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https://www.readbyqxmd.com/read/27926989/targeting-gm-csf-in-epithelial-and-vascular-remodeling-in-experimental-eosinophilic-esophagitis
#1
Eóin N McNamee, Kathryn A Biette, Juliet Hammer, Rachel Harris, Heather Miyazawa, James J Lee, Glenn T Furuta, Joanne C Masterson
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-mediated clinicopathologic disease of the esophagus characterized by an eosinophil-predominant inflammatory infiltrate. A clinical hallmark is extensive tissue remodeling including basal zone hyperplasia, fibrosis and angiogenesis. However, the cellular mechanisms responsible for these processes are not fully defined. We hypothesized that targeting GM-CSF (an agonist cytokine linked with eosinophil survival and activation) would be protective in a pre-clinical model of EoE...
December 7, 2016: Allergy
https://www.readbyqxmd.com/read/27926938/uncovering-the-pathogenic-landscape-of-helminth-opisthorchis-viverrini-infections-a-cross-sectional-study-on-contributions-of-physical-and-social-environment-and-healthcare-interventions
#2
Xueyuan Ong, Yi-Chen Wang, Paiboon Sithithaworn, Jutamas Namsanor, David Taylor, Luxana Laithavewat
BACKGROUND: Helminth infections have proven recalcitrant to control by chemotherapy in many parts of Southeast Asia and indeed farther afield. This study isolates and examines the influence of different aspects of the physical and social environment, and uneven intervention effort contributing to the pathogenic landscape of human Opisthorchis viverrini infections. METHODOLOGY: A cross-sectional survey, involving 632 participants, was conducted in four villages in northeast Thailand to examine the impact on prevalence and parasite burden of the reservoir dam environment, socio-economic, demographic, and behavioral factors, and health center intervention efforts...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#3
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926827/decoding-hand-gestures-from-primary-somatosensory-cortex-using-high-density-ecog
#4
Mariana P Branco, Zachary V Freudenburg, Erik J Aarnoutse, Martin G Bleichner, Mariska J Vansteensel, Nick F Ramsey
Electrocorticography (ECoG) based Brain-Computer Interfaces (BCIs) have been proposed as a way to restore and replace motor function or communication in severely paralyzed people. To date, most motor-based BCIs have either focused on the sensorimotor cortex as a whole or on the primary motor cortex (M1) as a source of signals for this purpose. Still, target areas for BCI are not confined to M1, and more brain regions may provide suitable BCI control signals. A logical candidate is the primary somatosensory cortex (S1), which not only shares similar somatotopic organization to M1, but also has been suggested to have a role beyond sensory feedback during movement execution...
December 4, 2016: NeuroImage
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#5
Christine Oswald, Mathieu Rappas, James Kean, Andrew S Doré, James C Errey, Kirstie Bennett, Francesca Deflorian, John A Christopher, Ali Jazayeri, Jonathan S Mason, Miles Congreve, Robert M Cooke, Fiona H Marshall
Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells. They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases. Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926691/on-treatment-blood-pressures-of-older-hypertensive-patients-in-canada-implications-for-systolic-blood-pressure-intervention-trial
#6
Jiri George Fodor, Penelope Baker, Li Chen, Frans H H Leenen
OBJECTIVE: The therapeutic target level for the blood pressure (BP) on antihypertensive drug treatment in older hypertensive patients is still extensively debated. We assessed the achieved BP levels in older treated hypertensive patients in a representative sample of the population. DESIGN: During the 2006 Ontario Survey on the Prevalence and Control of Hypertension, BP (using the SPRINT protocol) and treatment data were collected in 2551 respondents from a random and representative sample of the adult (20-79 years) population...
December 6, 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27926690/changes-of-blood-pressure-patterns-and-target-organ-damage-in-patients-with-chronic-kidney-disease-results-of-the-aprodite-2-study
#7
Ran-Hui Cha, Hajeong Lee, Jung Pyo Lee, Eunjeong Kang, Young Rim Song, Yon Su Kim, Sung Gyun Kim
OBJECTIVE: Blood pressure (BP) control is the most established practice for preventing the progression of chronic kidney disease (CKD). We examined the BP control and nocturnal dipping pattern changes in hypertensive patients with CKD and their effects on target organ damages. METHODS: We recruited 378 hypertensive CKD patients from four centers in Korea. The patients underwent clinic and ambulatory BP monitoring at the time of enrollment and 1 year later. RESULTS: The BP control states at the two time points were as follows: true controlled (16...
December 6, 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27926546/the-effect-of-chronic-kidney-disease-on-t-cell-alloimmunity
#8
Pamela D Winterberg, Mandy L Ford
PURPOSE OF REVIEW: Altered differentiation and activation of T-cell subsets occur in patients with chronic kidney disease (CKD), but the impact on graft rejection and protective immunity during transplantation are not fully understood. RECENT FINDINGS: Patients with CKD have decreased frequency of naïve T cells, accumulation of activated, terminally differentiated memory cells, and skewed regulatory versus T helper 17 ratio. Naïve and memory T-cell subsets do not appear to improve following kidney transplantation...
December 6, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27926529/altered-microrna-profiles-in-plasma-exosomes-from-mesial-temporal-lobe-epilepsy-with-hippocampal-sclerosis
#9
Shaofeng Yan, Hua Zhang, Wenyan Xie, Fangang Meng, Kai Zhang, Yin Jiang, Xin Zhang, Jianguo Zhang
Mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) is the most common type of focal epilepsy. The present study aimed to explore the expression and functions of exosomal microRNAs in mTLE-HS. A total of 50 microRNAs were found to be differentially expressed in mTLE-HS compared with healthy controls. Among them, 2 were increased and 48 were decreased. The 6 significant differentially expressed candidate microRNAs (miR-3613-5p, miR-4668-5p, miR-8071, miR-197-5p, miR-4322, and miR-6781-5p ) in exosome were validated...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926522/il-10-expression-defines-an-immunosuppressive-dendritic-cell-population-induced-by-antitumor-therapeutic-vaccination
#10
Diana Llopiz, Marta Ruiz, Stefany Infante, Lorea Villanueva, Leyre Silva, Sandra Hervas-Stubbs, Diego Alignani, Elizabeth Guruceaga, Juan J Lasarte, Pablo Sarobe
Vaccination induces immunostimulatory signals that are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Here we characterized IL-10-producing cells in different tumor models treated with therapeutic vaccines. Although several cell subsets produced IL-10 irrespective of treatment, an early vaccine-dependent induction of IL-10 was detected in dendritic cells (DC). IL-10 production defined a DC population characterized by a poorly mature phenotype, lower expression of T-cell stimulating molecules and upregulation of PD-L1...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926503/foxd3-is-a-tumor-suppressor-of-colon-cancer-by-inhibiting-egfr-ras-raf-mek-erk-signal-pathway
#11
Kun Li, Qunfeng Guo, Jun Yang, Hui Chen, Kewen Hu, Juan Zhao, Shunxin Zheng, Xiufeng Pang, Sufang Zhou, Yongyan Dang, Lei Li
Forkhead box D3 (FOXD3), as a transcriptional repressor, is well known to be involved in the regulation of development. Although FoxD3 is associated with several cancers, its role in colon cancer and the underlying mechanism are still unclear. Here, we first showed that FOXD3 knockdown dramatically increased the proliferation of human colon cancer cells, enhanced cell invasive ability and inhibited cell apoptosis. In vivo xenograft studies confirmed that the FOXD3-knockdown cells were more tumorigenic than the controls...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926500/the-association-between-clinical-prognostic-factors-and-epidermal-growth-factor-receptor-tyrosine-kinase-inhibitor-egfr-tki-efficacy-in-advanced-non-small-cell-lung-cancer-patients-a-retrospective-assessment-of-94-cases-with-egfr-mutations
#12
Jing-Hui Lin, Dong Lin, Ling Xu, Qiang Wang, Hui-Hua Hu, Hai-Peng Xu, Zhi-Yong He
OBJECTIVE: This study aimed to examine the association of clinical prognostic factors with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) efficacy in advanced non-small-cell lung cancer (NSCLC) patients. METHODS: The demographic and clinical characteristics of 94 patients with stage IV NSCLC were retrospectively reviewed, and the association between clinical factors and EGFR-TKIs efficacy was evaluated. RESULTS: Of the 94 stage IV NSCLC patients enrolled in this study, a 74...
December 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926496/the-therapeutic-potential-of-targeting-the-pi3k-pathway-in-pediatric-brain-tumors
#13
REVIEW
Hazel A Rogers, Jasper Estranero, Keshni Gudka, Richard G Grundy
Central nervous system tumors are the most common cancer type in children and the leading cause of cancer related deaths. There is therefore a need to develop novel treatments. Large scale profiling studies have begun to identify alterations that could be targeted therapeutically, including the phosphoinositide 3-kinase (PI3K) signaling pathway, which is one of the most commonly activated pathways in cancer with many inhibitors under clinical development. PI3K signaling has been shown to be aberrantly activated in many pediatric CNS neoplasms...
December 2, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926436/to-work-or-not-to-work-neural-representation-of-cost-and-benefit-of-instrumental-action
#14
N B Kroemer, C Burrasch, L Hellrung
By definition, instrumental actions are performed in order to obtain certain goals. Nevertheless, the attainment of goals typically implies obstacles, and response vigor is known to reflect an integration of subjective benefit and cost. Whereas several brain regions have been associated with cost/benefit ratio decision-making, trial-by-trial fluctuations in motivation are not well understood. We review recent evidence supporting the motivational implications of signal fluctuations in the mesocorticolimbic system...
2016: Progress in Brain Research
https://www.readbyqxmd.com/read/27925844/a-two-dose-heterologous-prime-boost-vaccine-regimen-eliciting-sustained-immune-responses-to-ebola-zaire-could-support-a-preventive-strategy-for-future-outbreaks
#15
Georgi Shukarev, Benoit Callendret, Kerstin Luhn, Macaya Douoguih, The Ebovac Consortium
The consequences of the 2013-16 Ebola Zaire virus disease epidemic in West Africa were grave. The economies, healthcare systems and communities of Guinea, Sierra Leone and Liberia were devastated by over 18 months of active Ebola virus transmission, followed by sporadic resurgences potentially related to sexual transmission by survivors with viral persistence in body fluids following recovery. The need to develop and implement strategies to prevent and mitigate future outbreaks is now beyond dispute. The potential for unpredictable outbreaks of indeterminate duration, and control challenges posed by the possibility of sporadic re-emergence, mean that implementation of an effective vaccination programme for outbreak containment necessitates a vaccine providing durable immunity...
December 7, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27925796/a-severe-asthma-disease-signature-from-gene-expression-profiling-of-peripheral-blood-from-u-biopred-cohorts
#16
Jeannette Bigler, Michael Boedigheimer, James P R Schofield, Paul J Skipp, Julie Corfield, Anthony Rowe, Ana R Sousa, Martin Timour, Lori Twehues, Xuguang Hu, Graham Roberts, Andrew A Welcher, Wen Yu, Kian F Chung, Ian M Adcock, Peter J Sterk, Ratko Djukanović
RATIONALE: Stratification of asthma at the molecular level, especially using accessible biospecimens, could greatly enable patient selection for targeted therapy. OBJECTIVES: To determine the value of blood to identify transcriptional differences between clinically defined asthmatic and non-asthmatic groups, identify potential patient subgroups based on gene expression, and explore biological pathways associated with identified differences. METHODS: Transcriptomics profiles were generated by microarray analysis of blood from 610 asthmatic and control participants in U-BIOPRED...
December 7, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27925645/taking-time-to-feel-our-body-steady-increases-in-heartbeat-perception-accuracy-and-decreases-in-alexithymia-over-9-months-of-contemplative-mental-training
#17
Boris Bornemann, Tania Singer
The ability to accurately perceive signals from the body has been shown to be important for physical and psychological health as well as understanding one's emotions. Despite the importance of this skill, often indexed by heartbeat perception accuracy (HBPa), little is known about its malleability. Here, we investigated whether contemplative mental practice can increase HBPa. In the context of a 9-month mental training study, the ReSource Project, two matched cohorts (n = 77 and n = 79) underwent three training modules of 3 months' duration that targeted attentional and interoceptive abilities (Presence module), socio-affective (Affect module), and socio-cognitive (Perspective module) abilities...
December 7, 2016: Psychophysiology
https://www.readbyqxmd.com/read/27925600/cooperative-robots-to-observe-moving-targets-review
#18
Asif Khan, Bernhard Rinner, Andrea Cavallaro
The deployment of multiple robots for achieving a common goal helps to improve the performance, efficiency, and/or robustness in a variety of tasks. In particular, the observation of moving targets is an important multirobot application that still exhibits numerous open challenges, including the effective coordination of the robots. This paper reviews control techniques for cooperative mobile robots monitoring multiple targets. The simultaneous movement of robots and targets makes this problem particularly interesting, and our review systematically addresses this cooperative multirobot problem for the first time...
December 1, 2016: IEEE Transactions on Cybernetics
https://www.readbyqxmd.com/read/27925598/evaluation-of-adherence-to-nutritional-intervention-through-trajectory-analysis
#19
Beatriz Sevilla-Villanueva, Karina Gibert, Miquel Sanchez-Marre, Montserrat Fito, Maria-Isabel Covas
Classical Pre-Post Intervention Studies are often analyzed using traditional statistics. Nevertheless, the nutritional interventions have small effects on the metabolism and traditional statistics are not enough to detect these subtle nutrient effects. Generally, this kind of studies assumes that the participants are adhered to the assigned dietary intervention and directly analyzes its effects over the target parameters. Thus, the evaluation of adherence is generally omitted. Although, sometimes, participants do not effectively adhere to the assigned dietary guidelines...
December 1, 2016: IEEE Journal of Biomedical and Health Informatics
https://www.readbyqxmd.com/read/27925476/immune-disease-associated-variants-in-gene-enhancers-point-to-bet-epigenetic-mechanisms-for-therapeutic-intervention
#20
David F Tough, Rab K Prinjha
Genome-wide association studies have identified thousands of single nucleotide polymorphisms in the human genome that are statistically associated with particular disease traits. In this Perspective, we review emerging data suggesting that most single nucleotide polymorphisms associated with immune-mediated diseases are found in regulatory regions of the DNA - parts of the genome that control expression of the protein encoding genes - rather than causing mutations in proteins. We discuss how the emerging understanding of particular gene regulatory regions, gene enhancers and the epigenetic mechanisms by which they are regulated is opening up new opportunities for the treatment of immune-mediated diseases, focusing particularly on the BET family of epigenetic reader proteins as potential therapeutic targets...
December 7, 2016: Epigenomics
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