Biology subjects

Peng, X.

Publications and source records attributed to Peng, X..

169 records · Page 10Linked to original sources

bioRxiv2018

Structure of the mouse TRPC4 ion channel

Members of the transient receptor potential (TRP) ion channels conduct cations into cells. They mediate functions ranging from neuronally-mediated hot and cold sensation to intracellular organellar and primary ciliary signaling. Structures belonging to the TRPV, TRPM, TRPP, TRPA and TRPML subfamilies have been solved, but to date, none of the founding canonical (TRPC) structures. Here we report an electron cryo-microscopy (cryo-EM) structure of TRPC4 in its apo state to an overall resolution of 3.3 [A]. The structure reveals an unusually complex architecture with a long pore loop stabilized by a disulfide bond. Beyond the shared tetrameric six-transmembrane fold, the TRPC4 structure deviates from other TRP channels with a unique cytosolic domain, this unique cytosolic N-terminal domain forms extensive aromatic contacts with the TRP and the C-terminal domains. The comparison of our structure with other known TRP structures provides molecular insights into TRPC4 ion selectivity and extends our knowledge of the diversity and evolution of the TRP channels.

biophysics↗

bioRxiv2018

Metabolomics and proteomics analyses of grain yield reduction in rice under abrupt drought-flood alternation

HighlightAbrupt drought-flood alteration is a frequent meteorological disaster that occurs during summer in southern China and the Yangtze river basin, which often causes a large area reduction of rice yield. We previously reported abrupt drought-flood alteration effects on yield and its components, physiological characteristics, matter accumulation and translocation, rice quality of rice. However, the molecular mechanism of rice yield reduction caused by abrupt drought-flood alternation has not been reported.\n\nIn this study, four treatments were provided, no drought and no floods (control), drought without floods (duration of drought 10 d), no drought with floods (duration of floods 8 d), and abrupt drought-flood alteration (duration of drought 10 d and floods 8 d). The quantitative analysis of spike metabolites was proceeded by LC-MS (liquid chromatograph-mass spectrometry) firstly. Then the Heat-map, PCA, PLS-DA, OPLS-DA and response ranking test of OPLS-DA model methods were used to analysis the function of differential metabolites (DMs) during the rice panicle differentiation stage under abrupt drought-flood alteration. In addition, relative quantitative analysis of spike total proteins under the treatment was conducted iTRAQ (isobaric tags for relative and absolute quantification) and LC-MS. In this study, 5708 proteins were identified and 4803 proteins were quantified. The identification and analysis of DEPs function suggested that abrupt drought-flood alteration treatment can promote carbohydrate metabolic, stress response, oxidation-reduction, defense response, and energy reserve metabolic process, etc, during panicle differentiation stage. In this study relative quantitative proteomics, metabolomics and physiology data (soluble protein content, superoxide dismutase activity, hydrogen peroxidase activity, peroxidase activity, malondialdehyde content, free proline content, soluble sugar content and net photosynthetic rate) analysis were applied to explicit the response mechanism of rice panicle differentiation stage under abrupt drought-flood alteration and provides a theoretical basis for the disaster prevention and mitigation.\n\nAbstractAbrupt drought-flood alternation is a meteorological disaster that frequently occurs during summer in southern China and the Yangtze river basin, often causing a significant loss of rice production. In this study, a quantitative analysis of spike metabolites was conducted via liquid chromatograph-mass spectrometry (LC-MS), and Heat-map, PCA, PLS-DA, OPLS-DA, and a response ranking test of OPLS-DA model methods were used to analyze functions of differential metabolites (DMs) during the rice panicle differentiation stage under abrupt drought-flood alternation. The results showed that 102 DMs were identified from the rice spike between T1 (abrupt drought-flood alternation) and CK0 (control) treatment, 104 DMs were identified between T1 and CK1 (drought) treatment and 116 DMs were identified between T1 and CK2 (flood) treatment. In addition, a relative quantitative analysis of spike total proteins was conducted using isobaric tags for relative and absolute quantification (iTRAQ) and LC-MS. The identification and analysis of DEPs functions indicates that abrupt drought-flood alternation treatment can promote carbohydrate metabolic, stress response, oxidation-reduction, defense response, and energy reserve metabolic process during the panicle differentiation stage. In this study, relative quantitative metabolomics and proteomics analyses were applied to explore the response mechanism of rice panicle differentiation in response to abrupt drought-flood alternation.\n\nAbbreviations

plant biology↗

bioRxiv2018

The plasma miR-122 basal levels respond to circulating catecholamine in rats

miR-122 in circulation is a promising non-invasive biomarker as a replacement or supplement of current serum biomarkers for liver injuries. But the concept was questioned by recent studies, mainly due to its release from hepatocytes in absence of overt cellular injuries. In this study, we reported that the hepatic metabolism of circulating catecholamines resulted in the release of hepatocyte-specific miR-122. Acute stress-induced hepatocellular deformation was histopathologically different from drug-induced liver injury with significant increases of plasma miR-122 levels. The basal levels of human plasma miR-122 could be significantly altered by emotional responses. Interday variances of plasma miR-122 measurements were reduced effectively by stress-relief measures. The metabolism of basal circulating norepinephrine and epinephrine in liver might contribute to the basal levels of plasma miRNAs expressed in hepatocytes.

molecular biology↗

bioRxiv2017

Sugar metabolism of the first thermophilic Planctomycetes Thermogutta terrifontis: comparative genomic and transcriptomic approache

Xanthan gum, a complex polysaccharide comprising glucose, mannose and glucuronic acid residues, is involved in numerous biotechnological applications in cosmetics, agriculture, pharmaceuticals, food and petroleum industries. Additionally, its oligosaccharides were shown to possess antimicrobial, antioxidant and few other properties. Yet, despite its extensive usage, little is known about xanthan gum degradation pathways and mechanisms.\n\nThermogutta terrifontis R1 was described as the first thermophilic representative of the Planctomycetes phylum. As other cultivated planctomycetes, it grows well on various carbohydrates including oligo- and polysaccharides, however, its capability of anaerobic growth with or without electron acceptors was a novel finding among the representatives of this phylum.\n\nThe aim of this work is to examine T. terrifontis catabolic pathways with a special focus on the xanthan gum degradation pathway using genomic and transriptomic sequencing. Genomic analysis revealed more than a hundred glycosidases, polysaccharide lyases and other CAZymes, involved in oligo- and polysaccharide degradation by T. terrifontis, proteins of central carbohydrate metabolism and aerobic and anaerobic respiration. Furthermore, the combination of genomic and transcriptomic approaches revealed a putative novel xanthan gum degradation pathway involving unusual catalytic steps and enzymes: novel glycosidase(s) of DUF1080 family, hydrolyzing xanthan gum beta-glucosidic backbone linkages and beta-mannosidases instead of xanthan lyases for degradation of terminal beta-mannosidic linkages. Surprisingly, the genes coding DUF1080 proteins were found in high number in T. terrifontis and in many other Planctomycetes genomes, which, together with our observation that xanthan gum being a selective substrate for many planctomycetes, supports the important role of DUF1080 in xanthan gum degradation. Our findings shed light on the metabolism of the first thermophilic planctomycete, capable to degrade a number of polysaccharides, either aerobically or anaerobically, including the biotechnologically important bacterial polysaccharide xanthan gum. The results serve as good foundation for future exploration of T. terrifontis and its enzymes in biotechnological applications.

microbiology↗

bioRxiv2017

Free-living human cells reconfigure their chromosomes in the evolution back to uni-cellularity

Cells of multi-cellular organisms evolve toward uni-cellularity in the form of cancer and, if humans intervene, continue to evolve in cell culture. During this process, gene dosage relationships may evolve in novel ways to cope with the new environment and may regress back to the ancestral unicellular state. In this context, the evolution of sex chromosomes vis-a-vis autosomes is of particular interest. Here, we report the chromosomal evolution in ~600 cancer cell lines. Many of them jettisoned either Y or the inactive X; thus, free-living male and female cells converge by becoming \"de-sexualized\". Surprisingly, the active X often doubled, accompanied by the addition of one haploid complement of autosomes, leading to an X:A ratio of 2:3 from the extant ratio of 1:2. Theoretical modeling of the frequency distribution of X:A karyotypes suggests that the 2:3 ratio confers a higher fitness and may reflect aspects of sex chromosome evolution.

genomics↗

bioRxiv2017

Inhibition of DNA2 nuclease as a therapeutic strategy targeting replication stress in cancer cells.

Replication stress is a characteristic feature of cancer cells, which is resulted from sustained proliferative signaling induced by activation of oncogenes or loss of tumor suppressors. In cancer cells, oncogene-induced replication stress manifests as replication-associated lesions, predominantly double-strand DNA breaks (DSBs). An essential mechanism utilized by cells to repair replication-associated DSBs is homologous recombination (HR). In order to overcome replication stress and survive, cancer cells often require enhanced HR repair capacity. Therefore, the key link between HR repair and cellular tolerance to replication-associated DSBs provides us with a mechanistic rationale for exploiting synthetic lethality between HR repair inhibition and replication stress. Our studies showed that DNA2 nuclease is an evolutionarily conserved essential component of HR repair machinery. Here we demonstrate that DNA2 is indeed overexpressed in pancreatic cancers, one of the deadliest and more aggressive forms of human cancers, where mutations in the KRAS are present in 90%-95% of cases. In addition, depletion of DNA2 significantly reduces pancreatic cancer cell survival and xenograft tumor growth, suggesting the therapeutic potential of DNA2 inhibition. Finally, we develop a robust high-throughput biochemistry assay to screen for inhibitors of the DNA2 nuclease activity. The top inhibitors were shown to be efficacious against both yeast Dna2 and human DNA2. Treatment of cancer cells with DNA2 inhibitors recapitulates phenotypes observed upon DNA2 depletion, including decreased DNA end resection and attenuation of HR repair. Similar to genetic ablation of DNA2, chemical inhibition of DNA2 selectively attenuates the growth of various cancer cells with oncogene-induced replication stress. Taken together, our findings open a new avenue to develop a new class of anti-cancer drugs by targeting druggable nuclease DNA2. We 4, 16. In propose DNA2 inhibition as new strategy in cancer therapy by targeting replication stress, a molecular property of cancer cells that is acquired as a result of oncogene activation instead of targeting undruggable oncoprotein itself such as KRAS.

molecular biology↗

bioRxiv2016

Isolator: accurate and stable analysis of isoform-level expression in RNA-Seq experiments

While RNA-Seq has enabled great progress towards the goal of wide-scale isoform-level mRNA quantification, short reads have limitations when resolving complex or similar sets of isoforms. As a result, estimates of isoform abundance carry far more uncertainty than those made at the gene level. When confronted with this uncertainty, commonly used methods produce estimates that are often high-variance--small perturbations in the data often produce dramatically different results, confounding downstream analysis. We introduce a new method, Isolator, which analyzes all samples in an experiment in unison using a simple Bayesian hierarchical model. Combined with aggressive bias correction, it produces estimates that are simultaneously accurate and show high agreement between samples. In a comprehensive comparison of accuracy and variance, we show that this property is unique to Isolator. We further demonstrate that the approach of modeling an entire experiment enables new analyses, which we demonstrate by examining splicing monotonicity across several time points in the development of human cardiomyocyte cells.

bioinformatics↗