Systems Biology
"systems biology"; +53 new citations
53 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/26
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.
"systems biology"; +37 new citations
37 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/24
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.
"systems biology"; +40 new citations
40 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/24
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.
Histone demethylases UTX and JMJD3 are required for NKT cell development in mice.
Histone demethylases UTX and JMJD3 are required for NKT cell development in mice.
Cell Biosci. 2017;7:25
Authors: Northrup D, Yagi R, Cui K, Proctor WR, Wang C, Placek K, Pohl LR, Wang R, Ge K, Zhu J, Zhao K
Abstract
BACKGROUND: Natural killer (NK)T cells and conventional T cells share phenotypic characteristic however they differ in transcription factor requirements and functional properties. The role of histone modifying enzymes in conventional T cell development has been extensively studied, little is known about the function of enzymes regulating histone methylation in NKT cells.
RESULTS: We show that conditional deletion of histone demethylases UTX and JMJD3 by CD4-Cre leads to near complete loss of liver NKT cells, while conventional T cells are less affected. Loss of NKT cells is cell intrinsic and not due to an insufficient selection environment. The absence of NKT cells in UTX/JMJD3-deficient mice protects mice from concanavalin A-induced liver injury, a model of NKT-mediated hepatitis. GO-analysis of RNA-seq data indicates that cell cycle genes are downregulated in UTX/JMJD3-deleted NKT progenitors, and suggest that failed expansion may account for some of the cellular deficiency. The phenotype appears to be demethylase-dependent, because UTY, a homolog of UTX that lacks catalytic function, is not sufficient to restore their development and removal of H3K27me3 by deletion of EZH2 partially rescues the defect.
CONCLUSIONS: NKT cell development and gene expression is sensitive to proper regulation of H3K27 methylation. The H3K27me3 demethylase enzymes, in particular UTX, promote NKT cell development, and are required for effective NKT function.
PMID: 28529687 [PubMed]
"systems biology"; +34 new citations
34 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/23
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.
Biomarkers in epilepsy-A modelling perspective.
Biomarkers in epilepsy-A modelling perspective.
Eur J Pharm Sci. 2017 May 17;:
Authors: van Dijkman SC, Voskuyl RA, de Lange EC
Abstract
Biomarkers can be categorised from type 0 (genotype or phenotype), through 6 (clinical scales), each level representing a part of the processes involved in the biological system and drug treatment. This classification facilitates the identification and connection of information required to fully (mathematically) model a disease and its treatment using integrated information from biomarkers. Two recent reviews thoroughly discussed the current status and development of biomarkers for epilepsy, but a path towards the integration of such biomarkers for the personalisation of anti-epileptic drug treatment is lacking. Here we aim to 1) briefly categorise the available epilepsy biomarkers and identify gaps, and 2) provide a modelling perspective on approaches to fill such gaps. There is mainly a lack of biomarker types 2 (target occupancy) and 3 (target activation). Current literature typically focuses on qualitative biomarkers for diagnosis and prediction of treatment response or failure, leaving a need for biomarkers that help to quantitatively understand the overall system to explain and predict differences in disease and treatment outcome. Due to the complexity of epilepsy, filling the biomarker gaps will require collaboration and expertise from the fields of systems biology and systems pharmacology.
PMID: 28528284 [PubMed - as supplied by publisher]
Sputum transcriptomics reveal up-regulation of IL-1 receptor family members in severe asthma.
Sputum transcriptomics reveal up-regulation of IL-1 receptor family members in severe asthma.
J Allergy Clin Immunol. 2017 May 17;:
Authors: Rossios C, Pavlidis S, Hoda U, Kuo CH, Wiegman C, Russell K, Sun K, Loza MJ, Baribaud F, Durham AL, Ojo O, Lutter R, Rowe A, Bansal A, Auffray C, Sousa A, Corfield J, Djukanovic R, Guo Y, Sterk PJ, Chung KF, Adcock IM, U-BIOPRED consortia project team
Abstract
BACKGROUND: Sputum analysis in asthma is used to define airway inflammatory processes and may guide therapy.
OBJECTIVE: To determine differential gene and protein expression in sputum samples from patients with severe asthma (SA) compared to mild-moderate non-smoking asthmatics (MMA).
METHODS: Induced sputum was obtained from non-smoking SA (SAn), smokers/ex-smokers with SA (SAsm), MMA and healthy non-smoking controls. Differential cell counts, microarray analysis of cell pellets and SOMAscan analysis of sputum analytes was performed. CRID3 was used to inhibit the inflammasome in a mouse model of severe asthma.
RESULTS: Eosinophilic and mixed neutrophilic/eosinophilic inflammation were more prevalent in SA compared to MMA. 42 genes probes were up-regulated (>2-fold) in SAn compared to MMA including IL-1R family and NRLP3 inflammasome members (FDR<0.05). The inflammasome proteins NLRP1, NLRP3 and NLRC4 were associated with neutrophilic asthma and with sputum IL-1β protein whilst eosinophilic asthma was associated with an IL-13-induced Th2 signature and IL1RL1 mRNA expression. These differences were sputum-specific since no activation of NLRP3 or enrichment of IL-1R family genes in bronchial brushings or biopsies in SA was observed. Expression of NLRP3 and of the IL-1R family genes was validated in the Airway Disease Endotyping for Personalized Therapeutics (ADEPT) cohort. Inflammasome inhibition using CRID3 prevented airway hyperresponsiveness and airway inflammation (both neutrophilia and eosinophilia) in a mouse model of severe allergic asthma.
CONCLUSION: IL1RL1 gene expression is associated with eosinophilic SA whilst NLRP3 inflammasome expression is highest in neutrophilic SA. Th2-driven eosinophilic inflammation and neutrophil-associated inflammasome activation may represent interacting pathways in SA.
PMID: 28528200 [PubMed - as supplied by publisher]
Maintenance of ATP Homeostasis Triggers Metabolic Shifts in Gas-Fermenting Acetogens.
Maintenance of ATP Homeostasis Triggers Metabolic Shifts in Gas-Fermenting Acetogens.
Cell Syst. 2017 May 16;:
Authors: Valgepea K, de Souza Pinto Lemgruber R, Meaghan K, Palfreyman RW, Abdalla T, Heijstra BD, Behrendorff JB, Tappel R, Köpke M, Simpson SD, Nielsen LK, Marcellin E
Abstract
Acetogens are promising cell factories for producing fuels and chemicals from waste feedstocks via gas fermentation, but quantitative characterization of carbon, energy, and redox metabolism is required to guide their rational metabolic engineering. Here, we explore acetogen gas fermentation using physiological, metabolomics, and transcriptomics data for Clostridium autoethanogenum steady-state chemostat cultures grown on syngas at various gas-liquid mass transfer rates. We observe that C. autoethanogenum shifts from acetate to ethanol production to maintain ATP homeostasis at higher biomass concentrations but reaches a limit at a molar acetate/ethanol ratio of ∼1. This regulatory mechanism eventually leads to depletion of the intracellular acetyl-CoA pool and collapse of metabolism. We accurately predict growth phenotypes using a genome-scale metabolic model. Modeling revealed that the methylene-THF reductase reaction was ferredoxin reducing. This work provides a reference dataset to advance the understanding and engineering of arguably the first carbon fixation pathway on Earth.
PMID: 28527885 [PubMed - as supplied by publisher]
Understanding aerobic/anaerobic metabolism in Caldibacillus debilis through a comparison with model organisms.
Understanding aerobic/anaerobic metabolism in Caldibacillus debilis through a comparison with model organisms.
Syst Appl Microbiol. 2017 Apr 13;:
Authors: Wushke S, Spicer V, Zhang XL, Fristensky B, Krokhin OV, Levin DB, Cicek N, Sparling R
Abstract
Caldibacillus debilis GB1 is a facultative anaerobe isolated from a thermophilic aero-tolerant cellulolytic enrichment culture. There is a lack of representative proteomes of facultative anaerobic thermophilic Bacillaceae, exploring aerobic/anaerobic expression. The C. debilis GB1 genome was sequenced and annotated, and the proteome characterized under aerobic and anaerobic conditions while grown on cellobiose. The draft sequence of C. debilis GB1 contains a 3,340,752 bp chromosome and a 5,386 bp plasmid distributed over 49 contigs. Two-dimensional liquid chromatography mass spectrometry/mass spectrometry was used with Isobaric Tags for Relative and Absolute Quantification (iTRAQ) to compare protein expression profiles, focusing on energy production and conversion pathways. Under aerobic conditions, proteins in glycolysis and pyruvate fermentation pathways were down-regulated. Simultaneously, proteins within the tricarboxylic acid cycle, pyruvate dehydrogenase, the electron transport chain, and oxygen scavenging pathways showed increased amounts. Under anaerobic conditions, protein levels in fermentation pathways were consistent with the generated end-products: formate, acetate, ethanol, lactate, and CO2. Under aerobic conditions CO2 and acetate production was consistent with incomplete respiration. Through a direct comparison with gene expression profiles from Escherichia coli, we show that global regulation of core metabolism pathways is similar in thermophilic and mesophilic facultative anaerobes of the Phylum Proteobacteria and Firmicutes.
PMID: 28527624 [PubMed - as supplied by publisher]
Making Time: Conservation of Biological Clocks from Fungi to Animals.
Making Time: Conservation of Biological Clocks from Fungi to Animals.
Microbiol Spectr. 2017 May;5(3):
Authors: Dunlap JC, Loros JJ
Abstract
The capacity for biological timekeeping arose at least three times through evolution, in prokaryotic cyanobacteria, in cells that evolved into higher plants, and within the group of organisms that eventually became the fungi and the animals. Neurospora is a tractable model system for understanding the molecular bases of circadian rhythms in the last of these groups, and is perhaps the most intensively studied circadian cell type. Rhythmic processes described in fungi include growth rate, stress responses, developmental capacity, and sporulation, as well as much of metabolism; fungi use clocks to anticipate daily environmental changes. A negative feedback loop comprises the core of the circadian system in fungi and animals. In Neurospora, the best studied fungal model, it is driven by two transcription factors, WC-1 and WC-2, that form the White Collar Complex (WCC). WCC elicits expression of the frq gene. FRQ complexes with other proteins, physically interacts with the WCC, and reduces its activity; the kinetics of these processes is strongly influenced by progressive phosphorylation of FRQ. When FRQ becomes sufficiently phosphorylated that it loses the ability to influence WCC activity, the circadian cycle starts again. Environmental cycles of light and temperature influence frq and FRQ expression and thereby reset the internal circadian clocks. The molecular basis of circadian output is also becoming understood. Taken together, molecular explanations are emerging for all the canonical circadian properties, providing a molecular and regulatory framework that may be extended to many members of the fungal and animal kingdoms, including humans.
PMID: 28527179 [PubMed - in process]
Gender Differences in the Association between Moderate Alcohol Consumption and Hearing Threshold Shifts.
Gender Differences in the Association between Moderate Alcohol Consumption and Hearing Threshold Shifts.
Sci Rep. 2017 May 19;7(1):2201
Authors: Lin YY, Chen HC, Lai WS, Wu LW, Wang CH, Lee JC, Kao TW, Chen WL
Abstract
Hearing loss is a global public health problem with a high prevalence, significantly impairing communication and leading to a decrease in the quality of life. The association between moderate alcohol consumption (MAC) and hearing impairment has been addressed in several studies with inconsistent results. The intent of our study is to clarify the correlation between MAC and the hearing threshold and further investigate the interplay between MAC and the hearing threshold categorized by gender. The study included 4,075 participants aged 20-69 years from the 1999-2004 data of National Health and Nutrition Examination Survey (NHANES). The associations among MAC, gender differences, and high-frequency and low-frequency hearing thresholds were analyzed. We found that current female drinkers with MAC tended to have lower hearing thresholds. There is a significant protective effect of MAC on hearing threshold shifts in the US adult population, especially in females. Our research was the first study to further indicate that there is a gender difference in the association between MAC and hearing impairment. In accordance with our results, if people drink, they should consume moderate rather than higher amounts, especially in women, which may result in a reduced risk of hearing loss.
PMID: 28526828 [PubMed - in process]
Cell fixation and preservation for droplet-based single-cell transcriptomics.
Cell fixation and preservation for droplet-based single-cell transcriptomics.
BMC Biol. 2017 May 19;15(1):44
Authors: Alles J, Karaiskos N, Praktiknjo SD, Grosswendt S, Wahle P, Ruffault PL, Ayoub S, Schreyer L, Boltengagen A, Birchmeier C, Zinzen R, Kocks C, Rajewsky N
Abstract
BACKGROUND: Recent developments in droplet-based microfluidics allow the transcriptional profiling of thousands of individual cells in a quantitative, highly parallel and cost-effective way. A critical, often limiting step is the preparation of cells in an unperturbed state, not altered by stress or ageing. Other challenges are rare cells that need to be collected over several days or samples prepared at different times or locations.
METHODS: Here, we used chemical fixation to address these problems. Methanol fixation allowed us to stabilise and preserve dissociated cells for weeks without compromising single-cell RNA sequencing data.
RESULTS: By using mixtures of fixed, cultured human and mouse cells, we first showed that individual transcriptomes could be confidently assigned to one of the two species. Single-cell gene expression from live and fixed samples correlated well with bulk mRNA-seq data. We then applied methanol fixation to transcriptionally profile primary cells from dissociated, complex tissues. Low RNA content cells from Drosophila embryos, as well as mouse hindbrain and cerebellum cells prepared by fluorescence-activated cell sorting, were successfully analysed after fixation, storage and single-cell droplet RNA-seq. We were able to identify diverse cell populations, including neuronal subtypes. As an additional resource, we provide 'dropbead', an R package for exploratory data analysis, visualization and filtering of Drop-seq data.
CONCLUSIONS: We expect that the availability of a simple cell fixation method will open up many new opportunities in diverse biological contexts to analyse transcriptional dynamics at single-cell resolution.
PMID: 28526029 [PubMed - in process]
"systems biology"; +17 new citations
17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/20
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.
"systems biology"; +20 new citations
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/19
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.
"systems biology"; +25 new citations
25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/19
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.
"systems biology"; +16 new citations
16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/18
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.
"systems biology"; +19 new citations
19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/18
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.
"systems biology"; +35 new citations
35 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/17
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.
"systems biology"; +44 new citations
44 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:
These pubmed results were generated on 2017/05/16
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.
Free chlorine and monochloramine inactivation kinetics of Aspergillus and Penicillium in drinking water.
Free chlorine and monochloramine inactivation kinetics of Aspergillus and Penicillium in drinking water.
Water Res. 2017 Apr 29;120:265-271
Authors: Ma X, Bibby K
Abstract
Fungi are near-ubiquitous in potable water distribution systems, but the disinfection kinetics of commonly identified fungi are poorly studied. In the present study, laboratory scale experiments were conducted to evaluate the inactivation kinetics of Aspergillus fumigatus, Aspergillus versicolor, and Penicillium purpurogenum by free chlorine and monochloramine. The observed inactivation data were then fit to a delayed Chick-Watson model. Based on the model parameter estimation, the Ct values (integrated product of disinfectant concentration C and contact time t over defined time intervals) for 99.9% inactivation of the tested fungal strains ranged from 48.99 mg min/L to 194.7 mg min/L for free chlorine and from 90.33 mg min/L to 531.3 mg min/L for monochloramine. Fungal isolates from a drinking water system (Aspergillus versicolor and Penicillium purpurogenum) were more disinfection resistant than Aspergillus fumigatus type and clinical isolates. The required 99.9% inactivation Ct values for the tested fungal strains are higher than E. coli, a commonly monitored indicator bacteria, and within a similar range for bacteria commonly identified within water distribution systems, such as Mycobacterium spp. and Legionella spp.
PMID: 28501787 [PubMed - as supplied by publisher]