Ebola Response: A Summary of Field Work Project

While epidemics and disease outbreaks are not uncommon world wide, the most recent outbreak of Ebola Virus Disease (EVD) has been the largest outbreak of the disease and the most wide spread in history. The outbreak has caused international concern and was declared a public health emergency of international concern by the World Health Organization (WHO) in August of 2014. Since the outbreak started there have been a total of 15,351 confirmed, probable and suspected cases of EVD reported in six affected countries including Guinea, Liberia, Mali, Sierra Leone, Spain and the United States. There have been 5459 reported deaths associated with EVD worldwide. In this paper, Ebola Response: A Summary of Field Work Project, Jeffrey Schmidt’s fieldwork with San Francisco General Hospital and Trauma Center and the San Francisco Department of Public Health is summarized. The main objective of the fieldwork project was to assist with developing an Ebola response plan and then test the response plan through simulations

The Good, the Bad, and the Rare: Memory for Partners in Social Interactions

For cooperation to evolve via direct reciprocity, individuals must track their partners' behavior to avoid exploitation. With increasing size of the interaction group, however, memory becomes error prone. To decrease memory effort, people could categorize partners into types, distinguishing cooperators and cheaters. We explored two ways in which people might preferentially track one partner type: remember cheaters or remember the rare type in the population. We assigned participants to one of three interaction groups which differed in the proportion of computer partners' types (defectors rare, equal proportion, or cooperators rare). We extended research on both hypotheses in two ways. First, participants experienced their partners repeatedly by interacting in Prisoner's Dilemma games. Second, we tested categorization of partners as cooperators or defectors in memory tests after a short and long retention interval (10 min and 1 week). Participants remembered rare partner types better than they remembered common ones at both retention intervals. We propose that the flexibility of responding to the environment suggests an ecologically rational memory strategy in social interactions

Environmental cues and constraints affecting the seasonality of dominant calanoid copepods in brackish, coastal waters: a case study of Acartia, Temora and Eurytemora species in the south-west Baltic

Information on physiological rates and tolerances helps one gain a cause-and-effect understanding of the role that some environmental (bottom–up) factors play in regulating the seasonality and productivity of key species. We combined the results of laboratory experiments on reproductive success and field time series data on adult abundance to explore factors controlling the seasonality of Acartia spp., Eurytemora affinis and Temora longicornis, key copepods of brackish, coastal and temperate environments. Patterns in laboratory and field data were discussed using a metabolic framework that included the effects of ‘controlling’, ‘masking’ and ‘directive’ environmental factors. Over a 5-year period, changes in adult abundance within two south-west Baltic field sites (Kiel Fjord Pier, 54°19′89N, 10°09′06E, 12–21 psu, and North/Baltic Sea Canal NOK, 54°20′45N, 9°57′02E, 4–10 psu) were evaluated with respect to changes in temperature, salinity, day length and chlorophyll a concentration. Acartia spp. dominated the copepod assemblage at both sites (up to 16,764 and 21,771 females m−3 at NOK and Pier) and was 4 to 10 times more abundant than E. affinis (to 2,939 m−3 at NOK) and T. longicornis (to 1,959 m−3 at Pier), respectively. Species-specific salinity tolerance explains differences in adult abundance between sampling sites whereas phenological differences among species are best explained by the influence of species-specific thermal windows and prey requirements supporting survival and egg production. Multiple intrinsic and extrinsic (environmental) factors influence the production of different egg types (normal and resting), regulate life-history strategies and influence match–mismatch dynamics

Altered Immune Responses in Rhesus Macaques Co-Infected with SIV and Plasmodium cynomolgi: An Animal Model for Coincident AIDS and Relapsing Malaria

BACKGROUND:Dual epidemics of the malaria parasite Plasmodium and HIV-1 in sub-Saharan Africa and Asia present a significant risk for co-infection in these overlapping endemic regions. Recent studies of HIV/Plasmodium falciparum co-infection have reported significant interactions of these pathogens, including more rapid CD4+ T cell loss, increased viral load, increased immunosuppression, and increased episodes of clinical malaria. Here, we describe a novel rhesus macaque model for co-infection that supports and expands upon findings in human co-infection studies and can be used to identify interactions between these two pathogens. METHODOLOGY/PRINCIPAL FINDINGS:Five rhesus macaques were infected with P. cynomolgi and, following three parasite relapses, with SIV. Compared to macaques infected with SIV alone, co-infected animals had, as a group, decreased survival time and more rapid declines in markers for SIV progression, including peripheral CD4+ T cells and CD4+/CD8+ T cell ratios. The naïve CD4+ T cell pool of the co-infected animals was depleted more rapidly than animals infected with SIV alone. The co-infected animals also failed to generate proliferative responses to parasitemia by CD4+ and CD8+ T cells as well as B cells while also having a less robust anti-parasite and altered anti-SIV antibody response. CONCLUSIONS/SIGNIFICANCE:These data suggest that infection with both SIV and Plasmodium enhances SIV-induced disease progression and impairs the anti-Plasmodium immune response. These data support findings in HIV/Plasmodium co-infection studies. This animal model can be used to further define impacts of lentivirus and Plasmodium co-infection and guide public health and therapeutic interventions

Adaptations to Submarine Hydrothermal Environments Exemplified by the Genome of Nautilia profundicola

Submarine hydrothermal vents are model systems for the Archaean Earth environment, and some sites maintain conditions that may have favored the formation and evolution of cellular life. Vents are typified by rapid fluctuations in temperature and redox potential that impose a strong selective pressure on resident microbial communities. Nautilia profundicola strain Am-H is a moderately thermophilic, deeply-branching Epsilonproteobacterium found free-living at hydrothermal vents and is a member of the microbial mass on the dorsal surface of vent polychaete, Alvinella pompejana. Analysis of the 1.7-Mbp genome of N. profundicola uncovered adaptations to the vent environment—some unique and some shared with other Epsilonproteobacterial genomes. The major findings included: (1) a diverse suite of hydrogenases coupled to a relatively simple electron transport chain, (2) numerous stress response systems, (3) a novel predicted nitrate assimilation pathway with hydroxylamine as a key intermediate, and (4) a gene (rgy) encoding the hallmark protein for hyperthermophilic growth, reverse gyrase. Additional experiments indicated that expression of rgy in strain Am-H was induced over 100-fold with a 20°C increase above the optimal growth temperature of this bacterium and that closely related rgy genes are present and expressed in bacterial communities residing in geographically distinct thermophilic environments. N. profundicola, therefore, is a model Epsilonproteobacterium that contains all the genes necessary for life in the extreme conditions widely believed to reflect those in the Archaean biosphere—anaerobic, sulfur, H2- and CO2-rich, with fluctuating redox potentials and temperatures. In addition, reverse gyrase appears to be an important and common adaptation for mesophiles and moderate thermophiles that inhabit ecological niches characterized by rapid and frequent temperature fluctuations and, as such, can no longer be considered a unique feature of hyperthermophiles

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Endogenous Retinoic Acid Activity in Principal Cells and Intercalated Cells of Mouse Collecting Duct System

Background: Retinoic acid is the bioactive derivative of vitamin A, which plays an indispensible role in kidney development by activating retinoic acid receptors. Although the location, concentration and roles of endogenous retinoic acid in postnatal kidneys are poorly defined, there is accumulating evidence linking post-natal vitamin A deficiency to impaired renal concentrating and acidifying capacity associated with increased susceptibility to urolithiasis, renal inflammation and scarring. The aim of this study is to examine the presence and the detailed localization of endogenous retinoic acid activity in neonatal, young and adult mouse kidneys, to establish a fundamental ground for further research into potential target genes, as well as physiological and pathophysiological roles of endogenous retinoic acid in the post-natal kidneys.Methodology/Principal Findings: RARE-hsp68-lacZ transgenic mice were employed as a reporter for endogenous retinoic acid activity that was determined by X-gal assay and immunostaining of the reporter gene product, beta-galactosidase. Double immunostaining was performed for beta-galactosidase and markers of kidney tubules to localize retinoic acid activity. Distinct pattern of retinoic acid activity was observed in kidneys, which is higher in neonatal and 1- to 3-week-old mice than that in 5- and 8-week-old mice. The activity was present specifically in the principal cells and the intercalated cells of the collecting duct system in all age groups, but was absent from the glomeruli, proximal tubules, thin limbs of Henle's loop and distal tubules.Conclusions/Significance: Endogenous retinoic acid activity exists in principal cells and intercalated cells of the mouse collecting duct system after birth and persists into adulthood. This observation provides novel insights into potential roles for endogenous retinoic acid beyond nephrogenesis and warrants further studies to investigate target genes and functions of endogenous retinoic acid in the kidney after birth, particularly in the collecting duct system