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https://www.readbyqxmd.com/read/27926996/small-molecule-modulator-of-sigma-2-receptor-is-neuroprotective-and-reduces-cognitive-deficits-and-neuro-inflammation-in-experimental-models-of-alzheimer-s-disease
#1
Bitna Yi, James J Sahn, Pooneh Memar Ardestani, Andrew K Evans, Luisa Scott, Jessica Z Chan, Sangeetha Iyer, Ashley Crisp, Gabriella Zuniga, Jonathan Pierce-Shimomura, Stephen F Martin, Mehrdad Shamloo
Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report the identification of a novel class of Sig2R binding ligands and their cellular and in vivo activity in experimental models of Alzheimer's disease (AD). We report that SAS-0132 and DKR-1051, selective ligands of Sig2R, modulate intracellular Ca(2+) levels in human SK-N-SH neuroblastoma cells. The Sig2R antagonists SAS-0132 and JVW-1009 are neuroprotective in a C...
December 7, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27926939/a-bystander-mechanism-explains-the-specific-phenotype-of-a-broadly-expressed-misfolded-protein
#2
Lauren Klabonski, Ji Zha, Lakshana Senthilkumar, Tali Gidalevitz
Misfolded proteins in transgenic models of conformational diseases interfere with proteostasis machinery and compromise the function of many structurally and functionally unrelated metastable proteins. This collateral damage to cellular proteins has been termed 'bystander' mechanism. How a single misfolded protein overwhelms the proteostasis, and how broadly-expressed mutant proteins cause cell type-selective phenotypes in disease are open questions. We tested the gain-of-function mechanism of a R37C folding mutation in an endogenous IGF-like C...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27924023/methsmrt-an-integrative-database-for-dna-n6-methyladenine-and-n4-methylcytosine-generated-by-single-molecular-real-time-sequencing
#3
Pohao Ye, Yizhao Luan, Kaining Chen, Yizhi Liu, Chuanle Xiao, Zhi Xie
DNA methylation is an important type of epigenetic modifications, where 5- methylcytosine (5mC), 6-methyadenine (6mA) and 4-methylcytosine (4mC) are the most common types. Previous efforts have been largely focused on 5mC, providing invaluable insights into epigenetic regulation through DNA methylation. Recently developed single-molecule real-time (SMRT) sequencing technology provides a unique opportunity to detect the less studied DNA 6mA and 4mC modifications at single-nucleotide resolution. With a rapidly increased amount of SMRT sequencing data generated, there is an emerging demand to systematically explore DNA 6mA and 4mC modifications from these data sets...
October 18, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27922032/chemically-induced-oxidative-stress-affects-ash-neuronal-function-and-behavior-in-c-elegans
#4
Eleni Gourgou, Nikos Chronis
Oxidative stress (OS) impact on a single neuron's function in vivo remains obscure. Using C. elegans as a model organism, we report the effect of paraquat (PQ)-induced OS on wild type worms on the function of the ASH polymodal neuron. By calcium (Ca(2+)) imaging, we quantified ASH activation upon stimulus delivery. PQ-treated worms displayed higher maximum depolarization (peak of the Ca(2+) transients) compared to untreated animals. PQ had a similar effect on the ASH neuron response time (rising slope of the Ca(2+) transients), except in very young worms...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919065/splicing-factor-1-modulates-dietary-restriction-and-torc1-pathway-longevity-in-c-elegans
#5
Caroline Heintz, Thomas K Doktor, Anne Lanjuin, Caroline C Escoubas, Yue Zhang, Heather J Weir, Sneha Dutta, Carlos Giovanni Silva-García, Gitte H Bruun, Ianessa Morantte, Gerta Hoxhaj, Brendan D Manning, Brage S Andresen, William B Mair
Ageing is driven by a loss of transcriptional and protein homeostasis and is the key risk factor for multiple chronic diseases. Interventions that attenuate or reverse systemic dysfunction associated with age therefore have the potential to reduce overall disease risk in the elderly. Precursor mRNA (pre-mRNA) splicing is a fundamental link between gene expression and the proteome, and deregulation of the splicing machinery is linked to several age-related chronic illnesses. However, the role of splicing homeostasis in healthy ageing remains unclear...
December 5, 2016: Nature
https://www.readbyqxmd.com/read/27917958/functional-complexity-emerging-from-anatomical-constraints-in-the-brain-the-significance-of-network-modularity-and-rich-clubs
#6
Gorka Zamora-López, Yuhan Chen, Gustavo Deco, Morten L Kringelbach, Changsong Zhou
The large-scale structural ingredients of the brain and neural connectomes have been identified in recent years. These are, similar to the features found in many other real networks: the arrangement of brain regions into modules and the presence of highly connected regions (hubs) forming rich-clubs. Here, we examine how modules and hubs shape the collective dynamics on networks and we find that both ingredients lead to the emergence of complex dynamics. Comparing the connectomes of C. elegans, cats, macaques and humans to surrogate networks in which either modules or hubs are destroyed, we find that functional complexity always decreases in the perturbed networks...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916661/tetrameric-assembly-of-k-channels-requires-er-located-chaperone-proteins
#7
Kai Li, Qiang Jiang, Xue Bai, Yi-Feng Yang, Mei-Yu Ruan, Shi-Qing Cai
Tetrameric assembly of channel subunits in the endoplasmic reticulum (ER) is essential for surface expression and function of K(+) channels, but the molecular mechanism underlying this process remains unclear. In this study, we found through genetic screening that ER-located J-domain-containing chaperone proteins (J-proteins) are critical for the biogenesis and physiological function of ether-a-go-go-related gene (ERG) K(+) channels in both Caenorhabditis elegans and human cells. Human J-proteins DNAJB12 and DNAJB14 promoted tetrameric assembly of ERG (and Kv4...
November 30, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27915107/association-between-the-agr-locus-and-the-presence-of-virulence-genes-and-pathogenesis-in-s-aureus-using-a-caenorhabditis-elegans-model
#8
Terissa A Thompson, Paul D Brown
BACKGROUND: S. aureus is a commensal pathogen with a virulon that is under agr control. agr dysfunction has been seen in clinical strains that do not respond positively to treatment. AIM: This study aimed to establish the association between the presence of genes in the virulon with agr present and to determine the relationship between agr presence or absence with pathogenicity. METHODS: PCR was used to identify the presence of the agr operon in 101 clinical S...
November 30, 2016: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/27914198/spatial-patterning-of-p-granules-by-rna-induced-phase-separation-of-the-intrinsically-disordered-protein-meg-3
#9
Jarrett Smith, Deepika Calidas, Helen Schmidt, Tu Lu, Dominique Rasoloson, Geraldine Seydoux
RNA granules are non-membrane bound cellular compartments that contain RNA and RNA binding proteins. The molecular mechanisms that regulate the spatial distribution of RNA granules in cells are poorly understood. During polarization of the C. elegans zygote, germline RNA granules, called P granules, assemble preferentially in the posterior cytoplasm. We present evidence that P granule asymmetry depends on RNA-induced phase separation of the granule scaffold MEG-3. MEG-3 is an intrinsically disordered protein that binds and phase separates with RNA in vitro...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27913619/the-caenorhabditis-elegans-nf2-merlin-molecule-nfm-1-non-autonomously-regulates-neuroblast-migration-and-interacts-genetically-with-the-guidance-cue-slt-1-slit
#10
Matthew P Josephson, Rana Aliani, Megan L Norris, Matthew E Ochs, Mahekta Gujar, Erik A Lundquist
During nervous system development, neurons and their progenitors migrate to their final destinations. In Caenorhabditis elegans, the bilateral Q neuroblasts and their descendants migrate long distances in opposite directions, despite being born in the same posterior region. QR on the right migrates anteriorly and generates the AQR neuron positioned near the head, and QL on the left migrates posteriorly, giving rise to the PQR neuron positioned near the tail. In a screen for genes required for AQR and PQR migration, we identified an allele of nfm-1, which encodes a molecule similar to vertebrate NF2/Merlin, an important tumor suppressor in humans...
December 2, 2016: Genetics
https://www.readbyqxmd.com/read/27913309/sequence-determinants-of-the-caenhorhabditis-elegansdopamine-transporter-dictating-in-vivoaxonal-export-and-synaptic-localization
#11
Sarah B Robinson, J Andrew Hardaway, Shannon L Hardie, Jane Wright, Ryan M Glynn, Daniel P Bermingham, Qiao Han, Sarah M Sturgeon, Phyllis Freeman, Randy D Blakely
The monoamine neurotransmitter dopamine (DA) acts across phylogeny to modulate both simple and complex behaviors. The presynaptic DA transporter (DAT) is a major determinant of DA signaling capacity in ensuring efficient extracellular DA clearance. In humans, DAT is also a major target for prescribed and abused psychostimulants. Multiple structural determinants of DAT function and regulation have been defined, though largely these findings have arisen from heterologous expression or ex vivo cell culture studies...
November 29, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27911941/copper-oxide-nanoparticles-impact-several-toxicological-endpoints-and-cause-neurodegeneration-in-caenorhabditis-elegans
#12
Michael J Mashock, Tyler Zanon, Anthony D Kappell, Lisa N Petrella, Erik C Andersen, Krassimira R Hristova
Engineered nanoparticles are becoming increasingly incorporated into technology and consumer products. In 2014, over 300 tons of copper oxide nanoparticles were manufactured in the United States. The increased production of nanoparticles raises concerns regarding the potential introduction into the environment or human exposure. Copper oxide nanoparticles commonly release copper ions into solutions, which contribute to their toxicity. We quantified the inhibitory effects of both copper oxide nanoparticles and copper sulfate on C...
2016: PloS One
https://www.readbyqxmd.com/read/27911392/optogenetic-random-mutagenesis-using-histone-minisog-in-c-elegans
#13
Kentaro Noma, Yishi Jin
Forward genetic screening in model organisms is the workhorse to discover functionally important genes and pathways in many biological processes. In most mutagenesis-based screens, researchers have relied on the use of toxic chemicals, carcinogens, or irradiation, which requires designated equipment, safety setup, and/or disposal of hazardous materials. We have developed a simple approach to induce heritable mutations in C. elegans using germline-expressed histone-miniSOG, a light-inducible potent generator of reactive oxygen species...
November 14, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27907064/nad-is-a-food-component-that-promotes-exit-from-dauer-diapause-in-caenorhabditis-elegans
#14
Mykola Mylenko, Sebastian Boland, Sider Penkov, Julio L Sampaio, Benoit Lombardot, Daniela Vorkel, Jean-Marc Verbavatz, Teymuras V Kurzchalia
The free-living soil nematode Caenorhabditis elegans adapts its development to the availability of food. When food is scarce and population density is high, worms enter a developmentally arrested non-feeding diapause stage specialized for long-term survival called the dauer larva. When food becomes available, they exit from the dauer stage, resume growth and reproduction. It has been postulated that compound(s) present in food, referred to as the "food signal", promote exit from the dauer stage. In this study, we have identified NAD+ as a component of bacterial extract that promotes dauer exit...
2016: PloS One
https://www.readbyqxmd.com/read/27906968/structural-and-functional-recovery-of-sensory-cilia-in-c-elegans-ift-mutants-upon-aging
#15
Astrid Cornils, Ashish K Maurya, Lauren Tereshko, Julie Kennedy, Andrea G Brear, Veena Prahlad, Oliver E Blacque, Piali Sengupta
The majority of cilia are formed and maintained by the highly conserved process of intraflagellar transport (IFT). Mutations in IFT genes lead to ciliary structural defects and systemic disorders termed ciliopathies. Here we show that the severely truncated sensory cilia of hypomorphic IFT mutants in C. elegans transiently elongate during a discrete period of adult aging leading to markedly improved sensory behaviors. Age-dependent restoration of cilia morphology occurs in structurally diverse cilia types and requires IFT...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27905558/microrna-mir-34-provides-robustness-to-environmental-stress-response-via-the-daf-16-network-in-c-elegans
#16
Meltem Isik, T Keith Blackwell, Eugene Berezikov
Diverse stresses and aging alter expression levels of microRNAs, suggesting a role for these posttranscriptional regulators of gene expression in stress modulation and longevity. Earlier studies demonstrated a central role for the miR-34 family in promoting cell cycle arrest and cell death following stress in human cells. However, the biological significance of this response was unclear. Here we show that in C. elegans mir-34 upregulation is necessary for developmental arrest, correct morphogenesis, and adaptation to a lower metabolic state to protect animals against stress-related damage...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27905396/atomic-structure-of-the-innexin-6-gap-junction-channel-determined-by-cryo-em
#17
Atsunori Oshima, Kazutoshi Tani, Yoshinori Fujiyoshi
Innexins, a large protein family comprising invertebrate gap junction channels, play an essential role in nervous system development and electrical synapse formation. Here we report the cryo-electron microscopy structures of Caenorhabditis elegans innexin-6 (INX-6) gap junction channels at atomic resolution. We find that the arrangements of the transmembrane helices and extracellular loops of the INX-6 monomeric structure are highly similar to those of connexin-26 (Cx26), despite the lack of significant sequence similarity...
December 1, 2016: Nature Communications
https://www.readbyqxmd.com/read/27902410/inhibition-of-quorum-sensing-controlled-virulence-factors-of-pseudomonas-aeruginosa-by-murraya-koenigii-essential-oil-a-study-in-a-caenorhabditis-elegans-infectious-model
#18
P Sankar Ganesh, Ravishankar Vittal Rai
The global emergence of antibiotic resistant strains of Pseudomonas aeruginosa poses a major threat in hospital environments as well as in the community. P. aeruginosa is an opportunistic human pathogen and it also infects a wide range of model organisms including the nematode Caenorhabditis elegans. Quorum sensing (QS) mediates cell-to-cell communication in bacteria and has an important role in regulating virulence genes, antibiotic resistance and biofilm formation which are crucial for establishment of the infection...
November 3, 2016: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/27901397/a-systems-toxicology-approach-reveals-the-wnt-mapk-crosstalk-pathway-mediated-reproductive-failure-in-caenorhabditis-elegans-exposed-to-graphene-oxide-go-but-not-to-reduced-graphene-oxide-rgo
#19
Nivedita Chatterjee, Young-Ho Kim, Jisu Yang, Carlos P Roca, Sang Woo Joo, Jinhee Choi
The potential hazards of graphene nanomaterials were investigated by exposing the nematode Caenorhabditis elegans to graphene oxide (GO) and reduced graphene oxide (rGO). The underlying mechanisms of the nano-bio interaction were addressed with an integrated systems toxicology approach using global transcriptomics, network-based pathway analysis, and experimental validation of the in-silico-derived hypotheses. Graphene oxide was found to reduce the worms' reproductive health to a greater degree than rGO, but it did not affect survival (24 h endpoint)...
November 30, 2016: Nanotoxicology
https://www.readbyqxmd.com/read/27896020/identification-of-phenolic-secondary-metabolites-from-schotia-brachypetala-sond-fabaceae-and-demonstration-of-their-antioxidant-activities-in-caenorhabditis-elegans
#20
Mansour Sobeh, Esraa ElHawary, Herbenya Peixoto, Rola M Labib, Heba Handoussa, Noha Swilam, Ahmed H El-Khatib, Farukh Sharapov, Tamer Mohamed, Sonja Krstin, Michael W Linscheid, Abdel Nasser Singab, Michael Wink, Nahla Ayoub
BACKGROUND: Schotia brachypetala Sond. (Fabaceae) is an endemic tree of Southern Africa whose phytochemistry and pharmacology were slightly studied. The present work aimed at profiling the major phenolics compounds present in the hydro-alcohol extract from S. brachypetala leaves (SBE) using LC/HRESI/MS/MS and NMR and prove their antioxidant capabilities using novel methods. METHODS: In vitro assays; DPPH, TEAC persulfate decolorizing kinetic and FRAP assays, and in vivo assays: Caenorhabditis elegans strains maintenance, Intracellular ROS in C...
2016: PeerJ
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