Testing Comparability Between Retrospective Life History Data and Prospective Birth Cohort Study Data

Objectives: To determine whether comparable prospective and retrospective data present the same association between childhood and life course exposures and mid-life wellbeing. Method: Prospective data is taken from the 1958 UK National Child Development Study at age 50 in 2008 and earlier sweeps (n = 8,033). Retrospective data is taken from the English Longitudinal Study of Ageing at ages 50-55 from a life history interview in 2007 (n = 921). Results: There is a high degree of similarity in the direction of association between childhood exposures that have been prospectively collected in National Child Development Study and retrospectively collected in English Longitudinal Study of Ageing and wellbeing outcomes in mid-life. However, the magnitude of these associations is attenuated substantially by the inclusion of measurements, which are difficult or impossible to capture retrospectively, and are only available in prospective data, such as childhood poverty, cognitive ability, and indices of social and emotional adjustment. Discussion: The findings on the one hand provide some reassurance to the growing literature using life history data to determine life course associations with later life wellbeing. On the other hand, the findings show an overestimation in the retrospective data, in part, arising from the absence in life history data of childhood measures that are not well suited to retrospective collection

Strict protected areas are essential for the conservation of larger and threatened mammals in a priority region of the Brazilian Cerrado

ssessing protected area (PA) effectiveness is key to ensure the objectives of habitat protection are being achieved. There is strong evidence that legal protection reduces loss of natural vegetation, but biodiversity loss can still happen without significant changes in vegetation cover. Here we use data from a specifically designed camera trap survey to conduct a counterfactual assessment of PA effectiveness at safeguarding local biodiversity in the Brazilian Cerrado. We surveyed the mammal community in 517 locations at the Sertão Veredas-Peruaçu mosaic, distributed across five strict PAs (264 survey sites in five arrays) and two multiple-use PAs with low management levels (253 survey sites in four arrays). We adopted a multi-species occupancy framework to analyse our dataset while also controlling for confounding factors not directly related to protection. Of the 21 species assessed, nine had higher occupancy in strict PAs, one had higher occupancy in multiple-use PAs, and ten did not respond to protection level. Site species richness was nearly twice as large in areas under stricter protection, with even greater differences for species richness of globally threatened and larger mammals (>15 kg). Overall we demonstrated that the strict PAs surveyed support higher mammal diversity than similar areas under less restrictive management, with a particular strong effect on larger and threatened species. Given that strict PAs cover only 3% of the Cerrado, our results suggest that expanding the area under strict protection is likely to benefit iconic species of the Brazilian savanna, such as the maned wolf and giant anteater

Change and Aging Senescence as an adaptation

Understanding why we age is a long-lived open problem in evolutionary biology. Aging is prejudicial to the individual and evolutionary forces should prevent it, but many species show signs of senescence as individuals age. Here, I will propose a model for aging based on assumptions that are compatible with evolutionary theory: i) competition is between individuals; ii) there is some degree of locality, so quite often competition will between parents and their progeny; iii) optimal conditions are not stationary, mutation helps each species to keep competitive. When conditions change, a senescent species can drive immortal competitors to extinction. This counter-intuitive result arises from the pruning caused by the death of elder individuals. When there is change and mutation, each generation is slightly better adapted to the new conditions, but some older individuals survive by random chance. Senescence can eliminate those from the genetic pool. Even though individual selection forces always win over group selection ones, it is not exactly the individual that is selected, but its lineage. While senescence damages the individuals and has an evolutionary cost, it has a benefit of its own. It allows each lineage to adapt faster to changing conditions. We age because the world changes.Comment: 19 pages, 4 figure

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This 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

Assessing the conservation value of secondary savanna for large mammals in the Brazilian Cerrado

Debate about the conservation value of secondary habitats has tended to focus on tropical forests, increasingly recognizing the role of secondary forests for biodiversity conservation. However, there remains a lack of information about the conservation value of secondary savannas. Here, we conducted a camera trap survey to assess the effect of secondary vegetation on large mammals in a Brazilian Cerrado protected area, using a single-season occupancy framework to investigate the response of individual species (species-level models) and of all species combined (community-level models). In addition, we investigated the cost effectiveness of different sampling designs to monitor globally threatened species in the study area. At the community level, savanna that regenerated from eucalyptus plantation had similar occupancy estimate as old growth areas. At the species level, none of the ten species individually assessed seemed to respond to succession stage, with greater support for the effect of other covariates on occupancy, such as distance from water and vegetation physiognomy. These results demonstrate that secondary vegetation does not appear to negatively impact large mammals in the study area and suggest that, given a favorable context, Cerrado mammals can recolonize and use secondary savannas that regenerated from clearcut. However, our study area should be considered a best-case scenario, as it retained key ecological attributes of high-value secondary habitats. Our simulations showed that a sampling design with 60 camera trap sites surveyed during nine occasions is appropriate to monitor most globally threatened species in the study area, and could be a useful starting point for new monitoring initiatives in other Cerrado areas

Reduced protein expression of the phosphodiesterases PDE4A4 and PDE4A8 in AIP mutation positive somatotroph adenomas

© 2018 Type 4 phosphodiesterases (PDE4s) of the large PDE enzyme superfamily have unique specificity for cAMP and may, therefore, be relevant for somatotroph tumorigenesis. Somatotroph adenomas typically overexpress PDEs probably as part of a compensatory mechanism to reduce cAMP levels. The rat PDE4A5 isoform (human homolog PDE4A4) interacts with the AIP protein, coded by a tumour suppressor gene mutated in a subgroup of familial isolated pituitary adenomas (FIPAs). PDE4A8 is the closest related isoform of PDE4A4. We aimed to evaluate the expression of both PDE4A4 and PDE4A8 in GH cells of AIP-mutated adenomas and compare their expression with that in GH cells from sporadic AIP-mutation negative GH-secreting adenomas, where we had shown previously that both PDE4A4 and PDE4A8 isoforms had been over-expressed. Confocal immunofluorescence analysis showed that both PDE4A8 and PDE4A4 had lower expression in AIP-mutated somatotropinoma samples compared to sporadic GH-secreting tumours (P < 0.0001 for both). Based on the association of low PDE4A4 and PDE4A8 expression with germline AIP-mutations positive samples we suggest that lack of AIP hinders the upregulation of PDE4A8 and PDE4A4 protein seen in sporadic somatotrophinomas. These data point to a unique disturbance of the cAMP-PDE pathway in AIP-mutation positive adenomas, which may help to explain their well-described poor response to somatostatin analogues.Grant sponsor: NIH RO1-GM58553 to GBB, The Bolger Prostate Cancer Research Fund to GBB, and the National Cancer Institute of the National Institutes of Health to the University of Alabama at Birmingham Comprehensive Cancer Center under award number P30 CA013148 (for generation of monoclonal antibodies

Effectiveness of DNA-recombinant anti-hepatitis B vaccines in blood donors: a cohort study

<p>Abstract</p> <p>Background</p> <p>Although various studies have demonstrated efficacy of DNA-recombinant anti-hepatitis B vaccines, their effectiveness in health care settings has not been researched adequately. This gap is particularly visible for blood donors, a group of significant importance in the reduction of transfusion-transmitted hepatitis B.</p> <p>Methods</p> <p>This is a double cohort study of 1411 repeat blood donors during the period 1998–2002, involving a vaccinated and an unvaccinated cohort, with matching of the two in terms of sex, age and residence. Average follow-up was 3.17 person-years. The outcome measure was infection with hepatitis B virus (HBV), defined by testing positive on serologic markers HBsAg or anti-HBC. All blood donors were from the blood bank in Joaçaba, federal state of Santa Catarina, Brazil.</p> <p>Results</p> <p>The cohorts did not differ significantly regarding sex, age and marital status but the vaccinated cohort had higher mean number of blood donations and higher proportion of those residing in the county capital Joaçaba. Hepatitis B incidences per 1000 person-years were zero among vaccinated and 2,33 among non-vaccinated, resulting in 100% vaccine effectiveness with 95% confidence interval from 30,1% to 100%. The number of vaccinated persons necessary to avoid one HBV infection in blood donors was estimated at 429 with 95% confidence interval from 217 to 21422.</p> <p>Conclusion</p> <p>The results showed very high effectiveness of DNA-recombinant anti-HBV vaccines in blood donors. Its considerable variation in this study is likely due to the limited follow-up and the influence of confounding factors normally balanced out in efficacy clinical trials.</p

Identifying and Seeing beyond Multiple Sequence Alignment Errors Using Intra-Molecular Protein Covariation

BACKGROUND: There is currently no way to verify the quality of a multiple sequence alignment that is independent of the assumptions used to build it. Sequence alignments are typically evaluated by a number of established criteria: sequence conservation, the number of aligned residues, the frequency of gaps, and the probable correct gap placement. Covariation analysis is used to find putatively important residue pairs in a sequence alignment. Different alignments of the same protein family give different results demonstrating that covariation depends on the quality of the sequence alignment. We thus hypothesized that current criteria are insufficient to build alignments for use with covariation analyses. METHODOLOGY/PRINCIPAL FINDINGS: We show that current criteria are insufficient to build alignments for use with covariation analyses as systematic sequence alignment errors are present even in hand-curated structure-based alignment datasets like those from the Conserved Domain Database. We show that current non-parametric covariation statistics are sensitive to sequence misalignments and that this sensitivity can be used to identify systematic alignment errors. We demonstrate that removing alignment errors due to 1) improper structure alignment, 2) the presence of paralogous sequences, and 3) partial or otherwise erroneous sequences, improves contact prediction by covariation analysis. Finally we describe two non-parametric covariation statistics that are less sensitive to sequence alignment errors than those described previously in the literature. CONCLUSIONS/SIGNIFICANCE: Protein alignments with errors lead to false positive and false negative conclusions (incorrect assignment of covariation and conservation, respectively). Covariation analysis can provide a verification step, independent of traditional criteria, to identify systematic misalignments in protein alignments. Two non-parametric statistics are shown to be somewhat insensitive to misalignment errors, providing increased confidence in contact prediction when analyzing alignments with erroneous regions because of an emphasis on they emphasize pairwise covariation over group covariation