DIAPH3 condensates formed by liquid-liquid phase separation act as a regulatory hub for stress-induced actin cytoskeleton remodeling.

Membraneless condensates, such as stress granules (SGs) and processing bodies (P-bodies), have attracted wide attention due to their unique feature of rapid response to stress without first requiring nuclear feedback. In this study, we identify diaphanous-related formin 3 (DIAPH3), an actin nucleator, as a scaffold protein to initiate liquid-liquid phase separation (LLPS) and form abundant cytosolic phase-separated DIAPH3 granules (D-granules) in mammalian cells such as HeLa, HEK293, and fibroblasts under various stress conditions. Neither mRNAs nor known stress-associated condensate markers, such as G3BP1, G3BP2, and TIA1 for SGs and DCP1A for P-bodies, are detected in D-granules. Using overexpression and knockout of DIAPH3, pharmacological interventions, and optogenetics, we further demonstrate that stress-induced D-granules spatially sequester DIAPH3 within the condensation to inhibit the assembly of actin filaments in filopodia. This study reveals that D-granules formed by LLPS act as a regulatory hub for actin cytoskeletal remodeling in response to stress.

Toxicity studies of nonylphenol and octylphenol: hormonal, hematological and biochemical effects in Clarias gariepinus.

Among the numerous chemicals discharged into aquatic ecosystems, nonylphenol (NP) and octylphenol (OP) have been shown to have a potent effect on the endocrine system of fish; this issue has been clearly dealt with in several studies. The objective of this study was to assess and compare the general toxicity of these estrogenic chemicals individually on Clarias gariepinus. Fish were exposed to different concentrations of both NP and OP (250, 500, 750 and 1000 µg l(-1) ) under semi-static conditions for a period of 7 days. The adverse effect was evaluated with use of blood cell counting, hemoglobin (Hb), hematocrit (HCT), hematimetric indices, bilirubin, protein, glucose, serum transaminases, serum phosphatases, lactate dehydrogenase and cortisol. The results showed a clear indication of anemia, increases in leukocyte count and bilirubin content and a reduction in plasma protein levels with higher concentrations of both the toxicants compared with controls. Furthermore, with all the concentrations the inevitable increase in serum cortisol and plasma glucose showed primary and secondary stress responses. Moreover, probable tissue damage gave rise to a series of fluctuations of enzyme levels at lower concentrations, but a decrease with higher concentrations showed the severity of the effect. Depending on the parameters examined, OP had a relatively greater effect than NP. Overall, these two chemicals seemingly affected hematology and the activity of some enzymes, leading to serious impairment of the metabolism and physiology of C. gariepinus.

Toxicological effects of arsenate exposure on hematological, biochemical and liver transaminases activity in an Indian major carp, Catla catla.

The impact of acute and sublethal toxicity of arsenate on hematological, biochemical and enzymological parameters of an Indian major carp Catla catla were estimated. The median lethal concentration of sodium arsenate to the fish Catla catla for 96h was found to be 43.78 mg/L. During acute treatment (43.78 mg/L), hemoglobin (Hb), hematocrit (Ht), red blood cell count (RBC), white blood cell count (WBC), plasma glucose, plasma protein, liver aspartate and alanine aminotransferase (AST and ALT) levels decreased, whereas corpuscular indices like mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC) increased in arsenate treated fish. In sublethal treatment (4.378 mg/L), Hb, Ht, RBC, plasma protein levels decreased while MCHC and plasma glucose levels increased throughout the exposure period. A biphasic trend was noticed in WBC, MCV, MCH, liver AST and ALT levels. The alterations of these parameters can be effectively used as a rapid method to assess health of fish exposed to arsenate in the aquatic environment.