Low major histocompatibility complex class II DQA diversity in the Giant Panda (Ailuropoda melanoleuca)

© 2007 Zhu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Population pharmacokinetics of Amisulpride in Chinese patients with schizophrenia with external validation: the impact of renal function

Introduction: Amisulpride is primarily eliminated via the kidneys. Given the clear influence of renal clearance on plasma concentration, we aimed to explicitly examine the impact of renal function on amisulpride pharmacokinetics (PK) via population PK modelling and Monte Carlo simulations.Method: Plasma concentrations from 921 patients (776 in development and 145 in validation) were utilized.Results: Amisulpride PK could be described by a one-compartment model with linear elimination where estimated glomerular filtration rate, eGFR, had a significant influence on clearance. All PK parameters (estimate, RSE%) were precisely estimated: apparent volume of distribution (645 L, 18%), apparent clearance (60.5 L/h, 2%), absorption rate constant (0.106 h−1, 12%) and coefficient of renal function on clearance (0.817, 10%). No other significant covariate was found. The predictive performance of the model was externally validated. Covariate analysis showed an inverse relationship between eGFR and exposure, where subjects with eGFR= 30 mL/min/1.73 m2 had more than 2-fold increase in AUC, trough and peak concentration. Simulation results further illustrated that, given a dose of 800 mg, plasma concentrations of all patients with renal impairment would exceed 640 ng/mL.Discussion: Our work demonstrated the importance of renal function in amisulpride dose adjustment and provided a quantitative framework to guide individualized dosing for Chinese patients with schizophrenia

Antioxidant Activities of Extract and Fractions from the Hypocotyls of the Mangrove Plant Kandelia candel

The antioxidant activities of 70% acetone extract (70% AE) from the hypocotyls of the mangrove plant Kandelia candel and its fractions of petroleum ether (PF), ethyl acetate (EF), water (WF), and the LF (WF fraction further purified through a Sephadex LH-20 column), were investigated by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and ferric reducing/antioxidant power (FRAP) assays. The results showed that all the extract and fractions possessed potent antioxidant activity. There was a significant linear correlation between the total phenolics concentration and the ferric reducing power or free radical scavenging activity of the extract and fractions. Among the extract and fractions, the LF fraction exhibits the best antioxidant performance. The MALDT-TOF MS and HPLC analyses revealed that the phenolic compounds associated with the antioxidant activity of the LF fraction contains a large number of procyanidins and a small amount of prodelphinidins, and the epicatechin is the main extension unit

A novel class of microRNA-recognition elements that function only within open reading frames.

MicroRNAs (miRNAs) are well known to target 3' untranslated regions (3' UTRs) in mRNAs, thereby silencing gene expression at the post-transcriptional level. Multiple reports have also indicated the ability of miRNAs to target protein-coding sequences (CDS); however, miRNAs have been generally believed to function through similar mechanisms regardless of the locations of their sites of action. Here, we report a class of miRNA-recognition elements (MREs) that function exclusively in CDS regions. Through functional and mechanistic characterization of these 'unusual' MREs, we demonstrate that CDS-targeted miRNAs require extensive base-pairing at the 3' side rather than the 5' seed; cause gene silencing in an Argonaute-dependent but GW182-independent manner; and repress translation by inducing transient ribosome stalling instead of mRNA destabilization. These findings reveal distinct mechanisms and functional consequences of miRNAs that target CDS versus the 3' UTR and suggest that CDS-targeted miRNAs may use a translational quality-control-related mechanism to regulate translation in mammalian cells

Observation of electron-antineutrino disappearance at Daya Bay

The Daya Bay Reactor Neutrino Experiment has measured a non-zero value for the neutrino mixing angle $\theta_{13}$ with a significance of 5.2 standard deviations. Antineutrinos from six 2.9 GW$_{\rm th}$ reactors were detected in six antineutrino detectors deployed in two near (flux-weighted baseline 470 m and 576 m) and one far (1648 m) underground experimental halls. With a 43,000 ton-GW_{\rm th}-day livetime exposure in 55 days, 10416 (80376) electron antineutrino candidates were detected at the far hall (near halls). The ratio of the observed to expected number of antineutrinos at the far hall is $R=0.940\pm 0.011({\rm stat}) \pm 0.004({\rm syst})$. A rate-only analysis finds $\sin^22\theta_{13}=0.092\pm 0.016({\rm stat})\pm0.005({\rm syst})$ in a three-neutrino framework.Comment: 5 figures. Version to appear in Phys. Rev. Let