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https://www.readbyqxmd.com/read/28437848/inferring-network-structure-in-non-normal-and-mixed-discrete-continuous-genomic-data
#1
Anindya Bhadra, Arvind Rao, Veerabhadran Baladandayuthapani
Inferring dependence structure through undirected graphs is crucial for uncovering the major modes of multivariate interaction among high-dimensional genomic markers that are potentially associated with cancer. Traditionally, conditional independence has been studied using sparse Gaussian graphical models for continuous data and sparse Ising models for discrete data. However, there are two clear situations when these approaches are inadequate. The first occurs when the data are continuous but display non-normal marginal behavior such as heavy tails or skewness, rendering an assumption of normality inappropriate...
April 24, 2017: Biometrics
https://www.readbyqxmd.com/read/28437839/semicarbazide-sensitive-amine-oxidase-vascular-adhesion-protein-1-inhibition-reduces-lipopolysaccharide-induced-neuroinflammation
#2
Serena Becchi, Alberto Buson, Jonathan Foot, Wolfgang Jarolimek, Bernard W Balleine
BACKGROUND AND PURPOSE: Neuroinflammation is initiated by a variety of stimuli including infections, sepsis, neurodegenerative diseases or traumatic brain injury and if not adequately controlled can lead to various degrees of neuronal damage and behavioural impairment. A critical event in the initial steps of inflammation is neutrophil extravasation. Semicarbazide sensitive amine oxidase (SSAO, also known as vascular adhesion protein 1 or VAP-1) regulates neutrophil adhesion and extravasation...
April 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28437628/advanced-biomaterials-and-microengineering-technologies-to-recapitulate-the-stepwise-process-of-cancer-metastasis
#3
REVIEW
Nitish Peela, Danh Truong, Harpinder Saini, Hunghao Chu, Samaneh Mashaghi, Stephanie L Ham, Sunil Singh, Hossein Tavana, Bobak Mosadegh, Mehdi Nikkhah
Cancer is one of the leading causes of death globally according to the World Health Organization. Although improved treatments and early diagnoses have reduced cancer related mortalities, metastatic disease remains a major clinical challenge. The local tumor microenvironment plays a significant role in cancer metastasis, where tumor cells respond and adapt to a plethora of biochemical and biophysical signals from stromal cells and extracellular matrix (ECM) proteins. Due to these complexities, there is a critical need to understand molecular mechanisms underlying cancer metastasis to facilitate the discovery of more effective therapies...
April 21, 2017: Biomaterials
https://www.readbyqxmd.com/read/28437467/mutant-uromodulin-expression-leads-to-altered-homeostasis-of-the-endoplasmic-reticulum-and-activates-the-unfolded-protein-response
#4
Céline Schaeffer, Stefania Merella, Elena Pasqualetto, Dejan Lazarevic, Luca Rampoldi
Uromodulin is the most abundant urinary protein in physiological conditions. It is exclusively produced by renal epithelial cells lining the thick ascending limb of Henle's loop (TAL) and it plays key roles in kidney function and disease. Mutations in UMOD, the gene encoding uromodulin, cause autosomal dominant tubulointerstitial kidney disease uromodulin-related (ADTKD-UMOD), characterised by hyperuricemia, gout and progressive loss of renal function. While the primary effect of UMOD mutations, retention in the endoplasmic reticulum (ER), is well established, its downstream effects are still largely unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28437460/an-aggregation-removal-model-for-the-formation-and-size-determination-of-post-synaptic-scaffold-domains
#5
Jonas Ranft, Leandro G Almeida, Pamela C Rodriguez, Antoine Triller, Vincent Hakim
The formation and stability of synapses are key questions in neuroscience. Post-synaptic domains have been classically conceived as resulting from local insertion and turnover of proteins at the synapse. However, insertion is likely to occur outside the post-synaptic domains and advances in single-molecule imaging have shown that proteins diffuse in the plane of the membrane prior to their accumulation at synapses. We quantitatively investigated this scenario using computer simulations and mathematical analysis, taking for definiteness the specific case of inhibitory synapse components, i...
April 24, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28437444/transcriptional-bursting-in-drosophila-development-stochastic-dynamics-of-eve-stripe-2-expression
#6
David M Holloway, Alexander V Spirov
Anterior-posterior (AP) body segmentation of the fruit fly (Drosophila) is first seen in the 7-stripe spatial expression patterns of the pair-rule genes, which regulate downstream genes determining specific segment identities. Regulation of pair-rule expression has been extensively studied for the even-skipped (eve) gene. Recent live imaging, of a reporter for the 2nd eve stripe, has demonstrated the stochastic nature of this process, with 'bursts' in the number of RNA transcripts being made over time. We developed a stochastic model of the spatial and temporal expression of eve stripe 2 (binding by transcriptional activators (Bicoid and Hunchback proteins) and repressors (Giant and Krüppel proteins), transcriptional initiation and termination; with all rate parameters constrained by features of the experimental data) in order to analyze the noisy experimental time series and test hypotheses for how eve transcription is regulated...
2017: PloS One
https://www.readbyqxmd.com/read/28437379/associations-of-lifetime-trauma-and-chronic-stress-with-c-reactive-protein-in-adults-ages-50-and-older-examining-the-moderating-role-of-perceived-control
#7
Ari J Elliot, Christopher J Mooney, Frank J Infurna, Benjamin P Chapman
OBJECTIVE: To investigate whether high perceived control mitigates systemic inflammatory risk associated with traumatic and chronic stress exposures in older adults. METHODS: A sample of community-dwelling adults ages 50 and older (N=4,779) was drawn from the Health and Retirement Study (HRS). Structural equation models tested interactions of lifetime trauma and chronic stress with mastery and perceived constraints predicting baseline levels and four-year change in C-reactive protein (CRP)...
April 21, 2017: Psychosomatic Medicine
https://www.readbyqxmd.com/read/28437249/the-differential-spatiotemporal-expression-pattern-of-shelterin-genes-throughout-lifespan
#8
Kay-Dietrich Wagner, Yilin Ying, Waiian Leong, Jie Jiang, Xuefei Hu, Yi Chen, Jean-François Michiels, Yiming Lu, Eric Gilson, Nicole Wagner, Jing Ye
Shelterin forms the core complex of telomere proteins and plays critical roles in protecting telomeres against unwanted activation of the DNA damage response and in Emaintaining telomere length homeostasis. Although shelterin expression is believed to be ubiquitous for stabilization of chromosomal ends. Evidences suggest that some shelterin subunits have tissue-specific functions. However, very little is known regarding how shelterin subunit gene expression is regulated during development and aging. Using two different animal models, the mouse and zebrafish, we reveal herein that shelterin subunits exhibit distinct spatial and temporal expression patterns that do not correlate with the proliferative status of the organ systems examined...
April 17, 2017: Aging
https://www.readbyqxmd.com/read/28437190/consuming-a-ketogenic-diet-while-receiving-radiation-and-chemotherapy-for-locally-advanced-lung-cancer-and-pancreatic-cancer-the-university-of-iowa-experience-of-two-phase-1-clinical-trials
#9
Amir Zahra, Melissa A Fath, Emyleigh Opat, Kranti A Mapuskar, Sudershan K Bhatia, Daniel C Ma, Samuel N Rodman Iii, Travis P Snyders, Catherine A Chenard, Julie M Eichenberger-Gilmore, Kellie L Bodeker, Logan Ahmann, Brian J Smith, Sandy A Vollstedt, Heather A Brown, Taher Abu Hejleh, Gerald H Clamon, Daniel J Berg, Luke I Szweda, Douglas R Spitz, John M Buatti, Bryan G Allen
Ketogenic diets are low in carbohydrates and high in fat, which forces cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Relative to normal cells, cancer cells are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. In this study we tested the hypothesis that a ketogenic diet concurrent with radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung cancer (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes...
April 24, 2017: Radiation Research
https://www.readbyqxmd.com/read/28437133/the-impact-of-the-centrifuge-characteristics-and-centrifugation-protocols-on-the-cells-growth-factors-and-fibrin-architecture-of-a-leukocyte-and-platelet-rich-fibrin-l-prf-clot-and-membrane
#10
David M Dohan Ehrenfest, Nelson R Pinto, Andrea Pereda, Paula Jiménez, Marco Del Corso, Byung-Soo Kang, Mauricio Nally, Nicole Lanata, Hom-Lay Wang, Marc Quirynen
L-PRF (leukocyte- and platelet-rich fibrin) is one of the four families of platelet concentrates for surgical use and is widely used in oral and maxillofacial regenerative therapies. The first objective of this article was to evaluate the mechanical vibrations appearing during centrifugation in four models of commercially available table-top centrifuges used to produce L-PRF and the impact of the centrifuge characteristics on the cell and fibrin architecture of a L-PRF clot and membrane. The second objective of this article was to evaluate how changing some parameters of the L-PRF protocol may influence its biological signature, independently from the characteristics of the centrifuge...
April 24, 2017: Platelets
https://www.readbyqxmd.com/read/28437096/importance-of-mm-polarization-in-qm-mm-studies-of-enzymatic-reactions-assessment-of-the-qm-mm-drude-oscillator-model
#11
Abir Ganguly, Eliot Boulanger, Walter Thiel
For accurate quantum mechanics/molecular mechanics (QM/MM) studies of enzymatic reactions, it is desirable to include MM polarization, for example by using the Drude oscillator (DO) model. For a long time, such studies were hampered by the lack of well-tested polarizable force fields for proteins. Following up on a recent preliminary QM/MM-DO assessment (J. Chem. THEORY: Comput. 2014, 10, 1795-1809) we now report a comprehensive investigation of the effects of MM polarization on two enzymatic reactions, namely the Claisen rearrangement in chorismate mutase and the hydroxylation reaction in p-hydroxybenzoate hydrolase, using the QM/CHARMM-DO model and two QM methods (B3LYP, OM2)...
April 24, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28437088/hilaq-a-novel-strategy-for-newly-synthesized-protein-quantification
#12
Yuanhui Ma, Daniel B McClatchy, Salim Barkallah, William W Wood, John R Yates Iii
Here we describe a new strategy, HILAQ (Heavy Isotope Labeled Azidohomoalanine Quantification), to rapidly quantify the molecular vulnerability profile to oxytosis, which is an oxidative stress-induced programed cell death pathway that has been reported to be involved in aging and neurodegenerative diseases. HILAQ was able to quantify 1,962 Newly Synthesized Proteins (NSPs) after 1h pulse labeling in HEK293T cell line, while 353 proteins were quantified using the previously published QuaNCAT protocol. HILAQ was successfully applied to the HT22 oxytosis model...
April 24, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28437083/dual-plug-and-display-synthetic-assembly-using-orthogonal-reactive-proteins-for-twin-antigen-immunization
#13
Karl Brune, Can Buldun, Yuanyuan Li, Iona Taylor, Florian Brod, Sumi Biswas, Mark Howarth
Engineering modular platforms to control biomolecular architecture can advance both the understanding and manipulation of biological systems. Icosahedral particles uniformly displaying single antigens stimulate potent immune activation and have been successful in various licensed vaccines. However, it remains challenging to display multiple antigens on a single particle, to induce broader immunity protective across strains or even against distinct diseases. Here we design a dually-addressable synthetic nanoparticle, by engineering the multimerizing coiled-coil IMX313 and two orthogonally-reactive split proteins...
April 24, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28437013/the-prognostic-value-of-b7-h6-protein-expression-in-human-oral-squamous-cell-carcinoma
#14
Jiongke Wang, Xin Jin, Jiajia Liu, Kui Zhao, Hao Xu, Jing Wen, Lu Jiang, Xin Zeng, Jing Li, Qianming Chen
OBJECTIVES: To investigate the expression and prognostic value of B7-H6 protein in oral squamous cell carcinoma tissues. MATERIALS AND METHODS: A total of 50 oral squamous cell carcinoma samples, 10 oral leukoplakia samples and 17 normal controls were included in the analysis. The expression of B7-H6 in oral squamous cell carcinoma, oral leukoplakia and normal controls was evaluated by immunohistochemical assay. RESULTS: The B7-H6 protein expression was significantly higher in oral squamous cell carcinoma tissues than that in normal oral mucosa...
April 24, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#15
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28436953/disruption-of-direct-3d-telomere-trf2-interaction-through-two-molecularly-disparate-mechanisms-is-a-hallmark-of-primary-hodgkin-and-reed-sternberg-cells
#16
Hans Knecht, Nathalie A Johnson, Tina Haliotis, Daniel Lichtensztejn, Sabine Mai
In classical Hodgkin's lymphoma (cHL), specific changes in the 3D telomere organization cause progression from mononuclear Hodgkin cells (H) to multinucleated Reed-Sternberg cells (RS). In a post-germinal center B-cell in vitro model, permanent latent membrane protein 1 (LMP1) expression, as observed in Epstein-Barr virus (EBV)-associated cHL, results in multinuclearity and complex chromosomal aberrations through downregulation of key element of the shelterin complex, the telomere repeat binding factor 2 (TRF2)...
April 24, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#17
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436950/mre11-stability-is-regulated-by-ck2-dependent-interaction-with-r2tp-complex
#18
P von Morgen, K Burdova, T G Flower, N J O'Reilly, S J Boulton, S J Smerdon, L Macurek, Z Hořejší
The MRN (MRE11-RAD50-NBS1) complex is essential for repair of DNA double-strand breaks and stalled replication forks. Mutations of the MRN complex subunit MRE11 cause the hereditary cancer-susceptibility disease ataxia-telangiectasia-like disorder (ATLD). Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436934/biopolymers-codelivering-engineered-t-cells-and-sting-agonists-can-eliminate-heterogeneous-tumors
#19
Tyrel T Smith, Howell F Moffett, Sirkka B Stephan, Cary F Opel, Amy G Dumigan, Xiuyun Jiang, Venu G Pillarisetty, Smitha P S Pillai, K Dane Wittrup, Matthias T Stephan
Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28436713/modified-dextran-heparin-based-triggered-release-microspheres-for-cardiovascular-delivery-of-therapeutic-drugs-using-protamine-as-a-stimulus
#20
Hoai X Nguyen, Edgar A O'Rear
In this study, we describe the synthesis of an amine-modified acetalated dextran polymer which is combined with heparin (HP) as the basis for a novel controlled release system. Dextran-amine (DEXAM) conjugates, synthesized using reductive amination, were incorporated into DEXAM/HP microspheres. HP binds to positively charged ammonium ions of the DEXAM conjugates, contributing to the structural integrity of the microspheres. Crystal violet (CV) was encapsulated inside DEXAM/HP microspheres as a model drug to test the system...
April 24, 2017: Journal of Microencapsulation
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