Interaction between Insecticide Exposure and Trematode Infection across Four Wood Frog Populations

Amphibian populations are declining worldwide due to a number of stressors including pesticides and parasites. Conservation of these animals can be complicated because populations can differ dramatically in response to the same stressor. When consistently exposed to pesticides, some populations evolve tolerance through the process of natural selection acting across multiple generations. Alternatively, populations that are intermittently exposed to pesticides induce tolerance within a single generation. To date, however, there have been few studies examining the costs associated with these different stress tolerance mechanisms. In this study, we examined how difference in stress tolerance influence susceptibility to parasitic infections. We collected wood frog tadpoles from four different populations: two with evolved tolerance to pesticides and two with the ability to induce pesticide tolerance. We exposed tadpoles from each population to sublethal doses of carbaryl (0 and 5 ppm) for 5 days. Tadpoles were allowed to acclimate in pesticide-free water for 2 days. After this acclimation period, we then exposed tadpoles to 0 or 50 trematode parasites (Echinostoma trivolvis) for 2 days and counted the number of parasites encysted within the body. Exposure to sublethal carbaryl decreased susceptibility to trematodes for tadpole populations with evolved pesticide tolerance. In contrast, exposure to sublethal carbaryl increased susceptibility to trematodes for tadpole populations with induced pesticide tolerance. This suggests that populations with the ability to induce pesticide tolerance incur the cost of increased disease risk. This has important conservation implications for understanding a population’s history and defending against disease

Phenotypic Transition of the Collecting Duct Epithelium in Congenital Urinary Tract Obstruction

Epithelial-mesenchymal transition (EMT) has emerged in recent years as an important process in the development of organ fibrosis in many human diseases. Our previous experience in a nonhuman primate model of obstructive nephropathy suggested that EMT of collecting duct epithelium contributes to the development of interstitial fibrosis. In this study we demonstrate for the first time in humans that obstructed fetal collecting duct epithelium undergoes transition to mesenchymal phenotype, characterized by decreased expression of epithelial markers, de novo expression of mesenchymal markers with subsequent loss of cell-cell interaction, disruption of the basement membrane, and increased deposition of extracellular matrix into the expanded interstitium of the obstructed kidney. The results of this study therefore support the previous findings from animal studies and suggest that EMT of the collecting duct epithelium might contribute to the development of interstitial fibrosis in human fetal obstructive nephropathy

Physical and mental quality of life in patients with end-stage liver disease and their informal caregivers

Background & Aims Management of end-stage liver disease (ESLD) has implications for not only patients’ quality of life (QOL), but also their caregivers’. We aimed to identify characteristics of patients with ESLD and their caregivers that are associated with QOL. Methods We obtained cross-sectional baseline data from patients and their caregivers (132 dyads; 62% were married or partners), recruited from outpatient hepatology clinics within 2 healthcare centers. Patients were included if their model for end-stage liver disease score was 15 or more; caregivers were identified by the patient as the primary informal caregiver. QOL was measured by the SF-36 and relationship quality using the mutuality scale. We measured uncertainty using the uncertainty in illness scales for patients and caregivers. Multilevel modeling was used to analyze the data. Results Refractory ascites was associated with worse physical QOL for patients (unstandardized beta [B], –9.19; standard error [SE], 2.28) and caregivers (B, –5.41; SE, 2.33); history of hepatic encephalopathy was associated with worse patient physical QOL (B, –3.86; SE, 1.65). High levels of uncertainty were associated with worse physical and mental QOL for both members of the dyads; relationship quality was significantly associated with patient mental QOL (B, 2.73; SE, 1.19). Conclusions Clinicians and researchers should consider the effects of ESLD on caregivers as well as their patients to optimize the QOL for both

Persistent Organic Pollutant in the Venetian coastal environment

The Venetian coastal area is characterized by a strong anthropogenic impact and its quality is very important because of local economical activities, such as tourism or fishing. In the context of the Water Framework Directive (WFD, 2000/60/EC), the aim of the project Q-ALiVe (Qualità dell’Ambiente Litoraneo Veneto) is to check the environmental quality of the Venetian coastal area and whether rivers contamination could influence it. We studied an area going from the mouth of the Adige river to the Malamocco inlet of the Venice lagoon (including the mouth of the Brenta river and the Chioggia lagoon inlet), to distance from the coast of up to about a kilometer. In this work we presented the data relative to Persistent Organic Pollutants (POPs) as PCBs, PBDEs and PAHs, in samples of seawater. Samples were collected during four different sampling campaigns, in different seasons (June 2011, August 2011, September 2011, November 2011); in each sampling campaign we collected 10 samples of surface water. Analytical samples procedures for POPs include liquid-liquid continuous extraction, followed by an automated purification step, with neutral silica columns. Analysis were made by HRGC-HRMS (PCBs) or HRGC-LRMS (PAHs and PBDEs). Quantification was made by isotope dilution. Results suggest a negligible influence of rivers contamination to the quality of the sea facing the city of Chioggia and the Venice lagoon. Funds for this work were provided, in the framework of Q-ALiVe Project, by the Regione del Veneto - L.R. 15/07

The birth of a human-specific neural gene by incomplete duplication and gene fusion

Background: Gene innovation by duplication is a fundamental evolutionary process but is difficult to study in humans due to the large size, high sequence identity, and mosaic nature of segmental duplication blocks. The human-specific gene hydrocephalus-inducing 2, HYDIN2, was generated by a 364 kbp duplication of 79 internal exons of the large ciliary gene HYDIN from chromosome 16q22.2 to chromosome 1q21.1. Because the HYDIN2 locus lacks the ancestral promoter and seven terminal exons of the progenitor gene, we sought to characterize transcription at this locus by coupling reverse transcription polymerase chain reaction and long-read sequencing. Results: 5' RACE indicates a transcription start site for HYDIN2 outside of the duplication and we observe fusion transcripts spanning both the 5' and 3' breakpoints. We observe extensive splicing diversity leading to the formation of altered open reading frames (ORFs) that appear to be under relaxed selection. We show that HYDIN2 adopted a new promoter that drives an altered pattern of expression, with highest levels in neural tissues. We estimate that the HYDIN duplication occurred ~3.2 million years ago and find that it is nearly fixed (99.9%) for diploid copy number in contemporary humans. Examination of 73 chromosome 1q21 rearrangement patients reveals that HYDIN2 is deleted or duplicated in most cases. Conclusions: Together, these data support a model of rapid gene innovation by fusion of incomplete segmental duplications, altered tissue expression, and potential subfunctionalization or neofunctionalization of HYDIN2 early in the evolution of the Homo lineage

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients

INTRODUCTION: The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. METHODS: A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. RESULTS: After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7–3.9%), 10.7% (95% CI 6.3–14.9%), and 15.5% (95% CI 7.6–22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5–7.9%), 17.8% (95% CI 11.8–23.3%), and 19.9% (95% CI 14.2–25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. CONCLUSION: In this large, population-based study of lymph node-negative patients not treated with chemotherapy, the Recurrence Score was strongly associated with risk of breast cancer death among ER-positive, tamoxifen-treated and -untreated patients

Assemblathon 2: evaluating de novo methods of genome assembly in three vertebrate species

Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions: Many current genome assemblers produced useful assemblies, containing a significant representation of their genes and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another

Comparative phylogeography of reef fishes from the Gulf of Aden to the Arabian Sea reveals two cryptic lineages

Arabian Sea is a heterogeneous region with high coral cover and warm stable conditions at the western end (Djibouti), in contrast to sparse coral cover, cooler temperatures, and upwelling at the eastern end (southern Oman). We tested for barriers to dispersal across this region (including the Gulf of Aden and Gulf of Oman), using mitochondrial DNA surveys of 11 reef fishes. Study species included seven taxa from six families with broad distributions across the Indo-Pacific and four species restricted to the Arabian Sea (and adjacent areas). Nine species showed no significant genetic partitions, indicating connectivity among contrasting environments spread across 2000 km. One butterflyfish (Chaetodon melannotus) and a snapper (Lutjanus kasmira) showed phylogenetic divergences of d = 0.008 and 0.048, respectively, possibly indicating cryptic species within these broadly distributed taxa. These genetic partitions at the western periphery of the Indo-Pacific reflect similar partitions recently discovered at the eastern periphery of the Indo-Pacific (the Hawaiian and the Marquesan Archipelagos), indicating that these disjunctive habitats at the ends of the range may serve as evolutionary incubators for coral reef organisms. © 2017 Springer-Verlag Berlin HeidelbergTh

Transforming Epidemiology for 21st Century Medicine and Public Health

In 2012, the National Cancer Institute (NCI) engaged the scientific community to provide a vision for cancer epidemiology in the 21st century. Eight overarching thematic recommendations, with proposed corresponding actions for consideration by funding agencies, professional societies, and the research community emerged from the collective intellectual discourse. The themes are (i) extending the reach of epidemiology beyond discovery and etiologic research to include multilevel analysis, intervention evaluation, implementation, and outcomes research; (ii) transforming the practice of epidemiology by moving towards more access and sharing of protocols, data, metadata, and specimens to foster collaboration, to ensure reproducibility and replication, and accelerate translation; (iii) expanding cohort studies to collect exposure, clinical and other information across the life course and examining multiple health-related endpoints; (iv) developing and validating reliable methods and technologies to quantify exposures and outcomes on a massive scale, and to assess concomitantly the role of multiple factors in complex diseases; (v) integrating “big data” science into the practice of epidemiology; (vi) expanding knowledge integration to drive research, policy and practice; (vii) transforming training of 21st century epidemiologists to address interdisciplinary and translational research; and (viii) optimizing the use of resources and infrastructure for epidemiologic studies. These recommendations can transform cancer epidemiology and the field of epidemiology in general, by enhancing transparency, interdisciplinary collaboration, and strategic applications of new technologies. They should lay a strong scientific foundation for accelerated translation of scientific discoveries into individual and population health benefits