New Jersey Center for Tourette Syndrome Sharing Repository: methods and sample description

<p>Abstract</p> <p>Background</p> <p>Tourette Syndrome is a neuropsychiatric disorder characterized by chronic motor and phonic tics. Affected individuals and their family members are at an increased risk for other neuropsychiatric conditions including obsessive-compulsive disorder and attention deficit hyperactivity disorder. While there is consistent evidence that genetic factors play a significant etiologic role, no replicable susceptibility alleles have thus far been identified.</p> <p>Description</p> <p>Here we discuss a sharing resource of clinical and genetic data, the New Jersey Center for Tourette Syndrome Sharing Repository, whose goal is to provide clinical data, DNA, and lymphoblastoid cell lines to qualified researchers.</p> <p>Conclusion</p> <p>Opening access to the data and patient material to the widest possible research community will hasten the identification of causal genetic factors and facilitate better understanding and treatment of this often impairing disorder.</p

A possible role for miRNA silencing in disease phenotype variation in Swedish transthyretin V30M carriers

Our results are the first to show the presence of a 3'UTR polymorphism on the V30M haplotype in Swedish carriers, which can serve as a miRNA binding site potentially leading to down-regulated expression from the mutated TTR allele. This finding may be related to the low penetrance and high age at onset of the disease observed in the Swedish patient population

Tear fluid biomarkers in ocular and systemic disease: potential use for predictive, preventive and personalised medicine

In the field of predictive, preventive and personalised medicine, researchers are keen to identify novel and reliable ways to predict and diagnose disease, as well as to monitor patient response to therapeutic agents. In the last decade alone, the sensitivity of profiling technologies has undergone huge improvements in detection sensitivity, thus allowing quantification of minute samples, for example body fluids that were previously difficult to assay. As a consequence, there has been a huge increase in tear fluid investigation, predominantly in the field of ocular surface disease. As tears are a more accessible and less complex body fluid (than serum or plasma) and sampling is much less invasive, research is starting to focus on how disease processes affect the proteomic, lipidomic and metabolomic composition of the tear film. By determining compositional changes to tear profiles, crucial pathways in disease progression may be identified, allowing for more predictive and personalised therapy of the individual. This article will provide an overview of the various putative tear fluid biomarkers that have been identified to date, ranging from ocular surface disease and retinopathies to cancer and multiple sclerosis. Putative tear fluid biomarkers of ocular disorders, as well as the more recent field of systemic disease biomarkers, will be shown

The Pioneer Anomaly

Radio-metric Doppler tracking data received from the Pioneer 10 and 11 spacecraft from heliocentric distances of 20-70 AU has consistently indicated the presence of a small, anomalous, blue-shifted frequency drift uniformly changing with a rate of ~6 x 10^{-9} Hz/s. Ultimately, the drift was interpreted as a constant sunward deceleration of each particular spacecraft at the level of a_P = (8.74 +/- 1.33) x 10^{-10} m/s^2. This apparent violation of the Newton's gravitational inverse-square law has become known as the Pioneer anomaly; the nature of this anomaly remains unexplained. In this review, we summarize the current knowledge of the physical properties of the anomaly and the conditions that led to its detection and characterization. We review various mechanisms proposed to explain the anomaly and discuss the current state of efforts to determine its nature. A comprehensive new investigation of the anomalous behavior of the two Pioneers has begun recently. The new efforts rely on the much-extended set of radio-metric Doppler data for both spacecraft in conjunction with the newly available complete record of their telemetry files and a large archive of original project documentation. As the new study is yet to report its findings, this review provides the necessary background for the new results to appear in the near future. In particular, we provide a significant amount of information on the design, operations and behavior of the two Pioneers during their entire missions, including descriptions of various data formats and techniques used for their navigation and radio-science data analysis. As most of this information was recovered relatively recently, it was not used in the previous studies of the Pioneer anomaly, but it is critical for the new investigation.Comment: 165 pages, 40 figures, 16 tables; accepted for publication in Living Reviews in Relativit

Autism genetic database (AGD): a comprehensive database including autism susceptibility gene-CNVs integrated with known noncoding RNAs and fragile sites

<p>Abstract</p> <p>Background</p> <p>Autism is a highly heritable complex neurodevelopmental disorder, therefore identifying its genetic basis has been challenging. To date, numerous susceptibility genes and chromosomal abnormalities have been reported in association with autism, but most discoveries either fail to be replicated or account for a small effect. Thus, in most cases the underlying causative genetic mechanisms are not fully understood. In the present work, the Autism Genetic Database (AGD) was developed as a literature-driven, web-based, and easy to access database designed with the aim of creating a comprehensive repository for all the currently reported genes and genomic copy number variations (CNVs) associated with autism in order to further facilitate the assessment of these autism susceptibility genetic factors.</p> <p>Description</p> <p>AGD is a relational database that organizes data resulting from exhaustive literature searches for reported susceptibility genes and CNVs associated with autism. Furthermore, genomic information about human fragile sites and noncoding RNAs was also downloaded and parsed from miRBase, snoRNA-LBME-db, piRNABank, and the MIT/ICBP siRNA database. A web client genome browser enables viewing of the features while a web client query tool provides access to more specific information for the features. When applicable, links to external databases including GenBank, PubMed, miRBase, snoRNA-LBME-db, piRNABank, and the MIT siRNA database are provided.</p> <p>Conclusion</p> <p>AGD comprises a comprehensive list of susceptibility genes and copy number variations reported to-date in association with autism, as well as all known human noncoding RNA genes and fragile sites. Such a unique and inclusive autism genetic database will facilitate the evaluation of autism susceptibility factors in relation to known human noncoding RNAs and fragile sites, impacting on human diseases. As a result, this new autism database offers a valuable tool for the research community to evaluate genetic findings for this complex multifactorial disorder in an integrated format. AGD provides a genome browser and a web based query client for conveniently selecting features of interest. Access to AGD is freely available at <url>http://wren.bcf.ku.edu/</url>.</p

Transcriptome-Wide Prediction of miRNA Targets in Human and Mouse Using FASTH

Transcriptional regulation by microRNAs (miRNAs) involves complementary base-pairing at target sites on mRNAs, yielding complex secondary structures. Here we introduce an efficient computational approach and software (FASTH) for genome-scale prediction of miRNA target sites based on minimizing the free energy of duplex structure. We apply our approach to identify miRNA target sites in the human and mouse transcriptomes. Our results show that short sequence motifs in the 5′ end of miRNAs frequently match mRNAs perfectly, not only at validated target sites but additionally at many other, energetically favourable sites. High-quality matching regions are abundant and occur at similar frequencies in all mRNA regions, not only the 3′UTR. About one-third of potential miRNA target sites are reassigned to different mRNA regions, or gained or lost altogether, among different transcript isoforms from the same gene. Many potential miRNA target sites predicted in human are not found in mouse, and vice-versa, but among those that do occur in orthologous human and mouse mRNAs most are situated in corresponding mRNA regions, i.e. these sites are themselves orthologous. Using a luciferase assay in HEK293 cells, we validate four of six predicted miRNA-mRNA interactions, with the mRNA level reduced by an average of 73%. We demonstrate that a thermodynamically based computational approach to prediction of miRNA binding sites on mRNAs can be scaled to analyse complete mammalian transcriptome datasets. These results confirm and extend the scope of miRNA-mediated species- and transcript-specific regulation in different cell types, tissues and developmental conditions

Tourette disorder spectrum maps to chromosome 14q31.1 in an Italian kindred

Tourette syndrome (TS) is a frequent neuropsychiatric disorder of unknown etiology. A number of chromosomal regions have been nominated as TS loci in linkage studies, but confirmation has met with limited success and causative mutations have not yet been definitely identified. Furthermore, TS, chronic tics, and obsessive–compulsive disorder (OCD) occur at increased frequencies among TS relatives, supporting the view that these phenotypes represent parts of the same genetically determined spectrum. We ascertained a four-generation Italian kindred segregating TS, chronic multiple motor tics (CMT), and OCD, and we performed a ten-centimorgan (cM) genome-wide linkage scan in order to map the underlying genetic defect. Suggestive linkage to chromosome 14q31.1 (multipoint LOD = 2.4) was detected by affected-only analysis under an autosomal dominant model and a narrower phenotype definition (only the subjects with TS and CMT were considered as affected). The linkage peak increased and it approached genome-wide significance (LOD = 3.29) when a broader phenotype definition was adopted (subjects with TS, CMT, and OCD considered as affected). Haplotype analysis defined a ∼2.3 cM critical region, shared by all the relatives with TS, CMT, or OCD. In conclusion, we provide strong evidence for linkage of TS spectrum to chromosome 14q31.1. Suggestive linkage to an overlapping region of chromosome 14q was reported in a recent scan of TS sibling pairs. This region might therefore contain an important gene for TS, and it should be prioritized for further study

The Effect of Central Loops in miRNA:MRE Duplexes on the Efficiency of miRNA-Mediated Gene Regulation

MicroRNAs (miRNAs) guide posttranscriptional repression of mRNAs. Hundreds of miRNAs have been identified but the target identification of mammalian mRNAs is still a difficult task due to a poor understanding of the interaction between miRNAs and the miRNA recognizing element (MRE). In recent research, the importance of the 5′ end of the miRNA:MRE duplex has been emphasized and the effect of the tail region addressed, but the role of the central loop has largely remained unexplored. Here we examined the effect of the loop region in miRNA:MRE duplexes and found that the location of the central loop is one of the important factors affecting the efficiency of gene regulation mediated by miRNAs. It was further determined that the addition of a loop score combining both location and size as a new criterion for predicting MREs and their cognate miRNAs significantly decreased the false positive rates and increased the specificity of MRE prediction

Evaluation of a multiple ecological level child obesity prevention program: Switch® what you Do, View, and Chew

<p>Abstract</p> <p>Background</p> <p>Schools are the most frequent target for intervention programs aimed at preventing child obesity; however, the overall effectiveness of these programs has been limited. It has therefore been recommended that interventions target multiple ecological levels (community, family, school and individual) to have greater success in changing risk behaviors for obesity. This study examined the immediate and short-term, sustained effects of the Switch program, which targeted three behaviors (decreasing children's screen time, increasing fruit and vegetable consumption, and increasing physical activity) at three ecological levels (the family, school, and community).</p> <p>Methods</p> <p>Participants were 1,323 children and their parents from 10 schools in two states. Schools were matched and randomly assigned to treatment and control. Measures of the key behaviors and body mass index were collected at baseline, immediately post-intervention, and 6 months post-intervention.</p> <p>Results</p> <p>The effect sizes of the differences between treatment and control groups ranged between small (Cohen's <it>d </it>= 0.15 for body mass index at 6 months post-intervention) to large (1.38; parent report of screen time at 6 months post-intervention), controlling for baseline levels. There was a significant difference in parent-reported screen time at post-intervention in the experimental group, and this effect was maintained at 6 months post-intervention (a difference of about 2 hours/week). The experimental group also showed a significant increase in parent-reported fruit and vegetable consumption while child-reported fruit and vegetable consumption was marginally significant. At the 6-month follow-up, parent-reported screen time was significantly lower, and parent and child-reported fruit and vegetable consumption was significantly increased. There were no significant effects on pedometer measures of physical activity or body mass index in the experimental group. The intervention effects were moderated by child sex (for fruit and vegetable consumption, physical activity, and weight status), family involvement (for fruit and vegetable consumption), and child body mass index (for screen time). The perception of change among the experimental group was generally positive with 23% to 62% indicating positive changes in behaviors.</p> <p>Conclusion</p> <p>The results indicate that the Switch program yielded small-to-modest treatment effects for promoting children's fruit and vegetable consumption and minimizing screen time. The Switch program offers promise for use in youth obesity prevention.</p

How Plastic Can Phenotypic Plasticity Be? The Branching Coral Stylophora pistillata as a Model System

Phenotypic plasticity enables multicellular organisms to adjust morphologies and various life history traits to variable environmental challenges. Here, we elucidate fixed and plastic architectural rules for colony astogeny in multiple types of colonial ramets, propagated by cutting from genets of the branching coral Stylophora pistillata from Eilat, the Red Sea. We examined 16 morphometric parameters on 136 one-year old S. pistillata colonies (of seven genotypes), originating from small fragments belonging, each, to one of three single-branch types (single tips, start-up, and advanced bifurcating tips) or to structural preparative manipulations (representing a single or two growth axes). Experiments were guided by the rationale that in colonial forms, complexity of evolving phenotypic plasticity can be associated with a degree of structural modularity, where shapes are approached by erecting iterative growth patterns at different levels of coral-colony organization. Analyses revealed plastic morphometric characters at branch level, and predetermined morphometric traits at colony level (only single trait exhibited plasticity under extreme manipulation state). Therefore, under the experimental manipulations of this study, phenotypic plasticity in S. pistillata appears to be related to branch level of organization, whereas colony traits are controlled by predetermined genetic architectural rules. Each level of organization undergoes its own mode of astogeny. However, depending on the original ramet structure, the spherical 3-D colonial architecture in this species is orchestrated and assembled by both developmental trajectories at the branch level, and traits at the colony level of organization. In nature, branching colonial forms are often subjected to harsh environmental conditions that cause fragmentation of colony into ramets of different sizes and structures. Developmental traits that are plastic, responding to fragment structure and are not predetermine in controlling astogeny, allow formation of species-specific architecture product through integrated but variable developmental routes. This adaptive plasticity or regeneration is an efficient mechanism by which isolated fragments of branching coral species cope with external environmental forces