59 research outputs found

    Environmental Romanticism: The “Protection” of Nature Perpetuates Erasures of Indigenous Existence from Their Traditional Territories

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    This paper was originally written for Clifford Atleo’s Resource and Environmental Management (REM) 407: Indigenous Governance and Resource Relationships. The assignment asked students to engage with a subject of our choosing, related to any of the themes raised in class in greater depth. The paper uses the APA citation style. The essay investigates how environmentalism of the late 20th- and early 21st-century is embedded with the sentiment of keeping the wild intact. However, this conception of the natural environment as uninhabited and wild negates Indigenous presence on the land. Thus, environmental romanticizations of nature invalidate Indigenous self-determination while authorizing erasures of Indigenous existence in their unceded traditional territories. The paper explores the themes of Indigenous resource relationships, co-management, and environmentalism through case studies in Clayoquot Sound and Bella Bella, British Columbia, Canada

    Santa Clara - A LEED Certified Home

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    Santa Clara, a residence located in Dana Point, California, has been designed as a LEED Certified home. LEED, Leadership in Energy and Environmental Design, is a certification program for green building. There are various ratings that can be earned for homes including Certified, Silver, Gold and Platinum. In order to gain certification, a minimum of forty points must be obtained using the LEED V4 Homes and Multi-Family Midrise scorecard. This scorecard has eight categories, including: Location and Transportation, Sustainable Sites, Water Efficiency, Energy and Atmosphere, Materials and Resources, Indoor Environmental Quality, Innovation, and Regional Priority. Each category consists of prerequisites that are required as well as credits that can be obtained to earn points. The purpose of fulfilling these credits is to create a home that has better air quality, uses less energy and has less impact on the environment. An added benefit of having a LEED Certified home means lower utility bills for the homeowner. The site for Santa Clara is located at Lot Forty-One in the Strand Point community. Landscaping, including a pool and spa, are important to the homeowner. This must be considered while choosing LEED credits to obtain. The largest categories effected by the landscaping and pool are the Water Efficiency and Sustainable Sites. There are steps that can be taken to use less water even with the use of a pool and spa. After evaluating the homeowner’s wants and needs, forty-six points will be earned, allowing the home to become certified as LEED Bronze. A detailed list of how to achieve each point will be created, and proper evidence and documentation will be provided to show completion of each one

    Microencapsulated Dopamine (DA)-Induced Restitution of Function in 6-OHDA-Denervated Rat Striatum in vivo: Comparison Between Two Microsphere Excipients

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    Biodegradable controlled-release microsphere systems made with the biocompatible biodegradable polyester excipient poly [DL lactide-co-glycolide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microspheres encapsulated within two different polymer excipients into denervated- striatal tissue assures a prolonged release of the transmitter in vivo. Moreover, in this regard, the results show that there were clear cut temporal differences in the effect of the two DA microsphere formulations compared in this study, probably reflecting variations in the actual composition (i.e., lactide to glycolide ratio) of the two copolymer excipients examined. This technology has considerable potential for basic research with possible clinical application

    The novel cyst nematode effector protein 30D08 targets host nuclear functions to alter gene expression in feeding sites

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    • Cyst nematodes deliver effector proteins into host cells to manipulate cellular processes and establish a metabolically hyperactive feeding site. The novel 30D08 effector protein is produced in the dorsal gland of parasitic juveniles, but its function has remained unknown. • We demonstrate that expression of 30D08 contributes to nematode parasitism, the protein is packaged into secretory granules, and is targeted to the plant nucleus where it interacts with SMU2 (homologue of suppressor of mec-8 and unc-52 2), an auxiliary spliceosomal protein. • We show that SMU2 is expressed in feeding sites and a smu2 mutant is less susceptible to nematode infection. In Arabidopsis expressing 30D08 under the SMU2 promoter, several genes were found to be alternatively spliced and the most abundant functional classes represented among differentially expressed genes were involved in RNA processing, transcription and binding, as well as in development, hormone and secondary metabolism representing key cellular processes known to be important for feeding site formation. • In conclusion, we demonstrated that the 30D08 effector is secreted from the nematode and targeted to the plant nucleus where its interaction with a host auxiliary spliceosomal protein may alter the pre-mRNA splicing and expression of a subset of genes important for feeding site formation

    Plasma Bile Acid Concentrations in Patients with Human Immunodeficiency Virus Infection Receiving Protease Inhibitor Therapy: Possible Implications for Hepatotoxicity

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    To evaluate whether patients with human immunodeficiency virus (HIV) infection who were receiving protease inhibitor therapy had altered bile acid concentrations compared with noninfected control subjects, and whether bile acid concentrations could predict the onset of hepatotoxicity caused by protease inhibitors

    Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease

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    Inherited retinal disease is a common cause of visual impairment and represents a highly heterogeneous group of conditions. Here, we present findings from a cohort of 722 individuals with inherited retinal disease, who have had whole-genome sequencing (n = 605), whole-exome sequencing (n = 72), or both (n = 45) performed, as part of the NIHR-BioResource Rare Diseases research study. We identified pathogenic variants (single-nucleotide variants, indels, or structural variants) for 404/722 (56%) individuals. Whole-genome sequencing gives unprecedented power to detect three categories of pathogenic variants in particular: structural variants, variants in GC-rich regions, which have significantly improved coverage compared to whole-exome sequencing, and variants in non-coding regulatory regions. In addition to previously reported pathogenic regulatory variants, we have identified a previously unreported pathogenic intronic variant in CHM\textit{CHM} in two males with choroideremia. We have also identified 19 genes not previously known to be associated with inherited retinal disease, which harbor biallelic predicted protein-truncating variants in unsolved cases. Whole-genome sequencing is an increasingly important comprehensive method with which to investigate the genetic causes of inherited retinal disease.This work was supported by The National Institute for Health Research England (NIHR) for the NIHR BioResource – Rare Diseases project (grant number RG65966). The Moorfields Eye Hospital cohort of patients and clinical and imaging data were ascertained and collected with the support of grants from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, National Health Service Foundation Trust, and UCL Institute of Ophthalmology, Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, the Foundation Fighting Blindness (USA), and Retinitis Pigmentosa Fighting Blindness. M.M. is a recipient of an FFB Career Development Award. E.M. is supported by UCLH/UCL NIHR Biomedical Research Centre. F.L.R. and D.G. are supported by Cambridge NIHR Biomedical Research Centre

    Prevalence and architecture of de novo mutations in developmental disorders.

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    The genomes of individuals with severe, undiagnosed developmental disorders are enriched in damaging de novo mutations (DNMs) in developmentally important genes. Here we have sequenced the exomes of 4,293 families containing individuals with developmental disorders, and meta-analysed these data with data from another 3,287 individuals with similar disorders. We show that the most important factors influencing the diagnostic yield of DNMs are the sex of the affected individual, the relatedness of their parents, whether close relatives are affected and the parental ages. We identified 94 genes enriched in damaging DNMs, including 14 that previously lacked compelling evidence of involvement in developmental disorders. We have also characterized the phenotypic diversity among these disorders. We estimate that 42% of our cohort carry pathogenic DNMs in coding sequences; approximately half of these DNMs disrupt gene function and the remainder result in altered protein function. We estimate that developmental disorders caused by DNMs have an average prevalence of 1 in 213 to 1 in 448 births, depending on parental age. Given current global demographics, this equates to almost 400,000 children born per year

    Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

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    Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

    DNA Methylation Signatures of Depressive Symptoms in Middle-aged and Elderly Persons:Meta-analysis of Multiethnic Epigenome-wide Studies

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    IMPORTANCE Depressive disorders arise from a combination of genetic and environmental risk factors. Epigenetic disruption provides a plausible mechanism through which gene-environment interactions lead to depression. Large-scale, epigenome-wide studies on depression are missing, hampering the identification of potentially modifiable biomarkers.OBJECTIVE To identify epigenetic mechanisms underlying depression in middle-aged and elderly persons, using DNA methylation in blood.DESIGN, SETTING, AND PARTICIPANTS To date, the first cross-ethnic meta-analysis of epigenome-wide association studies (EWAS) within the framework of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium was conducted. The discovery EWAS included 7948 individuals of European origin from 9 population-based cohorts. Participants who were assessed for both depressive symptoms and whole-blood DNA methylation were included in the study. Results of EWAS were pooled using sample-size weighted meta-analysis. Replication of the top epigenetic sites was performed in 3308 individuals of African American and European origin from 2 population-based cohorts.MAIN OUTCOMES AND MEASURES Whole-blood DNA methylation levels were assayed with Illumina-Infinium Human Methylation 450K BeadChip and depressive symptoms were assessed by questionnaire.RESULTS The discovery cohorts consisted of 7948 individuals (4104 [51.6%] women) with a mean (SD) age of 65.4 (5.8) years. The replication cohort consisted of 3308 individuals (2456 [74.2%) women) with a mean (SD) age of 60.3 (6.4) years. The EWAS identified methylation of 3 CpG sites to be significantly associated with increased depressive symptoms: cg04987734 (P = 1.57 x 10(-)(08); n = 11 256; CDC42BPB gene), cg12325605 (P = 5.24 x 10(-09); n = 11256; ARHGEF3 gene), and an intergenic CpG site cg14023999 (P = 5.99 x 10(-)(08); n = 11256; chromosome = 15q261). The predicted expression of the CDC42BPB gene in the brain (basal ganglia) (effect, 0.14; P = 2.7 x 10(-03)) and of ARHGEF3 in fibroblasts (effect. -0.48; P = 9.8 x 10(-)(04) ) was associated with major depression.CONCLUSIONS AND RELEVANCE This study identifies 3 methylated sites associated with depressive symptoms. All 3 findings point toward axon guidance as the common disrupted pathway in depression. The findings provide new insights into the molecular mechanisms underlying the complex pathophysiology of depression. Further research is warranted to determine the utility of these findings as biomarkers of depression and evaluate any potential role in the pathophysiology of depression and their downstream clinical effects. (C) 2018 American Medical Association. All lights reserved

    The landscape of tolerated genetic variation in humans and primates.

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    Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases
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