scholarly journals Auxin treatment increases lifespan in Caenorhabditis elegans

Biology Open ◽  
2021 ◽  
Vol 10 (5) ◽  
Author(s):  
Julia A. Loose ◽  
Arjumand Ghazi
Keyword(s):  
Caenorhabditis Elegans ◽  
Prolonged Exposure ◽  
Model Systems ◽  
Multiple Model ◽  
Protein Inactivation ◽  
Somatic Tissues ◽  
Arabidopsis Proteins ◽  
Indole 3 Acetic Acid ◽  
Transgenic Strains

ABSTRACT The auxin-inducible degradation system (AID) has proven to be a highly versatile technology for rapid, robust and reversible depletion of proteins in multiple model systems. In recent years, AID has been adapted into the nematode Caenorhabditis elegans as a tool for conditional protein knockdown. Numerous transgenic strains have been created that, upon auxin exposure, undergo protein inactivation in the worm germline or somatic tissues, both during development and in young adults. Since longevity assays often involve long-term gene- and protein-manipulation, the facility for spatiotemporally precise and extended protein removal makes AID a potentially highly valuable tool for aging biology. However, whether auxins themselves impact worm longevity has not been directly addressed. Here, we show that prolonged exposure to indole 3-acetic acid (IAA), the auxin used in worm AID studies, extends lifespan. We also report that two transgenic strains expressing Arabidopsis proteins that are key components of the AID platform are longer lived than wild-type animals. Together, our results highlight the necessity for exercising caution while utilizing AID for longevity studies and in interpreting the resulting data. This article has an associated First Person interview with the first author of the paper.

scholarly journals Impact of Prolonged Exposure of Eleven Years to Hot Seawater on the Degradation of a Thermoset Composite

Polymers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 2154
Author(s):  
Amir Hussain Idrisi ◽  
Abdel-Hamid I. Mourad ◽  
Muhammad M. Sherif
Keyword(s):  
Exposure Time ◽  
Prolonged Exposure ◽  
Mechanical Performance ◽  
Matrix Cracking ◽  
Pull Out ◽  
Strength Based ◽  
Different Temperatures ◽  
River Line ◽  
Composite Samples

This paper presents a long-term experimental investigation of E-glass/epoxy composites’ durability exposed to seawater at different temperatures. The thermoset composite samples were exposed to 23 °C, 45 °C and 65 °C seawater for a prolonged exposure time of 11 years. The mechanical performance as a function of exposure time was evaluated and a strength-based technique was used to assess the durability of the composites. The experimental results revealed that the tensile strength of E-glass/epoxy composite was reduced by 8.2%, 29.7%, and 54.4% after immersion in seawater for 11 years at 23 °C, 45 °C, and 65 °C, respectively. The prolonged immersion in seawater resulted in the plasticization and swelling in the composite. This accelerated the rate of debonding between the fibers and matrix. The failure analysis was conducted to investigate the failure mode of the samples. SEM micrographs illustrated a correlation between the fiber/matrix debonding, potholing, fiber pull-out, river line marks and matrix cracking with deterioration in the tensile characteristics of the thermoset composite.

scholarly journals Onset and Resolution of Key Adverse Events in Valbenazine-Treated Patients with Tardive Dyskinesia: Pooled Analyses from Two Long-Term Clinical Trials

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 151-151
Author(s):  
Stephen R. Marder ◽  
Jean-Pierre Lindenmayer ◽  
Chirag Shah ◽  
Tara Carmack ◽  
Angel S. Angelov ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Tardive Dyskinesia ◽  
Suicidal Behavior ◽  
Prolonged Exposure ◽  
First Occurrence ◽  
Balance Disorder ◽  
Clinical Interest ◽  
Post Hoc

AbstractObjectiveTardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics and other dopamine receptor blocking agents. Long-term safety of the approved TD medication, valbenazine, was demonstrated in 2 clinical trials (KINECT 3 [NCT02274558], KINECT 4 [NCT02405091]). Data from these trials were analyzed post hoc to evaluate the onset and resolution of adverse events (AEs).MethodsParticipants in KINECT 3 and KINECT 4 received up to 48 weeks of once-daily valbenazine (40 or 80 mg). Data from these studies were pooled and analyzed to assess the incidence, time to first occurrence, and resolution for the following AEs of potential clinical interest: akathisia, balance disorder, dizziness, parkinsonism, somnolence/sedation, suicidal behavior/ideation, and tremor.ResultsIn the pooled population (N=314), all AEs of potential clinical interest occurred in <10% of participants, with somnolence (9.6%), suicidal behavior/ideation (6.4%), and dizziness (5.7%) being the most common AEs. Mean time to first occurrence ranged from 36 days (akathisia [n=9]) to 224 days (parkinsonism [n=2]). By end of study (or last study visit), resolution of AEs was as follows: 100% (suicidal ideation/behavior, parkinsonism); >85% (somnolence/sedation, dizziness); >70% (akathisia, balance disorder, tremor).ConclusionsIn long-term clinical trials, the incidence of AEs of potential clinical interest was low (<10%) and most were resolved by end of treatment (>70–100%). All patients taking valbenazine should be routinely monitored for AEs, particularly those that may exacerbate the motor symptoms associated with TD.FundingNeurocrine Biosciences, Inc.

scholarly journals Spectrum of variations in dog-1/FANCJ and mdf-1/MAD1 defective Caenorhabditis elegans strains after long-term propagation

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Maja Tarailo-Graovac ◽  
Tammy Wong ◽  
Zhaozhao Qin ◽  
Stephane Flibotte ◽  
Jon Taylor ◽  
...  
Keyword(s):  
Caenorhabditis Elegans

Northeast Atlantic storminess in centennial reanalyses

2021 ◽  
Author(s):  
Oliver Krueger ◽  
Frauke Feser ◽  
Christopher Kadow ◽  
Ralf Weisse
Keyword(s):  
Climate Models ◽  
Numerical Models ◽  
Geostrophic Wind ◽  
Model Systems ◽  
Storm Activity ◽  
Northeast Atlantic ◽  
Wind Speeds ◽  
Long Term Trends ◽  
Storm Index

&lt;p&gt;Global atmospheric reanalyses are commonly applied for the validation of climate models, diagnostic studies, and driving higher resolution numerical models with the emphasis on assessing climate variability and long-term trends. Over recent years, longer reanalyses spanning a period of more than hundred years have become available. In this study, the variability and long-term trends of storm activity is assessed over the northeast Atlantic in modern centennial reanalysis datasets, namely ERA-20cm, ERA-20c, CERA-20c, and the 20CR-reanalysis suite with 20CRv3 being the most recent one. All reanalyses, except from ERA-20cm, assimilate surface pressure observations, whereby ERA-20C and CERA-20c additionally assimilate surface winds. For the assessment, the well-established storm index of higher annual percentiles of geostrophic wind speeds derived from pressure observations at sea level over a relatively densely monitored marine area is used.&lt;/p&gt;&lt;p&gt;The results indicate that the examined centennial reanalyses are not able to represent long-term trends of storm activity over the northeast Atlantic, particularly in the earlier years of the period examined when compared with the geostrophic wind index based on pressure observations. Moreover, the reanalyses show inconsistent long-term behaviour when compared with each other. Only in the latter half of the 20th century, the variability of reanalysed and observed storminess time series starts to agree with each other. Additionally, 20CRv3, the most recent centennial reanalysis examined, shows markedly improved results with increased uncertainty, albeit multidecadal storminess variability does not match observed values in earlier times before about 1920.&lt;/p&gt;&lt;p&gt;The behaviour shown by the centennial reanalyses are likely caused by the increasing number of assimilated observations, changes in the observational databases used, and the different underlying numerical model systems. Furthermore, the results derived from the ERA-20cm reanalysis that does not assimilate any pressure or wind observations suggests that the variability and uncertainty of storminess over the northeast Atlantic is high making it difficult to determine storm activity when numerical models are not bound by observations. The results of this study imply and reconfirm previous findings that the assessment of long-term storminess trends and variability in centennial reanalyses remains a rather delicate matter, at least for the northeast Atlantic region.&lt;/p&gt;

scholarly journals Decreased calmodulin recruitment triggers PMCA4 dysfunction and pancreatic injury in cystic fibrosis

2020 ◽  
Author(s):  
Tamara Madácsy ◽  
Árpad Varga ◽  
Noémi Papp ◽  
Barnabás Deák ◽  
Bálint Tél ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Intracellular Signaling ◽  
Pancreatic Injury ◽  
Exocrine Pancreatic Function ◽  
Model Systems ◽  
Multiple Model ◽  
Calmodulin Binding ◽  
Ductal Cells ◽  
Pancreatic Damage ◽  
Intracellular Ca

ABSTRACTExocrine pancreatic damage is a common complication of cystic fibrosis (CF), which can significantly debilitate the quality of life and life expectancy of CF patients. The cystic fibrosis transmembrane conductance regulator (CFTR) has a major role in pancreatic ductal ion secretion, however, it presumably has an influence on intracellular signaling as well. Here we describe in multiple model systems, including iPSC-derived human pancreatic organoids from CF patients, that the activity of PMCA4 is impaired by the decreased expression of CFTR in ductal cells. The regulation of PMCA4, which colocalizes and physically interacts with CFTR on the apical membrane of the ductal cells, is dependent on the calmodulin binding ability of CFTR. Moreover, CFTR seems to be involved in the process of the apical recruitment of calmodulin, which enhances its role in calcium signaling and homeostasis. Sustained intracellular Ca2+ elevation in CFTR KO cells undermined the mitochondrial function and increased apoptosis. Based on these, the prevention of sustained intracellular Ca2+ overload may improve the exocrine pancreatic function and may have a potential therapeutic aspect in CF.

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