PlantSimLab - a modeling and simulation web tool for plant biologists.

BACKGROUND: At the molecular level, nonlinear networks of heterogeneous molecules control many biological processes, so that systems biology provides a valuable approach in this field, building on the integration of experimental biology with mathematical modeling. One of the biggest challenges to making this integration a reality is that many life scientists do not possess the mathematical expertise needed to build and manipulate mathematical models well enough to use them as tools for hypothesis generation. Available modeling software packages often assume some modeling expertise. There is a need for software tools that are easy to use and intuitive for experimentalists. RESULTS: This paper introduces PlantSimLab, a web-based application developed to allow plant biologists to construct dynamic mathematical models of molecular networks, interrogate them in a manner similar to what is done in the laboratory, and use them as a tool for biological hypothesis generation. It is designed to be used by experimentalists, without direct assistance from mathematical modelers. CONCLUSIONS: Mathematical modeling techniques are a useful tool for analyzing complex biological systems, and there is a need for accessible, efficient analysis tools within the biological community. PlantSimLab enables users to build, validate, and use intuitive qualitative dynamic computer models, with a graphical user interface that does not require mathematical modeling expertise. It makes analysis of complex models accessible to a larger community, as it is platform-independent and does not require extensive mathematical expertise

Attributes of context relevant to healthcare professionals' use of research evidence in clinical practice: a multi-study analysis

Background: To increase the likelihood of successful implementation of evidence-based practices, researchers, knowledge users, and healthcare professionals must consider aspects of context that promote and hinder implementation in their setting. The purpose of the current study was to identify contextual attributes and their features relevant to implementation by healthcare professionals and compare and contrast these attributes and features across different clinical settings and healthcare professional roles. Methods: We conducted a secondary analysis of 145 semi-structured interviews comprising 11 studies (10 from Canada and one from Australia) investigating healthcare professionals’ perceived barriers and enablers to their use of research evidence in clinical practice. The data was collected using semi-structured interview guides informed by the Theoretical Domains Framework across different healthcare professional roles, settings, and practices. We analyzed these data inductively, using constant comparative analysis, to identify attributes of context and their features reported in the interviews. We compared these data by (1) setting (primary care, hospital-medical/surgical, hospital-emergency room, hospital-critical care) and (2) professional role (physicians and residents, nurses and organ donor coordinators). Results: We identified 62 unique features of context, which we categorized under 14 broader attributes of context. The 14 attributes were resource access, work structure, patient characteristics, professional role, culture, facility characteristics, system features, healthcare professional characteristics, financial, collaboration, leadership, evaluation, regulatory or legislative standards, and societal influences. We found instances of the majority (n = 12, 86%) of attributes of context across multiple (n = 6 or more) clinical behaviors. We also found little variation in the 14 attributes of context by setting (primary care and hospitals) and professional role (physicians and residents, and nurses and organ donor coordinators). Conclusions: There was considerable consistency in the 14 attributes identified irrespective of the clinical behavior, setting, or professional role, supporting broad utility of the attributes of context identified in this study. There was more variation in the finer-grained features of these attributes with the most substantial variation being by setting

Androgen Receptor Copy Number Variation and Androgenetic Alopecia: A Case-Control Study

BACKGROUND: The functional polymorphism that explains the established association of the androgen receptor (AR) with androgenetic alopecia (AGA) remains unidentified, but Copy Number Variation (CNV) might be relevant. CNV involves changes in copy number of large segments of DNA, leading to the altered dosage of gene regulators or genes themselves. Two recent reports indicate regions of CNV in and around AR, and these have not been studied in relation to AGA. The aim of this preliminary case-control study was to determine if AR CNV is associated with AGA, with the hypothesis that CNV is the functional AR variant contributing to this condition. METHODOLOGY/PRINCIPAL FINDINGS: Multiplex Ligation-dependent Probe Amplification was used to screen for CNV in five AR exons and a conserved, non-coding region upstream of AR in 85 men carefully selected as cases and controls for maximal phenotypic contrast. There was no evidence of CNV in AR in any of the cases or controls, and thus no evidence of significant association between AGA and AR CNV. CONCLUSIONS/SIGNIFICANCE: The results suggest this form of genomic variation at the AR locus is unlikely to predispose to AGA

Foreign policy beliefs and support for Stephen Harper and the Conservative Party

Similar to other recent Canadian elections, foreign policy did not feature prominently in the 2011 federal election campaign. In fact, many doubt Canadian public opinion on international affairs is linked to the actions taken by recent Governments. In this paper, we examine Canadian public opinion toward a range of foreign policy issues and argue that the survey questions measure two latent dimensions —militarism and internationalism. Our survey evidence indicates the existence of an “issue public” which is prepared to endorse military action and is skeptical of human rights and overseas aid programs, and this group is far more supportive of Prime Minister Harper and the Conservative Party than other Canadians. The absence of an elite discussion, either among politicians or between media elites, about the direction of Canadian foreign policy does not prevent the Canadian voter from thinking coherently about questions pertaining to this issue domain and employing these beliefs to support or oppose political parties and their leaders

Well-width dependence of exciton-phonon scattering in InxGa1 - xAs/GaAs single quantum wells

The temperature and density dependencies of the exciton dephasing time in In0.18Ga0.82As/GaAs single quantum wells with different thicknesses have been measured by degenerate four-wave mixing. The exciton-phonon scattering contribution to the dephasing is isolated by extrapolating the dephasing rate to zero-exciton density. From the temperature dependence of this rate we have deduced the linewidth broadening coefficients for acoustic and optical phonons. We find acoustic-phonon coefficients that increase from 1.6 to 3 μeV/K when increasing the well width from 1 to 4 nm. This is in quantitative agreement with theoretical predictions when the spatial extension of the exciton wave function, strongly penetrating into the GaAs barrier in thin InxGa1-xAs quantum wells, is taken into account. The optical-phonon coefficient does not show a systematic dependence on well thickness, and is comparable with the value for bulk GaAs

Stakeholder Perspectives of Attributes and Features of Context Relevant to Knowledge Translation in Health Settings: A Multi-Country Analysis

Background Context is recognized as important to successful knowledge translation (KT) in health settings. What is meant by context, however, is poorly understood. The purpose of the current study was to elicit tacit knowledge about what is perceived to constitute context by conducting interviews with a variety of health system stakeholders internationally so as to compile a comprehensive list of contextual attributes and their features relevant to KT in healthcare. Methods A descriptive qualitative study design was used. Semi-structured interviews were conducted with health system stakeholders (change agents/KT specialists and KT researchers) in four countries: Australia, Canada, the United Kingdom, and the United States. Interview transcripts were analyzed using inductive thematic content analysis in four steps: (1) selection of utterances describing context, (2) coding of features of context, (3) categorizing of features into attributes of context, (4) comparison of attributes and features by: country, KT experience, and role. Results A total of 39 interviews were conducted. We identified 66 unique features of context, categorized into 16 attributes. One attribute, Facility Characteristics, was not represented in previously published KT frameworks. We found instances of all 16 attributes in the interviews irrespective of country, level of experience with KT, and primary role (change agent/KT specialist vs. KT researcher), revealing robustness and transferability of the attributes identified. We also identified 30 new context features (across 13 of the 16 attributes). Conclusion The findings from this study represent an important advancement in the KT field; we provide much needed conceptual clarity in context, which is essential to the development of common assessment tools to measure context to determine which context attributes and features are more or less important in different contexts for improving KT success

Bacterial RuBisCO Is Required for Efficient Bradyrhizobium/Aeschynomene Symbiosis

Rhizobia and legume plants establish symbiotic associations resulting in the formation of organs specialized in nitrogen fixation. In such organs, termed nodules, bacteria differentiate into bacteroids which convert atmospheric nitrogen and supply the plant with organic nitrogen. As a counterpart, bacteroids receive carbon substrates from the plant. This rather simple model of metabolite exchange underlies symbiosis but does not describe the complexity of bacteroids' central metabolism. A previous study using the tropical symbiotic model Aeschynomene indica/photosynthetic Bradyrhizobium sp. ORS278 suggested a role of the bacterial Calvin cycle during the symbiotic process. Herein we investigated the role of two RuBisCO gene clusters of Bradyrhizobium sp. ORS278 during symbiosis. Using gene reporter fusion strains, we showed that cbbL1 but not the paralogous cbbL2 is expressed during symbiosis. Congruently, CbbL1 was detected in bacteroids by proteome analysis. The importance of CbbL1 for symbiotic nitrogen fixation was proven by a reverse genetic approach. Interestingly, despite its symbiotic nitrogen fixation defect, the cbbL1 mutant was not affected in nitrogen fixation activity under free living state. This study demonstrates a critical role for bacterial RuBisCO during a rhizobia/legume symbiotic interaction

Prescribing patterns in dementia: a multicentre observational study in a German network of CAM physicians

<p>Abstract</p> <p>Background</p> <p>Dementia is a major and increasing health problem worldwide. This study aims to investigate dementia treatment strategies among physicians specialised in complementary and alternative medicine (CAM) by analysing prescribing patterns and comparing them to current treatment guidelines in Germany.</p> <p>Methods</p> <p>Twenty-two primary care physicians in Germany participated in this prospective, multicentre observational study. Prescriptions and diagnoses were reported for each consecutive patient. Data were included if patients had at least one diagnosis of dementia according to the 10th revision of the International Classification of Diseases during the study period. Multiple logistic regression was used to determine factors associated with a prescription of any anti-dementia drug including <it>Ginkgo biloba</it>.</p> <p>Results</p> <p>During the 5-year study period (2004-2008), 577 patients with dementia were included (median age: 81 years (IQR: 74-87); 69% female). Dementia was classified as unspecified dementia (57.2%), vascular dementia (25.1%), dementia in Alzheimer's disease (10.4%), and dementia in Parkinson's disease (7.3%). The prevalence of anti-dementia drugs was 25.6%. The phytopharmaceutical <it>Ginkgo biloba </it>was the most frequently prescribed anti-dementia drug overall (67.6% of all) followed by cholinesterase inhibitors (17.6%). The adjusted odds ratio (AOR) for receiving any anti-dementia drug was greater than 1 for neurologists (AOR = 2.34; CI: 1.59-3.47), the diagnosis of Alzheimer's disease (AOR = 3.28; CI: 1.96-5.50), neuroleptic therapy (AOR = 1.87; CI: 1.22-2.88), co-morbidities hypertension (AOR = 2.03; CI: 1.41-2.90), and heart failure (AOR = 4.85; CI: 3.42-6.88). The chance for a prescription of any anti-dementia drug decreased with the diagnosis of vascular dementia (AOR = 0.64; CI: 0.43-0.95) and diabetes mellitus (AOR = 0.55; CI: 0.36-0.86). The prescription of <it>Ginkgo biloba </it>was associated with sex (female: AOR = 0.41; CI: 0.19-0.89), patient age (AOR = 1.06; CI: 1.02-1.10), treatment by a neurologist (AOR = 0.09; CI: 0.03-0.23), and the diagnosis of Alzheimer's disease (AOR = 0.07; CI: 0.04-0.16).</p> <p>Conclusions</p> <p>This study provides a comprehensive analysis of everyday practice for treatment of dementia in primary care in physicians with a focus on CAM. The prescribing frequency for anti-dementia drugs is equivalent to those found in other German studies, while the administration of <it>Ginkgo biloba </it>is significantly higher.</p

De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

On the power and the systematic biases of the detection of chromosomal inversions by paired-end genome sequencing

One of the most used techniques to study structural variation at a genome level is paired-end mapping (PEM). PEM has the advantage of being able to detect balanced events, such as inversions and translocations. However, inversions are still quite difficult to predict reliably, especially from high-throughput sequencing data. We simulated realistic PEM experiments with different combinations of read and library fragment lengths, including sequencing errors and meaningful base-qualities, to quantify and track down the origin of false positives and negatives along sequencing, mapping, and downstream analysis. We show that PEM is very appropriate to detect a wide range of inversions, even with low coverage data. However, % of inversions located between segmental duplications are expected to go undetected by the most common sequencing strategies. In general, longer DNA libraries improve the detectability of inversions far better than increments of the coverage depth or the read length. Finally, we review the performance of three algorithms to detect inversions -SVDetect, GRIAL, and VariationHunter-, identify common pitfalls, and reveal important differences in their breakpoint precisions. These results stress the importance of the sequencing strategy for the detection of structural variants, especially inversions, and offer guidelines for the design of future genome sequencing projects