1.Identification of Residues Controlling Restriction versus Enhancing Activities of IFITM Proteins on Entry of Human Coronaviruses.
Zhao X;Sehgal M;Hou Z;Cheng J;Shu S;Wu S;Guo F;Le Marchand SJ;Lin H;Chang J;Guo JT J Virol. 2018 Feb 26;92(6). pii: e01535-17. doi: 10.1128/JVI.01535-17. Print 2018 Mar 15.
Interferon-induced transmembrane proteins (IFITMs) are restriction factors that inhibit the infectious entry of many enveloped RNA viruses. However, we demonstrated previously that human IFITM2 and IFITM3 are essential host factors facilitating the entry of human coronavirus (HCoV) OC43. In a continuing effort to decipher the molecular mechanism underlying IFITM differential modulation of HCoV entry, we investigated the roles of structural motifs important for IFITM protein posttranslational modifications, intracellular trafficking, and oligomerization in modulating the entry of five HCoVs. We found that three distinct mutations in IFITM1 or IFITM3 converted the host restriction factors to enhance entry driven by the spike proteins of severe acute respiratory syndrome coronavirus (SARS-CoV) and/or Middle East respiratory syndrome coronavirus (MERS-CoV). First, replacement of IFITM3 tyrosine 20 with either alanine or aspartic acid to mimic unphosphorylated or phosphorylated IFITM3 reduced its activity to inhibit the entry of HCoV-NL63 and -229E but enhanced the entry of SARS-CoV and MERS-CoV. Second, replacement of IFITM3 tyrosine 99 with either alanine or aspartic acid reduced its activity to inhibit the entry of HCoV-NL63 and SARS-CoV but promoted the entry of MERS-CoV.
2.Short exposure to low concentrations of alcohol during embryonic development has only subtle and strain- dependent effect on the levels of five amino acid neurotransmitters in zebrafish.
Mahabir S;Chatterjee D;Gerlai R Neurotoxicol Teratol. 2018 Jul - Aug;68:91-96. doi: 10.1016/j.ntt.2018.05.005. Epub 2018 Jun 7.
The zebrafish has been successfully employed to model and study the effects of embryonic alcohol exposure. Short exposure to low alcohol concentrations during embryonic development has been shown to significantly disrupt social behavior as well as the dopaminergic and serotoninergic systems in zebrafish. However, analysis of potential effects of embryonic alcohol exposure on other amino acid neurotransmitter systems has not been performed. Here we analyzed neurochemicals obtained from adult AB and TU strain zebrafish that were immersed in 0.00% (control), 0.25%, 0.50%, 0.75% or 1.00% alcohol solution (vol/vol%) at 24 h post-fertilization for 2 h. From whole brain extracts, we quantified glutamate, aspartate, glycine, taurine and GABA levels using high performance liquid chromatography (HPLC). We found embryonic alcohol exposure not to have any significant effect on the levels of glutamate, aspartate, glycine and GABA in both AB and TU zebrafish. AB zebrafish showed a significant elevation of taurine levels, but only in the highest alcohol dose group compared to control. These results, albeit mainly negative, together with prior findings suggest that behavioral abnormalities resulting from embryonic alcohol exposure described before for AB zebrafish may primarily be due to altered dopaminergic and serotoninergic mechanisms.
3.Anti-Diabetic Effects of
Moezi L;Arshadi SS;Motazedian T;Seradj SH;Dehghani F Iran J Pharm Res. 2018 Winter;17(1):353-364.
Diabetes mellitus is a group of metabolic disorders characterized by elevated blood sugar and abnormalities in insulin secretion and action. There are many anti-diabetic plants, which might supply useful sources for developing new medicines that can be used in treatment of diabetes mellitus. The primary objective of the present investigation is to evaluate the anti-diabetic properties of the aerial parts of ;Amygdalus lycioides; in streptozocin-induced diabetic rats. Sixty rats were divided into 6 groups: streptozocin-induced diabetic control, insulin-treated diabetic group, and four ;Amygdalus lycioides;-treated diabetic groups (125, 250, 500, and 1000 mg/kg/day). After 2 weeks of plant extract administration, the effects of extracts on blood glucose, body weight, BUN, creatinine, total cholesterol, LDL, HDL, triglyceride, total protein, Na, K, and plasma enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase) were analyzed. The pancreas of rats was also stained for stereological studies. Phytochemical evaluation of this extract showed the presence of flavonoids and tannins compounds. Glucose serum levels and glucose tolerance test showed a decrease in treatment with ;Amygdalus lycioides; (1000 mg/kg).
