91 research outputs found

    SLC25A22 is a novel gene for migrating partial seizures in infancy

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    Objective To identify a genetic cause for migrating partial seizures in infancy (MPSI). Methods We characterized a consanguineous pedigree with MPSI and obtained DNA from affected and unaffected family members. We analyzed single nucleotide polymorphism 500K data to identify regions with evidence of linkage. We performed whole exome sequencing and analyzed homozygous variants in regions of linkage to identify a candidate gene and performed functional studies of the candidate gene SLC25A22. Results In a consanguineous pedigree with 2 individuals with MPSI, we identified 2 regions of linkage, chromosome 4p16.1-p16.3 and chromosome 11p15.4-pter. Using whole exome sequencing, we identified 8 novel homozygous variants in genes in these regions. Only 1 variant, SLC25A22 c.G328C, results in a change of a highly conserved amino acid (p.G110R) and was not present in control samples. SLC25A22 encodes a glutamate transporter with strong expression in the developing brain. We show that the specific G110R mutation, located in a transmembrane domain of the protein, disrupts mitochondrial glutamate transport. Interpretation We have shown that MPSI can be inherited and have identified a novel homozygous mutation in SLC25A22 in the affected individuals. Our data strongly suggest that SLC25A22 is responsible for MPSI, a severe condition with few known etiologies. We have demonstrated that a combination of linkage analysis and whole exome sequencing can be used for disease gene discovery. Finally, as SLC25A22 had been implicated in the distinct syndrome of neonatal epilepsy with suppression bursts on electroencephalogram, we have expanded the phenotypic spectrum associated with SLC25A22. Ann Neurol 2013;74:873-882 © 2013 American Neurological Association

    CHMP1A encodes an essential regulator of BMI1-INK4A in cerebellar development

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    Charged multivesicular body protein 1A (CHMP1A; also known as chromatin-modifying protein 1A) is a member of the ESCRT-III (endosomal sorting complex required for transport-III) complex but is also suggested to localize to the nuclear matrix and regulate chromatin structure. Here, we show that loss-of-function mutations in human CHMP1A cause reduced cerebellar size (pontocerebellar hypoplasia) and reduced cerebral cortical size (microcephaly). CHMP1A-mutant cells show impaired proliferation, with increased expression of INK4A, a negative regulator of stem cell proliferation. Chromatin immunoprecipitation suggests loss of the normal INK4A repression by BMI in these cells. Morpholino-based knockdown of zebrafish chmp1a resulted in brain defects resembling those seen after bmi1a and bmi1b knockdown, which were partially rescued by INK4A ortholog knockdown, further supporting links between CHMP1A and BMI1-mediated regulation of INK4A. Our results suggest that CHMP1A serves as a critical link between cytoplasmic signals and BMI1-mediated chromatin modifications that regulate proliferation of central nervous system progenitor cells

    Job satisfaction of the academic staff of the vocational schools of the foundation and public universities: Sample of Turkey

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    Purpose: This study aims to highlight the differences between the public and foundation universities determining the level of job satisfaction of academic personnel working at vocational schools within the body of public and foundation universities in Turkey. Design/methodology/approach: In the present study, the questionnaire developed by Ardic and Bas and used in a similar study is taken as the basis for this study. Some amendments have been made to the instrument. The reliability of the questionnaire was evaluated using the Cronbach alpha coefficient and some statistical methods such as independent samples t test and chi-square test depending on the data. Differences of opinion based on demographic characteristics are presented giving the frequencies and percentages of demographic characteristics of the data. Findings: Three questions were focused on in the present study: the first is to present the most important factor affecting the job satisfaction or dissatisfaction of the academic personnel working at the public and foundation universities; the second is to determine whether there is a difference between public and foundation universities and the third is to set forth the reasons of these differences, if any. Research limitations/implications: The current study selected 12,160 academic personnel throughout Turkey and the questionnaire was used as a data collection instrument. The instrument could not be delivered to all the personnel. This is because it was not possible to have access to the e-mail addresses of some of the academic personnel, some of the e-mail addresses were not in use or out of date while some personnel do not use the internet. Originality/value: The aim of this study is to determine job satisfaction level of academic personnel working in vocational high schools operating under the umbrella of state and foundation universities, which offer educational services in Turkey. Since no study is encountered as a result of the literature survey made, that addressed especially the level of the job satisfaction of the academic staff working in the vocational schools in Turkey in a way to cover all public and foundation universities, such a study was made for the purpose of removing the deficiency in this subject. © Emerald Group Publishing Limited

    An experimental investigation of kinetic energy and momentum correction coefficients in compound channels [Bileşik Kesitlerde Enerji ve Momentum Düzeltme Katsayilarinin Deneysel İrdelenmesi]

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    In this study, vertical and lateral velocity distribution in a compound channel cross section was measured to investigate kinetic energy and momentum correction coefficients for eight different test discharges. Experiments were carried out for supercritical flow conditions. Froude number (Fr) was varied between 1.04 and 1.1, as depth ratio (Dr) changed 0.16 and 0.48. Kinetic energy and momentum correction coefficients, ? and ß, were computed for each experimental condition. Results were compared with findings taken from the experimental works carried out in different cross-sectional shaped flumes. As a result, for 48 different experimental test case, kinetic energy and momentum correction coefficients, ? and ß, were computed as 1.15 and 1.08, respectively

    Effect of the Froude number on assessment of the bridge afflux

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    This paper presents the findings of laboratory model testing of arch and straight-deck bridge constrictions, in a symmetrical compound channel flume having different roughness conditions. Four different types of bridge models, namely a single-opening, semicircular arch bridge, a multiple-opening, semicircular arch bridge, a single opening, elliptic arch bridge, and a straight-deck bridge with and without piers, were used in the testing programme. The validity of the Biery and Delleur method developed for the single cross-sectional-shaped arch bridge constrictions was examined for a compound channel case. The effect of different definitions of the Froude number on the application of the Biery and Delleur method was also investigated. The results showed that the Biery and Delleur method agreed reasonably well with the University of Birmingham data presented in the current study, provided that the Froude number was defined in the same way as originally envisaged. Significant errors may result, however, from using this method with definitions of the Froude number that are more appropriate to compound channels

    Improving bridge afflux prediction for overbank flows

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    Tests were carried out to investigate bridge afflux phenomena for bridge constrictions in a compound channel flume. The flume had different roughness configurations in the main channel and floodplains. All tests were undertaken for the condition of no eccentricity and no entrance rounding. The normal crossing (? = 0°) and two different skew angles (? = 30° and 45°) were tested for different arch and flat soffit type bridge models. For each set of experiments, the Froude number for normal depth, afflux ratio and blockage ratio (area of bridge below water level to total flow area) were obtained based on an analogical method developed previously. These quantities were analysed to obtain a simple practical afflux equation. This afflux equation was also applied to field data collected by the US Geological Survey and the results were compared with those obtained using the more complex methods such as HEC-2, WSPRO and USBPR
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