Isolation and antigenicity evaluation of &#946-lactoglobulin from buffalo milk

Buffalo &#946-lactoglobulin in phosphate buffer (0.02 M, pH6.8) was adsorbed on DEAE-Sepharose Fast Flow gel, and eluted with a linear gradient of NaCl (0-0.5 M) in 0.02 M phosphate buffer, pH 6.8. A furtherpurification was performed on Sephadex G-75 gel by loading a concentrated and dialyzed fraction of samples containing buffalo &#946-lactoglobulin from ion-exchange chromatography, and seperating at a flow rate of 0.15 ml/min in 0.02 M phosphate buffer, pH 6.8. The purity of the isolated buffalo &#946-lactoglobulin was above 90% in comparison to the standard bovine &#946-lactoglobulin by SDS-PAGE and IEF-PAGE. The antigencity of the buffalo &#946-lactoglobulin was evualuted by indirect ELISA, Westernblotting and inhibition ELISA with anti-buffalo and anti-bovine &#946-lactoglobulin rabbit serum. The results showed that buffalo &#946-lactoglobulin could be seperated and purified by anion-exchange chromatography combined with gel filtration chromatography, and with a well-preserved antigenicity

Diverse auto-curriculum is critical for successful real-world multiagent learning systems

Multiagent reinforcement learning (MARL) has achieved a remarkable amount of success in solving various types of video games. A cornerstone of this success is the auto-curriculum framework, which shapes the learning process by continually creating new challenging tasks for agents to adapt to, thereby facilitating the acquisition of new skills. In order to extend MARL methods to real-world domains outside of video games, we envision in this blue sky paper that maintaining a diversity-aware auto-curriculum is critical for successful MARL applications. Specifically, we argue that behavioural diversity is a pivotal, yet under-explored, component for real-world multiagent learning systems, and that significant work remains in understanding how to design a diversity-aware auto-curriculum. We list four open challenges for auto-curriculum techniques, which we believe deserve more attention from this community. Towards validating our vision, we recommend modelling realistic interactive behaviours in autonomous driving as an important test bed, and recommend the SMARTS/ULTRA benchmark

Endogenous pH-responsive nanoparticles with programmable size changes for targeted tumor therapy and imaging applications.

Nanotechnology-based antitumor drug delivery systems, known as nanocarriers, have demonstrated their efficacy in recent years. Typically, the size of the nanocarriers is around 100 nm. It is imperative to achieve an optimum size of these nanocarriers which must be designed uniquely for each type of delivery process. For pH-responsive nanocarriers with programmable size, changes in pH (~6.5 for tumor tissue, ~5.5 for endosomes, and ~5.0 for lysosomes) may serve as an endogenous stimulus improving the safety and therapeutic efficacy of antitumor drugs. This review focuses on current advanced pH-responsive nanocarriers with programmable size changes for anticancer drug delivery. In particular, pH-responsive mechanisms for nanocarrier retention at tumor sites, size reduction for penetrating into tumor parenchyma, escaping from endo/lysosomes, and swelling or disassembly for drug release will be highlighted. Additional trends and challenges of employing these nanocarriers in future clinical applications are also addressed

Ellagic acid, a phenolic compound, exerts anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer

Anti-angiogenesis targeting VEGFR-2 has been considered as an important strategy for cancer therapy. Ellagic acid is a naturally existing polyphenol widely found in fruits and vegetables. It was reported that ellagic acid interfered with some angiogenesis-dependent pathologies. Yet the mechanisms involved were not fully understood. Thus, we analyzed its anti-angiogenesis effects and mechanisms on human breast cancer utilizing in-vitro and in-vivo methodologies. The in-silico analysis was also carried out to further analyze the structure-based interaction between ellagic acid and VEGFR-2. We found that ellagic acid significantly inhibited a series of VEGF-induced angiogenesis processes including proliferation, migration, and tube formation of endothelial cells. Besides, it directly inhibited VEGFR-2 tyrosine kinase activity and its downstream signaling pathways including MAPK and PI3K/Akt in endothelial cells. Ellagic acid also obviously inhibited neo-vessel formation in chick chorioallantoic membrane and sprouts formation of chicken aorta. Breast cancer xenografts study also revealed that ellagic acid significantly inhibited MDA-MB-231 cancer growth and P-VEGFR2 expression. Molecular docking simulation indicated that ellagic acid could form hydrogen bonds and aromatic interactions within the ATP-binding region of the VEGFR-2 kinase unit. Taken together, ellagic acid could exert anti-angiogenesis effects via VEGFR-2 signaling pathway in breast cancer. © 2012 The Author(s).published_or_final_versio

Simultaneous determination of diphenylarsinic and phenylarsinic acids in amended soils by optimized solvent extraction coupled to HPLC-MS/MS

A solvent extraction method coupled to high-performance liquid chromatography with tandem mass spectrometry detection (HPLC-MS/MS) was developed and validated for the simultaneous determination of soil diphenylarsinic acid (DPAA) and phenylarsinic acid (PAA). Several extraction solvents were evaluated with respect to the degree of soil extract-induced matrix effects and the recovery values for DPAA and PAA in the four studied soil matrices. Validation data showed that solvent extraction had a negligible impact on the accurate quantification of DPAA. In contrast, only with disodium hydrogen phosphate extraction did the method give both limited matrix effects (102-107%) with a coefficient of variation 74.03%) were obtained for both analytes. The results show that the proposed solvent extraction method coupled to HPLC-MS/MS analysis can provide accurate and reliable determinations of DPAA and PAA in soil samples. (C) 2015 Elsevier B.V. All rights reserved

Disease-Associated Mutations Prevent GPR56-Collagen III Interaction

GPR56 is a member of the adhesion G protein-coupled receptor (GPCR) family. Mutations in GPR56 cause a devastating human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). Using the N-terminal fragment of GPR56 (GPR56N) as a probe, we have recently demonstrated that collagen III is the ligand of GPR56 in the developing brain. In this report, we discover a new functional domain in GPR56N, the ligand binding domain. This domain contains four disease-associated mutations and two N-glycosylation sites. Our study reveals that although glycosylation is not required for ligand binding, each of the four disease-associated mutations completely abolish the ligand binding ability of GPR56. Our data indicates that these four single missense mutations cause BFPP mostly by abolishing the ability of GPR56 to bind to its ligand, collagen III, in addition to affecting GPR56 protein surface expression as previously shown

Upregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cells

© 2015 Macmillan Publishers Limited. All rights reserved. microRNA-34a (miR-34a) and sirtuin 1 (SirT1) have been extensively studied in tumour biology and longevityaging, but little is known about their functional roles in smooth muscle cell (SMC) differentiation from pluripotent stem cells. Using well-established SMC differentiation models, we have demonstrated that miR-34a has an important role in SMC differentiation from murine and human embryonic stem cells. Surprisingly, deacetylase sirtuin 1 (SirT1), one of the top predicted targets, was positively regulated by miR-34a during SMC differentiation. Mechanistically, we demonstrated that miR-34a promoted differentiating stem cells' arrest at G0G1 phase and observed a significantly decreased incorporation of miR-34a and SirT1 RNA into Ago2-RISC complex upon SMC differentiation. Importantly, we have identified SirT1 as a transcriptional activator in the regulation of SMC gene programme. Finally, our data showed that SirT1 modulated the enrichment of H3K9 tri-methylation around the SMC gene-promoter regions. Taken together, our data reveal a specific regulatory pathway that miR-34a positively regulates its target gene SirT1 in a cellular context-dependent and sequence-specific manner and suggest a functional role for this pathway in SMC differentiation from stem cells in vitro and in vivo

Groundwater Nitrogen Pollution and Assessment of Its Health Risks: A Case Study of a Typical Village in Rural-Urban Continuum, China

Protecting groundwater from nitrogen contamination is an important public-health concern and a major national environmental issue in China. In this study, we monitored water quality in 29 wells from 2009 to 2010 in a village in Shanghai city, whick belong to typical rural-urban continuum in China. The total N and NO3-N exhibited seasonal changes, and there were large fluctuations in NH4-N in residential areas, but without significant seasonal patterns. NO2-N in the water was not stable, but was present at high levels. Total N and NO3-N were significantly lower in residential areas than in agricultural areas. The groundwater quality in most wells belonged to Class III and IV in the Chinese water standard, which defines water that is unsuitable for human consumption. Our health risk assessments showed that NO3-N posed the greatest carcinogenic risk, with risk values ranging from 19×10−6 to 80×10−6, which accounted for more than 90% of the total risk in the study area

Design and rationale of the HCC BRIDGE study in China: a longitudinal, multicenter cohort trial in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>More than 50% of the worldwide cases of hepatocellular carcinoma occur in China, and this malignancy currently represents the country's second leading cause of cancer death in cities and the leading cause in rural areas. Despite recent advances in the control and management of hepatocellular carcinoma within China, this disease remains a major health care issue. The global HCC BRIDGE study, designed to assess patterns of hepatocellular carcinoma therapy use and associated outcomes across real-world clinical practice, has recently been expanded as a national study in China, allowing a detailed analysis of hepatocellular carcinoma in this important country.</p> <p>Methods/Design</p> <p>The global HCC BRIDGE study is a multiregional longitudinal cohort trial including patients newly diagnosed with hepatocellular carcinoma between January 1, 2005, and June 30, 2011, who are receiving treatment for hepatocellular carcinoma via sites in the Asia-Pacific, European, and North American regions. The HCC BRIDGE China national study comprises the portion of the global HCC BRIDGE study conducted within mainland China. Patients will be followed from time of diagnosis of hepatocellular carcinoma (post-January 1, 2005) to time of death or December 31, 2011, whichever comes first. Data will be collected on demographic/clinical characteristics, relevant laboratory values, hepatocellular carcinoma/underlying liver disease treatment, tumor response, adverse events, hospitalizations, and overall survival. The primary study end point is overall survival; secondary end points are disease progression, treatment-limiting adverse events, and treatment failure.</p> <p>Results</p> <p>At the time of writing, 15 sites have selected for participation across all 7 traditional regions of China (North, North-East, East, South, South-West, North-West, and Central). The anticipated study population from the China national study is approximately 9000 patients.</p> <p>Discussion</p> <p>Findings from the HCC BRIDGE China national study, the first geographically representative study of hepatocellular carcinoma in China, will contribute to the understanding of patterns of therapy use and related clinical outcomes and will provide further information on continuing unmet needs for hepatocellular carcinoma throughout this important country.</p