Antigen recognition by the T cell receptor (TCR) directs the assembly of essential signaling complexes known as SLP-76 (also known as LCP2) microclusters. Here, we show that the interaction of the adhesion and degranulation-promoting adaptor protein (ADAP; also known as FYB1) with SLP-76 enables the formation of persistent microclusters and the stabilization of T cell contacts, promotes integrin-independent adhesion and enables the upregulation of CD69. By analyzing point mutants and using a novel phosphospecific antibody, we show that Y595 is essential for normal ADAP function, that virtually all tyrosine phosphorylation of ADAP is restricted to a Y595-phosphorylated (pY595) pool, and that multivalent interactions between the SLP-76 SH2 domain and its binding sites in ADAP are required to sustain ADAP phosphorylation. Although pY595 ADAP enters SLP-76 microclusters, nonphosphorylated ADAP is enriched in protrusive actin-rich structures. The pre-positioning of ADAP at the contact sites generated by these structures favors the retention of nascent SLP-76 oligomers and their assembly into persistent microclusters. Although ADAP is frequently depicted as an effector of SLP-76, our findings reveal that ADAP acts upstream of SLP-76 to convert labile, Ca 2+-competent microclusters into stable adhesive junctions with enhanced signaling potential.

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Objective In sub-Saharan Africa, 45% of the rural population uses boreholes (BHs). Despite recent gains in improved water access and coverage, parallel use of unimproved sources persists. Periodic infrastructure disrepair contributes to non-exclusive use of BHs. Our study describes functionality of BHs in 2014, 2015, and 2016 in 15 rural towns in the Eastern Region of Ghana sourced from three groundwater quality clusters (high iron, high salinity, and control). We also assess factors affecting cross-sectional and longitudinal functionality using logistic regression. Results BH functionality rates ranged between 81 and 87% and were similar across groundwater quality clusters. Of 51 BHs assessed in all three years, 34 (67%) were consistently functional and only 3 (6%) were consistently broken. There was a shift toward proactive payment for water over the course of the study in the control and high-salinity clusters. Payment mechanism, population served, presence of nearby alternative water sources, and groundwater quality cluster were not significant predictors of cross-sectional or longitudinal BH functionality. However, even in the high iron cluster, where water quality is poor and no structured payment mechanism for water exists, BHs are maintained, showing that they are important community resources.

Background:We studied women enrolled in the Boston Mammography Cohort Study to investigate whether subgroups defined by age, race, or family history of breast cancer experienced differences in trends of screening or diagnostic imaging rates during the COVID-19 lockdown and had slower rebound in trends of these rates during reopening.Methods:We compared trends of monthly breast cancer screening and diagnostic imaging rates over time between the pre-COVID-19, lockdown, and reopening periods and tested for differences in the monthly trend within the same period by age (<50 vs ≥50), race (White vs non-White), and first-degree family history of breast cancer (yes vs no).Results:Overall, we observed a decline in breast cancer screening and diagnostic imaging rates. The monthly trend of breast cancer screening rates for women age ≥50 was 5% higher (p=0.005) in the pre-COVID-19 period but was 19% lower in the reopening phase than that of women aged <50 (p<0.001). White participants had 36% higher monthly trend of breast cancer diagnostic imaging rates than non-White participants (p=0.018).Discussion:The rebound in screening was lower in women age ≥50 and lower in non-White women for diagnostic imaging. Careful attention must be paid as the COVID-19 recovery continues to ensure equitable resumption of care.Funding:The project was supported by the Breast Cancer Research Foundation (RT). Researchers were supported by the University of Louisville CIEHS P30 ES030283 (NCD), K01CA188075 (ETW), T32CA09001 (NCD, MOS, MEB) P30 ES000002 (JH, FL), and NIH/NCI K00 CA212222 (MEB). This manuscript is the responsibility of the authors and does not represent the official views of the National Institutes of Health.