1,042 research outputs found

    An Ogle-B Christmas

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    Regulation of crystallin gene expression

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    Gender differences in emotionality and sociability in children with autism spectrum disorders

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    BackgroundFour times as many males are diagnosed with high functioning autism compared to females. A growing body of research that focused on females with autism spectrum disorder (ASD) questions the assumption of gender invariance in ASD. Clinical observations suggest that females with ASD superficially demonstrate better social and emotional skills than males with ASD, which may camouflage other diagnostic features. This may explain the under-diagnosis of females with ASD.MethodsWe hypothesised that females with ASD would display better social skills than males with ASD on a test of friendship and social function. One hundred and one 10- to 16-year-olds (ASD females, n&thinsp;=&thinsp;25; typically developing (TD) females, n&thinsp;=&thinsp;25; ASD males, n&thinsp;=&thinsp;25; TD males, n&thinsp;=&thinsp;26) were interviewed (using the friendship questionnaire (FQ)) with high scores indicating the child has close, empathetic and supportive relationships. One parent of each child completed the FQ to assess whether there are differences in perception of friendships between parents and children.ResultsIt was found that, independent of diagnosis, females demonstrated higher scores on the FQ than males. Further, regardless of gender, children with ASD demonstrated lower scores than TD children. Moreover, the effect of ASD was independent of gender. Interestingly, females with ASD and TD males displayed similar scores on the FQ.ConclusionsThis finding is supported by clinical reports that females with ASD have more developed social skills than males with ASD. Further research is now required to examine the underlying causes for this phenomenon in order to develop gender-appropriate diagnostic criteria and interventions for ASD.<br /

    Are Both Symmetric and Buckled Dimers on Si(100) Minima? Density Functional and Multireference Perturbation Theory Calculations

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    We report a spin-unrestricted density functional theory(DFT) solution at the symmetric dimer structure for cluster models of Si(100). With this solution, it is shown that the symmetric structure is a minimum on the DFTpotential energy surface, although higher in energy than the buckled structure. In restricted DFT calculations the symmetric structure is a saddle point connecting the two buckled minima. To further assess the effects of electron correlation on the relative energies of symmetric versus buckled dimers on Si(100), multireference second order perturbation theory (MRMP2) calculations are performed on these DFT optimized minima. The symmetric structure is predicted to be lower in energy than the buckled structure via MRMP2, while the reverse order is found by DFT. The implications for recent experimental interpretations are discussed

    Susceptibility of Human Prion Protein to Conversion by Chronic Wasting Disease Prions

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    Chronic wasting disease (CWD) is a contagious and fatal neurodegenerative disease and a serious animal health issue for deer and elk in North America. The identification of the first cases of CWD among free-ranging reindeer and moose in Europe brings back into focus the unresolved issue of whether CWD can be zoonotic like bovine spongiform encephalopathy. We used a cell-free seeded protein misfolding assay to determine whether CWD prions from elk, white-tailed deer, and reindeer in North America can convert the human prion protein to the disease-associated form. We found that prions can convert, but the efficiency of conversion is affected by polymorphic variation in the cervid and human prion protein genes. In view of the similarity of reindeer, elk, and white-tailed deer in North America to reindeer, red deer, and roe deer, respectively, in Europe, a more comprehensive and thorough assessment of the zoonotic potential of CWD might be warranted

    Selective inhibition of histamine-evoked Ca2+ signals by compartmentalized cAMP in human bronchial airway smooth muscle cells.

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    Intracellular Ca2+ and cAMP typically cause opposing effects on airway smooth muscle contraction. Receptors that stimulate these pathways are therapeutic targets in asthma and chronic obstructive pulmonary disease. However, the interactions between different G protein-coupled receptors (GPCRs) that evoke cAMP and Ca2+ signals in human bronchial airway smooth muscle cells (hBASMCs) are poorly understood. We measured Ca2+ signals in cultures of fluo-4-loaded hBASMCs alongside measurements of intracellular cAMP using mass spectrometry or [3H]-adenine labeling. Interactions between the signaling pathways were examined using selective ligands of GPCRs, and inhibitors of Ca2+ and cAMP signaling pathways. Histamine stimulated Ca2+ release through inositol 1,4,5-trisphosphate (IP3) receptors in hBASMCs. β2-adrenoceptors, through cAMP and protein kinase A (PKA), substantially inhibited histamine-evoked Ca2+ signals. Responses to other Ca2+-mobilizing stimuli were unaffected by cAMP (carbachol and bradykinin) or minimally affected (lysophosphatidic acid). Prostaglandin E2 (PGE2), through EP2 and EP4 receptors, stimulated formation of cAMP and inhibited histamine-evoked Ca2+ signals. There was no consistent relationship between the inhibition of Ca2+ signals and the amounts of intracellular cAMP produced by different stimuli. We conclude that β-adrenoceptors, EP2 and EP4 receptors, through cAMP and PKA, selectively inhibit Ca2+ signals evoked by histamine in hBASMCs, suggesting that PKA inhibits an early step in H1 receptor signaling. Local delivery of cAMP within hyperactive signaling junctions mediates the inhibition

    Academic Contrapower Harassment and Student Evaluations: The Gendered Experience of Bullying, Intimidation, and Entitlement

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    Student evaluations are subjective and oftentimes arbitrary, skewed by stereotypes students have of the professor rather than the actual merit of the instructional style. Yet student evaluations are frequently necessary for promotion and tenure requirements regardless of known gender bias. As such, student evaluations have the potential to foster a culture of academic contrapower harassment (ACPH). A convenience sample of 150 professors and instructors (41.3% male, 56.7%, female, and 2% declined to specify) from two separate liberal arts colleges were surveyed to explore the gendered differences of perceived bullying of professors by students on anonymous student evaluations. Using Pearson’s chi-square test for independence (categorical variables), results support differences in the psychological consequences of student evaluations between male and female faculty but fail to confirm instances of ACPH

    Human stem cell-derived astrocytes replicate human prions in a PRNP genotype-dependent manner.

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    Prions are infectious agents that cause neurodegenerative diseases such as Creutzfeldt-Jakob disease (CJD). The absence of a human cell culture model that replicates human prions has hampered prion disease research for decades. In this paper, we show that astrocytes derived from human induced pluripotent stem cells (iPSCs) support the replication of prions from brain samples of CJD patients. For experimental exposure of astrocytes to variant CJD (vCJD), the kinetics of prion replication occur in a prion protein codon 129 genotype-dependent manner, reflecting the genotype-dependent susceptibility to clinical vCJD found in patients. Furthermore, iPSC-derived astrocytes can replicate prions associated with the major sporadic CJD strains found in human patients. Lastly, we demonstrate the subpassage of prions from infected to naive astrocyte cultures, indicating the generation of prion infectivity in vitro. Our study addresses a long-standing gap in the repertoire of human prion disease research, providing a new in vitro system for accelerated mechanistic studies and drug discovery

    Cardiovascular disease in a cohort exposed to the 1940-45 Channel Islands occupation

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    BACKGROUND To clarify the nature of the relationship between food deprivation/undernutrition during pre- and postnatal development and cardiovascular disease (CVD) in later life, this study examined the relationship between birth weight (as a marker of prenatal nutrition) and the incidence of hospital admissions for CVD from 1997–2005 amongst 873 Guernsey islanders (born in 1923–1937), 225 of whom had been exposed to food deprivation as children, adolescents or young adults (i.e. postnatal undernutrition) during the 1940–45 German occupation of the Channel Islands, and 648 of whom had left or been evacuated from the islands before the occupation began. METHODS Three sets of Cox regression models were used to investigate (A) the relationship between birth weight and CVD, (B) the relationship between postnatal exposure to the occupation and CVD and (C) any interaction between birth weight, postnatal exposure to the occupation and CVD. These models also tested for any interactions between birth weight and sex, and postnatal exposure to the occupation and parish of residence at birth (as a marker of parish residence during the occupation and related variation in the severity of food deprivation). RESULTS The first set of models (A) found no relationship between birth weight and CVD even after adjustment for potential confounders (hazard ratio (HR) per kg increase in birth weight: 1.12; 95% confidence intervals (CI): 0.70 – 1.78), and there was no significant interaction between birth weight and sex (p = 0.60). The second set of models (B) found a significant relationship between postnatal exposure to the occupation and CVD after adjustment for potential confounders (HR for exposed vs. unexposed group: 2.52; 95% CI: 1.54 – 4.13), as well as a significant interaction between postnatal exposure to the occupation and parish of residence at birth (p = 0.01), such that those born in urban parishes (where food deprivation was worst) had a greater HR for CVD than those born in rural parishes. The third model (C) found no interaction between birth weight and exposure to the occupation (p = 0.43). CONCLUSION These findings suggest that the levels of postnatal undernutrition experienced by children, adolescents and young adults exposed to food deprivation during the 1940–45 occupation of the Channel Islands were a more important determinant of CVD in later life than the levels of prenatal undernutrition experienced in utero prior to the occupatio

    Human prostate sphere-forming cells represent a subset of basal epithelial cells capable of glandular regeneration in vivo.

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    BackgroundProstate stem/progenitor cells function in glandular development and maintenance. They may be targets for tumor initiation, so characterization of these cells may have therapeutic implications. Cells from dissociated tissues that form spheres in vitro often represent stem/progenitor cells. A subset of human prostate cells that form prostaspheres were evaluated for self-renewal and tissue regeneration capability in the present study.MethodsProstaspheres were generated from 59 prostatectomy specimens. Lineage marker expression and TMPRSS-ERG status was determined via immunohistochemistry and fluorescence in situ hybridization (FISH). Subpopulations of prostate epithelial cells were isolated by cell sorting and interrogated for sphere-forming activity. Tissue regeneration potential was assessed by combining sphere-forming cells with rat urogenital sinus mesenchyme (rUGSM) subcutaneously in immunocompromised mice.ResultsProstate tissue specimens were heterogeneous, containing both benign and malignant (Gleason 3-5) glands. TMPRSS-ERG fusion was found in approximately 70% of cancers examined. Prostaspheres developed from single cells at a variable rate (0.5-4%) and could be serially passaged. A basal phenotype (CD44+CD49f+CK5+p63+CK8-AR-PSA-) was observed among sphere-forming cells. Subpopulations of prostate cells expressing tumor-associated calcium signal transducer 2 (Trop2), CD44, and CD49f preferentially formed spheres. In vivo implantation of sphere-forming cells and rUGSM regenerated tubular structures containing discreet basal and luminal layers. The TMPRSS-ERG fusion was absent in prostaspheres derived from fusion-positive tumor tissue, suggesting a survival/growth advantage of benign prostate epithelial cells.ConclusionHuman prostate sphere-forming cells self-renew, have tissue regeneration capability, and represent a subpopulation of basal cells
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