PIN6 is required for nectary auxin response and short stamen development

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/1/tpj12184-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/2/tpj12184.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/3/tpj12184-sup-0004-FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/4/tpj12184-sup-0003-FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/5/tpj12184-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98417/6/tpj12184-sup-0005-FigS5.pd

Mutation p.R356Q in the Collybistin Phosphoinositide Binding Site Is Associated With Mild Intellectual Disability

The recruitment of inhibitory GABAA receptors to neuronal synapses requires a complex interplay between receptors, neuroligins, the scaffolding protein gephyrin and the GDP-GTP exchange factor collybistin (CB). Collybistin is regulated by protein-protein interactions at the N-terminal SH3 domain, which can bind neuroligins 2/4 and the GABAAR a2 subunit. Collybistin also harbors a RhoGEF domain which mediates interactions with gephyrin and catalyzes GDP-GTP exchange on Cdc42. Lastly, collybistin has a pleckstrin homology (PH) domain, which binds phosphoinositides, such as phosphatidylinositol 3-phosphate (PI3P/PtdIns3P) and phosphatidylinositol 4-monophosphate (PI4P/PtdIns4P). PI3P located in early/sorting endosomes has recently been shown to regulate the postsynaptic clustering of gephyrin and GABAA receptors and consequently the strength of inhibitory synapses in cultured hippocampal neurons. This process is disrupted by mutations in the collybistin gene (ARHGEF9), which cause X-linked intellectual disability (XLID) by a variety of mechanisms converging on disrupted gephyrin and GABAA receptor clustering at central synapses. Here we report a novel missense mutation (chrX:62875607C>T, p.R356Q) in ARHGEF9 that affects one of the two paired arginine residues in the PH domain that were predicted to be vital for binding phosphoinositides. Functional assays revealed that recombinant collybistin CB3SH3-R356Q was deficient in PI3P binding and was not able to translocate EGFP-gephyrin to submembrane microaggregates in an in vitro clustering assay. Expression of the PI3P-binding mutants CB3SH3-R356Q and CB3SH3-R356N/R357N in cultured hippocampal neurones revealed that the mutant proteins did not accumulate at inhibitory synapses, but instead resulted in a clear decrease in the overall number of synaptic gephyrin clusters compared to controls. Molecular dynamics simulations suggest that the p.R356Q substitution influences PI3P binding by altering the range of structural conformations adopted by collybistin. Taken together, these results suggest that the p.R356Q mutation in ARHGEF9 is the underlying cause of XLID in the probands, disrupting gephyrin clustering at inhibitory GABAergic synapses via loss of collybistin PH domain phosphoinositide binding

2017 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1004/thumbnail.jp

Gender Differences in Stigma and HIV-Related Quality of Life People Living with HIV

We hypothesized that HIV-related stigma would be related to poorer HIV-related quality of life (HIV-QOL) in people living with HIV (PLWH), and that this relationship would be stronger in women living with HIV (WLWH) than in men living with HIV (MLWH). 105 PLWH completed an online survey including measures of demographics, HIV-related stigma, and HIV-QOL. Results suggest that higher levels of HIV-stigma were associated with poorer HIV-QOL, and that in some cases, this relationship was stronger for WLWH than for MLWH. It is possible that WLWH have unique HIV-related experiences affecting their quality of life that are not shared by MLWH

Benefit Finding Moderates the Relationship Between HIV-Related Stigma and Psychological Well-Being

We hypothesized that benefit finding would moderate the relationship between HIV-related stigma and psychological well-being in people living with HIV (PLWH). 106 PLWH completed an online survey that included measures of demographics, HIV-related stigma, benefit finding, and psychological well-being (depression, anxiety, anger). Results suggest that higher levels of benefit finding offset the negative effects of HIV-related stigma on anger. However, for individuals who fail to find benefits in their illness diagnosis, experiencing stigma may be associated with increased levels of anger

Stigma, Medication Concerns, and Medication Adherence in People Living With HIV

We hypothesized that higher levels of felt or enacted stigma would be related to poorer medication adherence, and that this relationship would be mediated by indicators of HIVrelated quality of life (HIV-QOL) including medication concerns, disclosure concerns, and perceptions of health provider treatment. 98 people living with HIV (PLWH) who were all currently taking ART medications completed an online survey that included measures of demographics, HIV-related stigma, medication, and HIV-QOL. Results suggested that concerns about medication accounted for the relationship between enacted HIV-related stigma and medication adherence