IVSPlat 1.0: an integrated virtual screening platform with a molecular graphical interface

<p>Abstract</p> <p>Background</p> <p>The virtual screening (VS) of lead compounds using molecular docking and pharmacophore detection is now an important tool in drug discovery. VS tasks typically require a combination of several software tools and a molecular graphics system. Thus, the integration of all the requisite tools in a single operating environment could reduce the complexity of running VS experiments. However, only a few freely available integrated software platforms have been developed.</p> <p>Results</p> <p>A free open-source platform, IVSPlat 1.0, was developed in this study for the management and automation of VS tasks. We integrated several VS-related programs into a molecular graphics system to provide a comprehensive platform for the solution of VS tasks based on molecular docking, pharmacophore detection, and a combination of both methods. This tool can be used to visualize intermediate and final results of the VS execution, while also providing a clustering tool for the analysis of VS results. A case study was conducted to demonstrate the applicability of this platform.</p> <p>Conclusions</p> <p>IVSPlat 1.0 provides a plug-in-based solution for the management, automation, and visualization of VS tasks. IVSPlat 1.0 is an open framework that allows the integration of extra software to extend its functionality and modified versions can be freely distributed. The open source code and documentation are available at <url>http://kyc.nenu.edu.cn/IVSPlat/.</url></p

Genetic Structure of the Tree Peony (Paeonia rockii) and the Qinling Mountains as a Geographic Barrier Driving the Fragmentation of a Large Population

Tree peonies are great ornamental plants associated with a rich ethnobotanical history in Chinese culture and have recently been used as an evolutionary model. The Qinling Mountains represent a significant geographic barrier in Asia, dividing mainland China into northern (temperate) and southern (semi-tropical) regions; however, their flora has not been well analyzed. In this study, the genetic differentiation and genetic structure of Paeonia rockii and the role of the Qinling Mountains as a barrier that has driven intraspecific fragmentation were evaluated using 14 microsatellite markers.Twenty wild populations were sampled from the distributional range of P. rockii. Significant population differentiation was suggested (F(ST) value of 0.302). Moderate genetic diversity at the population level (H(S) of 0.516) and high population diversity at the species level (H(T) of 0.749) were detected. Significant excess homozygosity (F(IS) of 0.076) and recent population bottlenecks were detected in three populations. Bayesian clusters, population genetic trees and principal coordinate analysis all classified the P. rockii populations into three genetic groups and one admixed Wenxian population. An isolation-by-distance model for P. rockii was suggested by Mantel tests (r = 0.6074, P<0.001) and supported by AMOVA (P<0.001), revealing a significant molecular variance among the groups (11.32%) and their populations (21.22%). These data support the five geographic boundaries surrounding the Qinling Mountains and adjacent areas that were detected with Monmonier's maximum-difference algorithm.Our data suggest that the current genetic structure of P. rockii has resulted from the fragmentation of a formerly continuously distributed large population following the restriction of gene flow between populations of this species by the Qinling Mountains. This study provides a fundamental genetic profile for the conservation and responsible exploitation of the extant germplasm of this species and for improving the genetic basis for breeding its cultivars

Chronic disease prevalence and care among the elderly in urban and rural Beijing, China - a 10/66 Dementia Research Group cross-sectional survey

<p>Abstract</p> <p>Background</p> <p>Demographic ageing is occurring at an unprecedented rate in China. Chronic diseases and their disabling consequences will become much more common. Public policy has a strong urban bias, and older people living in rural areas may be especially vulnerable due to limited access to good quality healthcare, and low pension coverage. We aim to compare the sociodemographic and health characteristics, health service utilization, needs for care and informal care arrangements of representative samples of older people in two Beijing communities, urban Xicheng and rural Daxing.</p> <p>Methods</p> <p>A one-phase cross-sectional survey of all those aged 65 years and over was conducted in urban and rural catchment areas in Beijing, China. Assessments included questionnaires, a clinical interview, physical examination, and an informant interview. Prevalence of chronic diseases, self-reported impairments and risk behaviours was calculated adjusting for household clustering. Poisson working models were used to estimate the independent effect of rural versus urban residence, and to explore the predictors of health services utilization.</p> <p>Results</p> <p>We interviewed 1002 participants in rural Daxing, and 1160 in urban Xicheng. Those in Daxing were more likely to be younger, widowed, less educated, not receiving a pension, and reliant on family transfers. Chronic diseases were more common in Xicheng, when based on self-report rather than clinical assessment. Risk exposures were more common in Daxing. Rural older people were much less likely to access health services, controlling for age and health. Community health services were ineffective, particularly in Daxing, where fewer than 3% of those with hypertension were adequately controlled. In Daxing, care was provided by family, who had often given up work to do so. In Xicheng, 45% of those needing care were supported by paid caregivers. Caregiver strain was higher in Xicheng. Dementia was strongly associated with care needs and caregiver strain, but not with medical helpseeking.</p> <p>Conclusion</p> <p>Apparent better health in Daxing might be explained by under-diagnosis, under-reporting or selective mortality. Far-reaching structural reforms may be needed to improve access and strengthen rural healthcare. The impact of social and economic change is already apparent in Xicheng, with important implications for future long-term care.</p

Proteostasis Dysregulation in Pancreatic Cancer

The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (PDAC), has a dismal 5-year survival rate of less than 5%. Radical surgical resection, in combination with adjuvant chemotherapy, provides the best option for long-term patient survival. However, only approximately 20% of patients are resectable at the time of diagnosis, due to locally advanced or metastatic disease. There is an urgent need for the identification of new, specific, and more sensitive biomarkers for diagnosis, prognosis, and prediction to improve the treatment options for pancreatic cancer patients. Dysregulation of proteostasis is linked to many pathophysiological conditions, including various types of cancer. In this review, we report on findings relating to the main cellular protein degradation systems, the ubiquitin-proteasome system (UPS) and autophagy, in pancreatic cancer. The expression of several components of the proteolytic network, including E3 ubiquitinligases and deubiquitinating enzymes, are dysregulated in PDAC, which accounts for approximately 90% of all pancreatic malignancies. In the future, a deeper understanding of the emerging role of proteostasis in pancreatic cancer has the potential to provide clinically relevant biomarkers and new strategies for combinatorial therapeutic options to better help treat the patients.Peer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac