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https://www.readbyqxmd.com/read/29789604/plasma-membrane-lat-activation-precedes-vesicular-recruitment-defining-two-phases-of-early-t-cell-activation
#1
Lakshmi Balagopalan, Jason Yi, Tiffany Nguyen, Katherine M McIntire, Adam S Harned, Kedar Narayan, Lawrence E Samelson
The relative importance of plasma membrane-localized LAT versus vesicular LAT for microcluster formation and T-cell receptor (TCR) activation is unclear. Here, we show the sequence of events in LAT microcluster formation and vesicle delivery, using lattice light sheet microscopy to image a T cell from the earliest point of activation. A kinetic lag occurs between LAT microcluster formation and vesicular pool recruitment to the synapse. Correlative 3D light and electron microscopy show an absence of vesicles at microclusters at early times, but an abundance of vesicles as activation proceeds...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29777684/repositioning-of-anti-cancer-drug-candidate-azd7762-to-an-anti-allergic-drug-suppressing-ige-mediated-mast-cells-and-allergic-responses-via-the-inhibition-of-lyn-and-fyn
#2
Young Hwan Park, Do Kyun Kim, Hyun Woo Kim, Hyuk Soon Kim, Dajeong Lee, Min Bum Lee, Keun Young Min, Jimo Koo, Su Jeong Kim, Changhee Kang, Young Mi Kim, Hyung Sik Kim, Wahn Soo Choi
Mast cells are critical effector cells in IgE-mediated allergic responses. The aim of this study was to investigate the anti-allergic effects of 3-[(aminocarbonyl)amino]-5-(3-fluorophenyl)-N-(3S)-3-piperidinyl-2-thiophenecarboxamide (AZD7762) in vitro and in vivo. AZD7762 inhibited the antigen-stimulated degranulation from RBL-2H3 (IC50 , ∼ 27.9 nM) and BMMCs (IC50 , ∼ 99.3 nM) in a dose-dependent manner. AZD7762 also inhibited the production of TNF-α and IL-4. As the mechanism of its action, AZD7762 inhibited the activation of Syk and its downstream signaling proteins, such as Linker of activated T cells (LAT), phospholipase (PL) Cγ1, Akt, and mitogen-activated protein (MAP) kinases (Erk1 / 2, p38, and JNK) in mast cells...
May 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29771833/proptosis-correction-in-pre-adolescent-patients-with-syndromic-craniosynostosis-by-le-fort-iii-distraction-osteogenesis
#3
Travis L Gibson, Barry H Grayson, Joseph G McCarthy, Pradip R Shetye
Le Fort III distraction osteogenesis may be indicated in the treatment of syndromic craniosynostosis with severe midface retrusion and proptosis. This study assesses the stability of proptosis correction over 10-years.A retrospective review identified 15 patients with syndromic craniosynostosis treated by Le Fort III distraction prior to age 10 (9 males, 6 females; age 4.9 ± 1.5 years). Untreated, non-craniosynostotic age- and gender-matched controls were obtained from historical growth records. Lateral cephalometric tracings at pre-surgery (T1), immediate (T2), 1 year (T3), 5 years (T4), and 10 years (T5) (n = 11) post-distraction were superimposed using the best-fit of cranial base...
May 15, 2018: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/29766547/potent-and-selective-cc-chemokine-receptor-1-antagonists-labeled-with-carbon-13-carbon-14-and-tritium
#4
Bachir Latli, Matt Hrapchak, Maxim Cheveliakov, Jonathan T Reeves, Maurice Marsini, Carl A Busacca, Chris H Senanayake
1-(4-Fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (2-methanesulfonyl-pyridin-4-ylmethyl)-amide (1) and its analogs (2) and (3) are potent CCR1 antagonists intended for the treatment of rheumatoid arthritis. The detailed syntheses of these three compounds labeled with carbon-13 as well as the preparation of (1) and (2) labeled with carbon-14, and (1) labeled with tritium, are described.
May 15, 2018: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29761512/oral-anticoagulation-and-left-atrial-thrombi-resolution-in-non-rheumatic-atrial-fibrillation-or-flutter-a-systematic-review-and-meta-analysis
#5
Norman C Wang, Matthew D Sather, Aliza Hussain, Andrew D Althouse, Evan C Adelstein, Sandeep K Jain, William E Katz, Alaa A Shalaby, Andrew H Voigt, Samir Saba
BACKGROUND: Oral anticoagulation (OAC) is prescribed for left atrial thrombi (LAT) in non-rheumatic atrial fibrillation (AF) and/or atrial flutter (AFL). The study objective was to review the existing evidence regarding LAT resolution in non-rheumatic AF and/or AFL with OAC agents. METHODS: Data sources included PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) between January 1, 1991 and February 1, 2017. English-language studies that assessed LAT resolution with OAC agents in subjects with non-rheumatic AF and/or AFL, by serial transesophageal echocardiography (TEE), and with follow-up times ≥3 weeks and < 1 year were selected...
May 14, 2018: Pacing and Clinical Electrophysiology: PACE
https://www.readbyqxmd.com/read/29755848/ct-dose-modulation-using-automatic-exposure-control-in-whole-body-pet-ct-effects-of-scout-imaging-direction-and-arm-positioning
#6
Yusuke Inoue, Kazunori Nagahara, Hiroko Kudo, Hiroyasu Itoh
Automatic exposure control (AEC) modulates tube current and consequently X-ray exposure in CT. We investigated the behavior of AEC systems in whole-body PET/CT. CT images of a whole-body phantom were acquired using AEC on two scanners from different manufactures. The effects of scout imaging direction and arm positioning on dose modulation were evaluated. Image noise was assessed in the chest and upper abdomen. On one scanner, AEC using two scout images in the posteroanterior (PA) and lateral (Lat) directions provided relatively constant image noise along the z-axis with the arms at the sides...
2018: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29752476/author-correction-genetic-homogeneity-of-goat-malaria-parasites-in-asia-and-africa-suggests-their-expansion-with-domestic-goat-host
#7
Morakot Kaewthamasorn, Mika Takeda, Tawee Saiwichai, Jesse N Gitaka, Sonthaya Tiawsirisup, Yuhei Imasato, Ehab Mossaad, Ali Sarani, Winai Kaewlamun, Manun Channumsin, Suchart Chaiworakul, Wichit Katepongpun, Surapong Teeveerapunya, Jarus Panthong, Dominic K Mureithi, Saw Bawm, Lat Lat Htun, Mar Mar Win, Ahmed Ali Ismail, Abdalla Mohamed Ibrahim, Keisuke Suganuma, Hassan Hakimi, Ryo Nakao, Ken Katakura, Masahito Asada, Osamu Kaneko
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
May 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29750233/description-of-an-in-vivo-oral-mucosa-hsv-1-infection-model-in-mice
#8
Leidy Y Bastidas-Legarda, Edgar O Beltrán, Lina M Marín-Gallón, Jaime E Castellanos, Sonia P Bohórquez
In this work, we established an in vivo murine model of herpes simplex virus type 1 (HSV-1) infection involving inoculation by scarification of the oral mucosain order to study its dissemination towards the trigeminal ganglion (TG). Both viral DNA and infectious virions were detected on the third day postinfection (p.i.). Viral proteins revealed by immunohistochemistry were mainly found at seven days p.i., when the latency-associated transcript (LAT) was also detected. This model simulated the dissemination process of HSV-1, which could be used to study herpes pathogenesis starting in the oral mucosa...
December 2017: Acta Odontológica Latinoamericana: AOL
https://www.readbyqxmd.com/read/29747325/-association-between-the-ratio-of-early-diastolic-transmitral-velocity-to-early-diastolic-mitral-annular-velocity-and-invasive-measured-left-atrial-pressure-in-patients-with-atrial-fibrillation-and-preserved-left-ventricular-ejection-fraction
#9
G G Ma, L G Fang, P Gao, Z W Cheng, T B Chen, X Lin, K A Cheng, H Deng, Q Fang
Objective: To evaluate the association between the ratio of early diastolic transmitral velocity to early diastolic mitral annular velocity (E/E') and left atrial pressure (LAP) estimated from invasive catheter measurements in patients with atrial fibrillation (AF). Methods: A total of 46 consecutive patients with non-valvular AF and preserved left ventricular ejection fraction (LVEF) admitted in our department to receive the first radiofrequency ablation from May to July 2017 were included. All patients underwent echocardiography at 24-48 hours before radiofrequency ablation, and LAP was invasively measured during the ablation procedure...
April 24, 2018: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/29746705/a-new-method-for-ct-dose-estimation-by-determining-patient-water-equivalent-diameter-from-localizer-radiographs-geometric-transformation-and-calibration-methods-using-readily-available-phantoms
#10
Da Zhang, Georgeta Mihai, Larry G Barbaras, Olga R Brook, Matthew R Palmer
PURPOSE: Water equivalent diameter (Dw) reflects patient's attenuation and is a sound descriptor of patient size, and is used to determine size specific dose estimator from a CT exam. Calculating Dw from CT localizer radiographs makes it possible to utilize Dw before actual scans, and minimizes truncation errors due to limited to utilize Dw before actual scans, and minimizes truncation errors due to limited reconstructed fields of view. One obstacle preventing the user community from implementing this useful tool is the necessity to calibrate localizer pixel values so as to represent water equivalent attenuation...
May 10, 2018: Medical Physics
https://www.readbyqxmd.com/read/29730974/effect-of-breathing-type-on-electromyographic-activity-of-respiratory-muscles-during-tooth-clenching-at-different-decubitus-positions
#11
Rodolfo Miralles, Natalia Andrea Gamboa, Mario Felipe Gutiérrez, Hugo Santander, Saúl Valenzuela, Ricardo Bull, Aler Daniel Fuentes, Rosa Córdova
Objective To compare the effect of breathing type on electromyographic (EMG) activity of respiratory muscles during tooth clenching at different decubitus positions. Methods Forty young men participants were included, 11 with upper costal, 9 with mixed, and 20 with costo-diaphragmatic breathing type. EMG recordings of diaphragm (DIA), external intercostal (EIC), sternocleidomastoid (SCM), and latissimus dorsi (LAT) muscles during tooth clenching in the intercuspal position were performed in dorsal, left lateral, and ventral decubitus positions...
May 7, 2018: Cranio: the Journal of Craniomandibular Practice
https://www.readbyqxmd.com/read/29730476/aicar-antiproliferative-properties-involve-the-ampk-independent-activation-of-the-tumor-suppressors-lats-1-and-2
#12
Chloé Philippe, Benoît Pinson, Jim Dompierre, Véronique Pantesco, Benoît Viollet, Bertrand Daignan-Fornier, Michel Moenner
AICAR (Acadesine) is a pharmacological precursor of purine nucleotide biosynthesis with anti-tumoral properties. Although recognized as an AMP mimetic activator of the protein kinase AMPK, the AICAR monophosphate derivative ZMP was also shown to mediate AMPK-independent effects. In order to unveil these AMPK-independent functions, we performed a transcriptomic analysis in AMPKα1/α2 double knockout murine embryonic cells. Kinetic analysis of the cellular response to AICAR revealed the up-regulation of the large tumor suppressor kinases (Lats) 1 and 2 transcripts, followed by the repression of numerous genes downstream of the transcriptional regulators Yap1 and Taz...
May 3, 2018: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29724057/attenuated-phenotype-and-immunogenic-characteristics-of-a-mutated-herpes-simplex-virus-1-strain-in-the-rhesus-macaque
#13
Shengtao Fan, Xingli Xu, Yun Liao, Yongrong Wang, Jianbin Wang, Min Feng, Lichun Wang, Ying Zhang, Zhanlong He, Fengmei Yang, Nigel W Fraser, Qihan Li
Herpes simplex virus type 1(HSV-1) presents a conundrum to public health worldwide because of its specific pathogenicity and clinical features. Some experimental vaccines, such as the recombinant viral glycoproteins, exhibit the viral immunogenicity of a host-specific immune response, but none of these has achieved a valid epidemiological protective efficacy in the human population. In the present study, we constructed an attenuated HSV-1 strain M3 through the partial deletion of UL7, UL41 , and the latency-associated transcript ( LAT ) using the CRISPR/Cas9 system...
May 2, 2018: Viruses
https://www.readbyqxmd.com/read/29722252/creatine-monohydrate-supplementation-during-eight-weeks-of-progressive-resistance-training-increases-strength-in-as-little-as-two-weeks-without-reducing-markers-of-muscle-damage
#14
Mojtaba Kaviani, Aboozar Abassi, Philip D Chilibeck
BACKGROUND: Creatine supplementation (Cr) increases strength during resistance training, but the time course of this strength increase is unclear. The aim was to determine the precise time course by which Cr could increase strength and whether Cr prevents muscle damage during eight weeks of resistance training. METHODS: Young males were randomized (double blind) to Cr (n=9, 0.07g/kg/d) and placebo (n=9) during 8-weeks of resistance training (3d/week). Strength was assessed across six exercises every two weeks...
May 2, 2018: Journal of Sports Medicine and Physical Fitness
https://www.readbyqxmd.com/read/29720520/herpes-simplex-virus-2-latency-associated-transcript-lat-region-mutations-do-not-identify-a-role-for-lat-associated-micro-rnas-in-viral-reactivation-in-the-guinea-pig-genital-model
#15
Yoshiki Kawamura, Marta Bosch-Marce, Shuang Tang, Amita Patel, Philip R Krause
Despite the long-standing observation that herpes simplex virus (HSV) Latency-Associated Transcript (LAT) promoter-deletion viruses show impaired recurrence phenotypes in relevant animal models, the mechanism by which these sequences exert this phenotypic effect is unknown. We constructed and evaluated four mutant HSV-2 viruses with targeted mutations in the LAT promoter and LAT-associated miRNAs affecting (1) the LAT TATA box, (2) the LAT ICP4-binding site, (3) miR-I and miR-II (miR-I/II), which both target ICP34...
May 2, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29717161/weighted-multi-marker-genetic-risk-scores-for-incident-coronary-heart-disease-among-individuals-of-african-latino-and-east-asian-ancestry
#16
Carlos Iribarren, Meng Lu, Eric Jorgenson, Manuel Martínez, Carla Lluis-Ganella, Isaac Subirana, Eduardo Salas, Roberto Elosua
We examined the clinical utility of two multi-locus genetic risk scores (GRSs) previously validated in Europeans among persons of African (AFR; n = 2,089), Latino (LAT; n = 4,349) and East-Asian (EA; n = 4,804) ancestry. We used data from the GERA cohort (30-79 years old, 68 to 73% female). We utilized two GRSs with 12 and 51 SNPs, respectively, and the Framingham Risk Score (FRS) to estimate 10-year CHD risk. After a median 8.7 years of follow-up, 450 incident CHD events were documented (95 in AFR, 316 in LAT and 39 EA, respectively)...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29717064/glycerol-monolaurate-induces-filopodia-formation-by-disrupting-the-association-between-lat-and-slp-76-microclusters
#17
Michael S Zhang, Phuong M Tran, Alexander J Wolff, Mikaela M Tremblay, Micaela G Fosdick, Jon C D Houtman
Glycerol monolaurate (GML) is a monoglyceride with potent antimicrobial properties that suppresses T cell receptor (TCR)-induced signaling and T cell effector function. Actin rearrangement is needed for the interaction of T cells with antigen-presenting cells and for migration to sites of infection. Because of the critical role actin rearrangement plays in T cell effector function, we analyzed the effect of GML on the rearrangement of the actin cytoskeleton after TCR activation. We found that GML-treated human T cells were less adherent than untreated T cells and did not form actin ring structures but instead developed numerous inappropriate actin-mediated filopodia...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29717062/vegf-neuropilin-2-signaling-promotes-stem-like-traits-in-breast-cancer-cells-by-taz-mediated-repression-of-the-rac-gap-%C3%AE-2-chimaerin
#18
Ameer L Elaimy, Santosh Guru, Cheng Chang, Jianhong Ou, John J Amante, Lihua Julie Zhu, Hira Lal Goel, Arthur M Mercurio
The role of vascular endothelial growth factor (VEGF) signaling in cancer is not only well known in the context of angiogenesis but also important in the functional regulation of tumor cells. Autocrine VEGF signaling mediated by its co-receptors called neuropilins (NRPs) appears to be essential for sustaining the proliferation and survival of cancer stem cells (CSCs), which are implicated in mediating tumor growth, progression, and drug resistance. Therefore, understanding the mechanisms involved in VEGF-mediated support of CSCs is critical to successfully treating cancer patients...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29707457/lateral-branch-of-the-thoracodorsal-nerve-lat-branch-transfer-for-biceps-reinnervation
#19
M Asher Schusterman, Rishi Jindal, Jignesh V Unadkat, Alexander M Spiess
In cases of significant upper extremity trauma, the thoracodorsal nerve is a reliable secondary option for the restoration of elbow flexion. In all previous descriptions, however, the entire nerve is transferred. We describe a case utilizing the lateral thoracodorsal nerve (LaT) branch for biceps reinnervation with an associated cadaver study. Transfer of the LaT branch to the biceps branch was performed on a patient who had sustained a traumatic brachial plexus injury that left him without elbow flexion. Also, 4 cadavers (8 upper extremities) were dissected to identify the bifurcation of the thoracodorsal nerve and confirm the feasibility of transferring the LaT branch to the biceps motor branch...
March 2018: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/29704439/histone-deacetylase-inhibitor-chidamide-promotes-reactivation-of-latent-hiv-by-introducing-histone-acetylation
#20
Qiyuan Kuai, Xiaofan Lu, Zhixin Qiao, Rui Wang, Yanbing Wang, Sanxian Ye, Min He, Yu Wang, Tong Zhang, Hao Wu, Suping Ren, Qun Yu
Highly active antiretroviral therapy (HAART) can reduce the HIV viral load in the plasma to undetectable levels. However, due to the presence of latent HIV reservoirs, it is difficult to completely eradicate HIV in infected patients. Our objective was to assess the potency of chidamide, a novel histone deacetylase inhibitor (HDACi) recently approved for cancer treatment by the China Food and Drug Administration (CFDA), to reactivate latent HIV-1 via histone acetylation. Viral reactivities of chidamide were accessed in two latent HIV pseudotype virus cell reporter systems (J-Lat Tat-GFP Clone A72 and TZM-bl), a latently infected full-length HIV virus cell system (U1/HIV), and resting CD4+ T cells from nine HIV-infected patients under HAART with undetectable viral load...
April 28, 2018: Journal of Medical Virology
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