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Research shows that racial discrimination results in adverse behavioral health outcomes for African American young adults, including risk for depression, anxiety, and substance use. Although high levels of mindfulness have been shown to reduce risk for such health outcomes, it is unknown whether mindfulness can reduce risk as a consequence of racial discrimination, particularly among African Americans. Three-hundred and eighty-eight African American young adults between the ages of 18–24 (M=20.6, 62% female) completed measures assessing past year experiences of racial discrimination, depressive symptoms, anxiety symptoms, alcohol use, and trait mindfulness. A positive correlation was found between racial discrimination and the behavioral health outcomes, as well as a negative correlation between mindfulness and the behavioral health outcomes. Moreover, mindfulness was found to significantly moderate the effect of racial discrimination on mood symptoms. Although mindfulness was found to lessen the effect of racial discrimination on alcohol use, this difference was not statistically significant. In line with previous literature, racial discrimination was shown to have a negative impact on behavioral health outcomes among African Americans. Moreover, our findings provide support for the buffering effect of mindfulness on mood symptoms as a consequence discrimination. This suggests that increasing mindfulness may be an effective strategy to include in interventions targeting improvement in mood symptoms for African American young adults. However, alternative strategies may be more appropriate to address outcomes, such as alcohol use, as a consequence of racial discrimination.

Outer membrane proteins (OMPs) in Gram-negative bacteria are essential for a number of cellular functions including nutrient transport and drug efflux. Escherichia coli BamA is an essential component of the OMP β-barrel assembly machinery and a potential novel antibacterial target that has been proposed to undergo large (~15 Å) conformational changes. Here, we explored methods to isolate anti-BamA monoclonal antibodies (mAbs) that might alter the function of this OMP and ultimately lead to bacterial growth inhibition. We first optimized traditional immunization approaches but failed to identify mAbs that altered cell growth after screening >3000 hybridomas. We then developed a “targeted boost-and-sort” strategy that combines bacterial cell immunizations, purified BamA protein boosts, and single hybridoma cell sorting using amphipol-reconstituted BamA antigen. This unique workflow improves the discovery efficiency of FACS + mAbs by >600-fold and enabled the identification of rare anti-BamA mAbs with bacterial growth inhibitory activity in the presence of a truncated lipopolysaccharide layer. These mAbs represent novel tools for dissecting the BamA-mediated mechanism of β-barrel folding and our workflow establishes a new template for the efficient discovery of novel mAbs against other highly dynamic membrane proteins.

We previously reported that a (CTG)n expansion causes spinocerebellar ataxia type 8 (SCA8), a slowly progressive ataxia with reduced penetrance. We now report a transgenic mouse model in which the full-length human SCA8 mutation is transcribed using its endogenous promoter. (CTG)116 expansion, but not (CTG)11 control lines, develop a progressive neurological phenotype with in vivo imaging showing reduced cerebellar-cortical inhibition. 1C2-positive intranuclear inclusions in cerebellar Purkinje and brainstem neurons in SCA8 expansion mice and human SCA8 autopsy tissue result from translation of a polyglutamine protein, encoded on a previously unidentified antiparallel transcript (ataxin 8, ATXN8) spanning the repeat in the CAG direction. The neurological phenotype in SCA8 BAC expansion but not BAC control lines demonstrates the pathogenicity of the (CTG-CAG)n expansion. Moreover, the expression of noncoding (CUG)n expansion transcripts (ataxin 8 opposite strand, ATXN8OS) and the discovery of intranuclear polyglutamine inclusions suggests SCA8 pathogenesis involves toxic gain-of-function mechanisms at both the protein and RNA levels.

We have discovered that beta-III spectrin (SPTBN2) mutations cause spinocerebellar ataxia type 5 (SCA5) in an 11-generation American kindred descended from President Lincoln's grandparents and two additional families. Two families have separate in-frame deletions of 39 and 15 bp, and a third family has a mutation in the actin/ARP1 binding region. Beta-III spectrin is highly expressed in Purkinje cells and has been shown to stabilize the glutamate transporter EAAT4 at the surface of the plasma membrane. We found marked differences in EAAT4 and GluRdelta2 by protein blot and cell fractionation in SCA5 autopsy tissue. Cell culture studies demonstrate that wild-type but not mutant beta-III spectrin stabilizes EAAT4 at the plasma membrane. Spectrin mutations are a previously unknown cause of ataxia and neurodegenerative disease that affect membrane proteins involved in glutamate signaling.

The hypothesis tested is whether lesbianism implies psychopathology. The MMPI was given to 26 nonpatient lesbians who were professionally employed full time, and the results were compared to those for a group of 29 similarly employed heterosexual women. With the exception of the Sc scale, no difference was found on the clinical scales. The lesbian group achieved a significantly higher elevation than the nonlesbians on the Mf and Sc scales. Further analysis of the data on the Sc subscales indicated no difference on the pathological part of the scale, but rather a difference in degree of social alienation. Analysis of the data according to a second variable, living status, found significant differences and has important implications for future studies of the lesbian population. Single women, regardless of sexual orientation, scored significantly higher on scales K and Pa and on the Pa subscale naivete. A significant interaction between sexual orientation and living status was achieved on one scale, the F scale.