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 2017/11/10

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 2017/11/10

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 2017/11/09

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 2017/11/09

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.

56 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 2017/11/08

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.

56 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 2017/11/08

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.

45 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 2017/11/07

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.

Maternal sepsis in the era of genomic medicine.

Arch Gynecol Obstet. 2017 Nov 04;:

Authors: Kouskouti C, Evangelatos N, Brand A, Kainer F

Abstract
PURPOSE: Maternal sepsis remains one of the leading causes of direct and indirect maternal mortality both in high- and low-income environments. In the last two decades, systems biology approaches, based on '-omics' technologies, have started revolutionizing the diagnosis and management of the septic syndrome. The scope of this narrative review is to present an overview of the basic '-omics' technologies, exemplified by cases relevant to maternal sepsis.
METHODS: Narrative review of the new '-omics' technologies based on a detailed review of the literature.
RESULTS: After presenting the main 'omics' technologies, we discuss their limitations and the need for integrated approaches that encompass research efforts across multiple '-omics' layers in the '-omics' cascade between the genome and the phenome.
CONCLUSIONS: Systems biology approaches are revolutionizing the research landscape in maternal sepsis. There is a need for increased awareness, from the side of health practitioners, as a requirement for the effective implementation of the new technologies in the research and clinical practice in maternal sepsis.

PMID: 29103195 [PubMed - as supplied by publisher]

Insights into visual pigment adaptation and diversity from model ecological and evolutionary systems.

Curr Opin Genet Dev. 2017 Nov 02;47:110-120

Authors: Hauser FE, Chang BS

Abstract
Sensory systems provide valuable insight into the evolution of molecular mechanisms underlying organismal anatomy, physiology, and behaviour. Visual pigments, which mediate the first step in visual transduction, offer a unique window into the relationship between molecular variation and visual performance, and enhance our understanding of how ecology, life history, and physiology may shape genetic variation across a variety of organisms. Here we review recent work investigating vertebrate visual pigments from a number of perspectives. Opsin gene duplication, loss, differential expression, structural variation, and the physiological context in which they operate, have profoundly shaped the visual capabilities of vertebrates adapting to novel environments. We note the importance of conceptual frameworks in investigating visual pigment diversity in vertebrates, highlighting key examples including evolutionary transitions between different photic environments, major shifts in life history evolution and ecology, evolutionary innovations in visual system anatomy and physiology, as well as shifts in visually mediated behaviours and behavioural ecology. We emphasize the utility of studying visual pigment evolution in the context of these different perspectives, and demonstrate how the integrative approaches discussed in this review contribute to a better understanding of the underlying molecular processes mediating adaptation in sensory systems, and the contexts in which they occur.

PMID: 29102895 [PubMed - as supplied by publisher]

Regulatory Dynamics Determine Cell Fate following Abrupt Antibiotic Exposure.

Cell Syst. 2017 Oct 31;:

Authors: Schultz D, Palmer AC, Kishony R

Abstract
Bacterial resistance mechanisms must cope with transient fast-changing conditions. These systems are often repressed in the absence of the drug, and it is unclear how their regulation can provide a quick response when challenged. Here, we focus on the tet operon, which provides resistance to tetracycline through efflux pump TetA. We show that, somewhat counterintuitively, prompt expression of the TetA repressor TetR is key for cellular survival upon abrupt drug exposure. Tracking individual cells upon exposure, we find that differences in the rate of TetR elevation result in three distinct cell fates: recovery (high rate), death due to excess TetA (intermediate rate), and death from the drug (low rate). A surge of TetR expression optimizes the response by allowing sensitive detection of both the initial rise and the later decline of intracellular drug, avoiding an undesirable overshoot in TetA expression. These results show how regulatory circuits of resistance genes have evolved for optimized dynamics.

PMID: 29102611 [PubMed - as supplied by publisher]

Systematic Analysis of the Determinants of Gene Expression Noise in Embryonic Stem Cells.

Cell Syst. 2017 Oct 31;:

Authors: Faure AJ, Schmiedel JM, Lehner B

Abstract
Isogenic cells in a common environment show substantial cell-to-cell variation in gene expression, often referred to as "expression noise." Here, we use multiple single-cell RNA-sequencing datasets to identify features associated with high or low expression noise in mouse embryonic stem cells. These include the core promoter architecture of a gene, with CpG island promoters and a TATA box associated with low and high noise, respectively. High noise is also associated with "conflicting" chromatin states-the absence of transcription-associated histone modifications or the presence of repressive ones in active genes. Genes regulated by pluripotency factors through super-enhancers show high and correlated expression variability, consistent with fluctuations in the pluripotent state. Together, our results provide an integrated view of how core promoters, chromatin, regulation, and pluripotency fluctuations contribute to the variability of gene expression across individual stem cells.

PMID: 29102610 [PubMed - as supplied by publisher]

Glutaredoxin-2 controls cardiac mitochondrial dynamics and energetics in mice, and protects against human cardiac pathologies.

Redox Biol. 2017 Oct 26;14:509-521

Authors: Kanaan GN, Ichim B, Gharibeh L, Maharsy W, Patten DA, Xuan JY, Reunov A, Marshall P, Veinot J, Menzies K, Nemer M, Harper ME

Abstract
Glutaredoxin 2 (GRX2), a mitochondrial glutathione-dependent oxidoreductase, is central to glutathione homeostasis and mitochondrial redox, which is crucial in highly metabolic tissues like the heart. Previous research showed that absence of Grx2, leads to impaired mitochondrial complex I function, hypertension and cardiac hypertrophy in mice but the impact on mitochondrial structure and function in intact cardiomyocytes and in humans has not been explored. We hypothesized that Grx2 controls cardiac mitochondrial dynamics and function in cellular and mouse models, and that low expression is associated with human cardiac dysfunction. Here we show that Grx2 absence impairs mitochondrial fusion, ultrastructure and energetics in primary cardiomyocytes and cardiac tissue. Moreover, provision of the glutathione precursor, N-acetylcysteine (NAC) to Grx2-/- mice did not restore glutathione redox or prevent impairments. Using genetic and histopathological data from the human Genotype-Tissue Expression consortium we demonstrate that low GRX2 is associated with fibrosis, hypertrophy, and infarct in the left ventricle. Altogether, GRX2 is important in the control of cardiac mitochondrial structure and function, and protects against human cardiac pathologies.

PMID: 29101900 [PubMed - as supplied by publisher]

Inter-residue, inter-protein and inter-family coevolution: bridging the scales.

Curr Opin Struct Biol. 2017 Nov 01;50:26-32

Authors: Szurmant H, Weigt M

Abstract
Interacting proteins coevolve at multiple but interconnected scales, from the residue-residue over the protein-protein up to the family-family level. The recent accumulation of enormous amounts of sequence data allows for the development of novel, data-driven computational approaches. Notably, these approaches can bridge scales within a single statistical framework. Although being currently applied mostly to isolated problems on single scales, their immense potential for an evolutionary informed, structural systems biology is steadily emerging.

PMID: 29101847 [PubMed - as supplied by publisher]

Testing of tuberculosis infection among Chinese adolescents born after terminating the Bacillus Calmette-Guérin booster vaccination: subgroup analysis of a population-based cross-sectional study.

Front Med. 2017 Nov 03;:

Authors: Li H, Xin H, Qian S, Li X, Zhang H, Li M, Feng B, Jin Q, Gao L

Abstract
The prevalence of tuberculosis infection among adolescents born after terminating the Bacillus Calmette-Guérin (BCG) booster vaccination in China was estimated using tuberculin skin testing (TST) and QuantiFERON-TB Gold assay (QFT) to investigate the influence of neonatal BCG vaccination on the performance of TST. Data analysis was conducted for 2831 eligible participants aged 5-15 years from the baseline survey of a population-based multi-center prospective study. The prevalence rates of TST (induration = 10 mm) and QFT positivity were 9.3% (264/2827) and 2.5% (71/2831), respectively. The rate of QFT indeterminate result was 2.2% (62/2831). The overall agreement between TST and QFT was low (concordance = 88.0%; ? coefficient = 0.125). Only TST was positively associated with BCG vaccination with an adjusted odds ratio of 1.71 [95% confidence interval, 1.26-2.31]. A history of close contact with patients of active TB was significantly associated with positivity for TST and QFT. Our results suggested that BCG neonatal vaccination still affects TST performance, and a twostep approach might be considered for TB infection testing among adolescents in China.

PMID: 29101754 [PubMed - as supplied by publisher]

SNARE phosphorylation: a control mechanism for insulin-stimulated glucose transport and other regulated exocytic events.

Biochem Soc Trans. 2017 Nov 03;:

Authors: Laidlaw KME, Livingstone R, Al-Tobi M, Bryant NJ, Gould GW

Abstract
Trafficking within eukaryotic cells is a complex and highly regulated process; events such as recycling of plasma membrane receptors, formation of multivesicular bodies, regulated release of hormones and delivery of proteins to membranes all require directionality and specificity. The underpinning processes, including cargo selection, membrane fusion, trafficking flow and timing, are controlled by a variety of molecular mechanisms and engage multiple families of lipids and proteins. Here, we will focus on control of trafficking processes via the action of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) family of proteins, in particular their regulation by phosphorylation. We will describe how these proteins are controlled in a range of regulated trafficking events, with particular emphasis on the insulin-stimulated delivery of glucose transporters to the surface of adipose and muscle cells. Here, we focus on a few examples of SNARE phosphorylation which exemplify distinct ways in which SNARE machinery phosphorylation may regulate membrane fusion.

PMID: 29101310 [PubMed - as supplied by publisher]

β-Actin-dependent global chromatin organization and gene expression programs control cellular identity.

FASEB J. 2017 Nov 03;:

Authors: Xie X, Almuzzaini B, Drou N, Kremb S, Yousif A, Farrants AÖ, Gunsalus K, Percipalle P

Abstract
During differentiation and development, cell fate and identity are established by waves of genetic reprogramming. Although the mechanisms are largely unknown, during these events, dynamic chromatin reorganization is likely to ensure that multiple genes involved in the same cellular functions are coregulated, depending on the nuclear environment. In this study, using high-content screening of embryonic fibroblasts from a β-actin knockout (KO) mouse, we found major chromatin rearrangements and changes in histone modifications, such as methylated histone (H)3-lysine-(K)9. Genome-wide H3K9 trimethylation-(Me)3 landscape changes correlate with gene up- and down-regulation in β-actin KO cells. Mechanistically, we found loss of chromatin association by the Brahma-related gene (Brg)/Brahma-associated factor (BAF) chromatin remodeling complex subunit Brg1 in the absence of β-actin. This actin-dependent chromatin reorganization was concomitant with the up-regulation of sets of genes involved in angiogenesis, cytoskeletal organization, and myofibroblast features in β-actin KO cells. Some of these genes and phenotypes were gained in a β-actin dose-dependent manner. Moreover, reintroducing a nuclear localization signal-containing β-actin in the knockout cells affected nuclear features and gene expression. Our results suggest that, by affecting the genome-wide organization of heterochromatin through the chromatin-binding activity of the BAF complex, β-actin plays an essential role in the determination of gene expression programs and cellular identity.-Xie, X., Almuzzaini, B., Drou, N., Kremb, S., Yousif, A., Östlund Farrants, A.-K., Gunsalus, K., Percipalle, P. β-Actin-dependent global chromatin organization and gene expression programs control cellular identity.

PMID: 29101221 [PubMed - as supplied by publisher]

Synthesis and biological evaluation of Santacruzamate-A based analogues.

Bioorg Med Chem. 2017 Oct 20;:

Authors: Randino R, Gazzerro P, Mazitschek R, Rodriquez M

Abstract
Several derivatives of Santacruzamate-A, a natural product that is structurally related to SAHA, were synthesized to explore the potential of carbamates and oxalylamides as novel biasing element for targeting the catalytic site of zinc-dependent histone deacetylases (HDACs). An additional class of Santacruzamate-A derivatives was synthesized to investigate the influence of the cap group and the linker element on HDAC inhibitory activity. All compounds were evaluated in dose response for their in vitro cytotoxic activity in MTT assay in HCT116 cells. HDAC inhibitory activity was evaluated in vitro by western blot analysis for histone hyperacetylation assay and biochemically for representative human HDACs isoforms. Two novel compounds were identified to exhibit potent time dependent anti proliferative activity. However, unlike hydroxamic acid analogues, the tested Santacruzamate-A derivatives showed no noticeable HDAC inhibitory activity. The ethylcarbamate moiety as unusual zinc-binding group displayed no ability to coordinate the zinc ion and thus, presumably, was not able to reproduce known inhibitor-substrate zinc-binding group interactions with the HDAC catalytic site. This study confirmed that the accommodation of the zinc-binding group is deeply critical of the positioning of the linker and the projection of the cap group toward the different surface pockets of the enzyme.

PMID: 29100734 [PubMed - as supplied by publisher]

Glyoxalase 1 copy number variation in patients with well differentiated gastro-entero-pancreatic neuroendocrine tumours (GEP-NET).

Oncotarget. 2017 Sep 29;8(44):76961-76973

Authors: Xue M, Shafie A, Qaiser T, Rajpoot NM, Kaltsas G, James S, Gopalakrishnan K, Fisk A, Dimitriadis GK, Grammatopoulos DK, Rabbani N, Thornalley PJ, Weickert MO

Abstract
Background: The glyoxalase-1 gene (GLO1) is a hotspot for copy-number variation (CNV) in human genomes. Increased GLO1 copy-number is associated with multidrug resistance in tumour chemotherapy, but prevalence of GLO1 CNV in gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) is unknown.
Methods: GLO1 copy-number variation was measured in 39 patients with GEP-NET (midgut NET, n = 25; pancreatic NET, n = 14) after curative or debulking surgical treatment. Primary tumour tissue, surrounding healthy tissue and, where applicable, additional metastatic tumour tissue were analysed, using real time qPCR. Progression and survival following surgical treatment were monitored over 4.2 ± 0.5 years.
Results: In the pooled GEP-NET cohort, GLO1 copy-number in healthy tissue was 2.0 in all samples but significantly increased in primary tumour tissue in 43% of patients with pancreatic NET and in 72% of patients with midgut NET, mainly driven by significantly higher GLO1 copy-number in midgut NET. In tissue from additional metastases resection (18 midgut NET and one pancreatic NET), GLO1 copy number was also increased, compared with healthy tissue; but was not significantly different compared with primary tumour tissue. During mean 3 - 5 years follow-up, 8 patients died and 16 patients showed radiological progression. In midgut NET, a high GLO1 copy-number was associated with earlier progression. In NETs with increased GLO1 copy number, there was increased Glo1 protein expression compared to non-malignant tissue.
Conclusions: GLO1 copy-number was increased in a large percentage of patients with GEP-NET and correlated positively with increased Glo1 protein in tumour tissue. Analysis of GLO1 copy-number variation particularly in patients with midgut NET could be a novel prognostic marker for tumour progression.

PMID: 29100361 [PubMed]

Cancer cell line specific co-factors modulate the FOXM1 cistrome.

Oncotarget. 2017 Sep 29;8(44):76498-76515

Authors: Wang Y, Ung MH, Xia T, Cheng W, Cheng C

Abstract
ChIP-seq has been commonly applied to identify genomic occupation of transcription factors (TFs) in a context-specific manner. It is generally assumed that a TF should have similar binding patterns in cells from the same or closely related tissues. Surprisingly, this assumption has not been carefully examined. To this end, we systematically compared the genomic binding of the cell cycle regulator FOXM1 in eight cell lines from seven different human tissues at binding signal, peaks and target genes levels. We found that FOXM1 binding in ER-positive breast cancer cell line MCF-7 are distinct comparing to those in not only other non-breast cell lines, but also MDA-MB-231, ER-negative breast cancer cell line. However, binding sites in MDA-MB-231 and non-breast cell lines were highly consistent. The recruitment of estrogen receptor alpha (ERα) caused the unique FOXM1 binding patterns in MCF-7. Moreover, the activity of FOXM1 in MCF-7 reflects the regulatory functions of ERα, while in MDA-MB-231 and non-breast cell lines, FOXM1 activities regulate cell proliferation. Our results suggest that tissue similarity, in some specific contexts, does not hold precedence over TF-cofactors interactions in determining transcriptional states and that the genomic binding of a TF can be dramatically affected by a particular co-factor under certain conditions.

PMID: 29100329 [PubMed]

Low BUB1 expression is an adverse prognostic marker in gastric adenocarcinoma.

Oncotarget. 2017 Sep 29;8(44):76329-76339

Authors: Stahl D, Braun M, Gentles AJ, Lingohr P, Walter A, Kristiansen G, Gütgemann I

Abstract
Gastric adenocarcinomas are associated with a poor prognosis due to the fact that the tumor has often metastasized by the time of diagnosis and prognostic markers are urgently needed to tailor treatment. We examined the expression of the mitotic spindle checkpoint protein BUB1 (budding uninhibited by benzimidazoles 1) and Ki-67 protein expression by immunohistochemistry in 218 patients with primary gastric adenocarcinomas. Tumors with low frequency of BUB1 expression were associated with larger tumor size (pT) (p < 0.001), higher incidence of lymph node metastases (pN) (p = 0.027), distant metastases (pM) (p = 0.006) and higher UICC stage (p < 0.001). Furthermore, BUB1 expression was inversely correlated with residual tumor stage (p = 0.038). Abundant BUB1 protein expression correlated with frequent Ki-67 protein expression (p < 0.001) and low BUB1 expression was associated with shorter survival (p < 0.001). Univariate and multivariate analyses confirmed BUB1 to be an independent prognostic marker in gastric cancer (p = 0.021).

PMID: 29100315 [PubMed]