scholarly journals The relationship between phosphine resistance and genetic determinants of longevity: phosphine toxicology and mechanisms of its resistance investigated by a novel high-throughput model organism analysis system for Caenorhabditis elegans

2019 ◽  
Author(s):  
Timothy Puckering
2019 ◽  
Author(s):  
Shannon C. Brady ◽  
Stefan Zdraljevic ◽  
Karol W. Bisaga ◽  
Robyn E. Tanny ◽  
Daniel E. Cook ◽  
...  

ABSTRACTBleomycin is a powerful chemotherapeutic drug used to treat a variety of cancers. However, individual patients vary in their responses to bleomycin. The identification of genetic differences that underlie this response variation could improve treatment outcomes by tailoring bleomycin dosages to each patient. We used the model organism Caenorhabditis elegans to identify genetic determinants of bleomycin-response differences by performing linkage mapping on recombinants derived from a cross between the laboratory strain (N2) and a wild strain (CB4856). This approach identified a small genomic region on chromosome V that underlies bleomycin-response variation. Using near-isogenic lines and strains with CRISPR-Cas9 mediated deletions and allele replacements, we discovered that a novel nematode-specific gene (scb-1) is required for bleomycin resistance. Although the mechanism by which this gene causes variation in bleomycin responses is unknown, we suggest that a rare variant present in the CB4856 strain might cause differences in the potential stress-response function of scb-1 between the N2 and CB4856 strains, thereby leading to differences in bleomycin resistance.


Author(s):  
Ali Mohammed Alzahrani ◽  
Msaad Alzhrani ◽  
Saeed Nasser Alshahrani ◽  
Wael Alghamdi ◽  
Mazen Alqahtani ◽  
...  

This study aimed to systematically review research investigating the association between hip muscle strength and dynamic knee valgus (DKV). Four databases (MEDLINE, PubMed, CINAHL, and SPORTDiscus) were searched for journal articles published from inception to October 2020. Seven studies investigating the association between hip muscle strength and DKV using a two-dimensional motion analysis system in healthy adults were included. The relationship between hip abductor muscle strength and DKV was negatively correlated in two studies, positively correlated in two studies, and not correlated in three studies. The DKV was associated with reduced hip extensor muscle strength in two studies and reduced hip external rotator muscle strength in two studies, while no correlation was found in three and five studies for each muscle group, respectively. The relationship between hip muscle strength, including abductors, extensors, and external rotators and DKV is conflicting. Considering the current literature limitations and variable methodological approaches used among studies, the clinical relevance of such findings should be interpreted cautiously. Therefore, future studies are recommended to measure the eccentric strength of hip muscles, resembling muscular movement during landing. Furthermore, high-demand and sufficiently challenging functional tasks revealing lower limb kinematic differences, such as cutting and jumping tasks, are recommended for measuring the DKV.


2009 ◽  
Vol 41 (10) ◽  
pp. 738-744 ◽  
Author(s):  
Miguel A. Medina ◽  
John T. Nguyen ◽  
Michael M. McCormack ◽  
Mark A. Randolph ◽  
William G. Austen

1996 ◽  
Vol 85 (4) ◽  
pp. 901-912 ◽  
Author(s):  
Michael C. Crowder ◽  
Laynie D. Shebester ◽  
Tim Schedl

Background The nematode Caenorhabditis elegans offers many advantages as a model organism for studying volatile anesthetic actions. It has a simple, well-understood nervous system; it allows the researcher to do forward genetics; and its genome will soon be completely sequenced. C. elegans is immobilized by volatile anesthetics only at high concentrations and with an unusually slow time course. Here other behavioral dysfunctions are considered as anesthetic endpoints in C. elegans. Methods The potency of halothane for disrupting eight different behaviors was determined by logistic regression of concentration and response data. Other volatile anesthetics were also tested for some behaviors. Established protocols were used for behavioral endpoints that, except for pharyngeal pumping, were set as complete disruption of the behavior. Time courses were measured for rapid behaviors. Recovery from exposure to 1 or 4 vol% halothane was determined for mating, chemotaxis, and gross movement. All experiments were performed at 20 to 22 degrees C. Results The median effective concentration values for halothane inhibition of mating (0.30 vol%-0.21 mM), chemotaxis (0.34 vol%-0.24 mM), and coordinated movement (0.32 vol% - 0.23 mM) were similar to the human minimum alveolar concentration (MAC; 0.21 mM). In contrast, halothane produced immobility with a median effective concentration of 3.65 vol% (2.6 mM). Other behaviors had intermediate sensitivities. Halothane's effects reached steady-state in 10 min for all behaviors tested except immobility, which required 2 h. Recovery was complete after exposure to 1 vol% halothane but was significantly reduced after exposure to immobilizing concentrations. Conclusions Volatile anesthetics selectively disrupt C. elegans behavior. The potency, time course, and recovery characteristics of halothane's effects on three behaviors are similar to its anesthetic properties in vertebrates. The affected nervous system molecules may express structural motifs similar to those on vertebrate anesthetic targets.


2010 ◽  
Vol 38 (1) ◽  
pp. 172-176 ◽  
Author(s):  
Jeff W. Barclay ◽  
Margaret E. Graham ◽  
Mark R. Edwards ◽  
James R. Johnson ◽  
Alan Morgan ◽  
...  

Acute exposure to ethanol is known to modulate signalling within the nervous system. Physiologically these effects are both presynaptic and postsynaptic in origin; however, considerably more research has focused primarily on postsynaptic targets. Recent research using the model organism Caenorhabditis elegans has determined a role for specific proteins (Munc18-1 and Rab3) and processes (synaptic vesicle recruitment and fusion) in transducing the presynaptic effects of ethanol. In the present paper, we review these results, identifying the proteins and protein interactions involved in ethanol sensitivity and discuss their links with mammalian studies of alcohol abuse.


Author(s):  
Matthew Glover Addo ◽  
Raynald Cossard ◽  
Damien Pichard ◽  
Kwasi Obiri-Danso ◽  
Agnès Rötig ◽  
...  

2021 ◽  
Vol 64 (4) ◽  
pp. 1247-1258
Author(s):  
Yang Li ◽  
Lizhang Xu ◽  
Zhipeng Gao ◽  
En Lu ◽  
Yaoming Li

HighlightsThe relationship of vibration and header loss was studied by multi-point vibration measurement and loss collection test.There was an approximately linear positive correlation between total header vibration and total rapeseed header loss.The header frame was analyzed and optimized through modal simulation and testing.The total rapeseed header loss of the improved header was reduced by 33.2% to 46.9%.Abstract. In view of the current large rapeseed header losses of rape combine harvesters, the effects of the header on rapeseed header loss were studied from the perspective of vibration. First, the vibrations at various measuring points on the header during rape harvest were studied using a data acquisition and analysis system while performing collection tests of rapeseed header loss with the sample slot method. The relationships between total header vibration and total rapeseed header loss and between vertical cutter vibration and rapeseed vertical cutter loss were shown to have a positive correlation, and they all increased with the increase in engine speed. Vertical cutter loss accounted for 31.2% to 42.4% of the total rapeseed header loss. Modal analysis and optimization of the header frame were then performed by simulation and test. The natural frequencies of the first-order and second-order modes of the optimized header were increased, and the possibility of resonance with other working parts was eliminated. Finally, the improved header was tested during rape harvest. The results showed that the total vibration of the improved header was reduced by 19.9% to 43.9%, and the total rapeseed header loss was reduced by 33.2% to 46.9%. The vertical cutter vibration was reduced by 30.5% to 49.8%, and the rapeseed vertical cutter loss was reduced by 20.8% to 34.7%. In addition, the vibration and rapeseed loss of the improved header had relatively slow rates of increase with the increase in engine speed. The method of reducing rapeseed loss by reducing the header vibration achieved an obvious and positive effect. Keywords: Frame optimization, Modal analysis, Rape combine harvester, Rapeseed header loss, Vibration.


Sign in / Sign up

Export Citation Format

Share Document