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[
WormBook,
2005]
In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the global, epigenetic regulation of X chromosomes that is maintained throughout the lifetime of hermaphrodites.
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[
Genetics,
2019]
The Genetics Society of America's (GSA) Thomas Hunt Morgan Medal honors researchers for lifetime achievement in genetics. The recipient of the 2018 Morgan Medal, Barbara J. Meyer of the Howard Hughes Medical Institute and the University of California, Berkeley, is recognized for her career-long, groundbreaking investigations of how chromosome behaviors are controlled. Meyer's work has revealed mechanisms of sex determination and dosage compensation in <i>Caenorhabditis elegans</i> that continue to serve as the foundation of diverse areas of study on chromosome structure and function today, nearly 40 years after she began her work on the topic.
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[
J Nematol,
2009]
The antibiotic 2,4-diacetylphloroglucinol (DAPG) is produced by some isolates of the beneficial bacterium Pseudomonas fluorescens. DAPG is toxic to many organisms, and crop yield increases have been reported after application of DAPG-producing P. fluorescens. This study was conducted to determine whether DAPG is toxic to selected nematodes. The plant-parasitic nematodes Heterodera glycines, Meloidogyne incognita, Pratylenchus scribneri and Xiphinema americanum, and the bacterial-feeding nematodes Caenorhabditis elegans, Pristionchus pacificus, and Rhabditis rainai, were immersed in concentrations ranging from 0 to 100 g/ml DAPG. Egg hatch and viability of juveniles and adults were determined. DAPG was toxic to X. americanum adults, with an LD of 8.3 g/ml DAPG. DAPG decreased M. incognita egg hatch, but stimulated C. elegans hatch during the first hours of incubation. Viability of M. incognita J2 and of C. elegans J1 and adults was not affected. There were no observed effects on the other nematodes. The study indicated that DAPG is not toxic to all nematodes, and did not affect the tested species of beneficial bacterial-feeding nematodes. Augmentation of DAPG-producing P. fluorescens populations for nematode biocontrol could be targeted to specific nematode species known to be affected by this compound and by other antibiotics produced by the bacteria, or these bacteria could be used for other possible effects, such as induced plant resistance.
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[
J Toxicol Environ Health B Crit Rev,
2014]
The use of pesticides is ubiquitous worldwide, and these chemicals exert adverse effects on both target and nontarget species. Understanding the modes of action of pesticides, as well as quantifying exposure concentration and duration, is an important goal of clinicians and environmental health scientists. Some chemical exposures result in adverse effects on the nervous system. The nematode Caenorhabditis elegans (C. elegans) is a model lab organism well established for studying neurotoxicity, since the components of its nervous system are mapped and known, and most of its neurotransmitters correspond to human homologs. This review encompasses published studies in which C. elegans nematodes were exposed to pesticides with known neurotoxic actions. Endpoints measured include changes in locomotion, feeding behavior, brood size, growth, life span, and cell death. From data presented, evidence indicates that C. elegans can serve a role in assessing the effects of neurotoxic pesticides at the sublethal cellular level, thereby advancing our understanding of the mechanisms underlying toxicity induced by these chemicals. A proposed toxicity testing scheme for water-soluble chemicals is also included.
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[
Science,
1996]
The DPY-26 protein is required in the nematode Caenorhabditis elegans for X-chromosome dosage compensation as well as for proper meiotic chromosome segregation. DPY-26 was shown to mediate both processes through its association with chromosomes. In somatic cells, DPY-26 associates specifically with hermaphrodite X chromosomes to reduce their transcript levels. In germ cells, DPY-26 associates with all meiotic chromosomes to mediate its role in chromosome segregation. The X-specific localization of DPY-26 requires two dosage compensation proteins (DPY-27 and DPY-30) and two proteins that coordinately control both sex determination and dosage compensation (SDC-2 and SDC-3).AD - Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.FAU - Lieb, J DAU - Lieb JDFAU - Capowski, E EAU - Capowski EEFAU - Meneely, PAU - Meneely PFAU - Meyer, B JAU - Meyer BJLA - engSI - GENBANK/U43562SI - GENBANK/Z70680ID - GM30702/GM/NIGMSID - HD24324/HD/NICHDID - T32 GM07127/GM/NIGMSPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Carrier Proteins)RN - 0 (DPY-27 protein)RN - 0 (Helminth Proteins)RN - 0 (Nuclear Proteins)SB - IM
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[
Biochemistry,
1987]
The major intestinal esterase from the nematode Caenorhabditis elegans has been purified to essential homogeneity. Starting from whole worms, the overall purification is 9000-fold with a 10% recovery of activity. The esterase is a single polypeptide chain of Mr 60,000 and is stoichiometrically inhibited by organophosphates. Substrate preferences and inhibition patterns classify the enzyme as a carboxylesterase (EC 3.1.1.1), but the physiological function is unknown. The sequence of 13 amino acid residues at the esterase N- terminus has been determined. This partial sequence shows a surprisingly high degree of similarity to the N-terminal sequence of two carboxylesterases recently isolated from Drosophila mojavensis [Pen, J., van Beeumen, J., & Beintema, J. J. (1986) Biochem. J. 238, 691-699].
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[
Science,
1996]
In nematodes, flies, and mammals, dosage compensation equalizes X-chromosome gene expression between the sexes through chromosome-wide regulatory mechanisms that function in one sex to adjust the levels of X-linked transcripts. Here, a dosage compensation complex was identified in the nematode Caenorhabditis elegans that reduces transcript levels from the two X chromosomes in hermaphrodites. This complex contains at least four proteins, including products of the dosage compensation genes
dpy-26 and
dpy-27. Specific localization of the complex to the hermaphrodite X chromosomes is conferred by XX-specific regulatory genes that coordinately control both sex determination and dosage compensation.AD - Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.FAU - Chuang, P TAU - Chuang PTFAU - Lieb, J DAU - Lieb JDFAU - Meyer, B JAU - Meyer BJLA - engID - GM30702/GM/NIGMSID - T32 GM07127/GM/NIGMSPT - Journal ArticleCY - UNITED STATESTA - ScienceJID - 0404511RN - 0 (Carrier Proteins)RN - 0 (DPY-27 protein)RN - 0 (Helminth Proteins)RN - 0 (Nuclear Proteins)RN - 0 (RNA, Helminth)RN - 0 (RNA, Messenger)SB - IM
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[
Cell,
2009]
Meiotic chromosome pairs must receive at least one crossover to ensure proper segregation at the first meiotic division. Mets and Meyer (2009) now present compelling evidence that the establishment of higher-order chromosome structure by a condensin complex regulates crossover recombination by controlling the distribution and frequency of meiotic double-strand breaks.
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[
Worm Breeder's Gazette,
1987]
Mutations in
dpy-27 and
dpy-28 affect the viability of XX but not XO animals. In addition, these mutations disrupt dosage compensation resulting in XX but not XO animals over-expressing their X-linked genes (as assayed by Northern analysis [Meyer and Casson, Cell 47:871 1986] and by morphogenetic assay [DeLong, et al. Genetics, in press]).
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[
International Worm Meeting,
2019]
Physical exercise exerts positive impacts on cognitive function, maintenance of skeletal muscle, and protection from age-related diseases. However, molecular mechanisms underlying those protections are not well understood. Furthermore, it is unknown what effects regular exercise training may have on other health-modifying factors such as environmental toxicant exposures. In this study, we used C. elegans to study the impact of long-term exercise training on dopaminergic neuronal health at baseline and after exposure to the pesticide rotenone. For exercise experiments, beginning at adult day 1, animals were transferred to unseeded agar plates without (control) or with liquid (causing worms to swim) for 90 minutes twice daily. This regimen was carried out for six days, and dopaminergic neuronal health was tested following exercise on adult day 6 and adult day 10. Exercise caused a reduction in age-related morphological changes to the dendrites of dopaminergic CEP neurons that was apparent by adult day 6 (p<0.05) and was much more dramatic by day 10 (p<0.0001). This was accompanied by a 20% greater (p<0.01) basal slowing rate in exercised animals (locomotion on food versus off food), a behavioral readout of dopaminergic neuron function. Furthermore, exercise was protective against dopaminergic neurodegeneration from rotenone exposures initiated on day 6. We also performed whole-animal RNA-seq analysis to determine pathways involved in exercise conditioning. Enriched pathways included lipid biosynthesis and metabolism, nucleoside metabolism, chemosensation, cellular signaling, and cellular respiration. In ongoing and future studies, we will interrogate pathways changed by exercise to determine which genes are involved in regulating exercise-induced neuroprotection. Together, these data will provide critical insights into the mechanisms underlying exercise benefits.