Massive rearrangements of cellular MicroRNA signatures are key drivers of hepatocyte dedifferentiation

Hepatocytes are dynamic cells that, upon injury, can alternate between nondividing differentiated and dedifferentiated proliferating states in vivo . However, in two‐dimensional cultures, primary human hepatocytes (PHHs) rapidly dedifferentiate, resulting in loss of hepatic functions that significantly limits their usefulness as an in vitro model of liver biology, liver diseases, as well as drug metabolism and toxicity. Thus, understanding the underlying mechanisms and stalling of the dedifferentiation process would be highly beneficial to establish more‐accurate and relevant long‐term in vitro hepatocyte models. Here, we present comprehensive analyses of whole proteome and transcriptome dynamics during the initiation of dedifferentiation during the first 24 hours of culture. We report that early major rearrangements of the noncoding transcriptome, hallmarked by increased expression of small nucleolar RNAs, long noncoding RNAs, microRNAs (miRNAs), and ribosomal genes, precede most changes in coding genes during dedifferentiation of PHHs, and we speculated that these modulations could drive the hepatic dedifferentiation process. To functionally test this hypothesis, we globally inhibited the miRNA machinery using two established chemically distinct compounds, acriflavine and poly‐l ‐lysine. These inhibition experiments resulted in a significantly impaired miRNA response and, most important, in a pronounced reduction in the down‐regulation of hepatic genes with importance for liver function. Thus, we provide strong evidence for the importance of noncoding RNAs, in particular, miRNAs, in hepatic dedifferentiation, which can aid the development of more‐efficient differentiation protocols for stem‐cell‐derived hepatocytes and broaden our understanding of the dynamic properties of hepatocytes with respect to liver regeneration. Conclusion: miRNAs are important drivers of hepatic dedifferentiation, and our results provide valuable information regarding the mechanisms behind liver regeneration and possibilities to inhibit dedifferentiation in vitro

Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system

Oligodendrocytes have been considered as a functionally homogeneous population in the central nervous system (CNS). We performed single-cell RNA sequencing on 5072 cells of the oligodendrocyte lineage from 10 regions of the mouse juvenile and adult CNS. Thirteen distinct populations were identified, 12 of which represent a continuum from Pdgfra(+) oligodendrocyte precursor cells (OPCs) to distinct mature oligodendrocytes. Initial stages of differentiation were similar across the juvenile CNS, whereas subsets of mature oligodendrocytes were enriched in specific regions in the adult brain. Newly formed oligodendrocytes were detected in the adult CNS and were responsive to complex motor learning. A second Pdgfra(+) population, distinct from OPCs, was found along vessels. Our study reveals the dynamics of oligodendrocyte differentiation and maturation, uncoupling them at a transcriptional level and highlighting oligodendrocyte heterogeneity in the CNS

Investigation of Buin Zahra Drinking Water Resources Quality by Using of GWQI

Background: Groundwater is often withdrawn for agricultural, municipal and industrial use by constructing and operating extraction wells. Nowadays, The need for clean water is increasing due to population growth and accelerated industrialization. From the viewpoint of WHO, approximately 80% of all human diseases caused by water. Groundwater can be a safe water for many communities and for this reason may be polluted by many ways. Therefore, it seems essential the protection and monitoring of them. The main object of this study was investigation the quality of Buin Zahra drinking water resources using GWQI. Methods: The current study was developed based on multivariate analysis to determine a groundwater quality index (GWQI) with using 9 GWQI parameters with the aim of monitoring the buin Zahra city. Sampling was carried out from seven city (Ardaq, Avaj, Buin Zahra, Shaal, Abgarm, Segzabad and Dansfhan) and representative wells that had the highest discharge. These water resources were monitored seasonally for a period of six month (between May to September). Results: The proportion of observed concentrations to the maximum allowable concentration is calculated as normalized value of each parameter in observing wells. Final indices for each well are calculated considering weight of each parameter. The measurement of parameters were experimented as a duplicate. The results showed that the lower levels of fluoride and higher values of parameters such as turbidity, total hardness, and magnesium in the selected wells that also higher than maximum contamination level for drinking purposes, with considering the rate of groundwater quality index. Conclusion: In terms of GWQI, the quality index of Ardaq, Buin Zahra, Shaal, Segzabad and Dansfhan wells were good, on the other hand. water quality in Avaj and Abgarm wells were in very good condition

Tandem Amine and Ruthenium-Catalyzed Hydrogenation of CO₂ to Methanol

This Communication describes the hydrogenation of carbon dioxide to methanol via tandem catalysis with dimethylamine and a homogeneous ruthenium complex. Unlike previous examples with homogeneous catalysts, this CO₂-to-CH₃OH process proceeds under basic reaction conditions. The dimethylamine is proposed to play a dual role in this system. It reacts directly with CO₂ to produce dimethylammonium dimethylcarbamate, and it also intercepts the intermediate formic acid to generate dimethylformamide. With the appropriate selection of catalyst and reaction conditions, >95% conversion of CO₂ was achieved to form a mixture of CH₃OH and dimethylformamide