Maternal obesity in females born small: pregnancy complications and offspring disease risk

Obesity is a major public health crisis, with 1.6 billion adults worldwide being classified as overweight or obese in 2014. Therefore, it is not surprising that the number of women who are overweight or obese at the time of conception is increasing. Obesity during pregnancy is associated with the development of gestational diabetes and preeclampsia. The developmental origins of health and disease hypothesis proposes that perturbations during critical stages of development can result in adverse fetal changes, which leads to an increased risk of developing diseases in adulthood. Of particular concern, children born to obese mothers are at a greater risk of developing cardiometabolic disease. One subset of the population who are predisposed to developing obesity are children born small for gestational age, which occurs in 10% of pregnancies worldwide. Epidemiological studies report that these growth restricted children have an increased susceptibility to type 2 diabetes, obesity and hypertension. Importantly during pregnancy, growth restricted females have a higher risk of developing cardiometabolic disease, indicating that they may have an exacerbated phenotype if they are also overweight or obese. Thus the development of early pregnancy interventions targeted to obese mothers may prevent their children from developing cardiometabolic disease in adulthood. This article is protected by copyright. All rights reserved

Anterior basolateral amygdala neurons comprise a remote fear memory engram

IntroductionThreatening environmental cues often generate enduring fear memories, but how these are formed and stored remains actively investigated. Recall of a recent fear memory is thought to reflect reactivation of neurons, in multiple brain regions, activated during memory formation, indicating that anatomically distributed and interconnected neuronal ensembles comprise fear memory engrams. The extent to which anatomically specific activation-reactivation engrams persist during long-term fear memory recall, however, remains largely unexplored. We hypothesized that principal neurons in the anterior basolateral amygdala (aBLA), which encode negative valence, acutely reactivate during remote fear memory recall to drive fear behavior.MethodsUsing adult offspring of TRAP2 and Ai14 mice, persistent tdTomato expression was used to “TRAP” aBLA neurons that underwent Fos-activation during contextual fear conditioning (electric shocks) or context only conditioning (no shocks) (n = 5/group). Three weeks later, mice were re-exposed to the same context cues for remote memory recall, then sacrificed for Fos immunohistochemistry.ResultsTRAPed (tdTomato +), Fos +, and reactivated (double-labeled) neuronal ensembles were larger in fear- than context-conditioned mice, with the middle sub-region and middle/caudal dorsomedial quadrants of aBLA displaying the greatest densities of all three ensemble populations. Whereas tdTomato + ensembles were dominantly glutamatergic in context and fear groups, freezing behavior during remote memory recall was not correlated with ensemble sizes in either group.DiscussionWe conclude that although an aBLA-inclusive fear memory engram forms and persists at a remote time point, plasticity impacting electrophysiological responses of engram neurons, not their population size, encodes fear memory and drives behavioral manifestations of long-term fear memory recall

A prospective phase I dose-escalation trial of stereotactic ablative radiotherapy (SABR) as an alternative to cytoreductive nephrectomy for inoperable patients with metastatic renal cell carcinoma

Background: Cytoreductive nephrectomy is thought to improve survival in metastatic renal cell carcinoma (mRCC). As many patients are ineligible for major surgery, we hypothesized that SABR could be a safe alternative. Methods: In this dose-escalation trial, inoperable mRCC patients underwent SABR targeting the entire affected kidney. Toxicity (CTCAE v3.0), quality of life (QoL), renal function, and tumour response (RECIST v1.0) were assessed. Results: Twelve patients of mostly intermediate (67%) or poor (25%) International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic class, median KPS of 70%, and median tumour size of 8.7 cm (range: 4.8-13.8) were enrolled in successive dose cohorts of 25 (n = 3), 30 (n = 6), and 35 Gy (n = 3) in 5 fractions. SABR was well tolerated with 3 grade 3 events: fatigue (2) and bone pain (1). QoL decreased for physical well-being (p = 0.016), but remained unchanged in other domains. SABR achieved a median tumour size reduction of - 17.3% (range: + 5.3 to - 54.4) at 5.3 months. All patients progressed systemically and median OS was 6.7 months. Crude median follow-up was 5.8 months. Conclusions: In non-operable mRCC patients, renal-ablative SABR to 35 Gy in 5 fractions yielded acceptable toxicity, renal function preservation, and stable QoL. SABR merits further prospective investigation as an alternative to cytoreductive nephrectomy

Genetic structure of First Nation communities in the Pacific Northwest

This study presents genetic data for nine Native American populations from northern North America. Analyses of genetic variation focus on the Pacific Northwest (PNW). Using mitochondrial, Y chromosomal and autosomal DNA variants, we aim to more closely address the relationships of geography and language with present genetic diversity among the regional PNW Native American populations. Patterns of genetic diversity exhibited by the three genetic systems were consistent with our hypotheses, in that we expected genetic variation to be more strongly explained by geographic proximity than linguistic structure. Our findings were corroborated through a variety on analytic approaches, with the unrooted trees for the three genetic systems consistently separating inland from coastal PNW populations. Furthermore, the AMOVA tests support the trends exhibited by the unrooted trees, with geographic partitioning of PNW populations (FCT = 19.43%, p = 0.010 ± 0.009) accounting for over twice as much of the observed genetic variation compared with linguistic partitioning of the same populations (FCT = 9.15%, p = 0.193 ± 0.013). These findings demonstrate a consensus with previous PNW population studies examining the relationships of genome-wide variation, mitochondrial haplogroup frequencies, and skeletal morphology with geography and language

Wet scavenging of soluble gases in DC3 deep convective storms using WRF-Chem simulations and aircraft observations

We examine wet scavenging of soluble trace gases in storms observed during the Deep Convective Clouds and Chemistry (DC3) field campaign. We conduct high-resolution simulations with the Weather Research and Forecasting model with Chemistry (WRF-Chem) of a severe storm in Oklahoma. The model represents well the storm location, size, and structure as compared with Next Generation Weather Radar reflectivity, and simulated CO transport is consistent with aircraft observations. Scavenging efficiencies (SEs) between inflow and outflow of soluble species are calculated from aircraft measurements and model simulations. Using a simple wet scavenging scheme, we simulate the SE of each soluble species within the error bars of the observations. The simulated SEs of all species except nitric acid (HNO_3) are highly sensitive to the values specified for the fractions retained in ice when cloud water freezes. To reproduce the observations, we must assume zero ice retention for formaldehyde (CH_2O) and hydrogen peroxide (H_2O_2) and complete retention for methyl hydrogen peroxide (CH_3OOH) and sulfur dioxide (SO_2), likely to compensate for the lack of aqueous chemistry in the model. We then compare scavenging efficiencies among storms that formed in Alabama and northeast Colorado and the Oklahoma storm. Significant differences in SEs are seen among storms and species. More scavenging of HNO_3 and less removal of CH_3OOH are seen in storms with higher maximum flash rates, an indication of more graupel mass. Graupel is associated with mixed-phase scavenging and lightning production of nitrogen oxides (NO_x), processes that may explain the observed differences in HNO_3 and CH_3OOH scavenging

Aerocapture Systems Analysis for a Titan Mission

Performance projections for aerocapture show a vehicle mass savings of between 40 and 80%, dependent on destination, for an aerocapture vehicle compared to an all-propulsive chemical vehicle. In addition aerocapture is applicable to multiple planetary exploration destinations of interest to NASA. The 2001 NASA In-Space Propulsion Program (ISP) technology prioritization effort identified aerocapture as one of the top three propulsion technologies for solar system exploration missions. An additional finding was that aerocapture needed a better system definition and that supporting technology gaps needed to be identified. Consequently, the ISP program sponsored an aerocapture systems analysis effort that was completed in 2002. The focus of the effort was on aerocapture at Titan with a rigid aeroshell system. Titan was selected as the initial destination for the study due to potential interest in a follow-on mission to Cassini/Huygens. Aerocapture is feasible, and the performance is adequate, for the Titan mission and it can deliver 2.4 times more mass to Titan than an all-propulsive system for the same launch vehicle

Baker Center Journal of Applied Public Policy, Vol. I No. I

Welcome to the first issue of the Baker Center Journal of Applied Public Policy. Throughout my many years of service, I always have been impressed with the tremendous good that can be accomplished through the creation and implementation of sound public policy. I hope that, along the way, I have contributed to the body of policies that help our nation function in a strong, effective, compassionate, and prosperous fashion. As we launch this new Journal, under the auspices of the Howard H. Baker Jr. Center for Public Policy at the University of Tennnnessee, I wanted to briefly expand on some of the reasons I believe that this journal is necessary and why I believe that research on public policy is so vitally important. This Journal aims to discuss applied public policy. The goal is not to engage in theoretical discussions, though I believe those are important. Instead, we hope that the Baker Journal will focus on the most current issues that directly affect our nation and our world on the operational, or mechanical level. We intend to engage a wide variety of contributors. Scholars, of course, will be asked to write on critical topics of research. We also aim to include contributions from those who draft, approve and execute public policy at the local, state, and national levels. Additionally, at least one article in each issue will be reserved for the work of a university-level student. Our approach is varied, and I know that the result will be an intellectually sound and extraordinarily interesting presentation of experiences and ideas.I am especially pleased that so many University of Tennnnessee students are involved in the formulation and operation of the Journal. Our editorial board is comprised of some of the University of Tennnnessee’s most promising undergraduate, graduate, and law school students. With dedicated assistance and oversight from faculty and from the Baker Center, this board of extraordinarily intelligent and committed students has worked very hard to make this Journal a reality. The Center has also formed a national advisory panel for the Journal. I am a member of that panel, and I must note that I am grateful for the involvement and support of my colleagues who have agreed to serve with me: Ms. Emily Reynolds, former Secretary of the United States Senate; Congressman Bob Clement, former Tennnnessee Congressman; Mr. Glennnn Reynolds, noted author and professor of law at the University of Tennnnessee; Dr. Joseph Cooper, an accomplished professor of political science at Johns Hopkins University; and Mr. John Seigenthaler, distinguished journalist and founder and director of the First Amendment Center at Vanderbilt University. I believe it is critical that we think deeply about the issues that are confronting us today. Our representative system of governance is based on an informed citizenry and informed public servants. From international issues such as the war on terror and energy challenges to more local but equally important topics such as sustainable development and education, we must commit ourselves to understanding all challenges free of partisan rhetoric. Only then can we confront them together. It is my hope that this Journal will add to that understanding and will speak to many audiences. From the classroom to the boardroom, from city hall to the halls of our legislatures, I believe the work put forward in our journal will be useful for everyone who wants to be informed and engaged. It is an exciting undertaking, and I thank you for your support

Transcriptomic Response of Fusarium verticillioides to Variably Inhibitory Environmental Isolates of Streptomyces

Fusarium verticillioides is a mycotoxigenic fungus that is a threat to food and feed safety due to its common infection of maize, a global staple crop. A proposed strategy to combat this threat is the use of biological control bacteria that can inhibit the fungus and reduce mycotoxin contamination. In this study, the effect of multiple environmental isolates of Streptomyces on F. verticillioides was examined via transcriptome analysis. The Streptomyces strains ranged from inducing no visible response to dramatic growth inhibition. Transcriptionally, F. verticillioides responded proportionally to strain inhibition with either little to no transcript changes to thousands of genes being differentially expressed. Expression changes in multiple F. verticillioides putative secondary metabolite gene clusters was observed. Interestingly, genes involved in the fusaric acid gene cluster were suppressed by inhibitory strains of Streptomyces. A F. verticillioides beta-lactamase encoding gene (FVEG_13172) was found to be highly induced by specific inhibitory Streptomyces strains and its deletion increased visible response to those strains. This study demonstrates that F. verticillioides does not have an all or nothing response to bacteria it encounters but rather a measured response that is strain specific and proportional to the strength of inhibition

Establishment, Immortalisation and Characterisation of Pteropid Bat Cell Lines

BACKGROUND: Bats are the suspected natural reservoir hosts for a number of new and emerging zoonotic viruses including Nipah virus, Hendra virus, severe acute respiratory syndrome coronavirus and Ebola virus. Since the discovery of SARS-like coronaviruses in Chinese horseshoe bats, attempts to isolate a SL-CoV from bats have failed and attempts to isolate other bat-borne viruses in various mammalian cell lines have been similarly unsuccessful. New stable bat cell lines are needed to help with these investigations and as tools to assist in the study of bat immunology and virus-host interactions. METHODOLOGY/FINDINGS: Black flying foxes (Pteropus alecto) were captured from the wild and transported live to the laboratory for primary cell culture preparation using a variety of different methods and culture media. Primary cells were successfully cultured from 20 different organs. Cell immortalisation can occur spontaneously, however we used a retroviral system to immortalise cells via the transfer and stable production of the Simian virus 40 Large T antigen and the human telomerase reverse transcriptase protein. Initial infection experiments with both cloned and uncloned cell lines using Hendra and Nipah viruses demonstrated varying degrees of infection efficiency between the different cell lines, although it was possible to infect cells in all tissue types. CONCLUSIONS/SIGNIFICANCE: The approaches developed and optimised in this study should be applicable to bats of other species. We are in the process of generating further cell lines from a number of different bat species using the methodology established in this study