Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102104/1/emboj7601065.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102104/2/emboj7601065-sup-0001.pd

How Distinctive are ADHD and RD? Results of a Double Dissociation Study

The nature of the comorbidity between Attention-Deficit/Hyperactivity Disorder (ADHD) and Reading Disability (RD) was examined using a double dissociation design. Children were between 8 and 12 years of age and entered into four groups: ADHD only (n = 24), ADHD+RD (n = 29), RD only (n = 41) and normal controls (n = 26). In total, 120 children participated in the study; 38 girls and 82 boys. Both ADHD and RD were associated with impairments in inhibition and lexical decision, although inhibition and lexical decision were more severely impaired in RD than in ADHD. Visuospatial working memory deficits were specific to children with only ADHD. It is concluded that there was overlap on lexical decision and to a lesser extent on inhibition between ADHD and RD. In ADHD, impairments were dependent on IQ, which suggest that the overlap in lexical decision and inhibition is different in origin for ADHD and RD. The ADHD only group was specifically characterized by deficits in visuospatial working memory. Hence, no double dissociation between ADHD and RD was found on executive functioning and lexical decision

Contribution of Intrinsic Reactivity of the HIV-1 Envelope Glycoproteins to CD4-Independent Infection and Global Inhibitor Sensitivity

Human immunodeficiency virus (HIV-1) enters cells following sequential activation of the high-potential-energy viral envelope glycoprotein trimer by target cell CD4 and coreceptor. HIV-1 variants differ in their requirements for CD4; viruses that can infect coreceptor-expressing cells that lack CD4 have been generated in the laboratory. These CD4-independent HIV-1 variants are sensitive to neutralization by multiple antibodies that recognize different envelope glycoprotein epitopes. The mechanisms underlying CD4 independence, global sensitivity to neutralization and the association between them are still unclear. By studying HIV-1 variants that differ in requirements for CD4, we investigated the contribution of CD4 binding to virus entry. CD4 engagement exposes the coreceptor-binding site and increases the “intrinsic reactivity” of the envelope glycoproteins; intrinsic reactivity describes the propensity of the envelope glycoproteins to negotiate transitions to lower-energy states upon stimulation. Coreceptor-binding site exposure and increased intrinsic reactivity promote formation/exposure of the HR1 coiled coil on the gp41 transmembrane glycoprotein and allow virus entry upon coreceptor binding. Intrinsic reactivity also dictates the global sensitivity of HIV-1 to perturbations such as exposure to cold and the binding of antibodies and small molecules. Accordingly, CD4 independence of HIV-1 was accompanied by increased susceptibility to inactivation by these factors. We investigated the role of intrinsic reactivity in determining the sensitivity of primary HIV-1 isolates to inhibition. Relative to the more common neutralization-resistant (“Tier 2-like”) viruses, globally sensitive (“Tier 1”) viruses exhibited increased intrinsic reactivity, i.e., were inactivated more efficiently by cold exposure or by a given level of antibody binding to the envelope glycoprotein trimer. Virus sensitivity to neutralization was dictated both by the efficiency of inhibitor/antibody binding to the envelope glycoprotein trimer and by envelope glycoprotein reactivity to the inhibitor/antibody binding event. Quantitative differences in intrinsic reactivity contribute to HIV-1 strain variability in global susceptibility to neutralization and explain the long-observed relationship between increased inhibitor sensitivity and decreased entry requirements for target cell CD4

The Human Sweet Tooth

Humans love the taste of sugar and the word "sweet" is used to describe not only this basic taste quality but also something that is desirable or pleasurable, e.g., la dolce vita. Although sugar or sweetened foods are generally among the most preferred choices, not everyone likes sugar, especially at high concentrations. The focus of my group's research is to understand why some people have a sweet tooth and others do not. We have used genetic and molecular techniques in humans, rats, mice, cats and primates to understand the origins of sweet taste perception. Our studies demonstrate that there are two sweet receptor genes (TAS1R2 and TAS1R3), and alleles of one of the two genes predict the avidity with which some mammals drink sweet solutions. We also find a relationship between sweet and bitter perception. Children who are genetically more sensitive to bitter compounds report that very sweet solutions are more pleasant and they prefer sweet carbonated beverages more than milk, relative to less bitter-sensitive peers. Overall, people differ in their ability to perceive the basic tastes, and particular constellations of genes and experience may drive some people, but not others, toward a caries-inducing sweet diet. Future studies will be designed to understand how a genetic preference for sweet food and drink might contribute to the development of dental caries

General practitioner views about discussing sexual issues with patients with coronary heart disease: a national survey in Ireland

<p>Abstract</p> <p>Background</p> <p>Sexual problems are common among people with coronary heart disease and can adversely affect patients' quality of life. GPs are ideally placed to deal with these problems. Research suggests that GPs are reluctant to address sexual problems but little is known about what currently takes place in practice. The aim of this study was to examine GPs' self-reported behaviour and attitudes to discussing sexual problems with people with coronary heart disease.</p> <p>Method</p> <p>Design: A cross-sectional survey which administered 230 postal questionnaires to a nationally representative, stratified random sample of GPs in the Republic of Ireland. GPs were asked about current practice, knowledge, awareness and confidence in dealing with sexual problems, barriers to addressing sexual problems, and about improving services in this area.</p> <p>Results</p> <p>Responses were available for 61 GPs (27% response rate). Seventy percent of GPs reported that they rarely or never discussed sexual problems with coronary patients. While all GPs believed addressing sexual problems was important, many GPs reported lacking awareness, knowledge and confidence in addressing sexual problems. The main barriers were lack of time, feeling the patient wasn't ready and lack of training in the area. GPs wanted more training and guidelines for practice.</p> <p>Conclusions</p> <p>There is currently no standardised protocol for GPs for dealing with sexual problems among coronary patients. Awareness of these issues appears to be low among GPs. Services could be improved by developing practice guidelines for brief, effective actions or assessments, providing training in the area and improving information resources and support services for referral.</p

Predicting peer-assisted study session attendance

© The Author(s) 2017. Peer-assisted study session attendance is associated with multiple indicators of student success. However, attendance levels are generally low. We applied an extended theory of planned behaviour model, incorporating student role identity, to the prediction of peer-assisted study session attendance. Participants were 254 undergraduate students enrolled in 24 peer-assisted study session supported units. Attitudes, subjective norms and perceived behavioural control each had a significant direct effect on attendance intentions, which had a significant direct effect on attendance. All three predictors also had significant indirect effects on attendance, mediated by intentions. After controlling for intentions, only perceived behavioural control had a significant direct effect on attendance. The model accounted for 61% and 42% of the variance in intentions and attendance, respectively. Student role identity did not improve the predictive utility of the model. Theory of planned behaviour–informed strategies for increasing peer-assisted study session attendance are recommended

Estudo fenotípico e genotípico da resistência aos macrolídeos de "Streptococcus pneumoniae" isolados em hospitais de Porto Alegre - RS

OBJETIVO: O objetivo deste estudo foi determinar a prevalência do S. pneumoniae resistente aos macrolídeos e identificar suas características fenotípicas e genotípicas. MÉTODOS: Amostras de S. pneumoniae isoladas entre maio de 2002 e agosto de 2004, em Porto Alegre (RS), a partir de materiais clínicos coletados de diferentes sítios anatômicos foram analisadas. Para o teste de difusão em ágar foram utilizados discos de eritromicina, claritromicina, azitromicina e clindamicina. As concentrações inibitórias mínimas de eritromicina foram determinadas nos isolados resistentes aos macrolídeos pelo método de diluição em ágar. Os fenótipos dos isolados resistentes aos macrolídeos foram investigados pelo teste de difusão em ágar e a genotipagem pela reação em cadeia da polimerase. RESULTADOS: Foram avaliados 229 isolados de pneumococos, e 12 mostraram-se resistentes aos macrolídeos (5,2%). Entre estes, 9 apresentaram o fenótipo MLSB (75%) e 3 o fenótipo M (25%). A reação em cadeia da polimerase indicou que 8 isolados com o fenótipo MLSB portavam apenas o gene ermB, enquanto que o gene mefE estava presente em todos os 3 isolados com o fenótipo M. Um isolado com o fenótipo MLSB apresentou ambos os genes. CONCLUSÃO: A resistência aos macrolídeos do S. pneumoniae em Porto Alegre permanece baixa, sendo devida principalmente à presença do gene ermB, com expressão do fenótipo MLSB.<br>OBJECTIVE: The aim of this study was to determine the prevalence of macrolide-resistant S. pneumoniae and to identify its phenotypic and genotypic characteristics. METHODS: Strains of S. pneumoniae isolated in the city of Porto Alegre between May 2002 and August 2004 from samples collected from different anatomical sites were analyzed. For the agar diffusion test, disks of erythromycin, clarithromycin, azithromycin and clindamycin were used. The minimum inhibitory concentrations of erythromycin were determined for macrolide-resistant isolates by the agar dilution method. Macrolide-resistant isolates were phenotyped by agar diffusion test and genotyped by polymerase chain reaction. RESULTS: A total of 229 pneumococcal strains were evaluated, 12 (5.2%) of which were macrolide-resistant. Among the 12 resistant strains, 9 (75%) presented the MLSB phenotype, and 3 (25%) presented the M phenotype. Polymerase chain reaction testing indicated that 8 MLSB phenotype isolates harbored the ermB gene only, whereas the mefE gene was present in all 3 M phenotype isolates. One MLSB phenotype isolate presented both genes. CONCLUSION: In Porto Alegre, the S. pneumoniae resistance to macrolides is still low since such resistance is due primarily to the presence of the ermB gene expressing the MLSB phenotype