398 research outputs found

    Alternative-Splicing in the Exon-10 Region of GABAA Receptor β2 Subunit Gene: Relationships between Novel Isoforms and Psychotic Disorders

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    BACKGROUND: Non-coding single nucleotide polymorphisms (SNPs) in GABRB2, the gene for beta(2)-subunit of gamma-aminobutyric acid type A (GABA(A)) receptor, have been associated with schizophrenia (SCZ) and quantitatively correlated to mRNA expression and alternative splicing. METHODS AND FINDINGS: Expression of the Exon 10 region of GABRB2 from minigene constructs revealed this region to be an "alternative splicing hotspot" that readily gave rise to differently spliced isoforms depending on intron sequences. This led to a search in human brain cDNA libraries, and the discovery of two novel isoforms, beta(2S1) and beta(2S2), bearing variations in the neighborhood of Exon-10. Quantitative real-time PCR analysis of postmortem brain samples showed increased beta(2S1) expression and decreased beta(2S2) expression in both SCZ and bipolar disorder (BPD) compared to controls. Disease-control differences were significantly correlated with SNP rs187269 in BPD males for both beta(2S1) and beta(2S2) expressions, and significantly correlated with SNPs rs2546620 and rs187269 in SCZ males for beta(2S2) expression. Moreover, site-directed mutagenesis indicated that Thr(365), a potential phosphorylation site in Exon-10, played a key role in determining the time profile of the ATP-dependent electrophysiological current run-down. CONCLUSION: This study therefore provided experimental evidence for the importance of non-coding sequences in the Exon-10 region in GABRB2 with respect to beta(2)-subunit splicing diversity and the etiologies of SCZ and BPD

    Moiré patterns observed in bi layer graphene irradiated with high energetic protons

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    Customarily, it is likely that irradiated graphene yield indication of per- turbations induced by irradiation. High Resolution Transmission Electron Micros- copy (HRTEM) analysis has been performed on proton irradiated graphene. The analysis indicates the existence of Moiré patterns produced by the rotations induced by the irradiation in between planes. The rotations measured fluctuate between 3 and 5 degrees respectively. These rotations may influence the electronic properties of the material under investigation. In order to explain the observed rotations in between planes, theoretical analysis were performed under the scheme of extended Hückel tight-binding method. Average total energy of the system was careful ana- lyzed throughout the experiment composed of two graphene layers with two carbon vacancies and then the replaced carbons were intercalated in between the two lay- ers. The results obtained indicate that the system remain semi metallic. Moreover, the theoretical results yielded that the 3 degree rotation is favored, although the 5 degree rotation is not discarded. Furthermore, energy bands as well as total and projected DOS were performed in order to provide more information about the electronic changes induced by the rotations applied to the system

    Mercury, cadmium, and lead levels in human placenta: a systematic review

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    BACKGROUND: Placental tissue may furnish information on the exposure of both mother and fetus. Mercury (Hg), cadmium (Cd), and lead (Pb) are toxicants of interest in pregnancy because they are associated with alterations in child development. OBJECTIVES: The aim of this study was to summarize the available information regarding total Hg, Cd, and Pb levels in human placenta and possible related factors. METHODS: We performed a systematic search of PubMed/MEDLINE, EMBASE, Lilacs, OSH, and Web of Science for original papers on total Hg, Cd, or Pb levels in human placenta that were published in English or Spanish (1976-2011). Data on study design, population characteristics, collection and analysis of placenta specimens, and main results were extracted using a standardized form. RESULTS: We found a total of 79 papers (73 different studies). Hg, Cd, and Pb levels were reported in 24, 46, and 46 studies, respectively. Most studies included small convenience samples of healthy pregnant women. Studies were heterogeneous regarding populations selected, processing of specimens, and presentation of results. Hg concentrations > 50 ng/g were found in China (Shanghai), Japan, and the Faroe Islands. Cd levels ranged from 1.2 ng/g to 53 ng/g and were highest in the United States, Japan, and Eastern Europe. Pb showed the greatest variability, with levels ranging from 1.18 ng/g in China (Shanghai) to 500 ng/g in a polluted area of Poland. CONCLUSION: The use of the placenta as a biomarker to assess heavy metals exposure is not properly developed because of heterogeneity among the studies. International standardized protocols are needed to enhance comparability and increase the usefulness of this promising tissue in biomonitoring studies.We thank the librarians of the Móstoles Hospital and of the National Health Sciences Library (ISCIII).S

    Self-reported sex differences in high-functioning adults with autism: a meta-analysis

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    Background: Sex differences in autistic symptomatology are believed to contribute to the mis- and missed diagnosis of many girls and women with an autism spectrum condition (ASC). Whilst recent years have seen the emergence of clinical and empirical reports delineating the profile of young autistic girls, recognition of sex differences in symptomatology in adulthood is far more limited. Methods: We chose here to focus on symptomatology as reported using a screening instrument, the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R). In a meta-analysis, we pooled and analysed RAADS-R data from a number of experimental groups. Analysis of variance (ANOVA) searched for the presence of main effects of Sex and Diagnosis and for interactions between these factors in our sample of autistic and non-autistic adults. Results: In social relatedness and circumscribed interests, main effects of Diagnosis revealed that as expected, autistic adults reported significantly greater lifetime prevalence of symptoms in these domains; an effect of Sex, in circumscribed interests, also suggested that males generally reported more prevalent symptoms than females. An interaction of Sex and Diagnosis in language symptomatology revealed that a normative sex difference in language difficulties was attenuated in autism. An interaction of Sex and Diagnosis in the sensorimotor domain revealed the opposite picture: a lack of sex differences between typically-developing men and women and a greater prevalence of sensorimotor symptoms in autistic women than autistic men. Conclusions: We discuss the literature on childhood sex differences in relation to those which emerged in our adult sample. Where childhood sex differences fail to persist in adulthood, several interpretations exist, and we discuss, for example, an inherent sampling bias that may mean that only autistic women most similar to the male presentation are diagnosed. The finding that sensorimotor symptomatology is more highly reported by autistic women is a finding requiring objective confirmation, given its potential importance in diagnosis

    Ameliorated ConA-Induced Hepatitis in the Absence of PKC-theta

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    Severe liver injury that occurs when immune cells mistakenly attack an individual's own liver cells leads to autoimmune hepatitis. In mice, acute hepatitis can be induced by concanavalin A (ConA) treatment, which causes rapid activation of CD1d-positive natural killer (NK) T cells. These activated NKT cells produce large amounts of cytokines, which induce strong inflammation that damages liver tissues. Here we show that PKC-θ−/− mice were resistant to ConA-induced hepatitis due to essential function of PKC-θ in NKT cell development and activation. A dosage of ConA (25 mg/kg) that was lethal to wild-type (WT) mice failed to induce death resulting from liver injury in PKC-θ−/− mice. Correspondingly, ConA-induced production of cytokines such as IFNγ, IL-6, and TNFα, which mediate the inflammation responsible for liver injury, were significantly lower in PKC-θ−/− mice. Peripheral NKT cells had developmental defects at early stages in the thymus in PKC-θ−/− mice, and as a result their frequency and number were greatly reduced. Furthermore, PKC-θ−/− bone marrow adoptively transferred to WT mice displayed similar defects in NKT cell development, suggesting an intrinsic requirement for PKC-θ in NKT cell development. In addition, upon stimulation with NKT cell-specific lipid ligand, peripheral PKC-θ−/− NKT cells produced lower levels of inflammatory cytokines than that of WT NKT cells, suggesting that activation of NKT cells also requires PKC-θ. Our results suggest PKC-θ is an essential molecule required for activation of NKT cell to induce hepatitis, and thus, is a potential drug target for prevention of autoimmune hepatitis

    Associations between healthy eating patterns and indicators of metabolic risk in postmenopausal women

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    <p>Abstract</p> <p>Background</p> <p>Since human diets contain many components that may work synergistically to prevent or promote disease, assessing diet quality may be informative. The purpose of this study was to investigate the association between quality diet, by using Healthy Eating Index (HEI), and metabolic risk indicators in postmenopausal women.</p> <p>Methods</p> <p>This cross-sectional study included a total of 173 Brazilian women, aged 45-75 years, seeking healthcare at a public outpatient center. Food consumption assessed by 24 h-recall food inquiry was used to calculate HEI scores: >80 implied diet good, 80-51 diet "needed improvement", and <51 diet poor. Anthropometric data included: body mass index (BMI = weight/height<sup>2</sup>), waist-circumference (WC), body fat (%BF) and lean mass (%LM). Data on total cholesterol (TC), high density lipoprotein cholesterol (HDLC), low density lipoprotein cholesterol (LDLC), and triglycerides (TG) were also collected. Fisher's Exact test, and logistic regression method (to determine odds ratio, OR) were used in the statistical analysis.</p> <p>Results</p> <p>Overweight and obesity were observed in 75.7% of the participants. Excessive %BF (> 35%) was observed in 56.1%, while %LM was reduced (< 70%) in 78.1%. WC was elevated (≥88 cm) in 72.3%. Based on HEI values, diet quality was good in 3% (5/173), needed improvement in 48.5% (84/173), and was poor in 48.5% (84/173) of the cases. In this group, 75% of women had high intakes of lipids (> 35%), predominantly saturated and monounsaturated fat. On average, plasma TC, LDLC, and TG levels were higher than recommended in 57.2%, 79.2% and 45.1% of the women, respectively, while HDLC was low in 50.8%. There was association between HEI scores and the %BF that it was higher among women with HEI score < 80 (p = 0.021). There were not observed significant risk associations between HEI and lipid profile.</p> <p>Conclusion</p> <p>Among the Brazilian postmenopausal women attending a public outpatient clinic, diet was considered to need improvement or to be of poor quality, attributed to high saturated fat ingestion, which probably caused a negative impact on metabolic risk indicators, namely body composition.</p

    Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

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    Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

    Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

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    The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse

    Evolutionary Map of the Universe: Tracing Clusters to High Redshift

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    The Australian SKA Pathfinder (ASKAP) is a new radio-telescope being built in Western Australia. One of the key surveys for which it is being built is EMU (Evolutionary Map of the Universe), which will make a deep (~10 {\mu}Jy/bm rms) radio continuum survey covering the entire sky as far North as +30\circ. EMU may be compared to the NRAO VLA Sky Survey (NVSS), except that it will have about 45 times the sensitivity, and five times the resolution. EMU will also have much better sensitivity to diffuse emission than previous large surveys, and is expected to produce a large catalogue of relics, tailed galaxies, and haloes, and will increase the number of known clusters by a significant factor. Here we describe the EMU project and its impact on the astrophysics of clusters.Comment: Accepted by J. Astrophys. Ast
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