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Purpose: We earlier reported that Sestrin2 regulates monocyte activation and atherogenic events through AMPK-mTOR nexus under high-glucose and dyslipidemic conditions. However, the statuses of Sestrins in diabetes and dyslipidemia are not known. We report here on the status of Sestrins and their association with diabetic dyslipidemia and atherosclerosis. Methods: Individuals with normal glucose tolerance (NGT) (n= 46), dyslipidemia (n= 42), and patients with Type 2 diabetes with (n= 41) and without dyslipidemia (n= 40) were recruited from a tertiary diabetes centre, Chennai, India to study the mRNA expression levels of Sestrins (1, 2, and 3) in monocytes by RT-qPCR. Serum levels of Sestrins were measured using ELISA. Atherogenic index of plasma was calculated as log (triglyceride/HDL). Results: mRNA expressions of Sestrin1 and Sestrin3 were significantly reduced in monocytes under dyslipidemic conditions but not in diabetes condition. Interestingly, Sestrin2 mRNA expression was significantly reduced in all disease conditions including dyslipidemia, and diabetes with and without dyslipidemia. Sestrin2 mRNA levels were negatively correlated with glycemic and lipid parameters and plasma atherogenic index. Furthermore, circulatory Sestrin2 was also found to be significantly decreased in dyslipidemia (415.2 ± 44.7 pg/ml), diabetes (375 ± 45 pg/ml), and diabetes with dyslipidemia (319.2 ± 26.3 pg/ml) compared to NGT (706.3 ± 77 pg/ml) and negatively correlated with glycemic, lipid parameters, and plasma atherogenic index. Conclusion: We report for the first time that Sestrins levels are significantly decreased in diabetes and dyslipidemic conditions. More strikingly, Sestrin2 had a strong association with atherogenic risk factors and severity of atherogenic index and we suggest that Sestrin2 may be used as a biomarker for assessing atherogenesis.

Leber congenital amaurosis (LCA) is an inherited retinal dystrophy that causes childhood blindness. Photoreceptors are especially sensitive to an intronic mutation in the cilia-related gene CEP290, which causes missplicing and premature termination, but the basis of this sensitivity is unclear. Here, we generated differentiated photoreceptors in three-dimensional optic cups and retinal pigment epithelium (RPE) from iPSCs with this common CEP290 mutation to investigate disease mechanisms and evaluate candidate therapies. iPSCs differentiated normally into RPE and optic cups, despite abnormal CEP290 splicing and cilia defects. The highest levels of aberrant splicing and cilia defects were observed in optic cups, explaining the retinal-specific manifestation of this CEP290 mutation. Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290, restoring normal cilia-based protein trafficking. These results provide a mechanistic understanding of the retina-specific phenotypes in CEP290 LCA patients and potential strategies for therapeutic intervention.

The present investigation was conducted to assess the suitability of three vegetable oils (sunflower oil, coconut oil and castor oil) as an alternative dietary lipid source for cod liver oil to culture Macrobrachium rosenbergiipost larvae (PLs). The experimental feeds contained 40% protein with separately incorporated three vegetable oils and cod liver oil. The feeding trial was conducted on M. rosenbergiiPL for 60days. In the final day of the experimental period, the survival rate, weight gain, length gain, specific growth rate and protein efficiency ratio of prawns showed no significance (P>0.05) between sunflower oil and cod liver oil incorporated feed fed groups. The coconut oil and castor oil showed lower performance when compared with cod liver oil. The present result showed biochemical accumulation of total protein, amino acids, carbohydrate and lipid in experimental groups. Also there is no significant difference in ash and mineral (Na+and K+) contents. Among the tested diets, the recorded growth rate and biochemical constituents of sunflower oil and cod liver oil incorporated feed fed groups were similar. The present results revealed that the sunflower oil was on par with cod liver oil. Hence, the sunflower oil can be incorporated in feed formulation for M. rosenbergiiPL culture. It can be concluded that the coconut oil and castor oil are not ideal vegetable lipid source with these concentrations which produced lower performance in survival, growth and biochemical compositions of M. rosenbergiiPL.

Background: Closely spaced thiols in proteins that interconvert between the dithiol form and disulfide bonds are called vicinal thiols. These thiols provide a mechanism to regulate protein function. We previously found that thiols in both αIIb and β3 of the αIIbβ3 fibrinogen receptor were required for platelet aggregation. Methods and Results: Using p‐chloromercuribenzene sulfonate (pCMBS) we provide evidence that surface thiols in αIIbβ3 are exposed during platelet activation. Phenylarsine oxide (PAO), a reagent that binds vicinal thiols, inhibits platelet aggregation and labeling of sulfhydryls in both αIIb and β3. For the aggregation and labeling studies, binding of PAO to vicinal thiols was confirmed by reversal of PAO binding with the dithiol reagent 2,3‐Dimercapto‐1‐propanesulfonic acid (DMPS). In contrast, the monothiol β‐mercaptoethanol did not reverse the effects of PAO. Additionally, PAO did not inhibit sulfhydryl labeling of the monothiol protein albumin, confirming the specificity of PAO for vicinal thiols in αIIbβ3. As vicinal thiols represent redox sensitive sites that can be regulated by reducing equivalents from the extracellular or cytoplasmic environment, they are likely to be important in regulating activation of αIIbβ3. Additionally, when the labeled integrin was passed though a lectin column containing wheat germ agglutinin and lentil lectin a substantial amount of non‐labeled αIIbβ3 eluted separately from the labeled receptor. This suggests that two populations of integrin exist on platelets that can be distinguished by thiol labeling. Conclusion: A vicinal thiol‐containing population of αIIbβ3 provides redox sensitive sites for regulation of αIIbβ3.

Fine particle fluorescent aluminous oxide materials like Cr3+-doped α-Al2O3(ruby), MgAl2O4, LaAlO3, Y3Al5O12and Ce3+-doped Y3Al5O12, LaMgAl11O19, CaAl12O19and CeMgAl11O19have been prepared by the combustion of the corresponding metal nitrate-aluminium nitrate-urea/carbohydrazide mixtures at 500°C in less than 5 min. Formation of these Cr3+- and Ce3+-doped aluminous oxides has been confirmed by their characteristic XRD, colour, UV-visible and fluorescence spectra as well as decay time measurements. Ruby (Cr3+/α-Al2O3) powder showed characteristic excitation bands at 406 and 548 nm and emission band at 695 nm with the decay time of 3·6 ms.