Notes

TMEM100 in a negative way controlled simply by microRNA‑106b helps cell apoptosis by simply controlling survivin phrase within NSCLC.
gingivalis and its adaptation to the nutritional condition of the host niche. Our findings support the model that in response to specific nutritional parameters, P. gingivalis has the potential to promote host colonization and development of a pathogenic community.Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS)  1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further develop a chromatin accessibility microarray methodology termed "ATAC-array", an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.Mercury is a potent neurotoxin that poses health risks to the global population. Anthropogenic mercury emissions to the atmosphere are projected to decrease in the future due to enhanced policy efforts such as the Minamata Convention, a legally-binding international treaty entered into force in 2017. Here, we report the development of a comprehensive climate-atmosphere-land-ocean-ecosystem and exposure-risk model framework for mercury and its application to project the health effects of future atmospheric emissions. Our results show that the accumulated health effects associated with mercury exposure during 2010-2050 are $19 (95% confidence interval 4.7-54) trillion (2020 USD) realized to 2050 (3% discount rate) for the current policy scenario. Our results suggest a substantial increase in global human health cost if emission reduction actions are delayed. This comprehensive modeling approach provides a much-needed tool to help parties to evaluate the effectiveness of Hg emission controls as required by the Minamata Convention.Decades of sustainable dam planning efforts have focused on containing dam impacts in regime conditions, when the dam is fully filled and operational, overlooking potential disputes raised by the filling phase. Here, we argue that filling timing and operations can catalyze most of the conflicts associated with a dam's lifetime, which can be mitigated by adaptive solutions that respond to medium-to-long term hydroclimatic fluctuations. Our retrospective analysis of the contested recent filling of Gibe III in the Omo-Turkana basin provides quantitative evidence of the benefits generated by adaptive filling strategies, attaining levels of hydropower production comparable with the historical ones while curtailing the negative impacts to downstream users. Our results can inform a more sustainable filling of the new megadam currently under construction downstream of Gibe III, and are generalizable to the almost 500 planned dams worldwide in regions influenced by climate feedbacks, thus representing a significant scope to reduce the societal and environmental impacts of a large number of new hydropower reservoirs.Sequence rewriting enables low-cost genome synthesis and the design of biological systems with orthogonal genetic codes. The error-free, robust rewriting of nucleotide sequences can be achieved with a complete annotation of gene regulatory elements. Here, we compare transcription in Caulobacter crescentus to transcription from plasmid-borne segments of the synthesized genome of C. Gefitinib ethensis 2.0. This rewritten derivative contains an extensive amount of supposedly neutral mutations, including 123'562 synonymous codon changes. The transcriptional landscape refines 60 promoter annotations, exposes 18 termination elements and links extensive transcription throughout the synthesized genome to the unintentional introduction of sigma factor binding motifs. We reveal translational regulation for 20 CDS and uncover an essential translational regulatory element for the expression of ribosomal protein RplS. The annotation of gene regulatory elements allowed us to formulate design principles that improve design schemes for synthesized DNA, en route to a bright future of iteration-free programming of biological systems.Triple negative breast cancer (TNBC) patients exhibit poor survival outcomes and lack effective targeted therapies. Using unbiased in vivo genome-wide CRISPR screening, we interrogated cancer vulnerabilities in TNBC and identified an interplay between oncogenic and tumor suppressor pathways. This study reveals tumor regulatory functions for essential components of the mTOR and Hippo pathways in TNBC. Using in vitro drug matrix synergy models and in vivo patient-derived xenografts, we further establish the therapeutic relevance of our findings and show that pharmacological inhibition of mTORC1/2 and oncoprotein YAP efficiently reduces tumorigenesis in TNBC. At the molecular level, we find that while verteporfin-induced YAP inhibition leads to apoptosis, torin1-mediated mTORC1/2 inhibition promotes macropinocytosis. Torin1-induced macropinocytosis further facilitates verteporfin uptake, thereby greatly enhancing its pro-apoptotic effects in cancer cells. Overall, our study underscores the power and robustness of in vivo CRISPR genome-wide screens in identifying clinically relevant and innovative therapeutic modalities in cancer.
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