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https://www.readbyqxmd.com/read/28526681/adoptive-transfer-of-phosphoantigen-specific-%C3%AE-%C3%AE-t-cell-subset-attenuates-mycobacterium-tuberculosis-infection-in-nonhuman-primates
#1
Arwa Qaqish, Dan Huang, Crystal Y Chen, Zhuoran Zhang, Richard Wang, Shengpu Li, Enzhuoa Yang, Yang Lu, Michelle H Larsen, William R Jacobs, Lixia Qian, James Frencher, Ling Shen, Zheng W Chen
The dominant Vγ2Vδ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γδ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M...
May 19, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28526583/the-connexin-43-c-terminus-a-tail-of-many-tales
#2
REVIEW
Edward Leithe, Marc Mesnil, Trond Aasen
Connexins are chordate gap junction channel proteins that, by enabling direct communication between the cytosols of adjacent cells, create a unique cell signalling network. Gap junctional intercellular communication (GJIC) has important roles in controlling cell growth and differentiation and in tissue development and homeostasis. Moreover, several non-canonical connexin functions unrelated to GJIC have been discovered. Of the 21 members of the human connexin family, connexin 43 (Cx43) is the most widely expressed and studied...
May 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28524818/fluorescence-lifetime-imaging-microscopy-reveals-rerouting-of-snare-trafficking-driving-dendritic-cell-activation
#3
Daniëlle Rianne José Verboogen, Natalia González Mancha, Martin Ter Beest, Geert van den Bogaart
SNARE proteins play a crucial role in intracellular trafficking by catalyzing membrane fusion, but assigning SNAREs to specific intracellular transport routes is challenging with current techniques. We developed a novel Förster resonance energy transfer-fluorescence lifetime imaging microscopy (FRET-FLIM)-based technique allowing visualization of real-time local interactions of fluorescently tagged SNARE proteins in live cells. We used FRET-FLIM to delineate the trafficking steps underlying the release of the inflammatory cytokine interleukin-6 (IL-6) from human blood-derived dendritic cells...
May 19, 2017: ELife
https://www.readbyqxmd.com/read/28523947/potentiation-of-trap-6-induced-platelet-dense-granule-release-by-blockade-of-p2y12-signaling-with-mrs2395
#4
Annachiara Mitrugno, Rachel A Rigg, Nicole B Laschober, Anh T P Ngo, Jiaqing Pang, Craig D Williams, Joseph E Aslan, Owen J T McCarty
The release of ADP from platelet dense granules and its binding to platelet P2Y12 receptors is key to amplifying the initial hemostatic response and propagating thrombus formation. P2Y12 has thus emerged as a therapeutic target to safely and effectively prevent secondary thrombotic events in patients with acute coronary syndrome or a history of myocardial infarction. Pharmacological inhibition of P2Y12 receptors represents a useful approach to better understand the signaling mediated by these receptors and to elucidate the role of these receptors in a multitude of platelet hemostatic and thrombotic responses...
May 19, 2017: Platelets
https://www.readbyqxmd.com/read/28523450/a-review-of-the-clinical-pharmacokinetics-pharmacodynamics-and-immunogenicity-of-vedolizumab
#5
REVIEW
Maria Rosario, Nathanael L Dirks, Catherine Milch, Asit Parikh, Michael Bargfrede, Tim Wyant, Eric Fedyk, Irving Fox
Vedolizumab is a humanized anti-α4β7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α4β7-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD), vedolizumab is administered as a 300 mg intravenous infusion. Vedolizumab undergoes a rapid, saturable, non-linear, target-mediated elimination process at low concentrations and a slower, linear, non-specific elimination process at higher concentrations...
May 18, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28523003/hpv16-e7-specific-activated-cd8-t-cells-in-e7-transgenic-skin-and-skin-grafts
#6
Seyed Davoud Jazayeri, Paula T Kuo, Graham Robert Leggatt, Ian H Frazer
Human papillomavirus (HPV) 16 E7 (E7) protein expression in skin promotes epithelial hyperproliferation and transformation to malignancy. Grafts of murine skin expressing E7 protein as a transgene in keratinocytes are not rejected from immunocompetent recipients, whereas grafts expressing ovalbumin (OVA), with or without coexpression of E7 protein, are promptly rejected, demonstrating that E7-associated non-antigen-specific local immunosuppression is not a major determinant of lack of rejection of E7 transgenic skin...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28522593/small-gtpase-rab1b-is-associated-with-atg9a-vesicles-and-regulates-autophagosome-formation
#7
Soichiro Kakuta, Junji Yamaguchi, Chigure Suzuki, Mitsuho Sasaki, Saiko Kazuno, Yasuo Uchiyama
ATG9 is a membrane protein that is essential for autophagy and is considered to be directly involved in the early steps of autophagosome formation. Yeast Atg9 is mainly localized to small vesicles (Atg9 vesicles), whereas mammalian ATG9A is reportedly localized to the trans-Golgi network, the endosomal compartment, and other unidentified membrane structures. To dissect the ATG9A-containing membranes, we examined the subcellular localization of ATG9A and performed immunoisolation of those membranes. ATG9A-green fluorescent protein in human culture cells was observed as numerous puncta that move rapidly throughout the cytoplasm...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28521427/immunoexpression-of-lactoferrin-in-triple-negative-breast-cancer-patients-a-proposal-to-select-a-less-aggressive-subgroup
#8
Antonio Ieni, Valeria Barresi, Luana Licata, Roberta Cardia, Carmine Fazzari, Giuseppe Nuciforo, Francesco Caruso, Michele Caruso, Vincenzo Adamo, Giovanni Tuccari
Triple-negative breast cancer (TNBC) indicates a subset of breast carcinomas that does not express estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). According to the literature, TNBCs are aggressive tumors, characterized by a high incidence of recurrence and a high risk of disease progression. Lactoferrin (LF) is a single-chain, iron-binding glycoprotein of ~700 amino acids, which is involved in a wide range of biological activities, including iron-trafficking and carcinogenesis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521025/mechanism-of-as2o3-induced-action-potential-prolongation-and-using-hips-cms-to-evaluate-the-rescue-efficacy-of-drugs-with-different-rescue-mechanism
#9
Meng Yan, Lifang Feng, Yanhui Shi, Junnan Wang, Yan Liu, Fengmei Li, Baoxin Li
Arsenic trioxide (As2O3) has been verified as a breakthrough in the management of acute promyelocytic leukemia in recent decades. However, cardiotoxicity, especially long QT syndrome (LQTS) has become the most important issue during As2O3 treatment. The characterized mechanisms behind this adverse effect are inhibition of cardiac hERG channel trafficking and increase of cardiac calcium currents. In our study, we found a new pathway underlying As2O3-induced cardiotoxicity that As2O3 accelerates lysosomal degradation of hERG on plasma membrane after using brefeldin A (BFA) to block protein trafficking...
May 17, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28515923/expression-of-cxcr-4-and-ido-in-human-colorectal-cancer-an-immunohistochemical-approach
#10
Masaichi Ogawa, Michiaki Watanabe, Takuo Hasegawa, Kohei Ichihara, Kazuhiko Yoshida, Katsuhiko Yanaga
C-X-C chemokine receptor type 4 (CXCR4), the receptor for the chemokine stromal cell-derived factor (SDF)-1 [also known as C-X-C motif chemokine 12 (CXCL12)], is involved in lymphocyte trafficking. Recent studies have demonstrated that, during pregnancy, a placental enzyme called indoleamine 2, 3-dioxygenase (IDO) exerts a key role in suppressing the maternal T-cell response against the fetus. In the present study, the significance of CXCR4 and IDO expression in human colorectal cancer (CRC) has been investigated by immunohistochemical assay, and their association with survival was analyzed...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28515724/an-analysis-of-trafficking-receptors-shows-that-cd44-and-p-selectin-glycoprotein-ligand-1-collectively-control-the-migration-of-activated-human-t-cells
#11
Amal J Ali, Ayman F Abuelela, Jasmeen S Merzaban
Selectins guide the traffic of activated T-cells through the blood stream by mediating their tethering and rolling onto inflamed endothelium, in this way acting as beacons to help navigate them to sites of inflammation. Here, we present a comprehensive analysis of E-selectin ligands expressed on activated human T-cells. We identified several novel glycoproteins that function as E-selectin ligands. Specifically, we compared the role of P-selectin glycoprotein ligand-1 (PSGL-1) and CD43, known E-selectin ligands, to CD44, a ligand that has not previously been characterized as an E-selectin ligand on activated human T-cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28515229/unique-cell-biological-profiles-of-retinal-disease-causing-missense-mutations-in-the-polarity-protein-crumbs
#12
Milena Pellikka, Ulrich Tepass
Mutations in human CRB1 are a major cause of retinal disease that lead to blindness. CRB1 is a transmembrane protein found in the inner segment of photoreceptor cells (PRCs) and the apical membrane of Müller glia. The function of the extracellular region of CRB1 is poorly understood although more than 80 disease-causing missense mutations have been mapped to it. We have recreated four mutations in Drosophila Crumbs (Crb) that affect different extracellular domains. Crb regulates epithelial polarity and growth, and contributes to PRC differentiation and survival...
May 17, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28514713/pattern-recognition-receptors-and-coordinated-cellular-pathways-involved-in-tuberculosis-immunopathogenesis-emerging-concepts-and-perspectives
#13
REVIEW
Abhishek Mishra, Shamim Akhtar, Chinnaswamy Jagannath, Arshad Khan
Pattern Recognition Receptors (PRRs) play a central role in the recognition of numerous pathogens, including Mycobacterium tuberculosis, resulting in activation of innate and adaptive immune responses. Besides Toll Like Receptors, C-type Lectin Receptors and Nod Like Receptors are now being recognized for their involvement in inducing immune response against M. tuberculosis infection. Although, a functional redundancy of the PRRs has also been reported in many studies, emerging evidences support the notion that a cooperative and coordinated response generated by these receptors is critical to sustain the full immune control of M...
May 14, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28512289/a-genetic-screen-in-combination-with-biochemical-analysis-in-saccharomyces-cerevisiae-indicates-that-phenazine-1-carboxylic-acid-is-harmful-to-vesicular-trafficking-and-autophagy
#14
Xiaolong Zhu, Yan Zeng, Xiu Zhao, Shenshen Zou, Ya-Wen He, Yongheng Liang
The environmentally friendly antibiotic phenazine-1-carboxylic acid (PCA) protects plants, mammals and humans effectively against various fungal pathogens. However, the mechanism by which PCA inhibits or kills fungal pathogens is not fully understood. We analyzed the effects of PCA on the growth of two fungal model organisms, Saccharomyces cerevisiae and Candida albicans, and found that PCA inhibited yeast growth in a dose-dependent manner which was inversely dependent on pH. In contrast, the commonly used antibiotic hygromycin B acted in a dose-dependent manner as pH increased...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507811/adoptive-natural-killer-cell-therapy-is-effective-in-reducing-pulmonary-metastasis-of-ewing-sarcoma
#15
Alexander A Tong, Hasan Hashem, Saada Eid, Frederick Allen, Daniel Kingsley, Alex Y Huang
The survival of patients with metastatic or relapsed Ewing sarcoma (ES) remains dismal despite intensification of combination chemotherapy and radiotherapy, precipitating the need for novel alternative therapies with minimal side effects. Natural killer (NK) cells are promising additions to the field of cellular immunotherapy. Adoptive NK cell therapy has shown encouraging results in hematological malignancies. Despite these initial promising successes, however, NK cell therapy for solid tumors remains to be investigated using in vivo tumor models...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28506987/development-of-the-larval-lymphatic-system-in-the-zebrafish
#16
Hyun Min Jung, Daniel Castranova, Matthew R Swift, Van N Pham, Marina Venero Galanternik, Sumio Isogai, Matthew G Butler, Timothy S Mulligan, Brant M Weinstein
The lymphatic vascular system is a hierarchically organized complex network essential for tissue fluid homeostasis, immune trafficking, and absorption of dietary fats in the human body. Despite its importance, the assembly of the lymphatic network is still not fully understood. The zebrafish is a powerful model organism that enables study of lymphatic vessel development using high-resolution imaging and sophisticated genetic and experimental manipulation. Although several studies have described early lymphatic development in the fish, lymphatic development at later stages has not been completely elucidated...
May 15, 2017: Development
https://www.readbyqxmd.com/read/28500977/endocytosis-and-intracellular-traffic-of-cholesterol-pdmaema-liposome-complexes-in-human-epithelial-like-cells
#17
F Szymanowski, A A Hugo, P Alves, P N Simões, A Gómez-Zavaglia, Pablo F Pérez
Liposomes are generally used as delivery systems, as they are capable of encapsulating a wide variety of molecules (i.e. plasmids, recombinant proteins, therapeutic drugs). However, liposomal drug delivery have to fulfill different requirements, such as the effective internalization by the target cells and avoidance of the degradative activity of the intracellular compartments. The use of polymer lipid complexes (PLCs), by including different polymers in the liposome formulation, could improve internalization and intracellular release of drugs...
May 1, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28498392/the-flightless-i-protein-interacts-with-rna-binding-proteins-and-is-involved-in-the-genome-wide-mrna-post-transcriptional-regulation-in-lung-carcinoma-cells
#18
Cuihua Wang, Kezhi Chen, Shengyou Liao, Wei Gu, Xinlei Lian, Jing Zhang, Xuejuan Gao, Xiaohui Liu, Tong Wang, Qing-Yu He, Gong Zhang, Langxia Liu
The flightless I protein (FLII) belongs to the gelsolin family. Its function has been associated with actin remodeling, embryonic development, wound repair, and more recently with cancer. The structure of FLII is characterized by the N-terminal leucine-rich repeats (LRR) and C-terminal gesolin related repeated units that are both protein-protein inter-action domains, suggesting that FLII may exert its function by interaction with other proteins. Therefore, systematic study of protein interactions of FLII in cells is important for the understanding of FLII functions...
May 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28498321/bdnf-binds-its-pro-peptide-with-high-affinity-and-the-common-val66met-polymorphism-attenuates-the-interaction
#19
Koichi Uegaki, Haruko Kumanogoh, Toshiyuki Mizui, Takatsugu Hirokawa, Yasuyuki Ishikawa, Masami Kojima
Most growth factors are initially synthesized as precursors then cleaved into bioactive mature domains and pro-domains, but the biological roles of pro-domains are poorly understood. In the present study, we investigated the pro-domain (or pro-peptide) of brain-derived neurotrophic factor (BDNF), which promotes neuronal survival, differentiation and synaptic plasticity. The BDNF pro-peptide is a post-processing product of the precursor BDNF. Using surface plasmon resonance and biochemical experiments, we first demonstrated that the BDNF pro-peptide binds to mature BDNF with high affinity, but not other neurotrophins...
May 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28495999/%C3%AE-arrestin-mediated-regulation-of-the-human-ether-a-go-go-related-gene-herg-potassium-channel
#20
Matthew G Sangoi, Shawn M Lamothe, Jun Guo, Tonghua Yang, Wentao Li, Ellen G Avery, John T Fisher, Shetuan Zhang
The rapidly activating delayed rectifier K(+) channel (IKr) is encoded by the human ether-a-go-go-related gene (hERG), which is important for the repolarization of the cardiac action potential. Mutations in hERG or drugs can impair the function or decrease the expression level of hERG channels, leading to long QT syndrome (LQTS). Thus, it is important to understand hERG channel trafficking and its regulation. For this purpose, G protein-coupled receptors (GPCRs), which regulate a vast array of cellular processes, represent a useful route...
May 11, 2017: Molecular Pharmacology
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