Meeting report: a hard look at the state of enamel research.

The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field

The liver X receptor pathway is highly upregulated in rheumatoid arthritis synovial macrophages and potentiates TLR-driven cytokine release

<p>Objectives: Macrophages are central to the inflammatory processes driving rheumatoid arthritis (RA) synovitis. The molecular pathways that are induced in synovial macrophages and thereby promote RA disease pathology remain poorly understood.</p> <p>Methods: We used microarray to characterise the transcriptome of synovial fluid (SF) macrophages compared with matched peripheral blood monocytes from patients with RA (n=8).</p> <p>Results: Using in silico pathway mapping, we found that pathways downstream of the cholesterol activated liver X receptors (LXRs) and those associated with Toll-like receptor (TLR) signalling were upregulated in SF macrophages. Macrophage differentiation and tumour necrosis factor α promoted the expression of LXRα. Furthermore, in functional studies we demonstrated that activation of LXRs significantly augmented TLR-driven cytokine and chemokine secretion.</p> <p>Conclusions: The LXR pathway is the most upregulated pathway in RA synovial macrophages and activation of LXRs by ligands present within SF augments TLR-driven cytokine secretion. Since the natural agonists of LXRs arise from cholesterol metabolism, this provides a novel mechanism that can promote RA synovitis.</p&gt

Evidence of Differential Allelic Effects between Adolescents and Adults for Plasma High-Density Lipoprotein

A recent meta-analysis of genome-wide association (GWA) studies identified 95 loci that influence lipid traits in the adult population and found that collectively these explained about 25–30% of heritability for each trait. Little is known about how these loci affect lipid levels in early life, but there is evidence that genetic effects on HDL- and LDL-cholesterol (HDL-C, LDL-C) and triglycerides vary with age. We studied Australian adults (N = 10,151) and adolescents (N = 2,363) who participated in twin and family studies and for whom we have lipid phenotypes and genotype information for 91 of the 95 genetic variants. Heterogeneity tests between effect sizes in adult and adolescent cohorts showed an excess of heterogeneity for HDL-C (pHet<0.05 at 5 out of 37 loci), but no more than expected by chance for LDL-C (1 out of 14 loci), or trigycerides (0 out 24). There were 2 (out of 5) with opposite direction of effect in adolescents compared to adults for HDL-C, but none for LDL-C. The biggest difference in effect size was for LDL-C at rs6511720 near LDLR, adolescents (0.021±0.033 mmol/L) and adults (0.157±0.023 mmol/L), pHet = 0.013; followed by ZNF664 (pHet = 0.018) and PABPC4 (pHet = 0.034) for HDL-C. Our findings suggest that some of the previously identified variants associate differently with lipid traits in adolescents compared to adults, either because of developmental changes or because of greater interactions with environmental differences in adults

Outflows from the youngest stars are mostly molecular

The formation of stars and planets is accompanied not only by the build-up of matter, namely accretion, but also by its expulsion in the form of highly supersonic jets that can stretch for several parsecs 1,2. As accretion and jet activity are correlated and because young stars acquire most of their mass rapidly early on, the most powerful jets are associated with the youngest protostars 3. This period, however, coincides with the time when the protostar and its surroundings are hidden behind many magnitudes of visual extinction. Millimetre interferometers can probe this stage but only for the coolest components 3. No information is provided on the hottest (greater than 1,000 K) constituents of the jet, that is, the atomic, ionized and high-temperature molecular gases that are thought to make up the jet’s backbone. Detecting such a spine relies on observing in the infrared that can penetrate through the shroud of dust. Here we report near-infrared observations of Herbig-Haro 211 from the James Webb Space Telescope, an outflow from an analogue of our Sun when it was, at most, a few times 104 years old. These observations\ua0reveal copious emission from hot molecules, explaining the origin of the ‘green fuzzies’ 4–7 discovered nearly two decades ago by the Spitzer Space Telescope 8. This outflow is found to be propagating slowly in comparison to its more evolved counterparts and, surprisingly, almost no trace of atomic or ionized emission is seen, suggesting its spine is almost purely molecular

The LCES HIRES/Keck Precision Radial Velocity Exoplanet Survey

This document is the Accepted Manuscript version of the following article: R. Paul Butler, et al, The LCES HIRES/Keck Precision Radial Velocity Exoplanet Survey, The Astronomical Journal, Vol 153 (5), 19 pp., published 13 April 2017. The Version of Record is available online at doi: https://doi.org/10.3847/1538-3881/aa66ca. Paper data available at: http://home.dtm.ciw.edu/ebps/data/. © 2017. The American Astronomical Society. All rights reserved.We describe a 20-year survey carried out by the Lick-Carnegie Exoplanet Survey Team (LCES), using precision radial velocities from HIRES on the Keck-I telescope to find and characterize extrasolar planetary systems orbiting nearby F, G, K, and M dwarf stars. We provide here 60,949 precision radial velocities for 1,624 stars contained in that survey. We tabulate a list of 357 significant periodic signals that are of constant period and phase, and not coincident in period and/or phase with stellar activity indices. These signals are thus strongly suggestive of barycentric reflex motion of the star induced by one or more candidate exoplanets in Keplerian motion about the host star. Of these signals, 225 have already been published as planet claims, 60 are classified as significant unpublished planet candidates that await photometric follow-up to rule out activity-related causes, and 54 are also unpublished, but are classified as "significant" signals that require confirmation by additional data before rising to classification as planet candidates. Of particular interest is our detection of a candidate planet with a minimum mass of 3.9 Earth masses and an orbital period of 9.9 days orbiting Lalande 21185, the fourth-closest main sequence star to the Sun. For each of our exoplanetary candidate signals, we provide the period and semi-amplitude of the Keplerian orbital fit, and a likelihood ratio estimate of its statistical significance. We also tabulate 18 Keplerian-like signals that we classify as likely arising from stellar activity.Peer reviewedFinal Accepted Versio

Community Service: Editor pride and user preference on local newspaper websites

Armed with readily accessible online traffic logs that provide detailed information about the items users are selecting to view, editors are voicing concern about the potential effect on their own content decisions. Through a survey of local British newspaper editors, this article examines the overlap between user preferences, as suggested by assessments of website traffic, and content that editors identify as their best. Results are considered in the context of two related subsets of agenda-setting theory, as well as the sociological process of “making news.” The study finds overlap between broad categories of stories preferred by editors and users, but a considerable disconnect over the nature of the items within those categories

Perceptions of Mental Health and Help-Seeking Behavior in an Urban Community in Vietnam: An Explorative Study

This explorative study assesses perceptions of mental health and help-seeking behavior among adults in Vietnam. Methods included questionnaires (200) and focus group discussions (eight). Respondents were often unable to name specific mental illnesses. Frequently mentioned symptoms of mental illness were talking nonsense, talking/laughing alone and wandering. Pressure/stress and studying/thinking too much were often identified causes. Most respondents showed a preference for medical treatment options, often in combination with family care. The results show that perceptions of mental health and help-seeking behaviour are influenced by a lack of knowledge and a mix of traditional and modern views

Understanding communication in counterterrorism crisis management.

This report describes the purpose and results of the two-year, Sandia-sponsored Laboratory Directed Research and Development (LDRD) project entitled Understanding Communication in Counterterrorism Crisis Management The purpose of this project was to facilitate the capture of key communications among team members in simulated training exercises, and to learn how to improve communication in that domain. The first section of this document details the scenario development aspects of the simulation. The second section covers the new communication technologies that were developed and incorporated into the Weapons of Mass Destruction Decision Analysis Center (WMD-DAC) suite of decision support tools. The third section provides an overview of the features of the simulation and highlights its communication aspects. The fourth section describes the Team Communication Study processes and methodologies. The fifth section discusses future directions and areas in which to apply the new technologies and study results obtained as a result of this LDRD

The mannose receptor (CD206) identifies a population of colonic macrophages in health and inflammatory bowel disease

To understand the contribution of mononuclear phagocytes (MNP), which include monocyte-derived intestinal macrophages, to the pathogenesis of inflammatory bowel disease (IBD), it is necessary to identify functionally-different MNP populations. We aimed to characterise intestinal macrophage populations in patients with IBD. We developed 12-parameter flow cytometry protocols to identify and human intestinal MNPs. We used these protocols to purify and characterize colonic macrophages from colonic tissue from patients with Crohn’s disease (CD), ulcerative colitis (UC), or non-inflamed controls, in a cross-sectional study. We identify macrophage populations (CD45+CD64+ HLA-DR+) and describe two distinct subsets, differentiated by their expression of the mannose receptor, CD206. CD206+ macrophages expressed markers consistent with a mature phenotype: high levels of CD68 and CD163, higher transcription of IL-10 and lower expression of TREM1. CD206− macrophages appear to be less mature, with features more similar to their monocytic precursors. We identified and purified macrophage populations from human colon. These appear to be derived from a monocytic precursor with high CCR2 and low CD206 expression. As these cells mature, they acquire expression of IL-10, CD206, CD63, and CD168. Targeting the newly recruited monocyte-derived cells may represent a fruitful avenue to ameliorate chronic inflammation in IBD