Accumulating evidence from murine studies suggests that the RhoA/ROCK pathway plays an important role in the development of autoimmune disorders. We previously demonstrated that ROCK inhibition ameliorates disease in MRL/lpr mice, a spontaneous model of lupus. This study aimed to explore the protective effects of the ROCK inhibitor fasudil in a distinct model of lupus, NZB/W F1 female mice, to assess the broad applicability of ROCK inhibition for the treatment of lupus. NZB/W F1 female mice were administered fasudil continuously in their drinking water starting at 18 or 24 weeks of age up until 44 weeks of age, or remained untreated. Fasudil treatment significantly improved survival and decreased proteinuria, particularly when treatment was started at 18 weeks. There was also a significant decrease in serum anti-dsDNA autoantibody production, glomerular IgG and C3 deposition, and glomerulonephritis. Analysis of the splenic lymphocyte compartment revealed reduced effector/memory CD4(+) T cell and plasma cell numbers in fasudil treated mice while the frequency of other B cell and T cell subsets was unchanged. These results thus indicate that fasudil can ameliorate disease in NZB/W F1 female mice, suggesting that ROCK inhibition might be broadly effective for the treatment of lupus.

Cold stress affects growth and development of rice plants from germination to reproductive stages. Thirty breeding lines/varieties including tolerant and susceptible check varieties were evaluated for cold tolerance at seedling and reproductive stage using artificially induced low temperature situations to understand the genetic relationship among them and to identify promising donors for cold tolerance. Three breeding lines, BR8253-9-3-4-3, IR77497-31-2-3-1and IR2266-42-6-2 demonstrated higher cold tolerance for the seedling stage (LD score <3.0). Molecular analysis revealed 68% genetic similarity among the genotypes. On average 64% of the breeding lines shared common alleles at any given locus ranging from 27% (RM22870) to 97% (RM186). UPGMA dendrogram showed that majority of the breeding lines showing 4-5 degrees of LD were grouped together. Two breeding lines, BR8258-7-1-5-2B2 and BR8258-7-1-5-2B3 having 86% common alleles showed low leaf discoloration (LD: 4) at seedling stage coupled with relatively low reduction in spikelet fertility (45.8% and 48.1%) and grain yield (43.3% and 39.1%). The gene diversity and PIC value revealed that seven SSR loci (RM1282, RM600, RM5349, RM6972, RM5847, RM5911, and RM511) might be the best markers to differentiate between tolerant and susceptible genotypes at reproductive stage. The breeding lines with tolerance to cold stress at the seedling and the reproductive stages identified from this study, and the SSR markers mentioned above could be useful for developing cold tolerance rice. Bangladesh Rice j. 2019, 23(2): 1-15