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https://www.readbyqxmd.com/read/28821398/urate-promotes-snca-%C3%AE-synuclein-clearance-via-regulating-mtor-dependent-macroautophagy
#1
Yu-Lan Sheng, Xing Chen, Xiao-Ou Hou, Xin-Yuan, Bao-Shi Yuan, Yu-Qing Yuan, Qi-Lin Zhang, Xian Cao, Chun-Feng Liu, Wei-Feng Luo, Li-Fang Hu
Serum urate levels are reported to be significantly lowered in patients with Parkinson's disease (PD) and inversely correlated to the risk and progression of PD. However, the mechanism by which urate affects PD is poorly understood. Here we showed that treatment with uric acid (UA) resulted in an autophagy activity enhancement in PC12 cells in dose- and time-dependent manners, as indicated by LC3-II increase and P62 decrease. Moreover, UA was still able to increase the LC3-II level and the number of LC3 puncta in the presence of Bafilomycin A1, a lysosomal inhibitor...
August 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28819100/blockage-of-the-lysosome-dependent-autophagic-pathway-contributes-to-complement-membrane-attack-complex-induced-podocyte-injury-in-idiopathic-membranous-nephropathy
#2
Wei Jing Liu, Zhi-Hang Li, Xiao-Cui Chen, Xiao-Lu Zhao, Zhen Zhong, Chen Yang, Hong-Luan Wu, Ning An, Wei-Yan Li, Hua-Feng Liu
Dysregulation of autophagy-mediated podocyte homeostasis is proposed to play a role in idiopathic membranous nephropathy (IMN). In the present study, autophagic activity and lysosomal alterations were investigated in podocytes of IMN patients and in cultured podocytes exposed to sublytic terminal complement complex, C5b-9. C5b-9 upregulated the number of LC3 positive puncta and the expression of p62 in patient podocytes and in C5b-9 injuried podocyte model. The lysosomal turnover of LC3-II was not influenced, although the BECN1 expression level was upregulated after exposure of podocytes to C5b-9...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812407/scaling-the-punctum-and-canaliculus-in-patients-undergoing-punctoplasty-surgery-a-prospective-cohort-study
#3
Nisha Nesaratnam, Krisztina Emeriewen, Julie Smith, Beena David, James Wawrzynski, Anant Sharma, George M Saleh
Optical Coherence Tomography (OCT) is a safe and non-invasive method of high-resolution cross-sectional imaging of tissue microstructures using infrared radiation. This study investigates how the appearance of the punctum and proximal canaliculus differs pre- and post-operatively in patients undergoing punctoplasty surgery. Patients with symptomatic punctal stenosis warranting punctoplasty surgery were prospectively invited to enrol from a single centre. Spectral OCT images of the lower punctae were captured with a Topcon 3D OCT 2000 machine pre- and post-operatively (at their follow-up appointment)...
August 16, 2017: Orbit
https://www.readbyqxmd.com/read/28808311/antitumor-properties-of-coenzyme-q0-against-human-ovarian-carcinoma-cells-via-induction-of-ros-mediated-apoptosis-and-cytoprotective-autophagy
#4
You-Cheng Hseu, Tai-Jung Tsai, Mallikarjuna Korivi, Jer-Yuh Liu, Hui-Jye Chen, Chung-Ming Lin, Yi-Chun Shen, Hsin-Ling Yang
Coenzyme Q0 (CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone) has been reported to exert anticancer properties against human breast/lung cancer cells. This study investigated the in vitro and in vivo anticancer properties of CoQ0 on human ovarian carcinoma (SKOV-3) cells and xenografted nude mice, and revealed the underlying molecular mechanism. CoQ0 induced G2/M arrest through downregulation of cyclin B1/A and CDK1/K2 expressions. CoQ0-induced autophagy as a survival mechanism was evidenced by increased accumulation of LC3-II, GFP-LC3 puncta, AVOs formation and Beclin-1/Bcl-2 dysregulation...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28806150/the-puncta-enigma
#5
Daniel J Klionsky
This Editor's Corner may sound like the title of a mystery novel, but it actually reflects a question I have about the puncta articles that appear in Autophagy. In particular, I am surprised by the number of solicitations sent out for puncta that are either ignored, or, less frequently, declined. It is not that I expect the principal investigator (PI) to find the invitation to write a punctum undeniably attractive. Rather, it is the unilateral decision that it is not worthwhile for graduate students or postdocs who performed the work---and likely wrote at least the first draft of the paper---to write the punctum...
August 14, 2017: Autophagy
https://www.readbyqxmd.com/read/28794026/mammalian-orthoreovirus-factories-modulate-stress-granule-protein-localization-by-interaction-with-g3bp1
#6
Promisree Choudhury, Luke Bussiere, Cathy L Miller
Mammalian orthoreovirus (MRV) infection induces phosphorylation of translation initiation factor eIF2α which promotes formation of discrete cytoplasmic inclusions, termed stress granules (SGs). SGs are emerging as a component of the innate immune response to virus infection, and modulation of SG assembly is a common mechanism employed by viruses to counter this antiviral response. We previously showed that MRV infection induces SGs early, then interferes with SG formation as infection proceeds. In this work, we found that SG associated proteins localized to the periphery of virus-encoded cytoplasmic structures, termed virus factories (VFs), where viral transcription, translation, and replication occur...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28793261/the-conserved-disease-associated-rna-binding-protein-dnab2-interacts-with-the-fragile-x-protein-ortholog-in-drosophila-neurons
#7
Rick S Bienkowski, Ayan Banerjee, J Christopher Rounds, Jennifer Rha, Omotola F Omotade, Christina Gross, Kevin J Morris, Sara W Leung, ChangHui Pak, Stephanie K Jones, Michael R Santoro, Stephen T Warren, James Q Zheng, Gary J Bassell, Anita H Corbett, Kenneth H Moberg
The Drosophila dNab2 protein is an ortholog of human ZC3H14, a poly(A) RNA binding protein required for intellectual function. dNab2 supports memory and axon projection, but its molecular role in neurons is undefined. Here, we present a network of interactions that links dNab2 to cytoplasmic control of neuronal mRNAs in conjunction with the fragile X protein ortholog dFMRP. dNab2 and dfmr1 interact genetically in control of neurodevelopment and olfactory memory, and their encoded proteins co-localize in puncta within neuronal processes...
August 8, 2017: Cell Reports
https://www.readbyqxmd.com/read/28777754/methionine-sulfoxide-reductase-b3-msrb3-protein-associates-with-synaptic-vesicles-and-its-expression-changes-in-the-hippocampi-of-alzheimer-s-disease-patients
#8
Stephanie L Adams, Laurent Benayoun, Kathy Tilton, Olivia R Chavez, Jayandra J Himali, Jan Krzysztof Blusztajn, Sudha Seshadri, Ivana Delalle
Genome-wide association studies (GWAS) identified susceptibility loci associated with decreased hippocampal volume, and found hippocampal subfield-specific effects at MSRB3 (methionine sulfoxide reductase-B3). The MSRB3 locus was also linked to increased risk for late onset Alzheimer's disease (AD). In this study, we uncovered novel sites of MsrB3 expression in CA pyramidal layer and arteriolar walls by using automated immunohistochemistry on hippocampal sections from 23 individuals accompanied by neuropathology reports and clinical dementia rating scores...
July 29, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28770114/human-app-gene-expression-alters-active-zone-distribution-and-spontaneous-neurotransmitter-release-at-the-drosophila-larval-neuromuscular-junction
#9
Ekaterina A Saburova, Alexander N Vasiliev, Violetta V Kravtsova, Elena V Ryabova, Andrey L Zefirov, Olga I Bolshakova, Svetlana V Sarantseva, Igor I Krivoi
This study provides further insight into the molecular mechanisms that control neurotransmitter release. Experiments were performed on larval neuromuscular junctions of transgenic Drosophila melanogaster lines with different levels of human amyloid precursor protein (APP) production. To express human genes in motor neurons of Drosophila, the UAS-GAL4 system was used. Human APP gene expression increased the number of synaptic boutons per neuromuscular junction. The total number of active zones, detected by Bruchpilot protein puncta distribution, remained unchanged; however, the average number of active zones per bouton decreased...
2017: Neural Plasticity
https://www.readbyqxmd.com/read/28767038/microtubule-dependent-ribosome-localization-in-c-elegans-neurons
#10
Kentaro Noma, Alexandr Goncharov, Mark H Ellisman, Yishi Jin
Subcellular localization of ribosomes defines the location and capacity for protein synthesis. Methods for in vivo visualizing ribosomes in multicellular organisms are desirable in mechanistic investigations of the cell biology of ribosome dynamics. Here, we developed an approach using split GFP for tissue-specific visualization of ribosomes in Caenorhabditis elegans. Labeled ribosomes are detected as fluorescent puncta in the axons and synaptic terminals of specific neuron types, correlating with ribosome distribution at the ultrastructural level...
August 2, 2017: ELife
https://www.readbyqxmd.com/read/28754687/cells-lay-their-own-tracks-optogenetic-cdc42-activation-stimulates-fibronectin-deposition-supporting-directed-migration
#11
Seth P Zimmerman, Sreeja B Asokan, Brian Kuhlman, James E Bear
Rho GTPase family members are known regulators of directed migration and therefore play key roles in processes including development, immune response and cancer metastasis. However, their individual contributions to these processes are complex. Here, we regulate the activity of two family members, Rac and Cdc42, by optogenetically recruiting specific GEF DH/PH domains to defined regions on the cell membrane. We find that the localized activation of both GTPases produce lamellipodia in cells plated on a fibronectin substrate...
July 28, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28748915/the-endoplasmic-reticulum-stress-autophagy-pathway-is-involved-in-apelin-13-induced-cardiomyocyte-hypertrophy-in-vitro
#12
Feng Xie, Di Wu, Shi-Fang Huang, Jian-Gang Cao, He-Ning Li, Lu He, Mei-Qing Liu, Lan-Fang Li, Lin-Xi Chen
Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001-2 μmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4)...
July 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28747503/identification-of-vaccinia-virus-replisome-and-transcriptome-proteins-by-ipond-coupled-with-mass-spectrometry
#13
Tatiana G Senkevich, George Katsafanas, Andrea Weisberg, Lisa R Olano, Bernard Moss
Poxviruses replicate within the cytoplasm and encode proteins for DNA and mRNA synthesis. To investigate poxvirus replication and transcription from a new perspective, we incorporated 5-ethynyl-2' -deoxyuridine (EdU) into nascent DNA in cells infected with vaccinia virus (VACV). The EdU-labeled DNA was conjugated to fluor- or biotin-azide and visualized by confocal, super resolution and transmission electron microscopy. Nuclear labeling decreased dramatically after infection, accompanied by intense labeling of cytoplasmic foci...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28746398/tomosyn-associates-with-secretory-vesicles-in-neurons-through-its-n-and-c-terminal-domains
#14
Cornelia J Geerts, Roberta Mancini, Ning Chen, Frank T W Koopmans, Ka Wan Li, August B Smit, Jan R T van Weering, Matthijs Verhage, Alexander J A Groffen
The secretory pathway in neurons requires efficient targeting of cargos and regulatory proteins to their release sites. Tomosyn contributes to synapse function by regulating synaptic vesicle (SV) and dense-core vesicle (DCV) secretion. While there is large support for the presynaptic accumulation of tomosyn in fixed preparations, alternative subcellular locations have been suggested. Here we studied the dynamic distribution of tomosyn-1 (Stxbp5) and tomosyn-2 (Stxbp5l) in mouse hippocampal neurons and observed a mixed diffuse and punctate localization pattern of both isoforms...
2017: PloS One
https://www.readbyqxmd.com/read/28743798/essential-basal-cytonemes-take-up-hedgehog-in-the-drosophila-wing-imaginal-disc
#15
Weitao Chen, Hai Huang, Ryo Hatori, Thomas B Kornberg
Morphogen concentration gradients that extend across developmental fields form by dispersion from source cells. In the Drosophila wing disc, Hedgehog (Hh) produced by posterior compartment cells distributes in a concentration gradient to adjacent cells of the anterior compartment. We monitored Hh:GFP after pulsed expression and analyzed movements and co-localization of Hh, Patched (Ptc) and Smoothened (Smo) proteins tagged with GFP or mCherry and expressed at physiological levels from bacterial artificial chromosome transgenes...
July 25, 2017: Development
https://www.readbyqxmd.com/read/28725967/%C3%AE-synuclein-transfer-between-neurons-and-astrocytes-indicates-that-astrocytes-play-a-role-in-degradation-rather-than-in-spreading
#16
Frida Loria, Jessica Y Vargas, Luc Bousset, Sylvie Syan, Audrey Salles, Ronald Melki, Chiara Zurzolo
Recent evidence suggests that disease progression in Parkinson's disease (PD) could occur by the spreading of α-synuclein (α-syn) aggregates between neurons. Here we studied the role of astrocytes in the intercellular transfer and fate of α-syn fibrils, using in vitro and ex vivo models. α-Syn fibrils can be transferred to neighboring cells; however, the transfer efficiency changes depending on the cell types. We found that α-syn is efficiently transferred from astrocytes to astrocytes and from neurons to astrocytes, but less efficiently from astrocytes to neurons...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28723268/assay-of-calcium-transients-and-synapses-in-rat-hippocampal-neurons-by-kinetic-image-cytometry-and-high-content-analysis-an-in-vitro-model-system-for-postchemotherapy-cognitive-impairment
#17
Patrick M McDonough, Natalie L Prigozhina, Ranor C B Basa, Jeffrey H Price
Postchemotherapy cognitive impairment (PCCI) is commonly exhibited by cancer patients treated with a variety of chemotherapeutic agents, including the endocrine disruptor tamoxifen (TAM). The etiology of PCCI is poorly understood. Our goal was to develop high-throughput assay methods to test the effects of chemicals on neuronal function applicable to PCCI. Rat hippocampal neurons (RHNs) were plated in 96- or 384-well dishes and exposed to test compounds (forskolin [FSK], 17β-estradiol [ES]), TAM or fulvestrant [FUL], aka ICI 182,780) for 6-14 days...
July 2017: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/28719204/norditerpenoids-and-dinorditerpenoids-from-the-seeds-of-podocarpus-nagi-as-cytotoxic-agents-and-autophagy-inducers
#18
Zhe-Ling Feng, Le-Le Zhang, Yuan-Dong Zheng, Qian-Yu Liu, Jing-Xin Liu, Lu Feng, Li Huang, Qing-Wen Zhang, Jin-Jian Lu, Li-Gen Lin
Nine new norditerpenoids and dinorditerpenoids, 2-oxonagilactone A (1), 7β-hydroxynagilactone D (2), nagilactones K and L (3 and 4), 3β-hydroxynagilactone L (5), 2β-hydroxynagilactone L (6), 3-epi-15-hydroxynagilactone D (7), 1α-chloro-2β,3β,15-trihydroxynagilactone L (8), and 15-hydroxynagilactone L (9), were isolated from the seeds of Podocarpus nagi, along with eight known analogues. The structures of the new compounds were established based on detailed NMR and HRESIMS analysis, as well as from their ECD spectra...
July 18, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28717168/dynamics-and-function-of-cxcr4-in-formation-of-the-granule-cell-layer-during-hippocampal-development
#19
Yuka Mimura-Yamamoto, Hiroshi Shinohara, Taichi Kashiwagi, Toru Sato, Seiji Shioda, Tatsunori Seki
In the developing hippocampus, granule cell progenitors (GCPs) arising in the ventricular zone (VZ) migrate to the subpial region, and form the granule cell layer (GCL) of the dentate gyrus (DG). To understand the mechanism of GCL formation, we investigated the dynamics and function of CXCR4 which is expressed by the GCPs and is a receptor of the CXCL12 chemokine secreted by cells surrounding the DG. In the VZ, CXCR4 was expressed on the plasma membrane of the GCPs. During their migration and in the DG, CXCR4 was internalized and accumulated as puncta close to the centrosomes, Golgi apparatus, and lysosomes...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716843/strength-in-numbers-phosphofructokinase-polymerization-prevails-in-the-liver
#20
Elma Zaganjor, Jessica B Spinelli, Marcia C Haigis
Numerous metabolic enzymes assemble into filamentous structures, which are thought to serve additional regulatory functions. In this issue, Webb et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201701084) show that the liver-specific isoform of phosphofructokinase-1 forms filaments in vitro and localizes as puncta in cells along the plasma membrane. This suggests spatial organization of glycolysis in higher organisms.
August 7, 2017: Journal of Cell Biology
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