Computational and phylogenetic validation of nematode horizontal gene transfer

Sequencing of expressed genes has shown that nematodes, particularly the plant-parasitic nematodes, have genes purportedly acquired from other kingdoms by horizontal gene transfer. The prevailing orthodoxy is that such transfer has been a driving force in the evolution of niche specificity, and a recent paper in BMC Evolutionary Biology that presents a detailed phylogenetic analysis of cellulase genes in the free-living nematode Pristionchus pacificus at the species, genus and family levels substantiates this hypothesis

Horizontally transferred genes in plant-parasitic nematodes: a high-throughput genomic approach

BACKGROUND: Published accounts of horizontally acquired genes in plant-parasitic nematodes have not been the result of a specific search for gene transfer per se, but rather have emerged from characterization of individual genes. We present a method for a high-throughput genome screen for horizontally acquired genes, illustrated using expressed sequence tag (EST) data from three species of root-knot nematode, Meloidogyne species. RESULTS: Our approach identified the previously postulated horizontally transferred genes and revealed six new candidates. Screening was partially dependent on sequence quality, with more candidates identified from clustered sequences than from raw EST data. Computational and experimental methods verified the horizontal gene transfer candidates as bona fide nematode genes. Phylogenetic analysis implicated rhizobial ancestors as donors of horizontally acquired genes in Meloidogyne. CONCLUSIONS: High-throughput genomic screening is an effective way to identify horizontal gene transfer candidates. Transferred genes that have undergone amelioration of nucleotide composition and codon bias have been identified using this approach. Analysis of these horizontally transferred gene candidates suggests a link between horizontally transferred genes in Meloidogyne and parasitism

Implementation in rehabilitation: a roadmap for practitioners and researchers

PURPOSE: Despite growth in rehabilitation research, implementing research findings into rehabilitation practice has been slow. This creates inequities for patients and is an ethical issue. However, methods to investigate and facilitate evidence implementation are being developed. This paper aims to make these methods relevant and accessible for rehabilitation researchers and practitioners.\ud METHODS: Rehabilitation practice is varied and complex and occurs within multilevel healthcare systems. Using a "road map" analogy, we describe how implementation concepts and theories can inform implementation strategies in rehabilitation. The roadmap involves a staged journey that considers: the nature of evidence; context for implementation; navigation tools for implementation; strategies to facilitate implementation; evaluation of implementation outcomes; and sustainability of implementation. We have developed a model to illustrate the journey, and four case studies exemplify implementation stages in rehabilitation settings. RESULTS AND CONCLUSIONS: Effective implementation strategies for the complex world of rehabilitation are urgently required. The journey we describe unpacks that complexity to provide a template for effective implementation, to facilitate translation of the growing evidence base in rehabilitation into improved patient outcomes. It emphasizes the importance of understanding context and application of relevant theory, and highlights areas which should be targeted in new implementation research in rehabilitation. Implications for rehabilitation Effective implementation of research evidence into rehabilitation practice has many interconnected steps and a roadmap analogy is helpful in defining them. Understanding context for implementation is critically important and using theory can facilitate development of understanding. Research methods for implementation in rehabilitation should be carefully selected and outcomes should evaluate implementation success as well as clinical change. Sustainability requires regular revisiting of the interconnected steps

Zinc-Regulated DNA Binding of the Yeast Zap1 Zinc-Responsive Activator

The Zap1 transcription factor of Saccharomyces cerevisiae plays a central role in zinc homeostasis by controlling the expression of genes involved in zinc metabolism. Zap1 is active in zinc-limited cells and repressed in replete cells. At the transcriptional level, Zap1 controls its own expression via positive autoregulation. In addition, Zap1's two activation domains are regulated independently of each other by zinc binding directly to those regions and repressing activation function. In this report, we show that Zap1 DNA binding is also inhibited by zinc. DMS footprinting showed that Zap1 target gene promoter occupancy is regulated with or without transcriptional autoregulation. These results were confirmed using chromatin immunoprecipitation. Zinc regulation of DNA binding activity mapped to the DNA binding domain indicating other parts of Zap1 are unnecessary for this control. Overexpression of Zap1 overrode DNA binding regulation and resulted in constitutive promoter occupancy. Under these conditions of constitutive binding, both the zinc dose response of Zap1 activity and cellular zinc accumulation were altered suggesting the importance of DNA binding control to zinc homeostasis. Thus, our results indicated that zinc regulates Zap1 activity post-translationally via three independent mechanisms, all of which contribute to the overall zinc responsiveness of Zap1

Operational definition of precipitated opioid withdrawal

Background Opioid withdrawal can be expressed as both a spontaneous and precipitated syndrome. Although spontaneous withdrawal is well-characterized, there is no operational definition of precipitated opioid withdrawal.MethodsPeople (N = 106) with opioid use disorder maintained on morphine received 0.4 mg intramuscular naloxone and completed self-report (Subjective Opiate Withdrawal Scale, SOWS), visual analog scale (VAS), Bad Effects and Sick, and observer ratings (Clinical Opiate Withdrawal Scale, COWS). Time to peak severity and minimal clinically important difference (MCID) in withdrawal severity were calculated. Principal component analysis (PCA) during peak severity were conducted and analyzed with repeated measures analyses of variance (ANOVA).ResultsWithin 60 min, 89% of people reported peak SOWS ratings and 90% of people had peak COWS scores as made by raters. Self-reported signs of eyes tearing, yawning, nose running, perspiring, hot flashes, and observed changes in pupil diameter and rhinorrhea/lacrimation were uniquely associated with precipitated withdrawal. VAS ratings of Bad Effect and Sick served as statistically significant severity categories (0, 1–40, 41–80, and 81–100) for MCID evaluations and revealed participants' identification with an increase of 10 [SOWS; 15% maximum percent effect (MPE)] and 6 (COWS; 12% MPE) points as meaningful shifts in withdrawal severity indicative of precipitated withdrawal.ConclusionData suggested that a change of 10 (15% MPE) and 6 (12% MPE) points on the SOWS and COWS, respectively, that occurred within 60 min of antagonist administration was identified by participants as a clinically meaningful increase in symptom severity. These data provide a method to begin examining precipitated opioid withdrawal

Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography.

Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using (18)F-sodium fluoride ((18)F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of (18)F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse (18)F-NaF binding. We show that (18)F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. (18)F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of (18)F-NaF may foster new approaches to developing treatments for vascular calcification.AI Wellcome Trust PhD Programme in Metabolic and Cardiovascular Disease Grant Number 096823/Z/11/Z, Wellcome Trust (WT103782AIA), British Heart Foundation (RG/10/007/28300, CH/09/002/26360, PG/12/8/29371), NHS Research Scotland and NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from the Nature Publishing Group via http://dx.doi.org/10.1038/ncomms849

Professional practices and opinions about services available to bilingual children with developmental disabilities:an international study

This study aimed to gather information from school- and clinic-based professionals about their practices and opinions pertaining to the provision of bilingual supports to students with developmental disabilities. Using an online survey, data were collected in six socio-culturally and linguistically diverse locations across four countries: the United States, Canada, the United Kingdom, and the Netherlands. In total, 361 surveys were included in the analysis from respondents who were primarily teachers and speech-language pathologists working in schools, daycares/preschools, or community-based clinics. The overall picture that emerged from the data reflected a disconnection between practice and opinion. In general, respondents believed that children with both mild and severe disabilities are capable of learning a second language, although their opinions were more neutral for the latter group. However, children with both mild and severe disabilities who spoke only a minority language at home had less access to services for second language learners than did their typically developing peers, although respondents agreed that such services should be more available. Regardless of clinical group, children who lived in homes where a minority language was spoken were often exposed to, assessed in, and treated in the majority language only; again, respondents generally disagreed with these practices. Finally, second language classes were less available to children in the two disability groups compared to typically developing bilingual children, with general agreement that the opportunity to acquire a second language should be more available, especially to those with mild disabilities. Although the results indicate that there is a considerable gap between current practices and professional opinions, professionals appear to be more supportive of bilingual educational opportunities for these populations than was suggested by previous research

A multi-site review of policies affecting opportunities for children with developmental disabilities to become bilingual

This review of special education and language-in-education policies at six sites in four countries (Canada, United States, United Kingdom, and Netherlands) aimed to determine the opportunities for bilingualism provided at school for children with developmental disabilities (DD). While research has demonstrated that children with DD are capable of learning more than one language (see Kay Raining Bird, Genesee, & Verhoeven, this issue), it was not clear whether recent policies reflect these findings. The review, conducted using the same protocol across sites, showed that special education policies rarely addressed second language learning explicitly. However, at all sites, the policies favoured inclusion and educational planning based on individual needs, and thus implied that students with DD would have opportunities for second language learning. The language-in-education policies occasionally specified the support individuals with special needs would receive. At some sites, policies and educational options provided little support for minority languages, a factor that could contribute to subtractive bilingualism. At others, we found stronger support for minority languages and optional majority languages: conditions that could be more conducive to additive bilingualism

Population exposure to trace elements in the Kilembe copper mine area, Western Uganda: a pilot study

The mining and processing of copper in Kilembe, Western Uganda, from 1956 to 1982 left over 15 Mt. of tailings containing cupriferous and cobaltiferous pyrite dumped within a mountain river valley. This pilot study was conducted to assess the nature and extent of risk to local populations from metal contamination arising from those mining activities. We determined trace element concentrations in mine tailings, soils, locally cultivated foods,house dust, drinking water and human biomarkers (toenails) using ICP-MS analysis of acid digested samples. The results showed that tailings, containing higher concentrations of Co, Cu, Ni and As compared with world average crust values had eroded and contaminated local soils. Pollution load indices revealed that 51% of agricultural soils sampled were contaminated with trace elements. Local water supplies were contaminated, with Co concentrations that exceeded Wisconsin (US) thresholds in 25% of domestic water supplies and 40% of Nyamwamba river water samples. Zinc exceeded WHO/FAO thresholds of 99.4 mg kg−1 in 36% of Amaranthus vegetable samples, Cu exceeded EC thresholds of 20 mg kg−1 in 19% of Amaranthus while Pb exceeded WHO thresholds of 0.3 mg kg−1 in 47% of Amaranthus vegetables. In bananas, 20% of samples contained Pb concentrations that exceeded the WHO/FAO recommended threshold of 0.3 mg kg−1. However, risk assessment of local foods and water, based on hazard quotients (HQ values) revealed no potential health effects. The high external contamination of volunteers' toenails with some elements (even after a washing process) calls into question their use as a biomarker for metal exposure in human populations where feet are frequently exposed to soil

Exclusive expression of MeCP2 in the nervous system distinguishes between brain and peripheral Rett syndrome-like phenotypes

This is a pre-copyedited, author-produced version of an article accepted for publication in Human Molecular Genetics following peer review. The version of record Ross, P. D., et al. (2016). "Exclusive expression of MeCP2 in the nervous system distinguishes between brain and peripheral Rett syndrome-like phenotypes." Human Molecular Genetics 25(20): 4389-4404.] is available online at: https://doi.org/10.1093/hmg/ddw269Work in SC’s laboratory was supported by the Biotechnology and Biological Sciences Research Council (PhD studentship for PDR), a consortium grant from the Rett Syndrome Research Trust, the Chief Scientist Office (Scottish Executive Health Department) [grant ETM/334], RS Macdonald Charitable Trust, Rosetrees Trust [grant M530], and the Rett Syndrome Association Scotland. Work in AB’s laboratory was supported by a Consortium Grant from the Rett Syndrome Research Trust, by Wellcome Trust programme grant [091580] and by Wellcome Trust Centre Core Grant [092076]. Funding to pay the Open Access publication charges for this article was provided by the Scottish Executive Health Department