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https://www.readbyqxmd.com/read/28918469/aversive-and-non-aversive-memory-impairment-in-the-mucopolysaccharidosis-ii-mouse-model
#1
Amanda Stapenhorst Azambuja, Lilian Correa, Bernardo Pappi Gabiatti, Giselle Renata Martins, Álvaro de Oliveira Franco, Maria Flávia Marques Ribeiro, Guilherme Baldo
Hunter syndrome (MPS II, OMIM 309900) is a lysosomal storage disorder due to deficient iduronate sulphatase activity. Patients present multiple cognitive alterations, and the aim of this work was to verify if MPS II mice also present some progressive cognitive alterations. For that, MPS II mice from 2 to 6 months of age were submitted to repeated open field and inhibitory avoidance tests to evaluate memory parameters. MPS II mice presented impaired memory at 6 months evaluated by open field test. They also performed poorly in the inhibitory avoidance test from 4 months...
September 16, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28918368/gnptab-missense-mutations-cause-loss-of-glcnac-1-phosphotransferase-activity-in-mucolipidosis-type-ii-through-distinct-mechanisms
#2
Nataniel Floriano Ludwig, Renata Voltolini Velho, Fernanda Sperb-Ludwig, Angelina Xavier Acosta, Erlane Marques Ribeiro, Chong Kim, Dafne Dain Gandelman Horovitz, Raquel Boy, Maria Juliana Rodovalho-Doriqui, Charles Marques Lourenço, Emerson Santana Santos, Thomas Braulke, Sandra Pohl, Ida Vanessa D Schwartz
Mucolipidoses (ML) II and III alpha/beta are lysosomal storage diseases caused by pathogenic mutations in GNPTAB encoding the α⁄β-subunit precursor of GlcNAc-1-phosphotransferase. To determine genotype-phenotype correlation and functional analysis of mutant GlcNAc-1-phosphotransferase, 13 Brazilian patients clinically and biochemical diagnosed for MLII or III alpha/beta were studied. By sequencing of genomic GNPTAB of the MLII and MLIII alpha/beta patients we identified six novel mutations: p.D76G, p.S385L, p...
September 13, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28918125/iodinated-chlorin-p6-copper-complex-induces-anti-proliferative-effect-in-oral-cancer-cells-through-elevation-of-intracellular-reactive-oxygen-species
#3
Paromita Sarbadhikary, Alok Dube
We investigated the anticancer chemotoxicity of previously reported iodinated chlorin p6 copper complex (ICp6-Cu), a novel chlorophyll derivative in which copper is attached to the side chain carboxylate groups via coordination. Human oral carcinoma cells NT8e, 4451 and the non-cancerous keratinocyte HaCaT cells were treated with ICp6-Cu for 48 h in dark and cell viability, proliferation and morphological alterations were examined. ICp6-Cu showed pronounced cytotoxicity in cancer cells with IC50 ∼40 μM, whereas, the viability of HaCaT cells was not affected...
September 13, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28918065/the-role-of-epigenetics-in-lysosomal-storage-disorders-uncharted-territory
#4
REVIEW
Shahzeb Hassan, Ellen Sidransky, Nahid Tayebi
The study of the contribution of epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs, to human disease has enhanced our understanding of different cellular processes and diseased states, as well as the effect of environmental factors on phenotypic outcomes. Epigenetic studies may be particularly relevant in evaluating the clinical heterogeneity observed in monogenic disorders. The lysosomal storage disorders are Mendelian disorders characterized by a wide spectrum of associated phenotypes, ranging from neonatal presentations to symptoms that develop in late adulthood...
August 1, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28918032/microrna-31-regulates-chemosensitivity-in-malignant-pleural-mesothelioma
#5
Hannah L Moody, Michael J Lind, Stephen G Maher
Malignant pleural mesothelioma (MPM) is associated with an extremely poor prognosis, and most patients initially are or rapidly become unresponsive to platinum-based chemotherapy. MicroRNA-31 (miR-31) is encoded on a genomic fragile site, 9p21.3, which is reportedly lost in many MPM tumors. Based on previous findings in a variety of other cancers, we hypothesized that miR-31 alters chemosensitivity and that miR-31 reconstitution may influence sensitivity to chemotherapeutics in MPM. Reintroduction of miR-31 into miR-31 null NCI-H2452 cells significantly enhanced clonogenic resistance to cisplatin and carboplatin...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28918021/in%C3%A2-vitro-selection-of-cell-internalizing-dna-aptamers-in-a-model-system-of-inflammatory-kidney-disease
#6
Glory Ranches, Melanie Lukasser, Herbert Schramek, Andreas Ploner, Taras Stasyk, Gert Mayer, Günter Mayer, Alexander Hüttenhofer
Chronic kidney disease (CKD) is a progressive pathological condition marked by a gradual loss of kidney function. Treatment of CKD is most effective when diagnosed at an early stage and patients are still asymptomatic. However, current diagnostic biomarkers (e.g., serum creatinine and urine albumin) are insufficient for prediction of the pathogenesis of the disease. To address this need, we applied a cell-SELEX (systematic evolution of ligands by exponential enrichment) approach and identified a series of DNA aptamers, which exhibit high affinity and selectivity for cytokine-stimulated cells, resembling some aspects of a CKD phenotype...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917946/cellular-uptake-and-intracellular-localization-of-poly-acrylic-acid-nanoparticles-in-a-rainbow-trout-oncorhynchus-mykiss-gill-epithelial-cell-line-rtgill-w1
#7
Lindsey C Felix, Van A Ortega, Greg G Goss
The ever-growing production of engineered nanoparticles (NPs) for use in many agricultural, commercial, consumer, and industrial applications will lead to their accidental or intentional release into the environment. Potential routes of environmental exposure include manufacturing or transport spills, disposal of NP-containing products down the drain and/or in landfills, as well as direct usage on agricultural land. Therefore, NPs will inevitably contaminate aquatic environments and interact with resident organisms...
September 7, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28916822/ampk-phosphorylation-of-ulk1-is-required-for-targeting-of-mitochondria-to-lysosomes-in-exercise-induced-mitophagy
#8
Rhianna C Laker, Joshua C Drake, Rebecca J Wilson, Vitor A Lira, Bevan M Lewellen, Karen A Ryall, Carleigh C Fisher, Mei Zhang, Jeffrey J Saucerman, Laurie J Goodyear, Mondira Kundu, Zhen Yan
Mitochondrial health is critical for skeletal muscle function and is improved by exercise training through both mitochondrial biogenesis and removal of damaged/dysfunctional mitochondria via mitophagy. The mechanisms underlying exercise-induced mitophagy have not been fully elucidated. Here, we show that acute treadmill running in mice causes mitochondrial oxidative stress at 3-12 h and mitophagy at 6 h post-exercise in skeletal muscle. These changes were monitored using a novel fluorescent reporter gene, pMitoTimer, that allows assessment of mitochondrial oxidative stress and mitophagy in vivo, and were preceded by increased phosphorylation of AMP activated protein kinase (Ampk) at tyrosine 172 and of unc-51 like autophagy activating kinase 1 (Ulk1) at serine 555...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916105/selective-imaging-of-cancer-cells-with-a-ph-activatable-lysosome-targeting-fluorescent-probe
#9
Rongguang Shi, Lu Huang, Xiaoxue Duan, Guohao Sun, Gui Yin, Ruiyong Wang, Jun-Jie Zhu
Fluorescence imaging with tumor-specific fluorescent probe has emerged as a tool to aid surgeons in the identification and removal of tumor tissue. We report here a new lysosome-targeting fluorescent probe (NBOH) with BODIPY fluorephore to distinguish tumor tissue out of normal tissue based on different pH environment. The probe exhibited remarkable pH-dependent fluorescence behavior in a wide pH range from 3.0 to 11.0, especially a sensitive pH-dependent fluorescence change at pH range between 3.5 and 5.5, corresponding well to the acidic microenvironment of tumor cells, in aqueous solution...
October 2, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28915706/the-role-of-autophagy-in-hepatocellular-carcinoma-friend-or-foe
#10
REVIEW
Lian Liu, Jia-Zhi Liao, Xing-Xing He, Pei-Yuan Li
Autophagy is an evolutionarily conserved lysosome-dependent catabolic process which degrades cell's components in order to recycle substrates to exert optimally and adapt to tough circumstances. It is a critical cellular homeostatic mechanism with stress resistance, immunity, antiaging, and pro-tumor or anti-tumor effects. Among these, the role of autophagy in cancer is the most eye-catching that is not immutable but dynamic and highly complex. Basal autophagy acts as a tumor suppressor by maintaining genomic stability in normal cells...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915639/heptamethine-carbocyanine-dz-1-dye-for-near-infrared-fluorescence-imaging-of-hepatocellular-carcinoma
#11
Jiaze An, Ningning Zhao, Caiqin Zhang, Yong Zhao, Dengxu Tan, Ya Zhao, Bing Bai, Hai Zhang, Boyang Jason Wu, Changhong Shi
Near-infrared fluorescence (NIRF) dyes have recently emerged as promising tools for non-invasive imaging of different types of cancers. Here, we explored the potential utility of a NIRF DZ-1 dye, with dual imaging and tumour targeting functions, in hepatocellular carcinoma (HCC). We showed the preferential uptake of DZ-1 by HCC cells in vitro and in derived subcutaneous/orthotopic tumour xenografts, accompanied by a minimal effect on normal cells. DZ-1 simplified tumour growth profiling as well, since we were able to correlate NIRF signals with tumour volume and/or tumour-emitting luminescence in mice...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915631/in-vivo-autophagy-and-biogenesis-of-autophagosomes-within-male-haploid-cells-during-spermiogenesis
#12
Ping Yang, Nisar Ahmed, Lingling Wang, Hong Chen, Yasir Waqas, Tengfei Liu, Abdul Haseeb, Nasrullah Bangulzai, Yufei Huang, Qiusheng Chen
Autophagy is a unique catabolic pathway that is linked to several physiological processes. However, its role in the process of spermiogenesis is largely unknown. The aim of the current study was to determine the in vivo role of autophagy and the origin of autophagosome membrane biogenesis within male haploid cells. Our immunohistochemistry results demonstrated that LC3 and ATG7 localization were increased dramatically in round to elongated spermatids (haploid cells) towards the lumen of seminiferous tubules, however, poorly expressed in the early stages of germ cells near the basal membrane...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915569/gabarapl1-tumor-suppressive-function-is-independent-of-its-conjugation-to-autophagosomes-in-mcf-7-breast-cancer-cells
#13
Laura Poillet-Perez, Marine Jacquet, Eric Hervouet, Thierry Gauthier, Annick Fraichard, Christophe Borg, Jean-René Pallandre, Bruno J Gonzalez, Yasmina Ramdani, Michaël Boyer-Guittaut, Régis Delage-Mourroux, Gilles Despouy
The GABARAPL1 protein belongs to the ATG8 family whose members are involved in autophagy. Our laboratory previously demonstrated that GABARAPL1 associates with autophagic vesicles, regulates autophagic flux and acts as a tumor suppressor protein in breast cancer. In this study, we aimed to determine whether GABARAPL1 conjugation to autophagosomes is necessary for its tumor suppressive functions using the MCF-7 breast cancer cell line overexpressing GABARAPL1 or a G116A mutant, which is unable to be lipidated and associated to autophagosomes...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915568/hyperosmotic-stress-stimulates-autophagy-via-polycystin-2
#14
Daniel Peña-Oyarzun, Rodrigo Troncoso, Catalina Kretschmar, Cecilia Hernando, Mauricio Budini, Eugenia Morselli, Sergio Lavandero, Alfredo Criollo
Various intracellular mechanisms are activated in response to stress, leading to adaptation or death. Autophagy, an intracellular process that promotes lysosomal degradation of proteins, is an adaptive response to several types of stress. Osmotic stress occurs under both physiological and pathological conditions, provoking mechanical stress and activating various osmoadaptive mechanisms. Polycystin-2 (PC2), a membrane protein of the polycystin family, is a mechanical sensor capable of activating the cell signaling pathways required for cell adaptation and survival...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914943/mammalian-cell-defence-mechanisms-against-the-cytotoxicity-of-nayf4-er-yb-gd-nanoparticles
#15
B Sikora, P Kowalik, J Mikulski, K Fronc, I Kamińska, M Szewczyk, A Konopka, K Zajdel, R Minikayev, K Sobczak, W Zaleszczyk, A Borodziuk, J Rybusiński, J Szczytko, A Sienkiewicz, T Wojciechowski, P Stępień, M Frontczak-Baniewicz, M Łapiński, G Wilczyński, W Paszkowicz, A Twardowski, D Elbaum
Water-soluble upconversion nanoparticles (UCNPs), based on polyvinylpyrrolidone (PVP)-coated NaYF4:Er(3+),Yb(3+),Gd(3+), with various concentrations of Gd(3+) ions and relatively high upconversion efficiencies, were synthesized. The internalization and cytotoxicity of the thus obtained UCNPs were evaluated in three cell lines (HeLa, HEK293 and astrocytes). No cytotoxicity was observed even at concentrations of UCNPs up to 50 μg ml(-1). The fate of the UCNPs within the cells was studied by examining their upconversion emission spectra with confocal microscopy and confirming these observations with transmission electron microscopy...
September 15, 2017: Nanoscale
https://www.readbyqxmd.com/read/28914814/zearalenone-zen-and-its-influence-on-regulation-of-gene-expression-in-carp-cyprinus-carpio-l-liver-tissue
#16
Constanze Pietsch
Zearalenone (ZEN) is a frequently-occurring mycotoxin in both animal and fish feeds. In order to characterize its effects on carp, three groups of fish were fed for 28 days with feeds contaminated with three different levels of ZEN (low: 332 µg kg(-1), medium: 621 µg kg(-1), and high: 797 µg kg(-1) feed). The reversibility of the effects of ZEN was assessed by feeding all of the groups with uncontaminated feed for a further 14 days. Gene expression of immune genes in the liver tissue of the fish was analysed, revealing reduced expressions of immune, antioxidative, and estrogen-related genes after the fish had been exposed to ZEN...
September 15, 2017: Toxins
https://www.readbyqxmd.com/read/28914427/the-clinical-and-genetic-spectrum-of-maroteaux-lamy-syndrome-mucopolysaccharidosis-vi-in-the-eastern-province-of-saudi-arabia
#17
Nouriya Abbas Al-Sannaa, Hind Yousif Al-Abdulwahed, Sami Ibrahim Al-Majed, Issam Hassan Bouholaigah
Mucopolysaccharidosis (MPS VI) or Maroteaux-Lamy syndrome is an autosomal recessive lysosomal storage disease caused by deficiency of the enzyme N-acetylgalactosamine 4-sulfatase or arylsulfatase B. It is involved in the degradation of glycosaminoglycans and characterized by a wide spectrum of clinical and genetic heterogeneity. So far, more than 150 mutations have been reported in the ARSB gene. Most of these mutations are either novel, private, or compound heterozygous making phenotype-genotype correlation as well as population screening difficult...
September 15, 2017: Journal of Community Genetics
https://www.readbyqxmd.com/read/28913343/exacerbating-and-reversing-lysosomal-storage-diseases-from-yeast-to-humans
#18
REVIEW
Tamayanthi Rajakumar, Andrew B Munkacsi, Stephen L Sturley
Lysosomal storage diseases (LSDs) arise from monogenic deficiencies in lysosomal proteins and pathways and are characterized by a tissue-wide accumulation of a vast variety of macromolecules, normally specific to each genetic lesion. Strategies for treatment of LSDs commonly depend on reduction of the offending metabolite(s) by substrate depletion or enzyme replacement. However, at least 44 of the ~50 LSDs are currently recalcitrant to intervention. Murine models have provided significant insights into our understanding of many LSD mechanisms; however, these systems do not readily permit phenotypic screening of compound libraries, or the establishment of genetic or gene-environment interaction networks...
August 25, 2017: Microbial Cell
https://www.readbyqxmd.com/read/28912673/improving-the-delivery-of-sod1-antisense-oligonucleotides-to-motor-neurons-using-calcium-phosphate-lipid-nanoparticles
#19
Liyu Chen, Clare Watson, Marco Morsch, Nicholas J Cole, Roger S Chung, Darren N Saunders, Justin J Yerbury, Kara L Vine
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease affecting the upper and lower motor neurons in the motor cortex and spinal cord. Abnormal accumulation of mutant superoxide dismutase I (SOD1) in motor neurons is a pathological hallmark of some forms of the disease. We have shown that the orderly progression of the disease may be explained by misfolded SOD1 cell-to-cell propagation, which is reliant upon its active endogenous synthesis. Reducing the levels of SOD1 is therefore a promising therapeutic approach...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28912590/the-importance-of-simulated-lung-fluid-slf-extractions-for-a-more-relevant-evaluation-of-the-oxidative-potential-of-particulate-matter
#20
Aude Calas, Gaëlle Uzu, Jean M F Martins, Didier Voisin, Lorenzo Spadini, Thomas Lacroix, Jean-Luc Jaffrezo
Particulate matter (PM) induces oxidative stress in vivo, leading to adverse health effects. Oxidative potential (OP) of PM is increasingly studied as a relevant metric for health impact (instead of PM mass concentration) as much of the ambient particle mass do not contribute to PM toxicity. Several assays have been developed to quantify PM oxidative potential and a widely used one is the acellular dithiothreitol (DTT) assay. However in such assays, particles are usually extracted with methanol or Milli-Q water which is unrepresentative of physiological conditions...
September 14, 2017: Scientific Reports
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