Cell-Surface Marker Signatures for the Isolation of Neural Stem Cells, Glia and Neurons Derived from Human Pluripotent Stem Cells

Neural induction of human pluripotent stem cells often yields heterogeneous cell populations that can hamper quantitative and comparative analyses. There is a need for improved differentiation and enrichment procedures that generate highly pure populations of neural stem cells (NSC), glia and neurons. One way to address this problem is to identify cell-surface signatures that enable the isolation of these cell types from heterogeneous cell populations by fluorescence activated cell sorting (FACS).We performed an unbiased FACS- and image-based immunophenotyping analysis using 190 antibodies to cell surface markers on naïve human embryonic stem cells (hESC) and cell derivatives from neural differentiation cultures. From this analysis we identified prospective cell surface signatures for the isolation of NSC, glia and neurons. We isolated a population of NSC that was CD184(+)/CD271(-)/CD44(-)/CD24(+) from neural induction cultures of hESC and human induced pluripotent stem cells (hiPSC). Sorted NSC could be propagated for many passages and could differentiate to mixed cultures of neurons and glia in vitro and in vivo. A population of neurons that was CD184(-)/CD44(-)/CD15(LOW)/CD24(+) and a population of glia that was CD184(+)/CD44(+) were subsequently purified from cultures of differentiating NSC. Purified neurons were viable, expressed mature and subtype-specific neuronal markers, and could fire action potentials. Purified glia were mitotic and could mature to GFAP-expressing astrocytes in vitro and in vivo.These findings illustrate the utility of immunophenotyping screens for the identification of cell surface signatures of neural cells derived from human pluripotent stem cells. These signatures can be used for isolating highly pure populations of viable NSC, glia and neurons by FACS. The methods described here will enable downstream studies that require consistent and defined neural cell populations

Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe

Assessing ecological risk on the Qinghai-Tibet Plateau based on future land use scenarios and ecosystem service values

As one of the world’s critical ecological regions – often called the “Third Pole” – the Qinghai-Tibet Plateau (QTP) has outstanding ecosystem service values (ESV). However, its variable climate and fragile environmental conditions make it vulnerable to disturbance by human activities. Based on land use data from 2000, 2010, and 2020, we developed three simulated scenarios of land use distribution on the QTP: business as usual (BAU), farmland protection (FP), and ecological protection (EP). Finally, we employed the Sharpe Index to evaluate ecological risk across the QTP. The results showed that from 2000 to 2020, land use change was mainly in the form of conversion of grassland to unused land, totaling an area of 63,717 km2. The ecosystem service value showed an increasing trend, from US$752.6 billion to US$783.0 from 2010 to 2020. The simulation results from the three scenarios revealed significant differences. Farmland area shows a declining trend in both the EP and BAU scenarios, while exhibiting an increasing trend in the FP scenario. Forest area on the plateau experiences a decreasing trend in the EP and BAU scenarios, but shows an increase in the FP scenario, predominantly in the southeastern region, including Sichuan and Yunnan provinces. The ecological risk assessment results indicate that the eastern region has higher ecological risk compared to the western region, highlighting the western region as a priority area for risk control. The expansion of built-up land and unused land has had significant impacts on regional ecological risk. Integrating risk assessment outcomes with land use planning to identify focal areas can provide guidance for the sustainable development of this globally important ecoregion

Evaluation of Two Parts of Lithocarpus polystachyus Rehd. from Different Chinese Areas by Multicomponent Content Determination and Pattern Recognition

The purpose of this work is to establish a new method using high-performance liquid chromatography-diode array detection (HPLC-DAD) with chemometrics analysis to determine the content of catechin, isoquercetin, astragalin, phloridzin, trilobatin, and phloretin for one flavanol and five flavonoids, filter out the key compounds, and evaluate the quality of 26 batches of tender leaves and flower spikes of Lithocarpus polystachyus Rehd. (LP) from ten areas in China. The result showed that the HPLC-DAD method had excellent performance for accurate quantification analysis. S3 (tender leaf from Lushan, Sichuan) had the highest contents for six measured chemicals with trilobatin content of up to 27.82% in dry weight. S22 (flower spike from Liangping, Chongqing) had the highest content of phloridzin (up to 7.28%). All samples were divided into three types based on spatial distribution using principal component analysis. The result showed that the tender leaves and flower spikes from the same areas had many similar properties, and there were significant differences between the samples from different regions. Furthermore, phloridzin and trilobatin were identified as chemical markers for quality evaluation of two parts with different tender leaves and flower spikes of LP from geographical areas by orthogonal partial least squares discrimination analysis. These results will be helpful to establish an effective and comprehensive evaluation system of the development and utilization of LP resources

SPTBN2 suppresses ferroptosis in NSCLC cells by facilitating SLC7A11 membrane trafficking and localization

The function of SLC7A11 in the process of ferroptosis is well-established, as it regulates the synthesis of glutathione (GSH), thereby influencing tumor development along with drug resistance in non-small cell lung cancer (NSCLC). However, the determinants governing SLC7A11's membrane trafficking and localization remain unknown. Our study identified SPTBN2 as a ferroptosis suppressor, enhancing NSCLC cells resistance to ferroptosis inducers. Mechanistically, SPTBN2, through its CH domain, interacted with SLC7A11 and connected it with the motor protein Arp1, thus facilitating the membrane localization of SLC7A11 — a prerequisite for its role as System Xc−, which mediates cystine uptake and GSH synthesis. Consequently, SPTBN2 suppressed ferroptosis through preserving the functional activity of System Xc− on the membrane. Moreover, Inhibiting SPTBN2 increased the sensitivity of NSCLC cells to cisplatin through ferroptosis induction, both in vitro and in vivo. Using Abrine as a potential SPTBN2 inhibitor, its efficacy in promoting ferroptosis and sensitizing NSCLC cells to cisplatin was validated. Collectively, SPTBN2 is a potential therapeutic target for addressing ferroptosis dysfunction and cisplatin resistance in NSCLC

Selection of Yield-Related Traits for Wheat Breeding in Semi-Arid Region

Wheat is an important cereal crop and one of the sources of nourishment and energy for humankind. But drought has affected wheat production seriously. This study has focused on wheat yield-related traits and tried to select suitable indexes for wheat breeding in semi-arid region. To this aim, a factorial experiment with two water regimes in field conditions was conducted. We found that the wheat line with higher grain yield also possessed higher spikelet number per spike (SN), 1000-kernel weight (TKW), and grain number per spike (GNPS) and the higher post-anthesis photosynthetic rate (Pn) than the others (P<0.05). The statistical analysis showed that under drought condition the higher grain yield was significantly associated with SN, TKW, GNPS and the higher post-anthesis Pn (P<0.05). Based on our findings, it is concluded that the post-anthesis Pn as physiological index and SN, TKW, and GNPS as agronomic trait are suitable in using selection indicators for wheat breeding in semi-arid region. (c) 2018 Friends Science Publishers

Joint Control of Net Primary Productivity by Climate and Soil Nitrogen in the Forests of Eastern China

The nature and extent of climate and soil nutrient controls in Chinese forests remain poorly resolved. Here, we synthesized the data on carbon-climate-soil in eastern China, and litter N was firstly taken into consideration, to examine the variation of net primary productivity (NPP) and its driving forces. Results showed that NPP had significant latitude pattern and varied substantially across climate zones. Bivariate analyses indicated that mean annual temperature (MAT), mean annual precipitation (MAP), soil N content (N-soil), and annual litter N (N-re) were the main controlling factors in spatial pattern of forest NPP. Notably, partial general linear model analysis revealed that MAT, MAP, and N-re jointly explained 84.8% of the spatial variation of NPP. Among the three major factors, N-re explained more variation of forest NPP than the other two factors, and MAT and MAP affected NPP mainly through the change of litter N rather than via themselves, highlighting the importance of litter N in estimating forest NPP. However, to accurately describe the pattern of forest NPP in China, more detailed field measurements and methodologies on NPP and relevant confounding factors should be addressed in future studies