Causal ALS genes impact the MHC class II antigen presentation pathway.

Mutations in RNA/DNA-binding proteins cause amyotrophic lateral sclerosis (ALS), but the underlying disease mechanisms remain unclear. Here, we report that a set of ALS-associated proteins, namely FUS, EWSR1, TAF15, and MATR3, impact the expression of genes encoding the major histocompatibility complex II (MHC II) antigen presentation pathway. Both subunits of the MHC II heterodimer, HLA-DR, are down-regulated in ALS gene knockouts/knockdown in HeLa and human microglial cells, due to loss of the MHC II transcription factor CIITA. Importantly, hematopoietic progenitor cells (HPCs) derived from human embryonic stem cells bearing the FUSR495X mutation and HPCs derived from C9ORF72 ALS patient induced pluripotent stem cells also exhibit disrupted MHC II expression. Given that HPCs give rise to numerous immune cells, our data raise the possibility that loss of the MHC II pathway results in global failure of the immune system to protect motor neurons from damage that leads to ALS.

Measurement invariance of a household water insecurity metric in Greater Accra, Ghana: Implications for test-retest reliability.

The mitigation of household water insecurity is recognized as an important component of global poverty alleviation, but until recently was difficult to measure. Several new metrics of household water insecurity have been proposed and validated, but few have been field-tested for reliability in diverse contexts. We used confirmatory factor analysis to test the psychometric equivalence of one such metric-the Household Water Insecurity Experiences (HWISE) scale-across two survey waves administered 18 months apart in similar climatic conditions among households in a peri-urban community outside of Accra, Ghana. The HWISE metric was not equivalent across survey waves, which may be attributable to the metric itself, sample size, subtle instrumentation changes, or other unobserved factors. Test-retest reliability may also be difficult to achieve given the dynamic nature of household water use, and we discuss the implications of using household water insecurity metrics as longitudinal measures of well-being in global anti-poverty programs.