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 2019/03/06

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.

57 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 2019/03/05

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.

Nuphar alkaloids induce very rapid apoptosis through a novel caspase-dependent but BAX/BAK-independent pathway.

Cell Biol Toxicol. 2019 Mar 02;:

Authors: Mallick DJ, Korotkov A, Li H, Wu J, Eastman A

Abstract
Nuphar alkaloids, originally isolated from water lilies, induce apoptosis in mammalian cells in less than 1 h, making them possibly the fastest known inducers. However, the mechanism by which this rapid apoptosis occurs remains unknown. We have investigated canonical aspects of apoptosis to determine how the nuphar alkaloid, (+)-6-hydroxythiobinupharidine (6HTBN), induces apoptosis. 6HTBN induced rapid apoptosis in various leukemia, lymphoma, and carcinoma cell lines, suggesting that its mechanism is cell-type independent. It also circumvented resistance of patient-derived chronic lymphocytic leukemia cells generated by co-culture on survival-promoting stroma. Intriguingly, 6HTBN failed to induce apoptosis in platelets. The mechanism of apoptosis involves activation of caspase 9 and caspase 3, but not caspase 8 as previously reported. The release of cytochrome c from mitochondria occurred even in the absence of BAX/BAK and in cells that retained mitochondrial membrane potential. These results suggest a novel mechanism of apoptosis that has previously not been reported. The molecular target of the nuphar alkaloids remains to be determined.

PMID: 30826899 [PubMed - as supplied by publisher]

The fickle CHO: a review of the causes, implications, and potential alleviation of the CHO cell line instability problem.

Curr Opin Biotechnol. 2019 Feb 28;60:128-137

Authors: Dahodwala H, Lee KH

Abstract
Chinese hamster ovary (CHO) cell-based bioproduction of recombinant proteins can now routinely achieve >5 g/L titers in fed-batches. This progress is partly due to the rapid adaptability of CHO cells to various genetic manipulations and changing process conditions. An inherently plastic genome allows for this adaptability; however, it also gives CHO cells the propensity for genomic rearrangements. In combination with the genomic and metabolic demand of high producer cells, CHO cell plasticity manifests itself in the bioproduction process as cell line instability, by way of a decline in productivity and product quality. In this review, we provide a definition for titer and quality stability and discuss the main causes of the CHO instability phenomenon and advances in clone selection and genetic manipulations. We also discuss advances in systems biology efforts that can provide new strategies for early prediction of CHO cell instability, which will help to identify multi-gram per liter titer cell lines that can maintain production stability and reproducible product quality over extended culture durations.

PMID: 30826670 [PubMed - as supplied by publisher]

Association between chronic obstructive pulmonary disease and interleukins gene variants: A systematic review and meta-analysis.

Cytokine. 2019 Feb 28;117:65-71

Authors: Ahmadi A, Ghaedi H, Salimian J, Azimzadeh Jamalkandi S, Ghanei M

Abstract
Interleukins are cytokines involved in systemic inflammation and immune system regulation. Many studies have investigated the association between common genetic variations in interleukin-coding genes and COPD susceptibility. In this study, a systematic review and meta-analysis was performed to evaluate the association between interleukin gene variations and COPD pathogenesis. Association studies were retrieved from PubMed and Google Scholar databases using the standard systematic search strategy. A total of 26 different studies evaluating eight polymorphisms in four interleukin genes were included in this study. In overall comparisons, IL1β-rs16944, -rs1143627, -rs1143634, IL13-rs20541 polymorphisms were found not to be associated with the increased risk for developing COPD. However, IL1RN-rs2234663 and IL13-rs1800925 showed a strong association with COPD. We showed that the CC genotype carriers of the IL6-rs1800795 are at significantly higher risk of developing COPD (OR = 1.31, 95% CI: 1.04-1.64, P = 0.01) compared to GG carriers. In case of IL6-rs1800796, individuals with CC and CG genotypes showed a lower risk to develop COPD (OR = 0.46, 95%CI: 0.32-0.66, P > 0.00). This updated meta-analysis strongly supports the association of IL1RN-rs2234663, IL6-rs1800795, -rs1800795 and IL13-rs1800925 variants with COPD.

PMID: 30826601 [PubMed - as supplied by publisher]

Nerve-mediated expression of histone deacetylases regulates limb regeneration in axolotls.

Dev Biol. 2019 Feb 28;:

Authors: Wang MH, Wu CH, Huang TY, Sung HW, Chiou LL, Lin SP, Lee HS

Abstract
Axolotls have amazing abilities to regenerate their lost limbs. Nerve and wound epidermis have great impacts on this regeneration. Histone deacetylases (HDACs) have been shown to play roles in the regeneration of amphibian tails and limbs. In this study, a bi-phasic up-regulation of HDAC1 was noted before early differentiation stage of axolotl limb regeneration. Limb regeneration was delayed in larvae incubated with an HDAC inhibitor MS-275. Local injection of MS-275 or TSA, another HDAC inhibitor, into amputation sites of the juveniles did not interfere with wound healing but more profoundly inhibited local HDAC activities and blastema formation/limb regeneration. Elevation of HDAC1 expression was more apparent in wound epidermis than in mesenchyme. Prior denervation prohibited this elevation and limb regeneration. Supplementation of nerve factors BMP7, FGF2, and FGF8 in the stump ends after amputation on denervated limbs not only enabled HDAC1 up-regulation but also led to more extent of limb regeneration. In conclusion, nerve-mediated HDAC1 expression is required for blastema formation and limb regeneration.

PMID: 30826398 [PubMed - as supplied by publisher]

ATXR5/6 Forms Alternative Protein Complexes with PCNA and the Nucleosome Core Particle.

J Mol Biol. 2019 Feb 28;:

Authors: Davarinejad H, Joshi M, Ait-Hamou N, Munro K, Couture JF

Abstract
The proliferating cell nuclear antigen (PCNA) is a sliding clamp associated with DNA polymerases which serves as a binding platform for the recruitment of regulatory proteins linked to DNA damage repair, cell cycle regulation and epigenetic signaling. The histone H3 lysine-27 (H3K27) mono-methyltransferase ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5/6 (ATXR5/6) associates with PCNA and this interaction has been proposed to act as a key determinant controlling the reestablishment of H3K27 mono-methylation following replication. In this study, we provide biochemical evidence showing that PCNA inhibits ATXR6 enzymatic activity. The structure of the ATXR6 PCNA Interacting Peptide (PIP) in complex with PCNA indicates that a trio of hydrophobic residues contribute to the binding of the enzyme to the sliding clamp. Finally, despite the presence of three PIP binding clefts, only two molecules of ATXR6 binds to PCNA likely enabling the recruitment of a third protein to the sliding clamp. Collectively, these results rule out the model wherein PCNA bound ATXR6 actively reestablish H3K27 mono-methylation following DNA replication and provide insights into the role of ATXR5 PIP motif in its interaction with PCNA.

PMID: 30826376 [PubMed - as supplied by publisher]

Metabolomics profiling and pathway analysis of human plasma and urine reveal further insights into the multifactorial nature of Coronary Artery Disease (CAD).

Clin Chim Acta. 2019 Feb 28;:

Authors: Amin AM, Mostafa H, Arif NH, Kader MASKA, Hay YK

Abstract
BACKGROUND: Coronary artery disease (CAD) claims lives yearly. Nuclear magnetic resonance (1H NMR) metabolomics analysis is efficient in identifying metabolic biomarkers which lend credence to diagnosis. We identified CAD metabotypes and its implicated pathways using 1H NMR analysis.
METHODS: We analysed plasma and urine samples of 50 stable CAD patients and 50 healthy controls using 1H NMR. Orthogonal partial least square discriminant analysis (OPLS-DA) followed by multivariate logistic regression (MVLR) models were developed to indicate the discriminating metabotypes.
RESULTS: Both plasma and urine OPLS-DA models had specificity, sensitivity and accuracy of 100%, 96% and 98%, respectively. Plasma MVLR model had specificity, sensitivity, accuracy and AUROC of 92%, 86%, 89% and 0.96, respectively. The MVLR model of urine had specificity, sensitivity, accuracy and AUROC of 90%, 80%, 85% and 0.92, respectively. 35 and 12 metabolites were identified in plasma and urine metabotypes, respectively. Metabolic pathway analysis revealed that urea cycle, aminoacyl-tRNA biosynthesis and synthesis and degradation of ketone bodies pathways were significantly disturbed in plasma, while methylhistidine metabolism and galactose metabolism pathways were significantly disturbed in urine. The enrichment over representation analysis against SNPs-associated-metabolite sets library revealed that 85 SNPs were significantly enriched in plasma metabotype.
CONCLUSIONS: Cardiometabolic diseases, dysbiotic gut-microbiota and genetic variabilities are largely implicated in the pathogenesis of CAD.

PMID: 30826371 [PubMed - as supplied by publisher]

Representation and relative abundance of cell-type selective markers in whole-kidney RNA-Seq data.

Kidney Int. 2019 Feb 25;:

Authors: Clark JZ, Chen L, Chou CL, Jung HJ, Lee JW, Knepper MA

Abstract
Bulk-tissue RNA-Seq is increasingly being used in the study of physiological and pathophysiological processes in the kidney; however, the presence of multiple cell types in kidney tissue complicates data interpretation. We addressed the question of which cell types are represented in whole-kidney RNA-Seq data in order to identify circumstances in which bulk-kidney RNA-Seq can be successfully interpreted. We carried out RNA-Seq in mouse whole kidneys and in microdissected renal tubule segments. To aid in the interpretation of the data, we compiled a database of cell-type selective protein markers for 43 cell types believed to be present in kidney tissue. The whole-kidney RNA-Seq analysis identified transcripts corresponding to 17,742 genes, distributed over 5 orders of magnitude of expression level. Markers for all 43 curated cell types were detectable. Analysis of the cellular makeup of mouse and rat kidney, calculated from published literature, suggests that proximal tubule cells account for more than half of the mRNA in a kidney. Comparison of RNA-Seq data from microdissected proximal tubules with data from whole kidney supports this view. RNA-Seq data for cell-type selective markers in bulk-kidney samples provide a valid means to identify changes in minority-cell abundances in kidney tissue. Because proximal tubules make up a substantial fraction of whole-kidney samples, changes in proximal tubule gene expression can be assessed presumptively by bulk-kidney RNA-Seq, although results could potentially be complicated by the presence of mRNA from other cell types.

PMID: 30826016 [PubMed - as supplied by publisher]

18 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 2019/03/03

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.

18 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 2019/03/03

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.

15 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 2019/03/02

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 2019/03/02

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 2019/03/01

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.

22 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 2019/02/28

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.

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 2019/02/27

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 2019/02/27

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.

58 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 2019/02/26

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.

Alterations in hippocampal inhibitory synaptic transmission in the R6/2 mouse model of Huntington's disease.

Neuroscience. 2019 Feb 21;:

Authors: Dargaei Z, Liang X, Serranilla M, Santos J, Woodin MA

Abstract
Huntington's disease (HD) is a genetic neurodegenerative disorder of the central nervous system characterized by choreatic movements, behavioral and psychiatric disturbances and cognitive impairments. Deficits in learning and memory are often the first signs of disease onset in both HD patients and mouse models of HD and are in part regulated by the hippocampus. In the R6/2 mouse model of HD, GABAergic transmission can be excitatory in the hippocampus and restoring inhibition can rescue the associated memory deficits. In the present study we determine that hippocampal GABAergic neurotransmission in the R6/2 mouse is disrupted as early as 4 weeks of age and is accompanied by alterations in the expression of key inhibitory proteins. Specifically, spontaneous inhibitory postsynaptic currents (sIPSCs) were initially increased in frequency at 4 postnatal weeks and subsequently decreased after the mice displayed the typical R6/2 behavioral phenotype at 10 weeks of age. Symptomatic mice also exhibited a change in the probability of GABA release and changes in the basic membrane properties including neuronal excitability and input resistance. These electrophysiological changes in presymptomatic and symptomatic R6/2 mice were further accompanied by alterations in the protein expression level of pre- and postsynaptic inhibitory markers. Taken together, the present findings demonstrate profound alterations in the inhibitory neurotransmission in the hippocampus across the lifespan of the disease, including prior to neuronal degeneration, which suggests that the inhibitory hippocampal synapses may prove useful as a target for future therapeutic design.

PMID: 30797895 [PubMed - as supplied by publisher]

Quantifying Drug Combination Synergy along Potency and Efficacy Axes.

Cell Syst. 2019 Feb 14;:

Authors: Meyer CT, Wooten DJ, Paudel BB, Bauer J, Hardeman KN, Westover D, Lovly CM, Harris LA, Tyson DR, Quaranta V

Abstract
Two goals motivate treating diseases with drug combinations: reduce off-target toxicity by minimizing doses (synergistic potency) and improve outcomes by escalating effect (synergistic efficacy). Established drug synergy frameworks obscure such distinction, failing to harness the potential of modern chemical libraries. We therefore developed multi-dimensional synergy of combinations (MuSyC), a formalism based on a generalized, multi-dimensional Hill equation, which decouples synergistic potency and efficacy. In mutant-EGFR-driven lung cancer, MuSyC reveals that combining a mutant-EGFR inhibitor with inhibitors of other kinases may result only in synergistic potency, whereas synergistic efficacy can be achieved by co-targeting mutant-EGFR and epigenetic regulation or microtubule polymerization. In mutant-BRAF melanoma, MuSyC determines whether a molecular correlate of BRAFi insensitivity alters a BRAF inhibitor's potency, efficacy, or both. These findings showcase MuSyC's potential to transform the enterprise of drug-combination screens by precisely guiding translation of combinations toward dose reduction, improved efficacy, or both.

PMID: 30797775 [PubMed - as supplied by publisher]