Gene expression in cardiac tissues from infants with idiopathic conotruncal defects

<p>Abstract</p> <p>Background</p> <p>Tetralogy of Fallot (TOF) is the most commonly observed conotruncal congenital heart defect. Treatment of these patients has evolved dramatically in the last few decades, yet a genetic explanation is lacking for the failure of cardiac development for the majority of children with TOF. Our goal was to perform genome wide analyses and characterize expression patterns in cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with tetralogy of Fallot.</p> <p>Methods</p> <p>We employed genome wide gene expression microarrays to characterize cardiovascular tissue (right ventricle, pulmonary valve and pulmonary artery) obtained at the time of reconstructive surgery from 19 children with TOF (16 idiopathic and three with 22q11.2 deletions) and compared gene expression patterns to normally developing subjects.</p> <p>Results</p> <p>We detected a signal from approximately 26,000 probes reflecting expression from about half of all genes, ranging from 35% to 49% of array probes in the three tissues. More than 1,000 genes had a 2-fold change in expression in the right ventricle (RV) of children with TOF as compared to the RV from matched control infants. Most of these genes were involved in compensatory functions (e.g., hypertrophy, cardiac fibrosis and cardiac dilation). However, two canonical pathways involved in spatial and temporal cell differentiation (WNT, <it>p </it>= 0.017 and Notch, <it>p </it>= 0.003) appeared to be generally suppressed.</p> <p>Conclusions</p> <p>The suppression of developmental networks may represent a remnant of a broad malfunction of regulatory pathways leading to inaccurate boundary formation and improper structural development in the embryonic heart. We suggest that small tissue specific genomic and/or epigenetic fluctuations could be cumulative, leading to regulatory network disruption and failure of proper cardiac development.</p

Vision in high-level football officials

YesOfficiating in football depends, at least to some extent, upon adequate visual function. However, there is no vision standard for football officiating and the nature of the relationship between officiating performance and level of vision is unknown. As a first step in characterising this relationship, we report on the clinically-measured vision and on the perceived level of vision in elite-level, Portuguese football officials. Seventy-one referees (R) and assistant referees (AR) participated in the study, representing 92% of the total population of elite level football officials in Portugal in the 2013/2014 season. Nine of the 22 Rs (40.9%) and ten of the 49 ARs (20.4%) were international-level. Information about visual history was also gathered. Perceived vision was assessed using the preference-values-assigned-to-global-visual-status (PVVS) and the Quality-of-Vision (QoV) questionnaire. Standard clinical vision measures (including visual acuity, contrast sensitivity and stereopsis) were gathered in a subset (n = 44, 62%) of the participants. Data were analysed according to the type (R/AR) and level (international/national) of official, and Bonferroni corrections were applied to reduce the risk of type I errors. Adopting criterion for statistical significance of p<0.01, PVVS scores did not differ between R and AR (p = 0.88), or between national- and international-level officials (p = 0.66). Similarly, QoV scores did not differ between R and AR in frequency (p = 0.50), severity (p = 0.71) or bothersomeness (p = 0.81) of symptoms, or between international-level vs national-level officials for frequency (p = 0.03) or bothersomeness (p = 0.07) of symptoms. However, international-level officials reported less severe symptoms than their national-level counterparts (p<0.01). Overall, 18.3% of officials had either never had an eye examination or if they had, it was more than 3 years previously. Regarding refractive correction, 4.2% had undergone refractive surgery and 23.9% wear contact lenses when officiating. Clinical vision measures in the football officials were similar to published normative values for young, adult populations and similar between R and AR. Clinically-measured vision did not differ according to officiating level. Visual acuity measured with and without a pinhole disc indicated that around one quarter of participants may be capable of better vision when officiating, as evidenced by better acuity (≥1 line of letters) using the pinhole. Amongst the clinical visual tests we used, we did not find evidence for above-average performance in elite-level football officials. Although the impact of uncorrected mild to moderate refractive error upon officiating performance is unknown, with a greater uptake of eye examinations, visual acuity may be improved in around a quarter of officials.Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013

A large-scale genome-wide association study meta-analysis of cannabis use disorder

Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10-9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86-0·93, p=6·46 × 10-9). Cannabis use disorder and cannabis use were genetically correlated (rg 0·50, p=1·50 × 10-21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder

Comprehensive two-dimensional gas chromatographic separations with a microfabricated thermal modulator

ABSTRACT This paper presents the first comprehensive two-dimensional gas chromatographic (GC×GC) separations of volatile organic compound (VOC) mixtures employing a microfabricated mid-point thermal modulator (μTM). The first-dimension column was coated with a non-polar polydimethylsiloxane (PDMS) film and the second-dimension column was coated with the polar polyethylene glycol (PEG) film. μTM heating and cooling rates of 2400 ° C/s and -168 °C/s, respectively, were achieved. The effects of system flow rate and the maximum and minimum μTM temperatures on the resolution and signal enhancement are explored with small sets of 5-7 VOCs for a fixed modulation period of 6 s. A structured 2-D chromatogram is produced and a 15-VOC GC×GC separation is achieved in 185 sec. This low-power, consumable-free μTM provides performance rivaling many commercial macroscale thermal modulators

Geologic Evaluation of Critical Production Parameters for Coalbed Methane Resources

Characterization of coalbed methane occurrence and producibility in the Black Warrior Basin of Alabama indicates that geological factors are the principal controls on the occurrence and producibility of coalbed methane. Results of engineering analysis indicate that application of completion and stimulation techniques may be used to increase recovery once favorable well sites are chosen. Sedimentologic and coal-quality parameters may be used to locate regions for coalbed methane development by characterizing the occurrence, rank, and grade of coal resources. However, high-productivity trends within those regions are localized, and geological data suggest that productivity trends may be predictable based on structural and hydrologic parameters. Several highly productive trends occur along northeast-oriented lineaments. These trends evidently are the surface expression of zones of enhanced permeability which apparently are related to fractures. Productive trends also are associated with areas of low reservoir pressure, and salinity maps indicate that fresh water has migrated toward these areas from the southeast margin of the basin. The available data indicate that structure and hydrology are critical production parameters that may be used to identify favorable well sites within regions containing significant, high-quality coal resources.Bureau of Economic Geolog