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https://www.readbyqxmd.com/read/29229615/defective-amplifying-pathway-of-%C3%AE-cell-secretory-response-to-glucose-in-type-2-diabetes-integrated-modeling-of-in-vitro-and-in-vivo-evidence
#1
Eleonora Grespan, Toni Giorgino, Silva Arslanian, Andrea Natali, Ele Ferrannini, Andrea Mari
In vivo studies have investigated the role of β-cell dysfunction in type 2 diabetes (T2D), while in vitro research on islets has elucidated key mechanisms controlling insulin secretion rate (ISR). However, the relevance of the cellular mechanisms identified in vitro, i.e., the triggering and amplifying pathways, has not been established in vivo Furthermore, the mechanisms underpinning β-cell dysfunction in T2D remain undetermined. We propose a unifying explanation of several characteristic features of insulin secretion, both in vitro and in vivo, using a mathematical model...
December 11, 2017: Diabetes
https://www.readbyqxmd.com/read/29228618/calcium-homeostasis-and-endoplasmic-reticulum-stress-are-involved-in-salvianolic-acid-b-offered-protection-against-cardiac-toxicity-of-arsenic-trioxide
#2
Jing-Yi Zhang, Bin Zhang, Min Wang, Wei Wang, Ping Liao, Gui-Bo Sun, Xiao-Bo Sun
Arsenic trioxide (ATO) is a potent anticancer agent used to treat acute promyelocytic leukemia. However, its cardiotoxicity limits ATO's widespread clinical use. Previous studies demonstrated that ATO may aggravate Ca2+ overload and promote endoplasmic reticulum stress (ERS). Salvianolic acid B (Sal B) is cardioprotective against ATO and enhances ATO's anticancer activities. The present study assessed whether the Sal B protective effect was related to maintenance of Ca2+ homeostasis and inhibition of ER stress...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29227474/a-proteolytic-fragment-of-histone-deacetylase-4-protects-the-heart-from-failure-by-regulating-the-hexosamine-biosynthetic-pathway
#3
Lorenz H Lehmann, Zegeye H Jebessa, Michael M Kreusser, Axel Horsch, Tao He, Mariya Kronlage, Matthias Dewenter, Viviana Sramek, Ulrike Oehl, Jutta Krebs-Haupenthal, Albert H von der Lieth, Andrea Schmidt, Qiang Sun, Julia Ritterhoff, Daniel Finke, Mirko Völkers, Andreas Jungmann, Sven W Sauer, Christian Thiel, Alexander Nickel, Michael Kohlhaas, Michaela Schäfer, Carsten Sticht, Christoph Maack, Norbert Gretz, Michael Wagner, Ali El-Armouche, Lars S Maier, Juan E Camacho Londoño, Benjamin Meder, Marc Freichel, Hermann-Josef Gröne, Patrick Most, Oliver J Müller, Stephan Herzig, Eileen E M Furlong, Hugo A Katus, Johannes Backs
The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP)...
December 11, 2017: Nature Medicine
https://www.readbyqxmd.com/read/29222635/cardiovascular-response-of-rat-aorta-to-di-2-ethylhexyl-phthalate-dehp-exposure
#4
Melissa Mariana, Joana Feiteiro, Elisa Cairrao
Phthalates are one of the main constituents of plastic, reaching up to 40% of the total plastic weight, and their main function is to impart flexibility/elasticity to polymers that would otherwise be rigid. Phthalates are known as endocrine disruptors, since they can interfere with hormone homeostasis. Regarding the cardiovascular system, it was already shown the effects of di-(2-ethylhexyl) phthalate (DEHP) exposure with significant changes in several calcium-handling proteins and an increase in the blood pressure of mice offspring, suggesting that DEHP leads to vasocontraction...
December 8, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29212933/characterization-of-an-influenza-virus-pseudotyped-with-ebolavirus-glycoprotein
#5
Julie Xiao, Pramila Rijal, Lisa Schimanski, Arun Kumar Tharkeshwar, Edward Wright, Wim Annaert, Alain Townsend
We have produced a new Ebola virus pseudotype: E-S-FLU, which can be handled in biosafety level-1/2 containment for laboratory analysis. E-S-FLU is a single cycle influenza virus coated with Ebolavirus glycoprotein, and it encodes enhanced green fluorescence protein as a reporter that replaces the influenza haemagglutinin. MDCK-SIAT1 cells were transduced to express Ebolavirus glycoprotein as a stable transmembrane protein for E-S-FLU production. Infection of cells by E-S-FLU was dependent on Niemann-Pick C1 protein, which is the well-characterized receptor for Ebola virus entry at the late endosome/lysosome membrane...
December 6, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29209189/spike-triggered-regression-for-synaptic-connectivity-reconstruction-in-neuronal-networks
#6
Yaoyu Zhang, Yanyang Xiao, Douglas Zhou, David Cai
How neurons are connected in the brain to perform computation is a key issue in neuroscience. Recently, the development of calcium imaging and multi-electrode array techniques have greatly enhanced our ability to measure the firing activities of neuronal populations at single cell level. Meanwhile, the intracellular recording technique is able to measure subthreshold voltage dynamics of a neuron. Our work addresses the issue of how to combine these measurements to reveal the underlying network structure. We propose the spike-triggered regression (STR) method, which employs both the voltage trace and firing activity of the neuronal population to reconstruct the underlying synaptic connectivity...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/29201273/proinflammatory-cytokines-are-soluble-mediators-linked-with-ventricular-arrhythmias-and-contractile-dysfunction-in-a-rat-model-of-metabolic-syndrome
#7
Evaristo Fernández-Sada, Alejandro Torres-Quintanilla, Christian Silva-Platas, Noemí García, B Cicero Willis, César Rodríguez-Rodríguez, Erasmo De la Peña, Judith Bernal-Ramírez, Niria Treviño-Saldaña, Yuriana Oropeza-Almazán, Elena C Castillo, Leticia Elizondo-Montemayor, Karla Carvajal, Gerardo García-Rivas
Metabolic syndrome (MS) increases cardiovascular risk and is associated with cardiac dysfunction and arrhythmias, although the precise mechanisms are still under study. Chronic inflammation in MS has emerged as a possible cause of adverse cardiac events. Male Wistar rats fed with 30% sucrose in drinking water and standard chow for 25-27 weeks were compared to a control group. The MS group showed increased weight, visceral fat, blood pressure, and serum triglycerides. The most important increases in serum cytokines included IL-1β (7-fold), TNF-α (84%), IL-6 (41%), and leptin (2-fold), the latter also showing increased gene expression in heart tissue (35-fold)...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29190010/are-mechanically-sensitive-regulators-involved-in-the-function-and-patho-physiology-of-cerebral-palsy-related-contractures
#8
Jessica Pingel, Frank Suhr
Skeletal muscle tissue is mechanosensitive, as it is able to sense mechanical impacts and to translate these into biochemical signals making the tissue adapt. Among its mechanosensitive nature, skeletal muscle tissue is the largest metabolic organ of the human body. Disturbances in skeletal muscle mechanosensing and metabolism cause and contribute to many diseases, i.e. muscular dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type 2. A less commonly focused muscle-related disorder is clinically known as muscle contractures that derive from cerebral palsy (CP) conditions in young and adults...
November 30, 2017: Journal of Muscle Research and Cell Motility
https://www.readbyqxmd.com/read/29155307/sex-steroids-and-the-kidney-role-in-renal-calcium-and-phosphate-handling
#9
REVIEW
Rougin Khalil, Na Ri Kim, Ferran Jardi, Dirk Vanderschueren, Frank Claessens, Brigitte Decallonne
Calcium and phosphate are vital for the organism and constitute essential components of the skeleton. Serum levels are tightly hormonally regulated and maintained by exchange with three major sources: the intestines, the kidney and the bone. The effects of sex steroids on the bone have been extensively studied and it is well known that sex steroid deficiency induces bone loss, indirectly influencing renal calcium and phosphate homeostasis. However, it is unknown whether sex steroids also directly regulate renal calcium and phosphate handling, hereby potentially indirectly impacting on bone...
November 20, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29150445/the-antiapoptotic-protein-hax-1-mediates-half-of-phospholamban-s-inhibitory-activity-on-calcium-cycling-and-contractility-in-the-heart
#10
Philip A Bidwell, Kobra Haghighi, Evangelia G Kranias
The antiapoptotic protein HS-associated protein X-1 (HAX-1) localizes to sarcoplasmic reticulum (SR) in the heart and interacts with the small membrane protein phospholamban (PLN), inhibiting the cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA2a) in the regulation of overall calcium handling and heart muscle contractility. However, because global HAX-1 deletion causes early lethality, how much endogenous HAX-1 contributes to PLN's inhibitory activity on calcium cycling is unknown. We therefore generated a cardiac-specific and inducible knockout mouse model...
November 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29149838/genetic-variation-in-populations-of-the-earthworm-lumbricus-rubellus-across-contaminated-mine-sites
#11
Craig Anderson, Luis Cunha, Pierfrancesco Sechi, Peter Kille, David Spurgeon
BACKGROUND: Populations of the earthworm, Lumbricus rubellus, are commonly found across highly contaminated former mine sites and are considered to have under-gone selection for mitigating metal toxicity. Comparison of adapted populations with those found on less contaminated soils can provide insights into ecological processes that demonstrate the long-term effects of soil contamination. Contemporary sequencing methods allow for portrayal of demographic inferences and highlight genetic variation indicative of selection at specific genes...
November 17, 2017: BMC Genetics
https://www.readbyqxmd.com/read/29149487/fabrication-of-chelate-setting-%C3%AE-tricalcium-phosphate-cement-using-sodium-citrate-and-sodium-alginate-as-mixing-solution-and-its-in-vivo-osteoconductivity
#12
Toshiisa Konishi, Poon Nian Lim, Michiyo Honda, Masaki Nagaya, Hiroshi Nagashima, Eng San Thian, Mamoru Aizawa
Moldable and injectable calcium-phosphate cements (CPCs) are material candidates for bone replacement applications. In the present study, we examined the effectiveness of sodium alginate and sodium citrate additives to the liquid phase of CPC, in improving its handling property as well as mechanical strength. The use of these additives enhanced the handling property significantly, in terms of consistency as compared to CPC without additives due to the liquefying effect caused by the adsorption of citrate ions on the cement particles...
November 17, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/29136828/compact-detectors-made-of-paired-leds-for-photometric-and-fluorometric-measurements-on-paper
#13
Marta Fiedoruk-Pogrebniak, Mateusz Granica, Robert Koncki
The utility of strikingly simple and cheap optoelectronic detectors operating according to a Paired-Emitter-Detector-Diode (PEDD) principle for microfluidic paper-based analytical devices (μPAD) has been experimentally confirmed. The prototypes of these compact detectors have been made of only two customary light emitting diodes without any additional optical parts like lens, filters, fibers etc. Moreover, for their operation economic and portable equipment is required (low-power circuit and ordinary voltmeter)...
February 1, 2018: Talanta
https://www.readbyqxmd.com/read/29134555/ciprofloxacin-loaded-calcium-alginate-wafers-prepared-by-freeze-drying-technique-for-potential-healing-of-chronic-diabetic-foot-ulcers
#14
Asif Ahmed, Giulia Getti, Joshua Boateng
Calcium alginate (CA) wafer dressings were prepared by lyophilization of hydrogels to deliver ciprofloxacin (CIP) directly to the wound site of infected diabetic foot ulcers (DFUs). The dressings were physically characterized by scanning electron microscopy (SEM), texture analysis (for mechanical and in vitro adhesion properties), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). Further, functional properties essential for wound healing, i.e., porosity, in vitro swelling index, water absorption (Aw), equilibrium water content (EWC), water vapor transmission rate (WVTR), evaporative water loss (EWL), moisture content, in vitro drug release and kinetics, antimicrobial activity, and cell viability (MTT assay) were investigated...
November 13, 2017: Drug Delivery and Translational Research
https://www.readbyqxmd.com/read/29129349/electrical-and-mechanical-alternans-during-ventricular-tachycardia-with-moderate-chronic-heart-failure
#15
Ikeotunye Royal Chinyere, Talal Moukabary, Steven Goldman, Elizabeth Juneman
A chronic heart failure (CHF) rat underwent epicardial programmed electrical stimulation (PES). Ventricular tachycardia (VT) developed during PES. Mechanical alternans was noted despite fixed tachycardia cycle length. Anti-tachycardia pacing attempts initiated a second VT that generated pulse intermittently and then degenerated into pulseless VT with electrical alternans.To our knowledge electrical and mechanical alternans have not been recorded in animal models of CHF during VT. The distinct events of mechanical alternans and electrical alternans may be indicative of progressively worsened calcium handling in the compromised cardiomyocytes...
September 23, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/29125993/substrate-and-mechanotransduction-influence-serca2a-localization-in-human-pluripotent-stem-cell-derived-cardiomyocytes-affecting-functional-performance
#16
Sebastian Martewicz, Elena Serena, Susi Zatti, Gordon Keller, Nicola Elvassore
Physical cues are major determinants of cellular phenotype and evoke physiological and pathological responses on cell structure and function. Cellular models aim to recapitulate basic functional features of their in vivo counterparts or tissues in order to be of use in in vitro disease modeling or drug screening and testing. Understanding how culture systems affect in vitro development of human pluripotent stem cell (hPSC)-derivatives allows optimization of cellular human models and gives insight in the processes involved in their structural organization and function...
October 16, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29123029/phenotypic-dissection-of-the-mouse-ren-1-d-knockout-by-complementation-with-human-renin
#17
Charlotte Buckley, Robert J Nelson, Linda J Mullins, Matthew Gf Sharp, Stewart Fleming, Christopher J Kenyon, Sabrina Semprini, Dominik Steppan, Janos Peti-Peterdi, Armin Kurtz, Helen Christian, John J Mullins
Normal renin synthesis and secretion is important for the maintenance of juxtaglomerular apparatus architecture. Mice lacking a functional Ren-1(d) gene are devoid of renal juxtaglomerular cell granules and exhibit an altered macula densa morphology. Due to the species-specificity of renin activity, transgenic mice are ideal models for experimentally investigating and manipulating expression patterns of the human renin gene in a native cellular environment without confounding Renin-angiotensin-system interactions...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29117223/sensitivity-analysis-revealing-the-effect-of-modulating-ionic-mechanisms-on-calcium-dynamics-in-simulated-human-heart-failure
#18
Maria T Mora, Jose M Ferrero, Lucia Romero, Beatriz Trenor
Abnormal intracellular Ca2+ handling is the major contributor to the depressed cardiac contractility observed in heart failure. The electrophysiological remodeling associated with this pathology alters both the action potential and the Ca2+ dynamics, leading to a defective excitation-contraction coupling that ends in mechanical dysfunction. The importance of maintaining a correct intracellular Ca2+ concentration requires a better understanding of its regulation by ionic mechanisms. To study the electrical activity and ionic homeostasis of failing myocytes, a modified version of the O'Hara et al...
2017: PloS One
https://www.readbyqxmd.com/read/29116357/injectable-biomechanically-robust-biodegradable-and-osseointegrative-bone-cement-for-percutaneous-kyphoplasty-and-vertebroplasty
#19
Huiling Liu, Bin Liu, Chunxia Gao, Bin Meng, Huilin Yang, Haiyang Yu, Lei Yang
PURPOSE: Poly(methyl methacrylate) (PMMA) cement is widely used for percutaneous kyphoplasty and vertebroplasty (PKP and PVP) but possesses formidable shortcomings due to non-degradability. Here, a biodegradable replacement is developed. METHODS: Calcium phosphate cement (CPC) was redesigned by incorporating starch and BaSO4 (new cement named as CPB). The biomechanical, biocompatibility, osseointegrative and handling properties of CPB were systematically evaluated in vitro and in vivo by the models of osteoporotic sheep vertebra, rat subcutaneous implantation and rat femoral defect...
November 7, 2017: International Orthopaedics
https://www.readbyqxmd.com/read/29110288/myocardial-perfusion-imaging-lessons-learned-and-work-to-be-done-update
#20
Ami E Iskandrian, Vasken Dilsizian, Ernest V Garcia, Rob S Beanlands, Manuel Cerqueira, Prem Soman, Daniel S Berman, Alberto Cuocolo, Andrew J Einstein, Charity J Morgan, Fadi G Hage, Heinrich R Schelbert, Jeroen J Bax, Joseph C Wu, Leslee J Shaw, Mehran M Sadeghi, Nagara Tamaki, Philipp A Kaufmann, Robert Gropler, Sharmila Dorbala, William Van Decker
As the second term of our commitment to Journal begins, we, the editors, would like to reflect on a few topics that have relevance today. These include prognostication and paradigm shifts; Serial testing: How to handle data? Is the change in perfusion predictive of outcome and which one? Ischemia-guided therapy: fractional flow reserve vs perfusion vs myocardial blood flow; positron emission tomography (PET) imaging using Rubidium-82 vs N-13 ammonia vs F-18 Flurpiridaz; How to differentiate microvascular disease from 3-vessel disease by PET? The imaging scene outside the United States, what are the differences and similarities? Radiation exposure; Special issues with the new cameras? Is attenuation correction needed? Are there normal databases and are these specific to each camera system? And finally, hybrid imaging with single-photon emission tomography or PET combined with computed tomography angiography or coronary calcium score...
November 6, 2017: Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology
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