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https://www.readbyqxmd.com/read/28346103/discovery-of-novel-gq-biased-lpa1-negative-allosteric-modulators
#1
Yuji Shimizu, Masaharu Nakayama
Lysophosphatidic acid (LPA) activates the G-protein-coupled receptor LPA1, which regulates various cellular processes, including cell proliferation and migration. Although LPA1 transduces cellular responses via Gq, Gi, and G12/13, associations between these signaling molecules and cellular phenotypes remain poorly characterized due to the lack of signal-specific pharmacological tools. Here, we characterized novel signal-biased modulators using multiple assays, including label-free impedance assays. LPA caused dramatic changes in cellular impedance in LPA1-expressing recombinant cells, which were susceptible to G-protein and protein kinase inhibitors...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28344158/laparoscopic-vs-open-approach-for-transverse-colon-cancer-a-systematic-review-and-meta-analysis-of-short-and-long-term-outcomes
#2
REVIEW
Christos Athanasiou, Jonathan Robinson, Marina Yiasemidou, Sonia Lockwood, Georgios A Markides
BACKGROUND: Transverse colon malignancies have been excluded from all randomized controlled trials comparing laparoscopic against open colectomies, potentially due to the advanced laparoscopic skills required for dissecting around the middle colic vessels and the associated morbidity. Concerns have been expressed that the laparospopic approach may compromise the oncological clearance in transverse colon cancer. This study aimed to comprehensively compare the laparoscopic (LPA) to the open (OPA) approach by performing a meta-analysis of long and short term outcomes...
March 24, 2017: International Journal of Surgery
https://www.readbyqxmd.com/read/28343281/using-patterns-of-genetic-association-to-elucidate-shared-genetic-etiologies-across-psychiatric-disorders
#3
Seung Bin Cho, Fazil Aliev, Shaunna L Clark, Amy E Adkins, Howard J Edenberg, Kathleen K Bucholz, Bernice Porjesz, Danielle M Dick
Twin studies indicate that latent genetic factors overlap across comorbid psychiatric disorders. In this study, we used a novel approach to elucidate shared genetic factors across psychiatric outcomes by clustering single nucleotide polymorphisms based on their genome-wide association patterns. We applied latent profile analysis (LPA) to p-values resulting from genome-wide association studies across three phenotypes: symptom counts of alcohol dependence (AD), antisocial personality disorder (ASP), and major depression (MD), using the European-American case-control genome-wide association study subsample of the collaborative study on the genetics of alcoholism (N = 1399)...
March 25, 2017: Behavior Genetics
https://www.readbyqxmd.com/read/28342860/functional-characterization-of-lysophosphatidic-acid-receptor-1-mutants-identified-in-rat-cancer-tissues
#4
Shoichi Ishii, Toshifumi Tsujiuchi, Nobuyuki Fukushima
Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts various cellular effects through activation of LPA receptors, LPA1-LPA6, in many types of cells including cancer cells. We recently found several missense mutations of Lpar1 in rat cancer tissues. One of these mutations is located at the extracellular tip of the seventh transmembrane domain of LPA1, and another three mutations are found within the NPXXY motif in the seventh transmembrane domain. These mutants are designated F295S LPA1 and P308S, I310T, and Y311H LPA1, respectively...
March 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28340224/the-association-of-context-specific-sitting-time-and-physical-activity-intensity-to-working-memory-capacity-and-academic-achievement-in-young-adults
#5
Mireia Felez-Nobrega, Charles H Hillman, Eva Cirera, Anna Puig-Ribera
To examine combined associations between self-reported context-specific sitting time (ST) and physical activity (PA) with working memory capacity (WMC) and academic achievement in a sample of Spanish adults. Undergraduate students ( n = 371; 21 years ± 3 years, 44% female) were recruited from University of Vic-Central University of Catalonia. Participants completed a 54-item survey that assessed socio-demographic variables (e.g. age, gender, academic year), min/week of light (LPA), moderate (MPA) and vigorous (VPA) intensity PA (International Physical Activity Questionnaire), min/day of domain-specific ST (Last 7 days sedentary behavior questionnaire) and academic performance (grade point average)...
March 18, 2017: European Journal of Public Health
https://www.readbyqxmd.com/read/28337305/rho-kinase-regulates-neurite-outgrowth-of-hippocampal-neurons-via-calcium-dependent-cytoskeleton-regulation
#6
Zhisheng Ji, Zhenbin Cai, Jifeng Zhang, Nannuan Liu, Jing Chen, Minghui Tan, Hongsheng Lin, Guoqing Guo
OBJECTIVE: To investigate whether calcium is involved in downstream signal transduction in neurite outgrowth regulated by Rho kinase. METHODS: In vitro primary hippocampal neurons were cultured and treated with Rho kinase agonist (LPA) or antagonist (Y-27632). Then, the cytoskeleton and neurite outgrowth were observed. After addition of calcium antagonist BAPTA/AM to reduce intracellular calcium, the cytoskeleton distribution and neurite outgrowth were observed...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28331837/public-health-relevance-of-non-tuberculous-mycobacteria-among-afb-positive-sputa
#7
Prabha Desikan, Karuna Tiwari, Nikita Panwalkar, Saima Khaliq, Manju Chourey, Reeta Varathe, Shaina Beg Mirza, Arun Sharma, Sridhar Anand, Manoj Pandey
BACKGROUND: Sputum smear microscopy for acid fast bacilli (AFB) is used by most public health programmes to detect tuberculosis. While most AFB in countries endemic for tuberculosis are Mycobacterium tuberculosis (MTB), some may also be non-tuberculous mycobacteria (NTM). The inability to differentiate NTM from MTB by sputum smear microscopy may lead to erroneous diagnoses of tuberculosis, leading in turn to inappropriate therapy. METHODS: This was a retrospective study of consecutive sputum samples received from November 2013 to March 2015 in the Department of Microbiology, Bhopal Memorial Hospital & Research Centre, Bhopal, India...
March 2017: Germs
https://www.readbyqxmd.com/read/28331820/correlation-in-histological-subtypes-with-high-resolution-computed-tomography-signatures-of-early-stage-lung-adenocarcinoma
#8
Yingying Miao, Jianya Zhang, Jiawei Zou, Qingqing Zhu, Tangfeng Lv, Yong Song
BACKGROUND: Uncertainty remains on the association between image characteristics of the nodules in computed tomography (CT) scans and lung adenocarcinoma histopathologic subtypes. We aimed to estimate the correlation between preoperative high resolution computed tomography (HRCT) scan and postoperative histopathology of stage IA lung adenocarcinoma in East Asian Chinese population. METHODS: We retrospectively reviewed the clinical records and HRCT images of 190 patients (106 female and 84 male) with resected, preoperatively untreated stage IA adenocarcinomas...
February 2017: Translational Lung Cancer Research
https://www.readbyqxmd.com/read/28328321/ultrafast-and-predictive-mass-spectrometry-based-autotaxin-assays-for-label-free-potency-screening
#9
Tom Bretschneider, Andreas Harald Luippold, Helmut Romig, Daniel Bischoff, Klaus Klinder, Paul Nicklin, Wolfgang Rist
Autotaxin (ATX) is a promising drug target for the treatment of several diseases, such as cancer and fibrosis. ATX hydrolyzes lysophosphatidyl choline (LPC) into bioactive lysophosphatidic acid (LPA). The potency of ATX inhibitors can be readily determined by using fluorescence-based LPC derivatives. While such assays are ultra-high throughput, they are prone to false positives compared to assays based on natural LPC. Here we report the development of ultrafast mass spectrometry-based ATX assays enabling the measurement of data points within 13 s, which is 10 times faster than classic liquid chromatography-mass spectrometry...
April 2017: SLAS Discov
https://www.readbyqxmd.com/read/28324037/autotaxin-is-regulated-by-glucose-and-insulin-in-adipocytes
#10
Kenneth D'Souza, Daniel A Kane, Mohamed Touaibia, Erin E Kershaw, Thomas Pulinilkunnil, Petra C Kienesberger
Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid. Despite recent studies implicating adipose-derived ATX in metabolic disorders including obesity and insulin resistance, the nutritional and hormonal regulation of ATX in adipocytes remains unclear. The present study examined the regulation of ATX in adipocytes by glucose and insulin and the role of ATX in adipocyte metabolism. Induction of insulin resistance in adipocytes with high glucose and insulin concentrations increased ATX secretion, whereas co-incubation with the insulin sensitizer, rosiglitazone, prevented this response...
January 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323698/hypertrophy-and-fibrosis-of-the-ligamentum-flavum-in-lumbar-spinal-stenosis-is-associated-with-increased-expression-of-lpa-and-lpar1
#11
Kai Zhang, Wei Sun, Xin-Yu Liu, Chang-Qing Zhao, Hua Li, Xiao-Jiang Sun, Xie You-Zhuan, Wei Ding, Jie Zhao
STUDY DESIGN: Histologic, immunohistochemical (IHC), and enzyme-linked immunosorbent assay analysis of the human ligamentum flavum (LF). OBJECTIVE: The purpose of this study was to determine the level of expression of lysophosphatidic acid (LPA) in the LF from lumbar spinal stenosis (LSS) patients and to analyze the relationship among LPA, LPA receptors (LPARs), and LF hypertrophy. SUMMARY OF BACKGROUND DATA: LF hypertrophy and fibrosis are important causes of LSS...
April 2017: Clinical Spine Surgery
https://www.readbyqxmd.com/read/28319587/sedentary-behavior-physical-activity-and-fitness-the-maastricht-study
#12
Jeroen Hpm van der Velde, Annemarie Koster, Julianne D van der Berg, Simone Js Sep, Carla Jh van der Kallen, Pieter C Dagnelie, Miranda T Schram, Ronald Ma Henry, Simone Jpm Eussen, Martien Cjm van Dongen, Coen DA Stehouwer, Nicolaas C Schaper, Hans Hcm Savelberg
PURPOSE: This cross-sectional study examined the mutual independent associations of sedentary behavior, lower intensity physical activity (LPA) and higher intensity physical activity HPA (an approximation of moderate to vigorous physical activity (MVPA) with cardio-respiratory fitness (CRF). METHODS: 2,024 participants were included from The Maastricht Study (mean±SD age: 59.7±8.1 years, 49.6% men). With the activPAL3 activity monitor we assessed sedentary time (ST), sedentary pattern variables (number of sedentary breaks, average sedentary bout duration, and number of prolonged sedentary bouts (≥30 min)), LPA, and HPA...
March 18, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28316912/intensity-of-commonly-reported-classroom-based-physical-activity-opportunities-in-public-schools
#13
Timothy K Behrens, Whitney M Holeva, Dick Carpenter, Elizabeth Tucker, Carmen Luna, John Donovan, Julaine Field, Cheryl Kelly
The purpose of this study was to examine the intensity levels of PA opportunities offered in public school classrooms. Schools (N = 101) in school districts (N = 25) reported PA opportunities offered in classrooms using an online data collection tool over a two-year period (2014-2016). Using a randomized sampling technique, 20-30% of teachers in each school were selected each week to report PA in their classroom. These responses resulted in N = 18,210 usable responses. A researcher determined the intensity of PA opportunities using the 2011 Compendium of Physical Activities as a guideline; two additional researchers confirmed the coded categories...
June 2017: Preventive Medicine Reports
https://www.readbyqxmd.com/read/28314177/gintonin-attenuates-depressive-like-behaviors-associated-with-alcohol-withdrawal-in-mice
#14
Hyeon-Joong Kim, Sang-Deuk Park, Ra Mi Lee, Byung-Hwan Lee, Sun-Hye Choi, Sung-Hee Hwang, Hyewhon Rhim, Hyoung-Chun Kim, Seung-Yeol Nah
BACKGROUND: Panax ginseng Meyer extracts have been used to improve mood and alleviate symptoms of depression. However, little is known about the extracts' active ingredients and the molecular mechanisms underlying their reported anti-depressive effects. METHODS: Gintonin is an exogenous lysophosphatidic acid (LPA) receptor ligand isolated from P. ginseng. BON cells, an enterochromaffin cell line, and C57BL/6 mice were used to investigate whether gintonin stimulates serotonin release...
March 9, 2017: Journal of Affective Disorders
https://www.readbyqxmd.com/read/28304307/logopenic-aphasia-due-to-a-strategic-stroke-new-evidence-from-a-single-case
#15
Javier Riancho, Ana Pozueta, Miguel Santos, Carmen Lage, José M Carril, Ignacio Banzo, Isabel Martínez-Rodriguez, Marilu Gorno-Tempini, Pascual Sánchez-Juan
Among primary progressive aphasias (PPAs), logopenic variant PPA (lv-PPA) is usually related to Alzheimer's disease. Although it has been widely clinically and pathologically evaluated, the topography in LPA is still controversial. We report a patient presenting with a logopenic syndrome due to a strategic lesion located in the superior and middle temporal gyrus and compare our findings with those of a PiB-PET positive lv-PPA patient matched by age, gender, and education. We consider that our study provides new anatomical clues to better understand the cognitive mechanisms underlying the logopenic syndrome...
March 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28299832/secular-and-longitudinal-physical-activity-changes-in-population-based-samples-of-children-and-adolescents
#16
Knut Eirik Dalene, Sigmund A Anderssen, Lars Bo Andersen, Jostein Steene-Johannessen, Ulf Ekelund, Bjørge H Hansen, Elin Kolle
PURPOSE: 1) To investigate if physical activity (PA) and sedentary time (ST) in 9- and 15-year-olds differed between 2005-06 and 2011-12 (secular change) and: 2) to investigate changes in PA and ST from age 9 to 15 (longitudinal change). METHODS: In 2005-06, we invited nationally representative samples of Norwegian 9- (n=1470) and 15-year-olds (n=1348) to participate. In 2011-12, we invited a new nationally representative sample of 9-year-olds (n=1945), whereas 15-year-olds (n=1759) were invited to participate either based on previous participation in 2005-06 or from a random sample of schools...
March 16, 2017: Scandinavian Journal of Medicine & Science in Sports
https://www.readbyqxmd.com/read/28298439/selective-export-of-autotoxin-from-the-endoplasmic-reticulum
#17
Lin Lyu, Baolu Wang, Chaoyang Xiong, Xiaotian Zhang, Xiaoyan Zhang, Junjie Zhang
Autotaxin (ATX) or ecto-nucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) is a secretory glycoprotein and functions as the key enzyme for lysophosphatidic acid (LPA) generation. The mechanism of ATX protein trafficking is largely unknown. Here we demonstrated that p23, a member of the p24 protein family, was the protein sorting receptor required for ER export of ATX. A di-phenylalanine (F838/F839) motif in human ATX C-terminal region was identified as a transport signal essential for the ATX-p23 interaction...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28291838/level-and-correlates-of-physical-activity-and-sedentary-behavior-in-patients-with-type-2-diabetes-a-cross-sectional-analysis-of-the-italian-diabetes-and-exercise-study_2
#18
Stefano Balducci, Valeria D'Errico, Jonida Haxhi, Massimo Sacchetti, Giorgio Orlando, Patrizia Cardelli, Nicolina Di Biase, Lucilla Bollanti, Francesco Conti, Silvano Zanuso, Antonio Nicolucci, Giuseppe Pugliese
OBJECTIVE: Patients with type 2 diabetes usually show reduced physical activity (PA) and increased sedentary (SED)-time, though to a varying extent, especially for low-intensity PA (LPA), a major determinant of daily energy expenditure that is not accurately captured by questionnaires. This study assessed the level and correlates of PA and SED-time in patients from the Italian Diabetes and Exercise Study_2 (IDES_2). METHODS: Three-hundred physically inactive and sedentary patients with type 2 diabetes were enrolled in the IDES_2 to be randomized to an intervention group, receiving theoretical and practical exercise counseling, and a control group, receiving standard care...
2017: PloS One
https://www.readbyqxmd.com/read/28290722/associations-of-a-social-network-typology-with-physical-and-mental-health-risks-among-older-adults-in-south-korea
#19
N S Park, Y Jang, B S Lee, D A Chiriboga, S Chang, S Y Kim
OBJECTIVES: The objectives of this study were to (1) develop an empirical typology of social networks in older Koreans; and (2) examine its effect on physical and mental health. METHOD: A sample of 6900 community-dwelling older adults in South Korea was drawn from the 2014 Korean National Elderly Survey. Latent profile analysis (LPA) was conducted to derive social network types using eight common social network characteristics (marital status, living arrangement, the number and frequency of contact with close family/relatives, the number and frequency of contact with close friends, frequency of participation in social activities, and frequency of having visitors at home)...
March 14, 2017: Aging & Mental Health
https://www.readbyqxmd.com/read/28283740/two-parameter-bifurcations-in-lpa-model
#20
Veronika Hajnová, Lenka Přibylová
The structured population LPA model is studied. The model describes flour beetle (Tribolium) population dynamics of four stage populations: eggs, larvae, pupae and adults with cannibalism between these stages. We concentrate on the case of non-zero cannibalistic rates of adults on eggs and adults on pupae and no cannibalism of larvae on eggs, but the results can be numerically continued to non-zero cannibalism of larvae on eggs. In this article two-parameter bifurcations in LPA model are analysed. Various stable and unstable invariant sets are found, different types of hysteresis are presented and abrupt changes in dynamics are simulated to explain the complicated way the system behaves near two-parameter bifurcation manifolds...
March 10, 2017: Journal of Mathematical Biology
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