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https://www.readbyqxmd.com/read/30006682/chlorogenic-acid-prevents-ampa-mediated-excitotoxicity-in-optic-nerve-oligodendrocytes-through-a-pkc-and-caspase-dependent-pathways
#1
Olfa Rebai, Mohamed Amri
In the CNS, including the optic nerve, oligodendrocytes play a critical role in the myelination of axons. Oligodendrocytes are exceptionally sensitive to insults to the CNS, such as injury, ischemia, or inflammation, which result in the loss of oligodendrocytes and myelin and eventually secondary axon degeneration. Oligodendrocytes are sensitive to excitotoxic insults mediated by overactivation of their AMPA ionotropic glutamate receptors. Phenolic compounds, which are widely distributed in fruits and vegetables, received the great attention of scientists due to their antioxidant activities and free radical scavenging abilities...
July 13, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/30006544/hhex-is-a-transcriptional-regulator-of-the-vegfc-flt4-prox1-signaling-axis-during-vascular-development
#2
Sébastien Gauvrit, Alethia Villasenor, Boris Strilic, Philip Kitchen, Michelle M Collins, Rubén Marín-Juez, Stefan Guenther, Hans-Martin Maischein, Nana Fukuda, Maurice A Canham, Joshua M Brickman, Clifford W Bogue, Padma-Sheela Jayaraman, Didier Y R Stainier
Formation of the lymphatic system requires the coordinated expression of several key regulators: vascular endothelial growth factor C (VEGFC), its receptor FLT4, and a key transcriptional effector, PROX1. Yet, how expression of these signaling components is regulated remains poorly understood. Here, using a combination of genetic and molecular approaches, we identify the transcription factor hematopoietically expressed homeobox (HHEX) as an upstream regulator of VEGFC, FLT4, and PROX1 during angiogenic sprouting and lymphatic formation in vertebrates...
July 13, 2018: Nature Communications
https://www.readbyqxmd.com/read/30006485/the-oncometabolite-d-2-hydroxyglutarate-is-an-intercellular-mediator-in-idh-mutant-gliomas-that-inhibits-both-complement-and-t-cells
#3
Lingjun Zhang, Mia Sorensen, Bjarne W Kristensen, Guido Reifenberger, Thomas M McIntyre, Feng Lin
PURPOSE: Somatic mutations in the isocitrate dehydrogenase (IDH)-1 and -2 genes are remarkably penetrant in diffuse gliomas. These highly effective gain-of-function mutations enable mutant IDH to efficiently metabolize isocitrate to D-2-hydroxyglutarate (D 2-HG) that accumulates to high concentrations within the tumor microenvironment. D 2-HG is an intracellular effector that promotes tumor growth through widespread epigenetic changes in IDH mutant tumor cells, but its potential role as an intercellular immune regulator remains understudied...
July 13, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/30006481/apoptosis-signal-regulating-kinase-1-ask1-inhibition-attenuates-human-airway-smooth-muscle-growth-and-migration-in-chronic-obstructive-pulmonary-disease-copd
#4
Mathew S Eapen, Anudeep Kota, Howard Vindin, Kielan D McAlinden, Dia Xenaki, Brian G Oliver, Deepak A Deshpande, Sukhwinder Singh Sohal, Pawan Sharma
Increased airway smooth muscle (ASM) mass is observed in COPD which is correlated with disease severity and negatively impact lung function. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase kinase kinase  activated by various stress stimuli, including reactive oxygen species, tumor necrosis factor-α, and lipopolysaccharide and is known to regulate cell proliferation...
July 13, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/30006392/-neospora-caninum-dense-granule-protein-7-regulates-pathogenesis-of-neosporosis-by-modulating-host-immune-response
#5
Yoshifumi Nishikawa, Naomi Shimoda, Ragab M Fereig, Tomoya Moritaka, Kousuke Umeda, Maki Nishimura, Fumiaki Ihara, Kaoru Kobayashi, Yuu Himori, Yutaka Suzuki, Hidefumi Furuoka
Neospora caninum is a protozoan parasite closely related to Toxoplasma gondii Neosporosis caused by N. caninum is considered one of the main causes of abortion in cattle and nervous-system dysfunction in dogs, and identification of the virulence factors of this parasite is important for the development of control measures. Here, we used a luciferase reporter assay to screen the dense granule proteins genes of N. caninum , and found that NcGRA6, NcGRA7, and NcGRA14 are involved in the activation of the NF-κB, calcium/calcineurin, and cAMP/PKA signals...
July 13, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/30006385/protein-kinase-a-mediated-phosphorylation-of-serine-357-of-the-mouse-prostacyclin-receptor-regulates-its-coupling-to-g-s-to-g-i-and-to-g-q-coupled-effector-signaling
#6
Orlaith A Lawler, Sinead M Miggin, B Therese Kinsella
No abstract text is available yet for this article.
July 13, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30006377/effector-t-cell-resistance-to-suppression-and-stat3-signaling-during-the-development-of-human-type-1-diabetes
#7
Emmi-Leena Ihantola, Tyyne Viisanen, Ahmad M Gazali, Kirsti Näntö-Salonen, Auni Juutilainen, Leena Moilanen, Reeta Rintamäki, Jussi Pihlajamäki, Riitta Veijola, Jorma Toppari, Mikael Knip, Jorma Ilonen, Tuure Kinnunen
Dysregulation of regulatory T cell (Treg)-mediated suppression and, in particular, resistance of CD4+ effector T cells (Teffs) to suppression have been implicated in the pathogenesis of human type 1 diabetes (T1D). However, the mechanistic basis behind this resistance and the time frame during which it develops in relation to the onset of clinical T1D remain unclear. In this study, we analyzed the capacity of peripheral blood Teffs isolated both from patients with T1D and from prediabetic at-risk subjects positive for multiple diabetes-associated autoantibodies (AAb+ ) to be suppressed by Tregs...
July 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/30006139/ethnic-variation-in-the-incidence-of-biliary-atresia-correlates-with-the-frequency-of-the-most-prevalent-haplotype-in-its-population
#8
Toshihiro Muraji, Hidenori Tanaka, Satoshi Ieiri
The cause of biliary atresia (BA) remains an enigma. However, an ethnic diversity in the incidence of BA is so unique that anthropological approach may provide some etiopathogenetic implications in the disease mechanism. We previously reported that an association of maternal microchimerism (MMc) in BA and a significant compatibility of HLA-A between the patient with BA and their mother. Acrossthe 10 countries (Japan, South Korea, Taiwan, Philippines, New Zealand (Maori population), UK, France, Germany, Norway, and Sweden), we determined the frequency of the most prevalentHLA haplotypes of each country from Allele Frequency Database and found that it was significantly correlated with the incidence of BA of the respective country (p =0...
July 10, 2018: Human Immunology
https://www.readbyqxmd.com/read/30005862/pathogenic-role-of-tissue-resident-memory-t-cells-in-autoimmune-diseases
#9
REVIEW
Haijing Wu, Wei Liao, Qianwen Li, Hai Long, Heng Yin, Ming Zhao, Vera Chan, Chak-Sing Lau, Qianjin Lu
The tissue-resident memory T (TRM ) cells constitute a newly identified subset of memory T cells which are non-circulating and they persist for long-term in epithelial barrier tissues, including skin, lung, gastrointestinal tract and reproductive tract, and in non-barrier tissues, including brain, kidney, pancreas and joint. These cells provide rapid on-site immune protection against previous exposed pathogens in peripheral tissues. There cells are transcriptionally, functionally and phenotypically distinguished from circulating effector memory T cells...
July 10, 2018: Autoimmunity Reviews
https://www.readbyqxmd.com/read/30004799/the-role-of-inflammatory-cytokines-in-creating-t-cell-exhaustion-in-cancer
#10
Milad Sabzevary-Ghahfarokhi, Hedayatollah Shirzad, Mahmoud Rafieian-Kopaei, Mahdi Ghatreh-Samani, Mojtaba Shohan
Secreted inflammatory cytokines are considered as critical mediators in the tumor microenvironment. Cancer cells play a significant role in the differentiation of effector T cells to exhausted T cells through mediator production. Effector T cells that undergo tumor microenvironment become terminally differentiated into exhausted T cells. These changes create an opportunity for tumorigenesis and invasion of cancer cells. Despite having some characteristics of effector T cells, the exhausted T cells lose their antitumor properties...
July 13, 2018: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/30004298/increased-rho-kinase-activity-in-patients-with-heart-ischemia-reperfusion
#11
Juan Zhang, Fei Xu, Xiao-Bo Liu, Shao-Jie Bi, Qing-Hua Lu
BACKGROUND/AIM: Rho kinase is a downstream effector of Rho GTPase that is known to regulate various pathological processes. The aim of this study was to evaluate the regulation of Rho kinase activity in leukocytes in patients with ischemia/reperfusion (I/R) injury. PATIENTS AND METHODS: We investigated 38 patients with acute ST-segment elevation myocardial infarction (STEMI), 26 patients with atherosclerosis (AS) and 22 normal subjects. All patients underwent coronary angiography (CAG) and all STEMI patients received primary percutaneous coronary intervention (PPCI) of the left anterior descending artery (LAD) within 12 h after chest pain on-set...
July 1, 2018: Perfusion
https://www.readbyqxmd.com/read/30004239/proteomics-reveals-rictor-as-a-non-canonical-tgfb-signaling-target-during-aneurysm-progression-in-marfan-mice
#12
Sarah J Parker, Aleksandr Stotland, Elena MacFarlane, Nicole Wilson, Amanda Orosco, Vidya Venkatraman, Kyle Madrid, Roberta A Gottlieb, Harry C Dietz, Jennifer E Van Eyk
OBJECTIVE: To (1) analyze the ascending aortic proteome within a mouse model of MFS (Fbn1C1041G/+ ) at early and late stages of aneurysm and subsequently to (2) test a novel hypothesis formulated based on this unbiased proteomic screen that links changes in integrin composition to TGFβ-dependent activation of the Rapamycin-Independent Component of TOR (Rictor) signaling pathway. Approach & Results. Ingenuity pathway analysis of over 1000 proteins quantified from in vivo MFS mouse aorta by data independent acquisition mass-spectrometry revealed a predicted upstream regulator, Rictor, that was selectively activated in aged MFS mice...
July 13, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/30003607/diacylglycerol-acyltransferase-1-is-activated-by-phosphatidate-and-inhibited-by-snrk1-catalyzed-phosphorylation
#13
Kristian Mark P Caldo, Wei Shen, Yang Xu, Linda Hanley-Bowdoin, Guanqun Chen, Randall Weselake, M Joanne Lemieux
Diacylglycerol acyltransferase 1 catalyzes the final and committed step in the Kennedy pathway for triacylglycerol (TAG) biosynthesis, and as such, elucidating its mode of regulation is critical to understand the fundamental aspects of carbon metabolism in oleaginous crops. In this study, purified Brassica napus diacylglycerol acyltransferase 1 (BnaDGAT1) in n-dodecyl-β-D-maltopyranoside micelles was lipidated to form mixed micelles and subjected to detailed biochemical analysis. The degree of mixed micelle fluidity appeared to influence acyltransferase activity...
July 13, 2018: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/30003499/gastrointestinal-manifestations-of-hypereosinophilic-syndromes-and-mast-cell-disorders-a-comprehensive-review
#14
REVIEW
Vivian C Nanagas, Anna Kovalszki
Hypereosinophilic syndrome and mastocytosis are relatively rare proliferative diseases encountered in the general population. However, allergists frequently consider these disorders in the differential of patients presenting with gastrointestinal, pulmonary, cutaneous, and allergic symptoms. Gastrointestinal symptoms are some of the most frequent and/or debilitating aspects of both disease states and in many cases lead to poor quality of life and functional limitation for the patient. They are the third most common clinical manifestation in hypereosinophilic syndrome and have been found to be the most distressful aspect of the disorder in those with systemic mastocytosis...
July 12, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/30003123/enteropathogenic-escherichia-coli-esph-mediated-rho-gtpase-inhibition-results-in-desmosomal-perturbations
#15
Jennifer Lising Roxas, Ross Calvin Monasky, Bryan Angelo P Roxas, Al B Agellon, Asad Mansoor, James B Kaper, Gayatri Vedantam, V K Viswanathan
Background & Aims: The diarrheagenic pathogen, enteropathogenic Escherichia coli (EPEC), uses a type III secretion system to deliver effector molecules into intestinal epithelial cells (IECs). While exploring the basis for the lateral membrane separation of EPEC-infected IECs, we observed infection-induced loss of the desmosomal cadherin desmoglein-2 (DSG2). We sought to identify the molecule(s) involved in, and delineate the mechanisms and consequences of, EPEC-induced DSG2 loss...
2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/30003059/effect-of-caspases-and-rankl-induced-by-heavy-force-in-orthodontic-root-resorption
#16
Yukari Minato, Masaru Yamaguchi, Mami Shimizu, Jun Kikuta, Takuji Hikida, Momoko Hikida, Masaaki Suemitsu, Kayo Kuyama, Kazutaka Kasai
Objective: Orthodontic root resorption (ORR) due to orthodontic tooth movement is a difficult treatment-related adverse event. Caspases are important effector molecules for apoptosis. At present, little is known about the mechanisms underlying ORR and apoptosis in the cementum. The aim of the present in vivo study was to investigate the expression of tartrate-resistant acid phosphatase (TRAP), caspase 3, caspase 8, and receptor activator of nuclear factor kappa-B ligand (RANKL) in the cementum in response to a heavy or an optimum orthodontic force...
July 2018: Korean Journal of Orthodontics
https://www.readbyqxmd.com/read/30002268/ultrafast-dynamics-driven-biomolecular-recognition-where-fast-activities-dictate-slow-events
#17
Priya Singh, Damayanti Bagchi, Samir Kumar Pal
In general, biological macromolecules require significant dynamical freedom to carry out their different functions, including signal transduction, metabolism, catalysis and gene regulation. Effectors (ligands, DNA and external milieu, etc) are considered to function in a purely dynamical manner by selectively stabilizing a specific dynamical state, thereby regulating biological function. In particular, proteins in presence of these effectors can exist in several dynamical states with distinct binding or enzymatic activity...
July 2018: Journal of Biosciences
https://www.readbyqxmd.com/read/30002193/tumor-suppressor-activity-of-selenbp1-a-direct-nkx2-1-target-in-lung-adenocarcinoma
#18
Deborah Ruth Caswell, Chen-Hua Chuang, Rosanna K Ma, Ian P Winters, Eric L Snyder, Monte M Winslow
The Nkx2-1 transcription factor in lung epithelial lineages promotes differentiation and suppresses malignant progression of lung adenocarcinoma. However, targets of Nkx2-1 that limit tumor growth and progression remain incompletely understood. Here, direct Nkx2-1 targets are identified whose expression correlates with Nkx2-1 activity in human lung adenocarcinoma. Selenium binding protein 1 (Selenbp1), an Nkx2-1 effector that limits phenotypes associated with lung cancer growth and metastasis, was investigated further...
July 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/30001906/caspase-1-3-8-and-antioxidant-enzyme-genes-are-key-molecular-effectors-following-vibrio-parahaemolyticus-and-aeromonas-veronii-infection-in-fish-leukocytes
#19
Martha Reyes-Becerril, Veronica Sanchez, Karen Delgado, Kevyn Guerra, Esteban Velazquez, Felipe Ascencio, Carlos Angulo
Caspases are a family of proteases involved in many important biological processes including apoptosis and inflammation. In order to get insights into the caspase gene family and antioxidant enzymes in Totoaba macdonaldi during bacterial infection, an in vitro assay was performed involving three different types of caspases (Casp-1, Casp-3 and Casp-8) and antioxidant enzymes (catalase, gluthathione peroxidase 1 and 4) after Vibrio parahaemolyticus and Aeromonas veronii infection, using head-kidney and spleen leukocytes from the teleost fish totoaba at 12 and 24 h post-exposure...
July 4, 2018: Immunobiology
https://www.readbyqxmd.com/read/30001524/malaria-vaccines-recent-advances-and-new-horizons
#20
REVIEW
Simon J Draper, Brandon K Sack, C Richter King, Carolyn M Nielsen, Julian C Rayner, Matthew K Higgins, Carole A Long, Robert A Seder
The development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum and P. vivax remains a key priority. Decades of endeavor have taught that achieving this goal will be challenging; however, recent innovation in malaria vaccine research and a diverse pipeline of novel vaccine candidates for clinical assessment provides optimism. With first-generation pre-erythrocytic vaccines aiming for licensure in the coming years, it is important to reflect on how next-generation approaches can improve on their success...
July 11, 2018: Cell Host & Microbe
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