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 2020/01/31

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.

20 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 2020/01/30

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.

26 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 2020/01/29

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.

27 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 2020/01/28

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.

Support of a molecular tumour board by an evidence-based decision management system for precision oncology.

Eur J Cancer. 2020 Jan 23;127:41-51

Authors: Lamping M, Benary M, Leyvraz S, Messerschmidt C, Blanc E, Kessler T, Schütte M, Lenze D, Jöhrens K, Burock S, Klinghammer K, Ochsenreither S, Sers C, Schäfer R, Tinhofer I, Beule D, Klauschen F, Yaspo ML, Keilholz U, Rieke DT

Abstract
BACKGROUND: Reliable and reproducible interpretation of molecular aberrations constitutes a bottleneck of precision medicine. Evidence-based decision management systems may improve rational therapy recommendations. To cope with an increasing amount of complex molecular data in the clinical care of patients with cancer, we established a workflow for the interpretation of molecular analyses.
METHODS: A specialized physician screened results from molecular analyses for potential biomarkers, irrespective of the diagnostic modality. Best available evidence was retrieved and categorized through establishment of an in-house database and interrogation of publicly available databases. Annotated biomarkers were ranked using predefined evidence levels and subsequently discussed at a molecular tumour board (MTB), which generated treatment recommendations. Subsequent translation into patient treatment and clinical outcomes were followed up.
RESULTS: One hundred patients were discussed in the MTB between January 2016 and May 2017. Molecular data were obtained for 70 of 100 patients (50 whole exome/RNA sequencing, 18 panel sequencing, 2 immunohistochemistry (IHC)/microsatellite instability analysis). The MTB generated a median of two treatment recommendations each for 63 patients. Thirty-nine patients were treated: 6 partial responses and 12 stable diseases were achieved as best responses. Genetic counselling for germline events was recommended for seven patients.
CONCLUSION: The development of an evidence-based workflow allowed for the clinical interpretation of complex molecular data and facilitated the translation of personalized treatment strategies into routine clinical care. The high number of treatment recommendations in patients with comprehensive genomic data and promising responses in patients treated with combination therapy warrant larger clinical studies.

PMID: 31982633 [PubMed - as supplied by publisher]

Clostridium cellulovorans metabolism of cellulose as studied by comparative proteomic approach.

J Proteomics. 2020 Jan 23;:103667

Authors: Usai G, Cirrincione S, Re A, Manfredi M, Pagnani A, Pessione E, Mazzoli R

Abstract
Clostridium cellulovorans is among the most promising candidates for consolidated bioprocessing (CBP) of cellulosic biomass to liquid biofuels (ethanol, butanol). C. cellulovorans metabolizes all the main plant polysaccharides and mainly produces butyrate. Since most butyrate and butanol biosynthetic reactions from acetyl-CoA are common, introduction of single heterologous alcohol/aldehyde dehydrogenase can divert the branching-point intermediate (butyryl-CoA) towards butanol production in this strain. However, engineering C. cellulovorans metabolic pathways towards industrial utilization requires better understanding of its metabolism. The present study aimed at improving comprehension of cellulose metabolism in C. cellulovorans by comparing growth kinetics, substrate consumption/product accumulation and whole-cell soluble proteome (data available via ProteomeXchange, identifier PXD015487) with those of the same strain grown on a soluble carbohydrate, glucose, as the main carbon source. Growth substrate-dependent modulations of the central metabolism were detected, including regulation of several glycolytic enzymes, fermentation pathways (e.g. hydrogenase, pyruvate formate lyase, phosphate transacetylase) and nitrogen assimilation (e.g. glutamate dehydrogenase). Overexpression of hydrogenase and increased ethanol production by glucose-grown bacteria suggest a more reduced redox state. Higher energy expenditure seems to occur in cellulose-grown C. cellulovorans (likely related to overexpression and secretion of (hemi-)cellulases), which induces up-regulation of ATP synthetic pathways, e.g. acetate production and ATP synthase. SIGNIFICANCE: C. cellulovorans can metabolize all the main plant polysaccharides (cellulose, hemicelluloses and pectins) and, unlike other well established cellulolytic microorganisms, can produce butyrate. C. cellulovorans is therefore among the most attractive candidates for direct fermentation of lignocellulose to high-value chemicals and, especially, n-butanol, i.e. one of the most promising liquid biofuels for the future. Recent studies aimed at engineering n-butanol production in C. cellulovorans represent milestones towards production of biofuels through one-step fermentation of lignocellulose but also indicated that more detailed understanding of the C. cellulovorans central carbon metabolism is essential to refine metabolic engineering strategies towards improved n-butanol production in this strain. The present study helped identifying key genes associated with specific catabolic reactions and indicated modulations of central carbon metabolism (including redox and energy balance) associated with cellulose consumption. This information will be useful to determine key enzymes and possible metabolic bottlenecks to be addressed towards improved metabolic engineering of this strain.

PMID: 31982546 [PubMed - as supplied by publisher]

Cancer Cells Employ Nuclear Caspase-8 to Overcome the p53-Dependent G2/M Checkpoint through Cleavage of USP28.

Mol Cell. 2020 Jan 13;:

Authors: Müller I, Strozyk E, Schindler S, Beissert S, Oo HZ, Sauter T, Lucarelli P, Raeth S, Hausser A, Al Nakouzi N, Fazli L, Gleave ME, Liu H, Simon HU, Walczak H, Green DR, Bartek J, Daugaard M, Kulms D

Abstract
Cytosolic caspase-8 is a mediator of death receptor signaling. While caspase-8 expression is lost in some tumors, it is increased in others, indicating a conditional pro-survival function of caspase-8 in cancer. Here, we show that tumor cells employ DNA-damage-induced nuclear caspase-8 to override the p53-dependent G2/M cell-cycle checkpoint. Caspase-8 is upregulated and localized to the nucleus in multiple human cancers, correlating with treatment resistance and poor clinical outcome. Depletion of caspase-8 causes G2/M arrest, stabilization of p53, and induction of p53-dependent intrinsic apoptosis in tumor cells. In the nucleus, caspase-8 cleaves and inactivates the ubiquitin-specific peptidase 28 (USP28), preventing USP28 from de-ubiquitinating and stabilizing wild-type p53. This results in de facto p53 protein loss, switching cell fate from apoptosis toward mitosis. In summary, our work identifies a non-canonical role of caspase-8 exploited by cancer cells to override the p53-dependent G2/M cell-cycle checkpoint.

PMID: 31982308 [PubMed - as supplied by publisher]

16 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 2020/01/26

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.

16 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 2020/01/26

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.

52 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 2020/01/25

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.

28 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 2020/01/24

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.

25 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 2020/01/23

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.

37 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 2020/01/22

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.

37 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 2020/01/22

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.

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 2020/01/21

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.

30 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 2020/01/21

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.

OptFill: A Tool for Infeasible Cycle-Free Gapfilling of Stoichiometric Metabolic Models.

iScience. 2019 Dec 18;23(1):100783

Authors: Schroeder WL, Saha R

Abstract
Stoichiometric metabolic modeling, particularly genome-scale models (GSMs), is now an indispensable tool for systems biology. The model reconstruction process typically involves collecting information from public databases; however, incomplete systems knowledge leaves gaps in any reconstruction. Current tools for addressing gaps use databases of biochemical functionalities to address gaps on a per-metabolite basis and can provide multiple solutions but cannot avoid thermodynamically infeasible cycles (TICs), invariably requiring lengthy manual curation. To address these limitations, this work introduces an optimization-based multi-step method named OptFill, which performs TIC-avoiding whole-model gapfilling. We applied OptFill to three fictional prokaryotic models of increasing sizes and to a published GSM of Escherichia coli, iJR904. This application resulted in holistic and infeasible cycle-free gapfilling solutions. In addition, OptFill can be adapted to automate inherent TICs identification in any GSM. Overall, OptFill can address critical issues in automated development of high-quality GSMs.

PMID: 31954977 [PubMed - as supplied by publisher]

Antioxidant activity and polyphenol composition of sugarcane molasses extract.

Food Chem. 2020 Jan 11;314:126180

Authors: Deseo MA, Elkins A, Rochfort S, Kitchen B

Abstract
The antioxidant activity of sugarcane molasses ethanol extract (ME) and its fraction (ME-RBF) was evaluated using ABTS, ORAC 6.0 and CAA assays and ME-RBF demonstrated 26-fold, 12-fold and 2-fold higher values, respectively than ME. Likewise, total polyphenol and flavonoid concentration in ME-RBF are more than 10-fold higher than ME, that suggested antioxidant activity is correlated with polyphenol composition. Quantitative analysis of 13 polyphenols (chlorogenic acid, caffeic acid, sinapic acid, syringic acid, vanillin, homoorientin, orientin, vitexin, swertisin, diosmin, apigenin, tricin and diosmetin) was carried out by LCMS. MS/MS analysis allowed the tentative identification of seven apigenin-C-glycosides, three methoxyluteolin-C-glycosides and three tricin-O-glycosides some of which have not been reported in sugarcane before to the best of our knowledge. The results demonstrated that sugarcane molasses can be used as potential source of polyphenols that can be beneficial to health.

PMID: 31954937 [PubMed - as supplied by publisher]

Faropenem resistance causes in vitro cross resistance to carbapenems in ESBL- producing Escherichia coli.

Int J Antimicrob Agents. 2020 Jan 16;:105902

Authors: Gandra S, Choi J, McElvania E, Green SJ, Harazin M, Thomson RB, Dantas G, Singh KS, Das S

Abstract
OBJECTIVE: Faropenem is an oral penem drug with activity against facultative gram-positive and gram-negative bacteria including CTX-M-15 type extended spectrum beta-lactamase (ESBL)- producing Enterobacteriales and anaerobic bacteria. Due to structural similarities there is a concern for the development of carbapenem cross-resistance; however, there are no studies confirming this. We examined if in vitro development of faropenem resistance in Escherichia coli isolates would result in cross-resistance to carbapenems.
METHODS: Four well characterized E. coli isolates from the US Centers for Disease Control and Prevention antibiotic resistance isolate bank were utilized. Three isolates (NSF1, NSF2, NSF3) are ESBL producers (CTX-M-15) and one (NSF4) is pan-susceptible. Faropenem minimum inhibitory concentrations (MICs) were determined and resistance was induced by serial passaging in increasing concentrations of faropenem. Susceptibility to carbapenems was determined and whole genome sequencing (WGS) was performed to identify the underlying genetic mechanism leading to carbapenem resistance.
RESULTS: Faropenem MIC increased from 1mg/L to 64mg/L within 10 days for NSF2 and NSF4 isolates, and from 2 mg/L to 64 mg/L within 7 days for NSF1 and NSF3 isolates. Reduced carbapenem susceptibility (ertapenem MIC ≥8 mg/L, doripenem/meropenem ≥2 mg/L, imipenem ≥1 mg/L) developed among three CTX-M-15 producing isolates that were faropenem resistant, but not in NSF4 isolate that lacked ESBL enzyme. WGS analysis revealed non-synonymous changes in ompC gene among three CTX-M-15 producing isolates, and a single nucleotide polymorphism in envZ gene in NSF4 isolate.
CONCLUSION: Induced resistance to faropenem causes cross-resistance to carbapenems among E. coli isolates containing CTX-M-15 type ESBL enzymes.

PMID: 31954833 [PubMed - as supplied by publisher]

Fatty acid profile of phospholipids and sphingomyelin in milk and regulation of sphingomyelin synthesis of mammary glands in cows receiving increasing levels of crushed sunflower seeds.

J Dairy Sci. 2020 Jan 15;:

Authors: Lashkari S, Moller JW, Jensen SK, Hellgren LI, Sørensen MT, Theil PK, Sejrsen K

Abstract
The objective of this study was to investigate the effect of increasing dietary supplementation of crushed sunflower seed (CSS) in the diet of dairy cows on the fatty acid (FA) composition of phospholipids and sphingomyelin in milk, and on mammary transcription of genes that are important for sphingomyelin de novo synthesis. Four groups of 6 cows received diets supplemented with CSS at 0% (control), or 5, 10, or 15% of dry matter for a 5-wk experimental period. Milk samples and mammary biopsies were collected at the end of the experiment. Phospholipid concentration in milk fat decreased linearly with CSS supplementation. Sphingomyelin concentration in milk fat was unaffected by CSS supplementation. Daily yield of phospholipids decreased linearly with CSS supplementation. Daily yield of sphingomyelin was not significantly affected. The CSS supplementation linearly increased the proportion of monounsaturated FA in milk phospholipids. The major isomer incorporated into phospholipids was C18:1 (n-9 cis), which showed a linear increase with CSS supplementation. The C22:0 proportion in sphingomyelin increased linearly with CSS supplementation and constituted between 15.2 to 25.4% of total FA in sphingomyelin. However, CSS supplementation linearly decreased C23:0 sphingomyelin. Mammary transcription of serine palmitoyl transferase, long chain subunit 1 and subunit 2, the rate-limiting enzymes in ceramide synthesis, showed a linear decrease with increasing CSS supplementation. In conclusion, the data showed that dietary supplementation of CSS linearly increased the proportion of unsaturated FA and monounsaturated FA in milk phospholipids with no effect on phospholipid concentration. In addition, CSS supplementation linearly decreased n-3 polyunsaturated fatty acid proportion in sphingomyelin. The results further showed that mammary transcription of important genes for sphingomyelin de novo synthesis is regulated by lipid supplementation.

PMID: 31954562 [PubMed - as supplied by publisher]