Feasibility of non-lethal approaches to protect riparian plants from foraging beavers in North America

Beavers in North America will occupy almost any wetland area containing available forage. Wetland restoration projects often provide the resources necessary for dispersing beavers to create desirable habitats. Their wide distribution and ability to disperse considerable distances almost assure that beavers will establish themselves in new wetlands. Although beavers are a natural and desirable component of a wetland ecosystem, their foraging behaviors can be destructive. Fencing may be a feasible approach to reduce damage to small, targeted areas, and textural repellents may provide some utility to protect established trees. However, these non-lethal approaches will be marginally effective when beaver populations become excessive. Beaver populations need to be maintained at levels that permit viable colonies while still permitting plant communities to flourish. This will require a better understanding of beaver movements, site and forage selection, and reproductive characteristics. This is particularly true when management objectives and regulations prohibit beaver removal from project sites

Genetic variation in the hypothalamic–pituitary–adrenal stress axis influences susceptibility to musculoskeletal pain: results from the EPIFUND study

<b>Objectives</b> To determine if genetic variation in genes in the hypothalamic–pituitary–adrenal (HPA) axis, the primary stress response system, influences susceptibility to developing musculoskeletal pain.<p></p> <b>Methods</b> Pain and comorbidity data was collected at three time points in a prospective population-based cohort study. Pairwise tagging single nucleotide polymorphisms (SNPs) were selected and genotyped for seven genes. Genetic association analysis was carried out using zero-inflated negative binomial regression to test for association between SNPs and the maximum number of pain sites across the three time points in participants reporting pain, reported as proportional changes with 95% CIs. SNPs were also tested for association with chronic widespread pain (CWP) using logistic regression reporting odds ratios and 95% CI.<p></p> <b>Results</b> A total of 75 SNPs were successfully genotyped in 994 participants including 164 cases with persistent CWP and 172 pain-free controls. Multiple SNPs in SERPINA6 were associated with the maximum number of pain sites; for example, each copy of the T allele of rs941601 was associated with having 16% (proportional change=1.16, 95% CI 1.04 to 1.28, p=0.006) more pain sites compared to participants with the CC genotype. SERPINA6 gene SNPs were also associated with CWP. Significant associations between the maximum number of pain sites and SNPs in the CRHBP and POMC genes were also observed and a SNP in MC2R was also associated with CWP. Associations between SNPs and comorbidity of poor sleep quality and depression explained some of the associations observed.<p></p> <b>Conclusions</b> Genetic variation in HPA axis genes was associated with musculoskeletal pain; however, some of the associations were explained by comorbidities. Replication of these findings is required in independent cohorts

Structural elements of an NRPS cyclization domain and its intermodule docking domain

Epothilones are thiazole-containing natural products with anticancer activity that are biosynthesized by polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) enzymes EpoA–F. A cyclization domain of EpoB (Cy) assembles the thiazole functionality from an acetyl group and L-cysteine via condensation, cyclization, and dehydration. The PKS carrier protein of EpoA contributes the acetyl moiety, guided by a docking domain, whereas an NRPS EpoB carrier protein contributes L-cysteine. To visualize the structure of a cyclization domain with an accompanying docking domain, we solved a 2.03-Å resolution structure of this bidomain EpoB unit, comprising residues M1-Q497 (62 kDa) of the 160-kDa EpoB protein. We find that the N-terminal docking domain is connected to the V-shaped Cy domain by a 20-residue linker but otherwise makes no contacts to Cy. Molecular dynamic simulations and additional crystal structures reveal a high degree of flexibility for this docking domain, emphasizing the modular nature of the components of PKS-NRPS hybrid systems. These structures further reveal two 20-Å-long channels that run from distant sites on the Cy domain to the active site at the core of the enzyme, allowing two carrier proteins to dock with Cy and deliver their substrates simultaneously. Through mutagenesis and activity assays, catalytic residues N335 and D449 have been identified. Surprisingly, these residues do not map to the location of the conserved HHxxxDG motif in the structurally homologous NRPS condensation (C) domain. Thus, although both C and Cy domains have the same basic fold, their active sites appear distinct

Structural elements of an NRPS cyclization domain and its intermodule docking domain

Epothilones are thiazole-containing natural products with anticancer activity that are biosynthesized by polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) enzymes EpoA-F. A cyclization domain of EpoB (Cy) assembles the thiazole functionality from an acetyl group and l-cysteine via condensation, cyclization, and dehydration. The PKS carrier protein of EpoA contributes the acetyl moiety, guided by a docking domain, whereas an NRPS EpoB carrier protein contributes l-cysteine. To visualize the structure of a cyclization domain with an accompanying docking domain, we solved a 2.03-A resolution structure of this bidomain EpoB unit, comprising residues M1-Q497 (62 kDa) of the 160-kDa EpoB protein. We find that the N-terminal docking domain is connected to the V-shaped Cy domain by a 20-residue linker but otherwise makes no contacts to Cy. Molecular dynamic simulations and additional crystal structures reveal a high degree of flexibility for this docking domain, emphasizing the modular nature of the components of PKS-NRPS hybrid systems. These structures further reveal two 20-A-long channels that run from distant sites on the Cy domain to the active site at the core of the enzyme, allowing two carrier proteins to dock with Cy and deliver their substrates simultaneously. Through mutagenesis and activity assays, catalytic residues N335 and D449 have been identified. Surprisingly, these residues do not map to the location of the conserved HHxxxDG motif in the structurally homologous NRPS condensation (C) domain. Thus, although both C and Cy domains have the same basic fold, their active sites appear distinct

Do genetic predictors of pain sensitivity associate with persistent widespread pain?

Genetic risk factors for pain sensitivity may also play a role in susceptibility to chronic pain disorders, in which subjects have low pain thresholds. The aim of this study was to determine if proposed functional single nucleotide polymorphisms (SNPs) in the GTP cyclohydrolase (GCH1) and μ opioid receptor (OPRM1) genes previously associated with pain sensitivity affect susceptibility to chronic widespread pain (CWP). Pain data was collected using body manikins via questionnaire at three time-points over a four year period from subjects aged 25-65 in the North-West of England as part of a population based cohort study, EPIFUND. CWP was defined at each time point using standard criteria. Three SNPs forming a proposed "pain-protective" haplotype in GCH1 (rs10483639, rs3783641 and rs8007267) and two SNPs in OPRM1 (rs1777971 (A118G) and rs563649) were genotyped in cases with persistent CWP (CWP present at ≥2 time-points) and controls who were pain-free at all time-points. The expectation-maximisation algorithm was used to estimate haplotype frequencies. The frequency of the "pain-protective" (CAT - C allele of rs10483639, A allele of rs3783641 and T allele of rs8007267) haplotype was compared to the frequency of the other haplotypes between cases and controls using the χ2 test. Allele frequencies and carriage of the minor allele was compared between cases and controls using χ2 tests for the OPRM1 SNPs. The frequency of the proposed GCH1 "pain-protective" haplotype (CAT) did not significantly differ between cases and controls and no significant associations were observed between the OPRM1 SNPs and CWP. In conclusion, there was no evidence of association between proposed functional SNPs, previously reported to influence pain sensitivity, in GCH1 and OPRM1 with CWP. Further evidence of null association in large independent cohorts is required to truly exclude these SNPs as genetic risk factors for CWP

Weight loss for women with and without polycystic ovary syndrome following a very low-calorie diet in a community-based setting with trained facilitators for 12 weeks.

Background: Polycystic ovary syndrome (PCOS) affects between 2% and 26% of reproductive-age women in the UK, and accounts for up to 75% of anovulatory infertility. The major symptoms include ovarian disruption, hyperandrogenism, insulin resistance, and polycystic ovaries. Interestingly, at least half of the women with PCOS are obese, with the excess weight playing a pathogenic role in the development and progress of the syndrome. The first-line treatment option for overweight/obese women with PCOS is diet and lifestyle interventions; however, optimal dietary guidelines are missing. Although many different dietary approaches have been investigated, data on the effectiveness of very low-calorie diets on PCOS are very limited. Materials and methods: The aim of this paper was to investigate how overweight/obese women with PCOS responded to LighterLife Total, a commercial very low-calorie diet, in conjunction with group behavioral change sessions when compared to women without PCOS (non-PCOS). Results: PCOS (n=508) and non-PCOS (n=508) participants were matched for age (age ±1 unit) and body mass index (body mass index ±1 unit). A 12-week completers analysis showed that the total weight loss did not differ significantly between PCOS (n=137) and non-PCOS participants (n=137) (-18.5±6.6 kg vs -19.4±5.7 kg, P=0.190). Similarly, the percentage of weight loss achieved by both groups was not significantly different (PCOS 17.1%±5.6% vs non-PCOS 18.2%±4.4%, P=0.08). Conclusion: Overall, LighterLife Total could be an effective weight-loss strategy in overweight/obese women with PCOS. However, further investigations are needed to achieve a thorough way of understanding the physiology of weight loss in PCOS

Identification of Anaplasma marginale Type IV Secretion System Effector Proteins

Anaplasma marginale, an obligate intracellular alphaproteobacterium in the order Rickettsiales, is a tick-borne pathogen and the leading cause of anaplasmosis in cattle worldwide. Complete genome sequencing of A. marginale revealed that it has a type IV secretion system (T4SS). The T4SS is one of seven known types of secretion systems utilized by bacteria, with the type III and IV secretion systems particularly prevalent among pathogenic Gram-negative bacteria. The T4SS is predicted to play an important role in the invasion and pathogenesis of A. marginale by translocating effector proteins across its membrane into eukaryotic target cells. However, T4SS effector proteins have not been identified and tested in the laboratory until now.Published copyLockwood, S., D. E. Voth, K. A. Brayton, P. A. Beare, W. C. Brown, R. A. Heinzen, and S. L. Broschat, Identification of Anaplasma marginale type IV secretion system effector proteins, PLoS ONE, Vol. 6, No. 11, e7724, Nov. 2011. DOI: 10.1371/journal.pone.0027724

Task 2: ShARe/CLEF eHealth evaluation lab 2014

This paper reports on Task 2 of the 2014 ShARe/CLEF eHealth evaluation lab which extended Task 1 of the 2013 ShARe/CLEF eHealth evaluation lab by focusing on template lling of disorder attributes. The task was comprised of two subtasks: attribute normalization (task 2a) and cue identication (task 2b).We instructed participants to develop a system which either kept or updated a default attribute value for each task. Participant systems were evaluated against a blind reference standard of 133 discharge summaries using Accuracy (task 2a) and F-score (task 2b). In total, ten teams participated in task 2a, and three teams in task 2b. For task 2a and 2b, the HITACHI team systems (run 2) had the highest performances, with an overall average average accuracy of 0.868 and F1-score (strict) of 0.676, respectively

Detection of circulating tumour DNA is associated with inferior outcomes in Ewing sarcoma and osteosarcoma: a report from the Children's Oncology Group.

BackgroundNew prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays.MethodsA NGS hybrid capture assay and an ultra-low-pass whole-genome sequencing assay were used to detect ctDNA in banked plasma from patients with EWS and osteosarcoma, respectively. Patients were coded as positive or negative for ctDNA and tested for association with clinical features and outcome.ResultsThe analytic cohort included 94 patients with EWS (82% from initial diagnosis) and 72 patients with primary localised osteosarcoma (100% from initial diagnosis). ctDNA was detectable in 53% and 57% of newly diagnosed patients with EWS and osteosarcoma, respectively. Among patients with newly diagnosed localised EWS, detectable ctDNA was associated with inferior 3-year event-free survival (48.6% vs. 82.1%; p = 0.006) and overall survival (79.8% vs. 92.6%; p = 0.01). In both EWS and osteosarcoma, risk of event and death increased with ctDNA levels.ConclusionsNGS assays agnostic of primary tumour sequencing results detect ctDNA in half of the plasma samples from patients with newly diagnosed EWS and osteosarcoma. Detectable ctDNA is associated with inferior outcomes

Considering Fish as Recipients of Ecosystem Services Provides a Framework to Formally Link Baseline, Development, and Post-operational Monitoring Programs and Improve Aquatic Impact Assessments for Large Scale Developments.

In most countries, major development projects must satisfy an Environmental Impact Assessment (EIA) process that considers positive and negative aspects to determine if it meets environmental standards and appropriately mitigates or offsets negative impacts on the values being considered. The benefits of before-after-control-impact monitoring designs have been widely known for more than 30 years, but most development assessments fail to effectively link pre- and post-development monitoring in a meaningful way. Fish are a common component of EIA evaluation for both socioeconomic and scientific reasons. The Ecosystem Services (ES) concept was developed to describe the ecosystem attributes that benefit humans, and it offers the opportunity to develop a framework for EIA that is centred around the needs of and benefits from fish. Focusing an environmental monitoring framework on the critical needs of fish could serve to better align risk, development, and monitoring assessment processes. We define the ES that fish provide in the context of two common ES frameworks. To allow for linkages between environmental assessment and the ES concept, we describe critical ecosystem functions from a fish perspective to highlight potential monitoring targets that relate to fish abundance, diversity, health, and habitat. Finally, we suggest how this framing of a monitoring process can be used to better align aquatic monitoring programs across pre-development, development, and post-operational monitoring programs