In vitro modeling of hepatocellular carcinoma molecular subtypes for anti-cancer drug assessment

Tractable experimental model that accounts for inter-tumor molecular heterogeneity is a key element of anti-cancer drug development. Hepatocellular carcinoma is known to exhibit highly heterogeneous molecular aberrations across the tumors, including somatic genetic and epigenetic alterations. Previous studies showed that molecular tumor subtypes determined by transcriptome, as a comprehensive functional readout, are reproducibly observed across global patient populations irrespective of geographic and etiological variations. Here we demonstrate that transcriptomic hepatocellular carcinoma subtypes, S1 and S2, determined by our previous transcriptome meta-analysis of multiple clinical hepatocellular carcinoma cohorts, are presented in a panel of hepatoma cell lines widely used by the research community. Interestingly, cell line that resembles gene expression pattern of S3 subtype, representing less aggressive tumors, was not identified in the panel. MYC pathway-activated S2-like cell lines showed higher sensitivity to a small molecule BET bromodomain inhibitor, (+)-JQ1, which has anti-MYC activity. These results support the use of hepatoma cell lines as models to evaluate molecular subtype-specific drug response, which is expected to lead to development of tailored, precision care of the patients with hepatocellular carcinoma

Molecular liver cancer prevention in cirrhosis by organ transcriptome analysis and lysophosphatidic acid pathway inhibition

Cirrhosis is a milieu that develops hepatocellular carcinoma (HCC), the second most lethal cancer worldwide. HCC prediction and prevention in cirrhosis are key unmet medical needs. Here we have established an HCC risk gene signature applicable to all major HCC etiologies: hepatitis B/C, alcohol, and non-alcoholic steatohepatitis. A transcriptome meta-analysis of >500 human cirrhotics revealed global regulatory gene modules driving HCC risk and the lysophosphatidic acid pathway as a central chemoprevention target. Pharmacological inhibition of the pathway in vivo reduced tumors and reversed the gene signature, which was verified in organotypic ex vivo culture of patient-derived fibrotic liver tissues. These results demonstrate the utility of clinical organ transcriptome to enable a strategy, namely, reverse-engineering precision cancer prevention

Amyloid and tau pathology associations with personality traits, neuropsychiatric symptoms, and cognitive lifestyle in the preclinical phases of sporadic and autosomal dominant Alzheimer’s disease

Background Major prevention trials for Alzheimer’s disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p = .014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p = .006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p = .005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression

Georeferenced soil information system: assessment of database

Land-use planning is a decision-making process that facilitates the allocation of land to different uses that provide optimal and sustainable benefit. As land-use is shaped by society–nature interaction, in land-use planning different components/facets play a significant role involving soil, water, climate, animal (ruminant/ non-ruminant) and others, including forestry and the environment needed for survival of mankind. At times these components are moderated by human interference. Thus land-use planning being a dynamic phenomenon is not guided by a single factor, but by a complex system working simultaneously,which largely affects the sustainability. To address such issues a National Agricultural Innovation Project (NAIP) on ‘Georeferenced soil information system for land-use planning and monitoring soil and land quality for agriculture’ was undertaken to develop threshold values of land quality parameters for land-use planning through quantitative land evaluation and crop modelling for dominant cropping systems in major agro-ecological sub-regions (AESRs) representing rice–wheat cropping system in the Indo-Gangetic Plains (IGP) and deep-rooted crops in the black soil regions (BSR). To assess the impact of landuse change, threshold land quality indicator values are used. A modified AESR map for agricultural landuse planning is generated for effective land-use planning

Soil information system: use and potentials in humid and semi-arid tropics

The articles presented in this special section emanated from the researches of consortium members of the National Agricultural Innovative Project (NAIP, Component 4) of the Indian Council of Agricultural Research (ICAR), New Delhi. These researches have helped develop a soil information system (SIS). In view of the changing scenario all over the world, the need of the hour is to get assistance from a host of researchers specialized in soils, crops, geology, geography and information technology to make proper use of the datasets. Equipped with the essential knowledge of data storage and retrieval for management recommendations, these experts should be able to address the issues of land degradation, biodiversity, food security, climate change and ultimately arrive at an appropriate agricultural land-use planning. Moreover, as the natural resource information is an essential prerequisite for monitoring and predicting global environmental change with special reference to climate and land use options, the SIS needs to be a dynamic exercise to accommodate temporal datasets, so that subsequently it should result in the evolution of the soil information technology. The database developed through this NAIP would serve as an example of the usefulness of the Consortium and the research initiative of ICAR involving experts from different fields to find out the potentials of the soils of humid and semi-arid bioclimatic systems of the country

Effect of Aqueous Dipolar Aprotic Solvents on Kinetics of Saponification of Some Acid Phthalic Esters

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Activation of phosphoinositide 3-kinase by D2 receptor prevents apoptosis in dopaminergic cell lines.

Whereas dopamine agonists are known to provide symptomatic benefits for Parkinson's disease, recent clinical trials suggest that they might also be neuroprotective. Laboratory studies demonstrate that dopamine agonists can provide neuroprotective effects in a number of model systems, but the role of receptor-mediated signalling in these effects is controversial. We find that dopamine agonists have robust, concentration-dependent anti-apoptotic activity in PC12 cells that stably express human D(2L) receptors from cell death due to H(2)O(2) or trophic withdrawal and that the protective effects are abolished in the presence of D(2)-receptor antagonists. D(2) agonists are also neuroprotective in the nigral dopamine cell line SN4741, which express endogenous D(2) receptors, whereas no anti-apoptotic activity is observed in native PC12 cells, which do not express detectable D(2) receptors. Notably, the agonists studied differ in their relative efficacy to mediate anti-apoptotic effects and in their capacity to stimulate [(35)S]guanosine 5'-[gamma-thio]triphosphate ([(35)S]GTP[S]) binding, an indicator of G-protein activation. Studies with inhibitors of phosphoinositide 3-kinase (PI 3-kinase), extracellular-signal-regulated kinase or p38 mitogen-activated protein kinase indicate that the PI 3-kinase pathway is required for D(2) receptor-mediated cell survival. These studies indicate that certain dopamine agonists can complex with D(2) receptors to preferentially transactivate neuroprotective signalling pathways and to mediate increased cell survival

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Not AvailableA survey was undertaken in the established benchmark (BM) soil series in different agro-ecological sub regions (AESR) of Black Soil Regions (BSR) in India with an objective to study the impacts of bio-climates, cropping systems and land use systems on the distribution of dehydrogenase activity (DHA) in different soil profiles. The DHA was found to decline with depth and the maximum activity was recorded within 0–30 cm soil depth. Cropping systems and bio-climates significantly (pb0.01) influence the DHA in soil. Significantly (pb0.01) higher DHA was recorded in Sub-humid moist (SHm) bio-climate (2.45 μg TPF g−1) followed by Semi-arid dry (SAd) (2.00 μg TPF g−1) and the least in arid bio-climate (1.62 μg TPF g−1). The average DHA in different bio-climates were in decreasing order of Sub-humidmoist>Semi-arid dry>Sub-humid dry>arid. Legume-based cropping system recorded higher DHA (2.32–2.88 μg TPF g−1) followed by cereal-based cropping system (1.29–2.82 μg TPF g−1). The average DHA in different cropping systems were in decreasing order of legume>cereals>cotton>sugarcane. The comparisons of DHA in different soils indicated significant differences (pb0.01) between the soil sub groups. High management practices found to significantly increase DHA (2.15 μg TPF g−1) compared to low management (1.78 μg TPF g−1), whilst no significant differences were found in DHA between irrigated and rainfed system.Not Availabl