scholarly journals Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

2019 ◽  
Author(s):  
Kelly H. Oh ◽  
Hongkyun Kim
Keyword(s):  
Muscle Strength ◽  
Muscle Weakness ◽  
Stress Responses ◽  
Ethanol Exposure ◽  
Mitochondrial Fragmentation ◽  
Mitochondrial Stress ◽  
C Elegans ◽  
Transcriptional Reprogramming ◽  
Alcoholic Myopathy ◽  
And Function

AbstractsChronic excessive ethanol consumption produces distinct toxic and adverse effects on different tissues. In skeletal muscle ethanol causes alcoholic myopathy characterized by myofiber atrophy and loss of muscle strength. Alcoholic myopathy is more prevalent than all inherited muscle diseases combined. Current evidence indicates that ethanol directly impairs muscle organization and function. However, the underlying mechanism by which ethanol causes its toxicity to muscle is poorly understood. Here, we show that the nematode C. elegans recapitulates key aspects of alcoholic myopathy when exposed to ethanol. As in mammals, ethanol exposure impairs muscle strength and organization and induces the expression of protective genes, including oxidative stress response. In addition, ethanol exposure causes a fragmentation of mitochondrial networks aligned with myofibril lattices. This ethanol-induced mitochondrial fragmentation is dependent on mitochondrial fission factor DRP-1 (dynamin-like protein 1), and its receptor proteins on the mitochondrial outer membrane. Our data indicate that this fragmentation contributes to activation of mitochondrial unfolded protein response (UPR). We also found that robust perpetual mitochondrial UPR activation effectively counters muscle weakness caused by ethanol exposure. Our results strongly suggest that modulation of mitochondrial stress responses provides a mechanism to ameliorate alcohol toxicity and damage to muscle.SignificanceChronic alcohol abuse causes the damage and toxicity to peripheral tissues, including muscle. Alcohol perturbs the structure and function of striated skeletal and cardiac muscles. These toxic effects of alcohol on striated muscles negatively impact morbidity and mortality to alcohol misusers. Here, we demonstrate that the nematode C. elegans also exhibits key features of alcoholic myopathy when exposed to ethanol. Ethanol exposure impairs muscle organization and strength, and induces the expression of genes that cope with alcohol toxicity. Particularly, we find that ethanol toxicity is centered on mitochondria, the power plants of the cell. As an adaptive protective response to mitochondrial dysfunction, ethanol-exposed cells induce global transcriptional reprogramming to restore normal mitochondrial function. Upregulation of this transcriptional reprogramming in C. elegans effectively blocks ethanol-induced muscle weakness, a key feature of alcoholic myopathy. Thus, the modulation of mitochondrial stress responses is a potentially promising therapeutic strategy to ameliorate alcohol toxicity to muscle.

scholarly journals Identification of Novel Therapeutic Targets for Polyglutamine Diseases That Target Mitochondrial Fragmentation

2021 ◽  
Vol 22 (24) ◽  
pp. 13447
Author(s):  
Annika Traa ◽  
Emily Machiela ◽  
Paige D. Rudich ◽  
Sonja K. Soo ◽  
Megan M. Senchuk ◽  
...  
Keyword(s):  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Cag Repeat ◽  
Mitochondrial Morphology ◽  
Polyglutamine Diseases ◽  
Mitochondrial Fragmentation ◽  
C Elegans ◽  
Beneficial Effects ◽  
Negative Side Effects ◽  
And Function

Huntington’s disease (HD) is one of at least nine polyglutamine diseases caused by a trinucleotide CAG repeat expansion, all of which lead to age-onset neurodegeneration. Mitochondrial dynamics and function are disrupted in HD and other polyglutamine diseases. While multiple studies have found beneficial effects from decreasing mitochondrial fragmentation in HD models by disrupting the mitochondrial fission protein DRP1, disrupting DRP1 can also have detrimental consequences in wild-type animals and HD models. In this work, we examine the effect of decreasing mitochondrial fragmentation in a neuronal C. elegans model of polyglutamine toxicity called Neur-67Q. We find that Neur-67Q worms exhibit mitochondrial fragmentation in GABAergic neurons and decreased mitochondrial function. Disruption of drp-1 eliminates differences in mitochondrial morphology and rescues deficits in both movement and longevity in Neur-67Q worms. In testing twenty-four RNA interference (RNAi) clones that decrease mitochondrial fragmentation, we identified eleven clones—each targeting a different gene—that increase movement and extend lifespan in Neur-67Q worms. Overall, we show that decreasing mitochondrial fragmentation may be an effective approach to treating polyglutamine diseases and we identify multiple novel genetic targets that circumvent the potential negative side effects of disrupting the primary mitochondrial fission gene drp-1.

scholarly journals The Effectiveness Of Quadriceps Strengthening Exercises Combined With Neuromuscular Electrical Stimulation on Patellofemoral Pain Syndrome

2017 ◽  
Vol 5 (2_suppl2) ◽  
pp. 2325967117S0010
Author(s):  
Sezen Karabörklü Argut ◽  
Nilgün Türker ◽  
Derya Çelik ◽  
Önder İsmet Kılıçoğlu
Keyword(s):  
Electrical Stimulation ◽  
Muscle Strength ◽  
Neuromuscular Electrical Stimulation ◽  
Pain Syndrome ◽  
Quadriceps Strength ◽  
Patellofemoral Pain ◽  
Group I ◽  
Strengthening Exercises ◽  
Group Ii ◽  
And Function

Objective: The weakness of the quadriceps strength in patellofemoral pain syndrome (PFPS) is very evident. Therefore, quadriceps strengthening exercises are very important part of the rehabilitation program. Neuromuscular Electrical Stimulation (NMES) is considered one of the methods for increasing quadriceps muscle strength. To evaluate the effectiveness of combined NMES and strengthening exercises to improve the recovery of quadriceps strength and function in patients with PFPS. Methods: This study was planned as a randomized controlled pilot study. A total of 27 patients (mean age=38.9±10.8 years, range=20-60 years; 16 females) with PFPS were assessed and randomly assigned into 2 groups. Group I received a standard program (quadriceps strengthening, hip strengthening and hamstring stretching) and NMES combined with quadriceps strengthening exercises simultaneously. Group II received the same standard program without NMES. Both groups were enrolled 3 times per week for 40 minutes per day in 6 weeks. Patients were assessed at the baseline, 3 rd, 6th, and 12th weeks of treatment. Quadriceps strength was evaluated by isokinetic dynamometer. The range of motion at testing was set between 0 for extension to 90 for flexion. The test was performed at 60 degrees/sn and concentric maximum peak torque value was recorded. Kujala and Lysholm scores were used for functional assessments. The data were analyzed using the SPSS 20.0. Shapiro-Wilk test was used to assess the distribution of data. The changes in dependent variables before treatment, 3 rd, 6th, and 12th weeks were analyzed using a 2 by 4 mixed-model analysis of variance (ANOVA). Pairwise comparisons with paired t test were used to determine whether the Group I or Group II, has changed over time. An intention- to- treat analysis was performed to impute values for missing data. An alpha level of 0.05 was established. Results: The study was completed with 20 patients. Group I (n=10; mean age=39.4±8.5 years; 7 females) and group II (n=10; mean age=43.2±11.7 years; 5 females) had no differences in pre-operative measures (p>.05). There was significant improvements in within groups statistics of all parameters for both groups (p<.05). No differences in quadriceps strength, Kujala and Lysholm scores between groups were found at the different time points (F= 0.86; p = 0.12, F=0,001; p =0.97, F=0.12; p=0.73, respectively) Conclusion: NMES combined with quadriceps strengthening exercises has no additional effect on PFPS patients’ on muscle strength and function. When considering these results, we believe that there is no need to continue the study in progress. [Table: see text]

scholarly journals The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To Regulate Caenorhabditis elegans Reversal Behavior

2019 ◽  
Vol 10 (1) ◽  
pp. 199-210 ◽  
Author(s):  
Chuanman Zhou ◽  
Jintao Luo ◽  
Xiaohui He ◽  
Qian Zhou ◽  
Yunxia He ◽  
...  
Keyword(s):  
Plant Hormone ◽  
Neuronal Excitability ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Link Type ◽  
Complex Functions ◽  
And Function ◽  
Multiple Loss

NALCN (Na+leak channel, non-selective) is a conserved, voltage-insensitive cation channel that regulates resting membrane potential and neuronal excitability. UNC79 and UNC80 are key regulators of the channel function. However, the behavioral effects of the channel complex are not entirely clear and the neurons in which the channel functions remain to be identified. In a forward genetic screen for C. elegans mutants with defective avoidance response to the plant hormone methyl salicylate (MeSa), we isolated multiple loss-of-function mutations in unc-80 and unc-79. C. elegans NALCN mutants exhibited similarly defective MeSa avoidance. Interestingly, NALCN, unc-80 and unc-79 mutants all showed wild type-like responses to other attractive or repelling odorants, suggesting that NALCN does not broadly affect odor detection or related forward and reversal behaviors. To understand in which neurons the channel functions, we determined the identities of a subset of unc-80-expressing neurons. We found that unc-79 and unc-80 are expressed and function in overlapping neurons, which verified previous assumptions. Neuron-specific transgene rescue and knockdown experiments suggest that the command interneurons AVA and AVE and the anterior guidepost neuron AVG can play a sufficient role in mediating unc-80 regulation of the MeSa avoidance. Though primarily based on genetic analyses, our results further imply that MeSa might activate NALCN by direct or indirect actions. Altogether, we provide an initial look into the key neurons in which the NALCN channel complex functions and identify a novel function of the channel in regulating C. elegans reversal behavior through command interneurons.

scholarly journals C. elegans germ granules require both assembly and localized regulators for mRNA repression

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Scott Takeo Aoki ◽  
Tina R. Lynch ◽  
Sarah L. Crittenden ◽  
Craig A. Bingman ◽  
Marvin Wickens ◽  
...  
Keyword(s):  
Liquid Droplet ◽  
Scaffolding Protein ◽  
P Granules ◽  
C Elegans ◽  
Cytoplasmic Rna ◽  
And Function ◽  
Rnp Granules ◽  
Key Residues ◽  
Reporter Mrna

AbstractCytoplasmic RNA–protein (RNP) granules have diverse biophysical properties, from liquid to solid, and play enigmatic roles in RNA metabolism. Nematode P granules are paradigmatic liquid droplet granules and central to germ cell development. Here we analyze a key P granule scaffolding protein, PGL-1, to investigate the functional relationship between P granule assembly and function. Using a protein–RNA tethering assay, we find that reporter mRNA expression is repressed when recruited to PGL-1. We determine the crystal structure of the PGL-1 N-terminal region to 1.5 Å, discover its dimerization, and identify key residues at the dimer interface. Mutations of those interface residues prevent P granule assembly in vivo, de-repress PGL-1 tethered mRNA, and reduce fertility. Therefore, PGL-1 dimerization lies at the heart of both P granule assembly and function. Finally, we identify the P granule-associated Argonaute WAGO-1 as crucial for repression of PGL-1 tethered mRNA. We conclude that P granule function requires both assembly and localized regulators.

scholarly journals Respiratory Muscle Weakness as a Risk Factor for Pneumonia in Older People

Gerontology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Tatsuma Okazaki ◽  
Yoshimi Suzukamo ◽  
Midori Miyatake ◽  
Riyo Komatsu ◽  
Masahiro Yaekashiwa ◽  
...  
Keyword(s):  
Risk Factor ◽  
Muscle Strength ◽  
Older People ◽  
Serum Albumin ◽  
Muscle Mass ◽  
Muscle Weakness ◽  
Fat Mass ◽  
Respiratory Muscle ◽  
Respiratory Muscle Strength ◽  
Respiratory Muscle Weakness

Introduction: The respiratory muscle strength regulates the effectiveness of coughing, which clears the airways and protects people from pneumonia. Sarcopenia is an aging-related loss of muscle mass and function, the worsening of which is associated with malnutrition. The loss of respiratory and swallowing muscle strength occurs with aging, but its effect on pneumonia is unclear. This study aimed to determine the risks of respiratory muscle weakness on the onset and relapse of pneumonia in older people in conjunction with other muscle-related factors such as malnutrition. Methods: We conducted a longitudinal study with 47 pneumonia inpatients and 35 non-pneumonia controls aged 70 years and older. We evaluated the strength of respiratory and swallowing muscles, muscle mass, and malnutrition (assessed by serum albumin levels and somatic fat) during admission and confirmed pneumonia relapse within 6 months. The maximal inspiratory and expiratory pressures determined the respiratory muscle strength. Swallowing muscle strength was evaluated by tongue pressure. Bioelectrical impedance analysis was used to evaluate the muscle and fat mass. Results: The respiratory muscle strength, body trunk muscle mass, serum albumin level, somatic fat mass, and tongue pressure were significantly lower in pneumonia patients than in controls. Risk factors for the onset of pneumonia were low inspiratory respiratory muscle strength (odds ratio [OR], 6.85; 95% confidence interval [CI], 1.56–30.11), low body trunk muscle mass divided by height2 (OR, 6.86; 95% CI, 1.49–31.65), and low serum albumin level (OR, 5.46; 95% CI, 1.51–19.79). For the relapse of pneumonia, low somatic fat mass divided by height2 was a risk factor (OR, 20.10; 95% CI, 2.10–192.42). Discussion/Conclusions: Respiratory muscle weakness, lower body trunk muscle mass, and malnutrition were risk factors for the onset of pneumonia in older people. For the relapse of pneumonia, malnutrition was a risk factor.

scholarly journals Physical and functional performance assessment in pediatric oncology: a systematic review

2021 ◽  
Author(s):  
Regine Söntgerath ◽  
Julia Däggelmann ◽  
Sabine V. Kesting ◽  
Corina S. Rueegg ◽  
Torge-Christian Wittke ◽  
...  
Keyword(s):  
Systematic Review ◽  
Muscle Strength ◽  
Physical Performance ◽  
Cardiorespiratory Fitness ◽  
Pediatric Cancer ◽  
Motor Performance ◽  
Performance Test ◽  
Functional Mobility ◽  
Cancer Type ◽  
And Function

Abstract Background Research indicates reduced physical performance from diagnosis into survivorship of pediatric cancer patients. However, there is no systematic information or guideline available on the methods to assess physical performance and function in this population. The purpose was to systematically compile and describe assessments of physical performance and function in patients and survivors of pediatric cancer, including cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait and motor performance test batteries. Methods We searched the databases PubMed, SPORTDiscus, and Cochrane Database and performed abstract and full-text selection of 2619 articles according to the Cochrane Handbook of Systematic Reviews. Information on patients characteristics, assessments, information on validity and reliability, and relevant references was extracted. Results In summary, 63 different assessments were found in 149 studies including 11639 participants. Most studies evaluated cardiorespiratory fitness and muscle strength with the majority conducted off treatment. Some outcomes (e.g. speed) and diagnoses (e.g. neuroblastoma) were severely underrepresented. With the exception of gait, leukemia patients represented the largest group of individuals tested. Conclusions Insufficient data and patient heterogeneity complicate uniform recommendations for assessments. Our results support researchers and practitioners in selecting appropriate assessment to meet their specific research questions or individual daily practice needs. Impact This systematic review includes 149 studies and provides a comprehensive summary of 63 assessments to evaluate cardiorespiratory fitness, muscle strength, speed, balance, flexibility, functional mobility, gait or motor performance test batteries in patients and survivors of pediatric cancer. We present the most studied fields within the pediatric cancer population, which are cardiorespiratory fitness and muscle strength, off treatment phase, and leukemia patients. We propose research priorities by identification of subgroups in terms of cancer type, phase of treatment, and outcome of interest that are underrepresented in studies currently available.

scholarly journals Correlation between age, muscle architecture, and muscle strength in children with Erb’s palsy

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Ahmed Saad Awad ◽  
Mostafa Soliman Ali ◽  
Mohamed Ismail Elassal
Keyword(s):  
Muscle Strength ◽  
Muscle Weakness ◽  
Muscle Thickness ◽  
Study Groups ◽  
Pennation Angle ◽  
Muscle Architecture ◽  
Active Movement ◽  
Significant Relation ◽  
Erb’S Palsy ◽  
Significant Difference

Abstract Background Muscle weakness is a widespread problem in children with Erb’s palsy as it can cause changes in muscle architecture parameters, which can be detected by ultrasonography. This study was conducted to determine the relation between age, muscle architecture, and muscle strength in children with Erb’s palsy. A total of 40 children with Erb’s palsy from both sexes aged 1–2.5 years were included in this study. Muscle thickness and pennation angle were measured by ultrasonography, and muscle strength was measured using the active movement scale. Results A significant relation was found between age, muscle thickness, pennation angle, and muscle strength (P < 0.05). Moreover, a significant difference was found in muscle architecture parameters during relaxation and contraction in both study groups and in each study group (P < 0.05). Conclusion Muscle weakness in children with Erb’s palsy has an effect on muscle architecture parameters, and these parameters also increase with age.

scholarly journals Genome-wide identification and analysis of class III peroxidases in Betula pendula

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Kewei Cai ◽  
Huixin Liu ◽  
Song Chen ◽  
Yi Liu ◽  
Xiyang Zhao ◽  
...  
Keyword(s):  
Stress Responses ◽  
Betula Pendula ◽  
Expression Patterns ◽  
Class Iii ◽  
Physiological Processes ◽  
Plant Life ◽  
Genome Wide ◽  
Plant Life Cycle ◽  
Class Iii Peroxidases ◽  
And Function

Abstract Background Class III peroxidases (POD) proteins are widely present in the plant kingdom that are involved in a broad range of physiological processes including stress responses and lignin polymerization throughout the plant life cycle. At present, POD genes have been studied in Arabidopsis, rice, poplar, maize and Chinese pear, but there are no reports on the identification and function of POD gene family in Betula pendula. Results We identified 90 nonredundant POD genes in Betula pendula. (designated BpPODs). According to phylogenetic relationships, these POD genes were classified into 12 groups. The BpPODs are distributed in different numbers on the 14 chromosomes, and some BpPODs were located sequentially in tandem on chromosomes. In addition, we analyzed the conserved domains of BpPOD proteins and found that they contain highly conserved motifs. We also investigated their expression patterns in different tissues, the results showed that some BpPODs might play an important role in xylem, leaf, root and flower. Furthermore, under low temperature conditions, some BpPODs showed different expression patterns at different times. Conclusions The research on the structure and function of the POD genes in Betula pendula plays a very important role in understanding the growth and development process and the molecular mechanism of stress resistance. These results lay the theoretical foundation for the genetic improvement of Betula pendula.

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