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Anna Raffaello, Cristina Mammucari, Gaia Gherardi, Rosario Rizzuto
In recent years, rapid discoveries have been made relating to Ca(2+) handling at specific organelles that have important implications for whole-cell Ca(2+) homeostasis. In particular, the structures of the endoplasmic reticulum (ER) Ca(2+) channels revealed by electron cryomicroscopy (cryo-EM), continuous updates on the structure, regulation, and role of the mitochondrial calcium uniporter (MCU) complex, and the analysis of lysosomal Ca(2+) signaling are milestones on the route towards a deeper comprehension of the complexity of global Ca(2+) signaling...
September 28, 2016: Trends in Biochemical Sciences
Hao Wu, Zhiwu Wang, Guozheng Yan, Wentian Jin, Shan Lu, Zerun Zhou
This article presents a novel puborectalis muscle artificial anal sphincter system (PM-AASS) with the module of sensory perception for treating severe faecal incontinence (FI). Due to the implantable feature of PM-AASS, this system applied low-power design and the total energy consumption could drop to 48.8 Ah/d. To reduce the injury of intestine and the pressure exerted on intestine, the actuator, including the structure of tings and the robot mechanism, of PM-AASS was presented and the middle ring was optimised...
September 30, 2016: Journal of Medical Engineering & Technology
Julieta Diaz-Juarez, Jorge Suarez, Federico Cividini, Brian T Scott, Tanja Diemer, Anzhi Dai, Wolfgang H Dillmann
Diabetic cardiomyopathy is associated with metabolic changes including decreased glucose oxidation (Gox) and increased fatty acid oxidation (FAox), which result in cardiac energetic deficiency. Diabetic hyperglycemia is a pathophysiological mechanism that triggers multiple maladaptive phenomena. The mitochondrial calcium uniporter (MCU) is the channel responsible for Ca(2+) uptake in mitochondria and free mitochondrial calcium concentration ([Ca(2+)]m) regulates mitochondrial metabolism. Experiments with cardiac myocytes (CM) exposed to simulated hyperglycemia revealed both reduced [Ca(2+)]m and MCU protein levels...
September 28, 2016: American Journal of Physiology. Cell Physiology
Barbara M Masser, Christopher R France, Lina K Himawan, Melissa K Hyde, Geoff Smith
BACKGROUND: Anxiety is a frequently cited barrier to blood donor recruitment. Although the mere presence of donation paraphernalia can heighten anxiety for some individuals, such stimuli are a necessary and unavoidable part of donation. Drawing on France and colleagues' research on tailored donor education and coping materials, the current study assessed whether modifying recruitment materials could improve donor recruitment in a context where anxiety is heightened. STUDY DESIGN AND METHODS: A field study comprising a 2 (presence or absence of a mobile blood collection unit [MCU]) × 2 (recruitment brochure: standard, coping) between-subjects design was conducted with 922 nondonors who believed themselves eligible to donate blood...
September 25, 2016: Transfusion
Pia A Elustondo, Matthew Nichols, George S Robertson, Evgeny V Pavlov
Calcium (Ca(2+)) plays diverse roles in all living organisms ranging from bacteria to humans. It is a structural element for bones, an essential mediator of excitation-contraction coupling, and a universal second messenger in the regulation of ion channel, enzyme and gene expression activities. In mitochondria, Ca(2+) is crucial for the control of energy production and cellular responses to metabolic stress. Ca(2+) uptake by the mitochondria occurs by the uniporter mechanism. The Mitochondrial Ca2+ Uniporter (MCU) protein has recently been identified as a core component responsible for mitochondrial Ca(2+) uptake...
September 24, 2016: Journal of Bioenergetics and Biomembranes
Zhigang Hong, Kuang-Hueih Chen, Asish Dasgupta, Francois Potus, Kimberly Dunham-Snary, Sebastien Bonnet, Lian Tian, Jennifer Fu, Sandra Breuils-Bonnet, Steeve Provencher, Danchen Wu, Jeffrey Mewburn, Mark L Ormiston, Stephen L Archer
RATIONALE: Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy characterized by excessive pulmonary artery smooth muscle cells (PASMC) proliferation, migration, and apoptosis-resistance. This cancer-like phenotype is promoted by increased cytosolic calcium ([Ca2+]cyto), aerobic glycolysis and mitochondrial fission. OBJECTIVES: To determine how changes in mitochondrial calcium uniporter complex (MCUC) function influence mitochondrial dynamics and contribute to PAH's cancer-like phenotype...
September 20, 2016: American Journal of Respiratory and Critical Care Medicine
Corina T Madreiter-Sokolowski, Christiane Klec, Warisara Parichatikanond, Sarah Stryeck, Benjamin Gottschalk, Sergio Pulido, Rene Rost, Emrah Eroglu, Nicole A Hofmann, Alexander I Bondarenko, Tobias Madl, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Recent studies revealed that mitochondrial Ca(2+) channels, which control energy flow, cell signalling and death, are macromolecular complexes that basically consist of the pore-forming mitochondrial Ca(2+) uniporter (MCU) protein, the essential MCU regulator (EMRE), and the mitochondrial Ca(2+) uptake 1 (MICU1). MICU1 is a regulatory subunit that shields mitochondria from Ca(2+) overload. Before the identification of these core elements, the novel uncoupling proteins 2 and 3 (UCP2/3) have been shown to be fundamental for mitochondrial Ca(2+) uptake...
September 19, 2016: Nature Communications
Tim König, Simon E Tröder, Kavya Bakka, Anne Korwitz, Ricarda Richter-Dennerlein, Philipp A Lampe, Maria Patron, Mareike Mühlmeister, Sergio Guerrero-Castillo, Ulrich Brandt, Thorsten Decker, Ines Lauria, Angela Paggio, Rosario Rizzuto, Elena I Rugarli, Diego De Stefani, Thomas Langer
Mutations in subunits of mitochondrial m-AAA proteases in the inner membrane cause neurodegeneration in spinocerebellar ataxia (SCA28) and hereditary spastic paraplegia (HSP7). m-AAA proteases preserve mitochondrial proteostasis, mitochondrial morphology, and efficient OXPHOS activity, but the cause for neuronal loss in disease is unknown. We have determined the neuronal interactome of m-AAA proteases in mice and identified a complex with C2ORF47 (termed MAIP1), which counteracts cell death by regulating the assembly of the mitochondrial Ca(2+) uniporter MCU...
October 6, 2016: Molecular Cell
Sergio De La Fuente, Celia Fernandez-Sanz, Caitlin Vail, Elorm J Agra, Kira Holmstrom, Junhui Sun, Jyotsna Mishra, Dewight Williams, Toren Finkel, Elizabeth Murphy, Suresh K Joseph, Shey-Shing Sheu, György Csordás
Control of myocardial energetics by Ca2+ signal propagation to the mitochondrial matrix includes local Ca2+ delivery from sarcoplasmic reticulum (SR) ryanodine receptors (RyR2) to the inner mitochondrial membrane (IMM) Ca2+ uniporter (mtCU). mtCU activity in cardiac mitochondria is relatively low, while the IMM surface is large, due to extensive cristae folding. Hence, stochastically distributed mtCU may not suffice to support local Ca2+ transfer. We hypothesized that mtCU concentrated at mitochondria-SR associations would promote the effective Ca2+ transfer...
September 16, 2016: Journal of Biological Chemistry
Iulia I Nita, Yaki Caspi, Sagi Gudes, Dimitri Fishman, Shaya Lev, Michal Hersfinkel, Israel Sekler, Alexander M Binshtok
The nociceptive noxious heat-activated receptor - TRPV1, conducts calcium and sodium, thus producing a depolarizing receptor potential, leading to activation of nociceptive neurons. TRPV1-mediated calcium and sodium influx is negatively modulated by calcium, via calcium-dependent desensitization of TRPV1 channels. A mitochondrial Ca(2+) uniporter - MCU, controls mitochondrial Ca(2+) entry while a sodium/calcium transporter - NCLX shapes calcium and sodium transients by mediating sodium entry into and removing calcium from the mitochondria...
September 11, 2016: Biochimica et Biophysica Acta
Corina T Madreiter-Sokolowski, Benjamin Gottschalk, Warisara Parichatikanond, Emrah Eroglu, Christiane Klec, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
BACKGROUND/AIMS: Resveratrol and its derivate piceatannol are known to induce cancer cell-specific cell death. While multiple mechanisms of actions have been described including the inhibition of ATP synthase, changes in mitochondrial membrane potential and ROS levels, the exact mechanisms of cancer specificity of these polyphenols remain unclear. This paper is designed to reveal the molecular basis of the cancer-specific initiation of cell death by resveratrol and piceatannol. METHODS: The two cancer cell lines EA...
2016: Cellular Physiology and Biochemistry
Catharina E van Ewijk, Gabriel E Jacobs, Armand R J Girbes
BACKGROUND: Delirium is a frequently occurring syndrome in patients admitted to the intensive care unit (ICU) or medium care unit (MCU), yet the pathophysiology remains poorly understood. An excess of central serotonin can lead to an altered mental status, associated with autonomic hyperactivity, and neuromuscular excitation. Drugs with serotonergic properties are frequently and for prolonged periods administered to ICU/MCU patients. Therefore, central serotonergic toxicity may constitute a predisposing, contributing or precipitating factor in the emergence of delirium...
December 2016: Annals of Intensive Care
Guoqiang Wang, Elisabeth Mémin, Ishwarya Murali, Lawrence D Gaspers
The damage to liver mitochondria is universally observed in both humans and animal models after excessive alcohol consumption.  Acute alcohol treatment has been shown to stimulate calcium (Ca(2+)) release from internal stores in hepatocytes.  The resultant increase in cytosolic Ca(2+) is expected to be accumulated by neighboring mitochondria, which could potentially lead to mitochondrial Ca(2+) overload and injury.  Our data indicate that total and free mitochondrial matrix Ca(2+) levels are, indeed, elevated in hepatocytes isolated from alcohol-fed rats compared to their pair-fed control littermates...
August 31, 2016: Biochemical Journal
Hui Qu, Fanchen Kong, Guanjun Wang, Mingfei Zhou
Heteronuclear transition metal carbonyl cluster cations FeM(CO)8(+) (M = Co, Ni and Cu) and MCu(CO)7(+) (M = Co and Ni) are produced via a laser vaporization supersonic cluster ion source in the gas phase, which are each mass-selected and studied by infrared photodissociation spectroscopy in the carbonyl stretching frequency region. Their geometric and electronic structures are established by comparison of the experimental spectra with those derived from density functional theoretical calculations. The FeM(CO)8(+) (M = Co, Ni, Cu) complexes are determined to have eclipsed (CO)5Fe-M(CO)3(+) structures, and the MCu(CO)7(+) (M = Co, Ni) ions are characterized to have staggered (CO)4M-Cu(CO)3(+) structures...
September 22, 2016: Journal of Physical Chemistry. A
Samuel K Lee, Santhanam Shanmughapriya, Mac C Y Mok, Zhiwei Dong, Dhanendra Tomar, Edmund Carvalho, Sudarsan Rajan, Murray S Junop, Muniswamy Madesh, Peter B Stathopulos
Calcium (Ca(2+)) flux into the matrix is tightly controlled by the mitochondrial Ca(2+) uniporter (MCU) due to vital roles in cell death and bioenergetics. However, the precise atomic mechanisms of MCU regulation remain unclear. Here, we solved the crystal structure of the N-terminal matrix domain of human MCU, revealing a β-grasp-like fold with a cluster of negatively charged residues that interacts with divalent cations. Binding of Ca(2+) or Mg(2+) destabilizes and shifts the self-association equilibrium of the domain toward monomer...
September 22, 2016: Cell Chemical Biology
Chengzhou Zhu, Qiurong Shi, Shaofang Fu, Junhua Song, Haibing Xia, Dan Du, Yuehe Lin
To accelerate hydrogel formation and further simplify the synthetic procedure, a series of MCu (M = Pd, Pt, and Au) bimetallic aerogels is synthesized from the in situ reduction of metal precursors through enhancement of the gelation kinetics at elevated temperature. Moreover, the resultant PdCu aerogel with ultrathin nanowire networks exhibits excellent electrocatalytic performance toward ethanol oxidation, holding promise in fuel-cell applications.
October 2016: Advanced Materials
Renyi Liu, Wei Fan, Karsten Krüger, Yu Xiao, Christian Pilat, Michael Seimetz, Robert Ringseis, Eveline Baumgart-Vogt, Klaus Eder, Norbert Weissmann, Frank-Christoph Mooren
PURPOSE: The study aimed to investigate the effects of chronic moderate exercise on regulation of intracellular calcium signaling as an important link to proliferation capacity in murine splenic T lymphocytes. METHODS: Male CD1 Swiss mice were randomly assigned either to a control group (CG) or an exercise group (EG). EG mice performed voluntary exercise for 3 months. Lymphocytes were isolated from murine spleens and intracellular calcium was determined using Fura-2(AM) and fluorescence spectrometry...
August 12, 2016: Medicine and Science in Sports and Exercise
Bruna Babic, Xavier Keutgen, Pavel Nockel, Markke Miettinen, Corina Millo, Peter Herscovitch, Dhaval Patel, Naris Nilubol, Craig Cochran, Phillip Gorden, Electron Kebebew
CONTEXT: Insulinomas are usually due to a solitary tumor, but they can be challenging to localize. CASE DESCRIPTION: A 66-year-old woman presented with a 1-year history of episodic neuroglycopenic hypoglycemia and was suspected of having an insulinoma. On a supervised fast, she was found to be hypoglycemic at 39 mg/dL, with an insulin of 40 μU/mL 26 hours into the fast and a proinsulin of 35 pmol/L. Contrast-enhanced computed tomography and magnetic resonance imaging did not localize a pancreatic lesion...
October 2016: Journal of Clinical Endocrinology and Metabolism
María Calvo-Rodríguez, Mónica García-Durillo, Carlos Villalobos, Lucía Núñez
Aging is associated to cognitive decline and susceptibility to neuron death, two processes related recently to subcellular Ca(2+) homeostasis. Memory storage relies on mushroom spines stability that depends on store-operated Ca(2+) entry (SOCE). In addition, Ca(2+) transfer from endoplasmic reticulum (ER) to mitochondria sustains energy production but mitochondrial Ca(2+) overload promotes apoptosis. We have addressed whether SOCE and ER-mitochondria Ca(2+) transfer are influenced by culture time in long-term cultures of rat hippocampal neurons, a model of neuronal aging...
August 5, 2016: Biochimica et Biophysica Acta
Lea K Seidlmayer, Johannes Kuhn, Annette Berbner, Paula-Anahi Arias-Loza, Tatjana Williams, Mathias Kaspar, Martin Czolbe, Jennifer Q Kwong, Jeffery D Molkentin, Katrin Gertrud Heinze, Elena N Dedkova, Oliver Ritter
AIMS: Elevated levels of inositol 1,4,5-trisphosphate (IP3) in adult cardiac myocytes are typically associated with the development of cardiac hypertrophy, arrhythmias, and heart failure. IP3 enhances intracellular Ca(2+ )release via IP3 receptors (IP3Rs) located at the sarcoplasmic reticulum (SR). We aimed to determine whether IP3-induced Ca(2+ )release affects mitochondrial function and determine the underlying mechanisms. METHODS AND RESULTS: We compared the effects of IP3Rs- and ryanodine receptors (RyRs)-mediated cytosolic Ca(2+ )elevation achieved by endothelin-1 (ET-1) and isoproterenol (ISO) stimulation, respectively, on mitochondrial Ca(2+ )uptake and adenosine triphosphate (ATP) generation...
October 2016: Cardiovascular Research
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