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especially lower serum levels of asparagine and serotonin, are associated with later diagnoses of alcohol-related diseases, even after adjustment for the baseline level of alcohol use.C4 crops of agricultural importance all belong to the NADP-malic enzyme (ME) subtype, and this subtype has been the template for C4 introductions into C3 crops, like rice, to improve their productivity. However, the ATP cost for the C4 cycle in both NADP-ME and NAD-ME subtypes accounts for > 40% of the total ATP requirement for CO2 assimilation. These high ATP costs, and the associated need for intense cyclic electron transport and low intrinsic quantum yield Φ CO 2 , are major constraints in realizing strong improvements of canopy photosynthesis and crop productivity. Based on mathematical modelling, we propose a C4 ideotype that utilizes low chloroplastic ATP requirements present in the nondomesticated phosphoenolpyruvate carboxykinase (PEP-CK) subtype. CHIR-99021 price The ideotype is a mixed form of NAD(P)-ME and PEP-CK types, requires no cyclic electron transport under low irradiances, and its theoretical Φ CO 2 is c. 25% higher than that of a C4 crop type. Its cell-type-specific ATP and NADPH requirements can be fulfilled by local energy production. The ideotype is projected to have c. 10% yield advantage over NADP-ME-type crops and > 50% advantage over C3 counterparts. The ideotype provides a unique (theoretical) case where Φ CO 2 could be improved, thereby paving a new avenue for improving photosynthesis in both C3 and C4 crops.
Long noncoding RNA (lncRNA) have been implicated in the etiology of alcohol use. Since lncRNA provide another layer of complexity to the transcriptome, assessing their expression in the brain is the first critical step toward understanding lncRNA functions in alcohol use and addiction. Thus, we sought to profile lncRNA expression in the nucleus accumbens (NAc) in a large postmortem alcohol brain sample.
LncRNA and protein-coding gene (PCG) expressions in the NAc from 41 subjects with alcohol dependence (AD) and 41 controls were assessed via a regression model. Weighted gene coexpression network analysis was used to identify lncRNA and PCG networks (i.e., modules) significantly correlated with AD. Within the significant modules, key network genes (i.e., hubs) were also identified. The lncRNA and PCG hubs were correlated via Pearson correlations to elucidate the potential biological functions of lncRNA. The lncRNA and PCG hubs were further integrated with GWAS data to identify expression quantitative trait ions for the lncRNA, and our genetic (cis-eQTL) analysis provides novel insights into the etiological mechanisms of AD.
Embryonic exposure to ethanol (EtOH) produces marked disturbances in neuronal development and alcohol-related behaviors, with low-moderate EtOH doses stimulating neurogenesis without producing apoptosis and high doses having major cytotoxic effects while causing gross morphological abnormalities. With the pro-inflammatory chemokine system, Cxcl12, and its main receptor Cxcr4, known to promote processes of neurogenesis, we examined here this neuroimmune system in the embryonic hypothalamus to test directly if it mediates the stimulatory effects low-moderate EtOH doses have on neuronal development.
We used the zebrafish (Danio rerio) model, which develops externally and allows one to investigate the developing brain in vivo with precise control of dose and timing of EtOH delivery in the absence of maternal influence. Zebrafish were exposed to low-moderate EtOH doses (0.1, 0.25, 0.5% v/v), specifically during a period of peak hypothalamic development from 22 to 24hours postfertilization, and in some tests weivation of this chemokine system, likely due to autocrine signaling of Cxcl12a at its Cxcr4b receptor within the neurons.
These results provide clear evidence that EtOH's stimulatory effects at low-moderate doses on the number of hypothalamic neurons early in development are mediated, in part, by increased transcription and intracellular activation of this chemokine system, likely due to autocrine signaling of Cxcl12a at its Cxcr4b receptor within the neurons.
Achievement of treatment targets among individuals with diabetes remains suboptimal in many parts of the globe. We aimed to assess changes in diabetes prevalence and achievement of diabetes care goals in South Asia using two consecutive cross-sectional population-based surveys.
Two representative samples of South Asian adults were recruited using identical methods from Chennai, Delhi, and Karachi in 2010-11 (n=16,288; response rate-94.7%) and 2015-16 (n=14,587; response rate-94.0%) through the Center for Cardio-metabolic Risk Reduction in South Asia (CARRS) Study. Quality of care goals were defined as HbA
<53mmol/mol (7.0%), blood pressure (BP) control <140/90mmHg, lipid control LDL cholesterol <2.56mmol/l (100mg/dl), and self-reported non-smoking.
Weighted prevalence of self-reported diabetes increased by 9.0% [13% (95%CI 13-14) to 15% (14-15)] while that of newly diagnosed diabetes decreased by 16% [6.1% (5.7-6.6) to 5.1% (4.6-5.6)]. There were improvements in achieving glycaemic (25% to 30%, p=0.002) and lipid (34% to 45%, p<0.001) goals, but no notable improvements in BP control or smoking status. The proportion of individuals with self-reported diabetes meeting more than one target also increased.
Diabetes prevalence continues to grow among urban South Asians and large gaps still exist in the attainment of treatment targets. Concerted policy, systemic, clinical and individual efforts are needed to close these care gaps.
Diabetes prevalence continues to grow among urban South Asians and large gaps still exist in the attainment of treatment targets. Concerted policy, systemic, clinical and individual efforts are needed to close these care gaps.Prostate-specific membrane antigen (PSMA)-targeted imaging and therapy of prostate cancer using theranostic pairs is rapidly changing clinical practice. To facilitate clinical trials, fully automated procedures for the radiosyntheses of [68 Ga]Ga-PSMA-11 and [177 Lu]Lu-PSMA-617 were developed from commercially available precursors using the cassette based iPHASE MultiSyn module. Formulated and sterile radiopharmaceuticals were obtained in 76 ± 3% (n = 20) and 91 ± 4% (n = 15) radiochemical yields after 17 and 20 min, respectively. Radiochemical purity was always >95% and molar activities exceeded 792 ± 100 and 88 ± 6 GBq/μmol, respectively. Quality control showed conformity with all relevant release criteria and radiopharmaceuticals were used in the clinic.
