Search

Summary Naked mole rat (NMR) is a valuable model for aging and cancer research due to its exceptional longevity and cancer resistance. We observed that the reprogramming efficiency of NMR fibroblasts in response to OSKM was drastically lower than that of mouse fibroblasts. Expression of SV40 LargeT antigen (LT) dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was sufficient to improve reprogramming efficiency, suggesting that NMR chromatin may be refractory to reprogramming. Analysis of the global histone landscape revealed that NMR had higher levels of repressive H3K27 methylation marks and lower levels of activating H3K27 acetylation marks than mouse. ATAC-seq revealed that in NMR, promoters of reprogramming genes were more closed than mouse promoters, while expression of LT led to massive opening of the NMR promoters. These results suggest that NMR displays a more stable epigenome that resists de-differentiation, contributing to the cancer resistance and longevity of this species.

Aegilops umbellulata (UU) is a wheat wild relative that has potential use in the genetic improvement of wheat. In this study, 46 Ae. umbellulata accessions were investigated for stripe rust resistance, heading date (HD), and the contents of iron (Fe), zinc (Zn), and seed gluten proteins. Forty-two of the accessions were classified as resistant to stripe rust, while the other four accessions were classified as susceptible to stripe rust in four environments. The average HD of Ae. umbellulata was significantly longer than that of three common wheat cultivars (180.9 d vs. 137.0 d), with the exception of PI226500 (138.9 d). The Ae. umbellulata accessions also showed high variability in Fe (69.74–348.09 mg kg–1) and Zn (49.83–101.65 mg kg–1) contents. Three accessions (viz., PI542362, PI542363, and PI554399) showed relatively higher Fe (230.96–348.09 mg kg–1) and Zn (92.46–101.65 mg kg–1) contents than the others. The Fe content of Ae. umbellulata was similar to those of Ae. comosa and Ae. markgrafii but higher than those of Ae. tauschii and common wheat. Aegilops umbellulata showed a higher Zn content than Ae. tauschii, Ae. comosa, and common wheat, but a lower content than Ae. markgrafii. Furthermore, Ae. umbellulata had the highest proportion of γ-gliadin among all the species investigated (Ae. umbellulata vs. other species=mean 72.11% vs. 49.37%; range: 55.33–86.99% vs. 29.60–67.91%). These results demonstrated that Ae. umbellulata exhibits great diversity in the investigated traits, so it can provide a potential gene pool for the genetic improvement of these traits in wheat.

Background: Little is known about the interplay among dairy intake, gut microbiota and cardiometabolic health in human prospective cohort studies. Methods: The present study included 1780 participants from the Guangzhou Nutrition and Health Study. We examined the prospective association between habitual dairy consumption (total dairy, milk, yogurt) and gut microbial composition using linear regression after adjusting for socio-demographic, lifestyle and dietary factors. The cross-sectional association of dairy-associated microbial features with cardiometabolic risk factors was examined with a linear regression model, adjusting for potential confounders. Serum metabolomic profiles were analyzed by partial correlation analysis. Findings: There was a significant overall difference in gut microbial community structure (β-diversity) comparing the highest with the lowest category for each of total dairy, milk and yogurt (P < 0.05). We observed that dairy-associated microbes and α-diversity indices were inversely associated with blood triglycerides, while positively associated with high-density lipoprotein cholesterol. A follow-up metabolomics analysis revealed the association of targeted serum metabolites with dairy-microbial features and cardiometabolic traits. Specifically, 2-hydroxy-3-methylbutyric acid, 2-hydroxybutyric acid and L-alanine were inversely associated with dairy-microbial score, while positively associated with triglycerides (FDR-corrected P < 0.1). Interpretation: Dairy consumption is associated with the gut microbial composition and a higher α-diversity, which provides new insights into the understanding of dairy-gut microbiota interactions and their relationship with cardiometabolic health. Funding: This work was supported by the National Natural Science Foundation of China, Zhejiang Ten-thousand Talents Program, Westlake University and the 5010 Program for Clinical Researches of the Sun Yat-sen University.

DNA methyltransferases (Dnmts) comprise a family of proteins which involved in the establishment and maintenance of DNA methylation patterns. In pig, the molecular characterization and tissue expression profile of Dnmt gene family are not clear. To solve this problem, reverse transcriptase PCR and rapid amplification of cDNA ends were used to clone the sequences of the porcine Dnmt2 and Dnmt3b genes. Furthermore, the mRNA expression profiles of Dnmt1, Dnmt2, Dnmt3a and Dnmt3b genes from 54 adult tissues and 2 entire fetuses of Rongchang pig were analyzed by quantitative real-time PCR (qRT-PCR). As a result, the lengths of porcine Dnmt2 and Dnmt3b gene cDNAs were 1 227 and 2 559 bp with cytosine-C5 specific DNA methylase domain, respectively. The four Dnmt genes were highly expressed in longissimus dorsi muscle (P

Trypanosome histone N-terminal sequences are very divergent from the other eukaryotes, although they are still decorated by post-translational modifications (PTMs). Here, we used a highly robust workflow to analyze histone PTMs in the parasite Trypanosoma cruzi using mass spectrometry-based (MS-based) data-independent acquisition (DIA). We adapted the workflow for the analysis of the parasite's histone sequences by modifying the software EpiProfile 2.0, improving peptide and PTM quantification accuracy. This workflow could now be applied to the study of 141 T. cruzi modified histone peptides, which we used to investigate the dynamics of histone PTMs along the metacyclogenesis and the life cycle of T. cruzi. Global levels of histone acetylation and methylation fluctuates along metacyclogenesis, however most critical differences were observed between parasite life forms. More than 66 histone PTM changes were detected. Strikingly, the histone PTM pattern of metacyclic trypomastigotes is more similar to epimastigotes than to cellular trypomastigotes. Finally, we highlighted changes at the H4 N-terminus and at H3K76 discussing their impact on the trypanosome biology. Altogether, we have optimized a workflow easily applicable to the analysis of histone PTMs in T. cruzi and generated a dataset that may shed lights on the role of chromatin modifications in this parasite. SIGNIFICANCE: Trypanosomes are unicellular parasites that have divergent histone sequences, no chromosome condensation and a peculiar genome/gene regulation. Genes are transcribed from divergent polycistronic regions and post-transcriptional gene regulation play major role on the establishment of transcripts and protein levels. In this regard, the fact that their histones are decorated with multiple PTMs raises interesting questions about their role. Besides, this digenetic organism must adapt to different environments changing its metabolism accordingly. As metabolism and epigenetics are closely related, the study of histone PTMs in trypanosomes may enlighten this strikingly, and not yet fully understood, interplay. From a biomedical perspective, the comprehensive study of molecular mechanisms associated to the metacyclogenesis process is essential to create better strategies for controlling Chagas disease., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ectomycorrhizal (ECM) fungi are closely related to vegetation compositions, edaphic properties, and site-specific processes. However, the coevolutionary mechanisms underlying the spatial distributions in floristic and ECM fungal composition in the context of biotic adaptations and abiotic variances remain unclear. We combine a total of 25 ECM fungus-associated environmental variables to impose three types of composite scores and then quantify the environmental gradients of geographical site, soil chemical property and vegetation functional trait across 122 grids of 20 m × 20 m in a 25-hm 2 forest plot. Significant dissimilarities in vegetational and ECM fungal abundance and composition existed along the above environmental gradients. Specifically, a contrasting floristic distribution (e.g., Betula platyphylla vs. Tilia mandshurica) existed between the northeastern and southwestern areas and was closely related to the nutrient and moisture gradients (with high levels in the west and low levels in the east). Furthermore, the ECM fungal communities were more abundant in the nutrient-poor and low-moisture environments than in the nutrient-rich and high-moisture environments, and the mixed-forest in the middle-gradient sites between the northeastern and southwestern areas harbored the highest ECM fungal diversity. These findings suggest that predictable within-site vegetation succession is closely related to ECM-associated determinants and the natural spatial heterogeneity of edaphic properties at a local scale., (Copyright © 2019. Published by Elsevier B.V.)

Database search is the dominant approach in high-throughput proteomic analysis. However, the interpretation rate of MS/MS spectra is very low in such a restricted mode, which is mainly due to unexpected modifications and irregular digestion types. In this study, we developed a new algorithm called Alioth, to be integrated into the search engine of pFind, for fast and accurate unrestricted database search on high-resolution MS/MS data. An ion index is constructed for both peptide precursors and fragment ions, by which arbitrary digestions and a single site of any modifications and mutations can be searched efficiently. A new re-ranking algorithm is used to distinguish the correct peptide-spectrum matches from random ones. The algorithm is tested on several HCD datasets and the interpretation rate of MS/MS spectra using Alioth is as high as 60%-80%. Peptides from semi- and non-specific digestions, as well as those with unexpected modifications or mutations, can be effectively identified using Alioth and confidently validated using other search engines. The average processing speed of Alioth is 5-10 times faster than some other unrestricted search engines and is comparable to or even faster than the restricted search algorithms tested.This article is part of a Special Issue entitled: Computational Proteomics., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Database search is the dominant approach in high-throughput proteomic analysis. However, the interpretation rate of MS/MS spectra is very low in such a restricted mode, which is mainly due to unexpected modifications and irregular digestion types. In this study, we developed a new algorithm called Alioth, to be integrated into the search engine of pFind, for fast and accurate unrestricted database search on high-resolution MS/MS data. An ion index is constructed for both peptide precursors and fragment ions, by which arbitrary digestions and a single site of any modifications and mutations can be searched efficiently. A new re-ranking algorithm is used to distinguish the correct peptide-spectrum matches from random ones. The algorithm is tested on several HCD datasets and the interpretation rate of MS/MS spectra using Alioth is as high as 60%-80%. Peptides from semi- and non-specific digestions, as well as those with unexpected modifications or mutations, can be effectively identified using Alioth and confidently validated using other search engines. The average processing speed of Alioth is 5-10 times faster than some other unrestricted search engines and is comparable to or even faster than the restricted search algorithms tested., (Copyright © 2015 Elsevier B.V. All rights reserved.)