Browsing by Subject "Membrane Glycoproteins"

Now showing 1 - 3 of 3
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    Active PSF shaping and adaptive optics enable volumetric localization microscopy through brain sections
    (Springer Nature, 2018-08) Mlodzianoski, Michael J.; Cheng-Hathaway, Paul J.; Bemiller, Shane M.; McCray, Tyler J.; Liu, Sheng; Miller, David A.; Lamb, Bruce T.; Landreth, Gary E.; Huang, Fang; Anatomy and Cell Biology, IU School of Medicine
    Application of single-molecule switching nanoscopy (SMSN) beyond the coverslip surface poses substantial challenges due to sample-induced aberrations that distort and blur single-molecule emission patterns. We combined active shaping of point spread functions and efficient adaptive optics to enable robust 3D-SMSN imaging within tissues. This development allowed us to image through 30-μm-thick brain sections to visualize and reconstruct the morphology and the nanoscale details of amyloid-β filaments in a mouse model of Alzheimer's disease.
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    Genetic variant predicts bevacizumab-induced hypertension in ECOG-5103 and ECOG-2100
    (Nature Publishing Group, 2014-09-09) Schneider, B. P.; Li, L.; Shen, F.; Miller, K. D.; Radovich, M.; O'Neill, A.; Gray, R. J.; Lane, D.; Flockhart, D. A.; Jiang, G.; Wang, Z.; Lai, D.; Koller, D.; Pratt, J. H.; Dang, C. T.; Northfelt, D.; Perez, E. A.; Shenkier, T.; Cobleigh, M.; Smith, M. L.; Railey, E.; Partridge, A.; Gralow, J.; Sparano, J.; Davidson, N. E.; Foroud, T.; Sledge, G. W.; Department of Medicine, IU School of Medicine
    Background: Bevacizumab has broad anti-tumour activity, but substantial risk of hypertension. No reliable markers are available for predicting bevacizumab-induced hypertension. Methods: A genome-wide association study (GWAS) was performed in the phase III bevacizumab-based adjuvant breast cancer trial, ECOG-5103, to evaluate for an association between genotypes and hypertension. GWAS was conducted in those who had experienced systolic blood pressure (SBP) >160 mm Hg during therapy using binary analysis and a cumulative dose model for the total exposure of bevacizumab. Common toxicity criteria (CTC) grade 3–5 hypertension was also assessed. Candidate SNP validation was performed in the randomised phase III trial, ECOG-2100. Results: When using the phenotype of SBP>160 mm Hg, the most significant association in SV2C (rs6453204) approached and met genome-wide significance in the binary model (P=6.0 × 10−8
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    TREM2 is associated with increased risk for Alzheimer's disease in African Americans
    (Springer (Biomed Central Ltd.), 2015) Jin, Sheng Chih; Carrasquillo, Minerva M.; Benitez, Bruno A.; Skorupa, Tara; Carrell, David; Patel, Dwani; Lincoln, Sarah; Krishnan, Siddharth; Kachadoorian, Michaela; Reitz, Christiane; Mayeux, Richard; Wingo, Thomas S.; Lah, James J.; Levey, Allan I.; Murrell, Jill; Hendrie, Hugh; Foroud, Tatiana; Graff-Radford, Neill R.; Goate, Alison M.; Cruchaga, Carlos; Ertekin-Taner, Nilüfer; Department of Psychiatry, IU School of Medicine
    BACKGROUND: TREM2 encodes for triggering receptor expressed on myeloid cells 2 and has rare, coding variants that associate with risk for late-onset Alzheimer's disease (LOAD) in Caucasians of European and North-American origin. This study evaluated the role of TREM2 in LOAD risk in African-American (AA) subjects. We performed exonic sequencing and validation in two independent cohorts of >800 subjects. We selected six coding variants (p.R47H, p.R62H, p.D87N, p.E151K, p.W191X, and p.L211P) for case-control analyses in a total of 906 LOAD cases vs. 2,487 controls. RESULTS: We identified significant LOAD risk association with p.L211P (p=0.01, OR=1.27, 95%CI=1.05-1.54) and suggestive association with p.W191X (p=0.08, OR=1.35, 95%CI=0.97-1.87). Conditional analysis suggests that p.L211P, which is in linkage disequilibrium with p.W191X, may be the stronger variant of the two, but does not rule out independent contribution of the latter. TREM2 p.L211P resides within the cytoplasmic domain and p.W191X is a stop-gain mutation within the shorter TREM-2V transcript. The coding variants within the extracellular domain of TREM2 previously shown to confer LOAD risk in Caucasians were extremely rare in our AA cohort and did not associate with LOAD risk. CONCLUSIONS: Our findings suggest that TREM2 coding variants also confer LOAD risk in AA, but implicate variants within different regions of the gene than those identified for Caucasian subjects. These results underscore the importance of investigating different ethnic populations for disease risk variant discovery, which may uncover allelic heterogeneity with potentially diverse mechanisms of action.