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https://www.readbyqxmd.com/read/28439258/diabetic-cardiomyopathy-an-immunometabolic-perspective
#1
REVIEW
Paras K Mishra, Wei Ying, Shyam Sundar Nandi, Gautam K Bandyopadhyay, Kaushik K Patel, Sushil K Mahata
The heart possesses a remarkable inherent capability to adapt itself to a wide array of genetic and extrinsic factors to maintain contractile function. Failure to sustain its compensatory responses results in cardiac dysfunction, leading to cardiomyopathy. Diabetic cardiomyopathy (DCM) is characterized by left ventricular hypertrophy and reduced diastolic function, with or without concurrent systolic dysfunction in the absence of hypertension and coronary artery disease. Changes in substrate metabolism, oxidative stress, endoplasmic reticulum stress, formation of extracellular matrix proteins, and advanced glycation end products constitute the early stage in DCM...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28426939/high-throughput-agonist-shift-assay-development-for-the-analysis-of-m1-positive-allosteric-modulators
#2
Michelle F Homsher, Douglas C Beshore, Jason Cassaday, Brian Squadroni, Elizabeth Mohammed, Michelle Hartnett, Stephen Day, Lei Ma, David Pechter, Michelle D Smith, Fredrick Monsma, Paul Zuck, Michael F Finley, Victor N Uebele, Jeffrey D Hermes
Agonist shift assays feature cross-titrations of allosteric modulators and orthosteric ligands. Information generated in agonist shift assays can include a modulator's effect on the orthosteric agonist's potency (alpha) and efficacy (beta), as well as direct agonist activity of the allosteric ligand (tauB) and the intrinsic binding affinity of the modulator to the unoccupied receptor (KB). Because of the heavy resource demand and complex data handling, these allosteric parameters are determined infrequently during the course of a drug discovery program and on a relatively small subset of compounds...
April 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28424375/mitochondria-a-central-target-for-sex-differences-in-pathologies
#3
REVIEW
Renée Ventura-Clapier, Maryline Moulin, Jérôme Piquereau, Christophe Lemaire, Mathias Mericskay, Vladimir Veksler, Anne Garnier
It is increasingly acknowledged that a sex and gender specificity affects the occurrence, development, and consequence of a plethora of pathologies. Mitochondria are considered as the powerhouse of the cell because they produce the majority of energy-rich phosphate bonds in the form of adenosine tri-phosphate (ATP) but they also participate in many other functions like steroid hormone synthesis, reactive oxygen species (ROS) production, ionic regulation, and cell death. Adequate cellular energy supply and survival depend on mitochondrial life cycle, a process involving mitochondrial biogenesis, dynamics, and quality control via mitophagy...
May 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28421533/changes-in-the-prefrontal-glutamatergic-and-parvalbumin-systems-of-mice-exposed-to-unpredictable-chronic-stress
#4
Ryan Shepard, Laurence Coutellier
The prefrontal cortex (PFC) is highly sensitive to the effects of stress, a known risk factor of mood disorders including anxiety and depression. Abnormalities in PFC functioning have been well described in humans displaying stress-induced depressive symptoms, and hypoactivity of the PFC is now recognized to be a key feature of the depressed brain. However, little is known about the causes and mechanisms leading to this altered prefrontal functional activity in the context of stress-related mood disorders. We previously showed that unpredictable chronic mild stress (UCMS) in mice increases prefrontal expression of parvalbumin (PV), an activity-dependent calcium-binding albumin protein expressed in a specific subtype of GABAergic neurons, highlighting a potential mechanism through which chronic stress leads to hypofunction of the PFC...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28421204/diabetic-cardiomyopathy-current-approach-and-potential-diagnostic-and-therapeutic-targets
#5
REVIEW
Georgiana-Emmanuela Gilca, Gabriela Stefanescu, Oana Badulescu, Daniela-Maria Tanase, Iris Bararu, Manuela Ciocoiu
Although ischemic heart disease is the major cause of death in diabetic patients, diabetic cardiomyopathy (DCM) is increasingly recognized as a clinically relevant entity. Considering that it comprises a variety of mechanisms and effects on cardiac function, increasing the risk of heart failure and worsening the prognosis of this patient category, DCM represents an important complication of diabetes mellitus, with a silent development in its earlier stages, involving intricate pathophysiological mechanisms, including oxidative stress, defective calcium handling, altered mitochondrial function, remodeling of the extracellular matrix, and consequent deficient cardiomyocyte contractility...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28418600/validation-of-a-laboratory-developed-test-of-human-sperm-capacitation
#6
Melissa A Moody, Cristina Cardona, Alana J Simpson, T Timothy Smith, Alexander J Travis, G Charles Ostermeier
Sperm must undergo capacitation to become fertilization competent. Here we validated that monosialotetrahexosylganglioside (GM1 ) localization patterns, which were assessed in the Cap-Score™ Sperm Function Test, reflect a capacitated state in human sperm. First, we defined patterns representing sperm that do or do not respond to stimuli for capacitation. Sperm with "capacitated" patterns had exposed acrosomal carbohydrates and underwent acrosome exocytosis in response to calcium ionophore (A23187). Precision was evaluated by percent change of the Cap-Score measured for 50, 100, 150, and 200 sperm...
April 18, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28417145/relationship-in-pacemaker-neurons-between-the-long-term-correlations-of-membrane-voltage-fluctuations-and-the-corresponding-duration-of-the-inter-spike-interval
#7
Alberto Seseña Rubfiaro, José Rafael Godínez, Juan Carlos Echeverría
Several studies of the behavior in the voltage and frequency fluctuations of the neural electrical activity have been performed. Here, we explored the particular association between behavior of the voltage fluctuations in the inter-spike segment (VFIS) and the inter-spike intervals (ISI) of F1 pacemaker neurons from H. aspersa, by disturbing the intracellular calcium handling with cadmium and caffeine. The scaling exponent α of the VFIS, as provided by detrended fluctuations analysis, in conjunction with the corresponding duration of ISI to estimate the determination coefficient R (2) (48-50 intervals per neuron, N = 5) were all evaluated...
April 17, 2017: Journal of Membrane Biology
https://www.readbyqxmd.com/read/28410273/up-regulation-of-intracellular-calcium-handling-underlies-the-recovery-of-endotoxemic-cardiomyopathy-in-mice
#8
Justin C Morse, Joanne Huang, Natasha Khona, Edward J Miller, Deborah A Siwik, Wilson S Colucci, Ion A Hobai
BACKGROUND: In surviving patients, sepsis-induced cardiomyopathy is spontaneously reversible. In the absence of any experimental data, it is generally thought that cardiac recovery in sepsis simply follows the remission of systemic inflammation. Here the authors aimed to identify the myocardial mechanisms underlying cardiac recovery in endotoxemic mice. METHODS: Male C57BL/6 mice were challenged with lipopolysaccharide (7 μg/g, intraperitoneally) and followed for 12 days...
April 14, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28408640/long-term-but-not-short-term-high-fat-diet-induces-fiber-composition-changes-and-impaired-contractile-force-in-mouse-fast-twitch-skeletal-muscle
#9
Hiroaki Eshima, Yoshifumi Tamura, Saori Kakehi, Nagomi Kurebayashi, Takashi Murayama, Kyoko Nakamura, Ryo Kakigi, Takao Okada, Takashi Sakurai, Ryuzo Kawamori, Hirotaka Watada
In this study, we investigated the effects of a short-term and long-term high-fat diet (HFD) on morphological and functional features of fast-twitch skeletal muscle. Male C57BL/6J mice were fed a HFD (60% fat) for 4 weeks (4-week HFD) or 12 weeks (12-week HFD). Subsequently, the fast-twitch extensor digitorum longus muscle was isolated, and the composition of muscle fiber type, expression levels of proteins involved in muscle contraction, and force production on electrical stimulation were analyzed. The 12-week HFD, but not the 4-week HFD, resulted in a decreased muscle tetanic force on 100 Hz stimulation compared with control (5...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28408494/o-glcnacylation-and-cardiovascular-disease
#10
REVIEW
JaLessa N Wright, Helen E Collins, Adam R Wende, John C Chatham
The post-translational modification of serine and threonine residues of proteins found in numerous subcellular locations by O-linked N-acetylglucosamine (O-GlcNAc) is emerging as a key mediator of many cardiovascular pathophysiological processes. Early studies implicated increased protein O-GlcNAcylation as contributing to the cardiovascular complications associated with diabetes, whereas subsequent studies demonstrated that acute increases in O-GlcNAc levels were protective against ischemia/reperfusion injury...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28406991/a-mathematical-model-for-active-contraction-in-healthy-and-failing-myocytes-and-left-ventricles
#11
Li Cai, Yongheng Wang, Hao Gao, Yiqiang Li, Xiaoyu Luo
Cardiovascular disease is one of the leading causes of death worldwide, in particular myocardial dysfunction, which may lead to heart failure eventually. Understanding the electro-mechanics of the heart will help in developing more effective clinical treatments. In this paper, we present a multi-scale electro-mechanics model of the left ventricle (LV). The Holzapfel-Ogden constitutive law was used to describe the passive myocardial response in tissue level, a modified Grandi-Pasqualini-Bers model was adopted to model calcium dynamics in individual myocytes, and the active tension was described using the Niederer-Hunter-Smith myofilament model...
2017: PloS One
https://www.readbyqxmd.com/read/28404582/histone-deacetylase-activity-modulates-exercise-induced-skeletal-muscle-plasticity-in-zebrafish-danio-rerio
#12
Alec Izaac Marcus Simmonds, Frank Seebacher
Aerobic exercise has a positive impact on animals by enhancing skeletal muscle function and locomotor performance. Responses of skeletal muscle to exercise involve changes in energy metabolism, calcium handling, and the composition of contractile protein isoforms, which together influence contractile properties. Histone deacetylases (HDAC) can cause short-term changes in gene expression, and may thereby mediate plasticity in contractile properties of skeletal muscle in response to exercise. The aim of this project was to determine (in zebrafish, Danio rerio) the traits that mediate inter-individual differences in sustained and sprint performance, and to determine whether inhibiting class I and II HDACs mediates exercise-induced changes in these traits...
April 12, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28395010/inflammation-and-metabolic-cardiomyopathy
#13
Kazuhiko Nishida, Kinya Otsu
Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signalling pathways are directly triggered by nutrients. The pro-inflammatory mediators in adipocytes and macrophages infiltrating adipose tissue promote both local and systemic pro-inflammatory status...
March 15, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28393127/novel-junctophilin-2-mutation-a405s-is-associated-with-basal-septal-hypertrophy-and-diastolic-dysfunction
#14
Ann P Quick, Andrew P Landstrom, Qiongling Wang, David L Beavers, Julia O Reynolds, Giselle Barreto-Torres, Viet Tran, Jordan Showell, Leonne E Philippen, Shaine A Morris, Darlene Skapura, J Martijn Bos, Steen E Pedersen, Robia G Pautler, Michael J Ackerman, Xander H T Wehrens
BACKGROUND: Hypertrophic cardiomyopathy (HCM), defined as asymmetric left ventricular hypertrophy, is a leading cause of cardiac death in the young. Perturbations in calcium (Ca(2+)) handling proteins have been implicated in the pathogenesis of HCM. JPH2-encoded junctophilin 2 is a major component of the junctional membrane complex, the subcellular microdomain involved in excitation-contraction coupling. We hypothesized that a novel JPH2 mutation identified in patients with HCM is causally linked to HCM, and alters intracellular Ca(2+) signaling in a pro-hypertrophic manner...
February 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28384221/kchip2-regulates-the-cardiac-ca2-transient-and-myocyte-contractility-by-targeting-ryanodine-receptor-activity
#15
Drew M Nassal, Xiaoping Wan, Haiyan Liu, Kenneth R Laurita, Isabelle Deschênes
Pathologic electrical remodeling and attenuated cardiac contractility are featured characteristics of heart failure. Coinciding with these remodeling events is a loss of the K+ channel interacting protein, KChIP2. While, KChIP2 enhances the expression and stability of the Kv4 family of potassium channels, leading to a more pronounced transient outward K+ current, Ito,f, the guinea pig myocardium is unique in that Kv4 expression is absent, while KChIP2 expression is preserved, suggesting alternative consequences to KChIP2 loss...
2017: PloS One
https://www.readbyqxmd.com/read/28376362/incorporation-of-plla-micro-fillers-for-mechanical-reinforcement-of-calcium-phosphate-cement
#16
Antonio G B Castro, Alessandro Polini, Zohal Azami, Sander C G Leeuwenburgh, John A Jansen, Fang Yang, Jeroen J J P van den Beucken
Calcium phosphate cements (CPCs) are biocompatible, resorbable, injectable and osteoconductive. Those properties render such materials suitable for applications where bone repair and regeneration is required However, their brittle nature limits their application only to non-load-bearing applications. The incorporation of long polymeric fibers can improve the mechanical properties of CPCs, but aggregation is a major problem. Instead, short polymeric fillers can be easily dispersed in the cement matrix, but their reinforcing effect has not been studied yet...
March 28, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28369518/misregulation-of-calcium-handling-proteins-promotes-hyperactivation-of-calcineurin-nfat-signaling-in-skeletal-muscle-of-dm1-mice
#17
Aymeric Ravel-Chapuis, Guy Bélanger, Jocelyn Côté, Robin N Michel, Bernard J Jasmin
Myotonic Dystrophy type 1 (DM1) is caused by an expansion of CUG repeats in DMPK mRNAs. This mutation affects alternative splicing through misregulation of RNA-binding proteins. Amongst pre-mRNAs that are misspliced, several code for proteins involved in calcium homeostasis suggesting that calcium-handling and signaling are perturbed in DM1. Here, we analyzed expression of such proteins in DM1 mouse muscle. We found that the levels of several sarcoplasmic reticulum proteins (SERCA1, sarcolipin and calsequestrin) are altered, likely contributing to an imbalance in calcium homeostasis...
March 27, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28349262/%C3%AE-alanine-supplementation-improves-in-vivo-fresh-and-fatigued-skeletal-muscle-relaxation-speed
#18
Rebecca Louise Jones, Cleveland Thomas Barnett, Joel Davidson, Billy Maritza, William D Fraser, Roger Harris, Craig Sale
PURPOSE: In fresh muscle, supplementation with the rate-limiting precursor of carnosine, β-alanine (BA), results in a decline in muscle half-relaxation time (HRT) potentially via alterations to calcium (Ca(2+)) handling. Accumulation of hydrogen cation (H(+)) has been shown to impact Ca(2+) signalling during muscular contraction, carnosine has the potential to serve as a cytoplasmic regulator of Ca(2+) and H(+) coupling, since it binds to both ions. The present study examined the effect of BA supplementation on intrinsic in-vivo isometric knee extensor force production and muscle contractility in both fresh and fatigued human skeletal muscle assessed during voluntary and electrically evoked (nerve and superficial muscle stimulation) contractions...
March 27, 2017: European Journal of Applied Physiology
https://www.readbyqxmd.com/read/28346014/intestinal-absorption-and-renal-reabsorption-of-calcium-throughout-postnatal-development
#19
Megan R Beggs, R Todd Alexander
Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood...
April 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28336810/role-of-transient-receptor-potential-vanilloid-1-trpv1-in-the-modulation-of-airway-smooth-muscle-tone-and-calcium-handling
#20
Gene T Yocum, Jun Chen, Christine H Choi, Elizabeth A Townsend, Yi Zhang, Dingbang Xu, Xiao Wen Fu, Michael J Sanderson, Charles W Emala
Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on airway nerve fibers that modulates afferent signals resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close association with sarco/endoplasmic reticulum Ca2+ ATPase 2...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
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