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T cell sensitivity

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https://www.readbyqxmd.com/read/28812327/design-and-synthesis-of-terephthalic-acid-based-histone-deacetylase-inhibitors-with-dual-stage-anti-plasmodium-activity
#1
Katharina Stenzel, Ming Jang Chua, Sandra Duffy, Yevgeniya Antonova-Koch, Stephan Meister, Alexandra Hamacher, Matthias U Kassack, Elizabeth A Winzeler, Vicky M Avery, Thomas Kurz, Katherine T Andrews, Finn Kristian Hansen
In this work we aimed to develop parasite-selective HDAC inhibitors with activity against the disease-causing asexual blood stages of Plasmodium as well as causal prophylactic and/or transmission blocking properties. We report the design, synthesis and biological testing of a series of 13 terephthalic acid-based histone deacetylase inhibitors. All compounds showed low cytotoxicity against human embryonic kidney (HEK293) cells (IC50 8 - >51 µM), with 11 also having sub-micromolar in vitro activity against drug-sensitive (3D7) and multi-drug resistant (Dd2) asexual blood stage Plasmodium falciparum parasites (IC50 ~ 0...
August 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28812148/local-recurrence-of-squamous-cell-carcinoma-of-the-head-and-neck-after-radio-chemo-therapy-diagnostic-performance-of-fdg-pet-mri-with-diffusion-weighted-sequences
#2
Minerva Becker, Arthur D Varoquaux, Christophe Combescure, Olivier Rager, Marc Pusztaszeri, Karim Burkhardt, Bénédicte M A Delattre, Pavel Dulguerov, Nicolas Dulguerov, Eirini Katirtzidou, Francesca Caparrotti, Osman Ratib, Habib Zaidi, Christoph D Becker
PURPOSE: To determine the diagnostic performance of FDG-PET/MRI with diffusion-weighted imaging (FDG-PET/DWIMRI) for detection and local staging of head and neck squamous cell carcinoma (HNSCC) after radio(chemo)therapy. MATERIALS AND METHODS: This was a prospective study that included 74 consecutive patients with previous radio(chemo)therapy for HNSCC and in whom tumour recurrence or radiation-induced complications were suspected clinically. The patients underwent hybrid PET/MRI examinations with morphological MRI, DWI and FDG-PET...
August 15, 2017: European Radiology
https://www.readbyqxmd.com/read/28812082/a-broader-view-on-ion-heating-in-traveling-wave-devices-using-fragmentation-of-csi-clusters-and-extent-of-h%C3%AB-migration-as-molecular-thermometers
#3
Frederik Lermyte, Frank Sobott
Electron transfer dissociation (ETD) is becoming increasingly important in mass spectrometry-based analysis of peptides and proteins. Supplemental collisional activation of undissociated electron transfer products can significantly increase fragmentation yield and sequence coverage, but hydrogen rearrangements - specifically, transfer of a hydrogen radical from a c to a z fragment - lead to distorted isotope distributions and increased potential for signal overlap. Concomitant collisional activation during the ion/ion reaction significantly reduces these rearrangements, but, in ion traps, also leads to lower reaction rates and reduced overlap of anion and cation clouds...
August 16, 2017: Analyst
https://www.readbyqxmd.com/read/28811651/inkt-cells-prevent-obesity-induced-hepatic-steatosis-in-mice-in-a-c-c-chemokine-receptor-7-dependent-manner
#4
H M Kim, R Lee, E S Lee, M H Kwon, J H Huh, B-E Kwon, E-K Park, S-Y Chang, M-N Kweon, P-H Kim, H-J Ko, C H Chung
Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are characterized by an increase in hepatic triglyceride content with infiltration of immune cells, which can cause steatohepatitis and hepatic insulin resistance. C-C chemokine receptor 7 (CCR7) is primarily expressed in immune cells, and CCR7 deficiency leads to the development of multi-organ autoimmunity, chronic renal disease, and autoimmune diabetes. Here, we investigated the effect of CCR7 on hepatic steatosis in a mouse model and its underlying mechanism...
August 16, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28811625/interleukin-7-in-the-transition-of-bone-marrow-progenitors-to-the-thymus
#5
Adam W Plumb, Abdalla Sheikh, Douglas A Carlow, Hermann J Ziltener, Ninan Abraham
Interleukin-7 (IL-7) is essential for the development of T cells in humans and mice where deficiencies in IL-7 signaling result in severe immunodeficiency. T cells require IL-7 at multiple points during development however it is unclear when IL-7 is first necessary. We observed that mice with impaired IL-7 signaling had a large reduction in the number of early thymic progenitors (ETPs) while mice that overexpress IL-7 had greatly increased numbers of ETPs. These results indicated that the development of ETPs is sensitive to IL-7...
August 16, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28810913/selinexor-kpt-330-demonstrates-anti-tumor-efficacy-in-preclinical-models-of-triple-negative-breast-cancer
#6
Natalia Paez Arango, Erkan Yuca, Ming Zhao, Kurt W Evans, Stephen Scott, Charissa Kim, Ana Maria Gonzalez-Angulo, Filip Janku, Naoto T Ueno, Debu Tripathy, Argun Akcakanat, Aung Naing, Funda Meric-Bernstam
BACKGROUND: Selinexor (KPT-330) is an oral agent that has been shown to inhibit the nuclear exporter XPO1. Given the pressing need for novel therapies for triple-negative breast cancer (TNBC), we sought to determine the antitumor effects of selinexor in vitro and in vivo. METHODS: Twenty-six breast cancer cell lines of different breast cancer subtypes were treated with selinexor in vitro. Cell proliferation assays were used to measure the half-maximal inhibitory concentration (IC50) and to test the effects in combination with chemotherapy...
August 15, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28810548/effect-of-follicular-helper-t-cells-on-the-pathogenesis-of-asthma
#7
Xiaojuan Ma, Zhan Sun, Pei Zhai, Wenyan Yu, Ting Wang, Fengsen Li, Jianbing Ding
Follicular helper T (TFH) cells are considered to be a separate T helper cell subset, specifically to help memory B cell participate in humoral immunity. It has been reported that there is an association between the imbalance of TFH function and certain autoimmune diseases. However, to the best of our knowledge, the effect of TFH cells on the process of bronchial asthma has not been investigated. The aim of the present study was to investigate the associated markers of TFH cells in bronchial asthma-induced mice...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28810531/mir-146a-overexpression-effectively-improves-experimental-allergic-conjunctivitis-through-regulating-cd4-cd25-t-cells
#8
Yang Yang, Xiaolong Yin, Jinglin Yi, Xiaowei Peng
OBJECTIVE: To study the mechanism of miR-146a in the regulation of allergic conjunctivitis (AC) through CD4(+)CD25(-)T cells. METHODS: BALB/c mice were sensitized with ragweed pollen (RW) and alum, and then challenged with RW. Eosinophil infiltration was determined using Giemsa assay. ELISA assay was performed to examine the level of antigen-specific IgE in the serum and cytokine levels in splenocytes. The expression of miR-146a was measured by qRT-PCR. Flow cytometric analysis was used to analyze the percentage of CD4(+)CD25(-)T cells and Tregs...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28810123/electrochemical-dissolution-of-iridium-and-iridium-oxide-par-ticles-in-acidic-media-transmission-electron-microscopy-electrochemical-flow-cell-coupled-to-inductively-coupled-plasma-mass-spectrometry-and-x-ray-absorption-spectros-copy-study
#9
Primož Jovanovič, Nejc Hodnik, Francisco Ruiz-Zepeda, Iztok Arcon, Barbara Jozinović, Milena Zorko, Marjan Bele, Martin Šala, Vid Simon Šelih, Samo B Hocevar, Miran Gaberscek
Iridium based particles as the most promising proton exchange membrane electrolyser electrocatalysts were investigated by transmission electron microscopy (TEM), and by coupling of electrochemical flow cell (EFC) with online inductively coupled plasma mass spectrometer (ICP-MS). Additionally, a thin-film rotating disc electrode (RDE), an identical location trans-mission and scanning electron microscopy (IL-TEM and IL-SEM) as well as an X-ray absorption spectroscopy (XAS) studies have been performed. Extremely sensitive online time-and potential-resolved electrochemical dissolution profiles revealed that iridium particles dissolved already well below oxygen evolution reaction (OER) potentials, presumably induced by iridium surface oxidation and reduction processes, also referred to as transient dissolution...
August 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28809682/an-optimization-and-comparative-study-of-air-coupled-cmut-cells-with-circular-and-annular-geometries
#10
Shuai Na, Zhenhao Li, Lawrence L P Wong, Albert I-H Chen, Mirek Macecek, John T W Yeow
Air-coupled capacitive micromachined ultrasonic transducers (CMUTs) with annular cell geometry have recently been reported to have a promising transmit sensitivity. This paper reports three optimization schemes, which further improve the transmit sensitivity and also help achieve a reasonable comparison between the novel annular and conventional circular cells. Lumped element models of both cell types with laminate plate structures are presented. Based on these models, a design optimization flow chart was constructed to facilitate analytical optimization on the three schemes...
August 14, 2017: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/28809398/precision-medicine-for-suicidality-from-universality-to-subtypes-and-personalization
#11
A B Niculescu, H Le-Niculescu, D F Levey, P L Phalen, H L Dainton, K Roseberry, E M Niculescu, J O Niezer, A Williams, D L Graham, T J Jones, V Venugopal, A Ballew, M Yard, T Gelbart, S M Kurian, A Shekhar, N J Schork, G E Sandusky, D R Salomon
Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a 'liquid biopsy' approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies...
August 15, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28808159/chronic-brucella-infection-induces-selective-and-persistent-ifn-%C3%AE-dependent-alterations-of-marginal-zone-macrophages-in-the-spleen
#12
Arnaud Machelart, Abir Khadrawi, Aurore Demars, Kevin Willemart, Carl De Trez, Jean-Jacques Letesson, Eric Muraille
The spleen is known as an important filter for blood-borne pathogens that are trapped by specialized macrophages in the marginal zone (MZ): the CD209(+) MZ macrophages (MZMs) and the CD169(+) marginal metallophilic macrophages (MMMs). Acute systemic infection strongly impacts MZ populations and the location of T and B lymphocytes. This phenomenon has been linked to reduced chemokine secretion by stromal cells. Brucella spp. are the causative agent of brucellosis, a widespread zoonotic disease. Here, we used B...
August 14, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28808038/the-phosphatidylinositol-3-kinase-pathway-as-a-potential-therapeutic-target-in-bladder-cancer
#13
Shuxiong Zeng, Yanjun Zhu, Ai-Hong Ma, Weimin Yu, Hongyong Zhang, Tzu-Yin Lin, Wei Shi, Clifford G Tepper, Paul T Henderson, Susan Airhart, Jianming Guo, Chuanliang Xu, Ralph de Vere White, Chong-Xian Pan
PURPOSE: Activation of the phosphatidylinositol 3-kinase (PI3K) pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action and resistant mechanisms of drugs targeting the PI3K pathway. EXPERIMENTAL DESIGN: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine...
August 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28808010/voltage-gated-calcium-flux-mediates-escherichia-coli-mechanosensation
#14
Giancarlo N Bruni, R Andrew Weekley, Benjamin J T Dodd, Joel M Kralj
Electrically excitable cells harness voltage-coupled calcium influx to transmit intracellular signals, typically studied in neurons and cardiomyocytes. Despite intense study in higher organisms, investigations of voltage and calcium signaling in bacteria have lagged due to their small size and a lack of sensitive tools. Only recently were bacteria shown to modulate their membrane potential on the timescale of seconds, and little is known about the downstream effects from this modulation. In this paper, we report on the effects of electrophysiology in individual bacteria...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28807994/a-novel-computational-model-predicts-key-regulators-of-chemokine-gradient-formation-in-lymph-nodes-and-site-specific-roles-for-ccl19-and-ackr4
#15
Mohammad Jafarnejad, David C Zawieja, Bindi S Brook, Robert J B Nibbs, James E Moore
The chemokine receptor CCR7 drives leukocyte migration into and within lymph nodes (LNs). It is activated by chemokines CCL19 and CCL21, which are scavenged by the atypical chemokine receptor ACKR4. CCR7-dependent navigation is determined by the distribution of extracellular CCL19 and CCL21, which form concentration gradients at specific microanatomical locations. The mechanisms underpinning the establishment and regulation of these gradients are poorly understood. In this article, we have incorporated multiple biochemical processes describing the CCL19-CCL21-CCR7-ACKR4 network into our model of LN fluid flow to establish a computational model to investigate intranodal chemokine gradients...
August 14, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28804630/protected-cytoskeletal-related-proteins-towards-a-resolution-of-contradictions-regarding-the-role-of-the-cytoskeleton-in-cancer
#16
Daniel T Segarra, John M Yavorski, George Blanck
Initial reports of the role of the cytoskeleton in cancer indicated that tumor cells with a more disorganized cytoskeleton were more tumorigenic. These reports were based on stains for the F-actin cytoskeleton, for example, using phalloidin or anti-F-actin antibody reagents, and gave a basic impression of F-actin-based cytoskeletal integrity. Later developments emphasized the significance of the cytoskeletal elements in cell migration, presumably associated with either basement membrane invasion or metastasis, or both, with several specific proteins implicated in the formation of cell invadopodia...
August 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28804489/normalized-synergy-predicts-that-cd8-co-receptor-contribution-to-t-cell-receptor-tcr-and-pmhc-binding-decreases-as-tcr-affinity-increases-in-human-viral-specific-t-cells
#17
Chad M Williams, Alexandra A Schonnesen, Shu-Qi Zhang, Ke-Yue Ma, Chenfeng He, Tori Yamamoto, S Gail Eckhardt, Christopher A Klebanoff, Ning Jiang
The discovery of naturally occurring T cell receptors (TCRs) that confer specific, high-affinity recognition of pathogen and cancer-associated antigens remains a major goal in cellular immunotherapies. The contribution of the CD8 co-receptor to the interaction between the TCR and peptide-bound major histocompatibility complex (pMHC) has previously been correlated with the activation and responsiveness of CD8(+) T cells. However, these studies have been limited to model systems of genetically engineered hybridoma TCRs or transgenic mouse TCRs against either a single epitope or an array of altered peptide ligands...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28802403/analytical-evaluation-of-quantiferon-plus-and-quantiferon-gold-in-tube-assays-in-subjects-with-or-without-tuberculosis
#18
E Petruccioli, V Vanini, T Chiacchio, G Cuzzi, D M Cirillo, F Palmieri, G Ippolito, D Goletti
The QuantiFERON-TB Gold Plus (QFT-Plus) represents the new QuantiFERON-TB Gold In-tube (QFT-GIT) to identify latent tuberculosis infection (LTBI). The main differences is the addition of a new tube containing shorter peptides stimulating CD8 T-cells. Aim of this study is to evaluate the accuracy of QFT-Plus compared with QFT-GIT in a cross sectional study of individuals with or without tuberculosis (TB). We enrolled 179 participants: 19 healthy donors, 58 LTBI, 33 cured TB and 69 active TB. QFT-Plus and QFT-GIT were performed...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802252/exploiting-radiation-induced-signaling-to-increase-the-susceptibility-of-resistant-cancer-cells-to-targeted-drugs-akt-and-mtor-inhibitors-as-an-example
#19
Iris Eke, Adeola Y Makinde, Molykutty J Aryankalayil, Veit Sandfort, Sanjeewani T Palayoor, Barbara H Rath, Lance Liotta, Mariaelena Pierobon, Emanuel F Petricoin, Matthew F Brown, Jayne M Stommel, Mansoor M Ahmed, C Norman Coleman
Implementing targeted drug therapy in radio-oncologic treatment regimens has greatly improved the outcome of cancer patients. However, the efficacy of molecular targeted drugs such as inhibitory antibodies or small molecule inhibitors essentially depends on target expression and activity, which both can change during the course of treatment. Radiotherapy has previously been shown to activate pro-survival pathways which can help tumor cells to adapt and thereby survive treatment. Therefore, we aimed to identify changes in signaling induced by radiation and evaluate the potential of targeting these changes with small molecules to increase the therapeutic efficacy on cancer cell survival...
August 11, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28802126/derp1-modified-dendritic-cells-attenuate-allergic-inflammation-by-regulating-the-development-of-t-helper-type1-th1-th2-cells-and-regulatory-t-cells-in-a-murine-model-of-allergic-rhinitis
#20
Shaoqing Yu, Bing Han, Shuangxi Liu, Hong Wang, Wenjie Zhuang, Yu Huang, Ruxin Zhang
The CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs) are known to regulate Th2-induced allergic rhinitis (AR). In this study, we evaluated the efficacy of Derp1-modified dendritic cells (DCs) in AR immunotherapy. Derp1 was synthesized and transfected into DCs to generate Derp1-modified DCs. Phenotypes of Derp1-modified DCs were analyzed with flow cytometry using antibodies against DC markers CD11c, CD11b, CD59, CD103 and Toll-like receptor 1(TLR1). Four groups of subject mice were formed; the controls were treated with immature DCs, while the AR mice models were sensitized with Derp1(AR) and treated with DCs(DC-AR) or Derp1-modified DCs (Derp1DC-AR)...
August 9, 2017: Molecular Immunology
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