Host Genetic Factors and Vaccine-Induced Immunity to HBV Infection: Haplotype Analysis

Hepatitis B virus (HBV) infection remains a significant health burden world-wide, although vaccines help decrease this problem. We previously identified associations of single nucleotide polymorphisms in several candidate genes with vaccine-induced peak antibody level (anti-HBs), which is predictive of long-term vaccine efficacy and protection against infection and persistent carriage; here we report on a haplotype-based analysis. A total of 688 SNPs from 117 genes were examined for a two, three and four sliding window haplotype analysis in a Gambian cohort. Analysis was performed on 197 unrelated individuals, 454 individuals from 174 families, and the combined sample (N = 651). Global and individual haplotype association tests were carried out (adjusted for covariates), employing peak anti-HBs level as outcome. Five genes (CD44, CD58, CDC42, IL19 and IL1R1) had at least one significant haplotype in the unrelated or family analysis as well as the combined analysis. Previous single locus results were confirmed for CD44 (combined global p = 9.1×10−5 for rs353644-rs353630-rs7937602) and CD58 (combined global p = 0.008 for rs1414275-rs11588376-rs1016140). Haplotypes in CDC42, IL19 and IL1R1 also associated with peak anti-HBs level. We have identified strong haplotype effects on HBV vaccine-induced antibody level in five genes, three of which, CDC42, IL19 and IL1R1, did not show evidence of association in a single SNP analyses and corroborated the majority of these effects in two datasets. The haplotype analysis identified associations with HBV vaccine-induced immunity in several new genes

Being user-oriented: convergences, divergences, and the potentials for systematic dialogue between disciplines and between researchers, designers, and providers

The challenge this panel addresses is drawn from intersecting literature reviews and critical commentaries focusing on: 1) user studies in multiple fields; and 2) the difficulties of bringing different disciplines and perspectives to bear on user‐oriented research, design, and practice. 1 The challenge is that while we have made some progress in collaborative work, we have some distance to go to become user‐oriented in inter‐disciplinary and inter‐perspective ways. The varieties of our approaches and solutions are, as some observers suggest, an increasing cacophony. One major difficulty is that most discussions are solution‐oriented, offering arguments of this sort ‐‐ if only we addressed users in this way… Each solution becomes yet another addition to the cacophony. This panel implements a central approach documented for its utility by communication researchers and long used by communication mediators and negotiators ‐‐ that of focusing not on communication but rather on meta‐communication: communicating about communication. The intent in the context of this panel is to help us refocus attention from too frequent polarizations between alternative solutions to the possibility of coming to understand what is behind the alternatives and where they point to experientially‐based convergences and divergences, both of which might potentially contribute to synergies. The background project for this panel comes from a series of in‐depth interviews with expert researchers, designers, and providers in three field groupings ‐‐ library and information science; human computer interaction/information technology; and communication and media studies. One set of interviews involved 5‐hour focus groups with directors of academic and public libraries serving 44 colleges and universities in central Ohio; the second involved one‐on‐one interviews averaging 50 minutes with 81 nationally‐internationally known experts in the 3 fields, 25‐27 interviews per field. Using Dervin\u27s Sense‐Making Methodological approach to interviewing, the expert interviews of both kinds asked each interviewee: what he/she considered to be the big unanswered questions about users and what explained why the questions have not been answered; and, what he/she saw as hindering versus helping in attempts to communicate about users across disciplinary and perspective gaps. 2 The panel consists of six teams, two from each field. Prior to the panel presentation at ASIST, each team will have read the set of interviews and completed impressionistic essays of what patterns and themes they saw as emerging. At this stage, team members will purposively not homogenize their differences and most will write solo‐authored essays that will be placed on a web‐site accessible to ASIST members prior to the November meeting. In addition, at least one systematic analysis will be completed and available online. 3 At the ASIST panel, each team\u27s leader will present a brief and intentionally provocative impressionist account of what his/her team came to understand about our struggles communicating across fields and perspectives about users. Again, each team will purposively not homogenize its own differences in viewpoints, but rather highlight them as fodder for discussion. A major purpose will be to invite audience members to join the panel in discussion. At least 20 minutes will be left open for this purpose

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Deletion of Wntless in myeloid cells exacerbates liver fibrosis and the ductular reaction in chronic liver injury

Background: Macrophages play critical roles in liver regeneration, fibrosis development and resolution. They are among the first responders to liver injury and are implicated in orchestrating the fibrogenic response via multiple mechanisms. Macrophages are also intimately associated with the activated hepatic progenitor cell (HPC) niche or ductular reaction that develops in parallel with fibrosis. Among the many macrophage-derived mediators implicated in liver disease progression, a key role for macrophage-derived Wnt proteins in driving pro-regenerative HPC activation towards a hepatocellular fate has been suggested. Wnt proteins, in general, however, have been associated with both pro-and anti-fibrogenic activities in the liver and other organs. We investigated the role of macrophage-derived Wnt proteins in fibrogenesis and HPC activation in murine models of chronic liver disease by conditionally deleting Wntless expression, which encodes a chaperone essential for Wnt protein secretion, in LysM-Cre-expressing myeloid cells (LysM-Wls mice)

Pleiotropy of cardiometabolic syndrome with obesity-related anthropometric traits determined using empirically derived kinships from the Busselton Health Study

Over two billion adults are overweight or obese and therefore at an increased risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits genetically correlated with CMS may provide insight into CMS aetiology. The aim of this study was to utilise an empirically derived genetic relatedness matrix to calculate heritabilities and genetic correlations between CMS and anthropometric traits to determine whether they share genetic risk factors (pleiotropy). We used genome-wide single nucleotide polymorphism (SNP) data on 4671 Busselton Health Study participants. Exploiting both known and unknown relatedness, empirical kinship probabilities were estimated using these SNP data. General linear mixed models implemented in SOLAR were used to estimate narrow-sense heritabilities (h 2 ) and genetic correlations (r g ) between 15 anthropometric and 9 CMS traits. Anthropometric traits were adjusted by body mass index (BMI) to determine whether the observed genetic correlation was independent of obesity. After adjustment for multiple testing, all CMS and anthropometric traits were significantly heritable (h 2 range 0.18–0.57). We identified 50 significant genetic correlations (r g range: - 0.37 to 0.75) between CMS and anthropometric traits. Five genetic correlations remained significant after adjustment for BMI [high density lipoprotein cholesterol (HDL-C) and waist–hip ratio; triglycerides and waist–hip ratio; triglycerides and waist–height ratio; non-HDL-C and waist–height ratio; insulin and iliac skinfold thickness]. This study provides evidence for the presence of potentially pleiotropic genes that affect both anthropometric and CMS traits, independently of obesity