Impacts of selected Ecological Focus Area options in European farmed landscapes on climate regulation and pollination services: a systematic map protocol

Background: This systematic map protocol responds to an urgent policy need to evaluate key environmental benefits of new compulsory greening measures in the European Union’s Common Agricultural Policy (CAP), with the aim of building a policy better linked to environmental performance. The systematic map will focus on Ecological Focus Areas (EFAs), in which larger arable farmers must dedicate 5% of their arable land to ecologically beneficial habitats, landscape features and land uses. The European Commission’s Joint Research Centre has used a software tool called the ‘EFA calculator’ to inform the European Commission about environmental benefits of EFA implementation. However, there are gaps in the EFA calculator’s coverage of ecosystem services, especially ‘global climate regulation’, and an opportunity to use systematic mapping methods to enhance its capture of evidence, in advance of forthcoming CAP reforms. We describe a method for assembling a database of relevant, peer-reviewed research conducted in all agricultural landscapes in Europe and neighbouring countries with similar biogeography, addressing the primary question: what are the impacts of selected EFA features in agricultural land on two policy-relevant ecosystem service outcomes—global climate regulation and pollination? The method is streamlined to allow results in good time for the current, time-limited opportunity to influence reforms of the CAP greening measures at European and Member State level. Methods: We will search four bibliographic databases in English, using a predefined and tested search string that focuses on a subset of EFA options and ecosystem service outcomes. The options and outcomes are selected as those with particular policy relevance and traction. Only articles in English will be included. We will screen search results at title, abstract and full text levels, recording the number of studies deemed non-relevant (with reasons at full text). A systematic map database that displays the meta-data (i.e. descriptive summary information about settings and methods) of relevant studies will be produced following full text assessment. The systematic map database will be published as a MS-Excel database. The nature and extent of the evidence base will be discussed, and the applicability of methods to convert the available evidence into EFA calculator scores will be assessed

Biological Process Linkage Networks

BACKGROUND. The traditional approach to studying complex biological networks is based on the identification of interactions between internal components of signaling or metabolic pathways. By comparison, little is known about interactions between higher order biological systems, such as biological pathways and processes. We propose a methodology for gleaning patterns of interactions between biological processes by analyzing protein-protein interactions, transcriptional co-expression and genetic interactions. At the heart of the methodology are the concept of Linked Processes and the resultant network of biological processes, the Process Linkage Network (PLN). RESULTS. We construct, catalogue, and analyze different types of PLNs derived from different data sources and different species. When applied to the Gene Ontology, many of the resulting links connect processes that are distant from each other in the hierarchy, even though the connection makes eminent sense biologically. Some others, however, carry an element of surprise and may reflect mechanisms that are unique to the organism under investigation. In this aspect our method complements the link structure between processes inherent in the Gene Ontology, which by its very nature is species-independent. As a practical application of the linkage of processes we demonstrate that it can be effectively used in protein function prediction, having the power to increase both the coverage and the accuracy of predictions, when carefully integrated into prediction methods. CONCLUSIONS. Our approach constitutes a promising new direction towards understanding the higher levels of organization of the cell as a system which should help current efforts to re-engineer ontologies and improve our ability to predict which proteins are involved in specific biological processes.Lynn and William Frankel Center for Computer Science; the Paul Ivanier center for robotics research and production; National Science Foundation (ITR-048715); National Human Genome Research Institute (1R33HG002850-01A1, R01 HG003367-01A1); National Institute of Health (U54 LM008748

Characterization of Rhodamine-123 as a Tracer Dye for Use In In vitro Drug Transport Assays

Fluorescent tracer dyes represent an important class of sub-cellular probes and allow the examination of cellular processes in real-time with minimal impact upon these processes. Such tracer dyes are becoming increasingly used for the examination of membrane transport processes, as they are easy-to-use, cost effective probe substrates for a number of membrane protein transporters. Rhodamine 123, a member of the rhodamine family of flurone dyes, has been used to examine membrane transport by the ABCB1 gene product, MDR1. MDR1 is viewed as the archetypal drug transport protein, and is able to efflux a large number of clinically relevant drugs. In addition, ectopic activity of MDR1 has been associated with the development of multiple drug resistance phenotype, which results in a poor patient response to therapeutic intervention. It is thus important to be able to examine the potential for novel compounds to be MDR1 substrates. Given the increasing use rhodamine 123 as a tracer dye for MDR1, a full characterisation of its spectral properties in a range of in vitro assay-relevant media is warranted. Herein, we determine λmax for excitation and emission or rhodamine 123 and its metabolite rhodamine 110 in commonly used solvents and extraction buffers, demonstrating that fluorescence is highly dependent on the chemical environment: Optimal parameters are 1% (v/v) methanol in HBSS, with λex = 505 nm, λem = 525 nm. We characterise the uptake of rhodamine 123 into cells, via both passive and active processes, and demonstrate that this occurs primarily through OATP1A2-mediated facilitated transport at concentrations below 2 µM, and via micelle-mediated passive diffusion above this. Finally, we quantify the intracellular sequestration and metabolism of rhodamine 123, demonstrating that these are both cell line-dependent factors that may influence the interpretation of transport assays

Monitoring Flower Visitation Networks and Interactions between Pairs of Bumble Bees in a Large Outdoor Flight Cage

This research was supported by a combined grant from the Wellcome Trust, the Biotechnology and Biological Sciences Research Council, and the Engineering and Physical Sciences Research Council (BB/F52765X/1). While writing, ML was supported by the IDEX of the Federal University of Toulouse (Starting and Emergence grants), the Fyssen foundation and the CNRS. NER was supported as the Rebanks Family Chair in Pollinator Conservation by The W. Garfield Weston Foundation. LC was supported by ERC Advanced Grant SpaceRadarPollinator and by a Royal Society Wolfson Research Merit Award

Prdm5 Regulates Collagen Gene Transcription by Association with RNA Polymerase II in Developing Bone

PRDM family members are transcriptional regulators involved in tissue specific differentiation. PRDM5 has been reported to predominantly repress transcription, but a characterization of its molecular functions in a relevant biological context is lacking. We demonstrate here that Prdm5 is highly expressed in developing bones; and, by genome-wide mapping of Prdm5 occupancy in pre-osteoblastic cells, we uncover a novel and unique role for Prdm5 in targeting all mouse collagen genes as well as several SLRP proteoglycan genes. In particular, we show that Prdm5 controls both Collagen I transcription and fibrillogenesis by binding inside the Col1a1 gene body and maintaining RNA polymerase II occupancy. In vivo, Prdm5 loss results in delayed ossification involving a pronounced impairment in the assembly of fibrillar collagens. Collectively, our results define a novel role for Prdm5 in sustaining the transcriptional program necessary to the proper assembly of osteoblastic extracellular matrix

Outcomes for depression and anxiety in primary care and details of treatment: a naturalistic longitudinal study

<p>Abstract</p> <p>Background</p> <p>There is little evidence as to whether or not guideline concordant care in general practice results in better clinical outcomes for people with anxiety and depression. This study aims to determine possible associations between guideline concordant care and clinical outcomes in general practice patients with depression and anxiety, and identify patient and treatment characteristics associated with clinical improvement.</p> <p>Methods</p> <p>This study forms part of the Netherlands Study of Depression and Anxiety (NESDA).</p> <p>Adult patients, recruited in general practice (67 GPs), were interviewed to assess DSM-IV diagnoses during baseline assessment of NESDA, and also completed questionnaires measuring symptom severity, received care, socio-demographic variables and social support both at baseline and 12 months later. The definition of guideline adherence was based on an algorithm on care received. Information on guideline adherence was obtained from GP medical records.</p> <p>Results</p> <p>721 patients with a current (6-month recency) anxiety or depressive disorder participated. While patients who received guideline concordant care (N = 281) suffered from more severe symptoms than patients who received non-guideline concordant care (N = 440), both groups showed equal improvement in their depressive or anxiety symptoms after 12 months. Patients who (still) had moderate or severe symptoms at follow-up, were more often unemployed, had smaller personal networks and more severe depressive symptoms at baseline than patients with mild symptoms at follow-up. The particular type of treatment followed made no difference to clinical outcomes.</p> <p>Conclusion</p> <p>The added value of guideline concordant care could not be demonstrated in this study. Symptom severity, employment status, social support and comorbidity of anxiety and depression all play a role in poor clinical outcomes.</p

Diffusion patterns of new anti-diabetic drugs into hospitals in Taiwan: the case of Thiazolidinediones for diabetes

<p>Abstract</p> <p>Background</p> <p>Diffusion of new drugs in the health care market affects patients' access to new treatment options and health care expenditures. We examined how a new drug class for diabetes mellitus, thiazolidinediones (TZDs), diffused in the health care market in Taiwan.</p> <p>Methods</p> <p>Assuming that monthly hospital prescriptions of TZDs could serve as a micro-market to perform drug penetration studies, we retrieved monthly TZD prescription data for 580 hospitals in Taiwan from Taiwan's National Health Insurance Research Database for the period between March 1, 2001 and December 31, 2005. Three diffusion parameters, time to adoption, speed of penetration (monthly growth on prescriptions), and peak penetration (maximum monthly prescription) were evaluated. Cox proportional hazards model and quantile regressions were estimated for analyses on the diffusion parameters.</p> <p>Results</p> <p>Prior hospital-level pharmaceutical prescription concentration significantly deterred the adoption of the new drug class (HR: 0.02, 95%CI = 0.01 to 0.04). Adoption of TZDs was slower in district hospitals (HR = 0.43, 95%CI = 0.24 to 0.75) than medical centers and faster in non-profit hospitals than public hospitals (HR = 1.79, 95%CI = 1.23 to 2.61). Quantile regression showed that penetration speed was associated with a hospital's prior anti-diabetic prescriptions (25%Q: 18.29; 50%Q: 25.57; 75%Q: 30.97). Higher peaks were found in hospitals that had adopted TZD early (25%Q: -40.33; 50%Q: -38.65; 75%Q: -32.29) and in hospitals in which the drugs penetrated more quickly (25%Q: 16.53; 50%Q: 24.91; 75%Q: 31.50).</p> <p>Conclusions</p> <p>Medical centers began to prescribe TZDs earlier, and they prescribed more TZDs at a faster pace. The TZD diffusion patterns varied among hospitals depending accreditation level, ownership type, and prescription volume of Anti-diabetic drugs.</p

Diffusion patterns of new anti-diabetic drugs into hospitals in Taiwan: the case of Thiazolidinediones for diabetes

<p>Abstract</p> <p>Background</p> <p>Diffusion of new drugs in the health care market affects patients' access to new treatment options and health care expenditures. We examined how a new drug class for diabetes mellitus, thiazolidinediones (TZDs), diffused in the health care market in Taiwan.</p> <p>Methods</p> <p>Assuming that monthly hospital prescriptions of TZDs could serve as a micro-market to perform drug penetration studies, we retrieved monthly TZD prescription data for 580 hospitals in Taiwan from Taiwan's National Health Insurance Research Database for the period between March 1, 2001 and December 31, 2005. Three diffusion parameters, time to adoption, speed of penetration (monthly growth on prescriptions), and peak penetration (maximum monthly prescription) were evaluated. Cox proportional hazards model and quantile regressions were estimated for analyses on the diffusion parameters.</p> <p>Results</p> <p>Prior hospital-level pharmaceutical prescription concentration significantly deterred the adoption of the new drug class (HR: 0.02, 95%CI = 0.01 to 0.04). Adoption of TZDs was slower in district hospitals (HR = 0.43, 95%CI = 0.24 to 0.75) than medical centers and faster in non-profit hospitals than public hospitals (HR = 1.79, 95%CI = 1.23 to 2.61). Quantile regression showed that penetration speed was associated with a hospital's prior anti-diabetic prescriptions (25%Q: 18.29; 50%Q: 25.57; 75%Q: 30.97). Higher peaks were found in hospitals that had adopted TZD early (25%Q: -40.33; 50%Q: -38.65; 75%Q: -32.29) and in hospitals in which the drugs penetrated more quickly (25%Q: 16.53; 50%Q: 24.91; 75%Q: 31.50).</p> <p>Conclusions</p> <p>Medical centers began to prescribe TZDs earlier, and they prescribed more TZDs at a faster pace. The TZD diffusion patterns varied among hospitals depending accreditation level, ownership type, and prescription volume of Anti-diabetic drugs.</p

Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types