951 research outputs found
Circumpolar Diversity and Geographic Differentiation of mtDNA in the Critically Endangered Antarctic Blue Whale (Balaenoptera musculus intermedia)
To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work.\ud
This is the publisherâs final pdf. The published article is copyrighted by the Public Library of Science and can be found at: http://www.plosone.org/home.action.The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC) during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131 degrees longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968 +/- 0.004), perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F-ST = 0.032, p<0.005) and microsatellite alleles (F-ST = 0.005, p<0.05) among the six Antarctic Areas historically used by the IWC for management of blue whales
Environmental Indicator Utility in Environmental Decision Making: A Multiple Case Study Analysis
An environmental indicator is a scientific measurement that tracks environmental conditions overtime. Indicators can be a powerful tool in performance-based management/measurement systems. Performance indicators focus attention on outcomes of programs and can be used for strategic planning, priority setting, resource allocation, and other decision-making processes. Many agencies (governmental and non-governmental) are using program results to improve performance and ensure accountability. There are numerous frameworks around which indicators are structured for utilization and a range of performance measures spanning the spectrum of indicator measures. The various frameworks and performance measures clarify the type of environmental information generated by measurement systems and its value to inform decision-making. Outcome measures positioned at the higher end of the indicator hierarchy, those that address reduction of environmental risk or impacts to the ecology and human health, are the most desirable for informing decision-making. The goal of this investigation is to evaluate how environmental indicators are used inside performance based management/measurement systems and assess the logic linking environmental information to planning, resources allocation and performance review to describe environmental progress and inform environmental decision-making.Master of Science in Public Healt
Integrative analysis identifies candidate tumor microenvironment and intracellular signaling pathways that define tumor heterogeneity in NF1
Neurofibromatosis type 1 (NF1) is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, whereas 40-60% of patients develop plexiform neurofibromas (pNFs), which are deeply embedded in the peripheral nerves. Patients with pNFs have a ~10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification of druggable pathways or other key molecular features could aid ongoing therapeutic discovery studies. In this work, we used statistical and machine learning methods to analyze 77 NF1 tumors with genomic data to characterize key signaling pathways that distinguish these tumors and identify candidates for drug development. We identified subsets of latent gene expression variables that may be important in the identification and etiology of cNFs, pNFs, other neurofibromas, and MPNSTs. Furthermore, we characterized the association between these latent variables and genetic variants, immune deconvolution predictions, and protein activity predictions
Listening to the Voices of Community Health Workers: A Multilevel, Culture-Centered Approach to Overcoming Structural Barriers in U.S. Latinx Communities
Community Health Workers (CHWs) are often incorporated into efforts to reduce health disparities for vulnerable populations. However, their voices are rarely the focus of research when considering how to increase their job effectiveness and sustainability. The current study addresses this gap by privileging the voices of 28 CHWs who work with Latinx communities in Nebraska through in-depth, semi-structured interviews. Using a multilevel, Culture-Centered Approach (CCA) to Health Communication, we identified two key structural communication issues: (a) increasing language accommodation and (b) increasing (and stabilizing) network integration across three ecological levels of health behavior (individual, microsystem, and exosystem). This study shows the uniquely valuable perspective that CHWs have as they navigate hierarchical health care structures and community cultures to meet the needs of their Latinx clients. Findings suggest that CHWs should be included in health care organization and policy discussions to reduce health disparities for Latinx populations
Tropism-Modification Strategies for Targeted Gene Delivery Using Adenoviral Vectors
Achieving high efficiency, targeted gene delivery with adenoviral vectors is a long-standing goal in the field of clinical gene therapy. To achieve this, platform vectors must combine efficient retargeting strategies with detargeting modifications to ablate native receptor binding (i.e. CAR/integrins/heparan sulfate proteoglycans) and âbridgingâ interactions. âBridgingâ interactions refer to coagulation factor binding, namely coagulation factor X (FX), which bridges hepatocyte transduction in vivo through engagement with surface expressed heparan sulfate proteoglycans (HSPGs). These interactions can contribute to the off-target sequestration of Ad5 in the liver and its characteristic dose-limiting hepatotoxicity, thereby significantly limiting the in vivo targeting efficiency and clinical potential of Ad5-based therapeutics. To date, various approaches to retargeting adenoviruses (Ad) have been described. These include genetic modification strategies to incorporate peptide ligands (within fiber knob domain, fiber shaft, penton base, pIX or hexon), pseudotyping of capsid proteins to include whole fiber substitutions or fiber knob chimeras, pseudotyping with non-human Ad species or with capsid proteins derived from other viral families, hexon hypervariable region (HVR) substitutions and adapter-based conjugation/crosslinking of scFv, growth factors or monoclonal antibodies directed against surface-expressed target antigens. In order to maximize retargeting, strategies which permit detargeting from undesirable interactions between the Ad capsid and components of the circulatory system (e.g. coagulation factors, erythrocytes, pre-existing neutralizing antibodies), can be employed simultaneously. Detargeting can be achieved by genetic ablation of native receptor-binding determinants, ablation of âbridging interactionsâ such as those which occur between the hexon of Ad5 and coagulation factor X (FX), or alternatively, through the use of polymer-coated âstealthâ vectors which avoid these interactions. Simultaneous retargeting and detargeting can be achieved by combining multiple genetic and/or chemical modifications
Investigation of chlorine radical chemistry in the Eyjafjallajkull volcanic plume using observed depletions in non-methane hydrocarbons
As part of the effort to understand volcanic plume composition and chemistry during the eruption of the Icelandic volcano Eyjafjallajkull, the CARIBIC atmospheric observatory was deployed for three special science flights aboard a Lufthansa passenger aircraft. Measurements made during these flights included the collection of whole air samples, which were analyzed for non-methane hydrocarbons (NMHCs). Hydrocarbon concentrations in plume samples were found to be reduced to levels below background, with relative depletions characteristic of reaction with chlorine radicals (Cl). Recent observations of halogen oxides in volcanic plumes provide evidence for halogen radical chemistry, but quantitative data for free halogen radical concentrations in volcanic plumes were absent. Here we present the first observation-based calculations of Cl radical concentrations in volcanic plumes, estimated from observed NMHC depletions. Inferred Cl concentrations were between 1.3 Ă 10 and 6.6 Ă 10 Cl cm. The relationship between NMHC variability and local lifetimes was used to investigate the ratio between OH and Cl within the plume, with [OH]/[Cl] estimated to be âŒ37. Copyright 2011 by the American Geophysical Union
In Vitro and In Vivo Evaluation of Human Adenovirus Type 49 as a Vector for Therapeutic Applications
The human adenovirus phylogenetic tree is split across seven species (AâG). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of pre-existing immunity detected across screened populations. However, many aspects of the basic virology of species Dâsuch as their cellular tropism, receptor usage, and in vivo biodistribution profileâremain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49)âa relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry, but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting, whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells, and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen, whilst avoiding liver interactions, such as intravascular vaccine applications
Safety of Daily Albuterol in Infants with a History of Bronchospasm: A Multi-Center Placebo Controlled Trial§
Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency
Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases.
Objective: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified.
Design: The study design comprised single-nucleotide polymorphism genotyping and mutation detection.
Setting: The study was conducted at secondary and tertiary referral centers.
Patients: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study.
Interventions: There were no interventions.
Results: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families.
Conclusions: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD
Effectiveness of quality improvement initiative (Guidelines Applied to Practice [GAP] project) in improving the care of medicare patients and women with acute myocardial infarction
- âŠ