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"systems biology"

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34 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 2018/06/07

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.

44 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 2018/06/06

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.

33 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 2018/06/05

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.

29 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 2018/06/05

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.

Exploitation of data from breeding programs supports rapid implementation of genomic selection for key agronomic traits in perennial ryegrass.

Theor Appl Genet. 2018 Jun 02;:

Authors: Pembleton LW, Inch C, Baillie RC, Drayton MC, Thakur P, Ogaji YO, Spangenberg GC, Forster JW, Daetwyler HD, Cogan NOI

Abstract
KEY MESSAGE: Exploitation of data from a ryegrass breeding program has enabled rapid development and implementation of genomic selection for sward-based biomass yield with a twofold-to-threefold increase in genetic gain. Genomic selection, which uses genome-wide sequence polymorphism data and quantitative genetics techniques to predict plant performance, has large potential for the improvement in pasture plants. Major factors influencing the accuracy of genomic selection include the size of reference populations, trait heritability values and the genetic diversity of breeding populations. Global diversity of the important forage species perennial ryegrass is high and so would require a large reference population in order to achieve moderate accuracies of genomic selection. However, diversity of germplasm within a breeding program is likely to be lower. In addition, de novo construction and characterisation of reference populations are a logistically complex process. Consequently, historical phenotypic records for seasonal biomass yield and heading date over a 18-year period within a commercial perennial ryegrass breeding program have been accessed, and target populations have been characterised with a high-density transcriptome-based genotyping-by-sequencing assay. Ability to predict observed phenotypic performance in each successive year was assessed by using all synthetic populations from previous years as a reference population. Moderate and high accuracies were achieved for the two traits, respectively, consistent with broad-sense heritability values. The present study represents the first demonstration and validation of genomic selection for seasonal biomass yield within a diverse commercial breeding program across multiple years. These results, supported by previous simulation studies, demonstrate the ability to predict sward-based phenotypic performance early in the process of individual plant selection, so shortening the breeding cycle, increasing the rate of genetic gain and allowing rapid adoption in ryegrass improvement programs.

PMID: 29860624 [PubMed - as supplied by publisher]

Metabolome changes are induced in the arbuscular mycorrhizal fungus Gigaspora margarita by germination and by its bacterial endosymbiont.

Mycorrhiza. 2018 Jun 02;:

Authors: Dearth SP, Castro HF, Venice F, Tague ED, Novero M, Bonfante P, Campagna SR

Abstract
Metabolomic profiling is becoming an increasingly important technique in the larger field of systems biology by allowing the simultaneous measurement of thousands of small molecules participating in and resulting from cellular reactions. In this way, metabolomics presents an opportunity to observe the physiological state of a system, which may provide the ability to monitor the whole of cellular metabolism as the technology progresses. The arbuscular mycorrhizal fungus Gigaspora margarita has not previously been explored with regard to metabolite composition. To develop a better understanding of G. margarita and the influences of its endosymbiont Candidatus Glomeribacter gigasporarum, a metabolomic analysis was applied to quiescent and germinated spores with and without endobacteria. Over 100 metabolites were identified and greater than 2600 unique unidentified spectral features were observed. Multivariate analysis of the metabolomes was performed, and a differentiation between all metabolic states of spores and spores hosting the endobacteria was observed. The known metabolites were recruited to many biochemical pathways, with many being involved in maintenance of the antioxidant potential, tyrosine metabolism, and melanin production. Each of the pathways had higher metabolite abundances in the presence of the endosymbiont. These metabolomics data also agree with previously reported transcriptomics results demonstrating the capability of this technique to confirm hypotheses and showing the feasibility of multi-omic approaches for the study of arbuscular mycorrhizal fungi and their endobacterial communities. Challenges still exist in metabolomic analysis, e.g., the identification of compounds is demanding due to incomplete libraries. A metabolomics technique to probe the effects of bacterial endosymbionts on fungal physiology is presented herein, and this method is useful for hypothesis generation as well as testing as noted above.

PMID: 29860608 [PubMed - as supplied by publisher]

The Orphan Receptor GPR35 Contributes to Angiotensin II-Induced Hypertension and Cardiac Dysfunction in Mice.

Am J Hypertens. 2018 May 31;:

Authors: Divorty N, Milligan G, Graham D, Nicklin SA

Abstract
BACKGROUND: The orphan receptor G protein-coupled receptor 35 (GPR35) has been associated with a range of diseases, including cancer, inflammatory bowel disease, diabetes, hypertension, and heart failure. To assess the potential for GPR35 as a therapeutic target in cardiovascular disease, this study investigated the cardiovascular phenotype of a GPR35 knockout mouse under both basal conditions and following pathophysiological stimulation.
METHODS: Blood pressure was monitored in male wild-type and GPR35 knockout mice over 7-14 days using implantable telemetry. Cardiac function and dimensions were assessed using echocardiography, and cardiomyocyte morphology evaluated histologically. Two weeks of angiotensin II (Ang II) infusion was used to investigate the effects of GPR35 deficiency under pathophysiological conditions. Gpr35 messenger RNA expression in cardiovascular tissues was assessed using quantitative polymerase chain reaction.
RESULTS: There were no significant differences in blood pressure, cardiac function, or cardiomyocyte morphology in GPR35 knockout mice compared with wild-type mice. Following Ang II infusion, GPR35 knockout mice were protected from significant increases in systolic, diastolic, and mean arterial blood pressure or impaired left ventricular systolic function, in contrast to wild-type mice. There were no significant differences in Gpr35 messenger RNA expression in heart, kidney, and aorta following Ang II infusion in wild-type mice.
CONCLUSIONS: Although GPR35 does not appear to influence basal cardiovascular regulation, these findings demonstrate that it plays an important pathological role in the development of Ang II-induced hypertension and impaired cardiac function. This suggests that GPR35 is a potential novel drug target for therapeutic intervention in hypertension.

PMID: 29860395 [PubMed - as supplied by publisher]

Systematic Identification of Druggable Epithelial-Stromal Crosstalk Signaling Networks in Ovarian Cancer.

J Natl Cancer Inst. 2018 May 31;:

Authors: Yeung TL, Sheng J, Leung CS, Li F, Kim J, Ho SY, Matzuk MM, Lu KH, Wong STC, Mok SC

Abstract
Background: Bulk tumor tissue samples are used for generating gene expression profiles in most research studies, making it difficult to decipher the stroma-cancer crosstalk networks. In the present study, we describe the use of microdissected transcriptome profiles for the identification of cancer-stroma crosstalk networks with prognostic value, which presents a unique opportunity for developing new treatment strategies for ovarian cancer.
Methods: Transcriptome profiles from microdissected ovarian cancer-associated fibroblasts (CAFs) and ovarian cancer cells from patients with high-grade serous ovarian cancer (n = 70) were used as input data for the computational systems biology program CCCExplorer to uncover crosstalk networks between various cell types within the tumor microenvironment. The crosstalk analysis results were subsequently used for discovery of new indications for old drugs in ovarian cancer by computational ranking of candidate agents. Survival analysis was performed on ovarian tumor-bearing Dicer/Pten double-knockout mice treated with calcitriol, a US Food and Drug Administration-approved agent that suppresses the Smad signaling cascade, or vehicle control (9-11 mice per group). All statistical tests were two-sided.
Results: Activation of TGF-β-dependent and TGF-β-independent Smad signaling was identified in a particular subtype of CAFs and was associated with poor patient survival (patients with higher levels of Smad-regulated gene expression by CAFs: median overall survival = 15 months, 95% confidence interval [CI] = 12.7 to 17.3 months; vs patients with lower levels of Smad-regulated gene expression: median overall survival = 26 months, 95% CI = 15.9 to 36.1 months, P = .02). In addition, the activated Smad signaling identified in CAFs was found to be targeted by repositioning calcitriol. Calcitriol suppressed Smad signaling in CAFs, inhibited tumor progression in mice, and prolonged the median survival duration of ovarian cancer-bearing mice from 36 to 48 weeks (P = .04).
Conclusions: Our findings suggest the feasibility of using novel multicellular systems biology modeling to identify and repurpose known drugs targeting cancer-stroma crosstalk networks, potentially leading to faster and more effective cures for cancers.

PMID: 29860390 [PubMed - as supplied by publisher]

Policy Lessons From Quantitative Modeling of Leprosy.

Clin Infect Dis. 2018 Jun 01;66(suppl_4):S281-S285

Authors: Medley GF, Blok DJ, Crump RE, Hollingsworth TD, Galvani AP, Ndeffo-Mbah ML, Porco TC, Richardus JH

Abstract
Recent mathematical and statistical modeling of leprosy incidence data provides estimates of the current undiagnosed population and projections of diagnosed cases, as well as ongoing transmission. Furthermore, modeling studies have been used to evaluate the effectiveness of proposed intervention strategies, such as postleprosy exposure prophylaxis and novel diagnostics, relative to current approaches. Such modeling studies have revealed both a slow decline of new cases and a substantial pool of undiagnosed infections. These findings highlight the need for active case detection, particularly targeting leprosy foci, as well as for continued research into innovative accurate, rapid, and cost-effective diagnostics. As leprosy incidence continues to decline, targeted active case detection primarily in foci and connected areas will likely become increasingly important.

PMID: 29860289 [PubMed - in process]

Assessing Strategies Against Gambiense Sleeping Sickness Through Mathematical Modeling.

Clin Infect Dis. 2018 Jun 01;66(suppl_4):S286-S292

Authors: Rock KS, Ndeffo-Mbah ML, Castaño S, Palmer C, Pandey A, Atkins KE, Ndung'u JM, Hollingsworth TD, Galvani A, Bever C, Chitnis N, Keeling MJ

Abstract
Background: Control of gambiense sleeping sickness relies predominantly on passive and active screening of people, followed by treatment.
Methods: Mathematical modeling explores the potential of 3 complementary interventions in high- and low-transmission settings.
Results: Intervention strategies that included vector control are predicted to halt transmission most quickly. Targeted active screening, with better and more focused coverage, and enhanced passive surveillance, with improved access to diagnosis and treatment, are both estimated to avert many new infections but, when used alone, are unlikely to halt transmission before 2030 in high-risk settings.
Conclusions: There was general model consensus in the ranking of the 3 complementary interventions studied, although with discrepancies between the quantitative predictions due to differing epidemiological assumptions within the models. While these predictions provide generic insights into improving control, the most effective strategy in any situation depends on the specific epidemiology in the region and the associated costs.

PMID: 29860287 [PubMed - in process]

Protective myoelectric activity at performing upper limb neurodynamic test 1 in breast cancer survivors. A cross-sectional observational study.

Musculoskelet Sci Pract. 2018 May 22;36:68-80

Authors: de la Rosa-Díaz I, Torres-Lacomba M, Acosta-Ramírez P, Orive IG, Nee RJ, de la Villa-Polo P, Andrés-Esteban EM, Sánchez-Sánchez B

Abstract
Myoelectric activity and range of motion during ULNT1 were recorded in 62 breast cancer (BC) survivors who had axillary lymph node dissection (n = 30) or sentinel lymph node biopsy (n = 32) within the previous 18 months, and 63 age-matched healthy women. BC survivors' symptoms were reproduced by ULNT1 and exhibited greater myoelectric activity in the biceps brachii than healthy women (MD (95% CI): 21,26 (10,83-31,70)). No differences between the axillary lymph node dissection and sentinel lymph node biopsy groups (MD (95% CI): 8,47 (-7,84-24,79)) were found. Myoelectric activity in the triceps brachii was greater in the sentinel lymph node biopsy group (MD (95% CI): 2,70 (-2,06-7,60)). BC survivors exhibited less shoulder and elbow range of motion during ULNT1 than healthy women. Increased upper limb nerve mechanosensitivity in BC survivors was associated with a greater protective muscle response during ULNT1.

PMID: 29860136 [PubMed - as supplied by publisher]

Computation Resources for Molecular Biology: Special Issue 2018.

J Mol Biol. 2018 May 31;:

Authors: Sternberg MJE, Yosef N

PMID: 29860026 [PubMed - as supplied by publisher]

Tracking gene expression and oxidative damage of O2-stressed Clostridioides difficile by a multi-omics approach.

Anaerobe. 2018 May 31;:

Authors: Neumann-Schaal M, Metzendorf NG, Troitzsch D, Nuss AM, Hofmann JD, Beckstette M, Dersch P, Otto A, Sievers S

Abstract
Clostridioides difficile is the major pathogen causing diarrhea following antibiotic treatment. It is considered to be a strictly anaerobic bacterium, however, previous studies have shown a certain and strain-dependent oxygen tolerance. In this study, the model strain C. difficile 630Δerm was shifted to micro-aerobiosis and was found to stay growing to the same extent as anaerobically growing cells with only few changes in the metabolite pattern. However, an extensive change in gene expression was determined by RNA-Seq. The most striking adaptation strategies involve a change in the reductive fermentation pathways of the amino acids proline, glycine and leucine. But also a far-reaching restructuring in the carbohydrate metabolism was detected with changes in the phosphotransferase system (PTS) facilitated uptake of sugars and a repression of enzymes of glycolysis and butyrate fermentation. Furthermore, a temporary induction in the synthesis of cofactor riboflavin was detected possibly due to an increased demand for flavin mononucleotid (FMN) and flavin adenine dinucleotide (FAD) in redox reactions. However, biosynthesis of the cofactors thiamin pyrophosphate and cobalamin were repressed deducing oxidation-prone enzymes and intermediates in these pathways. Micro-aerobically shocked cells were characterized by an increased demand for cysteine and a thiol redox proteomics approach revealed a dramatic increase in the oxidative state of cysteine in more than 800 peptides after 15 min of micro-aerobic shock. This provides not only a catalogue of oxidation-prone cysteine residues in the C. difficile proteome but also puts the amino acid cysteine into a key position in the oxidative stress response. Our study suggests that tolerance of C. difficile towards O2 is based on a complex and far-reaching adjustment of global gene expression which leads to only a slight change in phenotype.

PMID: 29859941 [PubMed - as supplied by publisher]

Autotaxin exacerbates tumor progression by enhancing MEK1 and overriding the function of miR-489-3p.

Cancer Lett. 2018 May 30;:

Authors: Kuppa SS, Jia W, Liu S, Nguyen H, Smyth SS, Mills GB, Dobbin KK, Hardman WJ, Murph MM

Abstract
Upregulated expression of autotaxin, a secreted phospholipase and phosphodiesterase enzyme, appears in malignant disease. The identification of a circulating miRNA signature should distinguish autotaxin-mediated disease and also elucidate unknown molecular mechanisms that rationalize its malignant potential. Using female transgenic 'AT-ATX' mice, whereby human wild-type autotaxin is expressed in liver under the control of the alpha-1 antitrypsin promoter, transgenic animals express augmented autotaxin in circulation and a percentage develop tumors. Serum collected at necropsy had circulating miRNAs analyzed for statistical significance. The ensuing autotaxin-mediated miRNome differentiated between groups: healthy FVB/N mice versus AT-ATX mice with and without tumors. Intriguingly, miR-489-3p was sharply increased in AT-ATX tumor-bearing mice. Tissue analysis showed a correlation between miR-489-3p expression in tumors and surrounding milieu with autotaxin concentration in circulation. Sequence alignment suggested miR-489-3p targets MEK1, which was confirmed through in vitro studies. Exogenously added miR-489-3p, which decreases MEK1 in normal cells, dramatically increased MEK1 expression in cells stably expressing autotaxin. Taken together, this suggests that autotaxin overrides the normal regulatory function of miR-489-3p to inhibit MEK1 via coordinately increased miR-489-3p appearing in serum.

PMID: 29859298 [PubMed - as supplied by publisher]

Horizontal Gene Transfer Can Help Maintain the Equilibrium of Microbial Communities.

J Theor Biol. 2018 May 30;:

Authors: Fan Y, Xiao Y, Momeni B, Liu YY

Abstract
Horizontal gene transfer and species coexistence are two focal points in the study of microbial communities. The evolutionary advantage of horizontal gene transfer has not been well understood and is constantly being debated. Here we propose a simple population dynamics model based on the frequency-dependent genotype interactions to evaluate the influence of horizontal gene transfer on microbial communities. In particular, we examine the structural stability of coexistence (i.e., the capability of the system to maintain species coexistence in response to small changes in parameters), as well as the robustness (defined as the maximal degree of perturbation the system can sustain around a stable coexistence steady state) of microbial communities. We find that both structural stability of coexistence and robustness of the microbial community are strongly affected by the gene transfer rate and direction. An optimal gene flux can stablize the ecosystem, helping it recover from disturbance and maintain the species coexistence.

PMID: 29859211 [PubMed - as supplied by publisher]

Stage-dependent piRNAs in chicken implicated roles in modulating male germ cell development.

BMC Genomics. 2018 Jun 01;19(1):425

Authors: Chang KW, Tseng YT, Chen YC, Yu CY, Liao HF, Chen YC, Tu YE, Wu SC, Liu IH, Pinskaya M, Morillion A, Pain B, Lin SP

Abstract
BACKGROUND: The PIWI/piRNA pathway is a conserved machinery important for germ cell development and fertility. This piRNA-guided molecular machinery is best known for repressing derepressed transposable elements (TE) during epigenomic reprogramming. The extent to which piRNAs are involved in modulating transcripts beyond TEs still need to be clarified, and it may be a stage-dependent event. We chose chicken germline as a study model because of the significantly lower TE complexity in the chicken genome compared to mammalian species.
RESULTS: We generated high-confidence piRNA candidates in various stages across chicken germline development by 3'-end-methylation-enriched small RNA sequencing and in-house bioinformatics analysis. We observed a significant developmental stage-dependent loss of TE association and a shifting of the ping-pong cycle signatures. Moreover, the stage-dependent reciprocal abundance of LINE retrotransposons, CR1-C, and its associated piRNAs implicated the developmental stage-dependent role of piRNA machinery. The stage dependency of piRNA expression and its potential functions can be better addressed by analyzing the piRNA precursors/clusters. Interestingly, the new piRNA clusters identified from embryonic chicken testes revealed evolutionary conservation between chickens and mammals, which was previously thought to not exist.
CONCLUSIONS: In this report, we provided an original chicken RNA resource and proposed an analytical methodology that can be used to investigate stage-dependent changes in piRNA compositions and their potential roles in TE regulation and beyond, and also revealed possible conserved functions of piRNAs in developing germ cells.

PMID: 29859049 [PubMed - in process]

Mini-reviews based on the First Conference of the Institute of Stress Biology & Medicine "Systems Biology-Medicine and Stress".

Hormones (Athens). 2018 Mar;17(1):3-4

Authors: Chrousos GP, Pervanidou P, Dalla C

PMID: 29858863 [PubMed - in process]

Extension of C. elegans lifespan using the ·NO-delivery dinitrosyl iron complexes.

J Biol Inorg Chem. 2018 Jun 01;:

Authors: Huang HW, Lin YH, Lin MH, Huang YR, Chou CH, Hong HC, Wang MR, Tseng YT, Liao PC, Chung MC, Ma YJ, Wu SC, Chuang YJ, Wang HD, Wang YM, Huang HD, Lu TT, Liaw WF

Abstract
The ubiquitous and emerging physiology function of endogenous nitric oxide in vascular, myocardial, immune, and neuronal systems prompts chemists to develop a prodrug for the controlled delivery of ·NO in vivo and for the translational biomedical application. Inspired by the discovery of natural [Fe(NO)2] motif, herein, we develop the synthetic dinitrosyl iron complexes (DNICs) [Fe2(μ-SR)2(NO)4] (1) as a universal platform for the O2-triggered release of ·NO, for the regulation of ·NO-release kinetics (half-life = 0.6-27.4 h), and for the activation of physiological function of ·NO. Using C. elegans as a model organism, the ·NO-delivery DNIC 1 regulates IIS signaling pathway, AMPK signaling pathway, and mitochondrial function pathway to extend the lifespan and to delay the aging process based on the lifespan analysis, SA-βgal activity assay, and next-generation RNA sequencing analysis. This study unveils the anti-aging effect of ·NO and develops DNICs as a chemical biology probe for the continued discovery of unprecedented NO physiology.

PMID: 29858679 [PubMed - as supplied by publisher]

The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma.

Mol Ther Nucleic Acids. 2018 Jun 01;11:538-553

Authors: Zhao JF, Zhao Q, Hu H, Liao JZ, Lin JS, Xia C, Chang Y, Liu J, Guo AY, He XX

Abstract
Hepatocellular carcinoma (HCC) is a worldwide malignance, and the underlying mechanisms of this disease are not fully elucidated. In this study, the existence and function of achaete-scute homolog-1 (ASH1)-miR-375-YWHAZ signaling axis in HCC were determined. Our experiments and the Cancer Genome Atlas (TCGA) sequencing data analyses showed that ASH1 and miR-375 were significantly downregulated, whereas YWHAZ was significantly upregulated in HCC. Furthermore, we found that ASH1 positively regulates miR-375, and miR-375 directly downregulates its target YWHAZ. Gain- and loss-of-function study demonstrated ASH1 and miR-375 function as tumor suppressors, whereas YWHAZ acts as an oncogene in HCC. Animal experiment indicated that YWHAZ small interfering RNAs (siRNAs) (si-YWHAZ) delivered by nanoliposomes could suppress the growth of hepatoma xenografts and was well tolerant by nude mice. Further studies revealed that YWHAZ was involved in several protein networks, such as cell autophagy, epithelial-mesenchymal transition (EMT), apoptosis, cell cycle, invasion, and migration. In addition, the patient group with ASH1-high-expression-miR-375-high-expression-YWHAZ-low-expression was correlated with a better clinical prognosis compared with the opposite expression group. In conclusion, we proved the existence of ASH1-miR-375-YWHAZ signaling axis and interpreted its important role in driving HCC tumor progression.

PMID: 29858089 [PubMed]