Exploring polygenic contributors to subgroups of comorbid conditions in autism spectrum disorder

Individuals with autism spectrum disorder (ASD) have heterogeneous comorbid conditions. This study examined whether comorbid conditions in ASD are associated with polygenic risk scores (PRS) of ASD or PRS of comorbid conditions in non-ASD specific populations. Genome-wide single nucleotide polymorphism (SNP) data were obtained from 1386 patients with ASD from the Autism Genetic Resource Exchange (AGRE) study. After excluding individuals with missing clinical information concerning comorbid conditions, a total of 707 patients were included in the study. A total of 18 subgroups of comorbid conditions (‘topics’) were identified using a machine learning algorithm, topic modeling. PRS for ASD were computed using a genome-wide association meta-analysis of 18,381 cases and 27,969 controls. From these 18 topics, Topic 6 (over-represented by allergies) (p = 1.72 × 10−3) and Topic 17 (over-represented by sensory processing issues such as low pain tolerance) (p = 0.037) were associated with PRS of ASD. The associations between these two topics and the multi-locus contributors to their corresponding comorbid conditions based on non-ASD specific populations were further explored. The results suggest that these two topics were not associated with the PRS of allergies and chronic pain disorder, respectively. Note that characteristics of the present AGRE sample and those samples used in the original GWAS for ASD, allergies, and chronic pain disorder, may differ due to significant clinical heterogeneity that exists in the ASD population. Additionally, the AGRE sample may be underpowered and therefore insensitive to weak PRS associations due to a relatively small sample size. Findings imply that susceptibility genes of ASD may contribute more to the occurrence of allergies and sensory processing issues in individuals with ASD, compared with the susceptibility genes for their corresponding phenotypes in non-ASD individuals. Since these comorbid conditions (i.e., allergies and pain sensory issues) may not be attributable to the corresponding comorbidity-specific biological factors in non-ASD individuals, clinical management for these comorbid conditions may still depend on treatments for core symptoms of ASD

RGO/Nylon-6 composite mat with unique structural features and electrical properties obtained from electrospinning and hydrothermal process

In this work, the reduced graphene oxide (RGO) sheets were effectively uploaded through nylon-6 fibers using combined process of electrospinning and hydrothermal treatment. Good dispersion of graphene oxide (GO) with nylon-6 solution could allow to upload GO sheets through nylon-6 fibers and facilitate the formation of spider-wave-like nano-nets during electrospinning. GO sheets present on/into nylon-6 spider-wave-like nano-nets were further reduced to RGO using hydrothermal treatment. The impregnated GO sheets into nylon-6 nanofibers and their reduction during hydrothermal treatment were confirmed by FE-SEM, TEM, FT-IR and Raman spectra. The electrical characteristics of pristine nylon-6, GO/nylon-6 and RGO/nylon-6 nanofibers were investigated and it was found that RGO/nylon-6 composite mat had better electrical conductivity than others. The formation of spider-wave-like nano-nets as well as indirect route of incorporation of RGO sheets on electrospun nylon-6 mat may open a new direction for future graphene/polymer electronics. © 2013 The Korean Fiber Society and Springer Science+Business Media Dordrecht

Digit-only sauropod pes trackways from China - evidence of swimming or a preservational phenomenon?

For more than 70 years unusual sauropod trackways have played a pivotal role in debates about the swimming ability of sauropods. Most claims that sauropods could swim have been based on manus-only or manus-dominated trackways. However none of these incomplete trackways has been entirely convincing, and most have proved to be taphonomic artifacts, either undertracks or the result of differential depth of penetration of manus and pes tracks, but otherwise showed the typical pattern of normal walking trackways. Here we report an assemblage of unusual sauropod tracks from the Lower Cretaceous Hekou Group of Gansu Province, northern China, characterized by the preservation of only the pes claw traces, that we interpret as having been left by walking, not buoyant or swimming, individuals. They are interpreted as the result of animals moving on a soft mud-silt substrate, projecting their claws deeply to register their traces on an underlying sand layer where they gained more grip during progression. Other sauropod walking trackways on the same surface with both pes and manus traces preserved, were probably left earlier on relatively firm substrates that predated the deposition of soft mud and silt . Presently, there is no convincing evidence of swimming sauropods from their trackways, which is not to say that sauropods did not swim at all

Higher prevalence of smoking and lower BMI, waist circumference, cholesterol and triacylglyceride levels in Prague's homeless compared to a majority of the Czech population

BACKGROUND: Homeless people have higher morbidity and mortality rates than the general population. Research has shown that cardiovascular disease is the leading cause of death in older homeless adults. This study was undertaken to describe the prevalence of cardiovascular risk factors in the homeless population in Prague. METHODS: Data was obtained from a cross-sectional study carried out in 2003. Body mass index (BMI), waist circumference (WC), total cholesterol (TC), triacylglycerides (TAG) and smoking habits were assessed. The homeless participants in the study were recruited from a homeless center run by a Prague charitable organization called Naděje ("Hope") and at Prague's main railway station. Most participants were assessed at the Naděje center (134 persons) while the rest were assessed at Prague's Bulovka University Hospital (67 persons). RESULTS: A total of 201 homeless (174 males and 27 females) aged 19 – 70 years were examined. Mean values of BMI, WC, TC and TAG in homeless men and women were within normal limits. Compared with the majority of the Czech population, the homeless had significantly lower mean levels of TC and TAG and lower BMI and WC values. When compared to the majority of the Czech population, the incidence of smoking among the homeless was significantly higher. Among smokers in both populations, no differences were found in the number of cigarettes smoked per day. CONCLUSION: Classical cardiovascular risk factors such as TC, TAG, BMI and WC, are significantly lower in Prague's homeless minority than in the majority of the Czech population. However, the prevalence of smoking is much higher in the homeless population

Factors influencing the ownership and utilization of long-lasting insecticidal nets for malaria prevention in Ethiopia

Background Utilization of long-lasting insecticidal nets (LLINs) is regarded as key malaria prevention and control strategy. However, studies have reported a large gap in terms of both ownership and utilization particularly in the sub-Saharan Africa (SSA). With continual efforts to improve the use of LLIN and to progress malaria elimination, examining the factors influencing the ownership and usage of LLIN is of high importance. Therefore, the current study was conducted to examine the level of ownership and use of LLIN along with identification of associated factors at household level. Methods A cross-sectional study was conducted in Mirab Abaya District, Southern Ethiopia in June and July 2014. A total of 540 households, with an estimated 2690 members, were selected in four kebeles of the district known to have high incidence of malaria. Trained data collectors interviewed household heads to collect information on the knowledge, ownership and utilization of LLINs, which was complemented by direct observation on the conditions and use of the nets through house-to-house visit. Bivariate and multivariable logistic regression analyses were used to determine factors associated to LLIN use. Results Of 540 households intended to be included in the survey, 507 responded to the study (94.24% response rate), covering the homes of 2759 people. More than 58% of the households had family size >5 (the regional average), and 60.2% of them had at least one child below the age of 5 years. The ownership of at least one LLIN among households surveyed was 89.9%, and using at least one LLIN during the night prior to the survey among net owners was 85.1% (n = 456). Only 36.7% (186) mentioned at least as the mean of correct scores of all participants for 14 possible malaria symptoms and 32.7% (166) knew at least as the mean of correct scores of all participants for possible preventive methods. Over 30% of nets owned by the households were out of use. After controlling for confounding factors, having two or more sleeping places (adjusted odds ratio [aOR] = 2.58, 95% CI 1.17, 5.73), knowledge that LLIN prevents malaria (aOR = 2.51, 95% CI 1.17, 5.37), the presence of hanging bed nets (aOR = 19.24, 95% CI 9.24, 40.07) and walls of the house plastered or painted >12 months ago (aOR = 0.09, 95% CI 0.01, 0.71) were important predictors of LLIN utilization. Conclusions This study found a higher proportion of LLIN ownership and utilization by households than had previously been found in similar studies in Ethiopia, and in many studies in SSA. However, poor knowledge of the transmission mechanisms and the symptoms of malaria, and vector control measures to prevent malaria were evident. Moderate proportions of nets were found to be out of use or in poor repair. Efforts should be in place to maintain the current rate of utilization of LLIN in the district and improve on the identified gaps in order to support the elimination of malaria

Expression signatures of TP53 mutations in serous ovarian cancers

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>TP53 </it>gene are extremely common and occur very early in the progression of serous ovarian cancers. Gene expression patterns that relate to mutational status may provide insight into the etiology and biology of the disease.</p> <p>Methods</p> <p>The <it>TP53 </it>coding region was sequenced in 89 frozen serous ovarian cancers, 40 early stage (I/II) and 49 advanced stage (III/IV). Affymetrix U133A expression data was used to define gene expression patterns by mutation, type of mutation, and cancer stage.</p> <p>Results</p> <p>Missense or chain terminating (null) mutations in <it>TP53 </it>were found in 59/89 (66%) ovarian cancers. Early stage cancers had a significantly higher rate of null mutations than late stage disease (38% vs. 8%, p < 0.03). In advanced stage cases, mutations were more prevalent in short term survivors than long term survivors (81% vs. 30%, p = 0.0004). Gene expression patterns had a robust ability to predict <it>TP53 </it>status within training data. By using early versus late stage disease for out of sample predictions, the signature derived from early stage cancers could accurately (86%) predict mutation status of late stage cancers.</p> <p>Conclusions</p> <p>This represents the first attempt to define a genomic signature of <it>TP53 </it>mutation in ovarian cancer. Patterns of gene expression characteristic of <it>TP53 </it>mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of <it>TP53 </it>mutation in breast cancer.</p

Cellular Active N-Hydroxyurea FEN1 Inhibitors Block Substrate Entry to the Active Site

The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the first crystal structure of inhibitor-bound hFEN1 and show a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three such compounds had similar IC50 values but differed subtly in mode of action. One had comparable affinity for protein and protein– substrate complex and prevented reaction by binding to active site catalytic metal ions, blocking the unpairing of substrate DNA necessary for reaction. Other compounds were more competitive with substrate. Cellular thermal shift data showed engagement of both inhibitor types with hFEN1 in cells with activation of the DNA damage response evident upon treatment. However, cellular EC50s were significantly higher than in vitro inhibition constants and the implications of this for exploitation of hFEN1 as a drug target are discussed

Mapping Dirac quasiparticles near a single Coulomb impurity on graphene

The response of Dirac fermions to a Coulomb potential is predicted to differ significantly from how non-relativistic electrons behave in traditional atomic and impurity systems. Surprisingly, many key theoretical predictions for this ultra-relativistic regime have not been tested. Graphene, a two-dimensional material in which electrons behave like massless Dirac fermions, provides a unique opportunity to test such predictions. Graphene’s response to a Coulomb potential also offers insight into important material characteristics, including graphene’s intrinsic dielectric constant, which is the primary factor determining the strength of electron–electron interactions in graphene. Here we present a direct measurement of the nanoscale response of Dirac fermions to a single Coulomb potential placed on a gated graphene device. Scanning tunnelling microscopy was used to fabricate tunable charge impurities on graphene, and to image electronic screening around them for a Q = +1|e| charge state. Electron-like and hole-like Dirac fermions were observed to respond differently to a Coulomb potential. Comparing the observed electron–hole asymmetry to theoretical simulations has allowed us to test predictions for how Dirac fermions behave near a Coulomb potential, as well as extract graphene’s intrinsic dielectric constant: ε[subscript g] = 3.0±1.0. This small value of ε[subscript g] indicates that electron–electron interactions can contribute significantly to graphene properties.United States. Office of Naval Research. Multidisciplinary University Research Initiative (Award N00014-09-1-1066)United States. Dept. of Energy. Office of Science (Contract DE-AC02-05CH11231)National Science Foundation (U.S.) (Award DMR-0906539

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur