24 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 2019/05/17

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.

50 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 2019/05/16

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.

Identification of unique key genes and miRNAs in latent tuberculosis infection by network analysis.

Mol Immunol. 2019 May 10;112:103-114

Authors: Lin Y, Zhang Y, Yu H, Tian R, Wang G, Li F

Abstract
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M.tb). New cases are now mainly caused by the progression of latent tuberculosis infection (LTBI). Thus, methods to diagnose and treat LTBI are urgently needed to prevent the development of active TB in infected individuals and the subsequent spread of the disease. In this study, a systems biology approach was utilized to obtain numerous microarray data sets for mRNAs and microRNAs (miRNAs) expressed in the peripheral blood mononuclear cells (PBMCs) of TB patients and individuals with LTBI. Within these data sets, we identified the differentially expressed mRNAs and miRNAs and further investigated which differentially expressed genes and miRNAs were uniquely expressed during LTBI. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was employed to analyze the functional annotations and pathway classifications of the identified genes. To further understand the unique miRNA-gene regulatory network of LTBI, we constructed a protein-protein interaction (PPI) network for the targeted genes. The PPI network included 39 genes that were differentially and uniquely expressed in PBMCs of individuals with LTBI, and KEGG pathway enrichment analysis showed that these genes were predominantly involved in the PI3K-Akt signaling pathway, which plays an important role in chronic inflammation. DIANA TOOLs-mirPath analysis revealed that the identified miRNAs in the miRNA-gene regulatory network for LTBI were mainly associated with the Hippo signaling pathway, which functions in the development of inflammation. Quantitative real-time PCR verified the up expression of hsa-miR-212-3p and its predicted target gene -MAPK1 which had low expression and was a major component of the PPI network, and MAPK1 expression was correlated with the clinicopathological characteristics of LTBI by receiver operating characteristic (ROC) curve analysis. Therefore, MAPK1 has potential to be a new investigable marker during LTBI, which merits our further study and solution. The unique aberrant miRNA-gene regulatory network and the related PPI network identified in this study provide insight into the molecular mechanisms of the immune response to LTBI, and thus, may aid in the development of a novel treatment strategy.

PMID: 31082644 [PubMed - as supplied by publisher]

The Causes and Consequences of Genetic Interactions (Epistasis).

Annu Rev Genomics Hum Genet. 2019 May 13;:

Authors: Domingo J, Baeza-Centurion P, Lehner B

Abstract
The same mutation can have different effects in different individuals. One important reason for this is that the outcome of a mutation can depend on the genetic context in which it occurs. This dependency is known as epistasis. In recent years, there has been a concerted effort to quantify the extent of pairwise and higher-order genetic interactions between mutations through deep mutagenesis of proteins and RNAs. This research has revealed two major components of epistasis: nonspecific genetic interactions caused by nonlinearities in genotype-to-phenotype maps, and specific interactions between particular mutations. Here, we provide an overview of our current understanding of the mechanisms causing epistasis at the molecular level, the consequences of genetic interactions for evolution and genetic prediction, and the applications of epistasis for understanding biology and determining macromolecular structures. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 20 is August 30, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID: 31082279 [PubMed - as supplied by publisher]

Origanum vulgare terpenoids modulate Myrmica scabrinodis brain biogenic amines and ant behaviour.

PLoS One. 2018;13(12):e0209047

Authors: Mannino G, Abdi G, Maffei ME, Barbero F

Abstract
Coordinated social behaviour is fundamental for ant ecological success. However, even distantly-related organisms, such as plants, have evolved the ability to manipulate ant collective performances to their own advantage. In the parasitic system encompassing Maculinea butterflies, Myrmica ants, and Origanum vulgare plants, the ant-plant interaction elicits the release of a volatile terpenoid compound (carvacrol) which is used by the gravid butterfly to locate the ideal oviposition site. Here we show that this ant-plant association is maintained by the effect of O. vulgare terpenoids on ant behaviour and that food plants might gain protection by Myrmica ants by chemically manipulating workers to forage in their surroundings. The variation in the locomotor ability of three ant species (Formica cinerea, Tetramorium caespitum, and Myrmica scabrinodis) was studied after treatment with the two major O. vulgare terpenoid volatile compounds (i.e., carvacrol and thymol). The brain levels of three biogenic amines (dopamine, tyramine and serotonin) were analysed in ants exposed to the O. vulgare terpenoids by HPLC-ESI-MS/MS. Carvacrol and thymol increased the locomotor activity of all ant species tested, but if blended reduced the movement propensity of Myrmica scabrinodis. Dopamine and tyramine production was positively correlated with the worker locomotor activity. In Myrmica ants, both brain biogenic ammines were negatively correlated with the aggressive behaviour. Blends of O. vulgare volatiles affected the locomotor ability while increased the aggressiveness of Myrmica workers by altering the aminergic regulation in the ant brains. This behavioural manipulation, might enhance partner fidelity and plant protection. Our findings provide new insights supporting a direct role of plant volatiles in driving behavioural changes in social insects through biogenic amine modulation.

PMID: 30586439 [PubMed - indexed for MEDLINE]

Oriented Cell Division: The Pull of the Pole.

Dev Cell. 2018 12 17;47(6):686-687

Authors: Scepanovic G, Fernandez-Gonzalez R

Abstract
Cells are thought to divide along their longest axis. Now, two studies in Developmental Cell (Scarpa et al., 2018) and EMBO Journal (Finegan et al., 2018) reveal that in many instances, cell division orientation in vivo is not determined by cell shape, but rather by local anisotropies in cell mechanics.

PMID: 30562509 [PubMed - indexed for MEDLINE]

Parkinson-Associated SNCA Enhancer Variants Revealed by Open Chromatin in Mouse Dopamine Neurons.

Am J Hum Genet. 2018 12 06;103(6):874-892

Authors: McClymont SA, Hook PW, Soto AI, Reed X, Law WD, Kerans SJ, Waite EL, Briceno NJ, Thole JF, Heckman MG, Diehl NN, Wszolek ZK, Moore CD, Zhu H, Akiyama JA, Dickel DE, Visel A, Pennacchio LA, Ross OA, Beer MA, McCallion AS

Abstract
The progressive loss of midbrain (MB) dopaminergic (DA) neurons defines the motor features of Parkinson disease (PD), and modulation of risk by common variants in PD has been well established through genome-wide association studies (GWASs). We acquired open chromatin signatures of purified embryonic mouse MB DA neurons because we anticipated that a fraction of PD-associated genetic variation might mediate the variants' effects within this neuronal population. Correlation with >2,300 putative enhancers assayed in mice revealed enrichment for MB cis-regulatory elements (CREs), and these data were reinforced by transgenic analyses of six additional sequences in zebrafish and mice. One CRE, within intron 4 of the familial PD gene SNCA, directed reporter expression in catecholaminergic neurons from transgenic mice and zebrafish. Sequencing of this CRE in 986 individuals with PD and 992 controls revealed two common variants associated with elevated PD risk. To assess potential mechanisms of action, we screened >16,000 proteins for DNA binding capacity and identified a subset whose binding is impacted by these enhancer variants. Additional genotyping across the SNCA locus identified a single PD-associated haplotype, containing the minor alleles of both of the aforementioned PD-risk variants. Our work posits a model for how common variation at SNCA might modulate PD risk and highlights the value of cell-context-dependent guided searches for functional non-coding variation.

PMID: 30503521 [PubMed - indexed for MEDLINE]

Associations Between Soluble LDLR and Lipoproteins in a White Cohort and the Effect of PCSK9 Loss-of-Function.

J Clin Endocrinol Metab. 2018 09 01;103(9):3486-3495

Authors: Mayne J, Ooi TC, Tepliakova L, Seebun D, Walker K, Mohottalage D, Ning Z, Abujrad H, Mbikay M, Wassef H, Chrétien M, Figeys D

Abstract
Context: Elevated circulating cholesterol-rich low-density lipoprotein (LDL) particles increase coronary artery disease risk. Cell-surface hepatic LDL receptors (LDLRs) clear 70% of these particles from circulation. The ectodomain of LDLR is shed into circulation, preventing it from removing LDL particles. The role that LDLR ectodomain shedding plays as a regulatory mechanism is unknown.
Objective: We describe LDLR shedding via the relationships between circulating soluble LDLRs (sLDLRs) and serum lipoproteins, serum proprotein convertase subtilin/kexin type 9 (PCSK9; a negative regulator of LDLR), and clinical parameters in a white Canadian population.
Design: Population-based, cross-sectional study.
Settings: Clinical Research Center, The Ottawa Hospital, and Faculty of Medicine, University of Ottawa.
Participants: Two hundred seventy-three white Canadians.
Intervention: None.
Main Outcome Measures: sLDLR measured by ELISA; serum lipids and PCSK9, PCSK9 genotypes, and clinical parameters from previous analyses.
Results: sLDLRs correlated strongly with triglycerides (TG; r = 0.624, P < 0.0001) and moderately with LDL cholesterol (r = 0.384, P < 0.0001), and high-density lipoprotein cholesterol (r = -0.307, P = 0.0003). Only TG correlations were unaffected by PCSK9 variations. sLDLR levels were significantly elevated in those with TG >50th or LDL cholesterol >75th percentiles.
Conclusions: Serum sLDLR levels correlate with several lipoprotein parameters, especially TG, and the presence of PCSK9 loss-of-function variants alters sLDLR levels and correlations, except for TG. Ectodomain LDLR shedding has a role in LDL metabolism, distinct from PCSK9, with interplay between these two pathways that regulate cell-surface LDLRs. Findings suggest alteration of LDLR shedding could emerge as a target to treat dyslipidemia.

PMID: 29982529 [PubMed - indexed for MEDLINE]

Kinesin expands and stabilizes the GDP-microtubule lattice.

Nat Nanotechnol. 2018 05;13(5):386-391

Authors: Peet DR, Burroughs NJ, Cross RA

Abstract
Kinesin-1 is a nanoscale molecular motor that walks towards the fast-growing (plus) ends of microtubules, hauling molecular cargo to specific reaction sites in cells. Kinesin-driven transport is central to the self-organization of eukaryotic cells and shows great promise as a tool for nano-engineering 1 . Recent work hints that kinesin may also play a role in modulating the stability of its microtubule track, both in vitro2,3 and in vivo 4 , but the results are conflicting5-7 and the mechanisms are unclear. Here, we report a new dimension to the kinesin-microtubule interaction, whereby strong-binding state (adenosine triphosphate (ATP)-bound and apo) kinesin-1 motor domains inhibit the shrinkage of guanosine diphosphate (GDP) microtubules by up to two orders of magnitude and expand their lattice spacing by ~1.6%. Our data reveal an unexpected mechanism by which the mechanochemical cycles of kinesin and tubulin interlock, and so allow motile kinesins to influence the structure, stability and mechanics of their microtubule track.

PMID: 29531331 [PubMed - indexed for MEDLINE]

Single-cell sequencing reveals dissociation-induced gene expression in tissue subpopulations.

Nat Methods. 2017 09 29;14(10):935-936

Authors: van den Brink SC, Sage F, Vértesy Á, Spanjaard B, Peterson-Maduro J, Baron CS, Robin C, van Oudenaarden A

PMID: 28960196 [PubMed - indexed for MEDLINE]

49 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 2019/05/14

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.

Treatment with selenium-enriched Saccharomyces cerevisiae UFMG A-905 partially ameliorates mucositis induced by 5-fluorouracil in mice.

Cancer Chemother Pharmacol. 2019 May 11;:

Authors: Porto BAA, Monteiro CF, Souza ÉLS, Leocádio PCL, Alvarez-Leite JI, Generoso SV, Cardoso VN, Almeida-Leite CM, Santos DA, Santos JRA, Nicoli JR, Pessione E, Martins FS

Abstract
PURPOSE: Gastrointestinal mucositis is a major problem associated with cancer therapy. To minimize these deleterious effects, simultaneous administration of antioxidant components, such as selenium, can be considered. There is a growing interest in the use of yeasts because they are able to convert inorganic selenium into selenomethionine. In the present study, oral administration of Saccharomyces cerevisiae UFMG A-905 enriched with selenium was evaluated as an alternative in minimizing the side effects of 5FU-induced mucositis in mice.
METHODS: Mice body weight, food consumption, faeces consistency and the presence of blood in faeces were assessed daily during experimental mucositis induced by 5-fluorouracil (5FU). Blood was used for intestinal permeability determination, and small intestine for oxidative stress, immunological and histopathological examination.
RESULTS: The increased intestinal permeability observed with mucositis induction was partially reverted by S. cerevisiae and selenium-enriched yeast. Both treatments were able to reduce myeloperoxidase activity, but only selenium-enriched yeast reduced eosinophil peroxidase activity. CXCL1/KC levels, histopathological tissue damage and oxidative stress (lipid peroxidation and nitrite production) in the small intestine were reduced by both treatments; however, this reduction was always higher when treatment with selenium-enriched yeast was evaluated.
CONCLUSIONS: Results of the present study showed that the oral administration of S. cerevisiae UFMG A-905 protected mice against mucositis induced by 5-FU, and that this effect was potentiated when the yeast was enriched with selenium.

PMID: 31079219 [PubMed - as supplied by publisher]

Feathers of Humboldt penguin are suitable bioindicators of Rare Earth Elements.

Sci Total Environ. 2019 May 04;678:627-631

Authors: Squadrone S, Brizio P, Stella C, Favaro L, Da Rugna C, Florio D, Gridelli S, Abete MC

Abstract
Rare earth elements (REEs), also called lanthanides, are emerging contaminants worldwide, due to their unique physical and chemical characteristics that make them essential in a variety of industrial applications. However, there is still a gap in the knowledge of occurrence and accumulation of REEs in biota, and no investigations have yet been performed in penguin feathers, which have already been widely utilized as a non-invasive tool for the biomonitoring of trace elements. The concentrations of 16 REEs were investigated in a colony of Humboldt penguins (Spheniscus humboldti) housed at the Acquario di Cattolica (Italy). Multielement determination of REEs was performed by an Inductively Coupled Plasma-Mass Spectrometer after a microwave digestion of feathers. As this colony lives indoors in a controlled environment, it was the ideal choice for studying lanthanide occurrence in penguin feathers. Since there is a strict link between metal levels in feathers and the diet of penguins, their food (capelin) was also tested for REEs. Chondrite normalized values revealed the same pattern for REEs in feathers and fish, but REE concentrations were an order of magnitude higher in penguin feathers, demonstrating the suitability of this tissue as a bioindicator of REEs.

PMID: 31078853 [PubMed - as supplied by publisher]

CRISPR/Cas9 as a tool to dissect cancer mutations.

Methods. 2019 May 09;:

Authors: Sayed S, Paszkowski-Rogacz M, Schmitt L, Buchholz F

Abstract
The CRISPR/Cas9 system is transforming many biomedical disciplines, including cancer research. Through its flexible programmability and efficiency to induce DNA double strand breaks it has become straightforward to introduce cancer mutations into cells in vitro and/or in vivo. However, not all mutations contribute equally to tumorigenesis and distinguishing essential mutations for tumor growth and survival from biologically inert mutations is cumbersome. Here we present a method to screen for the functional relevance of mutations in high throughput in established cancer cell lines. We employ the CRISPR/Cas9 system to probe cancer vulnerabilities in a colorectal carcinoma cell line in an attempt to identify novel cancer driver mutations. We designed 100 high quality sgRNAs that are able to specifically cleave mutations present in the colorectal carcinoma cell line RKO. An all-in-one lentiviral library harboring these sgRNAs was then generated and used in a pooled screen to probe possible growth dependencies on these mutations. Genomic DNA at different time points were collected, the sgRNA cassettes were PCR amplified, purified and sgRNA counts were quantified by means of deep sequencing. The analysis revealed two sgRNAs targeting the same mutation (UTP14A: S99delS) to be depleted over time in RKO cells. Validation and characterization confirmed that the inactivation of this mutation impairs cell growth, nominating UTP14A: S99delS as a putative driver mutation in RKO cells. Overall, our approach demonstrates that the CRISPR/Cas9 system is a powerful tool to functionally dissect cancer mutations at large-scale.

PMID: 31078796 [PubMed - as supplied by publisher]

Organoid technology in cancer precision medicine.

Cancer Lett. 2019 May 09;:

Authors: Xia X, Li F, He J, Aji R, Gao D

Abstract
Organoid technology has been remarkably improved over the last decade. Various organoids have been derived from different types of tissues and recapitulate their organ-specific gene expression signatures, particular tissue spatial structures and functions of their original tissue. The patient-derived organoids (PDOs) have been used to elucidate crucial scientific questions, including the relationships between genetic/epigenetic alterations and drug responses, cell plasticity during disease progressions, and mechanisms of drug resistances. With the great expectations, PDOs will be widely used to facilitate the personalized medical decisions, which have the potential to profoundly improve patient outcomes. In this review, we will discuss the developmental details, current achievements, applications and challenges of organoid technology in precision cancer medicine.

PMID: 31078736 [PubMed - as supplied by publisher]

Adaptation of Human iPSC-Derived Cardiomyocytes to Tyrosine Kinase Inhibitors Reduces Acute Cardiotoxicity via Metabolic Reprogramming.

Cell Syst. 2019 Apr 30;:

Authors: Wang H, Sheehan RP, Palmer AC, Everley RA, Boswell SA, Ron-Harel N, Ringel AE, Holton KM, Jacobson CA, Erickson AR, Maliszewski L, Haigis MC, Sorger PK

Abstract
Tyrosine kinase inhibitors (TKIs) are widely used to treat solid tumors but can be cardiotoxic. The molecular basis for this toxicity and its relationship to therapeutic mechanisms remain unclear; we therefore undertook a systems-level analysis of human cardiomyocytes (CMs) exposed to four TKIs. CMs differentiated from human induced pluripotent stem cells (hiPSCs) were exposed to sunitinib, sorafenib, lapatinib, or erlotinib, and responses were assessed by functional assays, microscopy, RNA sequencing, and mass spectrometry (GEO: GSE114686; PRIDE: PXD012043). TKIs have diverse effects on hiPSC-CMs distinct from inhibition of tyrosine-kinase-mediated signal transduction; cardiac metabolism is particularly sensitive. Following sorafenib treatment, oxidative phosphorylation is downregulated, resulting in a profound defect in mitochondrial energetics. Cells adapt by upregulating aerobic glycolysis. Adaptation makes cells less acutely sensitive to sorafenib but may have long-term negative consequences. Thus, CMs exhibit adaptive responses to anti-cancer drugs conceptually similar to those previously shown in tumors to mediate drug resistance.

PMID: 31078528 [PubMed - as supplied by publisher]

14 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 2019/05/12

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.

14 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 2019/05/12

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.

32 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 2019/05/11

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.

32 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 2019/05/11

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.