13 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 2017/11/17

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.

13 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 2017/11/17

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.

19 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 2017/11/16

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.

19 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 2017/11/16

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.

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 2017/11/15

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.

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 2017/11/15

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.

53 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 2017/11/14

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.

53 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 2017/11/14

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.

Staged development of long lived TCRαβ Th17 resident memory T cell population to Candida albicans after skin infection.

J Allergy Clin Immunol. 2017 Nov 08;:

Authors: Park CO, Fu X, Jiang X, Pan Y, Teague JE, Collins N, Tian T, O'Malley JT, Emerson RO, Kim JH, Jung Y, Watanabe R, Fuhlbrigge RC, Carbone FR, Gebhardt T, Clark RA, Lin CP, Kupper TS

Abstract
BACKGROUND: Candida albicans is a dimorphic fungus to which humans are exposed early in life and by adulthood it is part of the mycobiome of skin and other tissues. Neonatal skin lacks resident memory T (TRM) cells, but in adults the C. albicans skin test is a surrogate for immunocompetence. Young adult mice raised under SPF conditions are naive to C. albicans, and have recently been shown to have an immune system resembling that of neonatal humans.
OBJECTIVE: We studied the evolution of the adaptive cutaneous immune response to Candida.
METHODS: We examined both human skin T cells and the de novo and memory immune responses in a mouse model of C. albicans skin infection.
RESULTS: In mice, the initial IL-17 producing cells after C. albicans infection were dermal γδ T cells, but by day 7 αβ Th17 T effector cells were predominant. By day 30, the majority of C. albicans reactive IL-17 producing T cells were CD4 TRM cells. Intravital microscopy showed that CD4 effector T cells were recruited to the site of primary infection and were highly motile 10 days post infection. Between 30-90 days post infection, these CD4 T cells became increasingly sessile, acquired expression of CD69 and CD103, and localized to the papillary dermis. These established TRM produced IL-17 upon challenge, while motile migratory memory T (TMM) cells did not. TRM rapidly clear an infectious challenge with C. albicans more effectively than re-circulating T cells, though both populations participate. We found that in normal human skin, IL-17 producing CD4+ TRM that responded to C. albicans in an MHC Class II restricted fashion could be readily identified.
CONCLUSIONS: These studies demonstrate that C. albicans infection of skin preferentially generates CD4+ IL-17 producing TRM, which mediate durable protective immunity.

PMID: 29128674 [PubMed - as supplied by publisher]

Systems cues governing IL6 signaling in leishmaniasis.

Cytokine. 2017 Nov 08;:

Authors: Soni B, Saha B, Singh S

Abstract
IL-6 has been proposed to favor the development of Th2 responses and play an important role in the communication between cells of multicellular organisms. They are involved in the regulation of complex cellular processes such as proliferation, differentiation and act as key player during inflammation and immune response. Th2 cytokines play an immunoregulatory role in early infection. Literature says in mice infected with L. major, IL-6 may promote the development of both Th1 and Th2 responses. IL-4 is also considered to be the signature cytokine of Th-2 response. IL-10 was initially characterized as a Th2 cytokine but later on it was proved to be a pleiotropic cytokine, secreted from different cell types including the macrophages. A major challenge is to understand how these complex non-linear processes are connected and regulated. Systems biology approaches may be used to tackle this challenge in an iterative process of quantitative mathematical analysis. In this study, we created an in silico model of IL6 mediated macrophage activation which suffers from an excessive impact of the negative feedback loop involving SOCS3. The strategy adopted in this framework may help to reduce the complexity of the leishmanial IL6 model analysis and also laydown various physiological or pathological conditions of IL6 signaling in future.

PMID: 29128405 [PubMed - as supplied by publisher]

NF-κB Dynamics Discriminate between TNF Doses in Single Cells.

Cell Syst. 2017 Nov 07;:

Authors: Zhang Q, Gupta S, Schipper DL, Kowalczyk GJ, Mancini AE, Faeder JR, Lee REC

Abstract
Although cytokine-dependent dynamics of nuclear factor κB (NF-κB) are known to encode information that regulates cell fate decisions, it is unclear whether single-cell responses are switch-like or encode more information about cytokine dose. Here, we measure the dynamic subcellular localization of NF-κB in response to a range of tumor necrosis factor (TNF) stimulation conditions to determine the prevailing mechanism of single-cell dose discrimination. Using an information theory formalism that accounts for signaling dynamics and non-responsive cell subpopulations, we find that the information transmission capacity of single cells exceeds that predicted from a switch-like response. Instead, we observe that NF-κB dynamics within single cells contain sufficient information to encode multiple, TNF-dependent cellular states, and have an activation threshold that varies across the population. By comparing single-cell responses to an internal, experimentally observed reference, we demonstrate that cells can grade responses to TNF across several orders of magnitude in concentration. This suggests that cells contain additional control points to fine-tune their cytokine responses beyond the decision to activate.

PMID: 29128333 [PubMed - as supplied by publisher]

The role of A-to-I RNA editing in cancer development.

Curr Opin Genet Dev. 2017 Nov 08;48:51-56

Authors: Xu X, Wang Y, Liang H

Abstract
Adenosine-to-inosine (A-to-I) RNA editing is the most common type of post-transcriptional nucleotide modification in humans, which is catalyzed in ADAR enzymes. Recent genomic studies have revealed thousands of altered RNA editing events in various cancer tissues, leading to diverse functional consequences. A critical role of individual A-to-I RNA editing events in cancer has been reported. Here, we review the current state of our knowledge on key A-to-I RNA editing events in coding and non-coding regions for their roles in cancer development and discuss their potential clinical utility. A better understanding of A-to-I RNA editing and its oncogenic mechanisms may facilitate the development of novel cancer therapeutic strategies.

PMID: 29127844 [PubMed - as supplied by publisher]

Mitochondrial gene polymorphism is associated with gut microbial communities in mice.

Sci Rep. 2017 Nov 10;7(1):15293

Authors: Hirose M, Künstner A, Schilf P, Sünderhauf A, Rupp J, Jöhren O, Schwaninger M, Sina C, Baines JF, Ibrahim SM

Abstract
Gut microbial communities are key mediators of health and disease and have the capacity to drive the pathogenesis of diverse complex diseases including metabolic and chronic inflammatory diseases as well as aging. Host genetics is also a major determinant of disease phenotypes, whereby two different genomes play a role, the nuclear (nDNA)- and mitochondrial genome (mtDNA). We investigated the impact of mutations in mtDNA on the gut microbiota using conplastic mouse strains exhibiting distinct mutations in their mtDNA on an identical nDNA. Each of three strain tested harbors a distinct gut microbiota, ranging from differences at the phylum- to operational taxonomic units level. The C57BL/6J-mt (FVB/NJ) strain, carrying a mutation in the mitochondrial ATP8 synthase gene, exhibits higher Firmicutes abundance than Bacteroidetes, indicating a possible indicative for metabolic dysfunctions. In line with this, the C57BL/6J-mt (FVB/NJ) displays a variety of different phenotypes, including increased susceptibility to metabolic-related and inflammatory disorders. Furthermore, we discuss the cross-talk between mitochondrial genome/mitochondria and commensal microbiota in relation to clinical phenotypes. In summary, we demonstrate that mutations in mtDNA lead to significant differences in the composition of gut microbial communities in mice. Such differences may facilitate the emergence of metabolic disease and therefore constitute potential therapeutic targets.

PMID: 29127319 [PubMed - in process]

Autophagy promotes escape from phosphatidylinositol 3-kinase inhibition in estrogen receptor-positive breast cancer.

FASEB J. 2017 Nov 10;:

Authors: Yang W, Hosford SR, Traphagen NA, Shee K, Demidenko E, Liu S, Miller TW

Abstract
Hyperactivation of the PI3K pathway has been implicated in resistance to antiestrogen therapies in estrogen receptor α (ER)-positive breast cancer, prompting the development of therapeutic strategies to inhibit this pathway. Autophagy has tumor-promoting and -suppressing roles and has been broadly implicated in resistance to anticancer therapies, including antiestrogens. Chloroquine (CQ) is an antimalarial and amebicidal drug that inhibits autophagy in mammalian cells and human tumors. Herein, we observed that CQ inhibited proliferation and autophagy in ER(+) breast cancer cells. PI3K inhibition with GDC-0941 (pictilisib) induced autophagy. Inhibition of autophagy using CQ or RNA interference potentiated PI3K inhibitor-induced apoptosis. Combined inhibition of PI3K and autophagy effectively induced mitochondrial membrane depolarization, which required the BH3-only proapoptotic proteins Bim and PUMA. Treatment with GDC-0941, CQ, or the combination, significantly suppressed the growth of ER(+) breast cancer xenografts in mice. In an antiestrogen-resistant xenograft model, GDC-0941 synergized with CQ to provide partial, but durable, tumor regression. These findings warrant clinical evaluation of therapeutic strategies to target ER, PI3K, and autophagy for the treatment of ER(+) breast cancer.-Yang, W., Hosford, S. R., Traphagen, N. A., Shee, K., Demidenko, E., Liu, S., Miller, T. W. Autophagy promotes escape from phosphatidylinositol 3-kinase inhibition in estrogen receptor-positive breast cancer.

PMID: 29127189 [PubMed - as supplied by publisher]

TIM-3 Engagement Promotes Effector Memory T Cell Differentiation of Human Antigen-Specific CD8 T Cells by Activating mTORC1.

J Immunol. 2017 Nov 10;:

Authors: Sabins NC, Chornoguz O, Leander K, Kaplan F, Carter R, Kinder M, Bachman K, Verona R, Shen S, Bhargava V, Santulli-Marotto S

Abstract
T cell expression of TIM-3 following Ag encounter has been associated with a continuum of functional states ranging from effector memory T cells to exhaustion. We have designed an in vitro culture system to specifically address the impact of anti-TIM-3/TIM-3 engagement on human Ag-specific CD8 T cells during a normal response to Ag and found that anti-TIM-3 treatment enhances T cell function. In our in vitro T cell culture system, MART1-specific CD8 T cells were expanded from healthy donors using artificial APCs. To ensure that the T cells were the only source of TIM-3, cells were rechallenged with peptide-loaded artificial APCs in the presence of anti-TIM-3 Ab. In these conditions, anti-TIM-3 treatment promotes generation of effector T cells as shown by acquisition of an activated phenotype, increased cytokine production, enhanced proliferation, and a transcription program associated with T cell differentiation. Activation of mTORC1 has been previously demonstrated to enhance CD8 T cell effector function and differentiation. Anti-TIM-3 drives CD8 T cell differentiation through activation of the mTORC1 as evidenced by increased levels of phosphorylated S6 protein and rhebl1 transcript. Altogether these findings suggest that anti-TIM-3, together with Ag, drives differentiation in favor of effector T cells via the activation of mTOR pathway. To our knowledge, this is the first report demonstrating that TIM-3 engagement during Ag stimulation directly influences T cell differentiation through mTORC1.

PMID: 29127145 [PubMed - as supplied by publisher]

Evidence of high transport and phosphorylation capacity for both glucose and fructose in the ruby-throated hummingbird (Archilochus colubris).

Comp Biochem Physiol B Biochem Mol Biol. 2017 Nov 07;:

Authors: Myrka AM, Welch KC

Abstract
Hummingbirds are able to fuel hovering flight entirely with recently ingested glucose or fructose. Among vertebrates, several steps of sugar flux from circulation to skeletal muscle are potentially rate-limiting, including transport into muscle and subsequent phosphorylation. While capacities for glucose flux are substantial, capacities for fructose flux are comparatively low. The mechanisms underlying apparent high rates of glucose and fructose oxidation in hummingbird flight muscle remain unclear. We examined relative expression of facilitative sugar transporters (GLUTs) and enzymes of fructolysis in ruby-throated hummingbird (Archilochus colubris) tissues involved in energy homeostasis and flight, via qPCR and measured hexokinase activity in pectoralis in vitro. We hypothesized that expression of these genes was upregulated in hummingbird flight muscle compared to other vertebrates. We found that hummingbird pectoralis had high relative transcript abundance of GLUT1 and GLUT5 compared to expression profiles of other vertebrates. In particular, GLUT5 expression in pectoralis was similar to that of intestine. We demonstrated minimal relative densities of fructolytic enzymes in pectoralis, suggesting that the ketohexokinase pathway does not rapidly metabolize fructose in these muscles. Instead, we found that the capacity for phosphorylation of either glucose or fructose by hexokinase is very high in pectoralis in vitro. The contributions of individual hexokinase isoforms remain to be determined. Our results further characterize the strategies by which hummingbirds, and perhaps other nectarivores, accomplish rapid sugar flux. High transport and sugar phosphorylation capacities appear to exist in flight muscle, though the enzymatic pathways that catalyze the phosphorylation of sugar in muscle remain uncertain.

PMID: 29127075 [PubMed - as supplied by publisher]

Fourier phase based depth-resolved nanoscale nuclear architecture mapping for cancer detection.

Methods. 2017 Nov 07;:

Authors: Uttam S, Liu Y

Abstract
Quantitative phase imaging (QPI) modality has been widely adopted in a variety of applications ranging from identifying photomask defects in lithography to characterizing cell structure and tissue morphology in cancer. Traditional QPI utilizes the electromagnetic phase of transmitted light to measure, with nanometer scale sensitivity, alterations in the optical thickness of a sample of interest. In our work, the QPI paradigm is generalized to study depth-resolved properties of phase objects with slowly varying refractive index without a strong interface by utilizing the Fourier phase associated with Fourier-domain optical coherence tomography (FD-OCT). Specifically, based on computing the Fourier phase of light back-scattered by cell nuclei, we have developed nanoscale nuclear architecture mapping (nanoNAM) method that quantifies, with nanoscale sensitivity, (a) the depth-resolved alterations in mean nuclear optical density, and (b) depth-resolved localized heterogeneity in optical density of the cell nuclei. We have used nanoNAM to detect malignant transformation in colon carcinogenesis, even in tissue that appears histologically normal according to pathologists, thereby showing its potential as a pathology aid in cases where pathology examination remains inconclusive, and for screening patient populations at risk of developing cancer. In this paper, we integrate all aspects of nanoNAM, from principle through instrumentation and analysis, to show that nanoNAM is a promising, low-cost, and label-free method for identifying pathologically indeterminate pre-cancerous and cancerous cells. Importantly, it can seamlessly integrate into the clinical pipeline by utilizing clinically prepared formalin-fixed, paraffin-embedded tissue sections.

PMID: 29127043 [PubMed - as supplied by publisher]

Machiavellian Tendencies Increase Following Damage to the Left Dorsolateral Prefrontal Cortex.

Neuropsychologia. 2017 Nov 07;:

Authors: Cohen-Zimerman S, Chau A, Krueger F, Gordon B, Grafman J

Abstract
Machiavellianism - a personality trait that is characterized by a tendency to distrust, deceive and exploit others - has been the focus of growing attention in psychological research. Neuroimaging studies of Machiavellianism highlight the influence of the dorsolateral prefrontal cortex (dlPFC) on Machiavellianism tendencies. However, knowledge regarding the causal role of the left and right dlPFC on Machiavellianism is still obscure. Here, we measured general Machiavellian tendencies, as well as two subscales (i.e., Machiavellian Views and Machiavellian Tactics) in a large sample of brain-injured patients (N=129) and non-brain-injured control participants (N=37) to determine whether Machiavellianism tendencies can be altered by brain damage. We analyzed Machiavellianism tendencies as a function of lesion location, with patients separated into four groups based on dlPFC damage: left dlPFC damage, right dlPFC damage, non-dlPFC damage, and healthy controls. We found that left dlPFC damage increased Machiavellianism in general, and Machiavellian perspective (views) in particular, but did not modulate behavior (tactics). Critically, left dlPFC damage predicted higher levels of Machiavellianism after controlling for general and emotional intelligence, linguistic abilities, empathy and psychopathology. These findings establish a causal role of the left dlPFC in modulating Machiavellian views, and indicate that one can hold Machiavellian views without necessarily endorsing Machiavellian tactics.

PMID: 29126929 [PubMed - as supplied by publisher]

Whole blood microRNA expression pattern differentiates patients with rheumatoid arthritis, their seropositive first-degree relatives, and healthy unrelated control subjects.

Arthritis Res Ther. 2017 Nov 10;19(1):249

Authors: Anaparti V, Smolik I, Meng X, Spicer V, Mookherjee N, El-Gabalawy H

Abstract
BACKGROUND: Epigenetic mechanisms can integrate gene-environment interactions that mediate disease transition from preclinical to clinically overt rheumatoid arthritis (RA). To better understand their role, we evaluated microRNA (miRNA, miR) expression profile in indigenous North American patients with RA who were positive for anticitrullinated protein antibodies; their autoantibody-positive, asymptomatic first-degree relatives (FDRs); and disease-free healthy control subjects (HCs).
METHODS: Total RNA was isolated from whole blood samples obtained from HC (n = 12), patients with RA (n = 18), and FDRs (n = 12). Expression of 35 selected relevant miRNAs, as well as associated downstream messenger RNA (mRNA) targets of miR-103a-3p, was determined by qRT-PCR.
RESULTS: Whole blood expression profiling identified significantly differential miRNA expression in patients with RA (13 miRNAs) and FDRs (10 miRNAs) compared with HCs. Among these, expression of miR-103a-3p, miR-155, miR-146a-5p, and miR-26b-3p was significantly upregulated, whereas miR-346 was significantly downregulated, in both study groups. Expression of miR-103a-3p was consistently elevated in FDRs at two time points 1 year apart. We also confirmed increased miR-103a-3p expression in peripheral blood mononuclear cells from patients with RA compared with HCs. Predicted target analyses of differentially expressed miRNAs in patients with RA and FDRs showed overlapping biological networks. Consistent with these curated networks, mRNA expression of DICER1, AGO1, CREB1, DAPK1, and TP53 was downregulated significantly with miR-103a-3p expression in FDRs.
CONCLUSIONS: We highlight systematically altered circulating miRNA expression in at-risk FDRs prior to RA onset, a profile they shared with patients with RA. Prominently consistent miR-103a-3p expression indicates its utility as a prognostic biomarker for preclinical RA while highlighting biological pathways important for transition to clinically detectable disease.

PMID: 29126434 [PubMed - in process]

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 2017/11/11

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.