Activation of cell-autonomous defense by the immune cytokine interferon-γ (IFN-γ) is critical to the control of life-threatening infections in humans. IFN-γ induces the expression of hundreds of host proteins in all nucleated cells and tissues, yet many of these proteins remain uncharacterized. We screened 19,050 human genes by CRISPR-Cas9 mutagenesis and identified IFN-γ–induced apolipoprotein L3 (APOL3) as a potent bactericidal agent protecting multiple non–immune barrier cell types against infection. Canonical apolipoproteins typically solubilize mammalian lipids for extracellular transport; APOL3 instead targeted cytosol-invasive bacteria to dissolve their anionic membranes into human-bacterial lipoprotein nanodiscs detected by native mass spectrometry and visualized by single-particle cryo–electron microscopy. Thus, humans have harnessed the detergent-like properties of extracellular apolipoproteins to fashion an intracellular lysin, thereby endowing resident nonimmune cells with a mechanism to achieve sterilizing immunity.

Network theory-based approaches provide valuable insights into the variations in global structural connectivity between different dynamical states of proteins. Our objective is to review network-based analyses to elucidate such variations, especially in the context of subtle conformational changes. We present technical details of the construction and analyses of protein structure networks, encompassing both the non-covalent connectivity and dynamics. We examine the selection of optimal criteria for connectivity based on the physical concept of percolation. We highlight the advantages of using side-chain-based network metrics in contrast to backbone measurements. As an illustrative example, we apply the described network approach to investigate the global conformational changes between the closed and partially open states of the SARS-CoV-2 spike protein. These conformational changes in the spike protein is crucial for coronavirus entry and fusion into human cells. Our analysis reveals global structural reorientations between the two states of the spike protein despite small changes between the two states at the backbone level. We also observe some differences at strategic locations in the structures, correlating with their functions, asserting the advantages of the side-chain network analysis. Finally, we present a view of allostery as a subtle synergistic-global change between the ligand and the receptor, the incorporation of which would enhance drug design strategies.

No abstract

Self-efficacy is central to community health workers' capacity and motivation to deliver evidence-based care; thus, validated measures of self-efficacy are needed to assess the effectiveness of community health worker programs. In this study, we culturally adapted and evaluated the General Self-Efficacy Scale among community health workers in Uganda using multiple methods. We adapted the ten-item General Self-Efficacy Scale through cross-cultural discussions within our multidisciplinary research team, translation from English into Luganda and back-translation into English, and six cognitive interviews with community health workers. We administered the adapted scale in a staged, two-part cross-sectional study, including a total of 147 community health workers. Exploratory factor analysis yielded three factors, which we labeled problem-solving, persistence, and resourcefulness. This three-factor solution had good model fit (standardized root mean square residual = 0.07) and explained 53.4% of the variance. We found evidence of convergent validity, as scores for the total scale were positively correlated with years of experience (r = 0.48; p < .001) and perceived social support (r = 0.39, p < .001). Scores were also higher among those with higher educational attainment in one-way analysis of variance and Bonferroni-corrected post hoc tests [F (2,72) = 9.16, p < .001]. We also found evidence of discriminant validity, as scores for the total scale were not correlated with age (r = − 0.07, p = .55), in agreement with literature showing that general self-efficacy is an age-independent construct. The internal consistency of the adapted scale was within the acceptable range for a pilot study (Cronbach's α = 0.61). This evaluation of a Uganda-adapted General Self-Efficacy Scale demonstrated promising psychometric properties; however, larger studies with repeated measures are warranted to further assess the adapted scale's factor structure, validity, reliability, and stability over time.