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https://www.readbyqxmd.com/read/27484700/mapping-epigenetic-changes-to-the-host-cell-genome-induced-by-burkholderia-pseudomallei-reveals-pathogen-specific-and-pathogen-generic-signatures-of-infection
#1
Deniz Cizmeci, Emma L Dempster, Olivia L Champion, Sariqa Wagley, Ozgur E Akman, Joann L Prior, Orkun S Soyer, Jonathan Mill, Richard W Titball
The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27371493/relation-of-genomic-variants-for-alzheimer-disease-dementia-to-common-neuropathologies
#2
Jose M Farfel, Lei Yu, Aron S Buchman, Julie A Schneider, Philip L De Jager, David A Bennett
OBJECTIVE: To investigate the associations of previously reported Alzheimer disease (AD) dementia genomic variants with common neuropathologies. METHODS: This is a postmortem study including 1,017 autopsied participants from 2 clinicopathologic cohorts. Analyses focused on 22 genomic variants associated with AD dementia in large-scale case-control genome-wide association study (GWAS) meta-analyses. The neuropathologic traits of interest were a pathologic diagnosis of AD according to NIA-Reagan criteria, macroscopic and microscopic infarcts, Lewy bodies (LB), and hippocampal sclerosis...
August 2, 2016: Neurology
https://www.readbyqxmd.com/read/27244899/fermt2-rs17125944-polymorphism-with-alzheimer-s-disease-risk-a-replication-and-meta-analysis
#3
Qiu-Yue Zhang, Hui-Fu Wang, Zhan-Jie Zheng, Ling-Li Kong, Meng-Shan Tan, Chen-Chen Tan, Wei Zhang, Zi-Xuan Wang, Lin Tan, Jin-Tai Yu, Lan Tan
A recent meta-analysis of genome-wide association studies (GWAS) in population of Caucasian identified a single nucleotide polymorphism (SNP) rs17125944 in the FERMT2 gene as a new susceptibility locus for late-onset Alzheimer's disease (LOAD). In order to validate the association of the rs17125944 polymorphism with LOAD risk in the northern Han Chinese, we recruited a case-control study of 2338 Han Chinese subjects (984 cases and 1354 age- and gender-matched controls). Our results demonstrated that there was no significant association between the rs17125944 polymorphism and LOAD (genotype: P = 0...
May 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27215977/mirna-dependent-target-regulation-functional-characterization-of-single-nucleotide-polymorphisms-identified-in-genome-wide-association-studies-of-alzheimer-s-disease
#4
Charlotte Delay, Benjamin Grenier-Boley, Philippe Amouyel, Julie Dumont, Jean-Charles Lambert
BACKGROUND: A growing body of evidence suggests that microRNAs (miRNAs) are involved in Alzheimer's disease (AD) and that some disease-associated genetic variants are located within miRNA binding sites. In the present study, we sought to characterize functional polymorphisms in miRNA target sites within the loci defined in earlier genome-wide association studies (GWAS). The main objectives of this study were to (1) facilitate the identification of the gene or genes responsible for the GWAS signal within a locus of interest and (2) determine how functional polymorphisms might be involved in the AD process (e...
2016: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/27107034/induction-of-expression-and-phosphorylation-of-heat-shock-protein-b5-cryab-in-rat-myometrium-during-pregnancy-and-labour
#5
J G Nicoletti, B G White, E I Miskiewicz, D J MacPhee
During pregnancy the myometrium undergoes a programme of differentiation induced by endocrine, cellular, and biophysical inputs. Small heat shock proteins (HSPs) are a family of ten (B1-B10) small-molecular-weight proteins that not only act as chaperones, but also assist in processes such as cytoskeleton rearrangements and immune system activation. Thus, it was hypothesized that HSPB5 (CRYAB) would be highly expressed in the rat myometrium during the contractile and labour phases of myometrial differentiation when such processes are prominent...
July 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/27064256/genome-wide-association-study-identifies-five-new-susceptibility-loci-for-primary-angle-closure-glaucoma
#6
Chiea Chuen Khor, Tan Do, Hongyan Jia, Masakazu Nakano, Ronnie George, Khaled Abu-Amero, Roopam Duvesh, Li Jia Chen, Zheng Li, Monisha E Nongpiur, Shamira A Perera, Chunyan Qiao, Hon-Tym Wong, Hiroshi Sakai, Mônica Barbosa de Melo, Mei-Chin Lee, Anita S Chan, Yaakub Azhany, Thi Lam Huong Dao, Yoko Ikeda, Rodolfo A Perez-Grossmann, Tomasz Zarnowski, Alexander C Day, Jost B Jonas, Pancy O S Tam, Tuan Anh Tran, Humaira Ayub, Farah Akhtar, Shazia Micheal, Paul T K Chew, Leyla A Aljasim, Tanuj Dada, Tam Thi Luu, Mona S Awadalla, Naris Kitnarong, Boonsong Wanichwecharungruang, Yee Yee Aung, Jelinar Mohamed-Noor, Saravanan Vijayan, Sripriya Sarangapani, Rahat Husain, Aliza Jap, Mani Baskaran, David Goh, Daniel H Su, Huaizhou Wang, Vernon K Yong, Leonard W Yip, Tuyet Bach Trinh, Manchima Makornwattana, Thanh Thu Nguyen, Edgar U Leuenberger, Ki-Ho Park, Widya Artini Wiyogo, Rajesh S Kumar, Celso Tello, Yasuo Kurimoto, Suman S Thapa, Kessara Pathanapitoon, John F Salmon, Yong Ho Sohn, Antonio Fea, Mineo Ozaki, Jimmy S M Lai, Visanee Tantisevi, Chaw Chaw Khaing, Takanori Mizoguchi, Satoko Nakano, Chan-Yun Kim, Guangxian Tang, Sujie Fan, Renyi Wu, Hailin Meng, Thi Thuy Giang Nguyen, Tien Dat Tran, Morio Ueno, Jose Maria Martinez, Norlina Ramli, Yin Mon Aung, Rigo Daniel Reyes, Stephen A Vernon, Seng Kheong Fang, Zhicheng Xie, Xiao Yin Chen, Jia Nee Foo, Kar Seng Sim, Tina T Wong, Desmond T Quek, Rengaraj Venkatesh, Srinivasan Kavitha, Subbiah R Krishnadas, Nagaswamy Soumittra, Balekudaru Shantha, Boon-Ang Lim, Jeanne Ogle, José P C de Vasconcellos, Vital P Costa, Ricardo Y Abe, Bruno B de Souza, Chelvin C Sng, Maria C Aquino, Ewa Kosior-Jarecka, Guillermo Barreto Fong, Vania Castro Tamanaja, Ricardo Fujita, Yuzhen Jiang, Naushin Waseem, Sancy Low, Huan Nguyen Pham, Sami Al-Shahwan, E Randy Craven, Muhammad Imran Khan, Rrima Dada, Kuldeep Mohanty, Muneeb A Faiq, Alex W Hewitt, Kathryn P Burdon, Eng Hui Gan, Anuwat Prutthipongsit, Thipnapa Patthanathamrongkasem, Mary Ann T Catacutan, Irene R Felarca, Chona S Liao, Emma Rusmayani, Vira Wardhana Istiantoro, Giulia Consolandi, Giulia Pignata, Carlo Lavia, Prin Rojanapongpun, Lerprat Mangkornkanokpong, Sunee Chansangpetch, Jonathan C H Chan, Bonnie N K Choy, Jennifer W H Shum, Hlaing May Than, Khin Thida Oo, Aye Thi Han, Victor H Yong, Xiao-Yu Ng, Shuang Ru Goh, Yaan Fun Chong, Martin L Hibberd, Mark Seielstad, Eileen Png, Sarah J Dunstan, Nguyen Van Vinh Chau, Jinxin Bei, Yi Xin Zeng, Abhilasha Karkey, Buddha Basnyat, Francesca Pasutto, Daniela Paoli, Paolo Frezzotti, Jie Jin Wang, Paul Mitchell, John H Fingert, R Rand Allingham, Michael A Hauser, Soon Thye Lim, Soo Hong Chew, Richard P Ebstein, Anavaj Sakuntabhai, Kyu Hyung Park, Jeeyun Ahn, Greet Boland, Harm Snippe, Richard Stead, Raquel Quino, Su Nyunt Zaw, Urszula Lukasik, Rohit Shetty, Mimiwati Zahari, Hyoung Won Bae, Nay Lin Oo, Toshiaki Kubota, Anita Manassakorn, Wing Lau Ho, Laura Dallorto, Young Hoon Hwang, Christine A Kiire, Masako Kuroda, Zeiras Eka Djamal, Jovell Ian M Peregrino, Arkasubhra Ghosh, Jin Wook Jeoung, Tung S Hoan, Nuttamon Srisamran, Thayanithi Sandragasu, Saw Htoo Set, Vi Huyen Doan, Shomi S Bhattacharya, Ching-Lin Ho, Donald T Tan, Ramanjit Sihota, Seng-Chee Loon, Kazuhiko Mori, Shigeru Kinoshita, Anneke I den Hollander, Raheel Qamar, Ya-Xing Wang, Yik Y Teo, E-Shyong Tai, Curt Hartleben-Matkin, David Lozano-Giral, Seang Mei Saw, Ching-Yu Cheng, Juan C Zenteno, Chi Pui Pang, Huong T T Bui, Owen Hee, Jamie E Craig, Deepak P Edward, Michiko Yonahara, Jamil Miguel Neto, Maria L Guevara-Fujita, Liang Xu, Robert Ritch, Ahmad Tajudin Liza-Sharmini, Tien Y Wong, Saleh Al-Obeidan, Nhu Hon Do, Periasamy Sundaresan, Clement C Tham, Paul J Foster, Lingam Vijaya, Kei Tashiro, Eranga N Vithana, Ningli Wang, Tin Aung
Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1...
May 2016: Nature Genetics
https://www.readbyqxmd.com/read/27005436/gene-based-aggregate-snp-associations-between-candidate-ad-genes-and-cognitive-decline
#7
Jasmine Nettiksimmons, Gregory Tranah, Daniel S Evans, Jennifer S Yokoyama, Kristine Yaffe
Single nucleotide polymorphisms (SNPs) in and near ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, complement receptor 1 (CR1), EPHA1, EXOC3L2, FERMT2, HLA cluster (DRB5-DQA), INPP5D, MEF2C, MS4A cluster (MS4A3-MS4A6E), NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1 have been associated with Alzheimer's disease (AD) in large meta-analyses. We aimed to determine whether established AD-associated genes are associated with longitudinal cognitive decline by examining aggregate variation across these gene regions...
April 2016: Age (2005-)
https://www.readbyqxmd.com/read/26543236/risk-prediction-for-sporadic-alzheimer-s-disease-using-genetic-risk-score-in-the-han-chinese-population
#8
RANDOMIZED CONTROLLED TRIAL
Qianyi Xiao, Zhi-Jun Liu, Sha Tao, Yi-Min Sun, Deke Jiang, Hong-Lei Li, Haitao Chen, Xu Liu, Brittany Lapin, Chi-Hsiung Wang, S Lilly Zheng, Jianfeng Xu, Zhi-Ying Wu
More than 30 independent single-nucleotide polymorphisms (SNPs) have been associated with Alzheimer's disease (AD) risk by genome-wide association studies (GWAS) in European. We aimed to confirm these SNPs in Chinese Han and investigate the utility of these genetic markers. We randomly divided 459 sporadic AD (SAD) patients and 751 cognitively normal controls into two sets (discovery and testing). Thirty-three SAD risk-associated SNPs were firstly tested in the discovery set. Significant SNPs were used to calculate genetic risk score (GRS) in the testing set...
November 10, 2015: Oncotarget
https://www.readbyqxmd.com/read/26474967/mir-138-mediated-regulation-of-kindlin-2-expression-modulates-sensitivity-to-chemotherapeutics
#9
Khalid Sossey-Alaoui, Edward F Plow
UNLABELLED: Prostate cancer is the second leading cause of cancer-related death in men, second only to lung cancer, mainly due to disease reoccurrence as a result to lack of response to androgen deprivation therapies (ADT) after castration. Patients with metastatic castration-resistant prostate cancer (mCRPC) have very limited treatment options, with docetaxel as the first-line standard of care, for which resistance to this chemotherapeutic ultimately develops. Therefore, finding ways to sensitize tumors to chemotherapies and to limit chemoresistance provides a viable strategy to extend the survival of mCRPC patients...
February 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/26188538/kindlin-3-fermt3-is-associated-with-unstable-atherosclerotic-plaques-anti-inflammatory-type-ii-macrophages-and-upregulation-of-beta-2-integrins-in-all-major-arterial-beds
#10
Niku Oksala, Jenita Pärssinen, Ilkka Seppälä, Norman Klopp, Thomas Illig, Reijo Laaksonen, Mari Levula, Emma Raitoharju, Ivana Kholova, Thanos Sioris, Mika Kähönen, Terho Lehtimäki, Vesa P Hytönen
BACKGROUND: Kindlins (FERMT) are cytoplasmic proteins required for integrin (ITG) activation, leukocyte transmigration, platelet aggregation and thrombosis. Characterization of kindlins and their association with atherosclerotic plaques in human(s) is lacking. METHODS AND RESULTS: Exploratory microarray (MA) was first performed followed by selective quantitative validation of robustly expressed genes with qRT-PCR low-density array (LDA). In LDA, ITGA1 (1.30-fold, p = 0...
September 2015: Atherosclerosis
https://www.readbyqxmd.com/read/26176019/the-temporal-specific-role-of-wnt-%C3%AE-catenin-signaling-during-myogenesis
#11
Akiko Suzuki, Anne Scruggs, Junichi Iwata
Disruption of WNT/β-catenin signaling causes muscle developmental defects. However, it has been unclear how WNT/β-catenin signaling regulates each step of myogenesis. The in vitro culture of primary myoblasts and C2C12 cells (a myoblast cell line) has the ability to differentiate into myofibers in culture with differentiation inducers. These in vitro systems are useful to investigate each step of muscle development, ranging from cell proliferation to homeostasis, under the control of experimental conditions...
2015: Journal of Nature and Science
https://www.readbyqxmd.com/read/25755281/wnt-%C3%AE-catenin-signaling-regulates-multiple-steps-of-myogenesis-by-regulating-step-specific-targets
#12
Akiko Suzuki, Richard C Pelikan, Junichi Iwata
Molecules involved in WNT/β-catenin signaling show specific spatiotemporal expression and play vital roles in myogenesis; however, it is still largely unknown how WNT/β-catenin signaling regulates each step of myogenesis. Here, we show that WNT/β-catenin signaling can control diverse biological processes of myogenesis by regulating step-specific molecules. In order to identify the temporally specific roles of WNT/β-catenin signaling molecules in muscle development and homeostasis, we used in vitro culture systems for both primary mouse myoblasts and C2C12 cells, which can differentiate into myofibers...
May 2015: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/25311924/genetics-of-alzheimer-s-disease
#13
REVIEW
Vincent Chouraki, Sudha Seshadri
Alzheimer's disease (AD) represents the main form of dementia, and is a major public health problem. Despite intensive research efforts, current treatments have only marginal symptomatic benefits and there are no effective disease-modifying or preventive interventions. AD has a strong genetic component, so much research in AD has focused on identifying genetic causes and risk factors. This chapter will cover genetic discoveries in AD and their consequences in terms of improved knowledge regarding the disease and the identification of biomarkers and drug targets...
2014: Advances in Genetics
https://www.readbyqxmd.com/read/25152024/mig-2-attenuates-cisplatin-induced-apoptosis-of-human-glioma-cells-in-vitro-through-akt-jnk-and-akt-p38-signaling-pathways
#14
Yun-wei Ou, Zi-tong Zhao, Chuan-yue Wu, Bai-nan Xu, Yong-mei Song, Qi-min Zhan
AIM: Mig-2 (also known as Kindlin-2 and FERMT2) is an important regulator of integrin activation and cell-extracellular matrix adhesion, and involved in carcinogenesis and tumor progression. The aim of this study was to investigate the role of mig-2 in cisplatin-induced apoptosis of human glioma cells in vitro. METHODS: The expression of mig-2 was modulated in human glioma H4, HS 683 and U-87 MG cells by transfection with a plasmid carrying mig-2 or mig-2 siRNA...
September 2014: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/25114068/genetic-determinants-of-disease-progression-in-alzheimer-s-disease
#15
Xingbin Wang, Oscar L Lopez, Robert A Sweet, James T Becker, Steven T DeKosky, Mahmud M Barmada, F Yesim Demirci, M Ilyas Kamboh
There is a strong genetic basis for late-onset Alzheimer's disease (LOAD); thus far 22 genes/loci have been identified that affect the risk of LOAD. However, the relationships among the genetic variations at these loci and clinical progression of the disease have not been fully explored. In the present study, we examined the relationships of 22 known LOAD genes to the progression of AD in 680 AD patients recruited from the University of Pittsburgh Alzheimer's Disease Research Center. Patients were classified as "rapid progressors" if the Mini-Mental State Examination (MMSE) changed ≥3 points in 12 months and "slow progressors" if the MMSE changed ≤2 points...
2015: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/25086068/differences-in-binding-to-the-ilk-complex-determines-kindlin-isoform-adhesion-localization-and-integrin-activation
#16
Clotilde Huet-Calderwood, Nina N Brahme, Nikit Kumar, Amy L Stiegler, Srikala Raghavan, Titus J Boggon, David A Calderwood
Kindlins are essential FERM-domain-containing focal adhesion (FA) proteins required for proper integrin activation and signaling. Despite the widely accepted importance of each of the three mammalian kindlins in cell adhesion, the molecular basis for their function has yet to be fully elucidated, and the functional differences between isoforms have generally not been examined. Here, we report functional differences between kindlin-2 and -3 (also known as FERMT2 and FERMT3, respectively); GFP-tagged kindlin-2 localizes to FAs whereas kindlin-3 does not, and kindlin-2, but not kindlin-3, can rescue α5β1 integrin activation defects in kindlin-2-knockdown fibroblasts...
October 1, 2014: Journal of Cell Science
https://www.readbyqxmd.com/read/25017053/analysis-of-gene-expression-for-studying-tumor-progression-the-case-of-glucocorticoid-administration
#17
Mario Huerta, José Fernández-Márquez, Jose Luis Cabello, Alberto Medrano, Enric Querol, Juan Cedano
BACKGROUND: Glucocorticoids are commonly used as adjuvant treatment for side-effects and have anti-proliferative activity in several tumors but, on the other hand, their proliferative effect has been reported in several studies, some of them involving the spread of cancer. We shall attempt to reconcile these incongruities from the genomic and tissue-physiology perspectives with our findings. METHODS: An accurate phenotype analysis of microarray data can help to solve multiple paradoxes derived from tumor-progression models...
October 1, 2014: Gene
https://www.readbyqxmd.com/read/24951455/alzheimer-s-disease-risk-genes-and-mechanisms-of-disease-pathogenesis
#18
REVIEW
Celeste M Karch, Alison M Goate
We review the genetic risk factors for late-onset Alzheimer's disease (AD) and their role in AD pathogenesis. More recent advances in understanding of the human genome-technologic advances in methods to analyze millions of polymorphisms in thousands of subjects-have revealed new genes associated with AD risk, including ABCA7, BIN1, CASS4, CD33, CD2AP, CELF1, CLU, CR1, DSG2, EPHA1, FERMT2, HLA-DRB5-DBR1, INPP5D, MS4A, MEF2C, NME8, PICALM, PTK2B, SLC24H4-RIN3, SORL1, and ZCWPW1. Emerging technologies to analyze the entire genome in large data sets have also revealed coding variants that increase AD risk: PLD3 and TREM2...
January 1, 2015: Biological Psychiatry
https://www.readbyqxmd.com/read/24829845/late-onset-alzheimer-s-disease-genes-and-the-potentially-implicated-pathways
#19
Samantha L Rosenthal, M Ilyas Kamboh
Late-onset Alzheimer's disease (LOAD) is a devastating neurodegenerative disease with no effective treatment or cure. In addition to APOE, recent large genome-wide association studies have identified variation in over 20 loci that contribute to disease risk: CR1, BIN1, INPP5D, MEF2C, TREM2, CD2AP, HLA-DRB1/HLA-DRB5, EPHA1, NME8, ZCWPW1, CLU, PTK2B, PICALM, SORL1, CELF1, MS4A4/MS4A6E, SLC24A4/RIN3,FERMT2, CD33, ABCA7, CASS4. In addition, rare variants associated with LOAD have also been identified in APP, TREM2 and PLD3 genes...
2014: Current Genetic Medicine Reports
https://www.readbyqxmd.com/read/24788522/genetic-variation-at-the-celf1-cugbp-elav-like-family-member-1-gene-locus-is-genome-wide-associated-with-alzheimer-s-disease-and-obesity
#20
Anke Hinney, Ozgür Albayrak, Jochen Antel, Anna-Lena Volckmar, Rebecca Sims, Jade Chapman, Denise Harold, Amy Gerrish, Iris M Heid, Thomas W Winkler, André Scherag, Jens Wiltfang, Julie Williams, Johannes Hebebrand
Deviations from normal body weight are observed prior to and after the onset of Alzheimer's disease (AD). Midlife obesity confers increased AD risk in later life, whereas late-life obesity is associated with decreased AD risk. The role of underweight and weight loss for AD risk is controversial. Based on the hypothesis of shared genetic variants for both obesity and AD, we analyzed the variants identified for AD or obesity from genome-wide association meta-analyses of the GERAD (AD, cases = 6,688, controls = 13,685) and GIANT (body mass index [BMI] as measure of obesity, n = 123,865) consortia...
June 2014: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
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