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 2020/02/18

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.

The biogenesis of mitochondrial intermembrane space proteins.

Biol Chem. 2020 Feb 01;:

Authors: Edwards R, Gerlich S, Tokatlidis K

Abstract
The mitochondrial intermembrane space (IMS) houses a large spectrum of proteins with distinct and critical functions. Protein import into this mitochondrial sub-compartment is underpinned by an intriguing variety of pathways, many of which are still poorly understood. The constricted volume of the IMS and the topological segregation by the inner membrane cristae into a bulk area surrounded by the boundary inner membrane and the lumen within the cristae is an important factor that adds to the complexity of the protein import, folding and assembly processes. We discuss the main import pathways into the IMS, but also how IMS proteins are degraded or even retro-translocated to the cytosol in an integrated network of interactions that is necessary to maintain a healthy balance of IMS proteins under physiological and cellular stress conditions. We conclude this review by highlighting new and exciting perspectives in this area with a view to develop a better understanding of yet unknown, likely unconventional import pathways, how presequence-less proteins can be targeted and the basis for dual localisation in the IMS and the cytosol. Such knowledge is critical to understand the dynamic changes of the IMS proteome in response to stress, and particularly important for maintaining optimal mitochondrial fitness.

PMID: 32061164 [PubMed - as supplied by publisher]

Emerging Frontiers in the Study of Molecular Evolution.

J Mol Evol. 2020 Feb 14;:

Authors: Liberles DA, Chang B, Geiler-Samerotte K, Goldman A, Hey J, Kaçar B, Meyer M, Murphy W, Posada D, Storfer A

Abstract
A collection of the editors of Journal of Molecular Evolution have gotten together to pose a set of key challenges and future directions for the field of molecular evolution. Topics include challenges and new directions in prebiotic chemistry and the RNA world, reconstruction of early cellular genomes and proteins, macromolecular and functional evolution, evolutionary cell biology, genome evolution, molecular evolutionary ecology, viral phylodynamics, theoretical population genomics, somatic cell molecular evolution, and directed evolution. While our effort is not meant to be exhaustive, it reflects research questions and problems in the field of molecular evolution that are exciting to our editors.

PMID: 32060574 [PubMed - as supplied by publisher]

Repurposing the Psoriasis Drug Oxarol to an ointment adjuvant for the influenza vaccine.

Int Immunol. 2020 Feb 15;:

Authors: Sato R, Makino-Okamura C, Lin Q, Wang M, Shoemaker J, Kurosaki T, Fukuyama H

Abstract
Aluminum precipitates have long been used as adjuvants for human vaccines, but there is a clear need for safer and more effective adjuvants. Here we report in a mouse model that the Psoriasis drug Oxarol ointment is a highly effective vaccine adjuvant. By applying Oxarol ointment onto skin, humoral responses and germinal center (GC) reactions were augmented, and the treated mice were protected from death caused by influenza virus infection. Keratinocyte-specific Vitamin D3 receptor (Vdr) gene expression was required for these responses through induction of the Thymic stromal lymphopoietin (Tslp) gene. Experiments involving administration of recombinant Tslp or, conversely, anti-Tslp antibody demonstrated that Tslp plays a key role in the GC reactions. Furthermore, cell type-specific Tslpr gene deletion or diphtheria toxin-mediated deletion of specific cell types, revealed that CD11c+ cells excluding Langerhans cells were responsible for the Oxarol-mediated GC reactions. These results indicate that active vitamin D3 is able to enhance the humoral response via Tslp induction in the skin and serves as a new vaccine adjuvant.

PMID: 32060507 [PubMed - as supplied by publisher]

A systems approach to infectious disease.

Nat Rev Genet. 2020 Feb 14;:

Authors: Eckhardt M, Hultquist JF, Kaake RM, Hüttenhain R, Krogan NJ

Abstract
Ongoing social, political and ecological changes in the 21st century have placed more people at risk of life-threatening acute and chronic infections than ever before. The development of new diagnostic, prophylactic, therapeutic and curative strategies is critical to address this burden but is predicated on a detailed understanding of the immensely complex relationship between pathogens and their hosts. Traditional, reductionist approaches to investigate this dynamic often lack the scale and/or scope to faithfully model the dual and co-dependent nature of this relationship, limiting the success of translational efforts. With recent advances in large-scale, quantitative omics methods as well as in integrative analytical strategies, systems biology approaches for the study of infectious disease are quickly forming a new paradigm for how we understand and model host-pathogen relationships for translational applications. Here, we delineate a framework for a systems biology approach to infectious disease in three parts: discovery - the design, collection and analysis of omics data; representation - the iterative modelling, integration and visualization of complex data sets; and application - the interpretation and hypothesis-based inquiry towards translational outcomes.

PMID: 32060427 [PubMed - as supplied by publisher]

Multiple Myeloma DREAM Challenge reveals epigenetic regulator PHF19 as marker of aggressive disease.

Leukemia. 2020 Feb 14;:

Authors: Mason MJ, Schinke C, Eng CLP, Towfic F, Gruber F, Dervan A, White BS, Pratapa A, Guan Y, Chen H, Cui Y, Li B, Yu T, Chaibub Neto E, Mavrommatis K, Ortiz M, Lyzogubov V, Bisht K, Dai HY, Schmitz F, Flynt E, Dan Rozelle, Danziger SA, Ratushny A, Multiple Myeloma DREAM Consortium, Dalton WS, Goldschmidt H, Avet-Loiseau H, Samur M, Hayete B, Sonneveld P, Shain KH, Munshi N, Auclair D, Hose D, Morgan G, Trotter M, Bassett D, Goke J, Walker BA, Thakurta A, Guinney J

Abstract
While the past decade has seen meaningful improvements in clinical outcomes for multiple myeloma patients, a subset of patients does not benefit from current therapeutics for unclear reasons. Many gene expression-based models of risk have been developed, but each model uses a different combination of genes and often involves assaying many genes making them difficult to implement. We organized the Multiple Myeloma DREAM Challenge, a crowdsourced effort to develop models of rapid progression in newly diagnosed myeloma patients and to benchmark these against previously published models. This effort lead to more robust predictors and found that incorporating specific demographic and clinical features improved gene expression-based models of high risk. Furthermore, post-challenge analysis identified a novel expression-based risk marker, PHF19, which has recently been found to have an important biological role in multiple myeloma. Lastly, we show that a simple four feature predictor composed of age, ISS, and expression of PHF19 and MMSET performs similarly to more complex models with many more gene expression features included.

PMID: 32060406 [PubMed - as supplied by publisher]

Tissue Determinants of Human NK Cell Development, Function, and Residence.

Cell. 2020 Feb 12;:

Authors: Dogra P, Rancan C, Ma W, Toth M, Senda T, Carpenter DJ, Kubota M, Matsumoto R, Thapa P, Szabo PA, Li Poon MM, Li J, Arakawa-Hoyt J, Shen Y, Fong L, Lanier LL, Farber DL

Abstract
Immune responses in diverse tissue sites are critical for protective immunity and homeostasis. Here, we investigate how tissue localization regulates the development and function of human natural killer (NK) cells, innate lymphocytes important for anti-viral and tumor immunity. Integrating high-dimensional analysis of NK cells from blood, lymphoid organs, and mucosal tissue sites from 60 individuals, we identify tissue-specific patterns of NK cell subset distribution, maturation, and function maintained across age and between individuals. Mature and terminally differentiated NK cells with enhanced effector function predominate in blood, bone marrow, spleen, and lungs and exhibit shared transcriptional programs across sites. By contrast, precursor and immature NK cells with reduced effector capacity populate lymph nodes and intestines and exhibit tissue-resident signatures and site-specific adaptations. Together, our results reveal anatomic control of NK cell development and maintenance as tissue-resident populations, whereas mature, terminally differentiated subsets mediate immunosurveillance through diverse peripheral sites. VIDEO ABSTRACT.

PMID: 32059780 [PubMed - as supplied by publisher]

EFMviz: A COBRA Toolbox extension to visualize Elementary Flux Modes in Genome-Scale Metabolic Models.

Metabolites. 2020 Feb 12;10(2):

Authors: Sarathy C, Kutmon M, Lenz M, Adriaens ME, Evelo CT, Arts ICW

Abstract
Elementary Flux Modes (EFMs) are a tool for constraint-based modeling and metabolic network analysis. However, systematic and automated visualization of EFMs, capable of integrating various data types is still a challenge. In this study, we developed an extension for the widely adopted COBRA Toolbox, EFMviz, for analysis and graphical visualization of EFMs as networks of reactions, metabolites and genes. The analysis workflow offers a platform for EFM visualization to improve EFM interpretability by connecting COBRA toolbox with the network analysis and visualization software Cytoscape. The biological applicability of EFMviz is demonstrated in two use cases on medium (Escherichia coli, iAF1260) and large (human, Recon 2.2) genome-scale metabolic models. EFMviz is open-source and integrated into COBRA Toolbox. The analysis workflows used for the two use cases are detailed in the two tutorials provided with EFMviz along with the data used in this study.

PMID: 32059585 [PubMed]

In Vivo Rate of Formaldehyde Condensation with Tetrahydrofolate.

Metabolites. 2020 Feb 12;10(2):

Authors: He H, Noor E, Ramos-Parra PA, García-Valencia LE, Patterson JA, Díaz de la Garza RI, Hanson AD, Bar-Even A

Abstract
Formaldehyde is a highly reactive compound that participates in multiple spontaneous reactions, but these are mostly deleterious and damage cellular components. In contrast, the spontaneous condensation of formaldehyde with tetrahydrofolate (THF) has been proposed to contribute to the assimilation of this intermediate during growth on C1 carbon sources such as methanol. However, the in vivo rate of this condensation reaction is unknown and its possible contribution to growth remains elusive. Here, we used microbial platforms to assess the rate of this condensation in the cellular environment. We constructed Escherichia coli strains lacking the enzymes that naturally produce 5,10-methylene-THF. These strains were able to grow on minimal medium only when equipped with a sarcosine (N-methyl-glycine) oxidation pathway that sustained a high cellular concentration of formaldehyde, which spontaneously reacts with THF to produce 5,10-methylene-THF. We used flux balance analysis to derive the rate of the spontaneous condensation from the observed growth rate. According to this, we calculated that a microorganism obtaining its entire biomass via the spontaneous condensation of formaldehyde with THF would have a doubling time of more than three weeks. Hence, this spontaneous reaction is unlikely to serve as an effective route for formaldehyde assimilation.

PMID: 32059429 [PubMed]

Mathematical Model of ATM Activation and Chromatin Relaxation by Ionizing Radiation.

Int J Mol Sci. 2020 Feb 12;21(4):

Authors: Li Y, Cucinotta FA

Abstract
We propose a comprehensive mathematical model to study the dynamics of ionizing radiation induced Ataxia-telangiectasia mutated (ATM) activation that consists of ATM activation through dual mechanisms: the initiative activation pathway triggered by the DNA damage-induced local chromatin relaxation and the primary activation pathway consisting of a self-activation loop by interplay with chromatin relaxation. The model is expressed as a series of biochemical reactions, governed by a system of differential equations and analyzed by dynamical systems techniques. Radiation induced double strand breaks (DSBs) cause rapid local chromatin relaxation, which is independent of ATM but initiates ATM activation at damage sites. Key to the model description is how chromatin relaxation follows when active ATM phosphorylates KAP-1, which subsequently spreads throughout the chromatin and induces global chromatin relaxation. Additionally, the model describes how oxidative stress activation of ATM triggers a self-activation loop in which PP2A and ATF2 are released so that ATM can undergo autophosphorylation and acetylation for full activation in relaxed chromatin. In contrast, oxidative stress alone can partially activate ATM because phosphorylated ATM remains as a dimer. The model leads to predictions on ATM mediated responses to DSBs, oxidative stress, or both that can be tested by experiments.

PMID: 32059363 [PubMed - in process]

62 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 2020/02/15

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.

62 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 2020/02/15

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 2020/02/14

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.

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 2020/02/14

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.

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 2020/02/13

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 2020/02/13

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 2020/02/12

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.

47 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 2020/02/11

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.

Generation of an induced pluripotent stem cell line SYSUi-003-A from a child with epilepsy carrying GRIN2A mutation.

Stem Cell Res. 2020 Jan 15;43:101706

Authors: Sun C, Yang M, Qin F, Guo R, Liang S, Hu H

Abstract
We generated iPSCs from peripheral blood mononuclear cells of a child with epilepsy carrying heterozygous missense mutation in GRIN2A, using integration free episomal vectors. These iPSCs express pluripotent markers, represent a normal karyotype and have the ability to differentiate into three germ layers.

PMID: 32036246 [PubMed - as supplied by publisher]

Safe prognostication following cardiac arrest: the role of the pharmacokinetics of fentanyl in patients treated with targeted-temperature management.

Resuscitation. 2020 Feb 06;:

Authors: Baldwin F, Gray R, Boyd O, Waxman D, Patel B, Allen M, Scutt G

Abstract
BACKGROUND: Neurological prognostication following cardiac arrest (CA) is complex and sedative agents may significantly impair responses to clinical examination. This study investigates the elimination of fentanyl in patients treated with targeted temperature management (TTM).
METHODS: We measured the blood concentration of fentanyl in 23 post-cardiac arrest patients treated with TTM following discontinuation of continuous infusion. Fentanyl was discontinued when the patients were rewarmed to a temperature of 36-36.5 °C and a blood sample taken 12 h later. Measured concentrations were compared with predicted concentrations using population pharmacokinetic parameters. Variables likely to prolong half-life were analysed using a multivariate regression model.
RESULTS: We found a statistically significant difference between median measured and predicted concentrations (measured 0.93 μg/L [range 0.11-8.29 μg/L] vs. predicted 0.30 μg/L [range 0.16-0.59 μg/L]; p < 0.05). Univariate analysis identified a significant relationship between estimated fentanyl half-life and serum lactate concentrations (r = 0.45, p < 0.05. Multivariate linear regression identified two variables (SAPS score, and genotype), which together were able to explain approximately 30% of the variation in the population (adjusted R2 = 0.3177, p = 0.0194). No significant relationships were found between fentanyl half-life and patients' clinical or biochemical variables or co-administration of drugs metabolised by cytochrome p450.
CONCLUSIONS: There is marked variation in the clearance of fentanyl following continuous infusion during TTM after CA which correlates with illness severity, lactate concentration and genetic polymorphisms of the cytochrome p450 liver enzymes. Sustained presence of fentanyl may influence response to neurological examination at 12 hours post discontinuation in patients receiving the drug as an infusion as part of TTM.

PMID: 32035995 [PubMed - as supplied by publisher]