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https://www.readbyqxmd.com/read/27874083/poly-l-ornithine-enhances-migration-of-neural-stem-progenitor-cells-via-promoting-%C3%AE-actinin-4-binding-to-actin-filaments
#1
Hongfei Ge, Anyong Yu, Jingyu Chen, Jichao Yuan, Yi Yin, Wangsheng Duanmu, Liang Tan, Yang Yang, Chuan Lan, Weixiang Chen, Hua Feng, Rong Hu
The recruitment of neural stem/progenitor cells (NSPCs) for brain restoration after injury is a promising regenerative therapeutic strategy. This strategy involves enhancing proliferation, migration and neuronal differentation of NSPCs. To date, the lack of biomaterials, which facilitate these processes to enhance neural regeneration, is an obstacle for the cell replacement therapies. Our previous study has shown that NSPCs grown on poly-L-ornithine (PO) could proliferate more vigorously and differentiate into more neurons than that on Poly-L-Lysine (PLL) and Fibronectin (FN)...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27742266/proteomic-analysis-of-muccopolysaccharidosis-i-mouse-brain-with-two-dimensional-polyacrylamide-gel-electrophoresis
#2
Li Ou, Michael J Przybilla, Chester B Whitley
Mucopolysaccharidosis type I (MPS I) is due to deficiency of α-l-iduronidase (IDUA) and subsequent storage of undegraded glycosaminoglycans (GAG). The severe form of the disease, known as Hurler syndrome, is characterized by mental retardation and neurodegeneration of unknown etiology. To identify potential biomarkers and unveil the neuropathology mechanism of MPS I disease, two-dimensional polyacrylamide gel electrophoresis (PAGE) and nanoliquid chromatography-tandem mass spectrometry (nanoLC-MS/MS) were applied to compare proteome profiling of brains from MPS I and control mice (5-month old)...
October 11, 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27613525/a-two-gene-prognostic-classifier-for-early-stage-lung-squamous-cell-carcinoma-in-multiple-large-scale-and-geographically-diverse-cohorts
#3
Rintaro Noro, Teruhide Ishigame, Naomi Walsh, Kouya Shiraishi, Ana I Robles, Bríd M Ryan, Aaron J Schetter, Elise D Bowman, Judith A Welsh, Masahiro Seike, Akihiko Gemma, Vidar Skaug, Steen Mollerup, Aage Haugen, Jun Yokota, Takashi Kohno, Curtis C Harris
INTRODUCTION: There are no validated molecular methods that prospectively identify patients with surgically resected lung squamous cell carcinoma (SCC) at high risk for recurrence. By focusing on the expression of genes with known functions in development of lung SCC and prognosis, we sought to develop a robust prognostic classifier of early-stage lung SCC. METHODS: The expression of 253 genes selected by literature search was evaluated in microarrays from 107 stage I/II tumors...
September 6, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27613243/crucial-genes-associated-with-diabetic-nephropathy-explored-by-microarray-analysis
#4
Zhikui Wang, Zhaoxia Wang, Zhongqi Zhou, Yueqin Ren
BACKGROUND: This study sought to investigate crucial genes correlated with diabetic nephropathy (DN), and their potential functions, which might contribute to a better understanding of DN pathogenesis. METHODS: The microarray dataset GSE1009 was downloaded from Gene Expression Omnibus, including 3 diabetic glomeruli samples and 3 healthy glomeruli samples. The differentially expressed genes (DEGs) were identified by LIMMA package. Their potential functions were then analyzed by the GO and KEGG pathway enrichment analyses using the DAVID database...
2016: BMC Nephrology
https://www.readbyqxmd.com/read/27573339/novel-nphs2-variant-in-patients-with-familial-steroid-resistant-nephrotic-syndrome-with-early-onset-slow-progression-and-dominant-inheritance-pattern
#5
Maija Suvanto, Jaakko Patrakka, Timo Jahnukainen, Pia-Maria Sjöström, Matti Nuutinen, Pekka Arikoski, Janne Kataja, Marjo Kestilä, Hannu Jalanko
BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is a common cause of end-stage renal disease in children but also occurs as an adult-onset condition. In a subset of SRNS patients, pathogenic variants are found in genes coding for podocyte foot process proteins. The aim of this study was to define the role of pathogenic variants in Finnish patients with familial and sporadic SRNS. METHODS: We analyzed SRNS-related genes NPHS1, NPHS2, NEPH1, ACTN4, TRPC6, INF2, WT1, CD2AP, LAMB2, and PLCE1 for disease-causing variants using direct sequencing of exons and intron/exon boundaries in all members of a family with dominant SRNS with early onset and slow progression to end-stage renal disease...
August 29, 2016: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/27546377/robust-identification-of-ptbp1-dependent-splicing-events-by-a-junction-centric-approach-in-xenopus-laevis
#6
Maud Noiret, Agnès Méreau, Gaëlle Angrand, Marion Bervas, Carole Gautier-Courteille, Vincent Legagneux, Stéphane Deschamps, Hubert Lerivray, Justine Viet, Serge Hardy, Luc Paillard, Yann Audic
Regulation of alternative splicing is an important process for cell differentiation and development. Down-regulation of Ptbp1, a regulatory RNA-binding protein, leads to developmental skin defects in Xenopus laevis. To identify Ptbp1-dependent splicing events potentially related to the phenotype, we conducted RNAseq experiments following Ptbp1 depletion. We systematically compared exon-centric and junction-centric approaches to detect differential splicing events. We showed that the junction-centric approach performs far better than the exon-centric approach in Xenopus laevis...
August 18, 2016: Developmental Biology
https://www.readbyqxmd.com/read/27166725/proteomic-identification-of-non-erythrocytic-alpha-spectrin-1-down-regulation-in-the-pre-optic-area-of-neonatally-estradiol-17%C3%AE-treated-female-adult-rats
#7
Vijayakumar Govindaraj, Addicam Jagannadha Rao
It is well established that sexually dimorphic brain regions, which are critical for reproductive physiology and behavior, are organized by steroid hormones during the first 2 weeks after birth in the rodents. In our recent observation, neonatal exposure to estradiol-17β (E2) in the female rat revealed increase in cyclooxygenase 2 (COX-2) level, sexually dimorphic nucleus (SDN)-pre-optic area (POA) size and down-regulation of synaptogenesis related genes in POA in the adult stage. In the present study, using the same animal model, the protein profile of control and neonatally E2-treated POA was compared by 1D-SDS-PAGE, and the protein that shows a change in abundance was identified by LC-MS/MS analysis...
June 1, 2016: Hormone Molecular Biology and Clinical Investigation
https://www.readbyqxmd.com/read/27155012/elucidation-of-tonic-and-activated-b-cell-receptor-signaling-in-burkitt-s-lymphoma-provides-insights-into-regulation-of-cell-survival
#8
Jasmin Corso, Kuan-Ting Pan, Roland Walter, Carmen Doebele, Sebastian Mohr, Hanibal Bohnenberger, Philipp Ströbel, Christof Lenz, Mikolaj Slabicki, Jennifer Hüllein, Federico Comoglio, Michael A Rieger, Thorsten Zenz, Jürgen Wienands, Michael Engelke, Hubert Serve, Henning Urlaub, Thomas Oellerich
Burkitt's lymphoma (BL) is a highly proliferative B-cell neoplasm and is treated with intensive chemotherapy that, because of its toxicity, is often not suitable for the elderly or for patients with endemic BL in developing countries. BL cell survival relies on signals transduced by B-cell antigen receptors (BCRs). However, tonic as well as activated BCR signaling networks and their relevance for targeted therapies in BL remain elusive. We have systematically characterized and compared tonic and activated BCR signaling in BL by quantitative phosphoproteomics to identify novel BCR effectors and potential drug targets...
May 17, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27121206/efficacy-of-adjuvant-chemotherapy-for-non-small-cell-lung-cancer-assessed-by-metastatic-potential-associated-with-actn4
#9
Nami Miura, Masahiro Kamita, Takanori Kakuya, Yutaka Fujiwara, Koji Tsuta, Hideaki Shiraishi, Fumitaka Takeshita, Takahiro Ochiya, Hirokazu Shoji, Wilber Huang, Yuichiro Ohe, Tesshi Yamada, Kazufumi Honda
Although several clinical trials have demonstrated the benefits of platinum-combined adjuvant chemotherapy for resected non-small cell lung cancer (NSCLC), predictive biomarkers for the efficacy of such therapy have not yet been identified. Selection of patients with high metastatic ability in the early stage of non-small cell lung cancer (NSCLC) has the potential to predict clinical benefit of adjuvant chemotherapy (ADJ).In order to develop a predictive biomarker for efficacy of ADJ, we reanalyzed patient data using a public database enrolled by JBR...
May 31, 2016: Oncotarget
https://www.readbyqxmd.com/read/27073851/lecithin-prevents-cortical-cytoskeleton-reorganization-in-rat-soleus-muscle-fibers-under-short-term-gravitational-disuse
#10
Irina V Ogneva, Nikolay S Biryukov
The aim of this study was to prevent the cortical cytoskeleton reorganization of rat soleus muscle fibers under short-term gravitational disuse. Once a day, we injected the right soleus muscle with 0.5 ml lecithin at a concentration of 200 mg/ml and the left soleus muscle with a diluted solution in an equal volume for 3 days prior to the experiment. To simulate microgravity conditions in rats, an anti-orthostatic suspension was used according to the Ilyin-Novikov method modified by Morey-Holton et al. for 6 hours...
2016: PloS One
https://www.readbyqxmd.com/read/27065319/%C3%AE-actinin-4-induces-the-epithelial-to-mesenchymal-transition-and-tumorigenesis-via-regulation-of-snail-expression-and-%C3%AE-catenin-stabilization-in-cervical-cancer
#11
H-T An, S Yoo, J Ko
α-Actinin-4 (ACTN4) is frequently amplified and overexpressed in various cancers. Although ACTN4 functions in cancer cell migration and invasion, the roles of ACTN4 during the epithelial-to-mesenchymal transition (EMT) and cervical cancer tumorigenesis are unknown. In this study, we investigated the function of ACTN4 in the progression of cervical cancer and the mechanisms of EMT and tumorigenesis induced by ACTN4. We found that ACTN4 induced EMT by upregulating Snail, which was dependent on the Akt signaling pathway in cervical cancer...
April 11, 2016: Oncogene
https://www.readbyqxmd.com/read/26740551/three-layered-proteomic-characterization-of-a-novel-actn4-mutation-unravels-its-pathogenic-potential-in-fsgs
#12
Malte P Bartram, Sandra Habbig, Caroline Pahmeyer, Martin Höhne, Lutz T Weber, Holger Thiele, Janine Altmüller, Nina Kottoor, Andrea Wenzel, Marcus Krueger, Bernhard Schermer, Thomas Benzing, Markus M Rinschen, Bodo B Beck
Genetic diseases constitute the most important cause for end-stage renal disease in children and adolescents. Mutations in the ACTN4 gene, encoding the actin-binding protein α-actinin-4, are a rare cause of autosomal dominant familial focal segmental glomerulosclerosis (FSGS). Here, we report the identification of a novel, disease-causing ACTN4 mutation (p.G195D, de novo) in a sporadic case of childhood FSGS using next generation sequencing. Proteome analysis by quantitative mass spectrometry (MS) of patient-derived urinary epithelial cells indicated that ACTN4 levels were significantly decreased when compared with healthy controls...
March 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/26683444/traumatically-injured-astrocytes-release-a-proteomic-signature-modulated-by-stat3-dependent-cell-survival
#13
Jaclynn Levine, Eunice Kwon, Pablo Paez, Weihong Yan, Gregg Czerwieniec, Joseph A Loo, Michael V Sofroniew, Ina-Beate Wanner
Molecular markers associated with CNS injury are of diagnostic interest. Mechanical trauma generates cellular deformation associated with membrane permeability with unknown molecular consequences. We used an in vitro model of stretch-injury and proteomic analyses to determine protein changes in murine astrocytes and their surrounding fluids. Abrupt pressure-pulse stretching resulted in the rapid release of 59 astrocytic proteins with profiles reflecting cell injury and cell death, i.e., mechanoporation and cell lysis...
May 2016: Glia
https://www.readbyqxmd.com/read/26538022/a-complex-of-rab13-with-mical-l2-and-%C3%AE-actinin-4-is-essential-for-insulin-dependent-glut4-exocytosis
#14
Yi Sun, Javier Jaldin-Fincati, Zhi Liu, Philip J Bilan, Amira Klip
Insulin promotes glucose uptake into skeletal muscle through recruitment of glucose transporter 4 (GLUT4) to the plasma membrane. Rab GTPases are molecular switches mobilizing intracellular vesicles, and Rab13 is necessary for insulin-regulated GLUT4-vesicle exocytic translocation in muscle cells. We show that Rab13 engages the scaffold protein MICAL-L2 in this process. RNA interference-mediated knockdown of MICAL-L2 or truncated MICAL-L2 (MICAL-L2-CT) impaired insulin-stimulated GLUT4 translocation. Insulin increased Rab13 binding to MICAL-L2, assessed by pull down and colocalization under confocal fluorescence and structured illumination microscopies...
January 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/26312134/the-actinin-family-of-actin-cross-linking-proteins-a-genetic-perspective
#15
Anita C H Murphy, Paul W Young
Actinins are one of the major actin cross-linking proteins found in virtually all cell types and are the ancestral proteins of a larger family that includes spectrin, dystrophin and utrophin. Invertebrates have a single actinin-encoding ACTN gene, while mammals have four. Mutations in all four human genes have now been linked to heritable diseases or traits. ACTN1 mutations cause macrothrombocytopenia, a platelet disorder characterized by excessive bleeding. ACTN2 mutations have been linked to a range of cardiomyopathies, and ACTN4 mutations cause a kidney condition called focal segmental glomerulosclerosis...
2015: Cell & Bioscience
https://www.readbyqxmd.com/read/26301083/the-role-of-alpha-actinin-4-in-human-kidney-disease
#16
Di Feng, Clark DuMontier, Martin R Pollak
Mutations in the Alpha-actinin-4 gene (ACTN4) cause a rare form of familial focal segmental glomerulosclerosis in humans. Individuals with kidney disease-associated ACTN4 mutations tend to have mild to moderate proteinuria, with many developing decreased kidney function progressing to end stage kidney disease. All of the disease-causing ACTN4 mutations identified to date are located within the actin-binding domain of the encoded protein, increasing its binding affinity to F-actin and leading to abnormal actin rich cellular aggregates...
2015: Cell & Bioscience
https://www.readbyqxmd.com/read/26288717/the-biological-role-of-actinin-4-actn4-in-malignant-phenotypes-of-cancer
#17
Kazufumi Honda
Invasion and metastasis are malignant phenotypes in cancer that lead to patient death. Cell motility is involved in these processes. In 1998, we identified overexpression of the actin-bundling protein actinin-4 in several types of cancer. Protein expression of actinin-4 is closely associated with the invasive phenotypes of cancers. Actinin-4 is predominantly expressed in the cellular protrusions that stimulate the invasive phenotype in cancer cells and is essential for formation of cellular protrusions such as filopodia and lamellipodia...
2015: Cell & Bioscience
https://www.readbyqxmd.com/read/26156092/focal-segmental-glomerulosclerosis-molecular-genetics-and-targeted-therapies
#18
REVIEW
Ying Maggie Chen, Helen Liapis
Recent advances show that human focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy caused by podocyte-specific gene mutations including NPHS1, NPHS2, WT-1, LAMB2, CD2AP, TRPC6, ACTN4 and INF2. This review focuses on genes discovered in the investigation of complex FSGS pathomechanisms that may have implications for the current FSGS classification scheme. It also recounts recent recommendations for clinical management of FSGS based on translational studies and clinical trials. The advent of next-generation sequencing promises to provide nephrologists with rapid and novel approaches for the diagnosis and treatment of FSGS...
July 9, 2015: BMC Nephrology
https://www.readbyqxmd.com/read/26012634/tandem-phosphorylation-within-an-intrinsically-disordered-region-regulates-actn4-function
#19
Timothy Travers, Hanshuang Shao, Brian A Joughin, Douglas A Lauffenburger, Alan Wells, Carlos J Camacho
Phosphorylated residues occur preferentially in the intrinsically disordered regions of eukaryotic proteins. In the disordered amino-terminal region of human α-actinin-4 (ACTN4), Tyr(4) and Tyr(31) are phosphorylated in cells stimulated with epidermal growth factor (EGF), and a mutant with phosphorylation-mimicking mutations of both tyrosines exhibits reduced interaction with actin in vitro. Cleavage of ACTN4 by m-calpain, a protease that in motile cells is predominantly activated at the rear, removes the Tyr(4) site...
May 26, 2015: Science Signaling
https://www.readbyqxmd.com/read/25960282/the-development-of-cisplatin-resistance-in-neuroblastoma-is-accompanied-by-epithelial-to-mesenchymal-transition-in-vitro
#20
Olga Piskareva, Harry Harvey, John Nolan, Ross Conlon, Leah Alcock, Patrick Buckley, Paul Dowling, Michael Henry, Finbarr O'Sullivan, Isabella Bray, Raymond L Stallings
Neuroblastoma is a challenging childhood malignancy, with a very high percentage of patients relapsing following acquisition of drug resistance, thereby necessitating the identification of mechanisms of drug resistance as well as new biological targets contributing to the aggressive pathogenicity of the disease. In order to investigate the molecular pathways that are involved with drug resistance in neuroblastoma, we have developed and characterised cisplatin resistant sublines SK-N-ASCis24, KellyCis83 and CHP-212Cis100, integrating data of cell behaviour, cytotoxicity, genomic alterations and modulation of protein expression...
August 10, 2015: Cancer Letters
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