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https://www.readbyqxmd.com/read/27930906/an-elegant-circuit-for-balancing-risk-and-reward
#1
Zhaoyu Li, Adam J Iliff, X Z Shawn Xu
Animals constantly encounter conflicting cues in natural environments. To survive and thrive, they must make appropriate behavioral decisions. In this issue, Ghosh et al. (2016) identified a neural circuit underlying multisensory threat-reward decision making using an elegant C. elegans model.
December 7, 2016: Neuron
https://www.readbyqxmd.com/read/27930654/whole-organism-developmental-expression-profiling-identifies-rab-28-as-a-novel-ciliary-gtpase-associated-with-the-bbsome-and-intraflagellar-transport
#2
Victor L Jensen, Stephen Carter, Anna A W M Sanders, Chunmei Li, Julie Kennedy, Tiffany A Timbers, Jerry Cai, Noemie Scheidel, Breandán N Kennedy, Ryan D Morin, Michel R Leroux, Oliver E Blacque
Primary cilia are specialised sensory and developmental signalling devices extending from the surface of most eukaryotic cells. Defects in these organelles cause inherited human disorders (ciliopathies) such as retinitis pigmentosa and Bardet-Biedl syndrome (BBS), frequently affecting many physiological and developmental processes across multiple organs. Cilium formation, maintenance and function depend on intracellular transport systems such as intraflagellar transport (IFT), which is driven by kinesin-2 and IFT-dynein motors and regulated by the Bardet-Biedl syndrome (BBS) cargo-adaptor protein complex, or BBSome...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27929719/nad-the-convergence-of-dna-repair-and-mitophagy
#3
Evandro F Fang, Vilhelm A Bohr
ATM is a 350 kDa serine/threonine kinase best known for its role in DNA repair and multiple cellular homeostasis pathways. Mutation in ATM causes the disease ataxia telangiectasia (A-T) with clinical features including ataxia, severe cerebellar atrophy and Purkinje cell loss. In a cross-species study, using primary rat neurons, the roundworm C. elegans, and a mouse model of A-T, we showed that loss of ATM induces mitochondrial dysfunction and compromised mitophagy due to NAD(+) insufficiency. Remarkably, NAD(+) repletion mitigates both the DNA repair defect and mitochondrial dysfunction in ATM-deficient neurons...
December 8, 2016: Autophagy
https://www.readbyqxmd.com/read/27929466/spatial-and-temporal-analysis-of-active-erk-in-the-c-elegans-germline
#4
Amanda L Gervaise, Swathi Arur
The evolutionarily conserved extracellular signal transducing RTK-RAS-ERK pathway is an important kinase-signaling cascade that controls multiple cellular and developmental processes principally via activation of ERK, the terminal kinase of the pathway. Tight regulation of ERK activity is essential for normal development and homeostasis; overly active ERK results in excessive cellular proliferation, while underactive ERK causes cell death. C. elegans is a powerful model system that has helped characterize the function and regulation of RTK-RAS-ERK signaling pathway during development...
November 29, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27928028/mitochondrial-pyruvate-carrier-regulates-autophagy-inflammation-and-neurodegeneration-in-experimental-models-of-parkinson-s-disease
#5
Anamitra Ghosh, Trevor Tyson, Sonia George, Erin N Hildebrandt, Jennifer A Steiner, Zachary Madaj, Emily Schulz, Emily Machiela, William G McDonald, Martha L Escobar Galvis, Jeffrey H Kordower, Jeremy M Van Raamsdonk, Jerry R Colca, Patrik Brundin
Mitochondrial and autophagic dysfunction as well as neuroinflammation are involved in the pathophysiology of Parkinson's disease (PD). We hypothesized that targeting the mitochondrial pyruvate carrier (MPC), a key controller of cellular metabolism that influences mTOR (mammalian target of rapamycin) activation, might attenuate neurodegeneration of nigral dopaminergic neurons in animal models of PD. To test this, we used MSDC-0160, a compound that specifically targets MPC, to reduce its activity. MSDC-0160 protected against 1-methyl-4-phenylpyridinium (MPP(+)) insult in murine and cultured human midbrain dopamine neurons and in an α-synuclein-based Caenorhabditis elegans model...
December 7, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27927209/coordinated-inhibition-of-c-ebp-by-tribbles-in-multiple-tissues-is-essential-for-caenorhabditis-elegans-development
#6
Kyung Won Kim, Nishant Thakur, Christopher A Piggott, Shizue Omi, Jolanta Polanowska, Yishi Jin, Nathalie Pujol
BACKGROUND: Tribbles proteins are conserved pseudokinases that function to control kinase signalling and transcription in diverse biological processes. Abnormal function in human Tribbles has been implicated in a number of diseases including leukaemia, metabolic syndromes and cardiovascular diseases. Caenorhabditis elegans Tribbles NIPI-3 was previously shown to activate host defense upon infection by promoting the conserved PMK-1/p38 mitogen-activated protein kinase (MAPK) signalling pathway...
December 7, 2016: BMC Biology
https://www.readbyqxmd.com/read/27927200/tribbles-ortholog-nipi-3-and-bzip-transcription-factor-cebp-1-regulate-a-caenorhabditis-elegans-intestinal-immune-surveillance-pathway
#7
Deborah L McEwan, Rhonda L Feinbaum, Nicholas Stroustrup, Wilhelm Haas, Annie L Conery, Anthony Anselmo, Ruslan Sadreyev, Frederick M Ausubel
BACKGROUND: Many pathogens secrete toxins that target key host processes resulting in the activation of immune pathways. The secreted Pseudomonas aeruginosa toxin Exotoxin A (ToxA) disrupts intestinal protein synthesis, which triggers the induction of a subset of P. aeruginosa-response genes in the nematode Caenorhabditis elegans. RESULTS: We show here that one ToxA-induced C. elegans gene, the Tribbles pseudokinase ortholog nipi-3, is essential for host survival following exposure to P...
December 7, 2016: BMC Biology
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
#8
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
#9
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/27925069/helminth-parasites-of-galictis-cuja-carnivora-mustelidae-from-localities-in-the-atlantic-forest-of-brazil
#10
Pilar Corrêa, Cecília Bueno, Fabiano Matos Vieira, Luís Cláudio Muniz-Pereira
The current study aimed to investigate the helminth parasites of a population of Galictis cuja (Carnivora, Mustelidae) that occur in Atlantic Forest in the Southeastern region of Brazil. We necropsied 18 specimens of G. cuja, collected between January 2009 and May 2014, ran over victims on BR-040 highway, between the municipalities of Duque de Caxias, state of Rio de Janeiro and Juiz de Fora, state of Minas Gerais, localities inserted in Atlantic rainforest Biome. A total of six species of helminths were identified: Dioctophyme renale, Molineus elegans, Physaloptera sp...
December 1, 2016: Revista Brasileira de Parasitologia Veterinária, Brazilian Journal of Veterinary Parasitology
https://www.readbyqxmd.com/read/27924578/discovering-functional-erk-substrates-regulating-caenorhabditis-elegans-germline-development
#11
Jessica Jie Chen, Swathi Arur
The Rat Sarcoma (RAS) GTPAse-mediated extracellular signal-regulated kinase (ERK) pathway regulates multiple biological processes across metazoans. In particular during Caenorhabditis elegans oogenesis, ERK signaling has been shown to regulate over seven distinct biological processes in a temporal and sequential manner. To fully elucidate how ERK signaling cascade orchestrates these different biological processes in vivo, identification of the direct functional substrates of the pathway is critical. This chapter describes the methods that were used to identify ERK substrates in a global manner and study their functions in the germline...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924023/methsmrt-an-integrative-database-for-dna-n6-methyladenine-and-n4-methylcytosine-generated-by-single-molecular-real-time-sequencing
#12
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/27923661/cdc-25-2-a-caenorhabditis-elegans-ortholog-of-cdc25-is-required-for-male-tail-morphogenesis
#13
Sangmi Oh, Sunghee Yoon, Esther Youn, Ichiro Kawasaki, Yhong-Hee Shim
Cell division cycle 25 (Cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression by activating cyclin-dependent kinases (Cdks) which are inactivated by Wee1/Myt1 kinases. It was previously reported that cdc-25.2 promotes oocyte maturation and intestinal cell divisions in Caenorhabditis elegans hermaphrodites. Here, we report a novel function of cdc-25.2 in male tail development which was significantly deformed by cdc-25.2 RNAi depletion and in cdc-25.2 mutant males. The deformation was also observed after RNAi depletion of other cell cycle regulators, cdk-1, cyb-3, cyd-1, and cyl-1...
December 3, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27922032/chemically-induced-oxidative-stress-affects-ash-neuronal-function-and-behavior-in-c-elegans
#14
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
#15
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/27918992/investigation-of-the-metabolites-of-the-hif-stabilizer-fg-4592-roxadustat-in-five-different-in-vitro-models-and-in-a-human-doping-control-sample-using-high-resolution-mass-spectrometry
#16
Annelie Hansson, Mario Thevis, Holly Cox, Geoff Miller, Daniel Eichner, Ulf Bondesson, Mikael Hedeland
FG-4592 is a hypoxia-inducible factor (HIF) stabilizer, which can increase the number of red blood cells in the body. It has not been approved by regulatory authorities, but is available for purchase on the Internet. Due to its ability to improve the oxygen transportation mechanism in the body, FG-4592 is of interest for doping control laboratories, but prior to this study, little information about its metabolism was available. In this study, the metabolism of FG-4592 was investigated in a human doping control sample and in five in vitro models: human hepatocytes and liver microsomes, equine liver microsomes and S9 fraction and the fungus Cunninghamella elegans...
November 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27917958/functional-complexity-emerging-from-anatomical-constraints-in-the-brain-the-significance-of-network-modularity-and-rich-clubs
#17
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
#18
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
#19
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
#20
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
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