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https://www.readbyqxmd.com/read/28821796/cathepsin-k-knockout-protects-against-cardiac-dysfunction-in-diabetic-mice
#1
Rui Guo, Yinan Hua, Olivia Rogers, Travis E Brown, Jun Ren, Sreejayan Nair
Diabetes is a major risk factor for cardiovascular disease and the lysosomal cysteine protease cathepsin K plays a critical role in cardiac pathophysiology. To expand upon our previous findings, we tested the hypothesis that, knockout of cathepsin K protects against diabetes-associated cardiac anomalies. Wild-type and cathepsin K knockout mice were rendered diabetic by streptozotocin (STZ) injections. Body weight, organ mass, fasting blood glucose, energy expenditure, cardiac geometry and function, cardiac histomorphology, glutathione levels and protein levels of cathepsin K and those associated with Ca(2+) handling, calcineurin/NFAT signaling, insulin signaling, cardiac apoptosis and fibrosis were determined...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821672/audio-visual-modulation-in-mouse-v1-depends-on-cross-modal-stimulus-configuration-and-congruency
#2
Guido T Meijer, Jorrit S Montijn, Cyriel M A Pennartz, Carien S Lansink
The sensory neocortex is a highly connected associative network, in which information from multiple senses is integrated, even at the level of the primary sensory areas. Although this view is supported by a growing body of empirical evidence, the neural mechanisms of cross-modal integration in primary sensory areas, such as the primary visual cortex (V1), are still largely unknown. Using two-photon calcium imaging in awake mice, we show that the encoding of audio-visual stimuli in V1 neuronal populations is highly dependent on the features of the stimulus constituents...
August 8, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821660/contribution-of-astroglial-cx43-hemichannels-to-the-modulation-of-glutamatergic-currents-by-d-serine-in-the-mouse-prefrontal-cortex
#3
Claire Meunier, Nan Wang, Chenju Yi, Glenn Dallerac, Pascal Ezan, Annette Koulakoff, Luc Leybaert, Christian Giaume
Astrocytes interact dynamically with neurons by modifying synaptic activity and plasticity. This interplay occurs through a process named gliotransmission, meaning that neuroactive molecules are released by astrocytes. Acting as a gliotransmitter, D-serine co-agonist of the NMDA receptor at the glycine binding site, can be released by astrocytes in a calcium [Ca(2+)]i-dependent manner. A typical feature of astrocytes is their high expression level of connexin43 (Cx43), a protein forming gap junction channels and hemichannels associated with dynamic neuroglial interactions...
August 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821436/carbon-quantum-dot-tailored-calcium-alginate-hydrogel-for-ph-responsive-controlled-delivery-of-vancomycin
#4
Niladri Sarkar, Gyanaranjan Sahoo, Rashmita Das, Gyanaranjan Prusty, Sarat K Swain
Herein, we demonstrate the preparation of highly luminescent carbon quantum dots (CQDs) from Aloe vera leaf gel; in just 2h at 250°C through carbonization pathway. The prepared CQDs are structurally characterized with high resolution transmission electron microscopy (HRTEM), hydrodynamic diameter and surface polarity, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), Raman, UV-visible absorption spectrophotometry and fluorescence spectroscopy. The functional carbon nanoparticles are observed as non-cytotoxic materials...
August 15, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28820965/systematic-identification-of-mcu-modulators-by-orthogonal-interspecies-chemical-screening
#5
Daniela M Arduino, Jennifer Wettmarshausen, Horia Vais, Paloma Navas-Navarro, Yiming Cheng, Anja Leimpek, Zhongming Ma, Alba Delrio-Lorenzo, Andrea Giordano, Cecilia Garcia-Perez, Guillaume Médard, Bernhard Kuster, Javier García-Sancho, Dejana Mokranjac, J Kevin Foskett, M Teresa Alonso, Fabiana Perocchi
The mitochondrial calcium uniporter complex is essential for calcium (Ca(2+)) uptake into mitochondria of all mammalian tissues, where it regulates bioenergetics, cell death, and Ca(2+) signal transduction. Despite its involvement in several human diseases, we currently lack pharmacological agents for targeting uniporter activity. Here we introduce a high-throughput assay that selects for human MCU-specific small-molecule modulators in primary drug screens. Using isolated yeast mitochondria, reconstituted with human MCU, its essential regulator EMRE, and aequorin, and exploiting a D-lactate- and mannitol/sucrose-based bioenergetic shunt that greatly minimizes false-positive hits, we identify mitoxantrone out of more than 600 clinically approved drugs as a direct selective inhibitor of human MCU...
August 17, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28820078/effects-of-excitotoxic-lesion-with-inhaled-anesthetics-on-nervous-system-cells-of-rodents
#6
Maria Fernanda Quiroz Padilla, Gemma Guillazo-Blanch, Magdy Sanchez, Maria Andrea Dominguez, Rosa Margaria Gomez
Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation...
August 17, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28819756/nanofibers-grafted-on-titanium-alloy-the-effects-of-fiber-alignment-and-density-on-osteoblast-mineralization
#7
Hsin-Yi Lin, Zhao-Xiang Peng
The surface of medical implant alloy Ti-6Al-4V was chemically modified to allow it to covalently bond with collagen/PVA nanofibers. These nanofibers were successfully attached to the Ti-6Al-4V surface in three different morphologies: randomly oriented high-density fiber, COL(H); randomly oriented low-density fiber, COL(L); and aligned high-density fiber, COL(A). The effects of the morphology of these covalently-bound collagen nanofibers on the growth and differentiation of osteoblasts were studied for 21 days...
August 17, 2017: Journal of Materials Science. Materials in Medicine
https://www.readbyqxmd.com/read/28819506/-parathyroid-carcinoma-about-a-case-and-review-of-the-literature
#8
Naourez Kolsi, Sondos Jellali, Jamel Koubaa
Parathyroid carcinoma is a very rare malignant tumor of the parathyroid gland. Clinically, this cancer is characterized by the presence of severe primary hyperparathyroidism. Diagnosis is based on histological examination but is not always easy. Surgery is the treatment of choice. We report the case of a 59-year old woman with a personal history of arterial hypertension and of recurrent renal lithiasis, presenting with diffuse bone pain associated with asthenia. Neck examination showed hard basi-cervical swelling with nonpalpable lower edge...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28819274/distinct-carbon-sources-affect-structural-and-functional-maturation-of-cardiomyocytes-derived-from-human-pluripotent-stem-cells
#9
Cláudia Correia, Alexey Koshkin, Patrícia Duarte, Dongjian Hu, Ana Teixeira, Ibrahim Domian, Margarida Serra, Paula M Alves
The immature phenotype of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) constrains their potential in cell therapy and drug testing. In this study, we report that shifting hPSC-CMs from glucose-containing to galactose- and fatty acid-containing medium promotes their fast maturation into adult-like CMs with higher oxidative metabolism, transcriptional signatures closer to those of adult ventricular tissue, higher myofibril density and alignment, improved calcium handling, enhanced contractility, and more physiological action potential kinetics...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819205/fast-wide-volume-functional-imaging-of-engineered-in-vitro-brain-tissues
#10
G Palazzolo, M Moroni, A Soloperto, G Aletti, G Naldi, M Vassalli, T Nieus, F Difato
The need for in vitro models that mimic the human brain to replace animal testing and allow high-throughput screening has driven scientists to develop new tools that reproduce tissue-like features on a chip. Three-dimensional (3D) in vitro cultures are emerging as an unmatched platform that preserves the complexity of cell-to-cell connections within a tissue, improves cell survival, and boosts neuronal differentiation. In this context, new and flexible imaging approaches are required to monitor the functional states of 3D networks...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28819010/new-insight-on-the-s100a1-stip1-complex-highlights-the-important-relationship-between-allostery-and-entropy-in-protein-function
#11
Nathaniel V Nucci
Calcium signaling serves as a nexus of many vital cellular processes. Of particular importance is the role the calcium signaling plays in the prevention of protein misfolding, and the S100 family of calcium-binding proteins is a key player in this pathway. While the S100 proteins carry out a range of roles, the interaction of S100A1 and the stress-inducible phosphoprotein 1 (STIP1) has been shown to be particularly important. A recent study by Maciejewski et al. in Biochemical Journal (Biochemical Journal (2017) 474, 1853-1866) revealed new insights into the nature of the S100A1-STIP1 interaction...
August 17, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28818673/1-25-dihydroxyvitamin-d3-induces-brain-proteomic-changes-in-cuprizone-mice-during-remyelination-involving-calcium-proteins
#12
Eystein Oveland, Agnes Nystad, Frode Berven, Kjell-Morten Myhr, Øivind Torkildsen, Stig Wergeland
Dietary supplementation of vitamin D is commonly recommended to patients with multiple sclerosis. We recently found that high-dose of the hormonally active 1,25-dihydroxyvitamin-D3 (1,25D) promotes myelin repair in the cuprizone model for de- and remyelination. In the present study, we quantified 5062 proteins, of which 125 were differentially regulated in brain tissue from 1,25D treated mice during remyelination, compared to placebo. Proteins upregulated in the early remyelination phase were involved in calcium binding, e...
August 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28818353/does-calcium-burden-impact-culprit-lesion-morphology-and-clinical-results-an-adapt-des-ivus-substudy
#13
Peiren Shan, Gary S Mintz, Bernhard Witzenbichler, D Christopher Metzger, Michael J Rinaldi, Peter L Duffy, Giora Weisz, Thomas D Stuckey, Bruce R Brodie, Philippe Généreux, Aaron Crowley, Ajay J Kirtane, Gregg W Stone, Akiko Maehara
BACKGROUND: Increasing coronary lesion calcification is thought to be associated with adverse percutaneous coronary intervention (PCI) and clinical outcomes. We investigated the effects of calcium burden on culprit lesion morphology and clinical events after intravascular ultrasound (IVUS)-guided PCI in the ADAPT-DES study. METHODS: ADAPT-DES was a prospective, multicenter registry of 8582 consecutive patients undergoing successful PCI using DES. A pre-specified virtual histology (VH)-IVUS substudy of 638 culprit lesions (638 patients) had both pre- and post-PCI VH-IVUS...
August 12, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28818166/assessment-of-quality-of-sleep-and-its-relationship-with-psychiatric-morbidity-and-socio-demographic-factors-in-the-patients-of-chronic-renal-disease-undergoing-hemodialysis
#14
Usama Bin Zubair, Batool Butt
OBJECTIVE: To assess the subjective sleep quality and its relationship with the presence of psychiatric morbidity in the patients suffering from chronic kidney disease (CKD) and undergoing the procedure of hemodialysis (HD); and analyze the associated socio-demographic factors. STUDY DESIGN: Cross-sectional descriptive study. PLACE AND DURATION OF STUDY: Nephrology Department, Military Hospital, Rawalpindi, from July to December 2016. METHODOLOGY: Patients of CKD undergoing the HD were included in the final analysis...
July 2017: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/28817799/human-astrocyte-maturation-captured-in-3d-cerebral-cortical-spheroids-derived-from-pluripotent-stem-cells
#15
Steven A Sloan, Spyros Darmanis, Nina Huber, Themasap A Khan, Fikri Birey, Christine Caneda, Richard Reimer, Stephen R Quake, Ben A Barres, Sergiu P Paşca
There is significant need to develop physiologically relevant models for investigating human astrocytes in health and disease. Here, we present an approach for generating astrocyte lineage cells in a three-dimensional (3D) cytoarchitecture using human cerebral cortical spheroids (hCSs) derived from pluripotent stem cells. We acutely purified astrocyte-lineage cells from hCSs at varying stages up to 20 months in vitro using immunopanning and cell sorting and performed high-depth bulk and single-cell RNA sequencing to directly compare them to purified primary human brain cells...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28816072/calcium-electroporation-for-treatment-of-cutaneous-metastases-a-randomized-double-blinded-phase-ii-study-comparing-the-effect-of-calcium-electroporation-with-electrochemotherapy
#16
H Falk, L W Matthiessen, G Wooler, J Gehl
BACKGROUND: Calcium electroporation is a novel anticancer treatment, which utilizes high voltage pulses to permeabilize cell membranes and expose the cell to supraphysiological doses of calcium. Preclinical studies on calcium electroporation have shown strikingly high tumor response with cell necrosis. Calcium electroporation builds on the treatment electrochemotherapy, where chemotherapeutic drugs, mostly bleomycin, are internalized by electroporation. This double-blinded randomized study compared calcium electroporation to electrochemotherapy in terms of objective response measured 6 months after treatment...
August 17, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28815458/backbone-and-side-chain-resonance-assignments-of-ca-2-4-calmodulin-bound-to-beta-calcineurin-a-cambd-peptide
#17
C Andrew Fowler, Maria F Núñez Hernandez, Susan E O'Donnell, Liping Yu, Madeline A Shea
Calcineurin (CaN) is a heterodimeric and highly conserved serine/threonine phosphatase (PP2B) that plays a critical role in coupling calcium signals to physiological processes including embryonic cardiac development, NF-AT-regulated gene expression in immune responses, and apoptosis. The catalytic subunit (CaNA) has three isoforms (α, β, and γ,) in humans and seven isoforms in Paramecium. In all eukaryotes, the EF-hand protein calmodulin (CaM) regulates CaN activity in a calcium-dependent manner. The N- and C-domains of CaM (CaMN and CaMC) recognize a CaM-binding domain (CaMBD) within an intrinsically disordered region of CaNA that precedes the auto-inhibitory domain (AID) of CaNA...
August 16, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28814738/identification-of-novel-non-secosteroidal-vitamin-d-receptor-agonists-with-potent-cardioprotective-effects-and%C3%A2-%C3%AF-%C3%AF-devoid-of-hypercalcemia
#18
Santosh A Khedkar, Mohammed A Samad, Sangita Choudhury, Ji Yoo Lee, Dongsheng Zhang, Ravi I Thadhani, S Ananth Karumanchi, Alan C Rigby, Peter M Kang
Vitamin D regulates many biological processes, but its clinical utility is limited by its hypercalcemic effect. Using a virtual screening platform to search novel chemical probes that activate the vitamin D signaling, we report discovery of novel non-steroidal small-molecule compounds that activate the vitamin D receptor (VDR), but are devoid of hypercalcemia. A lead compound (known as VDR 4-1) demonstrated potent transcriptional activities in a VDR reporter gene assay, and significantly ameliorated cardiac hypertrophy in cell culture studies and in animal models...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814603/single-nucleotide-polymorphisms-of-the-high-affinity-igg-receptor-fc%C3%AE-ri-reduce-immune-complex-binding-and-downstream-effector-functions
#19
Arianne M Brandsma, Toine Ten Broeke, Evelien van Dueren den Hollander, Thomas G Caniels, Tineke Kardol-Hoefnagel, Jürgen Kuball, Jeanette H W Leusen
Binding of IgG Abs to FcγRs on immune cells induces FcγR cross-linking that leads to cellular effector functions, such as phagocytosis, Ab-dependent cellular cytotoxicity, and cytokine release. However, polymorphisms in low affinity FcγRs have been associated with altered avidity toward IgG, thereby substantially impacting clinical outcomes of multimodular therapy when targeting cancer or autoimmune diseases with mAbs as well as the frequency and severity of autoimmune diseases. In this context, we investigated the consequences of three nonsynonymous single nucleotide polymorphisms (SNPs) for the high affinity receptor for IgG, FcγRI...
August 16, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28814523/screening-of-fda-approved-drugs-for-inhibitors-against-japanese-encephalitis-virus-infection
#20
Shaobo Wang, Yang Liu, Jiao Guo, Peilin Wang, Leike Zhang, Gengfu Xiao, Wei Wang
Japanese encephalitis virus (JEV), an arthropod-borne flavivirus, is a major cause of acute viral encephalitis in humans. There is no approved drug available for JEV-specific treatment, and the vaccines are not effective against all clinical JEV isolates. Herein, a high-throughput screening was performed against JEV from an FDA-approved drug library. Five hit drugs were identified that inhibited JEV infection with a selective index > 10. Antiviral activities of these five hit drugs against other flavivirus, including Zika virus, were also validated...
August 16, 2017: Journal of Virology
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