An Automated Method for Rapid Identification of Putative Gene Family Members in Plants

BACKGROUND: Gene duplication events have played a significant role in genome evolution, particularly in plants. Exhaustive searches for all members of a known gene family as well as the identification of new gene families has become increasingly important. Subfunctionalization via changes in regulatory sequences following duplication (adaptive selection) appears to be a common mechanism of evolution in plants and can be accompanied by purifying selection on the coding region. Such negative selection can be detected by a bias toward synonymous over nonsynonymous substitutions. However, the process of identifying this bias requires many steps usually employing several different software programs. We have simplified the process and significantly shortened the time required by condensing many steps into a few scripts or programs to rapidly identify putative gene family members beginning with a single query sequence. RESULTS: In this report we 1) describe the software tools (SimESTs, PCAT, and SCAT) developed to automate the gene family identification, 2) demonstrate the validity of the method by correctly identifying 3 of 4 PAL gene family members from Arabidopsis using EST data alone, 3) identify 2 to 6 CAD gene family members from Glycine max (previously unidentified), and 4) identify 2 members of a putative Glycine max gene family previously unidentified in any plant species. CONCLUSION: Gene families in plants, particularly that subset where purifying selection has occurred in the coding region, can be identified quickly and easily by integrating our software tools and commonly available contig assembly and ORF identification programs

TECNOB: study design of a randomized controlled trial of a multidisciplinary telecare intervention for obese patients with type-2 diabetes

Obesity is one of the most important medical and public health problems of our time: it increases the risk of many health complications such as hypertension, coronary heart disease and type 2 diabetes, needs long-lasting treatment for effective results and involves high public and private costs. Therefore, it is imperative that enduring and low-cost clinical programs for obesity and related co-morbidities are developed and evaluated. METHODS/DESIGN: TECNOB (TEChnology for OBesity) is a comprehensive two-phase stepped down program enhanced by telemedicine for the long-term treatment of obese people with type 2 diabetes seeking intervention for weight loss. Its core features are the hospital-based intensive treatment (1-month), that consists of diet therapy, physical training and psychological counseling, and the continuity of care at home using new information and communication technologies (ICT) such as internet and mobile phones. The effectiveness of the TECNOB program compared with usual care (hospital-based treatment only) will be evaluated in a randomized controlled trial (RCT) with a 12-month follow-up. The primary outcome is weight in kilograms. Secondary outcome measures are energy expenditure measured using an electronic armband, glycated hemoglobin, binge eating, self-efficacy in eating and weight control, body satisfaction, healthy habit formation, disordered eating-related behaviors and cognitions, psychopathological symptoms and weight-related quality of life. Furthermore, the study will explore what behavioral and psychological variables are predictive of treatment success among those we have considered. DISCUSSION: The TECNOB study aims to inform the evidence-based knowledge of how telemedicine may enhance the effectiveness of clinical interventions for weight loss and related type-2 diabetes, and which type of obese patients may benefit the most from such interventions. Broadly, the study aims also to have a effect on the theoretical model behind the traditional health care service, in favor of a change towards a new "health care everywhere" approach

Validation of an NSP-based (negative selection pattern) gene family identification strategy

<p>Abstract</p> <p>Background</p> <p>Gene family identification from ESTs can be a valuable resource for analysis of genome evolution but presents unique challenges in organisms for which the entire genome is not yet sequenced. We have developed a novel gene family identification method based on negative selection patterns (NSP) between family members to screen EST-generated contigs. This strategy was tested on five known gene families in Arabidopsis to see if individual paralogs could be identified with accuracy from EST data alone when compared to the actual gene sequences in this fully sequenced genome.</p> <p>Results</p> <p>The NSP method uniquely identified family members in all the gene families tested. Two members of the FtsH gene family, three members each of the PAL, RF1, and ribosomal L6 gene families, and four members of the CAD gene family were correctly identified. Additionally all ESTs from the representative contigs when checked against MapViewer data successfully identify the gene locus predicted.</p> <p>Conclusion</p> <p>We demonstrate the effectiveness of the NSP strategy in identifying specific gene family members in Arabidopsis using only EST data and we describe how this strategy can be used to identify many gene families in agronomically important crop species where they are as yet undiscovered.</p

Sclerostin: Current Knowledge and Future Perspectives

In recent years study of rare human bone disorders has led to the identification of important signaling pathways that regulate bone formation. Such diseases include the bone sclerosing dysplasias sclerosteosis and van Buchem disease, which are due to deficiency of sclerostin, a protein secreted by osteocytes that inhibits bone formation by osteoblasts. The restricted expression pattern of sclerostin in the skeleton and the exclusive bone phenotype of good quality of patients with sclerosteosis and van Buchem disease provide the basis for the design of therapeutics that stimulate bone formation. We review here current knowledge of the regulation of the expression and formation of sclerostin, its mechanism of action, and its potential as a bone-building treatment for patients with osteoporosis

Living in rural New England amplifies the risk of depression in patients with HIV

<p>Abstract</p> <p>Background</p> <p>The importance of depression as a complication of HIV infection is increasingly understood, and people living in rural areas are at increased risk for depression. However, it is not known whether living in rural areas amplifies the risk of depression in patients with HIV.</p> <p>Methods</p> <p>We compared the prevalence of depression between rural and metropolitan HIV patients seen at the Dartmouth-Hitchcock HIV Program in a retrospective cohort study. Using the validated Rural-Urban Commuting Area Score, we categorized patients as living in small town/rural areas, micropolitan or metropolitan towns. Then, using a multivariate logistic regression model to adjust for demographic factors that differed between rural and metropolitan patients, we estimated the impact of living in rural areas on the odds of depression.</p> <p>Results</p> <p>Among 646 patients with HIV (185 small town/rural, 145 micropolitan, 316 metropolitan), rural patients were older, white, male, and men who have sex with men (ANOVA, F-statistic < 0.05). The prevalence of depression was highest in rural patients (59.5 vs. 51.7 vs. 41.2%, F statistic < 0.001), particularly rural patients on antiretroviral therapy (72.4 vs. 53.5 vs. 38.2%, F-statistic < 0.001. A multivariate logistic regression model showed that the odds of depression in rural patients with HIV were 1.34 (P < 0.001).</p> <p>Conclusion</p> <p>HIV-infected patients living in rural areas, particularly those on antiretroviral therapy, are highly vulnerable to depression.</p

Evaluation of lifestyle interventions to treat elevated cardiometabolic risk in primary care (E-LITE): a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Efficacy research has shown that intensive individual lifestyle intervention lowers the risk for developing type 2 diabetes mellitus and the metabolic syndrome. Translational research is needed to test real-world models of lifestyle interventions in primary care settings.</p> <p>Design</p> <p>E-LITE is a three-arm randomized controlled clinical trial aimed at testing the feasibility and potential effectiveness of two lifestyle interventions: information technology-assisted self-management, either alone or in combination with care management by a dietitian and exercise counselor, in comparison to usual care. Overweight or obese adults with pre-diabetes and/or metabolic syndrome (n = 240) recruited from a community-based primary care clinic are randomly assigned to one of three treatment conditions. Treatment will last 15 months and involves a three-month intensive treatment phase followed by a 12-month maintenance phase. Follow-up assessment occurs at three, six, and 15 months. The primary outcome is change in body mass index. The target sample size will provide 80% power for detecting a net difference of half a standard deviation in body mass index at 15 months between either of the self-management or care management interventions and usual care at a two-sided α level of 0.05, assuming up to a 20% rate of loss to 15-month follow-up.</p> <p>Secondary outcomes include glycemic control, additional cardiovascular risk factors, and health-related quality of life. Potential mediators (e.g., treatment adherence, caloric intake, physical activity level) and moderators (e.g., age, gender, race/ethnicity, baseline mental status) of the intervention's effect on weight change also will be examined.</p> <p>Discussion</p> <p>This study will provide objective evidence on the extent of reductions in body mass index and related cardiometabolic risk factors from two lifestyle intervention programs of varying intensity that could be implemented as part of routine health care.</p> <p>Trial registration</p> <p>NCT00842426</p

The Glasgow Outcome Scale -- 40 years of application and refinement

The Glasgow Outcome Scale (GOS) was first published in 1975 by Bryan Jennett and Michael Bond. With over 4,000 citations to the original paper, it is the most highly cited outcome measure in studies of brain injury and the second most-cited paper in clinical neurosurgery. The original GOS and the subsequently developed extended GOS (GOSE) are recommended by several national bodies as the outcome measure for major trauma and for head injury. The enduring appeal of the GOS is linked to its simplicity, short administration time, reliability and validity, stability, flexibility of administration (face-to-face, over the telephone and by post), cost-free availability and ease of access. These benefits apply to other derivatives of the scale, including the Glasgow Outcome at Discharge Scale (GODS) and the GOS paediatric revision. The GOS was devised to provide an overview of outcome and to focus on social recovery. Since the initial development of the GOS, there has been an increasing focus on the multidimensional nature of outcome after head injury. This Review charts the development of the GOS, its refinement and usage over the past 40 years, and considers its current and future roles in developing an understanding of brain injury

Somatic PIK3R1 Variation as a Cause of Vascular Malformations and Overgrowth

PurposeSomatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1.MethodsAffected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity.ResultsThe phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone.ConclusionSomatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway

Incidence of self-reported brain injury and the relationship with substance abuse: findings from a longitudinal community survey

<p>Abstract</p> <p>Background</p> <p>Traumatic or serious brain injury (BI) has persistent and well documented adverse outcomes, yet 'mild' or 'moderate' BI, which often does not result in hospital treatment, accounts for half the total days of disability attributed to BI. There are currently few data available from community samples on the incidence and correlates of these injuries. Therefore, the study aimed to assess the 1) incidence of self-reported mild (not requiring hospital admission) and moderate (admitted to hospital)) brain injury (BI), 2) causes of injury 3) physical health scores and 4) relationship between BI and problematic alcohol or marijuana use.</p> <p>Methods</p> <p>An Australian community sequential-cohort study (cohorts aged 20-24, 40-44 and 60-64 years at wave one) used a survey methodology to assess BI and substance use at baseline and four years later.</p> <p>Results</p> <p>Of the 7485 wave one participants, 89.7% were re-interviewed at wave two. There were 56 mild (230.8/100000 person-years) and 44 moderate BI (180.5/100000 person-years) reported between waves one and two. Males and those in the 20-24 year cohort had increased risk of BI. Sports injury was the most frequent cause of BI (40/100) with traffic accidents being a greater proportion of moderate (27%) than mild (7%) BI. Neither alcohol nor marijuana problems at wave one were predictors of BI. BI was not a predictor of developing substance use problems by wave two.</p> <p>Conclusions</p> <p>BI were prevalent in this community sample, though the incidence declined with age. Factors associated with BI in community samples differ from those reported in clinical samples (e.g. typically traumatic brain injury with traffic accidents the predominate cause). Further, detailed evaluation of the health consequences of these injuries is warranted.</p