Identification of subfunctionalized aggregate-remodeling J-domain proteins in Arabidopsis thaliana.

J-domain proteins (JDPs) are critical components of the cellular protein quality control machinery, playing crucial roles in preventing the formation and, solubilization of cytotoxic protein aggregates. Bacteria, yeast, and plants additionally have large, multimeric heat shock protein 100 (Hsp100)-class disaggregases that resolubilize protein aggregates. JDPs interact with aggregated proteins and specify the aggregate-remodeling activities of Hsp70s and Hsp100s. However, the aggregate-remodeling properties of plant JDPs are not well understood. Here we identify eight orthologs of Sis1 (an evolutionarily conserved Class II JDP of budding yeast) in Arabidopsis thaliana with distinct aggregate-remodeling functionalities. Six of these JDPs associate with heat-induced protein aggregates in vivo and co-localize with Hsp101 at heat-induced protein aggregate centers. Consistent with a role in solubilizing cytotoxic protein aggregates, an atDjB3 mutant had defects in both solubilizing heat-induced aggregates and acquired thermotolerance as compared with wild-type seedlings. Next, we used yeast prions as protein aggregate models to show that the six JDPs have distinct aggregate-remodeling properties. Results presented in this study, as well as findings from phylogenetic analysis, demonstrate that plants harbor multiple, evolutionarily conserved JDPs with capacity to process a variety of protein aggregate conformers induced by heat and other stressors.

Gender disparity in maintenance hemodialysis units in South India: a cross-sectional observational study.

Background: Diseases manifest differently according to gender in many medical specialties. However, sex differences in kidney diseases have not been well explored worldwide, especially in India. These differences could also be attributed to sociocultural factors. Although CKD is more prevalent in women worldwide, most men are initiated on kidney replacement therapy (KRT). This study aimed to examine sex disparities in patients on maintenance hemodialysis. Materials and methods: A cross-sectional observational study was conducted in two maintenance hemodialysis units at the Institute of Nephrourology, a tertiary care referral government center in Bengaluru, India. Demographic characteristics and laboratory parameters were also recorded. Results: In total, 374 adult patients (aged >18 years) were included in the study. Most patients (72.7%) were men. Mean age in men was 46.95 ± 12.65 years, and women was 46.63 ± 13.66 years. There was no significant difference in marital status and the availability of caretakers between the groups. Spouses were the predominant caretakers for both sexes (64% men and 51% women, P = 0.14). Sons cared more for patients with mother than fathers (19.6% vs 8.8%, P = 0.074). Diabetic nephropathy was the most common cause of ESKD in both groups (33.1% vs 31.3%, P = 0.92). Men had a significantly longer duration of HTN and received more HD sessions per week than women. Mean hemoglobin (9.9 ± 1.79 vs 9.46 ± 1.47 g%) and mean serum creatinine (7.76 ± 2.65 vs 6.41 ± 2.27 mg/dl) were higher in men compared to women (P <0.002). Intradialytic complications, such as hypotension and cramps, were significantly more common in women than in men (P = 0.004). Most men (47.1%) were planning a kidney transplant (and were waitlisted) compared with fewer women (43%). There was no significant difference in the average number of hospitalizations per month or HD vintage. Conclusion: Women tend to initiate dialysis later, and a lesser number are waitlisted for kidney transplantation, which might be partly related to varying access to or delivery of health care services. Factors such as lack of education, insufficient identification of and strategies to address cultural obstacles to healthcare, and a shortage of financial means to afford medical care are potentially correctable elements that might explain this discrepancy.

C3 Dominant Collapsing Focal Segmental Glomerulosclerosis - A Report of Two Rare Cases.

Collapsing focal segmental glomerulosclerosis (FSGS) a heterogeneous group of disorders, rather than a single disease entity. Kidney biopsy shows segmental or globally collapsed, sclerotic glomerular capillaries. There is also hypertrophy and hyperplasia of overlying glomerular epithelial cells. Immuno-fluorescence is negative or has non-specific deposits of immunoglobulins and C3. We present two cases of C3 dominant collapsing FSGS. Both the cases were non-responsive to therapy and had a poor outcome. This calls for research to study the role of the complement pathway in the pathogenesis of FSGS.