The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder.

Mov Disord. 2017 Aug 26;:

Authors: Heintz-Buschart A, Pandey U, Wicke T, Sixel-Döring F, Janzen A, Sittig-Wiegand E, Trenkwalder C, Oertel WH, Mollenhauer B, Wilmes P

Abstract
BACKGROUND: Increasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD.
OBJECTIVES: To compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals.
METHODS: Microbiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed.
RESULTS: Differentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms.
CONCLUSION: Our study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 International Parkinson and Movement Disorder Society.

PMID: 28843021 [PubMed - as supplied by publisher]

Genome-wide Analysis of Protein-Coding Variants in Leprosy.

J Invest Dermatol. 2017 Aug 22;:

Authors: Liu H, Wang Z, Li Y, Yu G, Fu X, Wang C, Liu W, Yu Y, Bao F, Irwanto A, Liu J, Chu T, Andiappan AK, Maurer-Stroh S, Limviphuvadh V, Wang H, Mi Z, Sun Y, Sun L, Wang L, Wang C, You J, Li J, Foo JN, Liany H, Meah WY, Niu G, Yue Z, Zhao Q, Wang N, Yu M, Yu W, Cheng X, Khor CC, Sim KS, Aung T, Wang N, Wang D, Shi L, Ning Y, Zheng Z, Yang R, Li J, Yang J, Yan L, Shen J, Zhang G, Chen S, Liu J, Zhang F

Abstract
Although genome-wide association studies (GWAS) have greatly advanced our understanding on the contribution of common non-coding variants to leprosy susceptibility, protein-coding variants have not been systematically investigated. We carried out a three-stage genome-wide association study of protein-coding variants in 7,048 leprosy patients and 14,398 healthy controls of Han Chinese. Seven to our knowledge previously unreported coding variants at exome-wide significance were discovered, including two rare variants: rs145562243 in NCKIPSD (P = 1.71 × 10(-9), odds ratio (OR) = 4.35) and rs149308743 in CARD9 (P = 2.09 × 10(-8), OR = 4.75); three low frequency variants: rs76418789 in IL23R (P = 1.03 × 10(-10), OR = 1.36), rs146466242 in FLG (P = 3.39 × 10(-12), OR = 1.45), and rs55882956 in TYK2 (P = 1.04 × 10(-6), OR = 1.30); and two common variants: rs780668 in SLC29A3 (P = 2.17 × 10(-9), OR = 1.14) and rs181206 in IL27 (P = 1.08 × 10(-7), OR = 0.83). Discovered protein-coding variants, particularly low-frequency and rare ones, revealed involvement of skin barrier and endocytosis/phagocytosis/autophagy, besides known innate and adaptive immunity, in the pathogenesis of leprosy, highlighting the merits of protein coding variant studies for complex diseases.

PMID: 28842327 [PubMed - as supplied by publisher]

Oxalobacter formigenes-associated host features and microbial community structures examined using the American Gut Project.

Microbiome. 2017 Aug 25;5(1):108

Authors: Liu M, Koh H, Kurtz ZD, Battaglia T, PeBenito A, Li H, Nazzal L, Blaser MJ

Abstract
BACKGROUND: Increasing evidence shows the importance of the commensal microbe Oxalobacter formigenes in regulating host oxalate homeostasis, with effects against calcium oxalate kidney stone formation, and other oxalate-associated pathological conditions. However, limited understanding of O. formigenes in humans poses difficulties for designing targeted experiments to assess its definitive effects and sustainable interventions in clinical settings. We exploited the large-scale dataset from the American Gut Project (AGP) to study O. formigenes colonization in the human gastrointestinal (GI) tract and to explore O. formigenes-associated ecology and the underlying host-microbe relationships.
RESULTS: In >8000 AGP samples, we detected two dominant, co-colonizing O. formigenes operational taxonomic units (OTUs) in fecal specimens. Multivariate analysis suggested that O. formigenes abundance was associated with particular host demographic and clinical features, including age, sex, race, geographical location, BMI, and antibiotic history. Furthermore, we found that O. formigenes presence was an indicator of altered host gut microbiota structure, including higher community diversity, global network connectivity, and stronger resilience to simulated disturbances.
CONCLUSIONS: Through this study, we identified O. formigenes colonizing patterns in the human GI tract, potential underlying host-microbe relationships, and associated microbial community structures. These insights suggest hypotheses to be tested in future experiments. Additionally, we proposed a systematic framework to study any bacterial taxa of interest to computational biologists, using large-scale public data to yield novel biological insights.

PMID: 28841836 [PubMed - in process]

39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

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36 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

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"systems biology"

These pubmed results were generated on 2017/08/25

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Extracts of Salvia-Nelumbinis Naturalis Ameliorate Nonalcoholic Steatohepatitis via Inhibiting Gut-Derived Endotoxin Mediated TLR4/NF-κB Activation.

Evid Based Complement Alternat Med. 2017;2017:9208314

Authors: Shu X, Wang M, Xu H, Liu Y, Huang J, Yao Z, Zhang L

Abstract
Nonalcoholic steatohepatitis (NASH) is featured by the presence of hepatic steatosis combined with inflammation and hepatocellular injury. Gut-derived endotoxin plays a crucial role in the pathogenesis of NASH. Salvia-Nelumbinis naturalis (SNN), a formula of Traditional Chinese Medicine, has been identified to be effective for NASH, but the mechanisms were not thoroughly explored. In the present study, a NASH model was generated using C57BL/6 mice fed a high fat diet (HFD) supplemented periodically with dextran sulfate sodium (DSS) in drinking water for 12 weeks. Mice fed HFD alone (without DSS) or chow diet were used as controls. The NASH mice were given the SNN extracts in the following 4 weeks, while control mice were provided with saline. Mice fed HFD developed steatosis, and DSS supplementation resulted in NASH. The SNN extracts significantly improved metabolic disorders including obesity, dyslipidemia, and liver steatosis and reduced hepatic inflammation, circulating tumor necrosis factor-α (TNF-α), and lipopolysaccharide (LPS) levels. The beneficial effect of the SNN extracts was associated with restoration of intestinal conditions (microbiota, integrity of intestinal barrier) and inhibition of TLR4/NF-κB activation. These results suggest that the SNN extracts ameliorate NASH progression, possibly through blocking endotoxin related TLR4/NF-κB activation.

PMID: 28831287 [PubMed]

35 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/08/23

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39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/08/22

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Kinetic Modeling of Photorespiration.

Methods Mol Biol. 2017;1653:203-216

Authors: Zhao H, Xiao Y, Zhu XG

Abstract
Dynamic systems modeling is a method to study systematic properties of a complex system. The basic principles, procedures, and tools available to develop a dynamic systems model of complex metabolic processes are detailed. Here, a photosynthetic carbon metabolism model, which includes the Calvin Benson cycle, photorespiration, and starch and sucrose synthesis pathways, is used as an example to illustrate the whole process of model development.

PMID: 28822135 [PubMed - in process]

Genome-Scale Modeling of Photorespiratory Pathway Manipulation.

Methods Mol Biol. 2017;1653:195-202

Authors: Küken A, Nikoloski Z

Abstract
Quantifying the redistribution of metabolic reaction fluxes under experimental scenarios that affect the photorespiratory pathway can provide insights about the coupling of this pathway with other parts of metabolism. However, differential flux profiling on a genome-scale level remains the biggest challenge in modern systems biology. Here we present a protocol for applying a constraint-based approach, termed iReMet-Flux, that integrates data about relative metabolite levels in a stoichiometric metabolic model to predict differential fluxes at a genome-scale level under mild modeling assumptions. We demonstrate how iReMet-Flux can be employed to investigate the interplay between photorespiration and other pathways at a genome-scale level, and complements flux profiling methods based on radioactive tracer labeling.

PMID: 28822134 [PubMed - in process]

Measurement of Transcripts Associated with Photorespiration and Related Redox Signaling.

Methods Mol Biol. 2017;1653:17-29

Authors: Mhamdi A, Kerchev PI, Willems P, Noctor G, Van Breusegem F

Abstract
To study photorespiration and to characterize related components, gene expression analysis is a central approach. An overview of the experimental setup, protocols, and methods we use to investigate photorespiration-associated gene expression is presented. Within this chapter, we describe simple procedures to experimentally alter the photorespiratory flux and provide protocols for transcriptomic analysis with a focus on genes encoding photorespiratory proteins as well as those induced by photorespiratory hydrogen peroxide (H2O2). Examples of typical results are presented and their significance to understanding redox signaling is discussed.

PMID: 28822123 [PubMed - in process]

Nanomechanics of multidomain neuronal cell adhesion protein contactin revealed by single molecule AFM and SMD.

Sci Rep. 2017 Aug 18;7(1):8852

Authors: Mikulska-Ruminska K, Kulik AJ, Benadiba C, Bahar I, Dietler G, Nowak W

Abstract
Contactin-4 (CNTN4) is a complex cell adhesion molecule (CAM) localized at neuronal membranes, playing a key role in maintaining the mechanical integrity and signaling properties of the synapse. CNTN4 consists of six immunoglobulin C2 type (IgC2) domains and four fibronectin type III (FnIII) domains that are shared with many other CAMs. Mutations in CNTN4 gene have been linked to various psychiatric disorders. Toward elucidating the response of this modular protein to mechanical stress, we studied its force-induced unfolding using single molecule atomic force microscopy (smAFM) and steered molecular dynamics (SMD) simulations. Extensive smAFM and SMD data both indicate the distinctive mechanical behavior of the two types of modules distinguished by unique force-extension signatures. The data also reveal the heterogeneity of the response of the individual FNIII and IgC2 modules, which presumably plays a role in the adaptability of CNTN4 to maintaining cell-cell communication and adhesion properties under different conditions. Results show that extensive sampling of force spectra, facilitated by robot-enhanced AFM, can help reveal the existence of weak stabilizing interactions between the domains of multidomain proteins, and provide insights into the nanomechanics of such multidomain or heteromeric proteins.

PMID: 28821864 [PubMed - in process]

Extracting Intercellular Signaling Network of Cancer Tissues using Ligand-Receptor Expression Patterns from Whole-tumor and Single-cell Transcriptomes.

Sci Rep. 2017 Aug 18;7(1):8815

Authors: Zhou JX, Taramelli R, Pedrini E, Knijnenburg T, Huang S

Abstract
Many behaviors of cancer, such as progression, metastasis and drug resistance etc., cannot be fully understood by genetic mutations or intracellular signaling alone. Instead, they are emergent properties of the cell community which forms a tumor. Studies of tumor heterogeneity reveal that many cancer behaviors critically depend on intercellular communication between cancer cells themselves and between cancer-stromal cells by secreted signaling molecules (ligands) and their cognate receptors. We analyzed public cancer transcriptome database for changes in cell-cell interactions as the characteristic of malignancy. We curated a list (>2,500 ligand-receptor pairs) and identified their joint enrichment in tumors from TCGA pan-cancer data. From single-cell RNA-Seq data for a case of melanoma and the specificity of the ligand-receptor interactions and their gene expression measured in individual cells, we constructed a map of a cell-cell communication network that indicates what signal is exchanged between which cell types in the tumor. Such networks establish a new formal phenotype of cancer which captures the cell-cell communication structure - it may open new opportunities for identifying molecular signatures of coordinated behaviors of cancer cells as a population - in turn may become a determinant of cancer progression potential and prognosis.

PMID: 28821810 [PubMed - in process]

Obesity and fatty liver are prevented by inhibition of the aryl hydrocarbon receptor in both female and male mice.

Nutr Res. 2017 Aug;44:38-50

Authors: Moyer BJ, Rojas IY, Kerley-Hamilton JS, Nemani KV, Trask HW, Ringelberg CS, Gimi B, Demidenko E, Tomlinson CR

Abstract
Inhibition of the aryl hydrocarbon receptor (AHR) prevents Western diet-induced obesity and fatty liver in C57Bl/6J (B6) male mice. The AHR is a ligand-activated nuclear receptor that regulates genes involved in xenobiotic metabolism and T-cell differentiation. Here, we tested the hypothesis that AHR antagonism would also prevent obesity and fatty liver in female mice and that B6 mice (higher-affinity AHR) and congenic B6.D2 mice (lower-affinity AHR) would differentially respond to AHR inhibition. Female and male adult B6 and B6.D2 mice were fed control and Western diets with and without α-naphthoflavone (NF), an AHR inhibitor. A nonlinear mixed-model analysis was developed to project asymptote body mass. We found that obesity, adiposity, and liver steatosis were reduced to near control levels in all female and male B6 and B6.D2 experimental groups fed Western diet with NF. However, differences were noted in that female B6.D2 vs B6 mice on Western diet became more obese; and in general, female mice compared with male mice had a greater fat mass to body mass ratio, were less responsive to NF, and had reduced liver steatosis and hepatomegaly. We report that male mice fed Western diet containing NF or CH-223191, another AHR inhibitor, caused reduced mRNA levels of several liver genes involved in metabolism, including Cyp1b1 and Scd1, offering evidence for a possible mechanism by which the AHR regulates obesity. In conclusion, although there are some sex- and Ahr allelic-dependent differences, AHR inhibition prevents obesity and liver steatosis in both males and females regardless of the ligand-binding capacity of the AHR. We also present evidence consistent with the notion that an AHR-CYP1B1-SCD1 axis is involved in obesity, providing potentially convenient and effective targets for treatment.

PMID: 28821316 [PubMed - in process]

A cost-effective approach to produce (15)N-labelled amino acids employing Chlamydomonas reinhardtii CC503.

Microb Cell Fact. 2017 Aug 18;16(1):146

Authors: Nicolás Carcelén J, Marchante-Gayón JM, González PR, Valledor L, Cañal MJ, Alonso JIG

Abstract
BACKGROUND: The use of enriched stable isotopes is of outstanding importance in chemical metrology as it allows the application of isotope dilution mass spectrometry (IDMS). Primary methods based on IDMS ensure the quality of the analytical measurements and traceability of the results to the international system of units. However, the synthesis of isotopically labelled molecules from enriched stable isotopes is an expensive and a difficult task. Either chemical and biochemical methods to produce labelled molecules have been proposed, but so far, few cost-effective methods have been described.
RESULTS: The aim of this study was to use the microalgae Chlamydomonas reinhardtii to produce, at laboratory scale, (15)N-labelled amino acids with a high isotopic enrichment. To do that, a culture media containing (15)NH4Cl was used. No kinetic isotope effect (KIE) was observed. The labelled proteins biosynthesized by the microorganism were extracted from the biomass and the (15)N-labelled amino acids were obtained after a protein hydrolysis with HCl. The use of the wall deficient strain CC503 cw92 mt+ is fit for purpose, as it only assimilates ammonia as nitrogen source, avoiding isotope contamination with nitrogen from the atmosphere or the reagents used in the culture medium, and enhancing the protein extraction efficiency compared to cell-walled wild type Chlamydomonas. The isotopic enrichment of the labelled amino acids was calculated from their isotopic composition measured by gas chromatography mass spectrometry (GC-MS). The average isotopic enrichment for the 16 amino acids characterized was 99.56 ± 0.05% and the concentration of the amino acids in the hydrolysate ranged from 18 to 90 µg/mL.
CONCLUSIONS: Previously reported biochemical methods to produce isotopically labelled proteins have been applied in the fields of proteomics and fluxomics. For these approaches, low amounts of products are required and the isotopic enrichment of the molecules has never been properly determined. So far, only (13)C-labelled fatty acids have been isolated from labelled microalga biomass as valuable industrial products. In this study, we propose Chlamydomonas reinhardtii CC503 as a feasible microorganism and strain to produce labelled biomass from which a standard containing sixteen (15)N-labelled amino acids could be obtained.

PMID: 28821247 [PubMed - in process]

Evaluation of the impact of Illumina error correction tools on de novo genome assembly.

BMC Bioinformatics. 2017 Aug 18;18(1):374

Authors: Heydari M, Miclotte G, Demeester P, Van de Peer Y, Fostier J

Abstract
BACKGROUND: Recently, many standalone applications have been proposed to correct sequencing errors in Illumina data. The key idea is that downstream analysis tools such as de novo genome assemblers benefit from a reduced error rate in the input data. Surprisingly, a systematic validation of this assumption using state-of-the-art assembly methods is lacking, even for recently published methods.
RESULTS: For twelve recent Illumina error correction tools (EC tools) we evaluated both their ability to correct sequencing errors and their ability to improve de novo genome assembly in terms of contig size and accuracy.
CONCLUSIONS: We confirm that most EC tools reduce the number of errors in sequencing data without introducing many new errors. However, we found that many EC tools suffer from poor performance in certain sequence contexts such as regions with low coverage or regions that contain short repeated or low-complexity sequences. Reads overlapping such regions are often ill-corrected in an inconsistent manner, leading to breakpoints in the resulting assemblies that are not present in assemblies obtained from uncorrected data. Resolving this systematic flaw in future EC tools could greatly improve the applicability of such tools.

PMID: 28821237 [PubMed - in process]

Discovery of enzymatically depolymerized heparins capable of treating Bleomycin-induced pulmonary injury and fibrosis in mice.

Carbohydr Polym. 2017 Oct 15;174:82-88

Authors: Yan Y, Du S, Ji Y, Su N, Wang Y, Mei X, Zhu W, He D, Lu Y, Zhang C, Xing XH

Abstract
Heparin has recently been shown to slow down idiopathic pulmonary fibrosis (IPF) process and improve survival of patients in some cases. To improve the anti-IPF function while minimizing their side effects, we developed heparin libraries with different structures depolymerized by single or combined heparinases, and systematically screened the efficacy of the different heparins for treatment of Bleomycin-induced pulmonary injury and fibrosis using mice model. Then we characterized the structural properties of the components capable of treating pulmonary injury and fibrosis by use of chip-based amide hydrophilic interaction chromatography (HILIC)-fourier transform (FT)-ESI-MS, polyacrylamide gel electrophoresis (PAGE), and high performance liquid chromatography (HPLC). Our results showed that the depolymerized heparins with relative higher molecular weight (I-2 and III-2) by the respective heparinase I and III protected mice from the induced pulmonary injury and fibrosis. In addition, the selected depolymerized heparins inhibited high-mobility group protein B1 (HMGB-1) expression, prevented E-cadhesin from downregulation, and reduced fibroblasts accumulation in the mouse lung tissue. Our study suggested that the depolymerized heparins of I-2 and III-2 with the most significant efficacy might target several pathways in alleviating the induced pulmonary fibrosis.

PMID: 28821136 [PubMed - in process]

48 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/08/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

46 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/08/19

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.