Cytokines and Production of Aberrantly O-Glycosylated IgA1, the Main Autoantigen in IgA Nephropathy.

Immunoglobulin A (IgA) nephropathy is the most common primary glomerulonephritis worldwide, with no disease-specific treatment and up to 40% of patients progressing to kidney failure. IgA nephropathy (IgAN), characterized by IgA1-containing immunodeposits in the glomeruli, is considered to be an autoimmune disease in which the kidneys are injured as innocent bystanders. Glomerular immunodeposits are thought to originate from the circulating immune complexes that contain aberrantly O-glycosylated IgA1, the main autoantigen in IgAN, bound by IgG autoantibodies. A common clinical manifestation associated with IgAN includes synpharyngitic hematuria at disease onset or during disease activity. This observation suggests a connection of disease pathogenesis with an activated mucosal immune system of the upper-respiratory and/or gastrointestinal tract and IgA1 glycosylation. In fact, some cytokines can enhance production of aberrantly O-glycosylated IgA1. This process involves abnormal cytokine signaling in IgA1-producing cells from patients with IgAN. In this article, we present our view of pathogenesis of IgAN and review how some cytokines can contribute to the disease process by enhancing production of aberrantly glycosylated IgA1. We also review current clinical trials of IgAN based on cytokine-targeting therapeutic approaches.

Drought-Induced Root Pressure in Sorghum bicolor.

Root pressure, also manifested as profusive sap flowing from cut stems, is a phenomenon in some species that has perplexed biologists for much of the last century. It is associated with increased crop production under drought, but its function and regulation remain largely unknown. In this study, we investigated the initiation, mechanisms, and possible adaptive function of root pressure in six genotypes of Sorghum bicolor during a drought experiment in the greenhouse. We observed that root pressure was induced in plants exposed to drought followed by re-watering but possibly inhibited by 100% re-watering in some genotypes. We found that root pressure in drought stressed and re-watered plants was associated with greater ratio of fine: coarse root length and shoot biomass production, indicating a possible role of root allocation in creating root pressure and adaptive benefit of root pressure for shoot biomass production. Using RNA-Seq, we identified gene transcripts that were up- and down-regulated in plants with root pressure expression, focusing on genes for aquaporins, membrane transporters, and ATPases that could regulate inter- and intra-cellular transport of water and ions to generate positive xylem pressure in root tissue.

Survey of the Health of Urban Residents: a Community-Driven Assessment of Conditions Salient to the Health of Historically Excluded Populations in the USA.

BACKGROUND: Data from the Survey of the Health of Urban Residents (SHUR) identified connections between police brutality and medical mistrust, generating significant media, policy, and research attention. Amidst intersecting crises of COVID-19, racism, and police brutality, this report describes survey development and data collection procedures for the SHUR. BASIC PROCEDURES: We conducted focus groups with Black men, Latinxs, and immigrants in Allentown, Pennsylvania. Findings were used to develop and refine measures of conditions salient to the health of urban residents across the country. Quota sampling was employed; oversampling people of color and persons whose usual source of care was not a doctor's office. MAIN FINDINGS: Non-Hispanic Whites made up just under two thirds of the sample (63.65%, n = 2793). Black/African American respondents accounted for 14.2% of the sample (n = 623), while 11.62% (n = 510) were Latinx. Only 43.46% of respondents reported a doctor's office as their usual source of care. Novel measures of population-specific stressors include a range of negative encounters with the police, frequency of these encounters, and respondents' assessments of whether the encounters were necessary. SHUR assessed the likelihood of calling the police if there is a problem, worries about incarceration, and cause-specific stressors such as race-related impression management. PRINCIPAL CONCLUSIONS: SHUR (n = 4389) is a useful resource for researchers seeking to address the health implications of experiences not frequently measured by national health surveillance surveys. It includes respondents' zip codes, presenting the opportunity to connect these data with zip code-level health system, social and economic characteristics that shape health beyond individual factors.