Draft Genome Sequences of Four Saccharibacter sp. Strains Isolated from Native Bees.

The genus Saccharibacter is currently understudied, with only one described species, Saccharibacter floricola, isolated from a flower. In an effort to better understand the microbes that come in contact with native bee pollinators, we isolated and sequenced four additional strains of Saccharibacter from native bees in the genera Melissodes and Anthophora These genomes range in size from 2,104,494 to 2,316,791 bp (mean, 2,246,664 bp) and contain between 1,860 and 2,167 (mean, 2,060) protein-coding genes

Nuclear-localized focal adhesion kinase regulates inflammatory VCAM-1 expression.

Vascular cell adhesion molecule-1 (VCAM-1) plays important roles in development and inflammation. Tumor necrosis factor-α (TNF-α) and focal adhesion kinase (FAK) are key regulators of inflammatory and integrin-matrix signaling, respectively. Integrin costimulatory signals modulate inflammatory gene expression, but the important control points between these pathways remain unresolved. We report that pharmacological FAK inhibition prevented TNF-α-induced VCAM-1 expression within heart vessel-associated endothelial cells in vivo, and genetic or pharmacological FAK inhibition blocked VCAM-1 expression during development. FAK signaling facilitated TNF-α-induced, mitogen-activated protein kinase activation, and, surprisingly, FAK inhibition resulted in the loss of the GATA4 transcription factor required for TNF-α-induced VCAM-1 production. FAK inhibition also triggered FAK nuclear localization. In the nucleus, the FAK-FERM (band 4.1, ezrin, radixin, moesin homology) domain bound directly to GATA4 and enhanced its CHIP (C terminus of Hsp70-interacting protein) E3 ligase-dependent polyubiquitination and degradation. These studies reveal new developmental and anti-inflammatory roles for kinase-inhibited FAK in limiting VCAM-1 production via nuclear localization and promotion of GATA4 turnover

Validation and analysis of MOPITT CO observations of the Amazon Basin

We analyze satellite retrievals of carbon monoxide from the MOPITT (Measurements of Pollution in the Troposphere) instrument over the Amazon Basin, focusing on the MOPITT Version 6 "multispectral" retrieval product (exploiting both thermal-infrared and near-infrared channels). Validation results based on in situ vertical profiles measured between 2010 and 2013 are presented for four sites in the Amazon Basin. Results indicate a significant negative bias in retrieved lower-tropospheric CO concentrations. The possible influence of smoke aerosol as a source of retrieval bias is investigated using collocated Aerosol Robotic Network (AERONET) aerosol optical depth (AOD) measurements at two sites but does not appear to be significant. Finally, we exploit the MOPITT record to analyze both the mean annual cycle and the interannual variability of CO over the Amazon Basin since 2002

The Effectiveness of Maintenance Pharmacotherapies for Non-Small Cell Lung Cancer

Although current recommendations for the treatment of advanced non-small cell lung cancer (NSCLC) include a maximum of six cycles of platinum-based combination therapy as a first-line approach, most patients experience progression within 3–4 months. Therefore, a new treatment strategy, maintenance therapy, has been proposed, and several large randomized prospective controlled trials have shown benefits with maintenance therapy. Maintenance therapy can be classified as either continuation maintenance, which is defined as a prolongation of a part of the first-line chemotherapy or molecularly targeted agent until progression, or switch-maintenance, which is defined as the administration of a different cytotoxic chemotherapy or molecularly targeted agent immediately after induction therapy. In this article, recent results from large randomized phase III trials regarding maintenance therapy are reviewed in order to evaluate the role of maintenance therapy in NSCLC

Web platform vs in-person genetic counselor for return of carrier results from exome sequencing a randomized clinical trial

© 2018 American Medical Association. All rights reserved. IMPORTANCE A critical bottleneck in clinical genomics is the mismatch between large volumes of results and the availability of knowledgeable professionals to return them. OBJECTIVE To test whether a web-based platform is noninferior to a genetic counselor for educating patients about their carrier results from exome sequencing. DESIGN, SETTING, AND PARTICIPANTS A randomized noninferiority trial conducted in a longitudinal sequencing cohort at the National Institutes of Health from February 5, 2014, to December 16, 2016, was used to compare the web-based platform with a genetic counselor. Among the 571 eligible participants, 1 to 7 heterozygous variants were identified in genes that cause a phenotype that is recessively inherited. Surveys were administered after cohort enrollment, immediately following trial education, and 1 month and 6 months later to primarily healthy postreproductive participants who expressed interest in learning their carrier results. Both intention-to-treat and per-protocol analyses were applied. INTERVENTIONS A web-based platform that integrated education on carrier results with personal test results was designed to directly parallel disclosure education by a genetic counselor. The sessions took a mean (SD) time of 21 (10.6), and 27 (9.3) minutes, respectively. MAIN OUTCOMES AND MEASURES The primary outcomes and noninferiority margins (dNI) were knowledge (0 to 8, dNI = -1), test-specific distress (0 to 30, dNI = +1), and decisional conflict (15 to 75, dNI = +6). RESULTS After 462 participants (80.9%) provided consent and were randomized, all but 3 participants (n = 459) completed surveys following education and counseling; 398 (86.1%) completed 1-month surveys and 392 (84.8%) completed 6-month surveys. Participants were predominantly well-educated, non-Hispanic white, married parents; mean (SD) age was 63 (63.1) years and 246 (53.6%) were men. The web platform was noninferior to the genetic counselor on outcomes assessed at 1 and 6 months: knowledge (mean group difference, -0.18; lower limit of 97.5% CI, -0.63; dNI = -1), test-specific distress (median group difference, 0; upper limit of 97.5% CI, 0; dNI = +1), and decisional conflict about choosing to learn results (mean group difference, 1.18; upper limit of 97.5% CI, 2.66; dNI = +6). There were no significant differences between the genetic counselors and web-based platform detected between modes of education delivery in disclosure rates to spouses (151 vs 159; relative risk [RR], 1.04; 95% CI, 0.64-1.69; P > .99), children (103 vs 117; RR, 1.07; 95% CI, 0.85-1.36; P = .59), or siblings (91 vs 78; RR, 1.17; 95% CI, 0.94-1.46; P = .18). CONCLUSIONS AND RELEVANCE This trial demonstrates noninferiority of web-based return of carrier results among postreproductive, mostly healthy adults. Replication studies among younger and more diverse populations are needed to establish generalizability. Yet return of results via a web-based platform may be sufficient for subsets of test results, reserving genetic counselors for return of results with a greater health threat

Integrative analyses identify modulators of response to neoadjuvant aromatase inhibitors in patients with early breast cancer

Introduction Aromatase inhibitors (AIs) are a vital component of estrogen receptor positive (ER+) breast cancer treatment. De novo and acquired resistance, however, is common. The aims of this study were to relate patterns of copy number aberrations to molecular and proliferative response to AIs, to study differences in the patterns of copy number aberrations between breast cancer samples pre- and post-AI neoadjuvant therapy, and to identify putative biomarkers for resistance to neoadjuvant AI therapy using an integrative analysis approach. Methods Samples from 84 patients derived from two neoadjuvant AI therapy trials were subjected to copy number profiling by microarray-based comparative genomic hybridisation (aCGH, n = 84), gene expression profiling (n = 47), matched pre- and post-AI aCGH (n = 19 pairs) and Ki67-based AI-response analysis (n = 39). Results Integrative analysis of these datasets identified a set of nine genes that, when amplified, were associated with a poor response to AIs, and were significantly overexpressed when amplified, including CHKA, LRP5 and SAPS3. Functional validation in vitro, using cell lines with and without amplification of these genes (SUM44, MDA-MB134-VI, T47D and MCF7) and a model of acquired AI-resistance (MCF7-LTED) identified CHKA as a gene that when amplified modulates estrogen receptor (ER)-driven proliferation, ER/estrogen response element (ERE) transactivation, expression of ER-regulated genes and phosphorylation of V-AKT murine thymoma viral oncogene homolog 1 (AKT1). Conclusions These data provide a rationale for investigation of the role of CHKA in further models of de novo and acquired resistance to AIs, and provide proof of concept that integrative genomic analyses can identify biologically relevant modulators of AI response

Sperm death and dumping in Drosophila

Mating with more than one male is the norm for females of many species. In addition to generating competition between the ejaculates of different males, multiple mating may allow females to bias sperm use. In Drosophila melanogaster, the last male to inseminate a female sires approximately 80% of subsequent progeny. Both sperm displacement, where resident sperm are removed from storage by the incoming ejaculate of the copulating male, and sperm incapacitation, where incoming seminal fluids supposedly interfere with resident sperm, have been implicated in this pattern of sperm use. But the idea of incapacitation is problematic because there are no known mechanisms by which an individual could damage rival sperm and not their own. Females also influence the process of sperm use, but exactly how is unclear. Here we show that seminal fluids do not kill rival sperm and that any 'incapacitation' is probably due to sperm ageing during sperm storage. We also show that females release stored sperm from the reproductive tract (sperm dumping) after copulation with a second male and that this requires neither incoming sperm nor seminal fluids. Instead, males may cause stored sperm to be dumped or females may differentially eject sperm from the previous mating

Determination of Region of Influence Obtained by Aircraft Vertical Profiles Using the Density of Trajectories from the HYSPLIT Model

Aircraft atmospheric profiling is a valuable technique for determining greenhouse gas fluxes at regional scales (104–106 km2). Here, we describe a new, simple method for estimating the surface influence of air samples that uses backward trajectories based on the Lagrangian model Hybrid Single-Particle Lagrangian Integrated Trajectory Model (HYSPLIT). We determined “regions of influence” on a quarterly basis between 2010 and 2018 for four aircraft vertical profile sites: SAN and ALF in the eastern Amazon, and RBA and TAB or TEF in the western Amazon. We evaluated regions of influence in terms of their relative sensitivity to areas inside and outside the Amazon and their total area inside the Amazon. Regions of influence varied by quarter and less so by year. In the first and fourth quarters, the contribution of the region of influence inside the Amazon was 83–93% for all sites, while in the second and third quarters, it was 57–75%. The interquarter differences are more evident in the eastern than in the western Amazon. Our analysis indicates that atmospheric profiles from the western sites are sensitive to 42–52.2% of the Amazon. In contrast, eastern Amazon sites are sensitive to only 10.9–25.3%. These results may help to spatially resolve the response of greenhouse gas emissions to climate variability over Amazon