Biology subjects

Chen, L.

Publications and source records attributed to Chen, L..

At least 1,045 records · Page 58Linked to original sources

bioRxiv2017

Variations in δ13C of different plant organs: implications for post-photosynthetic fractionation

Compared to photosynthetic fractionation, the mechanism of post-photosynthetic carbon isotope fractionation is not well understood. The aim of this study was to investigate post-photosynthetic fractionation in both above and below ground tissues and to evaluate potential hypotheses explaining differences in carbon isotope composition ({delta}13C) among different plant organs, which can provide valuable insights into plant physiology. The results revealed that there is no significant day-night difference in{delta} 13C of twig phloem water soluble organic materials (WSOM), which could be explained by the unrestricted exchange of triose-phosphates between the chloroplast and cytoplasm and a time lag for carbohydrate exportation. Further, we found that{delta} 13C of twig phloem WSOM is more sensitive to plant water status than leaf WSOM. Analysis of{delta} 13C in different plant organs showed that the greatest 13C enrichment was recorded in stem phloem. Divergences in{delta} 13C of phloem WSOM among different plant organs were not likely to be explained by respiratory fractionation or time lag and were ascribed to transport of carbohydrates across organ boundaries and metabolic processes. Our study demonstrated that post-photosynthesis fractionation could not be ascribed to a single, unifying hypotheses; instead, it is the result of multiple processes.\n\nHighlight{delta}13C of twig phloem water soluble organic materials varied no clear diel pattern. In the leaf-twig-stem-root sequence, the greatest 13C enrichment was recorded in stem phloem.

ecology↗

bioRxiv2017

Highly tamoxifen-inducible principal-cell-specific Cre mice with complete fidelity in cell specificity and no leakiness

An ideal inducible system should be cell-specific and have absolute no background recombination without induction (i.e. no leakiness), a high recombination rate after induction, and complete fidelity in cell specificity (i.e. restricted recombination exclusively in cells where the driver gene is expressed). However, such an ideal mouse model remains unavailable for collecting duct research. Here, we report a mouse model that meets these criteria. In this model, a cassette expressing ERT2CreERT2 (ECE) is inserted at the ATG of the endogenous Aqp2 locus to disrupt Aqp2 function and to express ECE under the control of the Aqp2 promoter. The resulting allele is named Aqp2ECE. There was no indication of a significant impact of disruption of a copy of Aqp2 on renal function and blood pressure control in adult Aqp2ECE/+ heterozygotes. Without tamoxifen, Aqp2ECE did not activate a Cre-dependent red fluorescence protein (RFP) reporter in adult kidneys. A single injection of tamoxifen (2 mg) to adult mice enables Aqp2ECE to induce robust RFP expression in the whole kidney 24h post injection, with the highest recombination efficiency of 95% in the inner medulla. All RFP-labeled cells expressed principal cell markers (Aqp2 & Aqp3), but not intercalated cell markers (V-ATPase B1B2, and carbonic anhydrase II). Hence, Aqp2ECE confers principal cell-specific tamoxifen-inducible recombination with absolute no leakiness, high inducibility, and complete fidelity in cell specificity, which should be an important tool for temporospatial control of target genes in the principal cells and for Aqp2+ lineage tracing in adult mice.

genetics↗

bioRxiv2017

Use of a scoring strategy to determine clinical risk of progression and risk group-specific treatment adherence in subjects with latent tuberculosis infection

BackgroundAnnual incidence of active tuberculosis (TB) cases has plateaued in the US from 2013-2015. Most cases are from reactivation of latent tuberculosis infection (LTBI). A likely contributor is suboptimal LTBI treatment completion rates in subjects at high risk of developing active TB. It is unknown whether these patients are adequately identified and treated under current standard of care.\n\nMethodsIn this study, we sought to retrospectively assess the utility of an online risk calculator (tstin3d.com) in determining probability of LTBI and defining the characteristics and treatment outcomes of Low: 0-<10%, Intermediate: 10-<50% and High: 50-100% risk groups of asymptomatic subjects with LTBI seen between 2010-2015.\n\nResults51(41%), 46 (37%) and 28 (22%) subjects were in Low, Intermediate and High risk groups respectively. Tstin3d.com was useful in determining the probability of LTBI in tuberculin skin test positive US born subjects. Of 114 subjects with available treatment information, overall completion rate was 61% and rates of completion in Low (60%), Intermediate (63%) and High (57%) risk groups were equivalent. 75% subjects in the 3HP group completed treatment compared to 58% in the INH group. Provider documentation of important clinical risk factors was often incomplete. Logistic regression analysis showed no clear trends of treatment completion being associated with assessment of a risk factor.\n\nConclusionThese findings suggest tstin3d.com could be utilized in the US setting for risk stratification of patients with LTBI and select treatment based on risk. Current standard of care practice leads to subjects in all groups finishing treatment at equivalent rates.

epidemiology↗

bioRxiv2017

Neural code uses self-information principle to organize the brain’s universal cell-assembly coding

The brain generates cognition and behavior through firing changes of its neurons, yet, with enormous firing variability, the organizing principle underlying real-time neural code remains unclear. Here, we test the Neural Self-Information Theory that neural code is constructed via the self-information principle under which each inter-spike-interval (ISI) is inherently self-tagged with discrete information based on its relation to ISI variability-probability distribution - higher-probability ISIs, which reflect the balanced excitation-inhibition ground state, convey minimal information, whereas lower-probability ISIs, which signify statistical surprisals, carry more information. Moreover, temporally coordinated ISI surprisals across neural cliques intrinsically give rise to real-time cell-assembly neural code. As a result, this self-information-based neural coding is uniquely intrinsic to the neurons themselves, with no need for outside observers to set any reference point to manually mark external or internal inputs. Applying this neural self-information concept, we devised an unbiased general decoding strategy and successfully uncovered 15 distinct cell-assembly patterns from multiple cortical and hippocampal circuits associated with different sleep cycles, earthquake, elevator-drop, foot-shock experiences, navigation or various actions in five-choice visual-discrimination operant-conditioning tasks. Detailed analyses of all 15 cell assemblies revealed that ~20% of the skewed ISI distribution tails were responsible for the emergence of robust cell-assembly codes, conforming to the Pareto Principle. These findings support the notion that neural coding is organized via the self-information principle to generate real-time information across brain regions, cognitive modalities, and behaviors.

neuroscience↗

bioRxiv2017

Forward-reverse mutation cycles between stages of cancer development

Earlier, prominent occurrences of interstitial loss-of-heterozygosities (LOHs) were found in different cancers as a type of single-nucleotide-variations (SNVs), at rates far exceeding those of the commonly investigated gain-of-heterozygosities (GOHs) type of SNVs. Herein, such co-occurrences of LOHs and GOHs were confirmed in 102 cases of four cancer types analyzed with three different next-generation sequencing platforms, comparing non-tumor, paratumor, and tumor tissues with white-blood-cell controls; and in 246 pan-cancer cases of whole-genome tumor-control pairs. Unexpectedly, large numbers of SNVs enriched with CG>TG GOHs and copy-number-variations (CNVs) proximal to these GOHs were detected in the non-tumor tissues, which were extensively reversed in paratumors showing prominent TG>CG LOHs with proximal CNVs, and less so in tumors to form forward-reverse mutation cycles. Lineage effects in the reversions, likely resulting from directional selection, supported a sequential rather than parallel mode of evolution as described in a Stage Specific Populations model of cancer development.

cancer biology↗

bioRxiv2017

A set informative multiple autosomal markers for human identification: forensic research and population genetics analysis in a Chinese Xinjiang Hui group

In recent years, insertion/deletion (InDel) markers became a promising and useful supporting tool in forensic identification cases and biogeographic research field. In this study, 30 InDel loci were explored to reveal the genetic diversities and genetic relationships between Chinese Xinjiang Hui group and the 24 previously studied populations using varies methods such as forensic statistical parameter analysis, phylogenetic reconstruction, STRUCTURE analysis, multi-dimensional scaling, and principal component analysis. The observed heterozygosity and expected heterozygosity ranged from 0.1971 (HLD118) to 0.5092 (HLD 92), 0.2222 (HLD 114) to 0.5000 (HLD 6), respectively. Besides, after Bonferroni correction, no deviations from Hardy-Weinberg equilibrium tests were found at all 30 loci in Xinjiang Hui group. The cumulative probability of exclusion and combined discrimination power were 0.988849 and 0.99999999999378, respectively, which indicated that the 30 loci could be used as complementary genetic markers for paternity test and be qualified for personal identification in forensic cases. In this study, we found that Xinjiang Hui group had close relationships with most Chinese groups, especially Han populations, and all the results based on different genetic methods we used had a strong support for this finding. The 30 InDel loci has important significance in forensic identification research, in spite of this, for a better understanding of genetic background of the Chinese Xinjiang Hui group, molecular genetic genotyping at various genetic markers is necessary in future studies.\n\nSummary StatementWe report here, a promising Individual identification and population differentiation maker which could be used in forensic cases.

genetics↗

bioRxiv2017

Climate change will lead to pronounced shifts in the diversity of soil microbial communities

Soil bacteria are key to ecosystem function and maintenance of soil fertility. Leveraging associations of current geographic distributions of bacteria with historic climate, we predict that soil bacterial diversity will increase across the majority (~75%) of the Tibetan Plateau and northern North America if bacterial communities equilibrate with existing climatic conditions. This prediction is possible because the current distributions of soil bacteria have stronger correlations with climate from ~50 years ago than with current climate. This lag is likely associated with the time it takes for soil properties to adjust to changes in climate. The predicted changes are location specific and differ across bacterial taxa, including some bacteria that are predicted to have reductions in their distributions. These findings demonstrate the widespread influence that climate change will have on belowground diversity and highlight the importance of considering bacterial communities when assessing climate impacts on terrestrial ecosystems.\n\nIMPORTANCEThere have been many studies highlighting how plant and animal communities lag behind climate change, causing extinction and diversity debts that will slowly be paid as communities equilibrate. By virtue of their short generation times and dispersal abilities, soil bacteria might be expected to respond to climate change quickly and to be effectively in equilibrium with current climatic conditions. We found strong evidence to the contrary in Tibet and North America. These findings could significantly improve understanding of climate impacts on soil microbial communities.

ecology↗

bioRxiv2017

Transcriptomes of major renal collecting-duct cell types in mouse identified by single-cell RNA-Seq

Prior RNA sequencing (RNA-Seq) studies have identified complete transcriptomes for most renal epithelial cell types. The exceptions are the cell types that make up the renal collecting duct, namely intercalated cells (ICs) and principal cells (PCs), which account for only a small fraction of the kidney mass, but play critical physiological roles in the regulation of blood pressure, extracellular fluid volume and extracellular fluid composition. To enrich these cell types, we used fluorescence-activated cell sorting (FACS) that employed well established lectin cell surface markers for PCs and type B ICs, as well as a newly identified cell surface marker for type A ICs, viz. c-Kit. Single-cell RNA-Seq using the 1C- and PC-enriched populations as input enabled identification of complete transcriptomes of A-ICs, B-ICs and PCs. The data were used to create a freely-accessible online gene-expression database for collecting duct cells. This database allowed identification of genes that are selectively expressed in each cell type including cell-surface receptors, transcription factors, transporters and secreted proteins. The analysis also identified a small fraction of hybrid cells expressing both aquapor{inverted exclamation}n-2 and either anion exchanger 1 or pendrin transcripts. In many cases, mRNAs for receptors and their ligands were identified in different cells (e.g. Notch2 chiefly in PCs vs Jag1 chiefly in ICs) suggesting signaling crosstalk among the three cell types. The identified patterns of gene expression among the three types of collecting duct cells provide a foundation for understanding physiological regulation and pathophysiology in the renal collecting duct.\n\nSIGNIFICANCE STATEMENTA long-term goal in mammalian biology is to identify the genes expressed in every cell type of the body. In kidney, the expressed genes (\"transcriptome\") of all epithelial cell types have already been identified with the exception of the cells that make up the renal collecting duct, responsible for regulation of blood pressure and body fluid composition. Here, a technique called \"single-cell RNA-Seq\" was used in mouse to identify transcriptomes for the major collecting-duct cell types: type A intercalated cells, type B intercalated cells and principal cells. The information was used to create a publicly-accessible online resource. The data allowed identification of genes that are selectively expressed in each cell type, informative for cell-level understanding of physiology and pathophysiology.

physiology↗

bioRxiv2017

A stable beneficial symbiotic relationship between endophytic fungus Schizophyllum commune and host plant Panax ginseng

Endophytes and plants can establish specific long-term symbiosis through the accumulation of secondary metabolites. Interactions between microbial inhabitants represent a novel area of study for natural products research. In this study, a strain of endophyte 3R-2 that can enhance the biomass and contents of ginsenoside Rc, ginsenoside Rg2 and ginsenoside Rg3 of Panax ginseng hairy roots was screened out via HPLC, which was identified as Schizophyllum commune through the morphological and molecular identification. On the base, we found the infection of the endophyte were obviously observed widely in the P. ginseng and the strain formed a stable relationship with P. ginseng hairy roots in parenchyma cells around through tissues embedding slicing, HE ammonium silver staining and immunofluorescence staining. On the other hand, elicitors of fungus 3R-2 can also significantly promote hairy root growth and contents of several ginsenosides, even several times higher than 3R-2 mycelium did. Moreover, S. commune 3R-2 mycelium and its elicitor could enhance the transcriptional activity of key genes during the ginsenosides biosynthetic pathway dramatically. Thus, endophyte S. commune 3R-2 and its elicitor change the chemical substance content by regulating the expression of genes involved in the secondary metabolite biosynthetic pathway.

plant biology↗

bioRxiv2017

In vivo Imaging β-cell Function Reveals Two Waves of β-cell Maturation

The insulin-secreting cells generated from stem cells in vitro are less glucose responsive than primary {beta}-cells. To search for the missing ingredients that are needed for {beta}-cell maturation, we have longitudinally monitored function of every {beta}-cell in Tg (ins:Rcamp1.07) zebrafish embryos with a newly-invented two-photon light-sheet microscope. We have shown that {beta}-cell maturation begins from the islet mantle and propagates to the islet core during the hatching period, coordinated by the islet vascularization. Lower concentration of glucose is optimal to initiate {beta}-cell maturation, while increased glucose delivery to every cell through microcirculation is required for functional boosting of the {beta}-cells. Both the initiation and the boosting of {beta}-cell maturation demands activation of calcineurin/NFAT by glucose. Calcineurin activator combined with glucose promotes mouse neonatal {beta}-cells cultured in vitro to mature to a functional state similar to adult {beta}-cells, suggesting a new strategy for improving stem cell-derived {beta}-like cell function in vitro.

developmental biology↗

bioRxiv2017

Proteomic Architecture of Human Coronary and Aortic Atherosclerosis

The inability to detect premature atherosclerosis significantly hinders implementation of personalized therapy to prevent coronary heart disease. A comprehensive understanding of arterial protein networks and how they change in early atherosclerosis could identify new biomarkers for disease detection and improved therapeutic targets. Here we describe the human arterial proteome and the proteomic features strongly associated with early atherosclerosis based on mass-spectrometry analysis of coronary artery and aortic specimens from 100 autopsied young adults (200 arterial specimens). Convex analysis of mixtures, differential dependent network modeling and bioinformatic analyses defined the composition, network re-wiring and likely regulatory features of the protein networks associated with early atherosclerosis. Among other things the results reveal major differences in mitochondrial protein mass between the coronary artery and distal aorta in both normal and atherosclerotic samples - highlighting the importance of anatomic specificity and dynamic network structures in in the study of arterial proteomics. The publicly available data resource and the description of the analysis pipeline establish a new foundation for understanding the proteomic architecture of atherosclerosis and provide a template for similar investigations of other chronic diseases characterized by multi-cellular tissue phenotypes.\n\nHighlightsO_LILC MS/MS analysis performed on 200 human aortic or coronary artery samples\nC_LIO_LINumerous proteins, networks, and regulatory pathways associated with early atherosclerosis\nC_LIO_LIMitochondrial proteins mass and selected metabolic regulatory pathways vary dramatically by disease status and anatomic location\nC_LIO_LIPublically available data resource and analytic pipeline are provided or described in detail\nC_LI

molecular biology↗

bioRxiv2017

Draft genome of the Reindeer (Rangifer tarandus)

AbstractO_ST_ABSBackgroundC_ST_ABSReindeer (Rangifer tarandus) is the only fully domesticated species in the Cervidae family, and is the only cervid with a circumpolar distribution. Unlike all other cervids, female reindeer regularly grow cranial appendages (antlers, the defining characteristics of cervids), as well as males. Moreover, reindeer milk contains more protein and less lactose than bovids milk. A high quality reference genome of this specie will assist efforts to elucidate these and other important features in the reindeer.\n\nFindingsWe obtained 723.2 Gb (Gigabase) of raw reads by an Illumina Hiseq 4000 platform, and a 2.64 Gb final assembly, representing 95.7% of the estimated genome (2.76 Gb according to k-mer analysis), including 92.6% of expected genes according to BUSCO analysis. The contig N50 and scaffold N50 sizes were 89.7 kilo base (kb) and 0.94 mega base (Mb), respectively. We annotated 21,555 protein-coding genes and 1.07 Gb of repetitive sequences by de novo and homology-based prediction. Homology-based searches detected 159 rRNA, 547 miRNA, 1,339 snRNA and 863 tRNA sequences in the genome of R. tarandus. The divergence time between R. tarandus, and ancestors of Bos taurus and Capra hircus, is estimated to be 29.55 million years ago (Mya).\n\nConclusionsOur results provide the first high-quality reference genome for the reindeer, and a valuable resource for studying evolution, domestication and other unusual characteristics of the reindeer.

genomics↗

bioRxiv2017

Sleep Benefits Memory For Semantic Category Structure While Preserving Exemplar-Specific Information

Semantic memory encompasses knowledge about both the properties that typify concepts (e.g. robins, like all birds, have wings) as well as the properties that individuate conceptually related items (e.g. robins, in particular, have red breasts). We investigate the impact of sleep on new semantic learning using a property inference task in which both kinds of information are initially acquired equally well. Participants learned about three categories of novel objects possessing some properties that were shared among category exemplars and others that were unique to an exemplar, with exposure frequency varying across categories. In Experiment 1, memory for shared properties improved and memory for unique properties was preserved across a night of sleep, while memory for both feature types declined over a day awake. In Experiment 2, memory for shared properties improved across a nap, but only for the lower-frequency category, suggesting a prioritization of weakly learned information early in a sleep period. The increase was significantly correlated with amount of REM, but was also observed in participants who did not enter REM, suggesting involvement of both sleep stages. The results provide the first evidence that sleep improves memory for the shared structure of object categories, while simultaneously preserving object-unique information.

neuroscience↗

bioRxiv2017

Specific Virus-Host Genome Interactions Revealed By Tethered Chromosome Conformation Capture

Viruses have evolved a variety of mechanisms to interact with host cells for their adaptive benefits, including subverting host immune responses and hijacking host DNA replication/transcription machineries [1-3]. Although interactions between viral and host proteins have been studied extensively, little is known about how the vial genome may interact with the host genome and how such interactions could affect the activities of both the virus and the host cell. Since the three-dimensional organization of a genome can have significant impact on genomic activities such as transcription and replication, we hypothesize that such structure-based regulation of genomic functions also applies to viral genomes depending on their association with host genomic regions and their spatial locations inside the nucleus. Here, we used Tethered Chromosome Conformation Capture (TCC) to investigate viral-host genome interactions between the adenovirus and human lung fibroblast cells. We found viral-host genome interactions were enriched in certain active chromatin regions and chromatin domains marked by H3K27me3. The contacts by viral DNA seems to impact the structure and function of the host genome, leading to remodeling of the fibroblast epigenome. Our study represents the first comprehensive analysis of viral-host interactions at the genome structure level, revealing unexpectedly specific virus-host genome interactions. The non-random nature of such interactions indicates a deliberate but poorly understood mechanism for targeting of host DNA by foreign genomes.

microbiology↗

bioRxiv2017

Loss of MECP2 leads to telomere dysfunction and neuronal stress

To determine the role for mutations of MECP2 in Rett Syndrome, we generated isogenic lines of human iPSCs (hiPSCs), neural progenitor cells (NPCs), and neurons from patient fibroblasts with and without MECP2 expression in an attempt to recapitulate disease phenotypes in vitro. Molecular profiling uncovered neuronal specific gene expression changes including induction of a Senescence Associated Secretory Phenotype (SASP) program. Patient derived Neurons made without MECP2 show signs of stress, including induction of p53, and senescence. The induction of p53 appeared to affect dendritic branching in Rett neurons, as p53 inhibition restored dendritic complexity. These disease-in-a-dish data suggest that loss of MECP2 can lead to dendritic defects due to an increase in aspects of neuronal aging.

developmental biology↗

bioRxiv2017

Sympathetic Nerve Activity Promotes Cardiomyocyte Cell-Cycle Arrest And Binucleation

Adult mammalian hearts typically have little capacity to regenerate after injuries such as myocardial infarction. In contrast, neonatal mice during the first week of life possess an incredible ability to regenerate their hearts, though this capacity is lost shortly after birth. The physiological triggers mediating this transition remains poorly understood. In this study, we demonstrate that sympathetic nerve activity promotes cardiomyocyte cell-cycle arrest and binucleation. In mice hearts lacking sympathetic nerve inputs, we observe increased mononucleated cardiomyocyte numbers and elevated cardiomyocyte proliferation. Additionally, increased cardiomyocyte mononucleation and proliferation are observed in mice with genetic and pharmacological inhibition of {beta}-adrenergic receptors ({beta}ARs), which mediate sympathetic nerve signaling. Using in vitro cultures of neonatal cardiomyocytes, we demonstrate that activation of {beta}-adrenergic receptors results in decreased cardiomyocyte proliferation that is mediated through cyclic AMP-dependent protein kinase (PKA) signaling. Taken together, these results suggest that sympathetic nerve activity may play a role in limiting the ability of mammalian hearts to regenerate by restricting cardiomyocyte proliferation and promoting cytokinesis failure leading to multinucleation.

developmental biology↗

bioRxiv2017

An evolutionary module in central metabolism

Metabolic enzyme function and evolution is influenced by the larger context of a biochemical pathway - deleterious mutations or perturbations in one enzyme can often be compensated by mutations to others. To explore strategies for mapping adaptive dependencies between enzymes, we used a combination of comparative genomics and experiments to examine interactions with the model metabolic enzyme Dihydrofolate Reductase (DHFR). Biochemically, DHFR shares a metabolic intermediate with numerous folate metabolic enzymes. In contrast, comparative genomics analyses of synteny and gene co-occurrence indicate a sparse pattern of evolutionary couplings in which DHFR is coupled to the enzyme thymidylate synthase (TYMS), but is relatively independent from the rest of folate metabolism. To test this apparent modularity, we used quantitative growth rate measurements and forward evolution in E. coli to demonstrate that the two enzymes are coupled to one another, and can adapt independently from the remainder of the genome. Mechanistically, the coupling between DHFR and TYMS is driven by a constraint wherein TYMS activity must not greatly exceed that of DHFR - both to avoid depletion of reduced folates and prevent accumulation of the metabolic intermediate dihydrofolate. Extending our comparative genomics analyses genome-wide reveals over 200 gene pairs with statistical signatures similar to DHFR/TYMS, suggesting the possibility that cellular pathways might be decomposed into small adaptive units.

systems biology↗

bioRxiv2017

GMPR: A novel normalization method for microbiome sequencing data

SummaryNormalization is the first and a critical step in microbiome sequencing (microbiome-Seq) data analysis to account for variable library sizes. Though RNA-Seq based normalization methods have been adapted for microbiome-Seq data, they fail to consider the unique characteristics of microbiome-Seq data, which contain a vast number of zeros due to the physical absence or undersampling of the microbes. Normalization methods that specifically address the zeroinflation remain largely undeveloped. Here we propose GMPR - a simple but effective normalization method - for zeroinflated sequencing data such as microbiome-Seq data. Simulation studies and analyses of 38 real gut microbiome datasets from 16S rRNA gene amplicon sequencing demonstrated the superior performance of the proposed method.\n\nAvailability and Implementation GMPR is implemented in R andavailable at https://github.com/jchen1981/GMPR\n\nSupplementary InformationSupplementary data are available at Bioinformatics online.\n\nContactChen.Jun2@mayo.edu

bioinformatics↗