Unexpected CRISPR off-target mutation pattern in vivo are not typically germline-like [preprint]

A computationally evolutionary investigation was performed to re-analyze the WGS data of the two studies published in Nature Methods (2015, 2017) with opposite conclusions on CRISPR off-target mutations. Our analysis concluded that the so-called unexpected SNVs pattern obtained by the study of Schaefer et al. are not typically germline-like. Some of unusual and unidentified mutations may arise, but the real reasons remain to be explored. Based on the available data and a direct comparison of the two studies, we presented two possible reasons and future re-analysis directions that may contribute to such different conclusions. To characterize the authentic CRISPR-mediated mutations, we are required to have appropriate controls to rule out other sources of mutations, which will be needed for benchmarking of targeting safety of CRISPR-based gene therapy

Enhancement of thermoelectric figure-of-merit by resonant states of aluminium doping in lead selenide

By adding aluminium (Al) into lead selenide (PbSe), we successfully prepared n-type PbSe thermoelectric materials with a figure-of-merit (ZT) of 1.3 at 850 K. Such a high ZT is achieved by a combination of high Seebeck coefficient caused by very possibly the resonant states in the conduction band created by Al dopant and low thermal conductivity from nanosized phonon scattering centers.United States. Dept. of Energy. Office of Basic Energy Sciences (Solid-State Solar-Thermal Energy Conversion Center Award DE-SC0001299/DE-FG02-09ER46577

A compendium of genetic regulatory effects across pig tissues

The Farm Animal Genotype-Tissue Expression (FarmGTEx) project has been established to develop a public resource of genetic regulatory variants in livestock, which is essential for linking genetic polymorphisms to variation in phenotypes, helping fundamental biological discovery and exploitation in animal breeding and human biomedicine. Here we show results from the pilot phase of PigGTEx by processing 5,457 RNA-sequencing and 1,602 whole-genome sequencing samples passing quality control from pigs. We build a pig genotype imputation panel and associate millions of genetic variants with five types of transcriptomic phenotypes in 34 tissues. We evaluate tissue specificity of regulatory effects and elucidate molecular mechanisms of their action using multi-omics data. Leveraging this resource, we decipher regulatory mechanisms underlying 207 pig complex phenotypes and demonstrate the similarity of pigs to humans in gene expression and the genetic regulation behind complex phenotypes, supporting the importance of pigs as a human biomedical model.</p

PigBiobank: a valuable resource for understanding genetic and biological mechanisms of diverse complex traits in pigs

© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] fully unlock the potential of pigs as both agricultural species for animal-based protein food and biomedical models for human biology and disease, a comprehensive understanding of molecular and cellular mechanisms underlying various complex phenotypes in pigs and how the findings can be translated to other species, especially humans, are urgently needed. Here, within the Farm animal Genotype-Tissue Expression (FarmGTEx) project, we build the PigBiobank (http://pigbiobank.farmgtex.org) to systematically investigate the relationships among genomic variants, regulatory elements, genes, molecular networks, tissues and complex traits in pigs. This first version of the PigBiobank curates 71 885 pigs with both genotypes and phenotypes from over 100 pig breeds worldwide, covering 264 distinct complex traits. The PigBiobank has the following functions: (i) imputed sequence-based genotype-phenotype associations via a standardized and uniform pipeline, (ii) molecular and cellular mechanisms underlying trait-associations via integrating multi-omics data, (iii) cross-species gene mapping of complex traits via transcriptome-wide association studies, and (iv) high-quality results display and visualization. The PigBiobank will be updated timely with the development of the FarmGTEx-PigGTEx project, serving as an open-access and easy-to-use resource for genetically and biologically dissecting complex traits in pigs and translating the findings to other species.National Natural Science Foundation of China [32022078]; National Key R&D Program of China [2022YFF1000900]; Local Innovative and Research Teams Project of Guangdong Province [2019BT02N630]; China Agriculture Research System [CARS-35]. Funding for open access charge: National Natural Science Foundation of China [32022078].Peer reviewe

Plasm YKL-40 Levels Are Associated with Hypertension in Patients with Obstructive Sleep Apnea

Background. Obstructive sleep apnea (OSA) is a common disease. It can cause many serious complications. OSA may increase the risk of hypertension. However, the exact mechanism of OSA causing hypertension is not fully understood. YKL-40/chitinase-3-like protein-1 plays an important role in vascular injury, repair, and generation. We sought to explore the role of YKL-40 in endothelial dysfunction and hypertension in OSA patients. Methods. All subjects were examined by polysomnography (PSG) and the expression of YKL-40 in the plasm of the subjects was measured by luminex. Carotid intima-media thickness (CIMT) was measured by B-mode ultrasound. Results. According to the conditions of OSA and hypertension, we studied four groups of 157 subjects, including OSA group (OSA, N=77), OSA with hypertension group (OSA+HT, N=37), hypertension group (HT, N=20), and healthly group (Con, N=23). YKL-40 levels were significantly elevated in OSA, OSA+HT, and HT group compared to Con groups. We used the ROC to predict the sensitivity and specificity of YKL-40 in all OSA patients or all hyperpietic patients. For OSA patients, the AUC of YKL-40 is 0.807 (95% confidence interval 0.725–0.888; p<0.01). For hyperpietic patients, the AUC of YKL-40 is 0.656 (95% confidence interval 0.570–0.742, p=0.01). There was a significant correlation between the parameter of OSA and hypertension and YKL-40 (P<0.05) and a significant correlation between Max-CIMT and YKL-40 (P<0.05). Conclusion. Elevated circulating levels of YKL-40 are associated with hypertension in OSA patients. The specificity of YKL-40 suggests that it could be a potential biomarker for OSA and hypertension

Circulating Hepatocellular Carcinoma Cells are Characterized by CXCR4 and MMP26

Background/Aims: Primary hepatocellular carcinoma (HCC) is highly invasive, and often results in an early distal metastasis resulting in poor prognosis and therapeutic outcome. Cancer cells disseminating from the tumor and entering circulation are termed circulating tumor cells (CTCs). Although substantial progress has been made to identify those CTCs in HCC, no good marker (cocktail) has so far been identified. Methods: Since only tumorigenic CTCs form metastatic tumor in distal organs, we thus compared the HCC cells that form tumor spheres in culture to those that do not. We transduced HCC cells with a RFP reporter under MMP26 promoter and purified MMP26+CXCR4+ HCC cells. We examined tumor sphere formation in culture, presence of tumor cells in the circulation as well as capability of developing metastatic tumor after transplantation of MMP26+CXCR4+ HCC cells into nude mice, compared to other populations in HCC. Results: Sphere-forming HCC cells expressed high levels of MMP26 and CXCR4. MMP26+CXCR4+ HCC cells formed significantly more tumor spheres in culture, compared to MMP26-CXCR4-, MMP26-CXCR4+ or MMP26+CXCR4- HCC cells. Moreover, tumor cells were more frequently detected in the circulation when MMP26+CXCR4+ HCC cells were subcutaneously transplanted. Further, subcutaneous transplantation of MMP26+CXCR4+ HCC cells, but not transplantation of MMP26-CXCR4-, MMP26-CXCR4+ or MMP26+CXCR4-HCC cells significantly developed distal metastatic tumors. Conclusion: MMP26+CXCR4+ cells may be CTCs in HCC. Selective elimination of MMP26+CXCR4+ cells may substantially reduce HCC metastasis after primary tumor resection