The role of the cysteine-rich region of the β2 integrin subunit in the leukocyte function-associated antigen-1 (LFA-1, αLβ2, CD11a/CD18) heterodimer formation and ligand binding

The cysteine-rich region (CRR) of the β2 integrin subunit was replaced by that of β1 to give the chimera β2NV1. β2NV1 can combine with αL to form a variant leukocyte-function-associated antigen (LFA)-1 on COS cell surface, suggesting that the specificity of the β2 interaction with αL does not lie in the CRR. Unlike those expressing wild-type LFA-1, COS cells expressing αLβ2NV1 are constitutively active in intercellular adhesion molecule (ICAM)-1 adhesion. These results suggest that activation of LFA-1 involves the release of an intramolecular constraint, which is maintained, in part, by the authentic β2 CRR.     

Colorectal Cancers Mimic Structural Organization of Normal Colonic Crypts

Colonic crypts are stereotypical structures with distinct stem cell, proliferating, and differentiating compartments. Colorectal cancers derive from colonic crypt epithelia but, in contrast, form morphologically disarrayed glands. In this study, we investigated to which extent colorectal cancers phenocopy colonic crypt architecture and thus preserve structural organization of the normal intestinal epithelium. A subset of colon cancers showed crypt-like compartments with high WNT activity and nuclear β-Catenin at the leading tumor edge, adjacent proliferation, and enhanced Cytokeratin 20 expression in most differentiated tumor epithelia of the tumor center. This architecture strongly depended on growth conditions, and was fully reproducible in mouse xenografts of cultured and primary colon cancer cells. Full crypt-like organization was associated with low tumor grade and was an independent prognostic marker of better survival in a collection of 221 colorectal cancers. Our findings suggest that full activation of preserved intestinal morphogenetic programs in colon cancer requires in vivo growth environments. Furthermore, crypt-like architecture was linked with less aggressive tumor biology, and may be useful to improve current colon cancer grading schemes.     

Reducing HIV Risk among Transgender Women in Thailand: A Quasi-Experimental Evaluation of the Sisters Program

Transgender women are particularly at risk of HIV infection, but little evidence exists on effective HIV prevention strategies with this population. We evaluated whether Sisters, a peer-led program for transgender women, could reduce HIV risks in Pattaya, Thailand. The study used time-location sampling to recruit 308 transgender women in Pattaya into a behavioral survey in 2011. Coarsened exact matching was used to create statistically equivalent groups of program participants and non-participants, based on factors influencing likelihood of program participation. Using multivariable logistic regression, we estimated effects of any program participation and participation by delivery channel on: condom use at last sex; consistent condom and condom/water-based lubricant use in the past 3 months with commercial, casual, and regular partners; and receipt of HIV testing in the past 6 months. Program coverage reached 75% of the population. In a matched sub-sample (n = 238), participation in outreach was associated with consistent condom/water-based lubricant use with commercial partners (AOR 3.22, 95% CI 1.64–6.31). Attendance at the Sisters drop-in center was associated with receiving an HIV test (AOR 2.58, 95% CI 1.47–4.52). Dedicated transgender-friendly programs are effective at reducing HIV risks and require expansion to better serve this key population and improve HIV prevention strategies.