- Award ID(s):
- 1703846
- PAR ID:
- 10414207
- Date Published:
- Journal Name:
- Proceedings of the Second Conference on Causal Learning and Reasoning
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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null (Ed.)The low-density lipoprotein receptor (LDLR) is key to cellular cholesterol uptake and is also the main receptor for the vesicular stomatitis virus glycoprotein (VSV G). Here we show that in songbirds LDLR is highly divergent and lacks domains critical for ligand binding and cellular trafficking, inconsistent with universal structure conservation and function across vertebrates. Linked to the LDLR functional domain loss, zebra finches show inefficient infectivity by lentiviruses (LVs) pseudotyped with VSV G, which can be rescued by the expression of human LDLR. Finches also show an atypical plasma lipid distribution that relies largely on high-density lipoprotein (HDL). These findings provide insights into the genetics and evolution of viral infectivity and cholesterol transport mechanisms in vertebrates.more » « less
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Japanese adults typically have healthier lipid profiles than American and European adults and a lower prevalence and later onset of atherosclerotic cardiovascular disease (ASCVD). Many Japanese also have uniquely elevated levels of high-density lipoprotein cholesterol (HDL-C). The following analysis examined the relationship between HDL-C level and HDL-C peroxide content, a bioindicator of unhealthy lipid metabolism in Japanese adults. Blood samples were collected from 463 participants, 31–84 years of age, who lived in Tokyo. A second blood sample was collected 5 years later from 241 of the participants, allowing us to evaluate the temporal stability of the inverse correlation between HDL-C level and HDL-C peroxide content. Glucoregulation and inflammatory activity were assessed because both can be associated with dyslipidemia and HDL-C dysfunction. Obesity and central adiposity were also considered. Overall, women had healthier HDL-C profiles than men. Elevated HDL-C (>90 mg/dL) was common (16.6%) and found more often in women. Higher HDL-C peroxide content was associated with older age and central adiposity and incremented further when HA1c and CRP were higher. When assessed 5 years later, lower HDL-C peroxide content continued to be evident in adults with higher HDL-C. While similar associations have been described for other populations, most Japanese adults typically had healthier levels of HDL-C with lower HDL-C peroxide content than previously reported for American adults.
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Zeggini, Eleftheria (Ed.)Increasingly large Genome-Wide Association Studies (GWAS) have yielded numerous variants associated with many complex traits, motivating the development of “fine mapping” methods to identify which of the associated variants are causal. Additionally, GWAS of the same trait for different populations are increasingly available, raising the possibility of refining fine mapping results further by leveraging different linkage disequilibrium (LD) structures across studies. Here, we introduce multiple study causal variants identification in associated regions (MsCAVIAR), a method that extends the popular CAVIAR fine mapping framework to a multiple study setting using a random effects model. MsCAVIAR only requires summary statistics and LD as input, accounts for uncertainty in association statistics using a multivariate normal model, allows for multiple causal variants at a locus, and explicitly models the possibility of different SNP effect sizes in different populations. We demonstrate the efficacy of MsCAVIAR in both a simulation study and a trans-ethnic, trans-biobank fine mapping analysis of High Density Lipoprotein (HDL).more » « less
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ABSTRACT Objectives Among indigenous circumpolar populations, extreme seasonality influences food availability and energy metabolism. Furthermore, subsistence patterns and wage labor opportunities shift with season. Thus, health measures among circumpolar populations likely exhibit seasonal changes that are influenced by lifestyle factors. This study examines how markers of cardio‐metabolic health vary between summer and winter as a function of an individual's lifestyle and sex among the Yakut of northeastern Siberia.
Methods Anthropometric dimensions, serum lipids and glucose levels, blood pressure, and lifestyle data were collected for a sample of 115 Yakut participants (71 women, 44 men) in Berdygestiakh, Sakha Republic, Russia in the summer of 2009 and winter of 2011.
Results Men and women experienced significant increases in total and HDL cholesterol and triglyceride levels from summer to winter. Women exhibited winter‐time increases in adiposity and glucose levels. Men who reported greater market integration were more likely to have lower winter blood pressure levels. Additionally, time spent fishing was associated with lower winter‐time LDL cholesterol, while foraging time was associated with higher HDL cholesterol.
Conclusions While seasonal changes in anthropometric dimensions were modest, Yakut men and women experienced significant increases in total cholesterol and HDL cholesterol from summer to winter. These results also suggest that while Yakut individuals with greater subsistence participation are more buffered from adverse seasonal changes in cholesterol levels, they may be at a greater risk for winter increases in blood pressure. Furthermore, the interactions between lifestyle and seasonal change in metabolic health appear to differ between Yakut women and men. Am. J. Hum. Biol. 28:868–878, 2016. © 2016Wiley Periodicals, Inc.
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As a liquid approaches the gas state, the properties of the potential energy landscape (PEL) sampled by the system become anomalous. Specifically, (i) the mechanically stable local minima of the PEL [inherent structures (IS)] can exhibit cavitation above the so-called Sastry volume, v S , before the liquid enters the gas phase. In addition, (ii) the pressure of the liquid at the sampled IS [i.e., the PEL equation of state, P IS ( v)] develops a spinodal-like minimum at v S . We perform molecular dynamics simulations of a monatomic water-like liquid and verify that points (i) and (ii) hold at high temperatures. However, at low temperatures, cavitation in the liquid and the corresponding IS occurs simultaneously and a Sastry volume cannot be defined. Remarkably, at intermediate/high temperatures, the IS of the liquid can exhibit crystallization, i.e., the liquid regularly visits the regions of the PEL that belong to the crystal state. The model liquid considered also exhibits a liquid–liquid phase transition (LLPT) between a low-density and a high-density liquid (LDL and HDL). By studying the behavior of P IS ( v) during the LLPT, we identify a Sastry volume for both LDL and HDL. The HDL Sastry volume marks the onset above which IS are heterogeneous (composed of LDL and HDL particles), analogous to points (i) and (ii) above. However, the relationship between the LDL Sastry volume and the onset of heterogeneous IS is less evident. We conclude by presenting a thermodynamic argument that can explain the behavior of the PEL equation of state P IS ( v) across both the liquid–gas phase transition and LLPT.more » « less