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James M Battisti, Lance A Watson, Myo T Naung, Adam M Drobish, Ekaterina Voronina, Michael F Minnick
The nematode Caenorhabditis elegans is well established as a system for characterization and discovery of molecular mechanisms mediating microbe-specific inducible innate immune responses to human pathogens. Coxiella burnetii is an obligate intracellular bacterium that causes a flu-like syndrome in humans (Q fever), as well as abortions in domesticated livestock, worldwide. Initially, when wild type C. elegans (N2 strain) was exposed to mCherry-expressing C. burnetii (CCB) a number of overt pathological manifestations resulted, including intestinal distension, deformed anal region and a decreased lifespan...
November 24, 2016: Innate Immunity
Zoltán Serfőző, Kálmán Nacsa, Zoltán Veréb, Izabella Battonyai, Csaba Hegedűs, Csilla Balogh, Károly Elekes
Olfaction, a chemosensory modality, plays a pivotal role in the orientation and behavior of invertebrates. The central olfactory processing unit in terrestrial stylomatophoran snails is the procerebrum, which contains NO synthesizing interneurons, whose oscillatory currents are believed to be the base of odor evoked memory formation. Nevertheless, in this model the up- and downstream events of molecular cascades that trigger and follow NO release, respectively, have not been studied. Immunocytochemistry and flow cytometry studies performed on procerebral neural perikarya isolated from the snail Helix pomatia revealed cell populations with discrete DAF-2 fluorescence, indicating the release of different amounts of NO...
November 21, 2016: Cellular Signalling
David A Bulger, Tetsunari Fukushige, Sijung Yun, Robert K Semple, John A Hanover, Michael W Krause
Human exome sequencing has dramatically increased the rate of identification of diseaseassociated polymorphisms. However, examining the functional consequences of those variants has created an analytic bottleneck. Insulin-like signaling in Caenorhabditis elegans has long provided a model to assess consequences of human insulin signaling mutations, but this has not been evaluated in the context of current genetic tools. We have exploited strains derived from the Million Mutation Project and gene editing to explore further the evolutionary relationships and conservation between the human and C...
November 18, 2016: G3: Genes—Genomes—Genetics
Ai-Jun Ding, Gui-Sheng Wu, Bin Tang, Xuechuan Hong, Michael X Zhu, Huai-Rong Luo
With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C...
November 16, 2016: Molecular and Cellular Biochemistry
Laxmi Rathor, Aakanksha Pant, Harshika Awasthi, Dayanandan Mani, Rakesh Pandey
An Ayurvedic polyherbal extract (PHE) comprising six herbs viz. Berberis aristata, Cyperus rotundus, Cedrus deodara, Emblica officinalis, Terminalia chebula and Terminalia bellirica is mentioned as an effective anti-hyperglycemic agent in 'Charaka Samhita', the classical text of Ayurveda. Previously, antidiabetic drug metformin was found to elicit antiaging effects and PHE was also found to exhibit antidiabetic effects in humans. Therefore, we screened it for its in vivo antioxidant antiaging effect on stress and lifespan using human homologous Caenorhabditis elegans model system...
November 16, 2016: Biogerontology
Jonathan D Hibshman, Anthony Hung, L Ryan Baugh
Maternal effects of environmental conditions produce intergenerational phenotypic plasticity. Adaptive value of these effects depends on appropriate anticipation of environmental conditions in the next generation, and mismatch between conditions may contribute to disease. However, regulation of intergenerational plasticity is poorly understood. Dietary restriction (DR) delays aging but maternal effects have not been investigated. We demonstrate maternal effects of DR in the roundworm C. elegans. Worms cultured in DR produce fewer but larger progeny...
October 2016: PLoS Genetics
Adi Pinkas, Michael Aschner
Advanced glycation end-products (AGEs) are non-enzymatically glycated proteins, lipids and nucleic acids. These compounds both originate exogenously and are formed endogenously, and are associated, along with one of their receptors - RAGE, with a variety of pathologies and neurodegeneration. Some of their deleterious effects include affecting insulin signaling and FOXO-related pathways in both receptor-dependent and -independent manner. A potential ameliorating agent for these effects is insulin, which is being studied in several in vivo and in vitro models; one of these models is C...
October 5, 2016: Chemical Research in Toxicology
Marieke Visscher, Sasha De Henau, Mattheus H E Wildschut, Robert M van Es, Ineke Dhondt, Helen Michels, Patrick Kemmeren, Ellen A Nollen, Bart P Braeckman, Boudewijn M T Burgering, Harmjan R Vos, Tobias B Dansen
The balance between protein synthesis and protein breakdown is a major determinant of protein homeostasis, and loss of protein homeostasis is one of the hallmarks of aging. Here we describe pulsed SILAC-based experiments to estimate proteome-wide turnover rates of individual proteins. We applied this method to determine protein turnover rates in Caenorhabditis elegans models of longevity and Parkinson's disease, using both developing and adult animals. Whereas protein turnover in developing, long-lived daf-2(e1370) worms is about 30% slower than in controls, the opposite was observed in day 5 adult worms, in which protein turnover in the daf-2(e1370) mutant is twice as fast as in controls...
September 13, 2016: Cell Reports
Ineke Dhondt, Vladislav A Petyuk, Huaihan Cai, Lieselot Vandemeulebroucke, Andy Vierstraete, Richard D Smith, Geert Depuydt, Bart P Braeckman
Most aging hypotheses assume the accumulation of damage, resulting in gradual physiological decline and, ultimately, death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend the lifespan. However, lowering translational efficiency extends rather than shortens the lifespan in C. elegans. We studied turnover of individual proteins in the long-lived daf-2 mutant by combining SILeNCe (stable isotope labeling by nitrogen in Caenorhabditiselegans) and mass spectrometry...
September 13, 2016: Cell Reports
Gayeung Kwon, Jiyun Lee, Young-Hee Lim
Dairy Propionibacterium freudenreichii is a candidate non-lactic acid probiotic. However, little information is available on the effect of P. freudenreichii on lifespan extension in humans. The aim of this study was to evaluate the effects of P. freudenreichii on lifespan extension and to elucidate the mechanism of P. freudenreichii-dependent lifespan extension in Caenorhabditis elegans. The results showed that P. freudenreichii significantly (p < 0.05) extended the lifespan of C. elegans compared with Escherichia coli OP50, a standard food for the worm...
2016: Scientific Reports
Julianne Martell, Yonghak Seo, Daniel W Bak, Samuel F Kingsley, Heidi A Tissenbaum, Eranthie Weerapana
In the nematode Caenorhabditis elegans, inactivating mutations in the insulin/IGF-1 receptor, DAF-2, result in a 2-fold increase in lifespan mediated by DAF-16, a FOXO-family transcription factor. Downstream protein activities that directly regulate longevity during impaired insulin/IGF-1 signaling (IIS) are poorly characterized. Here, we use global cysteine-reactivity profiling to identify protein activity changes during impaired IIS. Upon confirming that cysteine reactivity is a good predictor of functionality in C...
August 18, 2016: Cell Chemical Biology
Hoon Jeon, Dong Seok Cha
The present study investigated the effects and underlying mechanism of ethylacetate fraction of Ribes fasciculatum (ERF) on the lifespan and stress tolerance using a Caenorhabditis elegans model. The longevity activity of ERF was determined by lifespan assay under normal culture condition. The survival rate of nematodes under various stress conditions was assessed to validate the effects of ERF on the stress tolerance. To determine the antioxidant potential of ERF, the superoxide dismutase (SOD) activities and intracellular reactive oxygen species (ROS) levels were investigated...
May 2016: Chinese Journal of Natural Medicines
Vikram Narayan, Tony Ly, Ehsan Pourkarimi, Alejandro Brenes Murillo, Anton Gartner, Angus I Lamond, Cynthia Kenyon
Effective network analysis of protein data requires high-quality proteomic datasets. Here, we report a near doubling in coverage of the C. elegans adult proteome, identifying >11,000 proteins in total with ∼9,400 proteins reproducibly detected in three biological replicates. Using quantitative mass spectrometry, we identify proteins whose abundances vary with age, revealing a concerted downregulation of proteins involved in specific metabolic pathways and upregulation of cellular stress responses with advancing age...
August 2016: Cell Systems
Shun Kitaoka, Anthony D Morielli, Feng-Qi Zhao
Insulin signaling plays a central role in the regulation of facilitative glucose transporters (GLUTs) in humans. To establish Caenorhabditis elegans (C. elegans) as a model to study the mechanism underlying insulin regulation of GLUT, we identified that FGT-1 is most likely the only functional GLUT homolog in C. elegans and is ubiquitously expressed. The FGT-1-mediated glucose uptake was almost completely defective in insulin/IGF-like signaling (IIS) mutants daf-2 and age-1, and this defect mainly resulted from the down-regulated FGT-1 protein expression...
June 2016: FEBS Open Bio
Shan-Qing Zheng, Xiao-Bing Huang, Ti-Kun Xing, Ai-Jun Ding, Gui-Sheng Wu, Huai-Rong Luo
Coffee and tea, two of the most popular drinks around the world, share many in common from chemical components to beneficial effects on human health. One of their shared components, the polyphenols, most notably chlorogenic acid (CGA), was supposed to account for many of the beneficial effects on ameliorating diseases occurred accompanying people aging, such as the antioxidant effect and against diabetes and cardiovascular disease. CGA is also present in many traditional Chinese medicines. However, the mechanism of these effects was vague...
July 4, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Udayakumar Prithika, Veerappan Deepa, Krishnaswamy Balamurugan
Heat shock proteins (HSPs) are highly chaperonic molecules that give immediate response during any stress, tissue damage or bacterial infections. In the present study, the role of HSPs upon bacterial encounter is studied by applying external heat induction to live Caenorhabditis elegans Heat shock was observed to increase the life span of wild type C. elegans upon pathogenic encounter, indicating a role of HSPs in bacterial infection and immunity. Similar increase in resistance towards pathogenesis observed in long-lived C...
August 2016: Innate Immunity
Huimin Peng, Zhaohan Wei, Hujie Luo, Yiting Yang, Zhengxing Wu, Lu Gan, Xiangliang Yang
Hesperidin, abundant in citrus fruits, has a wide range of pharmacological effects, including anticarcinogenic, anti-inflammatory, antioxidative, radioprotective, and antiviral activities. However, relatively few studies on the effects of hesperidin on lipid metabolism have been reported. Here, using Caenorhaditis elegans as a model animal, we found that 100 μM hesperidin significantly decreased fat accumulation in both high-fat worms cultured in nematode growth medium containing 10 mM glucose (83.5 ± 1.2% versus control by Sudan Black B staining and 87...
June 29, 2016: Journal of Agricultural and Food Chemistry
James Dillon, Lindy Holden-Dye, Vincent O'Connor, Neil A Hopper
Insulin signalling plays a significant role in both developmental programmes and pathways modulating the neuronal signalling that controls adult behaviour. Here, we have investigated insulin signalling in food-associated behaviour in adult C. elegans by scoring locomotion and feeding on and off bacteria, the worm's food. This analysis used mutants (daf-2, daf-18) of the insulin signalling pathway, and we provide evidence for an acute role for insulin signalling in the adult nervous system distinct from its impact on developmental programmes...
June 2016: Invertebrate Neuroscience: IN
Masahiro Tomioka, Yasuki Naito, Hidehito Kuroyanagi, Yuichi Iino
Alternative splicing generates protein diversity essential for neuronal properties. However, the precise mechanisms underlying this process and its relevance to physiological and behavioural functions are poorly understood. To address these issues, we focused on a cassette exon of the Caenorhabditis elegans insulin receptor gene daf-2, whose proper variant expression in the taste receptor neuron ASER is critical for taste-avoidance learning. We show that inclusion of daf-2 exon 11.5 is restricted to specific neuron types, including ASER, and is controlled by a combinatorial action of evolutionarily conserved alternative splicing factors, RBFOX, CELF and PTB families of proteins...
2016: Nature Communications
Pedro Reis Rodrigues, Tiffany K Kaul, Jo-Hao Ho, Mark Lucanic, Kristopher Burkewitz, William B Mair, Jason M Held, Laura M Bohn, Matthew S Gill
Under adverse environmental conditions the nematode Caenorhabditis elegans can enter an alternate developmental stage called the dauer larva. To identify lipophilic signaling molecules that influence this process, we screened a library of bioactive lipids and found that AM251, an antagonist of the human cannabinoid (CB) receptor, suppresses dauer entry in daf-2 insulin receptor mutants. AM251 acted synergistically with glucose supplementation indicating that the metabolic status of the animal influenced the activity of this compound...
2016: G3: Genes—Genomes—Genetics
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