Maternal exposure to childhood traumatic events, but not multi-domain psychosocial stressors, predict placental corticotrophin releasing hormone across pregnancy

Maternal psychosocial stress increases the risk of adverse birth and postnatal outcomes for the mother and child, but the role of maternal exposure to childhood traumatic events (CTE) and multi-domain psychosocial stressors for the level and rise of placental Corticotrophin-Releasing Hormone (pCRH) across pregnancy has been understudied. In a sociodemographically and racially diverse sample of 1303 women (64% Black, 36% White/others) with low-medical risk pregnancies at enrollment from Shelby County, Tennessee, USA, blood samples were drawn twice, corresponding roughly to second and third trimester, and extracted prior to conducting radioimmune assays for pCRH. Mothers reported CTE (physical abuse, sexual abuse, or family violence, in childhood), adulthood traumatic events, and interpersonal violence during pregnancy. Neighborhood crime/deprivation was derived using geospatially-linked objective databases. General linear and mixed models tested associations between stress exposure variables and pCRH levels and rate of rise, adjusting for obstetric/clinical/health related factors. Maternal CTE did not predict pCRH levels at time 1, but positively predicted levels at time 2, and the rate of rise in pCRH across pregnancy. Race did not moderate this association. No additional maternal stress exposures across adulthood or during pregnancy predicted pCRH outcomes. Findings indicate that childhood violence or abuse exposure can become biologically embedded in a manner predicting later prenatal physiology relevant for maternal and offspring health, and that such embedding may be specific to childhood, but not adulthood, stress. Findings also highlight the placental-fetal unit as a mechanistic pathway through which intergenerational transmission of the adverse effects of childhood adversities may occur.publishedVersio

BUDHIES - III : the fate of HI and the quenching of galaxies in evolving environments

In a hierarchical Universe clusters grow via the accretion of galaxies from the field, groups and even other clusters. As this happens, galaxies can lose and/or consume their gas reservoirs via different mechanisms, eventually quenching their star formation. We explore the diverse environmental histories of galaxies through a multiwavelength study of the combined effect of ram-pressure stripping and group 'processing' in Abell 963, a massive growing cluster at z = 0.2 from the Blind Ultra Deep HI Environmental Survey (BUDHIES). We incorporate hundreds of new optical redshifts (giving a total of 566 cluster members), as well as Subaru and XMM-Newton data from LoCuSS, to identify substructures and evaluate galaxy morphology, star formation activity, and HI content (via HI deficiencies and stacking) out to 3 x R-200. We find that Abell 963 is being fed by at least seven groups, that contribute to the large number of passive galaxies outside the cluster core. More massive groups have a higher fraction of passive and HI-poor galaxies, while low-mass groups host younger (often interacting) galaxies. For cluster galaxies not associated with groups we corroborate our previous finding that HI gas (if any) is significantly stripped via ram-pressure during their first passage through the intracluster medium, and find mild evidence for a starburst associated with this event. In addition, we find an overabundance of morphologically peculiar and/or star-forming galaxies near the cluster core. We speculate that these arise from the effect of groups passing through the cluster (post-processing). Our study highlights the importance of environmental quenching and the complexity added by evolving environments.Peer reviewe

Environmentally relevant iron oxide nanoparticles produce limited acute pulmonary effects in rats at realistic exposure levels

Iron is typically the dominant metal in the ultrafine fraction of airborne particulate matter. Various studies have investigated the toxicity of inhaled nano-sized iron oxide particles (FeOxNPs) but their results have been contradictory, with some indicating no or minor effects and others finding effects including oxidative stress and inflammation. Most studies, however, did not use materials reflecting the characteristics of FeOxNPs present in the environment. We, therefore, analysed the potential toxicity of FeOxNPs of different forms (Fe3O4 , α-Fe2O3 and γ-Fe2O3 ) reflecting the characteristics of high iron content nano-sized particles sampled from the environment, both individually and in a mixture (FeOx-mix). A preliminary in vitro study indicated Fe3O4 and FeOx-mix were more cytotoxic than either form of Fe2O3 in human bronchial epithelial cells (BEAS-2B). Follow-up in vitro (0.003, 0.03, 0.3 µg/mL, 24 h) and in vivo (Sprague–Dawley rats, nose-only exposure, 50 µg/m3 and 500 µg/m3 , 3 h/d × 3 d) studies therefore focused on these materials. Experiments in vitro explored responses at the molecular level via multi-omics analyses at concentrations below those at which significant cytotoxicity was evident to avoid detection of responses secondary to toxicity. Inhalation experiments used aerosol concentrations chosen to produce similar levels of particle deposition on the airway surface as were delivered in vitro. These were markedly higher than environmental concentrations. No clinical signs of toxicity were seen nor effects on BALF cell counts or LDH levels. There were also no significant changes in transcriptomic or metabolomic responses in lung or BEAS-2B cells to suggest adverse effects

The Palmer LTER: A Long-Term Ecological Research Program at Palmer Station, Antarctica

THE ANTARCTIC marine ecosystem-the assemblage of plants, animals, ocean, sea ice, and island components south of the Antarctic Convergence is among the largest readily defined ecosystems on Earth (36 X 106 km2 ) (Hedgpeth, 1977; Petit et al., 1991). This ecosystem is composed of an interconnected system of functionally distinct hydrographic and biogeochemical subdivisions (Treguer and Jacques, 1992) and includes open ocean, frontal regions, shelf-slope waters, sea ice, and marginal ice zones. Oceanic, atmospheric, and biogeochemical processes within this system are thought to be globally significant, have been infrequently studied, and are poorly understood relative to more accessible marine ecosystems (Harris and Stonehouse, 1991; Johannessen et al., 1994). The Palmer Long-Term Ecological Research (Palmer LTER) area west of the Antarctic Peninsula (Fig. la) is a complex combination of a coastal/continental shelf zone and a seasonal sea ice zone, because this area is swept by the yearly advance and retreat of sea ice. The Palmer LTER program is a multidisciplinary program established to study this polar marine ecosystem

Spag16, an Axonemal Central Apparatus Gene, Encodes a Male Germ Cell Nuclear Speckle Protein that Regulates SPAG16 mRNA Expression

Spag16 is the murine orthologue of Chlamydomonas reinhardtii PF20, a protein known to be essential to the structure and function of the “9+2” axoneme. In Chlamydomonas, the PF20 gene encodes a single protein present in the central pair of the axoneme. Loss of PF20 prevents central pair assembly/integrity and results in flagellar paralysis. Here we demonstrate that the murine Spag16 gene encodes two proteins: 71 kDa SPAG16L, which is found in all murine cells with motile cilia or flagella, and 35 kDa SPAG16S, representing the C terminus of SPAG16L, which is expressed only in male germ cells, and is predominantly found in specific regions within the nucleus that also contain SC35, a known marker of nuclear speckles enriched in pre-mRNA splicing factors. SPAG16S expression precedes expression of SPAG16L. Mice homozygous for a knockout of SPAG16L alone are infertile, but show no abnormalities in spermatogenesis. Mice chimeric for a mutation deleting the transcripts for both SPAG16L and SPAG16S have a profound defect in spermatogenesis. We show here that transduction of SPAG16S into cultured dispersed mouse male germ cells and BEAS-2B human bronchial epithelial cells increases SPAG16L expression, but has no effect on the expression of several other axoneme components. We also demonstrate that the Spag16L promoter shows increased activity in the presence of SPAG16S. The distinct nuclear localization of SPAG16S and its ability to modulate Spag16L mRNA expression suggest that SPAG16S plays an important role in the gene expression machinery of male germ cells. This is a unique example of a highly conserved axonemal protein gene that encodes two protein products with different functions

The conserved C-terminus of the PcrA/UvrD helicase interacts directly with RNA polymerase

Copyright: © 2013 Gwynn et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by a Wellcome Trust project grant to MD (Reference: 077368), an ERC starting grant to MD (Acronym: SM-DNA-REPAIR) and a BBSRC project grant to PM, NS and MD (Reference: BB/I003142/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Type-Specific Cervico-Vaginal Human Papillomavirus Infection Increases Risk of HIV Acquisition Independent of Other Sexually Transmitted Infections

Sexually transmitted infections (STIs) such as herpes simplex virus (HSV)-2 are associated with an increased risk of HIV infection. Human papillomavirus (HPV) is a common STI, but little is know about its role in HIV transmission. The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs.This prospective cohort study followed 2040 HIV-negative Zimbabwean women (average age 27 years, range 18-49 years) for a median of 21 months. Participants were tested quarterly for 29 HPV types (with L1 PCR primers) and HIV (antibody testing on blood samples with DNA or RNA PCR confirmation). HIV incidence was 2.7 per 100 woman-years. Baseline HPV prevalence was 24.5%, and the most prevalent HPV types were 58 (5.0%), 16 (4.7%), 70 (2.4%), and 18 (2.3%). In separate regression models adjusting for baseline variables (including age, high risk partner, positive test for STIs, positive HSV-2 serology and condom use), HIV acquisition was associated with having baseline prevalent infection with HPV 58 (aHR 2.13; 95% CI 1.09-4.15) or HPV 70 (aHR 2.68; 95% CI 1.08-6.66). In separate regression models adjusting for both baseline variables and time-dependent variables (including HSV-2 status, incident STIs, new sexual partner and condom use), HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type (aHR 1.70; 95% CI 1.02-2.85), any oncogenic HPV type (aHR 1.96; 95% CI 1.16-3.30), HPV 31 (aHR 4.25; 95% CI 1.81-9.97) or HPV 70 (aHR 3.30; 95% CI 1.50-7.20). Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition, regardless of whether HPV status at the HIV acquisition visit was included (aHR 1.95; 95% CI 1.19-3.21) or excluded (aHR 1.96; 95% CI 1.02-2.85) from the analysis.Cervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women, and specific HPV types were implicated in this association. The observational nature of our study precludes establishment of causation between HPV infection and HIV acquisition. However, given the high prevalence of HPV infection in women, further investigation of the role of HPV in HIV transmission is warranted

A Bayesian decision support sequential model for severity of illness predictors and intensive care admissions in pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality in the USA. Our objective was to assess the predictive value on critical illness and disposition of a sequential Bayesian Model that integrates Lactate and procalcitonin (PCT) for pneumonia. METHODS: Sensitivity and specificity of lactate and PCT attained from pooled meta-analysis data. Likelihood ratios calculated and inserted in Bayesian/ Fagan nomogram to calculate posttest probabilities. Bayesian Diagnostic Gains (BDG) were analyzed comparing pre and post-test probability. To assess the value of integrating both PCT and Lactate in Severity of Illness Prediction we built a model that combined CURB65 with PCT as the Pre-Test markers and later integrated the Lactate Likelihood Ratio Values to generate a combined CURB 65 + Procalcitonin + Lactate Sequential value. RESULTS: The BDG model integrated a CUBR65 Scores combined with Procalcitonin (LR+ and LR-) for Pre-Test Probability Intermediate and High with Lactate Positive Likelihood Ratios. This generated for the PCT LR+ Post-test Probability (POSITIVE TEST) Posterior probability: 93% (95% CI [91,96%]) and Post Test Probability (NEGATIVE TEST) of: 17% (95% CI [15-20%]) for the Intermediate subgroup and 97% for the high risk sub-group POSITIVE TEST: Post-Test probability:97% (95% CI [95,98%]) NEGATIVE TEST: Post-test probability: 33% (95% CI [31,36%]) . ANOVA analysis for CURB 65 (alone) vs CURB 65 and PCT (LR+) vs CURB 65 and PCT (LR+) and Lactate showed a statistically significant difference (P value = 0.013). CONCLUSIONS: The sequential combination of CURB 65 plus PCT with Lactate yielded statistically significant results, demonstrating a greater predictive value for severity of illness thus ICU level care

Coevolution of amino acid residues in the key photosynthetic enzyme Rubisco

<p>Abstract</p> <p>Background</p> <p>One of the key forces shaping proteins is coevolution of amino acid residues. Knowing which residues coevolve in a particular protein may facilitate our understanding of protein evolution, structure and function, and help to identify substitutions that may lead to desired changes in enzyme kinetics. Rubisco, the most abundant enzyme in biosphere, plays an essential role in the process of carbon fixation through photosynthesis, thus facilitating life on Earth. This makes Rubisco an important model system for studying the dynamics of protein fitness optimization on the evolutionary landscape. In this study we investigated the selective and coevolutionary forces acting on large subunit of land plants Rubisco using Markov models of codon substitution and clustering approaches applied to amino acid substitution histories.</p> <p>Results</p> <p>We found that both selection and coevolution shape Rubisco, and that positively selected and coevolving residues have their specifically favored amino acid composition and pairing preference. The mapping of these residues on the known Rubisco tertiary structures showed that the coevolving residues tend to be in closer proximity with each other compared to the background, while positively selected residues tend to be further away from each other. This study also reveals that the residues under positive selection or coevolutionary force are located within functionally important regions and that some residues are targets of both positive selection and coevolution at the same time.</p> <p>Conclusion</p> <p>Our results demonstrate that coevolution of residues is common in Rubisco of land plants and that there is an overlap between coevolving and positively selected residues. Knowledge of which Rubisco residues are coevolving and positively selected could be used for further work on structural modeling and identification of substitutions that may be changed in order to improve efficiency of this important enzyme in crops.</p