38 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 2019/06/19

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.

43 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 2019/06/18

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.

Immunization against Vibrio cholerae, ETEC, and EHEC with chitosan nanoparticle containing LSC chimeric protein.

Microb Pathog. 2019 Jun 13;:103600

Authors: Ghaffari Marandi BH, Zolfaghari MR, Kazemi R, Motamedi MJ, Amani J

Abstract
INTRODUCTION: Severe intestinal infections caused by V. cholerae, ETEC and EHEC have contributed to the mortality rate in developing countries. Vibrio Cholera, ETEC and EHEC bacterium with the production of CT, LT and Stx2 toxins respectively lead to severe watery and bloody diarrhea. This study aimed to investigate a trimeric vaccine candidate containing recombinant chimeric protein, encapsulate the protein in chitosan nanoparticles and assess its immunogenicity.
METHODS: The LSC recombinant gene was used. It is composed of LTB (L), STXB (S) and CTXB (C) subunits respectively. The LSC recombinant protein was expressed and purified and confirmed by western blotting. The purified protein was encapsulated in chitosan nanoparticles, and its size was measured. BalB/c mice were immunized in four groups through oral and injection methods by LSC protein. The antibody titer was then evaluated by ELISA, and finally, the challenge test of the toxins from all three bacteria was done on the immunized mouse.
RESULTS: After expression and purification LSC protein size of nanoparticles containing protein was measured at 104.6 nm. Nanoparticles were able to induce systemic and mucosal immune responses by generating a useful titer of IgG and IgA. The challenge results with LT, CT and Stx toxins showed that the LSC protein might partially neutralize the effect of toxins.
CONCLUSION: LSC chimeric protein with the simultaneous three essential antigens have a protective effect against the toxins produced by ETEC, EHEC and Vibrio cholera bacteria and it can be used in vaccines to prevent Diarrhea caused by these three bacteria.

PMID: 31202906 [PubMed - as supplied by publisher]

Activation of WNT and CREB signaling pathways in human neuronal cells in response to the Omega-3 fatty acid docosahexaenoic acid (DHA).

Mol Cell Neurosci. 2019 Jun 13;:

Authors: Zhao WN, Hylton NK, Wang J, Chindavong PS, Alural B, Kurtser I, Subramanian A, Mazitschek R, Perlis RH, Haggarty SJ

Abstract
A subset of individuals with major depressive disorder (MDD) elects treatment with complementary and alternative medicines (CAMs), including the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Previous studies in rodents suggests that DHA modulates neurodevelopmental processes, including adult neurogenesis and neuroplasticity, but the molecular and cellular mechanisms of DHA's potential therapeutic effect in the context of human neurobiology have not been well established. Here we sought to address this knowledge gap by investigating the effects of DHA using human iPSC-derived neural progenitor cells (NPCs) and post-mitotic neurons using pathway-selective reporter genes, multiplexed mRNA expression profiling, and a panel of metabolism-based viability assays. Finally, real-time, live-cell imaging was employed to monitor neurite outgrowth upon DHA treatment. Overall, these studies showed that DHA treatment (0-50 μM) significantly upregulated both WNT and CREB signaling pathways in human neuronal cells in a dose-dependent manner with 2 to 3-fold increases in pathway activation. Additionally, we observed that DHA treatment enhanced survival of iPSC-derived NPCs and differentiation of post-mitotic neurons with live-cell imaging revealing increased neurite outgrowth with DHA treatment within 24 h. Taken together, this study provides evidence that DHA treatment activates critical pathways regulating neuroplasticity, which may contribute to enhanced neuronal cell viability and neuronal connectivity. The extent to which these pathways represent molecular mechanisms underlying the potential beneficial effects of omega-3 fatty acids in MDD and other brain disorders merits further investigation.

PMID: 31202891 [PubMed - as supplied by publisher]

Transcriptome and Regulatory Network Analyses of CD19-CAR-T Immunotherapy for B-ALL.

Genomics Proteomics Bioinformatics. 2019 Jun 12;:

Authors: Zhang Q, Hu H, Chen SY, Liu CJ, Hu FF, Yu J, Wu Y, Guo AY

Abstract
Chimeric antigen receptor (CAR) T-cell therapy has exhibited dramatic anti-tumor efficacy in clinical trials. In this study, we reported the transcriptome profiles of bone marrow cells in four B-cell acute lymphoblastic leukemia (B-ALL) patients before and after CD19-specific CAR-T therapy. CD19-CAR-T therapy remarkably reduced the number of leukemia cells, and three patients achieved bone marrow remission (minimal residual disease negative). The efficacy of CD19-CAR-T therapy on B-ALL was positively correlated with the abundance of CAR and immune cell subpopulations, e.g., CD8+ T cells and natural killer (NK) cells, in the bone marrow. Additionally, CD19-CAR-T therapy mainly influenced the expression of genes linked to cell cycle and immune response pathways, including the NK cell mediated cytotoxicity and NOD-like receptor signaling pathways. The regulatory network analyses revealed that microRNAs (e.g., miR-148a-3p and miR-375), acting as oncogenes or tumor suppressors, could regulate the crosstalk between the genes encoding transcription factors (TFs; e.g., JUN and FOS) and histones (e.g., HIST1H4A and HIST2H4A) involved in CD19-CAR-T therapy. Furthermore, many long non-coding RNAs showed a high degree of co-expression with TFs or histones (e.g., FOS and HIST1H4B) and were associated with immune processes. These transcriptome analyses provided important clues for further understanding the gene expression and related mechanisms underlying the efficacy of CAR-T immunotherapy.

PMID: 31201998 [PubMed - as supplied by publisher]

Immunosenescence: A systems-level overview of immune cell biology and strategies for improving vaccine responses.

Exp Gerontol. 2019 Jun 12;:110632

Authors: Crooke SN, Ovsyannikova IG, Poland GA, Kennedy RB

Abstract
Immunosenescence contributes to a decreased capacity of the immune system to respond effectively to infections or vaccines in the elderly. The full extent of the biological changes that lead to immunosenescence are unknown, but numerous cell types involved in innate and adaptive immunity exhibit altered phenotypes and function as a result of aging. These manifestations of immunosenescence at the cellular level are mediated by dysregulation at the genetic level, and changes throughout the immune system are, in turn, propagated by numerous cellular interactions. Environmental factors, such as nutrition, also exert significant influence on the immune system during aging. While the mechanisms that govern the onset of immunosenescence are complex, systems biology approaches allow for the identification of individual contributions from each component within the system as a whole. Although there is still much to learn regarding immunosenescence, systems-level studies of vaccine responses have been highly informative and will guide the development of new vaccine candidates, novel adjuvant formulations, and immunotherapeutic drugs to improve vaccine responses among the aging population.

PMID: 31201918 [PubMed - as supplied by publisher]

Gain-of-function CEBPE mutation causes non-canonical autoinflammatory inflammasomopathy.

J Allergy Clin Immunol. 2019 Jun 12;:

Authors: Göös H, Fogarty CL, Sahu B, Plagnol V, Rajamäki K, Nurmi K, Liu X, Einarsdottir E, Jouppila A, Pettersson T, Vihinen H, Krjutskov K, Saavalainen P, Järvinen A, Muurinen M, Greco D, Scala G, Curtis J, Nordström D, Flaumenhaft R, Vaarala O, Kovanen PE, Keskitalo S, Ranki A, Kere J, Lehto M, Notarangelo LD, Nejentsev S, Eklund KK, Varjosalo M, Taipale J, Seppänen MR

Abstract
BACKGROUND: C/EBPε is a transcription factor involved in late myeloid lineage differentiation and cellular function. The only previously known disorder linked to C/EBPε is the autosomal recessive neutrophil-specific granule deficiency leading to severely impaired neutrophil function and early mortality.
OBJECTIVE: The aim was to molecularly characterize the effects of C/EBPε transcription factor's Arg219His mutation, identified in Finnish family with previously genetically uncharacterized autoinflammatory and immunodeficiency syndrome.
METHODS: Genetic analysis, proteomics, genome-wide transcriptional profiling by RNA-sequencing, ChIP-sequencing and assessment of the inflammasome function of primary macrophages were performed.
RESULTS: Studies revealed a novel mechanism of genome-wide gain-of-function that dysregulated transcription of 464 genes. Mechanisms involved dysregulated non-canonical inflammasome activation due to decreased association with transcriptional repressors leading to increased chromatin occupancy and considerable changes in transcriptional activity including increased expression of NLRP3 and constitutively expressed caspase-5 in macrophages.
CONCLUSION: We describe a novel autoinflammatory disease with defective neutrophil function caused by homozygous Arg219His mutation in transcription factor C/EBPε. Mutated C/EBPε acts as a regulator of both the inflammasome and interferome, and the Arg219His mutation causes the first human monogenic neomorphic and non-canonical inflammasomopathy/immunodeficiency. The mechanism, including widely dysregulated transcription, is likely not unique for C/EBPε. Similar multiomics approaches should as well be utilized in studying other transcription factor-associated diseases.

PMID: 31201888 [PubMed - as supplied by publisher]

Harnessing Human Microphysiology Systems as Key Experimental Models for Quantitative Systems Pharmacology.

Handb Exp Pharmacol. 2019 Jun 15;:

Authors: Taylor DL, Gough A, Schurdak ME, Vernetti L, Chennubhotla CS, Lefever D, Pei F, Faeder JR, Lezon TR, Stern AM, Bahar I

Abstract
Two technologies that have emerged in the last decade offer a new paradigm for modern pharmacology, as well as drug discovery and development. Quantitative systems pharmacology (QSP) is a complementary approach to traditional, target-centric pharmacology and drug discovery and is based on an iterative application of computational and systems biology methods with multiscale experimental methods, both of which include models of ADME-Tox and disease. QSP has emerged as a new approach due to the low efficiency of success in developing therapeutics based on the existing target-centric paradigm. Likewise, human microphysiology systems (MPS) are experimental models complementary to existing animal models and are based on the use of human primary cells, adult stem cells, and/or induced pluripotent stem cells (iPSCs) to mimic human tissues and organ functions/structures involved in disease and ADME-Tox. Human MPS experimental models have been developed to address the relatively low concordance of human disease and ADME-Tox with engineered, experimental animal models of disease. The integration of the QSP paradigm with the use of human MPS has the potential to enhance the process of drug discovery and development.

PMID: 31201557 [PubMed - as supplied by publisher]

Publisher Correction: Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics.

Nat Cell Biol. 2019 Jun 14;:

Authors: Carreras-Sureda A, Jaña F, Urra H, Durand S, Mortenson DE, Sagredo A, Bustos G, Hazari Y, Ramos-Fernández E, Sassano ML, Pihán P, van Vliet AR, González-Quiroz M, Torres AK, Tapia-Rojas C, Kerkhofs M, Vicente R, Kaufman RJ, Inestrosa NC, Gonzalez-Billault C, Wiseman RL, Agostinis P, Bultynck G, Court FA, Kroemer G, Cárdenas JC, Hetz C

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 31201389 [PubMed - as supplied by publisher]

Multi omics analysis of fibrotic kidneys in two mouse models.

Sci Data. 2019 Jun 14;6(1):92

Authors: Pavkovic M, Pantano L, Gerlach CV, Brutus S, Boswell SA, Everley RA, Shah JV, Sui SH, Vaidya VS

Abstract
Kidney fibrosis represents an urgent unmet clinical need due to the lack of effective therapies and an inadequate understanding of the molecular pathogenesis. We have generated a comprehensive and combined multi-omics dataset (proteomics, mRNA and small RNA transcriptomics) of fibrotic kidneys that is searchable through a user-friendly web application: http://hbcreports.med.harvard.edu/fmm/ . Two commonly used mouse models were utilized: a reversible chemical-induced injury model (folic acid (FA) induced nephropathy) and an irreversible surgically-induced fibrosis model (unilateral ureteral obstruction (UUO)). mRNA and small RNA sequencing, as well as 10-plex tandem mass tag (TMT) proteomics were performed with kidney samples from different time points over the course of fibrosis development. The bioinformatics workflow used to process, technically validate, and combine the single omics data will be described. In summary, we present temporal multi-omics data from fibrotic mouse kidneys that are accessible through an interrogation tool (Mouse Kidney Fibromics browser) to provide a searchable transcriptome and proteome for kidney fibrosis researchers.

PMID: 31201317 [PubMed - in process]

Identification of novel RAS signaling therapeutic vulnerabilities in Diffuse Intrinsic Pontine Gliomas.

Cancer Res. 2019 Jun 14;:

Authors: Koncar RF, Dey BR, Stanton AJ, Agrawal N, Wassell ML, McCarl LH, Locke AL, Sanders L, Morozova Vaske O, Myers MI, Hamilton RL, Carcaboso AM, Kohanbash G, Hu B, Amankulor NM, Felker J, Kambhampati M, Nazarian J, Becher OJ, James CD, Hashizume R, Broniscer A, Pollack IF, Agnihotri S

Abstract
Diffuse intrinsic pontine gliomas (DIPGs) are incurable brain tumors with an aggressive onset. Apart from irradiation, there are currently no effective therapies available for DIPG patients, who have a median survival time of less than one year. Most DIPG cells harbor mutations in genes encoding histone H3 (H3K27M) proteins, resulting in a global reduction of H3K27 trimethylation and activation of oncogenic signaling pathways. Here we show that the H3K27M mutations contribute to RAS pathway signaling, which is augmented by additional RAS activators including PDGFRA. H3K27M mutation led to increased expression of receptor tyrosine kinases (RTKs). A RAS pathway functional screen identified ERK5, but not ERK1/2, as a RAS pathway effector important for DIPG growth. Suppression of ERK5 decreased DIPG cell proliferation and induced apoptosis in vitro and in vivo. Additionally, depletion or inhibition of ERK5 significantly increased survival of mice intracranially engrafted with DIPG cells. Mechanistically, ERK5 directly stabilized the proto-oncogene MYC at the protein level. Collectively, our data demonstrate an underappreciated role of H3K27M in RAS activation and reveal novel therapeutic targets for treating DIPG tumors.

PMID: 31201162 [PubMed - as supplied by publisher]

A novel framework for MR image segmentation and quantification by using MedGA.

Comput Methods Programs Biomed. 2019 Jul;176:159-172

Authors: Rundo L, Tangherloni A, Cazzaniga P, Nobile MS, Russo G, Gilardi MC, Vitabile S, Mauri G, Besozzi D, Militello C

Abstract
BACKGROUND AND OBJECTIVES: Image segmentation represents one of the most challenging issues in medical image analysis to distinguish among different adjacent tissues in a body part. In this context, appropriate image pre-processing tools can improve the result accuracy achieved by computer-assisted segmentation methods. Taking into consideration images with a bimodal intensity distribution, image binarization can be used to classify the input pictorial data into two classes, given a threshold intensity value. Unfortunately, adaptive thresholding techniques for two-class segmentation work properly only for images characterized by bimodal histograms. We aim at overcoming these limitations and automatically determining a suitable optimal threshold for bimodal Magnetic Resonance (MR) images, by designing an intelligent image analysis framework tailored to effectively assist the physicians during their decision-making tasks.
METHODS: In this work, we present a novel evolutionary framework for image enhancement, automatic global thresholding, and segmentation, which is here applied to different clinical scenarios involving bimodal MR image analysis: (i) uterine fibroid segmentation in MR guided Focused Ultrasound Surgery, and (ii) brain metastatic cancer segmentation in neuro-radiosurgery therapy. Our framework exploits MedGA as a pre-processing stage. MedGA is an image enhancement method based on Genetic Algorithms that improves the threshold selection, obtained by the efficient Iterative Optimal Threshold Selection algorithm, between the underlying sub-distributions in a nearly bimodal histogram.
RESULTS: The results achieved by the proposed evolutionary framework were quantitatively evaluated, showing that the use of MedGA as a pre-processing stage outperforms the conventional image enhancement methods (i.e., histogram equalization, bi-histogram equalization, Gamma transformation, and sigmoid transformation), in terms of both MR image enhancement and segmentation evaluation metrics.
CONCLUSIONS: Thanks to this framework, MR image segmentation accuracy is considerably increased, allowing for measurement repeatability in clinical workflows. The proposed computational solution could be well-suited for other clinical contexts requiring MR image analysis and segmentation, aiming at providing useful insights for differential diagnosis and prognosis.

PMID: 31200903 [PubMed - in process]

34 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 2019/06/15

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.

32 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 2019/06/15

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.

93 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 2019/06/14

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.

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 2019/06/13

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.

Sequential Therapy with PARP and WEE1 Inhibitors Minimizes Toxicity while Maintaining Efficacy.

Cancer Cell. 2019 Jun 10;35(6):851-867.e7

Authors: Fang Y, McGrail DJ, Sun C, Labrie M, Chen X, Zhang D, Ju Z, Vellano CP, Lu Y, Li Y, Jeong KJ, Ding Z, Liang J, Wang SW, Dai H, Lee S, Sahni N, Mercado-Uribe I, Kim TB, Chen K, Lin SY, Peng G, Westin SN, Liu J, O'Connor MJ, Yap TA, Mills GB

Abstract
We demonstrate that concurrent administration of poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors is effective in inhibiting tumor growth but poorly tolerated. Concurrent treatment with PARP and WEE1 inhibitors induces replication stress, DNA damage, and abrogates the G2 DNA damage checkpoint in both normal and malignant cells. Following cessation of monotherapy with PARP or WEE1 inhibitors, effects of these inhibitors persist suggesting that sequential administration of PARP and WEE1 inhibitors could maintain efficacy while ameliorating toxicity. Strikingly, while sequential administration mirrored concurrent therapy in cancer cells that have high basal replication stress, low basal replication stress in normal cells protected them from DNA damage and toxicity, thus improving tolerability while preserving efficacy in ovarian cancer xenograft and patient-derived xenograft models.

PMID: 31185210 [PubMed - in process]

Selected Papers from the Workshop on Computational Biology: Joint with the International Joint Conference on Artificial Intelligence and the International Conference on Machine Learning, 2018.

J Comput Biol. 2019 Jun;26(6):507-508

Authors: Diallo AB, Nguifo EM, Dhifli W, Azizi E, Prabhakaran S, Tansey W

PMID: 31184954 [PubMed - in process]

Dynamical modelling of secondary metabolism and metabolic switches in Streptomyces xiamenensis 318.

R Soc Open Sci. 2019 Apr;6(4):190418

Authors: Zhu XM, Zhang XX, Cheng RT, Yu HL, Yuan RS, Bu XL, Xu J, Ao P, Chen YC, Xu MJ

Abstract
The production of secondary metabolites, while important for bioengineering purposes, presents a paradox in itself. Though widely existing in plants and bacteria, they have no definite physiological roles. Yet in both native habitats and laboratories, their production appears robust and follows apparent metabolic switches. We show in this work that the enzyme-catalysed process may improve the metabolic stability of the cells. The latter can be responsible for the overall metabolic behaviours such as dynamic metabolic landscape, metabolic switches and robustness, which can in turn affect the genetic formation of the organism in question. Mangrove-derived Streptomyces xiamenensis 318, with a relatively compact genome for secondary metabolism, is used as a model organism in our investigation. Integrated studies via kinetic metabolic modelling, transcriptase measurements and metabolic profiling were performed on this strain. Our results demonstrate that the secondary metabolites increase the metabolic fitness of the organism via stabilizing the underlying metabolic network. And the fluxes directing to NADH, NADPH, acetyl-CoA and glutamate provide the key switches for the overall and secondary metabolism. The information may be helpful for improving the xiamenmycin production on the strain.

PMID: 31183155 [PubMed]

Chloroplast calcium signalling quenches a thirst.

Nat Plants. 2019 Jun;5(6):559-560

Authors: Stael S

PMID: 31182841 [PubMed - in process]