A Pilot Study of Demographic and Dopaminergic Genetic Contributions to Weight Change in Kidney Transplant Recipients

Kidney transplant recipients often experience a significant amount of weight gain in the first year post-transplantation. While demographic factors such as age, race, and sex have been associated with weight gain in this population, these factors do not explain all of the variability seen. A number of studies have suggested that genetics also plays a critical role in weight changes. Recently, alterations in the activity of the neurotransmitter dopamine have been associated with weight change, and gene expression studies in kidney transplant recipients have supported this association. The purpose of this pilot study is to first examine the feasibility and methodology, and then to examine the associations of age, race, sex, and genotype for 13 SNPs and 3 VNTRs in 9 dopaminergic pathway genes (ANKK1, DRD2, DRD3, DRD4, SLC6A3/DAT1, MAOA, MAOB, COMT, CPE) for associations with percent weight change at 12 months post-transplantation. Seventy kidney transplant recipients had demographic and clinical data collected as a part of a larger observational study. DNA was extracted from repository buffy coat samples taken at the time of transplant, and genotyped using Taqman and PCR based methods. Three SNPs were independently associated with percent weight change: ANKK1 rs1800497 (r = -0.28, p = 0.05), SLC6A3/DAT1 rs6347 (p = 0.046), and CPE rs1946816 (p = 0.028). Stepwise regression modelling confirmed the combined associations of age (p = 0.0021), DRD4 VNTR 4/5 genotype (p = 0.0074), and SLC6A3/DAT1 rs6347 CC genotype (p = 0.0009) and TT genotype (p = 0.0004) with percent weight change in a smaller sample (n = 35) of these kidney transplant recipients that had complete genotyping. These associations indicate that there may be a genetic, and an age component to weight changes post transplantation.     

Study of PM10, PM2.5, and PM1 levels in during dust storms and local air pollution events in urban and rural sites in Tehran

The aim of this study is to survey the PM₁₀, PM_2.5, and PM₁ concentrations in rural and urban areas in Tehran province during cold, warm and dust storm days from December 22, 2016 to June 5, 2017 using Grimm Model aerosol spectrometer. During the study period, daily PM₁₀, PM_2.5, and PM₁ concentrations ranged from 27.2 to 244.96, 8.4 to 77.9, and 6.5 to 56.8 μg/m³ in urban sites, and 22.8 to 286.4, 6 to 41.1, and 2.1 to 20.2 μg/m³ in rural parts, respectively. Particularly, both daily WHO limits for outdoor PM₁₀ (50.0 μg/m³) and PM_2.5 (25.0 μg/m³) exceeded in 95% and 83% of the outdoor measurements in winter and 82% and 58% in total sampled days in urban site, respectively. The 24-h average PM₁₀ and PM_2.5 concentrations also exceeded by 59% and 18% in winter and by 36% and 14% of all sampling days in rural site, respectively. During the dust storm, the 24-h average PM₁₀, PM_2.5, and PM₁ concentrations were, respectively 4.7, 2, and 1.96 times higher than those in urban site and 2, 1.7, and 1.3 times more than those in rural site in all sampled days.     

Recent advances in polysaccharide bio-based flocculants

Natural polysaccharides, derived from biomass feedstocks, marine resources, and microorganisms, have been attracting considerable attention as benign and environmentally friendly substitutes for synthetic polymeric products. Besides many other applications, these biopolymers are rapidly emerging as viable alternatives to harmful synthetic flocculating agents for the removal of contaminants from water and wastewater. In recent years, a great deal of effort has been devoted to improve the production and performance of polysaccharide bio-based flocculants. In this review, current trends in preparation and chemical modification of polysaccharide bio-based flocculants and their flocculation performance are discussed. Aspects including mechanisms of flocculation, biosynthesis, classification, purification and characterization, chemical modification, the effect of physicochemical factors on flocculating activity, and recent applications of polysaccharide bio-based flocculants are summarized and presented.     

Radiosynthesis and in vivo evaluation of [11C]MOV as a PET imaging agent for COX-2

Radiosynthesis and in vivo evaluation of [¹¹C]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (methoxy analogue of valdecoxib, [¹¹C]MOV), a COX-2 inhibitor, was conducted in rat and baboon. Synthesis of the reference standard MOV (3), and its desmethyl precursor 2 for radiolabeling were performed using 1,2-diphenylethan-1-one as the starting material in five steps with 15% overall yield. Radiosynthesis of [¹¹C]MOV was accomplished in 40?±?10% yield and?>99% radiochemical purity by reacting the precursor 2 in dimethyl formamide (DMF) with [¹¹C]CH₃I followed by removal of the dimethoxytrityl (DMT) protective group using trifluroacetic acid. PET studies in anesthetized baboon showed very low uptake and homogeneous distribution of [¹¹C]MOV in brain. The radioligand underwent rapid metabolism in baboon plasma. MicroPET studies in male Sprague Dawley rats revealed [¹¹C]MOV binding in lower thorax. The tracer binding in rats was partially blocked in heart and duodenum by the administration of 1?mg/kg oral dose of COX-2 inhibitor valdecoxib.     

Ascorbate Transport and Intracellular Concentration in Cerebral Astrocytes

Abstract: Regulation of the initial rate of uptake and steady-state concentration of ascorbate (reduced vitamin C) was investigated in rat cerebral astrocytes. Although these cells did not synthesize vitamin C, they accumulated millimolar concentrations of ascorbate when incubated with medium containing the vitamin at a level (200 µ M ) typical of brain extracellular fluid. Initial rate of [¹⁴C]-ascorbate uptake and intracellular ascorbate concentration were dependent on extracellular Na⁺ and sensitive to the anion transport inhibitor sulfinpyrazone. Comparison of the efflux profiles of ascorbate and 2',7'-bis(carboxyethyl)-5 (or -6)-carboxyfluorescein from astrocytes permeabilized with digitonin localized most intracellular ascorbate to the cytosol. Pretreatment of astrocytes with dibutyryl cyclic AMP (dBcAMP) doubled their initial rate of sulfinpyrazone-sensitive [¹⁴C]ascorbate uptake compared with cells treated with either n -butyric acid or vehicle. dBcAMP also increased steady-state intracellular ascorbate concentration by 39%. The relatively small size of the change in astrocytic ascorbate concentration was explained by the finding that dBcAMP increased the rate of efflux of the vitamin from ascorbate-loaded cells. These results indicate that uptake and efflux pathways are stimulated by cyclic AMP-dependent mechanisms and that they regulate the cytosolic concentration of ascorbate in astrocytes.     

Humor as a Reward Mechanism: Event-Related Potentials in the Healthy and Diseased Brain

Humor processing involves distinct processing stages including incongruity detection, emotional response, and engagement of mesolimbic reward regions. Dysfunctional reward processing and clinical symptoms in response to humor have been previously described in both hypocretin deficient narcolepsy-cataplexy (NC) and in idiopathic Parkinson disease (PD). For NC patients, humor is the strongest trigger for cataplexy, a transient loss of muscle tone, whereas dopamine-deficient PD-patients show blunted emotional responses to humor. To better understand the role of reward system and the various contributions of hypocretinergic and dopaminergic mechanisms to different stages of humor processing we examined the electrophysiological response to humorous and neutral pictures when given as reward feedback in PD, NC and healthy controls. Humor compared to neutral feedback demonstrated modulation of early ERP amplitudes likely corresponding to visual processing stages, with no group differences. At 270 ms post-feedback, conditions showed topographical and amplitudinal differences for frontal and left posterior electrodes, in that humor feedback was absent in PD patients but increased in NC patients. We suggest that this effect relates to a relatively early affective response, reminiscent of increased amygdala response reported in NC patients. Later ERP differences, corresponding to the late positive potential, revealed a lack of sustained activation in PD, likely due to altered dopamine regulation in reward structures in these patients. This research provides new insights into the temporal dynamics and underlying mechanisms of humor detection and appreciation in health and disease.     

RPK1 and TOAD2 are two receptor-like kinases redundantly required for arabidopsis embryonic pattern formation

Although the basic plant body plan is established during embryogenesis, the molecular basis of embryonic patterning remains to be fully understood. We have identified two receptor-like kinases, RECEPTOR-LIKE PROTEIN KINASE1 (RPK1) and TOADSTOOL2 (TOAD2), required for Arabidopsis embryonic pattern formation. Genetic analysis indicates that RPK1 and TOAD2 have overlapping embryonic functions. The zygotic gene dosage of TOAD2 in an rpk1 background is of critical importance, suggesting that signaling mediated by RPK1 and TOAD2 must be above a threshold level for proper embryo development. The localization of RPK1 and TOAD2 translational fusions to GFP coupled with the analysis of cell-type-specific markers indicate that RPK1 and TOAD2 are redundantly required for both pattern formation along the radial axis and differentiation of the basal pole during early embryogenesis. We propose that RPK1 and TOAD2 receive intercellular signals and mediate intracellular responses that are necessary for embryonic pattern formation.