Lessons from Elwha Ecosystem Restoration: Integrating science, policy, and management

After decades of debate, planning, and environmental impact studies, the largest planned dam removal project in history was conducted on the Elwha River in Washington State, USA, from 2011 to 2014. Because this was such a unique and unprecedented project, the planning, implementation, and monitoring has occurred over 30 years and required diverse expertise across multiple stakeholders. This knowledge portfolio required that individuals and organizations with different missions collaborate effectively to ensure a successful project. The story of this river, with rugged headwaters, protected wilderness, legendary and culturally important salmon runs, and two hydroelectric dams whose placement marshaled wholesale socioeconomic and ecological changes, has become an iconic saga of change, perseverance and renewal. The two dams blocked fish migrations and disrupted sediment transport for a century, disrupting the ecological structure and function of the Elwha River. Removal of the 64-m and 32-m tall dams and the release of a large portion of the 21 million cubic meters of stored reservoir sediment, has provided a living laboratory to study the patterns, processes and outcomes of dam removal across freshwater, estuarine, and marine ecosystem boundaries from multiple scientific perspectives. This collaborative multidisciplinary approach has allowed us to improve our understanding of ecosystem responses and linkages while making the Elwha River one of the best studied dam removal projects

Sox2 Cooperates with Inflammation-Mediated Stat3 Activation in the Malignant Transformation of Foregut Basal Progenitor Cells

SummarySox2 regulates the self-renewal of multiple types of stem cells. Recent studies suggest it also plays oncogenic roles in the formation of squamous carcinoma in several organs, including the esophagus where Sox2 is predominantly expressed in the basal progenitor cells of the stratified epithelium. Here, we use mouse genetic models to reveal a mechanism by which Sox2 cooperates with microenvironmental signals to malignantly transform epithelial progenitor cells. Conditional overexpression of Sox2 in basal cells expands the progenitor population in both the esophagus and forestomach. Significantly, carcinoma only develops in the forestomach, where pathological progression correlates with inflammation and nuclear localization of Stat3 in progenitor cells. Importantly, co-overexpression of Sox2 and activated Stat3 (Stat3C) also transforms esophageal basal cells but not the differentiated suprabasal cells. These findings indicate that basal stem/progenitor cells are the cells of origin of squamous carcinoma and that cooperation between Sox2 and microenvironment-activated Stat3 is required for Sox2-driven tumorigenesis

Esophageal sphincter device for gastroesophageal reflux disease

BACKGROUND Patients with gastroesophageal reflux disease who have a partial response to proton-pump inhibitors often seek alternative therapy. We evaluated the safety and effectiveness of a new magnetic device to augment the lower esophageal sphincter. METHODS We prospectively assessed 100 patients with gastroesophageal reflux disease before and after sphincter augmentation. The study did not include a concurrent control group. The primary outcome measure was normalization of esophageal acid exposure or a 50% or greater reduction in exposure at 1 year. Secondary outcomes were 50% or greater improvement in quality of life related to gastroesophageal reflux disease and a 50% or greater reduction in the use of proton-pump inhibitors at 1 year. For each outcome, the prespecified definition of successful treatment was achievement of the outcome in at least 60% of the patients. The 3-year results of a 5-year study are reported. RESULTS The primary outcome was achieved in 64% of patients (95% confidence interval [CI], 54 to 73). For the secondary outcomes, a reduction of 50% or more in the use of proton-pump inhibitors occurred in 93% of patients, and there was improvement of 50% or more in quality-of-life scores in 92%, as compared with scores for patients assessed at baseline while they were not taking proton-pump inhibitors. The most frequent adverse event was dysphagia (in 68% of patients postoperatively, in 11% at 1 year, and in 4% at 3 years). Serious adverse events occurred in six patients, and in six patients the device was removed. CONCLUSIONS In this single-group evaluation of 100 patients before and after sphincter augmentation with a magnetic device, exposure to esophageal acid decreased, reflux symptoms improved, and use of proton-pump inhibitors decreased. Follow-up studies are needed to assess long-term safety. (Funded by Torax Medical; ClinicalTrials.gov number, NCT00776997.

Prion Uptake in the Gut: Identification of the First Uptake and Replication Sites

After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic cells (FDCs) before spreading to the nervous system. How prions are actually initially acquired from the gut lumen is not known. Using high-resolution immunofluorescence and cryo-immunogold electron microscopy, we report the trafficking of the prion protein (PrP) toward Peyer's patches of wild-type and PrP-deficient mice. PrP was transiently detectable at 1 day post feeding (dpf) within large multivesicular LAMP1-positive endosomes of enterocytes in the follicle-associated epithelium (FAE) and at much lower levels within M cells. Subsequently, PrP was detected on vesicles in the late endosomal compartments of macrophages in the subepithelial dome. At 7–21 dpf, increased PrP labelling was observed on the plasma membranes of FDCs in germinal centres of Peyer's patches from wild-type mice only, identifying FDCs as the first sites of PrP conversion and replication. Detection of PrP on extracellular vesicles displaying FAE enterocyte-derived A33 protein implied transport towards FDCs in association with FAE-derived vesicles. By 21 dpf, PrP was observed on the plasma membranes of neurons within neighbouring myenteric plexi. Together, these data identify a novel potential M cell-independent mechanism for prion transport, mediated by FAE enterocytes, which acts to initiate conversion and replication upon FDCs and subsequent infection of enteric nerves

Historic genetic structuring and paraphyly within the Great-tailed Grackle

The Great-tailed Grackle (Quiscalus mexicanus) and Boat-tailed Grackle (Q. major) are sister species that have expanded their ranges during historical times. This expansion has created an area of sympatry between these species in Texas and Louisiana, and between distinctive Great-tailed Grackle subspecies in the southwestern United States and northern Mexico. We investigated the evolutionary histories of both species using mitochondrial DNA sequence data and modern phylogenetic methods. Our results reveal genetic structure within Great-tailed, but not Boat-tailed Grackles. Great-tailed Grackles are separated into two clades, but range expansion in the north has led to secondary contact between them. Boat-tailed Grackles are monophyletic and are embedded within the Great-tailed Grackle assemblage, rendering the latter paraphyletic. These results reveal a complex phylogeographic pattern caused by recent range expansion and secondary contact of once allopatric units

Impact of aetiological screening of sexually transmitted infections during pregnancy on pregnancy outcomes in South Africa

Background Sexually transmitted infections (STIs) during pregnancy may increase the risk of adverse pregnancy outcomes. STI syndromic management is standard of care in South Africa but has its limitations. We evaluated the impact of diagnosing and treating curable STIs during pregnancy on adverse pregnancy and birth outcomes. Methods We combined data from two prospective studies of pregnant women attending public sector antenatal care (ANC) clinics in Tshwane District and Cape Town, South Africa. Pregnant women were enrolled, tested and treated for STIs. We evaluated the association between any STI at the first ANC visit and a composite adverse pregnancy outcome (miscarriage, stillbirth, preterm birth, early neonatal death, or low birthweight) using modified Poisson regression models, stratifying by HIV infection and adjusting for maternal characteristics. Results Among 619 women, 61% (n = 380) were from Tshwane District and 39% (n = 239) from Cape Town; 79% (n = 486) were women living with HIV. The prevalence of any STI was 37% (n = 228); C. trachomatis, 26% (n = 158), T. vaginalis, 18% (n = 120) and N. gonorrhoeae, 6% (n = 40). There were 93% (n = 574) singleton live births, 5% (n = 29) miscarriages and 2% (n = 16) stillbirths. Among the live births, there were 1% (n = 3) neonatal deaths, 7% (n = 35) low birthweight in full-term babies and 10% (n = 62) preterm delivery. There were 24% (n = 146) for the composite adverse pregnancy outcome. Overall, any STI diagnosis and treatment at first ANC visit was not associated with adverse outcomes in women living with HIV (adjusted relative risk (aRR); 1.43, 95% CI: 0.95–2.16) or women without HIV (aRR; 2.11, 95% CI: 0.89–5.01). However, C. trachomatis (aRR; 1.57, 95% CI: 1.04–2.39) and N. gonorrhoeae (aRR; 1.69, 95% CI: 1.09–3.08), were each independently associated with the composite adverse outcome in women living with HIV. Conclusion Treated STIs at the first ANC visit were not associated with adverse pregnancy outcome overall. In women living with HIV, C. trachomatis or N. gonorrhoeae at first ANC were each independently associated with adverse pregnancy outcome. Our results highlights complex interactions between the timing of STI detection and treatment, HIV infection and pregnancy outcomes, which warrants further investigation

Systematics and evolution of predatory flower flies (Diptera Syrphidae) based on exon-capture sequencing

Flower flies (Diptera: Syrphidae) are one of the most species-rich dipteran families and provide important ecosystem services such as pollination, biological control of pests, recycling of organic matter and redistributions of essential nutrients. Flower fly adults generally feed on pollen and nectar, but their larval feeding habits are strikingly diverse. In the present study, high-throughput sequencing was used to capture and enrich phylogenetically and evolutionary informative exonic regions. With the help of the baitfisher software, we developed a new bait kit (SYRPHIDAE1.0) to target 1945 CDS regions belonging to 1312 orthologous genes. This new bait kit was successfully used to exon capture the targeted loci in 121 flower fly species across the different subfamilies of Syrphidae. We analysed different amino acid and nucleotide data sets (1302 loci and 154 loci) with maximum likelihood and multispecies coalescent models. Our analyses yielded highly supported similar topologies, although the degree of the SRH (global stationarity, reversibility and homogeneity) conditions varied greatly between amino acid and nucleotide data sets. The sisterhood of subfamilies Pipizinae and Syrphinae is supported in all our analyses, confirming a common origin of taxa feeding on soft-bodied arthropods. Based on our results, we define Syrphini stat.rev. to include the genera Toxomerus and Paragus. Our divergence estimate analyses with beast inferred the origin of the Syrphidae in the Lower Cretaceous (125.5-98.5 Ma) and the diversification of predatory flower flies around the K-Pg boundary (70.61-54.4 Ma), coinciding with the rise and diversification of their prey.Peer reviewe