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https://www.readbyqxmd.com/read/29683502/the-c-terminus-of-the-amelogenin-peptide-influences-the-proliferation-of-human-bone-marrow-mesenchymal-stem-cells
#1
Ryo Kunimatsu, Tetsuya Awada, Yuki Yoshimi, Kazuyo Ando, Naoto Hirose, Yuki Tanne, Keisuke Sumi, Kotaro Tanimoto
BACKGROUND: Amelogenins are a family of enamel matrix proteins that are important for formation of enamel. Amelogenins may induce division of mesenchymal stem cells (MSCs), among others. Recently, the C-terminus of the amelogenin peptide (AMG-CP) has been shown to enhance the proliferation of cementoblast lineage cells. The role of the amelogenin peptide on the proliferation of human MSCs and related alterations in the intracellular signaling pathway were studied. METHODS: MSCs were exposed to AMG-CP in vitro...
April 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29679260/slow-release-of-hiv-1-protein-nef-from-vesicle-like-structures-is-inhibited-by-cytosolic-calcium-elevation-in-single-human-microglia
#2
Matjaž Stenovec, Eva Lasič, Pia Pužar Dominkuš, Saša Trkov Bobnar, Robert Zorec, Metka Lenassi, Marko Kreft
Once infected by HIV-1, microglia abundantly produce accessory protein Nef that enhances virus production and infectivity, but little is known about its intracellular compartmentalization, trafficking mode(s), and release from microglia. Here, we transfected immortalized human microglia with a plasmid encoding Nef tagged with green fluorescent protein (Nef.GFP) to biochemically and microscopically identify Nef.GFP-associated cellular compartments and examine their mobility and Nef release from cultured cells...
April 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29672446/the-effects-of-treadmill-exercise-on-autophagy-in-hippocampus-of-app-ps1-transgenic-mice
#3
Na Zhao, Xianliang Zhang, Chenghui Song, Youcai Yang, Biao He, Bo Xu
The β-amyloid (Aβ) deposition is one of the major pathological hallmark of Alzheimer's disease. Dysfunction in autophagy has been reported to lead to the Aβ deposition. The current study aimed to investigate the effects of treadmill exercise on autophagy activity and the Aβ deposition and to demonstrate whether exercise-induced reduction in the Aβ deposition was associated with changes in autophagy activity. APP/PS1 transgenic mice were divided into transgenic sedentary (TG-SED, n=12) and transgenic exercise (TG-EXE, n=12) groups...
April 18, 2018: Neuroreport
https://www.readbyqxmd.com/read/29668857/de-novo-mutations-of-the-atp6v1a-gene-cause-developmental-encephalopathy-with-epilepsy
#4
Anna Fassio, Alessandro Esposito, Mitsuhiro Kato, Hirotomo Saitsu, Davide Mei, Carla Marini, Valerio Conti, Mitsuko Nakashima, Nobuhiko Okamoto, Akgun Olmez Turker, Burcu Albuz, C Nur Semerci Gündüz, Keiko Yanagihara, Elisa Belmonte, Luca Maragliano, Keri Ramsey, Chris Balak, Ashley Siniard, Vinodh Narayanan, Chihiro Ohba, Masaaki Shiina, Kazuhiro Ogata, Naomichi Matsumoto, Fabio Benfenati, Renzo Guerrini
V-type proton (H+) ATPase (v-ATPase) is a multi-subunit proton pump that regulates pH homeostasis in all eukaryotic cells; in neurons, v-ATPase plays additional and unique roles in synapse function. Through whole exome sequencing, we identified de novo heterozygous mutations (p.Pro27Arg, p.Asp100Tyr, p.Asp349Asn, p.Asp371Gly) in ATP6V1A, encoding the A subunit of v-ATPase, in four patients with developmental encephalopathy with epilepsy. Early manifestations, observed in all patients, were developmental delay and febrile seizures, evolving to encephalopathy with profound delay, hypotonic/dyskinetic quadriparesis and intractable multiple seizure types in two patients (p...
April 13, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29659804/high-content-screen-for-modifiers-of-niemann-pick-type-c-disease-in-patient-cells
#5
Emily K Pugach, McKenna Feltes, Randal J Kaufman, Daniel S Ory, Anne G Bang
Niemann-Pick type C disease (NPC) is a rare lysosomal storage disease caused primarily by mutations in NPC1. NPC1 encodes the lysosomal cholesterol transport protein NPC1. The most common NPC1 mutation is a missense mutation (NPC1I1061T) that causes misfolding and rapid degradation of mutant protein in the endoplasmic reticulum. Cholesterol accumulates in enlarged lysosomes as a result of decreased levels of lysosomal NPC1I1061T protein in patient cells. There is currently no cure or FDA-approved treatment for patients...
April 12, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29655686/physakengose-g-induces-apoptosis-via-egfr-mtor-signaling-and-inhibits-autophagic-flux-in-human-osteosarcoma-cells
#6
Hua Lin, Chao Zhang, Hao Zhang, Yuan-Zheng Xia, Chuan-Yang Zhang, Jie Luo, Lei Yang, Ling-Yi Kong
BACKGROUND: Physakengose G (PG) is a new compound first isolated from Physalis alkekengi var. franchetii, an anticarcinogenic traditional Chinese medicine. PG has shown promising anti-tumor effects, but its underlying mechanisms remain unknown. PURPOSE: To investigate the anti-cancer effects of PG on human osteosarcoma cells and the underlying mechanisms. METHODS: Cell viability was measured by MTT assay. Apoptosis rates, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) generation, and acidic vesicular organelles (AVOs) formation were determined by flow cytometry...
March 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29622767/pex5-regulates-autophagy-via-the-mtorc1-tfeb-axis-during-starvation
#7
So Young Eun, Joon No Lee, In-Koo Nam, Zhi-Qiang Liu, Hong-Seob So, Seong-Kyu Choe, RaeKil Park
Defects in the PEX5 gene impair the import of peroxisomal matrix proteins, leading to nonfunctional peroxisomes and other associated pathological defects such as Zellweger syndrome. Although PEX5 regulates autophagy process in a stress condition, the mechanisms controlling autophagy by PEX5 under nutrient deprivation are largely unknown. Herein, we show a novel function of PEX5 in the regulation of autophagy via Transcription Factor EB (TFEB). Under serum-starved conditions, when PEX5 is depleted, the mammalian target of rapamycin (mTORC1) inhibitor TSC2 is downregulated, which results in increased phosphorylation of the mTORC1 substrates, including 70S6K, S6K, and 4E-BP-1...
April 6, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29617703/effects-of-ovarian-hormone-loss-on-neuritic-plaques-and-autophagic-flux-in-the-brains-of-adult-female-app-ps1-double-transgenic-mice
#8
Qiuhui Yao, Min Feng, Bo Yang, Zhimin Long, Shifang Luo, Min Luo, Guiqiong He, Kejian Wang
Epidemiologic studies have demonstrated that women account for two-thirds of Alzheimer's disease (AD) cases, for which the decline in circulating gonadal hormone is considered to be one of the major risk factors. In addition, ovarian hormone deficiency may affect β-amyloid (Aβ) deposition, which has a close relationship with autophagic flux. In this study, we investigated the impact of short-term or long-term ovarian hormone deprivation on two mouse models, the non-transgenic (wild-type) and the APP/PS1 double-transgenic AD (2×TgAD) model...
March 29, 2018: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/29581909/mechanically-induced-ca-2-oscillations-in-osteocytes-release-extracellular-vesicles-and-enhance-bone-formation
#9
Andrea E Morrell, Genevieve N Brown, Samuel T Robinson, Rachel L Sattler, Andrew D Baik, Gehua Zhen, Xu Cao, Lynda F Bonewald, Weiyang Jin, Lance C Kam, X Edward Guo
The vast osteocytic network is believed to orchestrate bone metabolic activity in response to mechanical stimuli through production of sclerostin, RANKL, and osteoprotegerin (OPG). However, the mechanisms of osteocyte mechanotransduction remain poorly understood. We've previously shown that osteocyte mechanosensitivity is encoded through unique intracellular calcium (Ca2+ ) dynamics. Here, by simultaneously monitoring Ca2+ and actin dynamics in single cells exposed to fluid shear flow, we detected actin network contractions immediately upon onset of flow-induced Ca2+ transients, which were facilitated by smooth muscle myosin and further confirmed in native osteocytes ex vivo...
2018: Bone Research
https://www.readbyqxmd.com/read/29580926/19q13-12-microdeletion-syndrome-fibroblasts-display-abnormal-storage-of-cholesterol-and-sphingolipids-in-the-endo-lysosomal-system
#10
Kexin Zhao, Aarnoud van der Spoel, Claudia Castiglioni, Sarah Gale, Hideji Fujiwara, Daniel S Ory, Neale D Ridgway
Microdeletions in 19q12q13.12 cause a rare and complex haploinsufficiency syndrome characterized by intellectual deficiency, developmental delays, and neurological movement disorders. Variability in the size and interval of the deletions makes it difficult to attribute the complex clinical phenotype of this syndrome to an underlying gene(s). As an alternate approach, we examined the biochemical and metabolic features of fibroblasts from an affected individual to derive clues as to the molecular basis for the syndrome...
March 24, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29570886/lysosomal-lamp1-immunoreactivity-exists-in-both-diffuse-and-neuritic-amyloid-plaques-in-the-human-hippocampus
#11
Sofia Hassiotis, Jim Manavis, Peter C Blumbergs, Kathryn J Hattersley, Julian M Carosi, Makoto Kamei, Timothy J Sargeant
Lysosomal vesicles around neuritic plaques are thought to drive Alzheimer's disease by providing ideal microenvironments for generation of amyloid-β. Although lysosomal vesicles are present at every amyloid plaque in mouse models of Alzheimer's disease, the number of amyloid plaques that contain lysosomal vesicles in the human brain remains unknown. This study aimed to quantify lysosomal vesicles at amyloid plaques in the human hippocampus. Lysosome associated membrane protein 1 (LAMP1)-positive vesicles accumulated in both diffuse (Aβ42-positive/AT8-negative) and neuritic (Aβ42-positive/AT8-positive) plaques in all regions analysed...
March 23, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29563863/mitofusin-dependent-er-stress-triggers-glial-dysfunction-and-nervous-system-degeneration-in-a-drosophila-model-of-friedreich-s-ataxia
#12
Oliver Edenharter, Stephan Schneuwly, Juan A Navarro
Friedreich's ataxia (FRDA) is the most important recessive ataxia in the Caucasian population. It is caused by a deficit of the mitochondrial protein frataxin. Despite its pivotal effect on biosynthesis of iron-sulfur clusters and mitochondrial energy production, little is known about the influence of frataxin depletion on homeostasis of the cellular mitochondrial network. We have carried out a forward genetic screen to analyze genetic interactions between genes controlling mitochondrial homeostasis and Drosophila frataxin...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29545877/3-methyladenine-and-dexmedetomidine-reverse-lipopolysaccharide-induced-acute-lung-injury-through-the-inhibition-of-inflammation-and-autophagy
#13
Dengfeng Ding, Shiyuan Xu, Hongfei Zhang, Wei Zhao, Xueping Zhang, Yuanxu Jiang, Ping Wang, Zhongliang Dai, Junzhi Zhang
The aim of the present study was to investigate the effects of 3-methyladenine (3-MA) and dexmedetomidine (DEX) pretreatment on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and the potential mechanism underlying the effects. LPS was instilled into the trachea of BALB/c mice to induce the ALI model. Solutions of 3-MA or DEX were intravenously injected into the mice 1 h later to establish the 3-MA and DEX groups. On days 1, 3 and 5 after the injections, arterial blood gas analysis was conducted, and the lung wet-dry weight ratio (W/D) was determined...
April 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29530281/single-nephron-proteomes-connect-morphology-and-function-in-proteinuric-kidney-disease
#14
Martin Höhne, Christian K Frese, Florian Grahammer, Claudia Dafinger, Giuliano Ciarimboli, Linus Butt, Julia Binz, Matthias J Hackl, Mahdieh Rahmatollahi, Martin Kann, Simon Schneider, Mehmet M Altintas, Bernhard Schermer, Thomas Reinheckel, Heike Göbel, Jochen Reiser, Tobias B Huber, Rafael Kramann, Tamina Seeger-Nukpezah, Max C Liebau, Bodo B Beck, Thomas Benzing, Andreas Beyer, Markus M Rinschen
In diseases of many parenchymatous organs, heterogeneous deterioration of individual functional units determines the clinical prognosis. However, the molecular characterization at the level of such individual subunits remains a technological challenge that needs to be addressed in order to better understand pathological mechanisms. Proteinuric glomerular kidney diseases are frequent and assorted diseases affecting a fraction of glomeruli and their draining tubules to variable extents, and for which no specific treatment exists...
March 9, 2018: Kidney International
https://www.readbyqxmd.com/read/29529328/fate-of-bacillus-cereus-within-phagocytic-cells
#15
Ivanna S Rolny, Silvia M Racedo, Pablo F Pérez
In this study we assessed the interaction of different strains of Bacillus cereus with murine peritoneal macrophages and cultured phagocytic cells (Raw 264.7 cells). Association, internalization, intracellular survival, routing of bacteria to different compartments and expression of MHCII were assessed in cells infected with different strains of B. cereus in vegetative form. Association values (adhering + internalized bacteria) and phagocytosis were higher for strain B10502 than those for strains 2 and M2. However, after 90 min interaction, intracellular survival was higher for strain 2 than for strains M2 and B10502...
December 2017: International Microbiology: the Official Journal of the Spanish Society for Microbiology
https://www.readbyqxmd.com/read/29526252/lamps-shedding-light-on-cancer-biology
#16
REVIEW
Federica Alessandrini, Laura Pezzè, Yari Ciribilli
Lysosomes are important cytoplasmic organelles whose critical functions in cells are increasingly being understood. In particular, despite the long-standing accepted concept about the role of lysosomes as cellular machineries solely assigned to degradation, it has been demonstrated that they play active roles in homeostasis and even in cancer biology. Indeed, it is now well documented that during the process of cellular transformation and cancer progression lysosomes are changing localization, composition, and volume and, through the release of their enzymes, lysosomes can also enhance cancer aggressiveness...
August 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/29514909/hiv-1-nef-antagonizes-serinc5-restriction-by-downregulation-of-serinc5-via-the-endosome-lysosome-system
#17
Jing Shi, Ran Xiong, Tao Zhou, Peiyi Su, Xihe Zhang, Xusheng Qiu, Hongmei Li, Sunan Li, Changqing Yu, Bin Wang, Chan Ding, Thomas E Smithgall, Yong-Hui Zheng
The primate lentiviral accessory protein Nef downregulates CD4 and MHC-I from the cell surface via independent endosomal trafficking pathways to promote viral pathogenesis. In addition, Nef antagonizes a novel restriction factor, SERINC5 (Ser5), to increase viral infectivity. To explore the molecular mechanism of Ser5 antagonism by Nef, we determined how Nef affects Ser5 expression and intracellular trafficking in comparison with CD4 and MHC-I. We confirm that Nef excludes Ser5 from HIV-1 virions by downregulating its cell surface expression via similar functional motifs required for CD4-downregulation...
March 7, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29512160/mr-and-tlr2-influence-phagosome-maturation-during-leishmania-infection
#18
Rachel E Polando, Blake C Jones, Cristina Ricardo, James Whitcomb, Wibke Ballhorn, Mary Ann McDowell
AIMS: Leishmania enter macrophages through receptor mediated phagocytosis and survive the harsh environment of a phagolysosome. Here, we investigated the interaction between MR, TLR2, and Leishmania, and the subsequent impact on phagosome maturation. METHODS AND RESULTS: Leishmania parasites are able to delay phagosome maturation, not reaching full maturation until five hours post engulfment. Here, maturation of Leishmania major and L. donovani containing phagosomes proceeded as expected in the WT macrophages becoming LAMP1 positive by 6 hours...
March 6, 2018: Parasite Immunology
https://www.readbyqxmd.com/read/29507050/proteomics-of-aspergillus-fumigatus-conidia-containing-phagolysosomes-identifies-processes-governing-immune-evasion
#19
Hella Schmidt, Sebastian Vlaic, Thomas Krüger, Franziska Schmidt, Johannes Balkenhohl, Thomas Dandekar, Reinhard Guthke, Olaf Kniemeyer, Thorsten Heinekamp, Axel A Brakhage
Invasive infections by the human pathogenic fungus Aspergillus fumigatus start with the outgrowth of asexual, airborne spores (conidia) into the lung tissue of immunocompromised patients. The resident alveolar macrophages phagocytose conidia, which end up in phagolysosomes. However, A. fumigatus conidia resist phagocytic degradation to a certain degree. This is mainly attributable to the pigment 1,8-dihydroxynaphthalene (DHN) melanin located in the cell wall of conidia, which manipulates the phagolysosomal maturation and prevents their intracellular killing...
March 5, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29498809/antibody-based-cell-surface-proteome-profiling-of-metastatic-breast-cancer-primary-explants-and-cell-lines
#20
Vera S Donnenberg, Jayce Jieming Zhang, Erika Moravcikova, Ernest Michael Meyer, Haihui Lu, Christian T Carson, Albert D Donnenberg
Flow cytometric cell surface proteomics provides a new and powerful tool to determine changes accompanying neoplastic transformation and invasion, providing clues to essential interactions with the microenvironment as well as leads for potential therapeutic targets. One of the most important advantages of flow cytometric cell surface proteomics is that it can be performed on living cells that can be sorted for further characterization and functional studies. Here, we document the surface proteome of clonogenic metastatic breast cancer (MBrCa) explants, which was strikingly similar to that of normal mesenchymal stromal cells (P = 0...
March 2, 2018: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
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