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Anna Slawinska, John C Hsieh, Carl J Schmidt, Susan J Lamont
Acute heat stress requires immediate adjustment of the stressed individual to sudden changes of ambient temperatures. Chickens are particularly sensitive to heat stress due to development of insufficient physiological mechanisms to mitigate its effects. One of the symptoms of heat stress is endotoxemia that results from release of the lipopolysaccharide (LPS) from the guts. Heat-related cytotoxicity is mitigated by the innate immune system, which is comprised mostly of phagocytic cells such as monocytes and macrophages...
2016: PloS One
Margit Fuchs, Marie-Chloé Boulanger, Herman Lambert, Jacques Landry, Josée N Lavoie
Cellular processes such as mitosis and cell differentiation are governed by changes in cell shape that largely rely on proper remodeling of the cell cytoskeletal structures. This involves the assembly-disassembly of higher-order macromolecular structures at a given time and location, a process that is particularly sensitive to perturbations caused by overexpression of proteins. Methods that can preserve protein homeostasis and maintain near-to-normal cellular morphology are highly desirable to determine the functional contribution of a protein of interest in a wide range of cellular processes...
2016: Journal of Visualized Experiments: JoVE
D Avila-Smirnow, L Gueneau, S Batonnet-Pichon, F Delort, H-M Bécane, K Claeys, M Beuvin, B Goudeau, J-P Jais, I Nelson, P Richard, R Ben Yaou, N B Romero, K Wahbi, S Mathis, T Voit, D Furst, P van der Ven, R Gil, P Vicart, M Fardeau, G Bonne, A Behin
Myofibrillar myopathies (MFM) are mostly adult-onset diseases characterized by progressive morphological alterations of the muscle fibers beginning in the Z-disk and the presence of protein aggregates in the sarcoplasm. They are mostly caused by mutations in different genes that encode Z-disk proteins, including DES, CRYAB, LDB3, MYOT, FLNC and BAG3. A large family of French origin, presenting an autosomal dominant pattern, characterized by cardiac arrhythmia associated to late-onset muscle weakness, was evaluated to clarify clinical, morphological and genetic diagnosis...
October 2016: Revue Neurologique
Amy E Vincent, John P Grady, Mariana C Rocha, Charlotte L Alston, Karolina A Rygiel, Rita Barresi, Robert W Taylor, Doug M Turnbull
Myofibrillar myopathies (MFM) are characterised by focal myofibrillar destruction and accumulation of myofibrillar elements as protein aggregates. They are caused by mutations in the DES, MYOT, CRYAB, FLNC, BAG3, DNAJB6 and ZASP genes as well as other as yet unidentified genes. Previous studies have reported changes in mitochondrial morphology and cellular positioning, as well as clonally-expanded, large-scale mitochondrial DNA (mtDNA) deletions and focal respiratory chain deficiency in muscle of MFM patients...
October 2016: Neuromuscular Disorders: NMD
Yoon Hee Kim, Ki Yun Kim, Do Youn Jun, Jong-Sik Kim, Young Ho Kim
Treatment of Jurkat T cells with the dynamin inhibitor, myristyl trimethyl ammonium bromides (MiTMAB) caused cytokinesis impairment and apoptotic DNA fragmentation along with down-regulation of anti-apoptotic BAG3 and Mcl-1 levels, Bak activation, mitochondrial membrane potential (Δψm) loss, activation of caspase-9 and -3, and PARP cleavage, without accompanying necrosis. Bcl-xL overexpression completely abrogated these MiTMAB-induced mitochondrial damage and resultant caspase cascade activation, except for impaired cytokinesis and down-regulated BAG3 and Mcl-1 levels...
September 30, 2016: Biochemical and Biophysical Research Communications
Massimo Ganassi, Daniel Mateju, Ilaria Bigi, Laura Mediani, Ina Poser, Hyun O Lee, Samuel J Seguin, Federica F Morelli, Jonathan Vinet, Giuseppina Leo, Orietta Pansarasa, Cristina Cereda, Angelo Poletti, Simon Alberti, Serena Carra
Stress granules (SGs) are ribonucleoprotein complexes induced by stress. They sequester mRNAs and disassemble when the stress subsides, allowing translation restoration. In amyotrophic lateral sclerosis (ALS), aberrant SGs cannot disassemble and therefore accumulate and are degraded by autophagy. However, the molecular events causing aberrant SG formation and the molecular players regulating this transition are largely unknown. We report that defective ribosomal products (DRiPs) accumulate in SGs and promote a transition into an aberrant state that renders SGs resistant to RNase...
September 1, 2016: Molecular Cell
N Campitiello, M Faenza, D Pagliara, C Baldi, P Zeppa, A Rosati, C Rubino
No abstract text is available yet for this article.
2016: Cell Death Discovery
Jennifer N Rauch, Erik R P Zuiderweg, Jason E Gestwicki
Heat shock cognate protein 70 (Hsc70) regulates protein homeostasis through its reversible interactions with client proteins. Hsc70 has two major domains: a nucleotide-binding domain (NBD), that hydrolyzes ATP, and a substrate-binding domain (SBD), where clients are bound. Members of the BAG family of co-chaperones, including Bag1 and Bag3, are known to accelerate release of both ADP and client from Hsc70. The release of nucleotide is known to be mediated by interactions between the conserved BAG domain and the Hsc70 NBD...
September 16, 2016: Journal of Biological Chemistry
Dong Yang, Ji Zhou, Hao Wang, Yutao Wang, Ge Yang, Yundong Zhang
Bcl2-associated athanogene 3 (BAG3), a co-chaperone of the heat shock protein (Hsp) 70, regulates various physiological and pathological processes. However, its role in human medulloblastoma has not been clarified. First of all, the expression of BAG3 was examined in formalin-fixed, paraffin-embedded specimens by immunohistochemical staining. And then, the prognostic role of BAG3 was analyzed in 51 medulloblastoma samples. Finally, the roles of BAG3 in the proliferation, migration, and invasion of Daoy medulloblastoma cell were investigated using a specific short hairpin RNA (shRNA)...
July 25, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Francesca D'Avila, Mirella Meregalli, Sara Lupoli, Matteo Barcella, Alessandro Orro, Francesca De Santis, Clementina Sitzia, Andrea Farini, Pasqualina D'Ursi, Silvia Erratico, Riccardo Cristofani, Luciano Milanesi, Daniele Braga, Daniele Cusi, Angelo Poletti, Cristina Barlassina, Yvan Torrente
Myofibrillar myopathies (MFMs) are genetically heterogeneous dystrophies characterized by the disintegration of Z-disks and myofibrils and are associated with mutations in genes encoding Z-disk or Z-disk-related proteins. The c.626 C > T (p.P209L) mutation in the BAG3 gene has been described as causative of a subtype of MFM. We report a sporadic case of a 26-year-old Italian woman, affected by MFM with axonal neuropathy, cardiomyopathy, rigid spine, who carries the c.626 C > T mutation in the BAG3 gene...
June 2016: Journal of Muscle Research and Cell Motility
Claire M Ouimet, Hao Shao, Jennifer N Rauch, Mohamed Dawod, Bryce Nordhues, Chad A Dickey, Jason E Gestwicki, Robert T Kennedy
Capillary electrophoresis (CE) has been identified as a useful platform for detecting, quantifying, and screening for modulators of protein-protein interactions (PPIs). In this method, one protein binding partner is labeled with a fluorophore, the protein binding partners are mixed, and then, the complex is separated from free protein to allow direct determination of bound to free ratios. Although it possesses many advantages for PPI studies, the method is limited by the need to have separation conditions that both prevent protein adsorption to capillary and maintain protein interactions during the separation...
August 16, 2016: Analytical Chemistry
Veronica Esposito, Carlo Baldi, Pio Zeppa, Michelina Festa, Luana Guerriero, Morena d'Avenia, Massimiliano Chetta, Fulvio Zullo, Vincenzo De Laurenzi, Maria Caterina Turco, Alessandra Rosati, Maurizio Guida
Endometrioid adenocarcinomas represent 80% of endometrial carcinomas(1) . Molecular features, including microsatellite instability, mutations of the PTEN, PIK3CA, K-Ras and β-catenin genes(1) and dysregulations in sncRNAs (small non coding RNAs) are described for this disease. However, mechanisms and molecules that determine cell survival and response/resistance to therapy in different subtypes of this tumour are not fully clarified(1) . This article is protected by copyright. All rights reserved.
July 14, 2016: Journal of Cellular Physiology
Rocio Toro, Alexandra Pérez-Serra, Oscar Campuzano, Javier Moncayo-Arlandi, Catarina Allegue, Anna Iglesias, Alipio Mangas, Ramon Brugada
BACKGROUND: Dilated cardiomyopathy, a major cause of chronic heart failure and cardiac transplantation, is characterized by left ventricular or biventricular heart dilatation. In nearly 50% of cases the pathology is inherited, and more than 60 genes have been reported as disease-causing. However, in 30% of familial cases the mutation remains unidentified even after comprehensive genetic analysis. This study clinically and genetically assessed a large Spanish family affected by dilated cardiomyopathy to search for novel variations...
2016: PloS One
Rudolf A Kley, Montse Olivé, Rolf Schröder
PURPOSE OF REVIEW: Myofibrillar myopathies (MFMs) are hereditary muscle disorders characterized by distinct histopathological features. This review provides an overview of recent research with respect to new disease genes, clinical phenotypes, insights into pathomechanisms and therapeutic strategies. RECENT FINDINGS: Beyond the known disease genes DES, FLNC, MYOT, CRYAB, ZASP, BAG3, FHL1 and TTN, mutations in PLEC, ACTA1, HSPB8 and DNAJB6 have also been associated with a MFM phenotype...
October 2016: Current Opinion in Neurology
Jiankai Zhang, Zhangyou He, Wenjian Xiao, Qingqing Na, Tianxiu Wu, Kaixin Su, Xiaojun Cui
BACKGROUND: Hypoxia is a well-known factor in the promotion of apoptosis, which contributes to the development of numerous cardiac diseases, such as heart failure and myocardial infarction. Inhibiting apoptosis is an important therapeutic strategy for the treatment of related heart diseases caused by ischemia/hypoxic injury. Previous studies have demonstrated that BAG3 plays an important role in cardiomyocyte apoptosis and survival. However, the role of BAG3 in hypoxia-induced cardiomyocyte apoptosis remains to be clarified...
2016: Cellular Physiology and Biochemistry
Farzaneh G Tahrir, Tijana Knezevic, Manish K Gupta, Jennifer Gordon, Joseph Y Cheung, Arthur M Feldman, Kamel Khalili
Mitochondrial abnormalities impact the development of myofibrillar myopathies. Therefore, understanding the mechanisms underlying the removal of dysfunctional mitochondria from cells is of great importance toward understanding the molecular events involved in the genesis of cardiomyopathy. Earlier studies have ascribed a role for BAG3 in the development of cardiomyopathy in experimental animals leading to the identification of BAG3 mutations in patients with heart failure which may play a part in the onset of disease development and progression...
July 6, 2016: Journal of Cellular Physiology
Megan T Quintana, Traci L Parry, Jun He, Cecelia C Yates, Tatiana N Sidorova, Katherine T Murray, James R Bain, Christopher B Newgard, Michael J Muehlbauer, Samuel C Eaton, Akinori Hishiya, Shin Takayama, Monte S Willis
The Bcl2-associated anthanogene (BAG) 3 protein is a member of the BAG family of cochaperones, which supports multiple critical cellular processes, including critical structural roles supporting desmin and interactions with heat shock proteins and ubiquitin ligases intimately involved in protein quality control. The missense mutation P209L in exon 3 results in a primarily cardiac phenotype leading to skeletal muscle and cardiac complications. At least 10 other Bag3 mutations have been reported, nine resulting in a dilated cardiomyopathy for which no specific therapy is available...
August 2016: American Journal of Pathology
Tatsuya Yunoki, Yoshiaki Tabuchi, Atsushi Hayashi, Takashi Kondo
BCL2-associated athanogene 3 (BAG3), a co-chaperone of the heat shock 70 kDa protein (HSPA) family of proteins, is a cytoprotective protein that acts against various stresses, including heat stress. The aim of the present study was to identify gene networks involved in the enhancement of hyperthermia (HT) sensitivity by the knockdown (KD) of BAG3 in human oral squamous cell carcinoma (OSCC) cells. Although a marked elevation in the protein expression of BAG3 was detected in human the OSCC HSC-3 cells exposed to HT at 44˚C for 90 min, its expression was almost completely suppressed in the cells transfected with small interfering RNA against BAG3 (siBAG) under normal and HT conditions...
July 2016: International Journal of Molecular Medicine
Angelica Van Goor, Anna Slawinska, Carl J Schmidt, Susan J Lamont
Differences in responses of chicken bone marrow derived dendritic cells (BMDC) to in vitro treatment with lipopolysaccharide (LPS), heat, and LPS + heat were identified. The Fayoumi is more disease resistant and heat tolerant than the Leghorn line. Nitric Oxide (NO) production, phagocytic ability, MHC II surface expression and mRNA expression were measured. NO was induced in BMDC from both lines in response to LPS and LPS + heat stimulation; Fayoumi produced more NO with LPS treatment. Fayoumi had higher phagocytic ability and MHC II surface expression...
October 2016: Developmental and Comparative Immunology
Laura Diaz-Hidalgo, Sara Altuntas, Federica Rossin, Manuela D'Eletto, Claudia Marsella, Maria Grazia Farrace, Laura Falasca, Manuela Antonioli, Gian Maria Fimia, Mauro Piacentini
Numerous studies are revealing a role of exosomes in intercellular communication, and growing evidence indicates an important function for these vesicles in the progression and pathogenesis of cancer and neurodegenerative diseases. However, the biogenesis process of exosomes is still unclear. Tissue transglutaminase (TG2) is a multifunctional enzyme with different subcellular localizations. Particularly, under stressful conditions, the enzyme has been also detected in the extracellular matrix, but the mechanism(s) by which TG2 is released outside the cells requires further investigation...
August 2016: Biochimica et Biophysica Acta
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