2021 Particle Grain-Size and Total Organic Content Analyses of Surface Sediments from Puget Sound and Elliot Bay near Seattle, WA

Sediment characteristics are important to analyze to connect environmental conditions to sea floor sediments and characteristics of interest (i.e., benthic communities). Total organic carbon can represent oxygenated or reduced environments and/or biological vitality depending on water depth. Grain-size can represent high or low energy if sandy or silty, and the variability of grain-sizes (sorting) can indicate stormy conditions, landslides, or dumping. Washington State Department of Ecology’s Marine Sediment Monitoring Team has provided sediment samples to the University of Washington Tacoma for analysis since 2014, supporting undergraduate research efforts. This poster will present data on total organic carbon and particle grain-size from samples collected in 2021 from the long-term stations, covering the whole Puget Sound, as well as a high-resolution sampling of Elliot Bay near Seattle, WA. Samples were collected using a Van Veen grab sampler, and then analyzed in the lab with a Beckman-Coulter Particle Size Analyzer for sediment grain-size. The loss-on-ignition technique was used to determine the total organic content. This study provides a foundation for scientists to utilize in understand and maintaining environmental health

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

The Burr Spring 2011

https://kent-islandora.s3.us-east-2.amazonaws.com/theburr/49/thumbnail.jp

Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target

Abdominal aortic aneurysm (AAA) is a common disease with substantial heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 141 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis explained AAA risk beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in AAA pathogenesis. These genes also indicate overlap between the development of AAA and other monogenic aortopathies, particularly via transforming growth factor β signaling. Motivated by the strong evidence for the role of lipid metabolism in AAA, we used Mendelian randomization to establish the central role of nonhigh-density lipoprotein cholesterol in AAA and identified the opportunity for repurposing of proprotein convertase, subtilisin/kexin-type 9 (PCSK9) inhibitors. This was supported by a study demonstrating that PCSK9 loss of function prevented the development of AAA in a preclinical mouse model. Genome-wide association meta-analysis of AAA identifies 121 independent risk loci and highlights potential therapeutic targets such as proprotein convertase, subtilisin/kexin-type 9 (PCSK9)

Acyl Glucuronide Metabolites of 6‑Chloro-5-[4-(1-hydroxycyclobutyl)phenyl]‑1<i>H</i>‑indole-3-carboxylic Acid (PF-06409577) and Related Indole-3-carboxylic Acid Derivatives are Direct Activators of Adenosine Monophosphate-Activated Protein Kinase (AMPK)

Studies on indole-3-carboxylic acid derivatives as direct activators of human adenosine monophosphate-activated protein kinase (AMPK) α1β1γ1 isoform have culminated in the identification of PF-06409577 (<b>1</b>), PF-06885249 (<b>2</b>), and PF-06679142 (<b>3</b>) as potential clinical candidates. Compounds <b>1</b>–<b>3</b> are primarily cleared in animals and humans via glucuronidation. Herein, we describe the biosynthetic preparation, purification, and structural characterization of the glucuronide conjugates of <b>1</b>–<b>3</b>. Spectral characterization of the purified glucuronides M1, M2, and M3 indicated that they were acyl glucuronide derivatives. In vitro pharmacological evaluation revealed that all three acyl glucuronides retained selective activation of β1-containing AMPK isoforms. Inhibition of de novo lipogenesis with representative parent carboxylic acids and their respective acyl glucuronide conjugates in human hepatocytes demonstrated their propensity to activate cellular AMPK. Cocrystallization of the AMPK α1β1γ1 isoform with <b>1</b>–<b>3</b> and M1–M3 provided molecular insights into the structural basis for AMPK activation by the glucuronide conjugates

Causes of Noncompliance with International Law: A Field Experiment on Anonymous Incorporation

20110302 into the Experiments on Governance and Politics Registry once that registry was begun at e-gap.org. Of those interventions registered, we report on the FATF, Premium, Corruption, and Terrorism conditions in this article. All other interventions outlined in the registered document are reported in other work. In our registration, we indicated that we would report results dichotomously as compliant or noncompliant, given a response. We still report response and nonresponse followed by a compliance level, but we expanded the set of possible types of compliance (nonresponse, noncompliance, partial compliance, compliance, and refusal). Presenting the information this way is more precise and is also consistent with the registry document because the fuller set of outcomes contains all information the dichotomized measures capture (se

Loss-of-function genomic variants highlight potential therapeutic targets for cardiovascular disease

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529:p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10-8) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD