharge timing, resources constraints, and organisational demands. Conclusion: From the perspective of stakeholders, the study elaborates the relationship between patient harms and systemic factors in the context of hospital discharge. It supports the importance of communication and collaboration across occupational and organisational boundaries, but also the challenges to supporting such communication with the inherent complexity of the care system

    Network effects, cooperation and entrepreneurial innovation in China

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    The rapid rise of an innovative private manufacturing economy in China challenges standard economic explanations of growth, which typically assume the existence of well-defined formal institutions such as property rights and company laws safeguarding investor and creditor interests. We highlight the social structure of cooperation that enables innovative activity in private manufacturing firms when formal property rights protection remains weak. We show how network effects linked to inter-firm cooperation in industrial clusters allowed private entrepreneurs to quickly develop reliable business norms to reduce the inherent risk of malfeasance and contract breach in formal and informal collaborative efforts. Survey data from a sample of 700 manufacturing firms located in China’s Yangzi Delta region confirms that both formal and informal types of inter-firm collaboration are effective, though in different areas of innovative activity

    Superplastic deformation of directionally solidified nanofibrillar Al2O3-Y3Al5O12-ZrO2 eutectics

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    Nanofibrillar Al2O3–Y3Al5O12–ZrO2 eutectic rods were manufactured by directional solidification from the melt at high growth rates in an inert atmosphere using the laser-heated floating zone method. Under conditions of cooperative growth, the ternary eutectic presented a homogeneous microstructure, formed by bundles of single-crystal c-oriented Al2O3 and Y3Al5O12 (YAG) whiskers of ≈100 nm in width with smaller Y2O3-doped ZrO2 (YSZ) whiskers between them. Owing to the anisotropic fibrillar microstructure, Al2O3–YAG–YSZ ternary eutectics present high strength and toughness at ambient temperature while they exhibit superplastic behavior at 1600 K and above. Careful examination of the deformed samples by transmission electron microscopy did not show any evidence of dislocation activity and superplastic deformation was attributed to mass-transport by diffusion within the nanometric domains. This combination of high strength and toughness at ambient temperature together with the ability to support large deformations without failure above 1600 K is unique and shows a large potential to develop new structural materials for very high temperature structural applications
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