scholarly journals Periodic ethanol supply as a path towards unlimited lifespan of C.elegans dauer larvae

2021 ◽  
Author(s):  
Xingyu Zhang ◽  
Sider Penkov ◽  
Teymuras V Kurzchalia ◽  
Vasily Zaburdeav
Keyword(s):  
Stress Resistance ◽  
Ethanol Concentration ◽  
Ethanol Metabolism ◽  
Feeding Frequency ◽  
Toxic Compounds ◽  
Dauer Larva ◽  
Stage Of Development ◽  
Metabolic Adaptations ◽  
Dauer Larvae ◽  
Harsh Conditions

The dauer larva is a specialized stage of development optimized for survival under harsh conditions that has been used as a model for stress resistance, metabolic adaptations, and longevity. Recent findings suggest that the dauer larva of C.elegans  may utilize external ethanol as an energy source to extend their lifespan. It was shown that while ethanol may serve as an effectively infinite source of energy, some toxic compounds accumulating as byproducts of its metabolism may lead to the damage of mitochondria and thus limit the lifespan of larvae. A minimal mathematical model was proposed to explain the connection between the lifespan of dauer larva and its ethanol metabolism. To explore theoretically if it is  possible to  extend even further the lifespan of dauer larvae, we incorporated two natural mechanisms describing the recovery of damaged mitochondria and elimination of toxic compounds, which were previously omitted in the model. Numerical simulations of the revised model suggest that while the ethanol concentration is constant, the lifespan still stays limited. However, if ethanol is supplied periodically, with a  suitable frequency and amplitude, the dauer could survive as long as we observe the system. Analytical methods further help to explain how the feeding frequency and amplitude affect the lifespan extension. Based on comparison of the model with experimental data for fixed ethanol concentration, we propose the range of feeding protocols that could lead to even longer dauer survival and can be tested experimentally.

scholarly journals OAC-39 is an O-acyltransferase required for the synthesis of maradolipids in the dauer larva of C. elegans

2021 ◽  
Author(s):  
Sider Penkov
Keyword(s):  
Food Availability ◽  
Stress Resistance ◽  
Physiological Function ◽  
Polar Lipids ◽  
Intestinal Cells ◽  
Apical Region ◽  
Hyperosmotic Shock ◽  
C Elegans ◽  
Dauer Larva ◽  
Dauer Larvae

Upon overcrowding or low food availability, the nematode C. elegans enters a specialized diapause stage for survival, called the dauer larva. The growth-arrested, non-feeding dauer larva undergoes a profound metabolic and physiologic switch underlying its extraordinary stress resistance and longevity. One of the metabolic signatures of dauer larvae is the accumulation of the disaccharide trehalose, which lowers the sensitivity of worms to desiccation and hyperosmotic shock. Previously, we have found that trehalose is incorporated as a headgroup into dauer-specific 6,6′-di-O-acyltrehalose lipids, named maradolipids. Despite comprising a bulk fraction of the polar lipids in dauer larvae, little is known about the physiological function of maradolipds because the enzyme(s) involved in their synthesis has not yet been identified. Here, we report that the dauer-upregulated O-acyltransferase homolog OAC-39 is essential for the synthesis of maradolipids. This enzyme is enriched at the apical region of the intestinal cells of dauer larvae, where it might participate in the structuring of the gut lumen. As OAC-39 is most probably responsible for the last step of maradolipid synthesis, its identification will pave the way for the elucidation of the function of this obscure class of lipids.

scholarly journals Two Pleiotropic Classes of daf-2 Mutation Affect Larval Arrest, Adult Behavior, Reproduction and Longevity in Caenorhabditis elegans

Genetics ◽  
1998 ◽  
Vol 150 (1) ◽  
pp. 129-155 ◽  
Author(s):  
David Gems ◽  
Amy J Sutton ◽  
Mark L Sundermeyer ◽  
Patrice S Albert ◽  
Kevin V King ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Adult Longevity ◽  
Temperature Sensitive ◽  
Adult Behavior ◽  
Dauer Larva ◽  
Class 1 ◽  
Low Levels ◽  
Dauer Larvae ◽  
Overlapping Classes ◽  
Receptor Family

Abstract The nematode Caenorhabditis elegans responds to overcrowding and scarcity of food by arresting development as a dauer larva, a nonfeeding, long-lived, stress-resistant, alternative third-larval stage. Previous work has shown that mutations in the genes daf-2 (encoding a member of the insulin receptor family) and age-1 (encoding a PI 3-kinase) result in constitutive formation of dauer larvae (Daf-c), increased adult longevity (Age), and increased intrinsic thermotolerance (Itt). Some daf-2 mutants have additional developmental, behavioral, and reproductive defects. We have characterized in detail 15 temperature-sensitive and 1 nonconditional daf-2 allele to investigate the extent of daf-2 mutant defects and to examine whether specific mutant traits correlate with each other. The greatest longevity seen in daf-2 mutant adults was approximately three times that of wild type. The temperature-sensitive daf-2 mutants fell into two overlapping classes, including eight class 1 mutants, which are Daf-c, Age, and Itt, and exhibit low levels of L1 arrest at 25.5°. Seven class 2 mutants also exhibit the class 1 defects as well as some or all of the following: reduced adult motility, abnormal adult body and gonad morphology, high levels of embryonic and L1 arrest, production of progeny late in life, and reduced brood size. The strengths of the Daf-c, Age, and Itt phenotypes largely correlated with each other but not with the strength of class 2-specific defects. This suggests that the DAF-2 receptor is bifunctional. Examination of the null phenotype revealed a maternally rescued egg, L1 lethal component, and a nonconditional Daf-c component. With respect to the Daf-c phenotype, the dauer-defective (Daf-d) mutation daf-12(m20) was epistatic to daf-2 class 1 alleles but not the severe class 2 alleles tested. All daf-2 mutant defects were suppressed by the daf-d mutation daf-16(m26). Our findings suggest a new model for daf-2, age-1, daf-12, and daf-16 interactions.

Characterization of lipopolysaccharide transport protein complex

2014 ◽  
Vol 9 (2) ◽  
pp. 131-138
Author(s):  
Quanju Xiang ◽  
Haiyan Wang ◽  
Zhongshan Wang ◽  
Yizheng Zhang ◽  
Changjiang Dong
Keyword(s):  
Transport Mechanism ◽  
Transport Proteins ◽  
Gram Negative Bacteria ◽  
Inner Membrane ◽  
Toxic Compounds ◽  
Outer Membranes ◽  
Harsh Conditions ◽  
Cytoplasmic Side

AbstractLipopolysaccharide (LPS) is an essential component of the outer membranes (OM) of most Gram-negative bacteria, which plays a crucial role in protection of the bacteria from toxic compounds and harsh conditions. The LPS is biosynthesized at the cytoplasmic side of inner membrane (IM), and then transported across the aqueous periplasmic compartment and assembled correctly at the outer membrane. This process is accomplished by seven LPS transport proteins (LptA-G), but the transport mechanism remains poorly understood. Here, we present findings by pull down assays in which the periplasmic component LptA interacts with both the IM complex LptBFGC and the OM complex LptDE in vitro, but not with complex LptBFG. Using purified Lpt proteins, we have successfully reconstituted the seven transport proteins as a complex in vitro. In addition, the LptC may play an essential role in regulating the conformation of LptBFG to secure the lipopolysaccharide from the inner membrane. Our results contribute to the understanding of lipopolysaccharide transport mechanism and will provide a platform to study the detailed mechanism of the LPS transport in vitro.

Developmental arrest inCaenorhabditis elegansdauer larvae causes high expression of enzymes involved in thymidylate biosynthesis, similar to that found inTrichinellamuscle larvae

Parasitology ◽  
2005 ◽  
Vol 131 (2) ◽  
pp. 247-254 ◽  
Author(s):  
P. WIŃSKA ◽  
B. GOŁOS ◽  
J. CIEŚLA ◽  
Z. ZIELIŃSKI ◽  
T. FRĄCZYK ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thymidine Kinase ◽  
Thymidylate Synthase ◽  
Trichinella Spiralis ◽  
Recombinant Protein Expression ◽  
C Elegans ◽  
Protein Levels ◽  
Dauer Larva ◽  
Muscle Larvae ◽  
Dauer Larvae

Crude extract specific activities of thymidylate synthase, dUTPase, thymidine kinase and dihydrofolate reductase were high during the development ofCaenorhabditis elegans, the dauer larva activities being similar to those previously determined inTrichinella spiralisandT. pseudospiralismuscle larvae (with the exception of thymidine kinase, not detected inTrichinella). High thymidylate synthase expression in developmentally arrested larvae, demonstrated also at the mRNA and protein levels, is in agreement with a global cell cycle arrest of dauer larvae and indicates this unusual cell cycle regulation pattern can be shared by developmentally arrested larvae ofC. elegansand the twoTrichnellaspecies. Hence, the phenomenon may be characteristic for developmentally arrested larvae of different nematodes, rather than specific for the parasiticTrichinellamuscle larvae. EndogenousC. elegansthymidylate synthase was purified and its molecular properties compared with those of the recombinant protein, expression of the latter inE. colicells confirming the NCBI database sequence identity.

scholarly journals Genetic analysis of chemosensory control of dauer formation in Caenorhabditis elegans.

Genetics ◽  
1992 ◽  
Vol 130 (1) ◽  
pp. 105-123 ◽  
Author(s):  
J J Vowels ◽  
J H Thomas
Keyword(s):  
Caenorhabditis Elegans ◽  
Genetic Analysis ◽  
Single Step ◽  
Genetic Interactions ◽  
The Other ◽  
Environmental Cues ◽  
Dauer Larva ◽  
Chemosensory Transduction ◽  
Dauer Formation ◽  
Dauer Larvae

Abstract Dauer larva formation in Caenorhabditis elegans is controlled by chemosensory cells that respond to environmental cues. Genetic interactions among mutations in 23 genes that affect dauer larva formation were investigated. Mutations in seven genes that cause constitutive dauer formation, and mutations in 16 genes that either block dauer formation or result in the formation of abnormal dauers, were analyzed. Double mutants between dauer-constitutive and dauer-defective mutations were constructed and characterized for their capacity to form dauer larvae. Many of the genes could be interpreted to lie in a simple linear epistasis pathway. Three genes, daf-16, daf-18 and daf-20, may affect downstream steps in a branched part of the pathway. Three other genes, daf-2, daf-3 and daf-5, displayed partial or complex epistasis interactions that were difficult to interpret as part of a simple linear pathway. Dauer-defective mutations in nine genes cause structurally defective chemosensory cilia, thereby blocking chemosensation. Mutations in all nine of these genes appear to fall at a single step in the epistasis pathway. Dauer-constitutive mutations in one gene, daf-11, were strongly suppressed for dauer formation by mutations in the nine cilium-structure genes. Mutations in the other six dauer-constitutive genes caused dauer formation despite the absence of functional chemosensory endings. These results suggest that daf-11 is directly involved in chemosensory transduction essential for dauer formation, while the other Daf-c genes play roles downstream of the chemosensory step.

Genetic Analysis of the Roles of daf28 and age-1 in Regulating Caenorhabditis elegans Dauer Formation

Genetics ◽  
1996 ◽  
Vol 143 (3) ◽  
pp. 1193-1205 ◽  
Author(s):  
Elizabeth A Malone ◽  
Takao Inoue ◽  
James H Thomas
Keyword(s):  
Life Span ◽  
Environmental Cues ◽  
Apparent Effect ◽  
Term Survival ◽  
Dauer Larva ◽  
Extend Life Span ◽  
Unique Aspect ◽  
Dauer Formation ◽  
Harsh Conditions

Abstract Based on environmental cues, the nervous system of Caenorhabditis ekgans regulates formation of the dauer larva, an alternative larval form specialized for long-term survival under harsh conditions. Mutations that cause constitutive or defective dauer formation (Daf-c or Daf-d) have been identified and the genes ordered in a branched pathway. Most Daf-c mutations also affect recovery from the dauer stage. The semidominant mutation daf-28(sa191) is Daf-c but has no apparent effect on dauer recovery. We use this unique aspect of daf28(sal91) to characterize the effects of several Daf-d and synthetic Daf-c mutations on dauer recovery. We present double mutant analysis that indicates that daf-28(saI91) acts at a novel point downstream in the genetic pathway for dauer formation. We also show that daf-28(sa191) causes a modest increase (12-13%) in life span. The phenotypes and genetic interactions of daf-28(sa191) are most similar to those of daf-2 and daf-23 mutations, which also cause a dramatic increase in life span. We present mapping and complementation data that suggest that daf-23 is the same gene as age-I, identified previously by mutations that extend life span. We find that age-l alleles are also Daf-c at 27°.

Use of a semicontinuous culture system (RUSITEC) to study the metabolism of ethanol in the rumen and its effects on ruminal digestion

1991 ◽  
Vol 71 (1) ◽  
pp. 115-123 ◽  
Author(s):  
Andrée Durix ◽  
C. Jean-Blain ◽  
H. P. Sallmann ◽  
J. P. Jouany
Keyword(s):  
Ethanol Concentration ◽  
Microbial Transformation ◽  
Ethanol Metabolism ◽  
In Vitro Digestibility ◽  
Semicontinuous Culture ◽  
Ethanol Addition ◽  
Micro Organisms ◽  
Ruminal Digestion ◽  
Qualitative Changes

The metabolism of ethanol by rumen micro-organisms and its effects on rumen fermentations have been studied in vitro in a semicontinuous fermentor (RUSITEC). Ethanol introduced in the fermentor at 1, 4 or 8 g d−1 L−1 of rumen juice induced important qualitative and quantitative modifications in the fermentation outputs. Total VFA production was increased from 5 to 40% according to the diet and ethanol concentration. Relative proportions of VFA were modified: caproate concentration increased three times, propionate and isovalerate concentrations decreased significantly in most cases. Methane production was increased. Whatever the ethanol concentration and the type of diet, in vitro digestibility parameters and end-products from solid feedstuffs stayed practically unchanged by ethanol addition. Except with the lowest supply (1 g d−1 L−1), ethanol induced an uncoupling effect on the metabolism of rumen bacteria and decreased biomass production. Radioactivity of 2-14C ethanol was recovered mainly in acetate (77–80%). Microbial transformation of ethanol in RUSITEC was limited regardless of ethanol concentration. Ethanol had a negligible effect on the digestibility of solid feedstuffs but induced consistent qualitative changes in rumen fermentations. Key word: Ethanol, metabolism, rumen, semicontinuous culture

scholarly journals Algal Toxic Compounds and Their Aeroterrestrial, Airborne and other Extremophilic Producers with Attention to Soil and Plant Contamination: A Review

Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 322
Author(s):  
Georg Gӓrtner ◽  
Maya Stoyneva-Gӓrtner ◽  
Blagoy Uzunov
Keyword(s):  
Functional Role ◽  
Hot Springs ◽  
Human Life ◽  
Extreme Environments ◽  
Algal Toxins ◽  
Toxic Compounds ◽  
Future Studies ◽  
Algal Assemblages ◽  
Extreme Habitats ◽  
Harsh Conditions

The review summarizes the available knowledge on toxins and their producers from rather disparate algal assemblages of aeroterrestrial, airborne and other versatile extreme environments (hot springs, deserts, ice, snow, caves, etc.) and on phycotoxins as contaminants of emergent concern in soil and plants. There is a growing body of evidence that algal toxins and their producers occur in all general types of extreme habitats, and cyanobacteria/cyanoprokaryotes dominate in most of them. Altogether, 55 toxigenic algal genera (47 cyanoprokaryotes) were enlisted, and our analysis showed that besides the “standard” toxins, routinely known from different waterbodies (microcystins, nodularins, anatoxins, saxitoxins, cylindrospermopsins, BMAA, etc.), they can produce some specific toxic compounds. Whether the toxic biomolecules are related with the harsh conditions on which algae have to thrive and what is their functional role may be answered by future studies. Therefore, we outline the gaps in knowledge and provide ideas for further research, considering, from one side, the health risk from phycotoxins on the background of the global warming and eutrophication and, from the other side, the current surge of interest which phycotoxins provoke due to their potential as novel compounds in medicine, pharmacy, cosmetics, bioremediation, agriculture and all aspects of biotechnological implications in human life.

scholarly journals Opposing directions of stage-specific body length change in a close relative of C. elegans

2020 ◽  
Author(s):  
Eric W. Hammerschmith ◽  
Gavin C. Woodruff ◽  
Patrick C. Phillips
Keyword(s):  
Body Size ◽  
Body Length ◽  
Developmental Stages ◽  
Parasitic Nematodes ◽  
Close Relative ◽  
Evolutionary Divergence ◽  
Fig Wasp ◽  
C Elegans ◽  
Dauer Larva ◽  
Dauer Larvae

AbstractBackgroundBody size is a fundamental organismal trait. However, as body size and ecological contexts change across developmental time, evolutionary divergence may cause unexpected patterns of body size diversity among developmental stages. This may be particularly evident in polyphenic developmental stages specialized for dispersal. The dauer larva is such a stage in nematodes, and Caenorhabditis species disperse by traveling on invertebrate carriers. Here, we describe the morphology of the dispersal dauer larva of the nematode Caenorhabditis inopinata, whose adults can grow to be nearly twice as long as its close relative, the model organism C. elegans.ResultsWe find that the C. inopinata dauer larva is shorter and fatter than those of its close relatives C. elegans, C. briggsae, and C. tropicalis, despite its much longer adult stage. Additionally, many C. inopinata dauer larvae were ensheathed, an apparent novelty in this lineage reminiscent of the infective juveniles of parasitic nematodes. We also found abundant variation in dauer formation frequency among twenty-four wild isolates of C. inopinata, with many strains unable to produce dauer larvae under laboratory conditions.ConclusionMost Caenorhabditis species thrive on rotting plants and disperse on snails, slugs, or isopods (among others) whereas C. inopinata is ecologically divergent and thrives in fresh Ficus septica figs and disperses on their pollinating wasps. These wasps are at least an order of magnitude smaller in length than the vectors of other Caenorhabditis species. While there is some unknown factor of the fig environment that promotes elongated body size in C. inopinata adults, the smaller size of its fig wasp carrier may be driving the reduced body length of its dauer larva. Thus ecological divergence across multiple developmental stages can promote unexpected and opposing changes in body size within a single species.

scholarly journals Suppressive Effect of Shiitake Extract on Plasma Ethanol Elevation

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2647
Author(s):  
Harumi Uto-Kondo ◽  
Ayaka Sakurai ◽  
Kazuki Ogawa ◽  
Yusuke Yamaguchi ◽  
Takeshi Saito ◽  
...  
Keyword(s):  
Alcohol Dehydrogenase ◽  
Aldehyde Dehydrogenase ◽  
Acid Content ◽  
Liver Diseases ◽  
Ethanol Concentration ◽  
Suppressive Effect ◽  
Ethanol Solution ◽  
Ethanol Metabolism ◽  
Functional Component ◽  
Alcoholic Liver Diseases

Alcohol is usually consumed with meals, but chronic consumption is a leading cause of alcoholic liver diseases. We investigated if shiitake extracts with a high lentinic acid content (Shiitake-H) and without lentinic acid (Shiitake-N) could suppress the elevation in plasma ethanol concentrations by accelerating ethanol metabolism and preventing ethanol absorption from the gut. Shiitake-H and Shiitake-N suppressed the elevation in concentrations of ethanol and acetaldehyde in plasma, and promoted the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the liver. However, these effects of Shiitake-H were more prominent than those of Shiitake-N. Furthermore, Shitake-H promoted ADH and ALDH activities in the stomach. We also examined the change in plasma ethanol concentration by injecting Shiitake-H or Shiitake-N into the ligated loop of the stomach or jejunum together with an ethanol solution. Shiitake-H suppressed the absorption of ethanol from the stomach and jejunum. In conclusion, Shiitake-H accelerates ethanol metabolism in the stomach and liver and inhibits ethanol absorption in the stomach and jejunum indicating that lentinic acid is a functional component in shiitake.

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