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Yulei Zhao, Tess Montminy, Taha Azad, Elizabeth Lightbody, Yawei Hao, Sandip SenGupta, Eric Asselin, Christopher Jb Nicol, Xiaolong Yang
Breast cancer (BC) is a leading cause of death in women worldwide. Active mutations of PI3K catalytic subunit PIK3CA (e.g., H1047R) and amplification of its homolog PIK3CB occur in many BC cases. In recent years, activation of the Transcriptional coactivator with PDZ binding motif (TAZ) and its paralog Yes-associated protein (YAP) have been found to be important for BC development and progression. However, there is no evidence that PI3K interacts with YAP/TAZ in mammary tumorigenesis. Using a systematic gain-of-function screen for kinases involved in mammary tumorigenesis, PIK3CB was identified as a transformation inducing kinase...
March 15, 2018: Molecular Cancer Research: MCR
Li-Na Wang, Mei-Hua Gao, Bing Wang, Bei-Bei Cong, Shu-Chao Zhang
Cluster of differentiation 59 (CD59) is a glycosylphosphatidylinositol-anchored protein. Cross-linking of CD59 with specific monoclonal antibodies can cause a series of intracellular signal transduction events. However, the underlying molecular mechanisms are poorly understood. Linker for activation of T-cells (LAT) is a crucial adaptor protein in T-cell signaling, and its phosphorylation and palmitoylation are essential for its localization and function. In a previous study by the present authors, it was demonstrated that CD59 may be responsible for LAT palmitoylation, thereby regulating T-cell signal transduction...
April 2018: Oncology Letters
T Azad, H J Janse van Rensburg, E D Lightbody, B Neveu, A Champagne, A Ghaffari, V R Kay, Y Hao, H Shen, B Yeung, B A Croy, K L Guan, F Pouliot, J Zhang, C J B Nicol, X Yang
The Hippo pathway is a central regulator of tissue development and homeostasis, and has been reported to have a role during vascular development. Here we develop a bioluminescence-based biosensor that monitors the activity of the Hippo core component LATS kinase. Using this biosensor and a library of small molecule kinase inhibitors, we perform a screen for kinases modulating LATS activity and identify VEGFR as an upstream regulator of the Hippo pathway. We find that VEGFR activation by VEGF triggers PI3K/MAPK signaling, which subsequently inhibits LATS and activates the Hippo effectors YAP and TAZ...
March 13, 2018: Nature Communications
Katrin Schelleckes, Boris Schmitz, Malte Lenders, Mirja Mewes, Stefan-Martin Brand, Eva Brand
KIBRA has been suggested as a key regulator of the hippo pathway, regulating organ size, cell contact inhibition as well as tissue regeneration and tumorigenesis. Recently, alterations of KIBRA expression caused by promotor methylation have been reported for several types of cancer. Our current study aimed to design an artificial transcription factor capable of re-activating expression of the tumor suppressor KIBRA and the hippo pathway. We engineered a new gene named 'ZFP226' encoding for a ~23 kDa fusion protein...
March 9, 2018: Scientific Reports
Benjamin Yeung, Prem Khanal, Virja Mehta, Laura Trinkle-Mulcahy, Xiaolong Yang
The Hippo pathway is a signalling cascade that plays important roles in organ size control, tumorigenesis, metastasis, stress response, stem cell differentiation and renewal during development and tissue homeostasis, and mechanotransduction. Recently, we and others have shown that loss of the Hippo pathway core component LATS or overexpression of its downstream targets YAP and its paralog TAZ causes resistance of cancer cells to anti-tubulin drugs. However, YAP and TAZ mediates anti-tubulin drug-induced apoptosis independent of its upstream regulator LATS and the Hippo pathway...
March 9, 2018: Molecular Cancer Research: MCR
Murray B Stein, Michael J McCarthy, Chia-Yen Chen, Sonia Jain, Joel Gelernter, Feng He, Steven G Heeringa, Ronald C Kessler, Matthew K Nock, Stephan Ripke, Xiaoying Sun, Gary H Wynn, Jordan W Smoller, Robert J Ursano
Insomnia is a worldwide problem with substantial deleterious health effects. Twin studies have shown a heritable basis for various sleep-related traits, including insomnia, but robust genetic risk variants have just recently begun to be identified. We conducted genome-wide association studies (GWAS) of soldiers in the Army Study To Assess Risk and Resilience in Servicemembers (STARRS). GWAS were carried out separately for each ancestral group (EUR, AFR, LAT) using logistic regression for each of the STARRS component studies (including 3,237 cases and 14,414 controls), and then meta-analysis was conducted across studies and ancestral groups...
March 8, 2018: Molecular Psychiatry
D H Costa-Rezende, G L Robledo, A Góes-Neto, M A Reck, E Crespo, E R Drechsler-Santos
Ganodermataceae is a remarkable group of polypore fungi, mainly characterized by particular double-walled basidiospores with a coloured endosporium ornamented with columns or crests, and a hyaline smooth exosporium. In order to establish an integrative morphological and molecular phylogenetic approach to clarify relationship of Neotropical Amauroderma within the Ganodermataceae family, morphological analyses, including scanning electron microscopy, as well as a molecular phylogenetic approach based on one (ITS) and four loci (ITS-5...
December 2017: Persoonia
Babak Alikhani, Tobias Getzin, Till Frederik Kaireit, Kristina Imeen Ringe, Leila Jamali, Frank Wacker, Thomas Werncke, Hans-Jürgen Raatschen
PURPOSE: The aim of this investigation is to establish the relationship between the size-dependent conversion factor (fsize ) and the body-mass-index (BMI) and to test whether BMI can be substituted for the conventionally used patients' anterior-posterior (AP) and lateral (LAT) dimensions for calculation of fsize . By calculating fsize on the basis of BMI instead of the AP and LAT measurements, size-specific dose estimates (SSDE) could be determined prior to image acquisition. METHODS: Our institute utilizes a dose monitoring software to record radiation exposure during CT examinations...
March 2018: European Journal of Radiology
Dhong Hyun Lee, Homayon Ghiasi
We found previously that altering macrophage polarization toward M2 responses by injection of colony stimulating factor-1 (CSF-1) was more effective in reducing both primary and latent infection in HSV-1 ocularly infected mice than M1 polarization by IFN-γ injection. Cytokines can coordinately regulate macrophage and TH responses, with IL-4 inducing TH 2 as well as M2 responses and IFN-γ inducing TH 1 as well as M1 responses. We have now differentiated the contributions of these immune compartments on protection against latency/reactivation and corneal scarring by comparing the effects of infection with recombinant HSV-1 in which the latency associated transcript (LAT) gene was replaced with either the IL-4 (HSV-IL-4) or IFN-γ (HSV-IFN-γ) genes using infection with the parental (LAT-negative) virus as a control...
February 28, 2018: Journal of Virology
Apoorva Verma, Fan Jing-Song, Megan L Finch-Edmondson, Adrian Velazquez-Campoy, Shanker Balasegaran, Marius Sudol, Jayaraman Sivaraman
YES-associated protein (YAP) is a major effector protein of the Hippo tumor suppressor pathway, and is phosphorylated by the serine/threonine kinase LATS. Their binding is mediated by the interaction between WW domains of YAP and PPxY motifs of LATS. Their isoforms, YAP2 and LATS1 contain two WW domains and two PPxY motifs respectively. Here, we report the study of the interaction of these domains both in vitro and in human cell lines, to better understand the mechanism of their binding. We show that there is a reciprocal binding preference of YAP2-WW1 with LATS1-PPxY2, and YAP2-WW2 with LATS1-PPxY1...
January 30, 2018: Oncotarget
Giorgia Sollai, Maurizio Biolchini, Roberto Crnjar
On the island of Sardinia the lepidopteran Papilio hospiton uses Ferula communis as exclusive host-plant. However, on the small island of Tavolara, adult females lay eggs on Seseli tortuosum, a plant confined to the island. When raised in captivity on Seseli only few larvae grew beyond the first-second instar. Host specificity of lepidopterans is determined by female oviposition preferences, but also by larval food acceptance, and adult and larval taste sensitivity may be related to host selection in both cases...
February 27, 2018: Insect Science
Yu Saito, Shota Moriya, Hiromi Kazama, Kazuhiro Hirasawa, Kana Miyahara, Hiroko Kokuba, Hirotsugu Hino, Hiroyuki Kikuchi, Naoharu Takano, Masaki Hiramoto, Kiyoaki Tsukahara, Keisuke Miyazawa
The maintenance of the intracellular level of amino acids is crucial for cellular homeostasis. This is carried out via the regulation of both the influx from the extracellular environment and the recycling of intracellular resources. Since epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, including gefitinib (GEF) have been reported to induce the apoptosis of several cancer cell lines, in the present study, we examined whether the cytotoxic effects of GEF are further enhanced under amino acid starvation (AAS) culture conditions...
February 23, 2018: International Journal of Oncology
Sheryll Lat, Wendy Mashlan, Susan Heffey, Bridie Jones
Sepsis is a common condition caused by the body's immune and coagulation systems being 'switched on' by the presence of infection, either through bacteria or viruses in the blood. If untreated, sepsis can be life-threatening and is a leading cause of death in hospital patients worldwide. However, awareness of sepsis is low. This article provides an overview of the important role played by nurses in acute hospital settings in the early identification and treatment of suspected sepsis in frail older patients, and in escalating the care and management of deteriorating patients...
February 26, 2018: Nursing Older People
Julijana Trifković, Ljubomir Jovanović, Miloje Đurić, Snežana Stevanović-Đorđević, Svetlana Milanović, Miodrag Lazarević, Željko Sladojević, Danijela Kirovski
Season may affect calves' thermal comfort and behavior, but the data related to the overall influence of seasonal variations on dams' colostrum and postnatal adaptive capability of calves are limited. The aim of this study was to measure the effects of a 49-day-long low air temperature (LAT) season (5.20 ± 0.46 °C mean air temperature) and a 53-day-long high air temperature (HAT) season (27.40 ± 0.39 °C mean air temperature) on dams' colostrum quality and physiological, biochemical, hormonal, and oxidative stress parameters of their calves during the first 7 days of life...
February 26, 2018: International Journal of Biometeorology
J Fedida, T Strisciuglio, M Sohal, M Wolf, K Van Beeumen, A Neyrinck, P Taghji, C Lepiece, A Almorad, Y Vandekerckhove, R Tavernier, M Duytschaever, S Knecht
PURPOSE: Catheter ablation is an effective treatment for premature ventricular complexes (PVCs). Activation mapping is accurate but requires PVCs at the time of the ablation. Pace-mapping correlation (PMC) is a supplemental tool recently developed as an integrated module for an electro-anatomical mapping platform. Our study sought to investigate whether pace-mapping technology provides similar ablation results in patients with low versus high idiopathic PVC burden at the time of ablation and the relationship between sites with the highest PMC and the earliest local activation time (LAT)...
February 24, 2018: Journal of Interventional Cardiac Electrophysiology: An International Journal of Arrhythmias and Pacing
Trevor Stack, Amir Vahabikashi, Mark Johnson, Evan Scott
Increased stiffness of Schlemm's canal endothelial cells (SC cells) is a major contributing factor to the increased pressure characteristic of primary open-angle glaucoma. New treatments for glaucoma are being developed using actin depolymerizers and rho kinase inhibitors to address this increased stiffness. However, these agents have off-target effects and are not as potent as had been hoped. We have developed a micellar nanocarrier assembled from poly(ethylene glycol)-bl-poly(propylene sulfide) copolymers capable of encapsulating latrunculin A (Lat A) with the goal of modulating SC cell stiffness...
February 22, 2018: Journal of Biomedical Materials Research. Part A
Fang-Zhou Liu, Hong-Tao Liao, Wei-Dong Lin, Yu-Mei Xue, Xian-Zhang Zhan, Xian-Hong Fang, Fang Rao, Hai Deng, Jun Huang, Jo-Jo Hai, Hung-Fat Tse, Shu-Lin Wu
OBJECTIVES: To investigate the relationship between hyperuricemia and left atrial thrombus (LAT)/spontaneous echo contrast (SEC) and to determine the predictive value of hyperuricemia in non-valvular (NV) atrial fibrillation (AF) patients. METHODS: The study retrospectively reviewed 1198 consecutive patients (male 801, female 397, and mean age of 56.84 ± 12.22) who were diagnosed with AF and accepted transesophageal echocardiography (TEE) prior to catheter ablation, appendage occlusion and electrical cardioversion using a single-center database...
February 2, 2018: International Journal of Cardiology
Robert Häsler, Christian Kautz, Ateequr Rehman, Rainer Podschun, Volker Gassling, Pius Brzoska, Jon Sherlock, Jan-Thorsten Gräsner, Gesine Hoppenstedt, Sabine Schubert, Astrid Ferlinz, Wolfgang Lieb, Matthias Laudes, Femke-Anouska Heinsen, Jens Scholz, Dag Harmsen, Andre Franke, Swantje Eisend, Thomas Kunze, Helmut Fickenscher, Stephan Ott, Philip Rosenstiel, Stefan Schreiber
BACKGROUND: Multidrug-resistant bacteria represent a substantial global burden for human health, potentially fuelled by migration waves: in 2015, 476,649 refugees applied for asylum in Germany mostly as a result of the Syrian crisis. In Arabic countries, multiresistant bacteria cause significant problems for healthcare systems. Currently, no data exist describing antibiotic resistances in healthy refugees. Here, we assess the microbial landscape and presence of antibiotic resistance genes (ARGs) in refugees and German controls...
February 20, 2018: Microbiome
Mikel M Arbulo-Echevarria, Isaac Narbona-Sánchez, Cecilia M Fernandez-Ponce, Inmaculada Vico-Barranco, Mª Dolores Rueda-Ygueravide, Michael L Dustin, Arkadiusz Miazek, Mª Carmen Duran-Ruiz, Francisco García-Cózar, Enrique Aguado
The adaptor protein linker for activation of T cells (LAT) has an essential role transducing activatory intracellular signals coming from the TCR/CD3 complex. Previous reports have shown that upon T-cell activation, LAT interacts with the tyrosine kinase Lck, leading to the inhibition of its kinase activity. LAT-Lck interaction seemed to depend on a stretch of negatively charged amino acids in LAT. Here, we have substituted this segment of LAT between amino acids 113 and 126 with a non-charged segment and expressed the mutant LAT (LAT-NIL) in J...
2018: Frontiers in Immunology
Jean-Marie Carpier, Andres E Zucchetti, Laurence Bataille, Stéphanie Dogniaux, Massiullah Shafaq-Zadah, Sabine Bardin, Marco Lucchino, Mathieu Maurin, Leonel D Joannas, Joao Gamelas Magalhaes, Ludger Johannes, Thierry Galli, Bruno Goud, Claire Hivroz
The adapter molecule linker for activation of T cells (LAT) orchestrates the formation of signalosomes upon T cell receptor (TCR) stimulation. LAT is present in different intracellular pools and is dynamically recruited to the immune synapse upon stimulation. However, the intracellular traffic of LAT and its function in T lymphocyte activation are ill defined. We show herein that LAT, once internalized, transits through the Golgi-trans-Golgi network (TGN), where it is repolarized to the immune synapse. This retrograde transport of LAT depends on the small GTPase Rab6 and the target soluble N -ethylmaleimide-sensitive factor attachment protein receptor (t-SNARE) Syntaxin-16, two regulators of the endosome-to-Golgi/TGN retrograde transport...
February 12, 2018: Journal of Experimental Medicine
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