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https://www.readbyqxmd.com/read/28487281/filamin-a-is-required-for-spindle-migration-and-asymmetric-division-in-mouse-oocytes
#1
HaiYang Wang, Jing Guo, ZiLi Lin, Suk Namgoong, Jeong Su Oh, Nam-Hyung Kim
Dynamic changes in the actin network are crucial for the cortical migration of spindles and establishment of polarity, to ensure asymmetric division during meiotic maturation. In this study, filamin A (FLNA) was found to be an essential actin regulator that controlled spindle migration and asymmetric division during oocyte meiosis. FLNA was localized in the cytoplasm and enriched at the cortex and near the chromosomes. Knockdown of FLNA impaired meiotic asymmetric division and spindle migration with a decrease in the amount of cytoplasmic actin mesh and cortical actin levels...
May 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28464104/postmortem-protein-degradation-is-a-key-contributor-to-fresh-pork-loin-tenderness
#2
K B Carlson, K J Prusa, C A Fedler, E M Steadham, A C Outhouse, D A King, E Huff-Lonergan, S M Lonergan
The objective of this study was to determine factors that influence tenderness independent of variation in pH, color, or marbling. To achieve the objective, 2 sample groups were chosen from a population of 159 pork loins aged 11 to 16 d. Predetermined ranges (ultimate pH, 5.54 to 5.86; marbling score, 1.0 to 3.0; percent total lipid, 1.61 to 3.37%) were defined for inclusion of individual loins in the study. The pork loins with the greatest ( = 12) and least ( = 12) Instron star probe values were assigned to 2 classification groups...
April 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28457011/diagnosis-of-inherited-platelet-disorders-on-a-blood-smear-a-tool-to-facilitate-worldwide-diagnosis-of-platelet-disorders
#3
Andreas Greinacher, Alessandro Pecci, Shinji Kunishima, Karina Althaus, Paquita Nurden, Carlo L Balduini, Tamam Bakchoul
BACKGROUND: Many hereditary thrombocytopenias and/or platelet function disorders have been identified, but diagnosis of these conditions remains challenging. Diagnostic laboratory techniques are available only in a few specialized centers and, using fresh blood, often require the patient to travel long distances. For the same reasons, patients living in developing countries usually have limited access to diagnosis. Further, the required amount of blood is often prohibitive for pediatric patients...
April 29, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28438486/pti-125-binds-and-reverses-an-altered-conformation-of-filamin-a-to-reduce-alzheimer-s-disease-pathogenesis
#4
Hoau-Yan Wang, Kuo-Chieh Lee, Zhe Pei, Amber Khan, Kalindi Bakshi, Lindsay H Burns
We show that amyloid-β1-42 (Aβ42) triggers a conformational change in the scaffolding protein filamin A (FLNA) to induce FLNA associations with α7-nicotinic acetylcholine receptor (α7nAChR) and toll-like receptor 4 (TLR4). These aberrant associations respectively enable Aβ42's toxic signaling via α7nAChR to hyperphosphorylate tau protein, and TLR4 activation to release inflammatory cytokines. PTI-125 is a small molecule that preferentially binds altered FLNA and restores its native conformation, restoring receptor and synaptic activities and reducing its α7nAChR/TLR4 associations and downstream pathologies...
March 31, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28436273/proteome-analysis-of-sheep-b-lymphocytes-in-the-course-of-bovine-leukemia-virus-induced-leukemia
#5
Michal Reichert
Presented are the results of a study of the expression pattern of different proteins in the course of bovine leukemia virus-induced leukemia in experimental sheep and I discuss how the obtained data may be useful in gaining a better understanding of the pathogenesis of the disease, diagnosis, and for the selection of possible therapeutic targets. In cattle, the disease is characterized by life-long persistent lymphocytosis leading to leukemia/lymphoma in about 5% of infected animals. In sheep, as opposed to cattle, the course of the disease is always fatal and clinical symptoms usually occur within a three-year period after infection...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28432720/androgen-receptor-dysfunction-as-a-prevalent-manifestation-in-young-male-carriers-of-a-flna-gene-mutation
#6
Laura Carrera-García, Maximiliano Francisco Rivas-Crespo, María Soledad Fernández García
Androgenic actions require the proper signal transmission by the androgen receptor (AR), a nuclear transcription factor. This is initially located in the cell cytoplasm and should translocates to the nucleus to interact with DNA. AR functional impairment causes diverse blockage degrees of androgenic steroid action, known as androgen insensitivity syndromes. Filamin A, a protein coded by the FLNA gene, is a co-activator of various cytoplasmic factors, including AR. The mutational inactivation of the FLNA gene induces insufficiency of translocation and activation of AR...
April 21, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28428218/gain-of-function-mutation-in-filamin-a-potentiates-platelet-integrin-%C3%AE-iib%C3%AE-3-activation
#7
Eliane Berrou, Frédéric Adam, Marilyne Lebret, Virginie Planche, Patricia Fergelot, Odile Issertial, Isabelle Coupry, Jean-Claude Bordet, Paquita Nurden, Dominique Bonneau, Estelle Colin, Cyril Goizet, Jean-Philippe Rosa, Marijke Bryckaert
OBJECTIVE: Dominant mutations of the X-linked filamin A (FLNA) gene are responsible for filaminopathies A, which are rare disorders including brain periventricular nodular heterotopia, congenital intestinal pseudo-obstruction, cardiac valves or skeleton malformations, and often macrothrombocytopenia. APPROACH AND RESULTS: We studied a male patient with periventricular nodular heterotopia and congenital intestinal pseudo-obstruction, his unique X-linked FLNA allele carrying a stop codon mutation resulting in a 100-amino acid-long FLNa C-terminal extension (NP_001447...
April 20, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28420501/bioinformatics-analysis-of-gene-expression-profiles-in-b-cells-of-postmenopausal-osteoporosis-patients
#8
Min Ma, Shulin Luo, Wei Zhou, Liangyu Lu, Junfeng Cai, Feng Yuan, Feng Yin
OBJECTIVE: The aim of this study was to gain a better understanding of the molecular mechanisms and identify more critical genes associated with the pathogenesis of postmenopausal osteoporosis (PMOP). MATERIALS AND METHODS: Microarray data of GSE13850 were download from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified either in B cells from postmenopausal female nonsmokers with high bone mineral density (BMD) compared with those with low BMD (defined as DEG1 group) or in B cells from postmenopausal female smokers with high BMD compared with postmenopausal female nonsmokers with high BMD (defined as DEG2 group)...
April 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28414314/cell-competition-with-normal-epithelial-cells-promotes-apical-extrusion-of-transformed-cells-through-metabolic%C3%A2-changes
#9
Shunsuke Kon, Kojiro Ishibashi, Hiroto Katoh, Sho Kitamoto, Takanobu Shirai, Shinya Tanaka, Mihoko Kajita, Susumu Ishikawa, Hajime Yamauchi, Yuta Yako, Tomoko Kamasaki, Tomohiro Matsumoto, Hirotaka Watanabe, Riku Egami, Ayana Sasaki, Atsuko Nishikawa, Ikumi Kameda, Takeshi Maruyama, Rika Narumi, Tomoko Morita, Yoshiteru Sasaki, Ryosuke Enoki, Sato Honma, Hiromi Imamura, Masanobu Oshima, Tomoyoshi Soga, Jun-Ichi Miyazaki, Michael R Duchen, Jin-Min Nam, Yasuhito Onodera, Shingo Yoshioka, Junichi Kikuta, Masaru Ishii, Masamichi Imajo, Eisuke Nishida, Yoichiro Fujioka, Yusuke Ohba, Toshiro Sato, Yasuyuki Fujita
Recent studies have revealed that newly emerging transformed cells are often apically extruded from epithelial tissues. During this process, normal epithelial cells can recognize and actively eliminate transformed cells, a process called epithelial defence against cancer (EDAC). Here, we show that mitochondrial membrane potential is diminished in RasV12-transformed cells when they are surrounded by normal cells. In addition, glucose uptake is elevated, leading to higher lactate production. The mitochondrial dysfunction is driven by upregulation of pyruvate dehydrogenase kinase 4 (PDK4), which positively regulates elimination of RasV12-transformed cells...
May 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28411558/sporadic-periventricular-nodular-heterotopia-classification-phenotype-and-correlation-with-filamin-a-mutations
#10
Wenyu Liu, Bo Yan, Dongmei An, Jiahe Xiao, Fayun Hu, Dong Zhou
OBJECTIVE: The purpose of this study was to better delineate the clinical spectrum of periventricular nodular heterotopia (PNH) in a large patient population after long term follow up. Specifically, this study aimed to relate PNH subtypes to clinical or epileptic outcomes, epileptic discharges and underlying Filamin A (FLNA) mutations by analyzing anatomical features. METHODS: The study included 100 patients with radiologically confirmed nodular heterotopia. Patients' FLNA gene sequences and medical records were analyzed...
April 4, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28391028/lncrna-expression-profile-of-%C3%AE-np63%C3%AE-in-cervical-squamous-cancers-and-its-suppressive-effects-on-lif-expression
#11
Lili Qian, Fei Xu, Xiaolin Wang, Ming Jiang, Juan Wang, Weiguo Song, Dabao Wu, Zhen Shen, Dingqing Feng, Bin Ling, Yong Cheng, Weihua Xiao, Ge Shan, Ying Zhou
We aim to determine the lncRNA targets of ΔNp63α in cervical cancer and molecular programs in cancerous differentiation. Different profiles of the lncRNAs were assayed and validated in overexpressing p63 SiHa cells (SiHa/ΔNp63α) and the control cell lines (SiHa/pCon). ENST00000422259, ENST00000447565 (Lnc-LIF-AS) and ENST00000469965, together with their related antisense mRNA DPYD (dihydropyrimidine dehydrogenase, a pyrimidine catabolic pathway gene), LIF (leukemia inhibitor factor) and FLNC (filamin C) were all notably differentially expressed in both ΔNp63α overexpression cells and knockdown cells...
April 6, 2017: Cytokine
https://www.readbyqxmd.com/read/28356264/screening-of-the-filamin-c-gene-in-a-large-cohort-of-hypertrophic-cardiomyopathy-patients
#12
Juan Gómez, Rebeca Lorca, Julian R Reguero, César Morís, María Martín, Salvador Tranche, Belén Alonso, Sara Iglesias, Victoria Alvarez, Beatriz Díaz-Molina, Pablo Avanzas, Eliecer Coto
BACKGROUND: Recent exome sequencing studies identified filamin C (FLNC) as a candidate gene for hypertrophic cardiomyopathy (HCM). Our aim was to determine the rate of FLNC candidate variants in a large cohort of HCM patients who were also sequenced for the main sarcomere genes. METHODS AND RESULTS: A total of 448 HCM patients were next generation-sequenced (semiconductor chip technology) for the MYH7, MYBPC3, TNNT2, TNNI3, ACTC1, TNNC1, MYL2, MYL3, TPM1, and FLNC genes...
April 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28348077/structural-and-thermodynamic-basis-of-a-frontometaphyseal-dysplasia-mutation-in-filamin-a
#13
Sujay S Ithychanda, Kevin Dou, Stephen P Robertson, Jun Qin
Filamin-mediated linkages between transmembrane receptors (TR) and the actin cytoskeleton are crucial for regulating many cytoskeleton-dependent cellular processes such as cell shape change and migration. A major TR binding site in the immunoglobulin repeat 21 (Ig21) of filamin is masked by the adjacent repeat Ig20 resulting in autoinhibition. The TR binding to this site triggers the relief of Ig20 and protein kinase A(PKA)-mediated phosphorylation of S2152, thereby dynamically regulating the TR-actin linkages...
March 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28344825/identification-of-filamin-a-and-b-as-potential-biomarkers-for-prostate-cancer
#14
Niven R Narain, Anne R Diers, Arleide Lee, Socheata Lao, Joyce Y Chan, Sally Schofield, Joe Andreazi, Rakibou Ouro-Djobo, Joaquin J Jimenez, Tracey Friss, Nikunj Tanna, Aditee Dalvi, Sihe Wang, Dustin Bunch, Yezhou Sun, Wenfang Wu, Khampaseuth Thapa, Stephane Gesta, Leonardo O Rodrigues, Viatcheslav R Akmaev, Vivek K Vishnudas, Rangaprasad Sarangarajan
AIM: A novel strategy for prostate cancer (PrCa) biomarker discovery is described. MATERIALS & METHODS: In vitro perturbation biology, proteomics and Bayesian causal analysis identified biomarkers that were validated in in vitro models and clinical specimens. RESULTS: Filamin-B (FLNB) and Keratin-19 were identified as biomarkers. Filamin-A (FLNA) was found to be causally linked to FLNB. Characterization of the biomarkers in a panel of cells revealed differential mRNA expression and regulation...
March 2017: Future Science OA
https://www.readbyqxmd.com/read/28301468/recessive-coding-and-regulatory-mutations-in-fblim1-underlie-the-pathogenesis-of-chronic-recurrent-multifocal-osteomyelitis-crmo
#15
Allison J Cox, Benjamin W Darbro, Ronald M Laxer, Gabriel Velez, Xinyu Bing, Alexis L Finer, Albert Erives, Vinit B Mahajan, Alexander G Bassuk, Polly J Ferguson
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare, pediatric, autoinflammatory disease characterized by bone pain due to sterile osteomyelitis, and is often accompanied by psoriasis or inflammatory bowel disease. There are two syndromic forms of CRMO, Majeed syndrome and DIRA, for which the genetic cause is known. However, for the majority of cases of CRMO, the genetic basis is unknown. Via whole-exome sequencing, we detected a homozygous mutation in the filamin-binding domain of FBLIM1 in an affected child with consanguineous parents...
2017: PloS One
https://www.readbyqxmd.com/read/28295715/grb7-protein-ra-domain-oligomerization
#16
Malika P Godamudunage, Albert Foster, Darius Warren, Barbara A Lyons
The growth factor receptor bound protein 7 (Grb7) is an adaptor protein that is often coamplified with the erythroblastosis oncogene B 2 receptor in 20% to 30% of breast cancer patients. Grb7 overexpression has been linked to increased cell migration and cancer metastasis. The ras associating and pleckstrin homology domain region of Grb7 has been reported to interact with various other downstream signaling proteins such as four and half Lin11, Isl-1, Mec-3 (LIM) domains isoform 2 and filamin α. These interactions are believed to play a role in regulating Grb7-mediated cell migration function...
March 14, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28238652/the-er-stress-sensor-perk-coordinates-er-plasma-membrane-contact-site-formation-through-interaction-with-filamin-a-and-f-actin-remodeling
#17
Alexander R van Vliet, Francesca Giordano, Sarah Gerlo, Inmaculada Segura, Sofie Van Eygen, Geert Molenberghs, Susana Rocha, Audrey Houcine, Rita Derua, Tom Verfaillie, Jeroen Vangindertael, Herlinde De Keersmaecker, Etienne Waelkens, Jan Tavernier, Johan Hofkens, Wim Annaert, Peter Carmeliet, Afshin Samali, Hideaki Mizuno, Patrizia Agostinis
Loss of ER Ca(2+) homeostasis triggers endoplasmic reticulum (ER) stress and drives ER-PM contact sites formation in order to refill ER-luminal Ca(2+). Recent studies suggest that the ER stress sensor and mediator of the unfolded protein response (UPR) PERK regulates intracellular Ca(2+) fluxes, but the mechanisms remain elusive. Here, using proximity-dependent biotin identification (BioID), we identified the actin-binding protein Filamin A (FLNA) as a key PERK interactor. Cells lacking PERK accumulate F-actin at the cell edges and display reduced ER-PM contacts...
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28231263/uniformity-under-in-vitro-conditions-changes-in-the-phenotype-of-cancer-cell-lines-derived-from-different-medulloblastoma-subgroups
#18
Petr Chlapek, Karel Zitterbart, Leos Kren, Lenka Filipova, Jaroslav Sterba, Renata Veselska
Medulloblastoma comprises four main subgroups (WNT, SHH, Group 3 and Group 4) originally defined by transcriptional profiling. In primary medulloblastoma tissues, these groups are thought to be distinguishable using the immunohistochemical detection of β-catenin, filamin A, GAB1 and YAP1 protein markers. To investigate the utility of these markers for in vitro studies using medulloblastoma cell lines, immunoblotting and indirect immunofluorescence were employed for the detection of β-catenin, filamin A, GAB1 and YAP1 in both DAOY and D283 Med reference cell lines and the panel of six medulloblastoma cell lines derived in our laboratory from the primary tumor tissues of known molecular subgroups...
2017: PloS One
https://www.readbyqxmd.com/read/28205584/a-postnatal-role-for-embryonic-myosin-revealed-by-myh3-mutations-that-alter-tgf%C3%AE-signaling-and-cause-autosomal-dominant-spondylocarpotarsal-synostosis
#19
Jennifer Zieba, Wenjuan Zhang, Jessica X Chong, Kimberly N Forlenza, Jorge H Martin, Kelly Heard, Dorothy K Grange, Merlin G Butler, Tjitske Kleefstra, Ralph S Lachman, Deborah Nickerson, Michael Regnier, Daniel H Cohn, Michael Bamshad, Deborah Krakow
Spondylocarpotarsal synostosis (SCT) is a skeletal disorder characterized by progressive vertebral, carpal and tarsal fusions, and mild short stature. The majority of affected individuals have an autosomal recessive form of SCT and are homozygous or compound heterozygous for nonsense mutations in the gene that encodes the cytoskeletal protein filamin B (FLNB), but a subset do not have FLNB mutations. Exome sequence analysis of three SCT patients negative for FLNB mutations identified an autosomal dominant form of the disease due to heterozygosity for missense or nonsense mutations in MYH3, which encodes embryonic myosin...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28202730/liquid-behavior-of-cross-linked-actin-bundles
#20
Kimberly L Weirich, Shiladitya Banerjee, Kinjal Dasbiswas, Thomas A Witten, Suriyanarayanan Vaikuntanathan, Margaret L Gardel
The actin cytoskeleton is a critical regulator of cytoplasmic architecture and mechanics, essential in a myriad of physiological processes. Here we demonstrate a liquid phase of actin filaments in the presence of the physiological cross-linker, filamin. Filamin condenses short actin filaments into spindle-shaped droplets, or tactoids, with shape dynamics consistent with a continuum model of anisotropic liquids. We find that cross-linker density controls the droplet shape and deformation timescales, consistent with a variable interfacial tension and viscosity...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
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