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C. elegans

Cheng-Wei Wu, Andrew Deonarine, Aaron Przybysz, Kevin Strange, Keith P Choe
SKN-1/Nrf are the primary antioxidant/detoxification response transcription factors in animals and they promote health and longevity in many contexts. SKN-1/Nrf are activated by a remarkably broad-range of natural and synthetic compounds and physiological conditions. Defining the signaling mechanisms that regulate SKN-1/Nrf activation provides insights into how cells coordinate responses to stress. Nrf2 in mammals is regulated in part by the redox sensor repressor protein named Keap1. In C. elegans, the p38 MAPK cascade in the intestine activates SKN-1 during oxidative stress by promoting its nuclear accumulation...
October 2016: PLoS Genetics
Kyung Suk Lee, Lucy E Lee, Erel Levine
Small animals such as the roundworm C. elegans are excellent models for studying bacterial infection and host response, as well as for genetic and chemical screens. A key methodology is the killing assay, in which the number of surviving animals is tracked as a function of the time post infection. This is a labor-intensive procedure, prone to human error and subjective choices, and often involves undesired perturbation to the animals and their environment. In addition, the survival of animals is just one aspect of a multi-dimensional complex biological process...
October 24, 2016: Scientific Reports
Hema Negi, Aparna Shukla, Feroz Khan, Rakesh Pandey
Remarkably the c-Jun-NH2-terminal kinase (JNK) pathway is all evolutionarily conserved across species. In view of the hypothesis that increased stress resistance subdue aging, we investigated the role of ursolic acid (3β-Hydroxy-urs-12-en-28-oic acid; UA) in the pioneering aging model Caenorhabditis elegans with an increase in mean and maximum lifespan by up to 30%. Our genetic study unravelled the underlying pathway where JNK-1 is acting independently of insulin-IGF-1 signalling (IIS) pathway to modulate longevity...
October 20, 2016: Biochemical and Biophysical Research Communications
Jyotiska Chaudhuri, Neelanjan Bose, Jianke Gong, David Hall, Alexander Rifkind, Dipa Bhaumik, T Harshani Peiris, Manish Chamoli, Catherine H Le, Jianfeng Liu, Gordon J Lithgow, Arvind Ramanathan, X Z Shawn Xu, Pankaj Kapahi
Reactive α-dicarbonyls (α-DCs), like methylglyoxal (MGO), accumulate with age and have been implicated in aging and various age-associated pathologies, such as diabetic complications and neurodegenerative disorders like Alzheimer's and Parkinson's diseases. Evolutionarily conserved glyoxalases are responsible for α-DC detoxification; however, their core biochemical regulation has remained unclear. We have established a Caenorhabditis elegans model, based on an impaired glyoxalase (glod-4/GLO1), to broadly study α-DC-related stress...
October 12, 2016: Current Biology: CB
S Lavarías, C Ocon, V López van Oosterom, A Laino, D A Medesani, A Fassiano, H Garda, J Donadelli, M Ríos de Molina, A Rodrigues Capítulo
The present study analyzes a battery of biomarkers in the water bug Belostoma elegans from a stream polluted with organic matter (OMS), and another one considered as reference site (RS) during spring-summer season (December to March). Biochemical parameters of glucidic, lipidic and oxidative metabolic pathways were analyzed in males and females of this insect. In general, no significant differences were observed in all biomarkers assayed between both sexes, except lactate concentration which was higher in males than in females (p < 0...
October 23, 2016: Environmental Science and Pollution Research International
Gölnur Fakhrullina, Farida Akhatova, Maria Kibardina, Denis Fokin, Rawil Fakhrullin
Here we introduce PeakForce Tapping non-resonance atomic force microscopy for imaging and nanomechanical mapping of Caenorhabditis elegans nematodes. The animals were imaged both in air and water at nanoscale resolution. Layer-by-layer glass surface modification was employed to secure the worms for imaging in water. Microtopography of head region, annuli, furrows, lateral alae and tail region was visualised. Analysis of nanoscale surface features obtained during AFM imaging of three larval and adult hermaphrodite nematodes in natural environment allowed for numerical evaluation of annuli periodicity, furrows depth and annuli roughness...
October 19, 2016: Nanomedicine: Nanotechnology, Biology, and Medicine
Anna Hegsted, Forrest A Wright, SarahBeth Votra, David Pruyne
Formins are regulators of actin filament dynamics. We demonstrate here that two formins, FHOD-1 and EXC-6, are important in the nematode Caenorhabditis elegans for ovulation, during which actomyosin contractions push a maturing oocyte from the gonad arm into a distensible bag-like organ, the spermatheca. EXC-6, a homolog of the disease-associated mammalian formin INF2, is highly expressed in the spermatheca, where it localizes to cell-cell junctions and to circumferential actin filament bundles. Loss of EXC-6 does not noticeably affect the organization the actin filament bundles, and causes only a very modest increase in the population of junction-associated actin filaments...
October 22, 2016: Cytoskeleton
Sangmi Oh, Ichiro Kawasaki, Jae-Hyung Park, Yhong-Hee Shim
Cell division cycle 25 (cdc25) is an evolutionarily conserved phosphatase that promotes cell cycle progression. Among the four cdc25 orthologs in Caenorhabditis elegans, we found that cdc-25.4 mutant males failed to produce outcrossed progeny. This was not caused by defects in sperm development, but by defects in male mating behavior. The cdc-25.4 mutant males showed various defects during male mating, including contact response, backing, turning, and vulva location. Aberrant turning behavior was the most prominent defect in the cdc-25...
October 21, 2016: G3: Genes—Genomes—Genetics
Lingfeng Meng, Albert Zhang, Yishi Jin, Dong Yan
Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4...
October 21, 2016: ELife
Young Joon Kwon, Marni J Falk, Michael J Bennett
CLN3 disease (Spielmeyer-Vogt-Sjogren-Batten disease, previously known as classic juvenile neuronal ceroid lipofuscinosis, NCL) is a pediatric-onset progressive neurodegenerative disease characterized by progressive vision loss, seizures, loss of cognitive and motor function, and early death. While no precise biochemical mechanism or therapies are known, the pathogenesis of CLN3 disease involves intracellular calcium accumulation that may trigger apoptosis. Our prior work in in vitro cell models of CLN3 deficiency suggested that FDA-approved calcium channel antagonists may have therapeutic value...
October 20, 2016: Journal of Inherited Metabolic Disease
Shaul Yogev, Roshni Cooper, Richard Fetter, Mark Horowitz, Kang Shen
Axonal microtubule (MT) arrays are the major cytoskeleton substrate for cargo transport. How MT organization, i.e., polymer length, number, and minus-end spacing, is regulated and how it impinges on axonal transport are unclear. We describe a method for analyzing neuronal MT organization using light microscopy. This method circumvents the need for electron microscopy reconstructions and is compatible with live imaging of cargo transport and MT dynamics. Examination of a C. elegans motor neuron revealed how age, MT-associated proteins, and signaling pathways control MT length, minus-end spacing, and coverage...
October 19, 2016: Neuron
Emily R Troemel
Microsporidia comprise a phylum of obligate intracellular pathogens related to fungi that infect virtually all animals. Recently, the nematode Caenorhabditis elegans has been developed as a convenient model for studying microsporidia infection in a whole-animal host through the identification and characterization of a natural microsporidian pathogen of this commonly studied laboratory organism. The C. elegans natural microsporidian pathogen is named Nematocida parisii, and it causes a lethal intestinal infection in C...
October 2016: Microbiology Spectrum
Mi-Sun Kwon, Jaewon Min, Hee-Yeon Jeon, Kwangwoo Hwang, Chuna Kim, Junho Lee, Je-Gun Joung, Woong-Yang Park, Hyunsook Lee
BRCA2 is a multifunctional tumor suppressor involved in homologous recombination (HR), mitotic checkpoint regulation, and telomere homeostasis. Absence of Brca2 in mice results in progressive shortening of telomeres and senescence, yet cells are prone to neoplastic transformation with elongated telomeres, suggesting that BRCA2 has positive and negative effects on telomere length regulation along the path to tumorigenesis. Using Caenorhabditis elegans as a model, we show here that depletion of BRC-2, an ortholog of BRCA2, paradoxically delays senescence in telomerase-deficient mutant worms...
October 2016: FEBS Open Bio
Cristina Matthewman, Tyne W Miller-Fleming, David M Miller, Laura Bianchi
Hyperactivated DEG/ENaC channels cause neuronal death mediated by intracellular Ca(2+) overload. Mammalian ASIC1a and C. elegans MEC-4(d) neurotoxic channels conduct both Na(+) and Ca(2+) raising the possibility that direct Ca(2+) influx through these channels contributes to the intracellular Ca(2+) overload. However, we showed that homologous C. elegans DEG/ENaC channel UNC-8(d) is not Ca(2+) permeable yet it is neurotoxic, suggesting that Na(+) influx is sufficient to induce cell death. Interestingly, UNC-8(d) shows small currents due to extracellular Ca(2+) block in the Xenopus oocytes expression system...
October 19, 2016: American Journal of Physiology. Cell Physiology
Jacques Pécréaux, Stefanie Redemann, Zahraa Alayan, Benjamin Mercat, Sylvain Pastezeur, Carlos Garzon-Coral, Anthony A Hyman, Jonathon Howard
Precise positioning of the mitotic spindle is important for specifying the plane of cell division, which in turn determines how the cytoplasmic contents of the mother cell are partitioned into the daughter cells, and how the daughters are positioned within the tissue. During metaphase in the early Caenorhabditis elegans embryo, the spindle is aligned and centered on the anterior-posterior axis by a microtubule-dependent machinery that exerts restoring forces when the spindle is displaced from the center. To investigate the accuracy and stability of centering, we tracked the position and orientation of the mitotic spindle during the first cell division with high temporal and spatial resolution...
October 18, 2016: Biophysical Journal
Antonia Piazzesi, Dražen Papić, Fabio Bertan, Paolo Salomoni, Pierluigi Nicotera, Daniele Bano
Chromatin structure orchestrates the accessibility to the genetic material. Replication-independent histone variants control transcriptional plasticity in postmitotic cells. The life-long accumulation of these histones has been described, yet the implications on organismal aging remain elusive. Here, we study the importance of the histone variant H3.3 in Caenorhabditis elegans longevity pathways. We show that H3.3-deficient nematodes have negligible lifespan differences compared to wild-type animals. However, H3...
October 18, 2016: Cell Reports
Daifeng Wang, Fei He, Sergei Maslov, Mark Gerstein
Gene expression is controlled by the combinatorial effects of regulatory factors from different biological subsystems such as general transcription factors (TFs), cellular growth factors and microRNAs. A subsystem's gene expression may be controlled by its internal regulatory factors, exclusively, or by external subsystems, or by both. It is thus useful to distinguish the degree to which a subsystem is regulated internally or externally-e.g., how non-conserved, species-specific TFs affect the expression of conserved, cross-species genes during evolution...
October 2016: PLoS Computational Biology
Juan Antonio Garcia-Martin, Amir H Bayegan, Ivan Dotu, Peter Clote
BACKGROUND: RNA inverse folding is the problem of finding one or more sequences that fold into a user-specified target structure s 0, i.e. whose minimum free energy secondary structure is identical to the target s 0. Here we consider the ensemble of all RNA sequences that have low free energy with respect to a given target s 0. RESULTS: We introduce the program RNAdualPF, which computes the dual partition function Z (∗), defined as the sum of Boltzmann factors exp(-E(a,s 0)/RT) of all RNA nucleotide sequences a compatible with target structure s 0...
October 19, 2016: BMC Bioinformatics
Mark D Mathew, Neal D Mathew, Angela Miller, Mike Simpson, Vinci Au, Stephanie Garland, Marie Gestin, Mark L Edgley, Stephane Flibotte, Aruna Balgi, Jennifer Chiang, Guri Giaever, Pamela Dean, Audrey Tung, Michel Roberge, Calvin Roskelley, Tom Forge, Corey Nislow, Donald Moerman
BACKGROUND: The lack of new anthelmintic agents is of growing concern because it affects human health and our food supply, as both livestock and plants are affected. Two principal factors contribute to this problem. First, nematode resistance to anthelmintic drugs is increasing worldwide and second, many effective nematicides pose environmental hazards. In this paper we address this problem by deploying a high throughput screening platform for anthelmintic drug discovery using the nematode Caenorhabditis elegans as a surrogate for infectious nematodes...
October 2016: PLoS Neglected Tropical Diseases
Robin van Schendel, Jane van Heteren, Richard Welten, Marcel Tijsterman
For more than half a century, genotoxic agents have been used to induce mutations in the genome of model organisms to establish genotype-phenotype relationships. While inaccurate replication across damaged bases can explain the formation of single nucleotide variants, it remained unknown how DNA damage induces more severe genomic alterations. Here, we demonstrate for two of the most widely used mutagens, i.e. ethyl methanesulfonate (EMS) and photo-activated trimethylpsoralen (UV/TMP), that deletion mutagenesis is the result of polymerase Theta (POLQ)-mediated end joining (TMEJ) of double strand breaks (DSBs)...
October 2016: PLoS Genetics
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