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https://www.readbyqxmd.com/read/28734827/multi-omics-analyses-of-starvation-responses-reveal-a-central-role-for-lipoprotein-metabolism-in-acute-starvation-survival-in-c-%C3%A2-elegans
#1
Eva Bang Harvald, Richard R Sprenger, Kathrine Brændgaard Dall, Christer S Ejsing, Ronni Nielsen, Susanne Mandrup, Alejandro Brenes Murillo, Mark Larance, Anton Gartner, Angus I Lamond, Nils J Færgeman
Starvation causes comprehensive metabolic changes, which are still not fully understood. Here, we used quantitative proteomics and RNA sequencing to examine the temporal starvation responses in wild-type Caenorhabditis elegans and animals lacking the transcription factor HLH-30. Our findings show that starvation alters the abundance of hundreds of proteins and mRNAs in a temporal manner, many of which are involved in central metabolic pathways, including lipoprotein metabolism. We demonstrate that premature death of hlh-30 animals under starvation can be prevented by knockdown of either vit-1 or vit-5, encoding two different lipoproteins...
July 12, 2017: Cell Systems
https://www.readbyqxmd.com/read/28733327/cenp-a-and-topoisomerase-ii-antagonistically-affect-chromosome-length
#2
A-M Ladouceur, Rajesh Ranjan, Lydia Smith, Tanner Fadero, Jennifer Heppert, Bob Goldstein, Amy Shaub Maddox, Paul S Maddox
The size of mitotic chromosomes is coordinated with cell size in a manner dependent on nuclear trafficking. In this study, we conducted an RNA interference screen of the Caenorhabditis elegans nucleome in a strain carrying an exceptionally long chromosome and identified the centromere-specific histone H3 variant CENP-A and the DNA decatenizing enzyme topoisomerase-II (topo-II) as candidate modulators of chromosome size. In the holocentric organism C. elegans, CENP-A is positioned periodically along the entire length of chromosomes, and in mitosis, these genomic regions come together linearly to form the base of kinetochores...
July 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28733033/discovery-of-small-molecule-inhibitors-for-the-c-elegans-caspase-ced-3-by-high-throughput-screening
#3
Scott Brantley, Steven W Cotten, David R Lamson, Ginger R Smith, Rihe Liu, Kevin P Williams
C.elegans has been widely used as a model organism for programmed cell death and apoptosis. Although, the CED-3 caspase is the primary effector of cell death in C. elegans, no selective inhibitors have been identified. Utilizing high-throughput screening with recombinant C. elegans CED-3 protein, we have discovered and confirmed 21 novel small molecule inhibitors. Six compounds had IC50 values < 10 μM. From these, four distinct chemotypes were identified. The inhibitor scaffolds described here could lead to the development of selective molecular probes to facilitate our understanding of programmed cell death in this model organism...
July 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28732158/deleterious-consequences-of-udp-galactopyranose-mutase-inhibition-for-nematodes
#4
Valerie J Winton, Alexander M Justen, Helen Deng, Laura L Kiessling
Parasitic nematodes pose a serious threat to agriculture, livestock, and human health. Increasing resistance to anti-parasitic agents underscores the need to replenish our anthelmintic arsenal. The non-pathogenic Caenorhabditis elegans, which serves as an effective model of parasitic helminths, has been used to search for new anthelmintic leads. We previously reported small-molecule inhibitors of the essential C. elegans protein UDP-galactopyranose mutase (UGM or Glf). This enzyme is required for the generation of galactofuranose (Galf)-containing glycans and is needed in nematodes for proper cuticle formation...
July 21, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28732077/mutations-in-the-caenorhabditis-elegans-orthologs-of-human-genes-required-for-mitochondrial-trna-modification-cause-similar-electron-transport-chain-defects-but-different-nuclear-responses
#5
Carmen Navarro-González, Ismaïl Moukadiri, Magda Villarroya, Ernesto López-Pascual, Simon Tuck, M-Eugenia Armengod
Several oxidative phosphorylation (OXPHOS) diseases are caused by defects in the post-transcriptional modification of mitochondrial tRNAs (mt-tRNAs). Mutations in MTO1 or GTPBP3 impair the modification of the wobble uridine at position 5 of the pyrimidine ring and cause heart failure. Mutations in TRMU affect modification at position 2 and cause liver disease. Presently, the molecular basis of the diseases and why mutations in the different genes lead to such different clinical symptoms is poorly understood...
July 21, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28728902/role-of-mirnas-in-development-and-disease-lessons-learnt-from-small-organisms
#6
REVIEW
Swati Chandra, Divya Vimal, Divya Sharma, Vipin Rai, Subash Chandra Gupta, D Kar Chowdhuri
MicroRNAs (miRNAs) constitute a class of small (21-24 nucleotides) non-coding RNAs that regulate gene expression at the post-transcriptional level. Caenorhabditis elegans, Drosophila melanogaster, and many other small organisms have been instrumental in deciphering the biological functions of miRNAs. While some miRNAs from small organisms are highly conserved across the taxa, others are organism specific. The miRNAs are known to play a crucial role during development and in various cellular functions such as cell survival, cell proliferation, and differentiation...
July 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28727758/longevity-effect-of-a-polysaccharide-from-chlorophytum-borivilianum-on-caenorhabditis-elegans-and-saccharomyces-cerevisiae
#7
Steve Thomas Pannakal, Sibylle Jäger, Albert Duranton, Amit Tewari, Subarna Saha, Aneesha Radhakrishnan, Nita Roy, Jean François Kuntz, Soraya Fermas, Darryl James, Jane Mellor, Namita Misra, Lionel Breton
The traditional Indian medicine, Ayurveda, provides insights and practical solutions towards a healthy life style. Rasayana is a branch of Ayurveda known for preserving and promoting health, enhancing the quality of life and delaying the aging process. In the traditional knowledge, the Rasayana herb, Chlorophytum borivilianum (C. borivilanum) is regarded as a general health promoting tonic that delays aging and increases lifespan, cognitive function and physical strength. Aging is a complex and multifactorial physiological phenomenon that manifests itself over a wide range of biological systems, tissues, and functions...
2017: PloS One
https://www.readbyqxmd.com/read/28724632/hydrogen-peroxide-produced-by-superoxide-dismutase-sod-2-is-required-for-sperm-activation-in-caenorhabditis-elegans
#8
Taro Sakamoto, Hirotaka Imai
Superoxide dismutase (SOD) is a ubiquitous antioxidant enzyme that catalytically converts the superoxide radical to hydrogen peroxide (H2O2). In mammals, high SOD activity can be detected in sperm and seminal plasma, and a correlation between loss of SOD activity and male infertility has been observed; however, the underlying mechanisms remain to be clarified. Here, we report that the deletion of two major SOD genes in Caenorhabditis elegans, sod-1 and sod-2, cause sperm activation defects, thereby leading to a significant reduction in brood size...
July 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28723566/genome-wide-rnai-screen-for-fat-regulatory-genes-in-c-%C3%A2-elegans-identifies-a-proteostasis-ampk-axis-critical-for-starvation-survival
#9
Christopher M Webster, Elizabeth C Pino, Christopher E Carr, Lianfeng Wu, Ben Zhou, Lucydalila Cedillo, Michael C Kacergis, Sean P Curran, Alexander A Soukas
Organisms must execute metabolic defenses to survive nutrient deprivation. We performed a genome-wide RNAi screen in Caenorhabditis elegans to identify fat regulatory genes indispensable for starvation resistance. Here, we show that opposing proteostasis pathways are principal determinants of starvation survival. Reduced function of cytoplasmic aminoacyl tRNA synthetases (ARS genes) increases fat mass and extends starvation survival, whereas reduced proteasomal function reduces fat and starvation survival. These opposing pathways converge on AMP-activated protein kinase (AMPK) as the critical effector of starvation defenses...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28721038/toxicity-based-toxicokinetic-toxicodynamic-assessment-of-bioaccumulation-and-nanotoxicity-of-zerovalent-iron-nanoparticles-in-caenorhabditis-elegans
#10
Ying-Fei Yang, Yi-Jun Lin, Chung-Min Liao
Elucidating the relationships between the toxicity-based-toxicokinetic (TBTK)/toxicodynamic (TD) properties of engineered nanomaterials and their nanotoxicity is crucial for human health-risk analysis. Zerovalent iron (Fe(0)) nanoparticles (NPs) are one of the most prominent NPs applied in remediating contaminated soils and groundwater. However, there are concerns that Fe(0)NP application contributes to long-term environmental and human health impacts. The nematode Caenorhabditis elegans is a surrogate in vivo model that has been successfully applied to assess the potential nanotoxicity of these nanomaterials...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28716951/a-calcium-diacylglycerol-stimulated-protein-kinase-c-c-elegans-pkc-2-links-thermal-signals-to-learned-behavior-by-acting-in-a-sensory-neuron-and-intestinal-cells
#11
Marianne Land, Charles S Rubin
Ca(2+) and diacylglycerol (DAG) activated protein kinase C (cPKC) promotes learning and behavioral plasticity. However, knowledge of in vivo regulation and exact functions of cPKCs that affect behavior is limited. We show that PKC-2, a C. elegans cPKC, is essential for a complex behavior, thermotaxis. C. elegans memorizes a nutrient-associated cultivation temperature (Tc) and migrates along Tc within a 17-25°C gradient. pkc-2 gene disruption abrogated thermotaxis; a PKC-2 transgene, driven by endogenous pkc-2 promoters, restored thermotaxis behavior in pkc-2(-/-) animals...
July 17, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28716930/conserved-gene-regulatory-module-specifies-lateral-neural-borders-across-bilaterians
#12
Yongbin Li, Di Zhao, Takeo Horie, Geng Chen, Hongcun Bao, Siyu Chen, Weihong Liu, Ryoko Horie, Tao Liang, Biyu Dong, Qianqian Feng, Qinghua Tao, Xiao Liu
The lateral neural plate border (NPB), the neural part of the vertebrate neural border, is composed of central nervous system (CNS) progenitors and peripheral nervous system (PNS) progenitors. In invertebrates, PNS progenitors are also juxtaposed to the lateral boundary of the CNS. Whether there are conserved molecular mechanisms determining vertebrate and invertebrate lateral neural borders remains unclear. Using single-cell-resolution gene-expression profiling and genetic analysis, we present evidence that orthologs of the NPB specification module specify the invertebrate lateral neural border, which is composed of CNS and PNS progenitors...
July 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28716093/c-elegans-sup-46-an-hnrnpm-family-rna-binding-protein-that-prevents-paternally-mediated-epigenetic-sterility
#13
Wendy L Johnston, Aldis Krizus, Arun K Ramani, Wade Dunham, Ji Young Youn, Andrew G Fraser, Anne-Claude Gingras, James W Dennis
BACKGROUND: In addition to DNA, gametes contribute epigenetic information in the form of histones and non-coding RNA. Epigenetic programs often respond to stressful environmental conditions and provide a heritable history of ancestral stress that allows for adaptation and propagation of the species. In the nematode C. elegans, defective epigenetic transmission often manifests as progressive germline mortality. We previously isolated sup-46 in a screen for suppressors of the hexosamine pathway gene mutant, gna-2(qa705)...
July 17, 2017: BMC Biology
https://www.readbyqxmd.com/read/28713491/mulberry-anthocyanin-extract-ameliorates-oxidative-damage-in-hepg2-cells-and-prolongs-the-lifespan-of-caenorhabditis-elegans-through-mapk-and-nrf2-pathways
#14
Fujie Yan, Yushu Chen, Ramila Azat, Xiaodong Zheng
Mulberry anthocyanins possess many pharmacological effects including liver protection, anti-inflammation, and anticancer. The aim of this study was to evaluate whether mulberry anthocyanin extract (MAE) exerts beneficial effects against oxidative stress damage in HepG2 cells and Caenorhabditis elegans. In vitro, MAE prevented cytotoxicity, increased glucose consumption and uptake, and eliminated excessive intracellular free radicals in H2O2-induced cells. Moreover, MAE pretreatment maintained Nrf2, HO-1, and p38 MAPK stimulation and abolished upregulation of p-JNK, FOXO1, and PGC-1α that were involved in oxidative stress and insulin signalling modulation...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28713422/computational-analysis-of-lifespan-experiment-reproducibility
#15
Michael Petrascheck, Dana L Miller
Independent reproducibility is essential to the generation of scientific knowledge. Optimizing experimental protocols to ensure reproducibility is an important aspect of scientific work. Genetic or pharmacological lifespan extensions are generally small compared to the inherent variability in mean lifespan even in isogenic populations housed under identical conditions. This variability makes reproducible detection of small but real effects experimentally challenging. In this study, we aimed to determine the reproducibility of C...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28710397/brain-specific-lamellipodin-knockout-results-in-hyperactivity-and-increased-anxiety-of-mice
#16
Cristian Bodo, Cathy Fernandes, Matthias Krause
Lamellipodin (Lpd) functions as an important signalling integrator downstream of growth factor and axon guidance receptors. Mechanistically, Lpd promotes actin polymerization by interacting with F-actin and the actin effectors Ena/VASP proteins and the SCAR/WAVE complex. Thereby, Lpd supports lamellipodia protrusion, cell migration and endocytosis. In the mammalian central nervous system, Lpd contributes to neuronal morphogenesis, neuronal migration during development and its C. elegans orthologue MIG-10 also supports synaptogenesis...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710264/two-novel-dissimilar-crystal-proteins-cry5ca1-and-cry5da1-synergistically-act-against-meloidogyne-incognita-and-delay-cry5ba-based-nematode-resistance
#17
Ce Geng, Yingying Liu, Miaomiao Li, Zhen Tang, Sajid Muhammad, Jinshui Zheng, Danfeng Wan, Donghai Peng, Lifang Ruan, Ming Sun
Cry proteins of Bacillus thuringiensis have been successfully used as biopesticides and transgenic crops throughout the world. However, resources against the most serious agricultural pathogens, plant root-knot nematodes, are limited. The genomes of several highly nematicidal virulent Bt strains from our laboratory have been sequenced, facilitating the identification of novel Cry proteins and other virulence factors. We identified two novel Cry proteins, Cry5Ca1 and Cry5Da1, that exhibit high toxicity against Meloidogyne incognita Using the Caenorhabditis elegans model, both Cry5 toxins showed to negatively affect nematode lifespan, fertility and survival...
July 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28710073/zinc-mediates-the-srebp-scd-axis-to-regulate-lipid-metabolism-in-caenorhabditis-elegans
#18
Jing-Jing Zhang, Jun-Jun Hao, Yu-Ru Zhang, Yan-Li Wang, Ming-Yi Li, Hui-Lai Miao, Xiao-Ju Zou, Bin Liang
Maintenance of lipid homeostasis is crucial for cells in response to lipid requirements or surplus. The SREBPs transcription factors play essential roles in regulating lipid metabolism and are associated with many metabolic diseases. However, SREBP regulation of lipid metabolism is still less understood. Here, we show that reduction of SBP-1, the only homologue of SREBPs in C. elegans, surprisingly leads to high level of zinc. On the contrary, zinc reduction by mutation of sur-7, encoding a member of the cation diffusion facilitator (CDF) family, restores the fat accumulation and fatty acid profile of sbp-1(ep79) mutant...
July 14, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28705837/cyb-1-a-c-elegans-b-type-cyclin-maintains-proper-position-and-number-of-centrosomes-during-spermatogenesis
#19
Sunghee Yoon, Ichiro Kawasaki, Yhong-Hee Shim
Depletion of cyb-1, a major B-type cyclin expressed during C. elegans spermatogenesis, caused a meiotic division arrest in diakinesis-stage spermatocytes with multiple and mispositioned centrosomes. Association of SUN-1 and ZYG-12, two nuclear membrane proteins, is critical for centrosome-nuclear envelope attachment. We found that sun-1 depletion caused centrosome defects similar to those caused by cyb-1 depletion in diakinesis-stage spermatocytes. In addition, Ser8 and Ser43 residues in SUN-1 were dephosphorylated in cyb-1-depleted diakinesis-stage spermatocytes...
July 13, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28704415/c-elegans-sma-10-regulates-bmp-receptor-trafficking
#20
Ryan J Gleason, Mehul Vora, Ying Li, Nanci S Kane, Kelvin Liao, Richard W Padgett
Signal transduction of the conserved transforming growth factor-β (TGFβ) family signaling pathway functions through two distinct serine/threonine transmembrane receptors, the type I and type II receptors. Endocytosis orchestrates the assembly of signaling complexes by coordinating the entry of receptors with their downstream signaling mediators. Recently, we showed that the C. elegans type I bone morphogenetic protein (BMP) receptor SMA-6, part of the TGFβ family, is recycled through the retromer complex while the type II receptor, DAF-4 is recycled in a retromer-independent, ARF-6 dependent manner...
2017: PloS One
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