Biology subjects

He, X.

Publications and source records attributed to He, X..

At least 19 recordsLinked to original sources

bioRxiv2018

Ultra-high throughput multiplexing and sequencing of >500 bp amplicon regions on the Illumina HiSeq 2500 platform

Amplification, sequencing and analysis of the 16S rRNA gene affords characterization of microbial community composition. As this tool has become more popular and amplicon-sequencing applications have grown in the total number of samples, growth in sample multiplexing is becoming necessary while maintaining high sequence quality and sequencing depth. Here, modifications to the Illumina HiSeq 2500 platform are described which produce greater multiplexing capabilities and 300 bp paired-end reads of higher quality than produced by the current Illumina MiSeq platform. To improve the feasibility and flexibility of this method, a 2-Step PCR amplification protocol is also described that allows for targeting of different amplicon regions, thus improving amplification success from low bacterial bioburden samples.\n\nImportanceAmplicon sequencing has become a popular and widespread tool for surveying microbial communities. Lower overall costs associated with high throughput sequencing have made it a widely-adopted approach, especially for projects which necessitate sample multiplexing to eliminate batch effect and reduced time to acquire data. The method for amplicon sequencing on the Illumina HiSeq 2500 platform described here provides improved multiplexing capabilities while simultaneously producing greater quality sequence data and lower per sample cost relative to the Illumina MiSeq platform, without sacrificing amplicon length. To make this method more flexible to various amplicon targeted regions as well as improve amplification from low biomass samples, we also present and validate a 2-Step PCR library preparation method.

microbiology↗

bioRxiv2018

Prioritizing risk genes for neurodevelopmental disorders using pathway information

Trio family and case-control studies of next-generation sequencing data have proven integral to understanding the contribution of rare inherited and de novo single-nucleotide variants to the genetic architecture of complex disease. Ideally, such studies should identify individual risk genes of moderate to large effect size to generate novel treatment hypotheses for further follow-up. However, due to insufficient power, gene set enrichment analyses have come to be relied upon for detecting differences between cases and controls, implicating sets of hundreds of genes rather than specific targets for further investigation. Here, we present a Bayesian statistical framework, termed gTADA, that integrates gene-set membership information with gene-level de novo and rare inherited case-control counts, to prioritize risk genes with excess rare variant burden within enriched gene sets. Applying gTADA to available whole-exome sequencing datasets for several neuropsychiatric conditions, we replicated previously reported gene set enrichments and identified novel risk genes. For epilepsy, gTADA prioritized 40 risk genes (posterior probabilities > 0.95), 6 of which replicate in an independent whole-genome sequencing study. In addition, 30/40 genes are novel genes. We found that epilepsy genes had high protein-protein interaction (PPI) network connectivity, and show specific expression during human brain development. Some of the top prioritized EPI genes were connected to a PPI subnetwork of immune genes and show specific expression in prenatal microglia. We also identified multiple enriched drug-target gene sets for EPI which included immunostimulants as well as known antiepileptics. Immune biology was supported specifically by case-control variants from familial epilepsies rather than do novo mutations in generalized encephalitic epilepsy.

genomics↗

bioRxiv2018

Context-dependent architecture of brain state dynamics is explained by white matter connectivity and theories of network control

A diverse white matter network and finely tuned neuronal membrane properties allow the brain to transition seamlessly between cognitive states. However, it remains unclear how static structural connections guide the temporal progression of large-scale brain activity patterns in different cognitive states. Here, we deploy an unsupervised machine learning algorithm to define brain states as time point level activity patterns from functional magnetic resonance imaging data acquired during passive visual fixation (rest) and an n-back working memory task. We find that brain states are composed of interdigitated functional networks and exhibit context-dependent dynamics. Using diffusion-weighted imaging acquired from the same subjects, we show that structural connectivity constrains the temporal progression of brain states. We also combine tools from network control theory with geometrically conservative null models to demonstrate that brains are wired to support states of high activity in default mode areas, while requiring relatively low energy. Finally, we show that brain state dynamics change throughout development and explain working memory performance. Overall, these results elucidate the structural underpinnings of cognitively and developmentally relevant spatiotemporal brain dynamics.

neuroscience↗

bioRxiv2018

mTADA: a framework for analyzing de novo mutations in multiple traits

Joint analysis of multiple traits can result in the identification of associations not found through the analysis of each trait in isolation. In addition, approaches that consider multiple traits can aid in the characterization of shared genetic etiology among those traits. In recent years, parent-offspring trio studies have reported an enrichment of de novo mutations (DNMs) in neuropsychiatric disorders. The analysis of DNM data in the context of neuropsychiatric disorders has implicated multiple putatively causal genes, and a number of reported genes are shared across disorders. However, a joint analysis method designed to integrate de novo mutation data from multiple studies has yet to be implemented. We here introduce multi pi e-trait TAD A (mTADA) which jointly analyzes two traits using DNMs from non-overlapping family samples. mTADA uses two single-trait analysis data sets to estimate the proportion of overlapping risk genes, and reports genes shared between and specific to the relevant disorders. We applied mTADA to >13,000 trios for six disorders: schizophrenia (SCZ), autism spectrum disorder (ASD), developmental disorders (DD), intellectual disability (ID), epilepsy (EPI), and congenital heart disease (CHD). We report the proportion of overlapping risk genes and the specific risk genes shared for each pair of disorders. A total of 153 genes were found to be shared in at least one pair of disorders. The largest percentages of shared risk genes were observed for pairs of DD, ID, ASD, and CHD (>20%) whereas SCZ, CHD, and EPI did not show strong overlaps In risk gene set between them. Furthermore, mTADA identified additional SCZ, EPI and CHD risk genes through integration with DD de novo mutation data. For CHD, using DD information, 31 risk genes with posterior probabilities > 0.8 were identified, and 20 of these 31 genes were not in the list of known CHD genes. We find evidence that most significant CHD risk genes are strongly expressed in prenatal stages of the human genes. Finally, we validated our findings for CHD and EPI in independent cohorts comprising 1241 CHD trios, 226 CHD singletons and 197 EPI trios. Multiple novel risk genes identified by mTADA also had de novo mutations in these independent data sets. The joint analysis method introduced here, mTADA, is able to identify risk genes shared by two traits as well as additional risk genes not found through single-trait analysis only. A number of risk genes reported by mTADA are identified only through joint analysis, specifically when ASD, DD, or ID are one of the two traits examined. This suggests that novel genes for the trait or a new trait might converge to a core gene list of the three traits.

genomics↗

bioRxiv2018

Centromere repositioning induced by inner kinetochore impairment generates a meiosis barrier

Centromeres dictate the sites for kinetochore assembly on chromosomes, while their own position on each chromosome is determined epigenetically by a specific histone H3 variant CENP-A. For all eukaryotic species, the chromosomal position of each centromere is distinct and inherited with high fidelity, although the mechanisms underlying the epigenetic stability and its functional significance remain largely unknown. Here in the fission yeast Schizosaccharomyces pombe, we show that mutations in inner kinetochore components influence centromeric chromatin organization to various levels. In extreme cases, a single deletion of wip1, mhf1 and mhf2 (the conserved CENP-T-W-S-X complex subunits) or double deletions of cnp3 (a homologue of mammalian CENP-C) and fta6 (a pombe specific component) induce centromere repositioning - inactivation of the original centromere and formation of a neocentromere - in one of the three chromosomes at random. Neocentromeres tend to locate in pericentromeric heterochromatin regions, although heterochromatin is not required for centromere inactivation. Cells carrying a neocentromere are competent in mitosis and in meiosis of homozygotes. However, when these cells are crossed to cells carrying the original centromere, the progeny suffers severe lethality due to defects in meiotic chromosome segregation. These results recapitulate a meiosis barrier that could initiate genetic divergence between two populations with mismatched centromeres, documenting a potential role of the Evolutionary New Centromeres (ENCs) in speciation.\n\nSignificance StatementIn eukaryotes, centromeres are chromosomal regions where kinetochores are assembled and the positions of centromeres are accurately inherited. While the centromere and kinetochore assembly are extensively studied, the mechanisms that each centromere maintain its identity on chromosomes are still not well understood. In this study, we demonstrated that the inner kinetochore is required for the normal centromere identity as single depletion of the inner kinetochore CENP-T-W-S-X complex or double deletions of cnp3/CENP-C and fta6 induce centromere repositioning. We further showed cells carrying a neocentromere are reproductively isolated from the wildtype population carrying the original centromere. Taken together, these results suggest that induced centromere repositioning mimics the evolutionary new centromeres and is sufficient to cause reproductive isolation.

cell biology↗

bioRxiv2018

Osteoblastic PLEKHO1 contributes to joint inflammation in rheumatoid arthritis

Osteoblasts participating in the inflammation regulation gradually obtain concerns. However, its role in joint inflammation of rheumatoid arthritis (RA) is largely unknown. Pleckstrin homology domain-containing family O member 1 (PLEKHO1) was previously identified as a negative regulator of osteogenic lineage activity. Here we demonstrated that PLEKHO1 was highly expressed in osteoblasts of articular specimens from RA patients and inflammatory arthritis mice. Genetic deletion of osteoblastic Plekho1 ameliorated joint inflammation in mice with collagen-induced arthritis (CIA) and K/BxN serum-transfer arthritis (STA), whereas overexpressing Plekho1 only within osteoblasts in CIA and STA mice demonstrated exacerbated local inflammation. Further in vitro studies indicated that PLEKHO1 was required for TRAF2-mediated RIP1 ubiquitination to activate NF-kB for inducing inflammatory cytokines production in osteoblasts. Moreover, osteoblastic PLEKHO1 inhibition improved joint inflammation and attenuated bone formation reduction in CIA mice and non-human primate arthritis model. These data strongly suggest that highly expressed PLEKHO1 in osteoblast mediates joint inflammation in RA. Targeting osteoblastic PLEKHO1 may exert dual therapeutic action of alleviating joint inflammation and promoting bone formation in RA.

cell biology↗

bioRxiv2018

Expression profile analysis of circular RNAs in essential hypertension by microarray and bioinformatics.

Circular RNAs (circRNAs), widely found in human cells, are involved in disease and play an important role in progression. To determine whether circRNAs are related in essential hypertension (EH), we analyzed the expression profile of circRNAs and miRNAs in 5 EH and 5 healthy controls cases which were screened by microarray. Through microarray data and public data analysis, differently expressed transcripts were divided into modules, and circRNAs were functionally annotated by miRNAs. The expression of two circRNAs, has_circ_0037909 and has_circ_0105015, were validated in EH by qRT-PCR, which may be associated with EH. Further analysis showed that two circRNAs might through immune system by up-regulation circRNAs and down-regulation expression. These circRNAs biological functions need to be further validated.

genetics↗

bioRxiv2018

Model-based analysis of positive selection significantly expands the list of cancer driver genes, including RNA methyltransferases

Identifying driver genes is a central problem in cancer biology, and many methods have been developed to identify driver genes from somatic mutation data. However, existing methods either lack explicit statistical models, or rely on very simple models that do not capture complex features in somatic mutations of driver genes. Here, we present driverMAPS (Model-based Analysis of Positive Selection), a more comprehensive model-based approach to driver gene identification. This new method explicitly models, at the single-base level, the effects of positive selection in cancer driver genes as well as highly heterogeneous background mutational process. Its selection model captures elevated mutation rates in functionally important sites using multiple external annotations, as well as spatial clustering of mutations. Its background mutation model accounts for both known covariates and unexplained local variation. Simulations under realistic evolutionary models demonstrate that driverMAPS greatly improves the power of driver gene detection over state-of-the-art approaches. Applying driverMAPS to TCGA data across 20 tumor types identified 159 new potential driver genes. Cross-referencing this list with data from external sources strongly supports these findings. The novel genes include the mRNA methytransferases METTL3-METTL14, and we experimentally validated METTL3 as a potential tumor suppressor gene in bladder cancer. Our results thus provide strong support to the emerging hypothesis that mRNA modification is an important biological process underlying tumorigenesis.

genomics↗

bioRxiv2018

Trio deep-sequencing does not reveal unexpected mutations in Cas9-edited monkeys

CRISPR-Cas9 is a widely-used genome editing tool, but its off-target effect remains a concern, especially in view of future clinical applications. Non-human primates (NHPs) share close genetic and physiological similarities with humans, making them an ideal preclinical model for developing Cas9-based therapies. However, no comprehensive in vivo off-target assessment has been conducted in NHPs. Here we performed whole genome trio sequencing of Cas9-treated monkeys. We found they only carried a small number of de novo mutations that can be explained by expected spontaneous mutations, and no unexpected mutations were detected.

bioengineering↗

bioRxiv2018

Integrating Hi-C and FISH data for modeling 3D organizations of chromosomes

The new advances in various experimental techniques that provide complementary in-formation about the spatial conformations of chromosomes have inspired researchers to develop computational methods to fully exploit the merits of individual data sources and combine them to improve the modeling of chromosome structure. In this paper, we propose GEM-FISH, a first method for reconstructing the 3D models of chromosomes through systematically integrating both Hi-C and FISH data with the prior biophysical knowledge of a polymer model. Comprehensive tests on a set of chromosomes for which both Hi-C and FISH data were available have demonstrated that GEM-FISH can reconstruct the 3D models of chromosomes with more accurate spatial organizations of TADs and compartments than using only Hi-C data. In addition, GEM-FISH can accurately capture the spatial proximity of loop loci and the colocalization of loci from the same sub-compartments. Moreover, our reconstructed 3D models of chromosomes revealed novel patterns of spatial distributions of super-enhancers which can provide useful insights into understanding the functional roles of these super-enhancers in gene regulation. All these results demonstrated that, through integrating both Hi-C and FISH data into a unified framework, GEM-FISH can provide a better tool for modeling the 3D organizations of chromosomes than using the Hi-C data alone.

bioinformatics↗

bioRxiv2018

Dynamics of the sex ratio in Tetrahymena thermophila

Sex is often hailed as one of the major successes in evolution, and in sexual organisms the maintenance of proper sex ratio is crucial. As a large unicellular eukaryotic lineage, ciliates exhibit tremendous variation in mating systems, especially the number of sexes and the mechanism of sex determination (SD), and yet how the populations maintain proper sex ratio is poorly understood. Here Tetrahymena thermophila, a ciliate with seven mating types (sexes) and probabilistic SD mechanism, is analyzed from the standpoint of population genetics. It is found based on a newly developed population genetics model that there are plenty of opportunities for both the co-existence of all seven sexes and the fixation of a single sex, pending on several factors, including the strength of natural selection. To test the validity of predictions, five experimental populations of T. thermophila were maintained in the laboratory so that the factors that can influence the dynamics of sex ratio could be controlled and measured. Furthermore, whole-genome sequencing was employed to examine the impact of newly arisen mutations. Overall, it is found that the experimental observations highly support theoretical predictions. It is expected that the newly established theoretical framework is applicable in principle to other multi-sex organisms to bring more insight into the understanding of the maintenance of multiple sexes in a natural population.

evolutionary biology↗

bioRxiv2018

Cohesin interacts with a panoply of splicing factors required for cell cycle progression and genomic organization

The cohesin complex regulates sister chromatid cohesion, chromosome organization, gene expression, and DNA repair. Here we report that endogenous human cohesin interacts with a panoply of splicing factors and RNA binding proteins, including diverse components of the U4/U6.U5 tri-snRNP complex and several splicing factors that are commonly mutated in cancer. The interactions are enhanced during mitosis, and the interacting splicing factors and RNA binding proteins follow the cohesin cycle and prophase pathway of regulated interactions with chromatin. Depletion of cohesin-interacting splicing factors results in stereotyped cell cycle arrests and alterations in genomic organization. These data support the hypothesis that splicing factors and RNA binding proteins control cell cycle progression and genomic organization via regulated interactions with cohesin and chromatin.\n\nOne Sentence SummaryEndogenous tagging reveals that cohesin interacts with diverse chromatin-bound splicing factors that regulate cell cycle progression and genomic organization in human cells.

cell biology↗

bioRxiv2018

DNA local structure decreases mutation rates

BackgroundMutation rates vary across the genome. Whereas many trans factors that influence mutation rates have been identified, as have specific sequence motifs at the 1-7 bp scale, cis elements remain poorly characterized. The lack of understanding why different sequences have different mutation rates hampers our ability to identify positive selection in evolution and to identify driver mutations in tumorigenesis.\n\nResultsHere we show, using a combination of synthetic genes and sequencing of thousands of isolated yeast colonies, that intrinsic DNA curvature is the major cis determinant of mutation rate. Mutation rate negatively correlates with DNA curvature within genes, and a 10% decrease in curvature results in a 70% increase in mutation rate. Consistently, both yeast cells and human tumors accumulate mutations in regions with small curvature. We further show that this effect is due to differences in the intrinsic mutation rate, likely due to differences in mutagen sensitivity, and not due to differences in the local activity of DNA repair.\n\nConclusionsOur study establishes a framework in understanding the cis properties of DNA sequence in modulating the local mutation rate and identifies a novel causal source of non-uniform mutation rates across the genome.

genetics↗

bioRxiv2018

Colonization of phosphate-solubilizing Pseudomonas sp. strain P34-L in the wheat rhizosphere and its effects on wheat growth and the expression of phosphate transporter gene TaPT4 in wheat

The ability to colonize the rhizosphere is an important basics requirement for field application of plant growth-promoting rhizobacteria (PGPR) strains. There are complex signal exchanges and mutual recognition between microbes and plants. In this study, phosphate-solubilizing Pseudomonas sp. P34, a PGPR strain with affinity to wheat, was isolated from the wheat rhizosphere by wheat germ agglutinin (WGA). The plasmid pTR102 harboring the luciferase luxAB gene was transferred into P34 to create P34-L. The labeled strain was used to track the temporal and spatial characteristics of colonization in wheat rhizosphere and its effects on wheat development. The transcript level of phosphate transporter gene TaPT4, a phosphorus deficiency indicator gene, in wheat roots was monitored by quantitative reverse-transcription PCR. The experimental results indicated that there was a high density of stain P34-L within the top 8-cm depth of the wheat rhizosphere on day 36 of wheat growth. The strain could survive in the wheat rhizosphere for a long time, and colonize new spaces in wheat rhizosphere following the extension of wheat roots. Compared with uninoculated wheat plants, those inoculated with P34-L showed significantly increased phosphorus accumulation in leaves, seedling fresh and dry weight, root fresh and dry weight, total root length, and number of root tips, forks, crossings, which showed a great value of application of the strain on wheat production by promoting the root growth and dry matter accumulation. Strain P34-L down-regulated the transcript level of TaPT4 in wheat roots, which means a well phosphorus supplementation environment was established by P34-L.\n\nImportanceMany PGPR strains often failed to achieve the desired effects when applied in the field. One major reason for the failure is lack of a special affinity between a certain strain and the target host plant, so those strains have low competitive ability with the indigenous microorganism, and unable to survive constantly in rhizosphere. In this work, a new technique to isolate wheat-specific phosphate-solubilizing PGPR strain by WGA was established. The isolate P34 was confirmed can colonize the wheat rhizosphere, and have significantly ability in promoting phosphorus absorption and wheat growth by luminescence labeling techniques. Furthermore, the phosphate-solubilizing ability of this affinity PGPR strain was verified in gene level by quantitative reverse-transcription PCR. These results lay a firm foundation for further research on the relationships between PGPR and their host plants. Meanwhile, this work supplied a potential ideal biofertilizer producing strain for sustainable agriculture.

microbiology↗

bioRxiv2018

The expression tractability of a biological trait

Understanding how gene expression is translated to phenotype is central to modern molecular biology, but the success is contingent on the intrinsic tractability of the specific traits under examination. However, an a priori estimate of trait tractability from the perspective of gene expression is unavailable. Motivated by the concept of entropy in a thermodynamic system, we here propose such an estimate (ST) by gauging the number (N) of different expression states that underlie the same trait abnormality, with large ST corresponding to large N. By analyzing over 200 yeast morphological traits we show that ST is constrained by natural selection, which builds co-regulated gene modules to minimize the total number of possible expression states. We further show that ST is a good measure of the titer of recurrent patterns of an expression-trait relationship, predicting the extent to which the trait could be deterministically understood with gene expression data.

genomics↗

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

Evidence of independent acquisition and adaption of ultra-small bacteria to human hosts across the highly diverse yet reduced genomes of the phylum Saccharibacteria

Recently, we discovered that a member of the Saccharibacteria/TM7 phylum (strain TM7x) isolated from the human oral cavity, has an ultra-small cell size (200-300nm), a highly reduced genome (705 Kbp) with limited de novo biosynthetic capabilities, and a very novel lifestyle as an obligate epibiont on the surface of another bacterium 1. There has been considerable interest in uncultivated phyla, particularly those that are now classified as the proposed candidate phyla radiation (CPR) reported to include 35 or more phyla and are estimated to make up nearly 15% of the domain Bacteria. Most members of the larger CPR group share genomic properties with Saccharibacteria including reduced genomes (<1Mbp) and lack of biosynthetic capabilities, yet to date, strain TM7x represents the only member of the CPR that has been cultivated and is one of only three CPR routinely detected in the human body. Through small subunit ribosomal RNA (SSU rRNA) gene surveys, members of the Saccharibacteria phylum are reported in many environments as well as within a diversity of host species and have been shown to increase dramatically in human oral and gut diseases. With a single copy of the 16S rRNA gene resolved on a few limited genomes, their absolute abundance is most often underestimated and their potential role in disease pathogenesis is therefore underappreciated. Despite being an obligate parasite dependent on other bacteria, six groups (G1-G6) are recognized using SSU rRNA gene phylogeny in the oral cavity alone. At present, only genomes from the G1 group, which includes related and remarkably syntenic environmental and human oral associated representatives1, have been uncovered to date. In this study we systematically captured the spectrum of known diversity in this phylum by reconstructing completely novel Class level genomes belonging to groups G3, G6 and G5 through cultivation enrichment and/or metagenomic binning from humans and mammalian rumen. Additional genomes for representatives of G1 were also obtained from modern oral plaque and ancient dental calculus. Comparative analysis revealed remarkable divergence in the host-associated members across this phylum. Within the human oral cavity alone, variation in as much as 70% of the genes from nearest oral clade (AAI 50%) as well as wide GC content variation is evident in these newly captured divergent members (G3, G5 and G6) with no environmental relatives. Comparative analyses suggest independent episodes of transmission of these TM7 groups into humans and convergent evolution of several key functions during adaptation within hosts. In addition, we provide evidence from in vivo collected samples that each of these major groups are ultra-small in size and are found attached to larger cells.

microbiology↗

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↗