124 research outputs found
Consent Searches in Montana: Basic Elements of the Test for Voluntariness
Consent Searches In Montana: Basic Elements Of The Test For Voluntarines
Consent Searches in Montana: Basic Elements of the Test for Voluntariness
Consent Searches In Montana: Basic Elements Of The Test For Voluntarines
Precision Cultural Practices for Commercial Vegetable Production (Bulletin #836)
The objectives of this bulletin are to present a summary of research on precision cultural practices by the LSU AgCenter, to explain and discuss the advantages of these cultural practices, and to recommend practices that should help commercial vegetable growers.https://digitalcommons.lsu.edu/agcenter_bulletins/1010/thumbnail.jp
Recurrent De Novo NAHR Reciprocal Duplications in the ATAD3 Gene Cluster Cause a Neurogenetic Trait with Perturbed Cholesterol and Mitochondrial Metabolism
Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The recessive form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates with a lethal metabolic disorder characterized by cardiomyopathy, corneal opacities, encephalopathy, hypotonia, and seizures in whom a monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis of the breakpoint junction fragment indicated that these 67 kb heterozygous duplications were likely mediated by non-allelic homologous recombination at regions of high sequence identity in ATAD3A exon 11 and ATAD3C exon 7. At the recombinant junction, the duplication allele produces a fusion gene derived from ATAD3A and ATAD3C, the protein product of which lacks key functional residues. Analysis of fibroblasts derived from two affected individuals shows that the fusion gene product is expressed and stable. These cells display perturbed cholesterol and mitochondrial DNA organization similar to that observed for individuals with severe ATAD3A deficiency. We hypothesize that the fusion protein acts through a dominant-negative mechanism to cause this fatal mitochondrial disorder. Our data delineate a molecular diagnosis for this disorder, extend the clinical spectrum associated with structural variation at the ATAD3 locus, and identify a third mutational mechanism for ATAD3 gene cluster variants. These results further affirm structural variant mutagenesis mechanisms in sporadic disease traits, emphasize the importance of copy number analysis in molecular genomic diagnosis, and highlight some of the challenges of detecting and interpreting clinically relevant rare gene rearrangements from next-generation sequencing data.This article is freely available via Open Access. Click on the publisher URL to access it via the publisher's site.We acknowledge funding from Wellcome ( 200990 ). S.E. is a Wellcome Senior Investigator. U.F.P. is supported by a predoctoral fellowship from the Basque Government ( PRE_2018_1_0253 ). M.M.O. is supported by a predoctoral fellowship from the University of the Basque Country ( UPV/EHU, PIF 2018 ). I.J.H. is supported by the Carlos III Health Program ( PI17/00380 ), and PaÃs Vasco Department of Health ( 2018111043 ; 2018222031 ). A.S. is supported by the UK Medical Research Council with a Senior Non-Clinical Fellowship ( MC_PC_13029 ). T. Harel is supported by the Israel Science Foundation grant 1663/17 . W.H.Y. is supported by the National Institute of General Medical Sciences of the National Institutes of Health through grant 5 P20 GM103636-07 . J.R.L. is supported by the US National Institute of Neurological Disorders and Stroke ( R35NS105078 ), the National Institute of General Medical Sciences ( R01GM106373 ), and the National Human Genome Research Institute and National Heart Lung and Blood Institute (NHGRI/NHBLI) to the Baylor-Hopkins Center for Mendelian Genomics (BHCMG, UM1 HG006542 ). R.W.T. is supported by the Wellcome Centre for Mitochondrial Research ( 203105/Z/16/Z ), the Medical Research Council (MRC) International Centre for Genomic Medicine in Neuromuscular Disease , Mitochondrial Disease Patient Cohort (UK) ( G0800674 ), the UK NIHR Biomedical Research Centre for Aging and Age-related disease award to the Newcastle upon Tyne Foundation Hospitals NHS Trust, the MRC/EPSRC Molecular Pathology Node , The Lily Foundation , and the UK NHS Highly Specialised Service for Rare Mitochondrial Disorders of Adults and Children . The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003). This study makes use of DECIPHER, which is funded by Wellcome. See Nature PMID: 25533962 or https://www.ddduk.org/access.html for full acknowledgment.pre-print, post-print (6 month embargo
Lead Bullet Fragments in Venison from Rifle-Killed Deer: Potential for Human Dietary Exposure
Human consumers of wildlife killed with lead ammunition may be exposed to health risks associated with lead ingestion. This hypothesis is based on published studies showing elevated blood lead concentrations in subsistence hunter populations, retention of ammunition residues in the tissues of hunter-killed animals, and systemic, cognitive, and behavioral disorders associated with human lead body burdens once considered safe. Our objective was to determine the incidence and bioavailability of lead bullet fragments in hunter-killed venison, a widely-eaten food among hunters and their families. We radiographed 30 eviscerated carcasses of White-tailed Deer (Odocoileus virginianus) shot by hunters with standard lead-core, copper-jacketed bullets under normal hunting conditions. All carcasses showed metal fragments (geometric mean = 136 fragments, range = 15–409) and widespread fragment dispersion. We took each carcass to a separate meat processor and fluoroscopically scanned the resulting meat packages; fluoroscopy revealed metal fragments in the ground meat packages of 24 (80%) of the 30 deer; 32% of 234 ground meat packages contained at least one fragment. Fragments were identified as lead by ICP in 93% of 27 samples. Isotope ratios of lead in meat matched the ratios of bullets, and differed from background lead in bone. We fed fragment-containing venison to four pigs to test bioavailability; four controls received venison without fragments from the same deer. Mean blood lead concentrations in pigs peaked at 2.29 µg/dL (maximum 3.8 µg/dL) 2 days following ingestion of fragment-containing venison, significantly higher than the 0.63 µg/dL averaged by controls. We conclude that people risk exposure to bioavailable lead from bullet fragments when they eat venison from deer killed with standard lead-based rifle bullets and processed under normal procedures. At risk in the U.S. are some ten million hunters, their families, and low-income beneficiaries of venison donations
Peptide-Based Scaffolds Support Human Cortical Progenitor Graft Integration to Reduce Atrophy and Promote Functional Repair in a Model of Stroke
Stem cell transplants offer significant hope for brain repair following ischemic damage. Pre-clinical work suggests that therapeutic mechanisms may be multi-faceted, incorporating bone-fide circuit reconstruction by transplanted neurons, but also protection/regeneration of host circuitry. Here, we engineered hydrogel scaffolds to form "bio-bridges" within the necrotic lesion cavity, providing physical and trophic support to transplanted human embryonic stem cell-derived cortical progenitors, as well as residual host neurons. Scaffolds were fabricated by the self-assembly of peptides for a laminin-derived epitope (IKVAV), thereby mimicking the brain's major extracellular protein. Following focal ischemia in rats, scaffold-supported cell transplants induced progressive motor improvements over 9 months, compared to cell- or scaffold-only implants. These grafts were larger, exhibited greater neuronal differentiation, and showed enhanced electrophysiological properties reflective of mature, integrated neurons. Varying graft timing post-injury enabled us to attribute repair to both neuroprotection and circuit replacement. These findings highlight strategies to improve the efficiency of stem cell grafts for brain repair
Two-dimensional Transport Induced Linear Magneto-Resistance in Topological Insulator BiSe Nanoribbons
We report the study of a novel linear magneto-resistance (MR) under
perpendicular magnetic fields in Bi2Se3 nanoribbons. Through angular dependence
magneto-transport experiments, we show that this linear MR is purely due to
two-dimensional (2D) transport, in agreement with the recently discovered
linear MR from 2D topological surface state in bulk Bi2Te3, and the linear MR
of other gapless semiconductors and graphene. We further show that the linear
MR of Bi2Se3 nanoribbons persists to room temperature, underscoring the
potential of exploiting topological insulator nanomaterials for room
temperature magneto-electronic applications.Comment: ACS Nano, in pres
The Mycobacterium tuberculosis Drugome and Its Polypharmacological Implications
We report a computational approach that integrates structural bioinformatics, molecular modelling and systems biology to construct a drug-target network on a structural proteome-wide scale. The approach has been applied to the genome of Mycobacterium tuberculosis (M.tb), the causative agent of one of today's most widely spread infectious diseases. The resulting drug-target interaction network for all structurally characterized approved drugs bound to putative M.tb receptors, we refer to as the ‘TB-drugome’. The TB-drugome reveals that approximately one-third of the drugs examined have the potential to be repositioned to treat tuberculosis and that many currently unexploited M.tb receptors may be chemically druggable and could serve as novel anti-tubercular targets. Furthermore, a detailed analysis of the TB-drugome has shed new light on the controversial issues surrounding drug-target networks [1]–[3]. Indeed, our results support the idea that drug-target networks are inherently modular, and further that any observed randomness is mainly caused by biased target coverage. The TB-drugome (http://funsite.sdsc.edu/drugome/TB) has the potential to be a valuable resource in the development of safe and efficient anti-tubercular drugs. More generally the methodology may be applied to other pathogens of interest with results improving as more of their structural proteomes are determined through the continued efforts of structural biology/genomics
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Acrylamide-Forming Potential and Agronomic Properties of Elite US Potato Germplasm from the National Fry Processing Trial
Processed potato (Solanum tuberosum L.) products, such as chips and French fries, contribute to the dietary intake of acrylamide, a suspected human carcinogen. One of the most promising approaches for reducing its consumption is to develop and commercialize new potato varieties with low acrylamide-forming potential. To facilitate this effort, a National Fry Processing Trial (NFPT) was conducted from 2011 to 2013 in five states. More than 140 advanced breeding lines were evaluated for tuber agronomic traits and biochemical properties from harvest through 8 mo of storage. Thirty-eight and 29 entries had significantly less acrylamide in French fries than standard varieties Russet Burbank and Ranger Russet, with reductions in excess of 50%, after one and 8 mo of storage, respectively. As in previous studies, the glucose content of raw tubers was predictive of acrylamide in finished French fries (R² = 0.64–0.77). Despite its role in acrylamide formation, tuber free asparagine was not significant, potentially because it showed relatively little variation in the NFPT population. Even when glucose was included in the model as a covariate, genotype was highly significant (p = 0.001) for predicting acrylamide, indicating there may be yet-unidentified genetic loci to target in breeding. The NFPT has demonstrated that there exist many elite US breeding lines with low acrylamide-forming potential. Our ongoing challenge is to combine this trait with complex quality attributes required by the fry processing industry.This is the publisher’s final pdf. The published article is copyrighted by the Crop Science Society of America and can be found at: https://dl.sciencesocieties.org/publications/c
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