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https://www.readbyqxmd.com/read/29351582/sco2-mutations-cause-early-onset-axonal-charcot-marie-tooth-disease-associated-with-cellular-copper-deficiency
#1
Adriana P Rebelo, Dimah Saade, Claudia P Pereira, Amjad Farooq, Tyler C Huff, Lisa Abreu, Carlos T Moraes, Diana Mnatsakanova, Kathy Mathews, Hua Yang, Eric A Schon, Stephan Zuchner, Michael E Shy
Recessive mutations in the mitochondrial copper-binding protein SCO2, cytochrome c oxidase (COX) assembly protein, have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency. Significantly expanding the known phenotypic spectrum, we identified compound heterozygous variants in SCO2 in two unrelated patients with axonal polyneuropathy, also known as Charcot-Marie-Tooth disease type 4. Different from previously described cases, our patients developed predominantly motor neuropathy, they survived infancy, and they have not yet developed the cardiomyopathy that causes death in early infancy in reported patients...
January 16, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29351565/sumo-targeting-of-a-stress-tolerant-ulp1-sumo-protease
#2
Jennifer Peek, Catherine Harvey, Dreux Gray, Danny Rosenberg, Likhitha Kolla, Reuben Levy-Myers, Rui Yin, Jonathan L McMurry, Oliver Kerscher
SUMO proteases of the SENP/Ulp family are master regulators of both sumoylation and desumoylation and regulate SUMO homeostasis in eukaryotic cells. SUMO conjugates rapidly increase in response to cellular stress, including nutrient starvation, hypoxia, osmotic stress, DNA damage, heat shock, and other proteotoxic stressors. Nevertheless, little is known about the regulation and targeting of SUMO proteases during stress. To this end we have undertaken a detailed comparison of the SUMO-binding activity of the budding yeast protein Ulp1 (ScUlp1) and its ortholog in the thermotolerant yeast Kluyveromyces marxianus, KmUlp1...
2018: PloS One
https://www.readbyqxmd.com/read/29351515/understanding-key-mechanisms-of-exercise-induced-cardiac-protection-to-mitigate-disease-current-knowledge-and-emerging-concepts
#3
Bianca C Bernardo, Jenny Y Y Ooi, Kate L Weeks, Natalie L Patterson, Julie R McMullen
The benefits of exercise on the heart are well recognized, and clinical studies have demonstrated that exercise is an intervention that can improve cardiac function in heart failure patients. This has led to significant research into understanding the key mechanisms responsible for exercise-induced cardiac protection. Here, we summarize molecular mechanisms that regulate exercise-induced cardiac myocyte growth and proliferation. We discuss in detail the effects of exercise on other cardiac cells, organelles, and systems that have received less or little attention and require further investigation...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29351511/chemogenetic-tools-for-causal-cellular-and-neuronal-biology
#4
Deniz Atasoy, Scott M Sternson
Chemogenetic technologies enable selective pharmacological control of specific cell populations. An increasing number of approaches have been developed that modulate different signaling pathways. Selective pharmacological control over G protein-coupled receptor signaling, ion channel conductances, protein association, protein stability, and small molecule targeting allows modulation of cellular processes in distinct cell types. Here, we review these chemogenetic technologies and instances of their applications in complex tissues in vivo and ex vivo...
January 1, 2018: Physiological Reviews
https://www.readbyqxmd.com/read/29351470/increased-pro-renin-receptor-expression-in-subfornical-organ-neurons-in-hypertensive-humans
#5
Silvana G Cooper, Darshan P Trivedi, Rieko Yamamoto, Caleb J Worker, Cheng-Yuan Feng, Jacob T Sorensen, Wei Yang, Zhenggang Xiong, Yumei Feng
The central nervous system plays an important role in essential hypertension in humans and in animal models of hypertension through modulation of sympathetic activity, and sodium and body fluid homeostasis. Data from animal models of hypertension suggest that the renin-angiotensin system in the subfornical organ (SFO) of the brain is critical for hypertension development. We recently reported that the brain (pro)renin receptor (PRR) is a novel component of the brain renin-angiotensin system and could be a key initiator of the pathogenesis of hypertension...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351467/from-ionic-to-cellular-variability-in-human-atrial-myocytes-an-integrative-computational-and-experimental-study
#6
Anna Muszkiewicz, Xing Liu, Alfonso Bueno-Orovio, Brodie A J Lawson, Kevin Burrage, Barbara Casadei, Blanca Rodriguez
Variability refers to differences in physiological function between individuals, which may translate into different disease susceptibility and treatment efficacy. Experiments in human cardiomyocytes face wide variability and restricted tissue access; under these conditions computational models are a useful complementary tool. We conducted a computational and experimental investigation in cardiomyocytes isolated from samples of the right atrial appendage of patients undergoing cardiac surgery to evaluate the impact of variability in action potentials (APs) and sub-cellular ionic densities on calcium transient dynamics...
December 22, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29351437/metabolic-reprogramming-in-the-pathogenesis-of-chronic-lung-diseases-including-bpd-copd-and-pulmonary-fibrosis
#7
Haifeng Zhao, Phyllis A Dennery, Hongwei Yao
The metabolism of nutrient substrates including glucose, glutamine and fatty acids provides acetyl-CoA for the tricarboxylic acid cycle to generate energy, and metabolites for the biosynthesis of biomolecules including nucleotides, proteins, and lipids. It has been shown that metabolism of glucose, fatty acid, and glutamine plays important roles in modulating cellular proliferation, differentiation, apoptosis, autophagy, senescence, and inflammatory responses. All these cellular processes contribute to the pathogenesis of chronic lung diseases, including bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis...
January 4, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351418/red-blood-cell-antibody-induced-anemia-causes-differential-degrees-of-tissue-hypoxia-in-kidney-and-brain
#8
Nikhil Mistry, C David Mazer, John G Sled, Alan H Lazarus, Lindsay S Cahill, Max Solish, Yu-Qing Zhou, Nadya Romanova, Alexander Gm Hare, Allan Doctor, Joseph A Fisher, Keith R Brunt, Jeremy A Simpson, Gregory M T Hare
Moderate anemia is associated with increased mortality and morbidity, including acute kidney injury (AKI), in surgical patients. A red blood cell (RBC)-specific antibody model was utilized to determine if moderate subacute anemia could result in tissue hypoxia as a potential mechanism of injury. Cardiovascular and hypoxic cellular responses were measured in transgenic mice capable of expressing hypoxia-inducible factor-1α (HIF-1α)-luciferase activity in vivo. Antibody-mediated anemia was associated with mild intravascular hemolysis (6 hours) and splenic RBC sequestration (day 4), resulting in a nadir hemoglobin concentration of 89{plus minus}13 g/L at day 4...
January 10, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29351417/zinc-regulates-vascular-endothelial-activities-through-zinc-sensing-receptor-znr-gpr39
#9
Donghui Zhu, Yingchao Su, Yufeng Zheng, Bingmei M Fu, Liping Tang, Yi-Xian Qin
Zn2+ is an essential element for cell survival/growth, and its deficiency is linked to many disorders. Extracellular Zn2+ concentration changes participate in modulating fundamental cellular processes such as proliferation, secretion, ion transport, and cell signal transduction in a mechanism that is not well understood. Here, we hypothesize that the Zn-sensing receptor ZnR/GPR39, found in tissues where dynamic Zn2+ homeostasis takes place, enables extracellular Zn2+ to trigger intracellular signaling pathways regulating key cell functions in vascular cells...
December 13, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351413/mitochondrial-content-is-preserved-throughout-disease-progression-in-the-mdx-mouse-model-of-duchenne-muscular-dystrophy-regardless-of-taurine-supplementation
#10
Robert G Barker, Victoria L Wyckelsma, Hongyang Xu, Robyn M Murphy
Mitochondrial dysfunction is a pathological feature of Duchenne muscular Dystrophy (DMD), a debilitating and fatal neuromuscular disorder characterised by progressive muscle wasting and weakness. Mitochondria are a source of cellular ATP and involved in Ca2+ regulation and apoptotic signalling. Ameliorating aberrant mitochondrial function has therapeutic potential for reducing DMD disease severity. The dystrophic mdx mouse exhibits peak muscle damage at 21-28d which stabilises after 8 weeks. The amino acid taurine is implicated in mitochondrial health and function, with endogenous concentrations low when measured during the cycle of peak muscle damage in mdx mice...
December 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351412/expression-of-ctgf-ccn2-in-response-to-lpa-is-stimulated-by-fibrotic-extracellular-matrix-via-the-integrin-fak-axis
#11
Camilo Riquelme-Guzman, Osvaldo Contreras, Enrique Brandan
Fibrosis is a common feature of several chronic diseases, and is characterized by exacerbated accumulation of extracellular matrix (ECM). Understanding the cellular and molecular mechanisms involved in the development of this condition is crucial for designing efficient treatments for those pathologies. Connective tissue growth factor (CTGF/CCN2) is a pleiotropic protein with strong pro-fibrotic activity. In this report, we present experimental evidence showing that ECM stimulates the synthesis of CTGF in response to lysophosphatidic acid (LPA)...
December 27, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351409/pharmacological-activation-of-ppar%C3%AE-inhibits-hypoxia-induced-proliferation-through-a-caveolin-1-targeted-and-dependent-mechanism-in-pasmcs
#12
Kai Yang, Mingming Zhao, Junyi Huang, Chenting Zhang, Qiu Yu Zheng, Yuqin Chen, Haiyang Jiang, Wenju Lu, Jian Wang
Previously, we and others have demonstrated that activation of peroxisome proliferator- activated receptor γ (PPARγ) by specific pharmacological agonists inhibits the pathogenesis of chronic hypoxia-induced pulmonary hypertension (CHPH) by suppressing the proliferation and migration in distal pulmonary arterial smooth muscle cells (PASMCs). Moreover, these beneficial effects of PPARγ are mediated by targeting the intracellular calcium homeostasis and store-operated calcium channel (SOCC) proteins, including the main caveolae component caveolin-1...
January 3, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351408/choroid-plexus-epithelial-cells-express-the-adhesion-protein-p-cadherin-at-cell-cell-contacts-and-syntaxin-4-in-the-luminal-membrane-domain
#13
Inga Baasch Christensen, Esben Nees Mogensen, Helle Hasager Damkier, Jeppe Praetorius
The choroid plexus epithelial cells (CPECs) belong to a small group of polarized cells, where the Na+,K+-ATPase is expressed in the luminal membrane. The basic polarity of the cells is, therefore, still debated. We investigated the subcellular distribution of an array of proteins known to play fundamental roles in either in establishing and maintaining basic cell polarity or the polarized delivery and recycling of plasma membrane proteins. Immunofluorescence histochemical analysis was applied to determine the subcellular localization of apical and basolateral membrane determinants...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351405/acute-down-regulation-of-mir-199a-attenuates-sepsis-induced-acute-lung-injury-by-targeting-sirt1
#14
Yang Liu, Hao Guan, Ju-Lei Zhang, Zhao Zheng, Hong-Tao Wang, Ke Tao, Shi-Chao Han, Lin-Lin Su, Dahai Hu
MiR-199a is a novel gene regulator with an important role in inflammation and lung injury. However, its role in the pathogenesis of sepsis-induced acute respiratory distress syndrome (ARDS) is currently unknown. Our study explored the role of miR-199a in sepsis-induced ARDS and its mechanism of action. First, we found that LPS could up-regulate miR-199a in alveolar macrophages. Down-regulation of miR-199a inhibited the up-regulation of inflammatory cytokines in alveolar macrophages and induced the remission of histopathologic changes, the reduction of pro-inflammatory cytokines, and the up-regulation of apoptosis protein expression in an ARDS lung, showing a protective role for miR-199a...
January 10, 2018: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29351332/impedance-spectroscopy-of-single-bacterial-nanofilament-reveals-water-mediated-charge-transfer
#15
Artem Grebenko, Vyacheslav Dremov, Petr Barzilovich, Anton Bubis, Konstantin Sidoruk, Tatiyana Voeikova, Zarina Gagkaeva, Timur Chernov, Evgeny Korostylev, Boris Gorshunov, Konstantin Motovilov
For decades respiratory chain and photosystems were the main firing field of the studies devoted to mechanisms of electron transfer in proteins. The concept of conjugated lateral electron and transverse proton transport during cellular respiration and photosynthesis, which was formulated in the beginning of 1960-s, has been confirmed by thousands of experiments. However, charge transfer in recently discovered bacterial nanofilaments produced by various electrogenic bacteria is regarded currently outside of electron and proton conjugation concept...
2018: PloS One
https://www.readbyqxmd.com/read/29351275/a-mathematical-model-for-il-6-mediated-stem-cell-driven-tumor-growth-and-targeted-treatment
#16
Fereshteh Nazari, Alexander T Pearson, Jacques Eduardo Nör, Trachette L Jackson
Targeting key regulators of the cancer stem cell phenotype to overcome their critical influence on tumor growth is a promising new strategy for cancer treatment. Here we present a modeling framework that operates at both the cellular and molecular levels, for investigating IL-6 mediated, cancer stem cell driven tumor growth and targeted treatment with anti-IL6 antibodies. Our immediate goal is to quantify the influence of IL-6 on cancer stem cell self-renewal and survival, and to characterize the subsequent impact on tumor growth dynamics...
January 19, 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29351274/dna-polymerase-iv-primarily-operates-outside-of-dna-replication-forks-in-escherichia-coli
#17
Sarah S Henrikus, Elizabeth A Wood, John P McDonald, Michael M Cox, Roger Woodgate, Myron F Goodman, Antoine M van Oijen, Andrew Robinson
In Escherichia coli, damage to the chromosomal DNA induces the SOS response, setting in motion a series of different DNA repair and damage tolerance pathways. DNA polymerase IV (pol IV) is one of three specialised DNA polymerases called into action during the SOS response to help cells tolerate certain types of DNA damage. The canonical view in the field is that pol IV primarily acts at replisomes that have stalled on the damaged DNA template. However, the results of several studies indicate that pol IV also acts on other substrates, including single-stranded DNA gaps left behind replisomes that re-initiate replication downstream of a lesion, stalled transcription complexes and recombination intermediates...
January 19, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29351249/utilizing-dietary-micronutrient-ratios-in-nutritional-research-may-be-more-informative-than-focusing-on-single-nutrients
#18
Owen J Kelly, Jennifer C Gilman, Jasminka Z Ilich
The 2015 US dietary guidelines advise the importance of good dietary patterns for health, which includes all nutrients. Micronutrients are rarely, if ever, consumed separately, they are not tissue specific in their actions and at the molecular level they are multitaskers. Metabolism functions within a seemingly random cellular milieu however ratios are important, for example, the ratio of adenosine triphosphate to adenosine monophosphate, or oxidized to reduced glutathione. Health status is determined by simple ratios, such as the waist hip ratio, or ratio of fat mass to lean mass...
January 19, 2018: Nutrients
https://www.readbyqxmd.com/read/29351231/molecular-network-based-identification-of-competing-endogenous-rnas-in-thyroid-carcinoma
#19
Minjia Lu, Xingyu Xu, Baohang Xi, Qi Dai, Chenli Li, Li Su, Xiaonan Zhou, Min Tang, Yuhua Yao, Jialiang Yang
RNAs may act as competing endogenous RNAs (ceRNAs), a critical mechanism in determining gene expression regulations in many cancers. However, the roles of ceRNAs in thyroid carcinoma remains elusive. In this study, we have developed a novel pipeline called Molecular Network-based Identification of ceRNA (MNIceRNA) to identify ceRNAs in thyroid carcinoma. MNIceRNA first constructs micro RNA (miRNA)-messenger RNA (mRNA)long non-coding RNA (lncRNA) networks from miRcode database and weighted correlation network analysis (WGCNA), based on which to identify key drivers of differentially expressed RNAs between normal and tumor samples...
January 19, 2018: Genes
https://www.readbyqxmd.com/read/29351204/mtor-cross-talk-in-cancer-and-potential-for-combination-therapy
#20
REVIEW
Fabiana Conciatori, Ludovica Ciuffreda, Chiara Bazzichetto, Italia Falcone, Sara Pilotto, Emilio Bria, Francesco Cognetti, Michele Milella
The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer...
January 19, 2018: Cancers
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