Serum microRNA-33 levels in pre-diabetic and diabetic patients

Molecular Biology Reports - Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and abnormal insulin secretion. MicroRNAs are small, non-coding RNAs that are able to affect...     

Contrast dependence of smooth pursuit eye movements following a saccade to superimposed targets

Dorsal stream areas provide motion information used by the oculomotor system to generate pursuit eye movements. Neurons in these areas saturate at low levels of luminance contrast. We therefore hypothesized that during the early phase of pursuit, eye velocity would exhibit an oculomotor gain function that saturates at low luminance contrast. To test this, we recorded eye movements in two macaques trained to saccade to an aperture in which a pattern of dots moved left or right. Shortly after the end of the saccade, the eyes followed the direction of motion with an oculomotor gain that increased with contrast before saturating. The addition of a second pattern of dots, moving in the opposite direction and superimposed on the first, resulted in a rightward shift of the contrast-dependent oculomotor gain function. The magnitude of this shift increased with the contrast of the second pattern of dots. Motion was nulled when the two patterns were equal in contrast. Next, we varied contrast over time. Contrast differences that disappeared before saccade onset biased post-saccadic eye movements at short latency. Changes in contrast occurring during or after saccade termination did not influence eye movements for approximately 150 ms. Earlier studies found that eye movements can be explained by a vector average computation when both targets are equal in contrast. We suggest that this averaging computation may reflect a special case of divisive normalization, yielding saturating contrast response functions that shift to the right with opposed motion, averaging motions when targets are equated in contrast.     

Eicosanoids from the Rhodophyta: new metabolism in the algae

Red marine algae are shown in this work to be a rich source of eicosanoid-type natural products. This is the first isolation of several of these mammalian arachidonic acid metabolites from any marine or terrestrial plant source (12-HETE, 12-HEPE, 6(E)-LTB4, hepoxilin B3). A few of these represent truly novel substances never previously isolated from nature [12(R), 13(S)-diHETE]. Inherent in these seaweed natural product structures is evidence for a highly evolved lipoxygenase-type metabolism that matches or exceeds the complexity of comparable metabolic routes in mammalian systems. As these compounds are produced by algae in relatively large quantities (0.1–5.0% of crude lipid extracts), these plants could be important commercial resources for these expensive and rare biochemicals. Further, we suggest that this metabolism is important to physiological processes in red algae that are completely unknown at present. For example, it is possible that they act in an exocrine sense to coordinate reproductive events, a hypothesis under current investigation through culture studies.This paper was presented at the mini-symposium Bioactive Compounds from Algae, Y. Shimizu, Convener.     

First report of computational protein–ligand docking to evaluate susceptibility to HIV integrase inhibitors in HIV-infected Iranian patients

BackgroundIran has recently included integrase (INT) inhibitors (INTIs) in the first‐line treatment regimen in human immunodeficiency virus (HIV)-infected patients. However, there is no bioinformatics data to elaborate the impact of resistance-associated mutations (RAMs) and naturally occurring polymorphisms (NOPs) on INTIs treatment outcome in Iranian patients.MethodIn this cross-sectional survey, 850 HIV-1-infected patients enrolled; of them, 78 samples had successful sequencing results for INT gene. Several analyses were performed including docking screening, genotypic resistance, secondary/tertiary structures, post-translational modification (PTM), immune epitopes, etc.ResultThe average docking energy (E value) of different samples with elvitegravir (EVG) and raltegravir (RAL) was more than other INTIs. Phylogenetic tree analysis and Stanford HIV Subtyping program revealed HIV-1 CRF35-AD was the predominant subtype (94.9%) in our cases; in any event, online subtyping tools confirmed A1 as the most frequent subtype. For the first time, CRF-01B and BF were identified as new subtypes in Iran. Decreased CD4 count was associated with several factors: poor or unstable adherence, naïve treatment, and drug user status.ConclusionAs the first bioinformatic report on HIV-integrase from Iran, this study indicates that EVG and RAL are the optimal INTIs in first-line antiretroviral therapy (ART) in Iranian patients. Some conserved motifs and specific amino acids in INT-protein binding sites have characterized that mutation(s) in them may disrupt INT-drugs interaction and cause a significant loss in susceptibility to INTIs. Good adherence, treatment of naïve patients, and monitoring injection drug users are fundamental factors to control HIV infection in Iran effectively.