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https://www.readbyqxmd.com/read/28445761/live-cell-super-resolution-reveals-f-actin-and-plasma-membrane-dynamics-at-the-t-cell-synapse
#1
George W Ashdown, Garth L Burn, David J Williamson, Elvis Pandžić, Ruby Peters, Michael Holden, Helge Ewers, Lin Shao, Paul W Wiseman, Dylan M Owen
The cortical actin cytoskeleton has been shown to be critical for the reorganization and heterogeneity of plasma membrane components of many cells, including T cells. Building on previous studies at the T cell immunological synapse, we quantitatively assess the structure and dynamics of this meshwork using live-cell superresolution fluorescence microscopy and spatio-temporal image correlation spectroscopy. We show for the first time, to our knowledge, that not only does the dense actin cortex flow in a retrograde fashion toward the synapse center, but the plasma membrane itself shows similar behavior...
April 25, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28434174/molecular-alterations-and-expression-dynamics-of-lats1-and-lats2-genes-in-non-small-cell-lung-carcinoma
#2
Showkat A Malik, Mosin S Khan, Majeed Dar, Mahboob Ul Hussain, Mohammad A Shah, Sheikh M Shafi, Syed Mudassar
Large tumor suppressor (LATS) is an important member of the Hippo pathway which can regulate organ size and cell proliferation. However, very little is known about the expression and clinical significance of LATS in lung cancer especially from this part of the world. We elucidated the frequency of LATS1 &LATS2 promoter hypermethylation (by methylation-specific PCR) and expression (by real-time PCR) in sixty nine (n = 69) Non-Small Cell Lung Cancer (NSCLC) patients and their corresponding normal lung tissue samples...
April 22, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28431512/hemoglobin-a1c-and-risk-of-left-atrial-thrombus-and-spontaneous-echo-contrast-in-non-valvular-atrial-fibrillation-patients
#3
Rong-Ren Kuang, Fang-Zhou Liu, Yun-Peng Li, Wei-Dong Lin, Hua-Sheng Liang, Ai-Hua Chen
OBJECTIVES: To evaluate the relationship between hemoglobin A1c (HbA1c) and risk of left atrial thrombus/spontaneous echo contrast (LAT/SEC) in non-valvular atrial fibrillation (AF) patients. METHODS: In this retrospective study, 1158 consecutive non-valvular AF patients undergoing transesophageal echocardiography prior to radiofrequency catheter ablation or electric cardioversion were enrolled. Baseline characteristics were collected and analyzed. RESULTS: There were 87 (7...
April 21, 2017: European Journal of Medical Research
https://www.readbyqxmd.com/read/28416659/deubiquitinase-yod1-potentiates-yap-taz-activities-through-enhancing-itch-stability
#4
Youngeun Kim, Wantae Kim, Yonghee Song, Jeong-Rae Kim, Kyungjoo Cho, Hyuk Moon, Simon Weonsang Ro, Eunjeong Seo, Yeon-Mi Ryu, Seung-Jae Myung, Eek-Hoon Jho
Hippo signaling controls the expression of genes regulating cell proliferation and survival and organ size. The regulation of core components in the Hippo pathway by phosphorylation has been extensively investigated, but the roles of ubiquitination-deubiquitination processes are largely unknown. To identify deubiquitinase(s) that regulates Hippo signaling, we performed unbiased siRNA screening and found that YOD1 controls biological responses mediated by YAP/TAZ. Mechanistically, YOD1 deubiquitinates ITCH, an E3 ligase of LATS, and enhances the stability of ITCH, which leads to reduced levels of LATS and a subsequent increase in the YAP/TAZ level...
April 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28415785/the-role-of-nitric-oxide-pathway-in-arginine-transport-and-growth-of-ipec-1-cells
#5
Hao Xiao, Liming Zeng, Fangyuan Shao, Bo Huang, Miaomiao Wu, Bie Tan, Yulong Yin
L-Arginine itself and its metabolite-nitric oxide play great roles in intestinal physiology. However, the molecular mechanism underlying nitric oxide pathway regulating L-Arginine transport and cell growth is not yet fully understood. We report that inhibition of nitric oxide synthase (NOS) significantly induced cell apoptosis (p < 0.05), and promoted the rate of Arginine uptake and the expressions of protein for CAT-2 and y+LAT-1 (p < 0.05), while reduced protein expression of CAT-1. And NOS inhibition markedly decreased the activation of mammalian target of rapamycin (mTOR) and PI3K-Akt pathways by Arginine in the IPEC-1 cells (p < 0...
March 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28412158/lidocaine-attenuation-testing-an-in-vivo-investigation-of-putative-lqt3-associated-variants-in-the-scn5a-encoded-sodium-channel
#6
M D Heather N Anderson, J Martijn Bos, Jamie D Kapplinger, Jana M Meskill, Dan Ye, Michael J Ackerman
BACKGROUND: Long QT type 3 (LQT3) accounts for 5-10% of LQTS and results from gain-of-function mutations in the SCN5A-encoded sodium channel. Nearly 2% of healthy individuals host rare SCN5A variants of uncertain significance (VUS). Distinction of true LQT3-causative mutations from background genetic noise is essential. OBJECTIVE: This study was designed to assess the utility of the lidocaine attenuation test (LAT) in evaluating patients with possible LQT3. METHODS: We reviewed LAT results and medical records for 25 patients with a possible LQT3-associated SCN5A variant...
April 12, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28407114/establishment-of-detailed-eye-model-of-adult-chinese-male-and-dose-conversion-coefficients-calculation-under-neutron-exposure
#7
Hongyu Zhu, Rui Qiu, Zhen Wu, Li Ren, Chunyan Li, Hui Zhang, Junli Li
The human eye lens is sensitive to radiation. ICRP-118 publication recommended a reduction of the occupational annual equivalent dose limit from 150 to 20 mSv, averaged over defined periods of 5 y. Therefore, it is very important to build a detailed eye model for the accurate dose assessment and radiation risk evaluation of eye lens. In this work, a detailed eye model was build based on the characteristic anatomic parameters of the Chinese adult male. This eye model includes seven main structures, which are scleral, choroid, lens, iris, cornea, vitreous body and aqueous humor...
April 12, 2017: Radiation Protection Dosimetry
https://www.readbyqxmd.com/read/28389113/mycobacterium-tuberculosis-lysine-%C3%A9-aminotransferase-a-potential-target-in-dormancy-benzothiazole-based-inhibitors
#8
Rudraraju Srilakshmi Reshma, Variam Ullas Jeankumar, Nidhi Kapoor, Shalini Saxena, Karyakulam Andrews Bobesh, Astakala Rishi Vachaspathy, Pappachan E Kolattukudy, Dharmarajan Sriram
MTB lysine-ɛ-aminotransferase (LAT) was found to play a crucial role in persistence and antibiotic tolerance. LAT serves as a potential target in the management of latent tuberculosis. In present work we attempted to derivatize the benzothiazole lead identified through high throughput virtual screening of Birla Institute of Technology and Science in house database. For Structure activity relationship purpose 22 derivatives were synthesized and characterized. Among synthesized compounds, eight compounds were found to be more efficacious in terms of LAT inhibition when compared to lead compound (IC50 10...
May 15, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28388929/novel-soil-inhabiting-clades-fill-gaps-in-the-fungal-tree-of-life
#9
Leho Tedersoo, Mohammad Bahram, Rasmus Puusepp, R Henrik Nilsson, Timothy Y James
BACKGROUND: Fungi are a diverse eukaryotic group of degraders, pathogens, and symbionts, with many lineages known only from DNA sequences in soil, sediments, air, and water. RESULTS: We provide rough phylogenetic placement and principal niche analysis for >40 previously unrecognized fungal groups at the order and class level from global soil samples based on combined 18S (nSSU) and 28S (nLSU) rRNA gene sequences. Especially, Rozellomycota (Cryptomycota), Zygomycota s...
April 8, 2017: Microbiome
https://www.readbyqxmd.com/read/28382373/antagonists-of-the-system-l-neutral-amino-acid-transporter-lat-promote-endothelial-adhesivity-of-human-red-blood-cells
#10
Laura Beth Mann Dosier, Vikram J Premkumar, Hongmei Zhu, Izzet Akosman, Michael F Wempe, Timothy J McMahon
The system L neutral amino acid transporter (LAT; LAT1, LAT2, LAT3, or LAT4) has multiple functions in human biology, including the cellular import of S-nitrosothiols (SNOs), biologically active derivatives of nitric oxide (NO). SNO formation by haemoglobin within red blood cells (RBC) has been studied, but the conduit whereby a SNO leaves the RBC remains unidentified. Here we hypothesised that SNO export by RBCs may also depend on LAT activity, and investigated the role of RBC LAT in modulating SNO-sensitive RBC-endothelial cell (EC) adhesion...
April 6, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28379525/local-activation-time-sampling-density-for-atrial-tachycardia-contact-mapping-how-much-is-enough
#11
Steven E Williams, James L Harrison, Henry Chubb, John Whitaker, Radek Kiedrowicz, Christopher A Rinaldi, Michael Cooklin, Matthew Wright, Steven Niederer, Mark D O'Neill
Aims: Local activation time (LAT) mapping forms the cornerstone of atrial tachycardia diagnosis. Although anatomic and positional accuracy of electroanatomic mapping (EAM) systems have been validated, the effect of electrode sampling density on LAT map reconstruction is not known. Here, we study the effect of chamber geometry and activation complexity on optimal LAT sampling density using a combined in silico and in vivo approach. Methods and results: In vivo 21 atrial tachycardia maps were studied in three groups: (1) focal activation, (2) macro-re-entry, and (3) localized re-entry...
April 3, 2017: Europace: European Pacing, Arrhythmias, and Cardiac Electrophysiology
https://www.readbyqxmd.com/read/28373985/association-of-chads2-and-cha2ds2-vasc-scores-with-left-atrial-thrombus-with-nonvalvular-atrial-fibrillation-a-single-center-based-retrospective-study-in-a-cohort-of-2695-chinese-subjects
#12
J Huang, S L Wu, Y M Xue, H W Fei, Q W Lin, S Q Ren, H T Liao, X Z Zhan, X H Fang, L Xu
The main mechanism of the CHADS2 and CHA2DS2-VASc scores to predict stroke in nonvalvular atrial fibrillation (NVAF) is still controversial. We evaluated the association of the CHADS2 and CHA2DS2-VASc scores with left atrial thrombus (LAT) as detected by transesophageal echocardiographic (TEE) and compared the predictive ability of these risk stratification schemes with nonvalvular atrial fibrillation (NVAF). Data from 2,695 consecutive NVAF patients in whom TEE was performed for screening LAT from July 2007 to February 2014 were analyzed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28373298/mob1-mediated-phospho-recognition-in-the-core-mammalian-hippo-pathway
#13
Amber L Couzens, Shawn Xiong, James Dr Knight, Daniel Y Mao, Sebastian Guettler, Sarah Picaud, Igor Kurinov, Panagis Filippakopoulos, Frank Sicheri, Anne-Claude Gingras
The Hippo tumor suppressor pathway regulates organ size and tissue homoeostasis in response to diverse signaling inputs. The core of the pathway consists of a short kinase cascade: MST1 and MST2 phosphorylate and activate LATS1 and LATS2, which in turn phosphorylate and inactivate key transcriptional co-activators, YAP1 and TAZ (gene WWTR1). The MOB1 adapter protein regulates both phosphorylation reactions firstly by concurrently binding to the upstream MST and downstream LATS kinases to enable the trans phosphorylation reaction, and secondly by allosterically activating the catalytic function of LATS1 and LATS2 to directly stimulate phosphorylation of YAP and TAZ...
April 3, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28373297/regulation-of-protein-interactions-by-mob1-phosphorylation
#14
Shawn Xiong, Amber L Couzens, Michelle J Kean, Daniel Y Mao, Sebastian Guettler, Igor Kurinov, Anne-Claude Gingras, Frank Sicheri
MOB1 is a multifunctional protein best characterized for its integrative role in regulating Hippo and NDR pathway signaling in metazoans and the Mitotic Exit Network in yeast. Human MOB1 binds both the upstream kinases MST1 and MST2 and the downstream AGC group kinases LATS1, LATS2, NDR1 and NDR2. Binding of MOB1 to MST1 and MST2 is mediated by its phosphopeptide-binding infrastructure, the specificity of which matches the phosphorylation consensus of MST1 and MST2. On the other hand, binding of MOB1 to the LATS and NDR kinases is mediated by a distinct interaction surface on MOB1...
April 3, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28372586/the-hippo-signaling-pathway-a-potential-therapeutic-target-is-reversed-by-a-chinese-patent-drug-in-rats-with-diabetic-retinopathy
#15
Gai-Mei Hao, Tian-Tian Lv, Yan Wu, Hong-Liang Wang, Wei Xing, Yong Wang, Chun Li, Zi-Jian Zhang, Zheng-Lin Wang, Wei Wang, Jing Han
BACKGROUND: The Hippo signaling pathway is reported to be involved in angiogenesis, but the roles of the Hippo pathway in diabetic retinopathy have not been addressed. Fufang Xueshuantong Capsule has been used to treat diabetic retinopathy in China; however, the effect of Fufang Xueshuantong Capsule on the Hippo pathway has not been investigated. METHODS: In this study, diabetes was induced in Sprague-Dawley rats with intraperitoneal injection of streptozotocin...
April 4, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28368303/identification-of-hiv-1-tat-associated-proteins-contributing-to-hiv-1-transcription-and-latency
#16
Maxime Junior Jean, Derek Power, Weili Kong, Huachao Huang, Netty Santoso, Jian Zhu
Human immunodeficiency virus type 1 (HIV-1) Tat is a virus-encoded trans-activator that plays a central role in viral transcription. We used our recently developed parallel analysis of in vitro translated open reading frames (ORFs) (PLATO) approach to identify host proteins that associate with HIV-1 Tat. From this proteomic assay, we identify 89 Tat-associated proteins (TAPs). We combine our results with other datasets of Tat or long terminal repeat (LTR)-associated proteins. For some of these proteins (NAT10, TINP1, XRCC5, SIN3A), we confirm their strong association with Tat...
April 1, 2017: Viruses
https://www.readbyqxmd.com/read/28363461/hsv1-latent-transcription-and-non-coding-rna-a-critical-retrospective
#17
REVIEW
Dane Phelan, Enrico R Barrozo, David C Bloom
Virologists have invested great effort into understanding how the herpes simplex viruses and their relatives are maintained dormant over the lifespan of their host while maintaining the poise to remobilize on sporadic occasions. Piece by piece, our field has defined the tissues in play (the sensory ganglia), the transcriptional units (the latency-associated transcripts), and the responsive genomic region (the long repeats of the viral genomes). With time, the observed complexity of these features has compounded, and the totality of viral factors regulating latency are less obvious...
March 6, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28341457/thyroid-hormone-transport-across-l-type-amino-acid-transporters-what-can-molecular-modelling-tell-us
#18
Gerd Krause, Katrin Manuela Hinz
Thyroid hormones (THs) and their derivatives require transmembrane transporters (TTs) to mediate their translocation across the cell membrane. Among these TTs, the L-type amino acid transporters (LAT) not only transport amino acids (AAs) but also certain THs and their derivatives. This review summarizes available knowledge concerning structure function patterns of the TH transport by LAT1 and LAT2. For example, LAT2 imports 3,3'-T2 and T3, but not rT3 and T4. In contrast to amino acids, THs are not at all exported by LAT2...
March 21, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28341051/whey-protein-derived-exosomes-increase-protein-synthesis-and-hypertrophy-in-c2-c12-myotubes
#19
C Brooks Mobley, Petey W Mumford, John J McCarthy, Michael E Miller, Kaelin C Young, Jeffrey S Martin, Darren T Beck, Christopher M Lockwood, Michael D Roberts
We sought to examine potential amino acid independent mechanisms whereby hydrolyzed whey protein (WP) affects muscle protein synthesis (MPS) and anabolism in vitro. Specifically, we tested (1) whether 3-h and 6-h treatments of WP, essential amino acids, or l-leucine (Leu) affected MPS, and whether 6-h treatments with low-, medium-, or high doses of WP versus Leu affected MPS; (2) whether knockdown of the primary Leu transporter affected WP- and Leu-mediated changes in MPS, mammalian target of rapamycin (mTOR) signaling responses, or both, following 6-h treatments; (3) whether exosomes isolated from WP (WP-EXO) affected MPS, mTOR signaling responses, or both, compared with untreated (control) myotubes, following 6-h, 12-h, and 24-h treatments, and whether they affected myotube diameter following 24-h and 48-h treatments...
January 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28338846/patient-exposure-during-plain-radiography-and-mammography-in-japan-in-1974-2014
#20
Yuta Matsunaga, Ai Kawaguchi, Kenichi Kobayashi, Masanao Kobayashi, Yasuki Asada, Kazuyuki Minami, Shoichi Suzuki, Koichi Chida
We investigated changes in the entrance skin dose (ESD) and the mean glandular dose (MGD) during plain radiography or mammography in Japan from 1974 to 2014. Surveys regarding the conditions used for plain radiography and mammography were performed throughout Japan in 1974, 1979, 1989, 1993, 1997, 2001, 2003, 2007, 2011 and 2014. The anatomical regions considered were categorised as follows: skull anteroposterior (AP), lumbar AP, lumbar lateral (LAT), pelvis (AP), ankle, chest posteroanterior (PA), Guthmann (lateral pelviography for pregnant women), infant hip joint and mammography...
March 1, 2017: Radiation Protection Dosimetry
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