scholarly journals KCNG1-Related Syndromic Form of Congenital Neuromuscular Channelopathy in a Crossbred Calf

Genes ◽  
2021 ◽  
Vol 12 (11) ◽  
pp. 1792
Author(s):  
Joana G. P. Jacinto ◽  
Irene M. Häfliger ◽  
Eylem Emek Akyürek ◽  
Roberta Sacchetto ◽  
Cinzia Benazzi ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Disease Model ◽  
Missense Variant ◽  
Muscle Stiffness ◽  
Potential Candidate ◽  
Myotonia Congenita ◽  
Craniofacial Dysmorphism ◽  
Gated Channel ◽  
Exercise Induced ◽  
The Right

Inherited channelopathies are a clinically and heritably heterogeneous group of disorders that result from ion channel dysfunction. The aim of this study was to characterize the clinicopathologic features of a Belgian Blue x Holstein crossbred calf with paradoxical myotonia congenita, craniofacial dysmorphism, and myelodysplasia, and to identify the most likely genetic etiology. The calf displayed episodes of exercise-induced generalized myotonic muscle stiffness accompanied by increase in serum potassium. It also showed slight flattening of the splanchnocranium with deviation to the right side. On gross pathology, myelodysplasia (hydrosyringomielia and segmental hypoplasia) in the lumbosacral intumescence region was noticed. Histopathology of the muscle profile revealed loss of the main shape in 5.3% of muscle fibers. Whole-genome sequencing revealed a heterozygous missense variant in KCNG1 affecting an evolutionary conserved residue (p.Trp416Cys). The mutation was predicted to be deleterious and to alter the pore helix of the ion transport domain of the transmembrane protein. The identified variant was present only in the affected calf and not seen in more than 5200 other sequenced bovine genomes. We speculate that the mutation occurred either as a parental germline mutation or post-zygotically in the developing embryo. This study implicates an important role for KCNG1 as a member of the potassium voltage-gated channel group in neurodegeneration. Providing the first possible KCNG1-related disease model, we have, therefore, identified a new potential candidate for related conditions both in animals and in humans. This study illustrates the enormous potential of phenotypically well-studied spontaneous mutants in domestic animals to provide new insights into the function of individual genes.

scholarly journals Thalamocortical Connectivity in Experimentally-Induced Migraine Attacks: A Pilot Study

2021 ◽  
Vol 11 (2) ◽  
pp. 165
Author(s):  
Daniele Martinelli ◽  
Gloria Castellazzi ◽  
Roberto De Icco ◽  
Ana Bacila ◽  
Marta Allena ◽  
...  
Keyword(s):  
Disease Model ◽  
Episodic Migraine ◽  
Wavelet Coherence ◽  
Test Time ◽  
Prodromal Phase ◽  
Brain Changes ◽  
The Right ◽  
Wavelet Coherence Analysis ◽  
Thalamic Function ◽  
Experimentally Induced

In this study we used nitroglycerin (NTG)-induced migraine attacks as a translational human disease model. Static and dynamic functional connectivity (FC) analyses were applied to study the associated functional brain changes. A spontaneous migraine-like attack was induced in five episodic migraine (EM) patients using a NTG challenge. Four task-free functional magnetic resonance imaging (fMRI) scans were acquired over the study: baseline, prodromal, full-blown, and recovery. Seed-based correlation analysis (SCA) was applied to fMRI data to assess static FC changes between the thalamus and the rest of the brain. Wavelet coherence analysis (WCA) was applied to test time-varying phase-coherence changes between the thalamus and salience networks (SNs). SCA results showed significantly FC changes between the right thalamus and areas involved in the pain circuits (insula, pons, cerebellum) during the prodromal phase, reaching its maximal alteration during the full-blown phase. WCA showed instead a loss of synchronisation between thalami and SN, mainly occurring during the prodrome and full-blown phases. These findings further support the idea that a temporal change in thalamic function occurs over the experimentally induced phases of NTG-induced headache in migraine patients. Correlation of FC changes with true clinical phases in spontaneous migraine would validate the utility of this model.

scholarly journals Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle

2015 ◽  
Vol 308 (9) ◽  
pp. C710-C719 ◽  
Author(s):  
Anna Vainshtein ◽  
Liam D. Tryon ◽  
Marion Pauly ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Acute Exercise ◽  
Transmembrane Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lipid Trafficking ◽  
Mitochondrial Transcription Factor ◽  
Energy Demands ◽  
Niemann Pick ◽  
Exercise Induced

Regular exercise leads to systemic metabolic benefits, which require remodeling of energy resources in skeletal muscle. During acute exercise, the increase in energy demands initiate mitochondrial biogenesis, orchestrated by the transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). Much less is known about the degradation of mitochondria following exercise, although new evidence implicates a cellular recycling mechanism, autophagy/mitophagy, in exercise-induced adaptations. How mitophagy is activated and what role PGC-1α plays in this process during exercise have yet to be evaluated. Thus we investigated autophagy/mitophagy in muscle immediately following an acute bout of exercise or 90 min following exercise in wild-type (WT) and PGC-1α knockout (KO) animals. Deletion of PGC-1α resulted in a 40% decrease in mitochondrial content, as well as a 25% decline in running performance, which was accompanied by severe acidosis in KO animals, indicating metabolic distress. Exercise induced significant increases in gene transcripts of various mitochondrial (e.g., cytochrome oxidase subunit IV and mitochondrial transcription factor A) and autophagy-related (e.g., p62 and light chain 3) genes in WT, but not KO, animals. Exercise also resulted in enhanced targeting of mitochondria for mitophagy, as well as increased autophagy and mitophagy flux, in WT animals. This effect was attenuated in the absence of PGC-1α. We also identified Niemann-Pick C1, a transmembrane protein involved in lysosomal lipid trafficking, as a target of PGC-1α that is induced with exercise. These results suggest that mitochondrial turnover is increased following exercise and that this effect is at least in part coordinated by PGC-1α. Anna Vainshtein received the AJP-Cell 2015 Paper of the Year award. Listen to a podcast with Anna Vainshtein and coauthor David A. Hood at http://ajpcell.podbean.com/e/ajp-cell-paper-of-the-year-2015-award-podcast/ .

scholarly journals Electromyographic Evaluation of the Shoulder Muscle after a Fatiguing Isokinetic Protocol in Recreational Overhead Athletes

2021 ◽  
Vol 18 (5) ◽  
pp. 2516
Author(s):  
Sebastian Klich ◽  
Adam Kawczyński ◽  
Bogdan Pietraszewski ◽  
Matteo Zago ◽  
Aiguo Chen ◽  
...  
Keyword(s):  
External Rotation ◽  
Shoulder Girdle ◽  
Median Frequency ◽  
Shoulder Injury ◽  
Overhead Athletes ◽  
Upper Trapezius ◽  
Main Effect ◽  
Shoulder Girdle Muscles ◽  
Exercise Induced ◽  
The Right

The goal of our study was to examine the muscle activity of the shoulder girdle after isokinetic fatigue, which may simulate muscle activities commonly occurring during specific sport-related activities in recreational overhead asymptomatic athletes. We hypothesized that exercise-induced fatigue, reported after isokinetic protocols, may cause a decrease in the median frequency (MF) of the upper trapezius (UT), infraspinatus (IS), and deltoid muscles. Twenty-four male overhead volleyball (n = 8), handball (n = 8), and tennis (n = 8) athletes participated in this study. All subjects were without shoulder injury history. The surface electromyography (SEMG) was collected on the right (dominant) side of the shoulder girdle muscles in the following order: UT, IS and anterior (DA), and posterior deltoideus (DP). The fatigue protocol consisted of three sets of 32 maximum isokinetic concentric contractions while performing shoulder internal and external rotation at an isokinetic speed of 120 o/s. The resultant difference in median frequency (ΔMF) values consistently dropped after the fatiguing tasks across all recorded muscles, in terms of the initial MF (MFINI = 65.1 ± 1.1 Hz) and final MF (MFFIN = 57.9 ± 0.9 Hz), and the main effect of time was significant (F(1,22) = 43.15, p < 0.001). MF values decreased mostly for IS (ΔMFIS = −9.9 ± 1.6 Hz) and DP (ΔMFPD = −9.5 ± 1.9 Hz) muscles, while DA and UT showed smaller changes (ΔMFDA = −6.9 ± 1.5 Hz) and (ΔMFUT = −3.2 ± 1.3 Hz). The results of our study show a meaningful contribution in determining increased fatigue of the shoulder girdle muscles during repeated isokinetic internal-external rotation protocols. We have also demonstrated a significant decrease in MF in all examined muscles, especially IS and DA.

Effect of unweighting on skeletal muscle use during exercise

1995 ◽  
Vol 79 (1) ◽  
pp. 168-175 ◽  
Author(s):  
L. L. Ploutz-Snyder ◽  
P. A. Tesch ◽  
D. J. Crittenden ◽  
G. A. Dudley
Keyword(s):  
Lower Limb ◽  
Weight Bearing ◽  
Muscle Group ◽  
Mr Images ◽  
Cross Sectional ◽  
Quadriceps Femoris Muscle ◽  
Before And After ◽  
Exercise Induced ◽  
The Right ◽  
Femoris Muscle

Exercise-induced spin-spin relaxation time (T2) shifts in magnetic resonance (MR) images were used to test the hypothesis that more muscle would be used to perform a given submaximal task after 5 wk of unweighting. Before and after unilateral lower limb suspension (ULLS), 7 subjects performed 5 sets of 10 unilateral concentric actions with the quadriceps femoris muscle group (QF) at each of 4 loads: 25, 40, 55, and 70% of maximum. T2-weighted MR images of the thigh were collected at rest and after each relative load. ULLS elicited a 20% decrease in strength of the left unweighted QF and a 14% decrease in average cross-sectional area (CSA) with no changes in the right weight-bearing QF. Average CSA of the left or right QF showing exercise-induced T2 shift increased as a function of exercise intensity both before and after ULLS. On average, 12 +/- 1, 15 +/- 2, 18 +/- 2, and 22 +/- 1 cm2 of either QF showed elevated T2 for the 25, 40, 55, and 70% loads, respectively, before ULLS. Average CSA of the left but not the right QF, showing elevated T2 after ULLS, was increased to 16 +/- 2, 23 +/- 3, 31 +/- 7, and 39 +/- 5 cm2, respectively. The results indicated that unweighting increased exercise-induced T2 shift in MR images, presumably due to greater muscle mass involvement in exercise after than before unweighting, suggesting a change in motor control.

scholarly journals Novel SCN5A and GPD1L Variants Identified in Two Unrelated Han-Chinese Patients With Clinically Suspected Brugada Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Meng Yuan ◽  
Yi Guo ◽  
Hong Xia ◽  
Hongbo Xu ◽  
Hao Deng ◽  
...  
Keyword(s):  
Brugada Syndrome ◽  
Missense Variant ◽  
Han Chinese ◽  
Chinese Patients ◽  
Splicing Variant ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
Gated Channel ◽  
Life Threatening ◽  
Glycerol 3 Phosphate Dehydrogenase

Brugada syndrome (BrS) is a complexly genetically patterned, rare, malignant, life-threatening arrhythmia disorder. It is autosomal dominant in most cases and characterized by identifiable electrocardiographic patterns, recurrent syncope, nocturnal agonal respiration, and other symptoms, including sudden cardiac death. Over the last 2 decades, a great number of variants have been identified in more than 36 pathogenic or susceptibility genes associated with BrS. The present study used the combined method of whole exome sequencing and Sanger sequencing to identify pathogenic variants in two unrelated Han-Chinese patients with clinically suspected BrS. Minigene splicing assay was used to evaluate the effects of the splicing variant. A novel heterozygous splicing variant c.2437-2A&gt;C in the sodium voltage-gated channel alpha subunit 5 gene (SCN5A) and a novel heterozygous missense variant c.161A&gt;T [p.(Asp54Val)] in the glycerol-3-phosphate dehydrogenase 1 like gene (GPD1L) were identified in these two patients with BrS-1 and possible BrS-2, respectively. Minigene splicing assay indicated the deletion of 15 and 141 nucleotides in exon 16, resulting in critical amino acid deletions. These findings expand the variant spectrum of SCN5A and GPD1L, which can be beneficial to genetic counseling and prenatal diagnosis.

scholarly journals Changes in the Stiffness of Thigh Muscles in the Left and Right Limbs During Six Weeks of Plyometric Training in Volleyball Players

2018 ◽  
Vol 25 (2) ◽  
pp. 20-24 ◽  
Author(s):  
Dariusz Mroczek ◽  
Edward Superlak ◽  
Marek Konefał ◽  
Krzysztof Maćkała ◽  
Paweł Chmura ◽  
...  
Keyword(s):  
Good Method ◽  
Optimal Level ◽  
Muscle Stiffness ◽  
Plyometric Training ◽  
Thigh Muscles ◽  
Left Limb ◽  
Significant Difference ◽  
Volleyball Players ◽  
Left And Right ◽  
The Right

Abstract Introduction. Monitoring muscle stiffness in athletes can be a good method of assessing fatigue caused by high training loads, and the early detection of fatigue can help prevent the occurrence of micro-trauma in the muscles that can cause contusions. The research carried out by Wilson et al. [1] confirmed that an optimal level of muscle stiffness is significantly correlated with high muscle loads. The aim of the current study was to determine changes in muscle stiffness of the left and right thighs during six weeks of plyometric training (PT) in volleyball players. Material and methods. The study involved 16 volleyball players from the second-league Opole University of Technology Club (age = 21.12 ± 1.66 years, height = 191.62 ± 5.73 cm, and weight = 86.25 ± 6.66 kg) with at least five years of competitive experience (7.5 ± 2.44 years). Muscle stiffness was measured during three stages of the plyometric training using a MYOTON PRO device (Estonia). Results. An RM-ANOVA analysis showed a significant difference in the resting stiffness of the semitendinosus (posterior thigh) muscles of the left and right limbs before the plyometric training began, but no significant differences were found in the stiffness of these muscles in the fourth or sixth weeks of training. The results of the measurement performed for the anterior muscles of the thigh did not reveal a significant difference in the stiffness of the left limb compared to that of the right limb in subsequent weeks of training. Conclusion. The loads used in plyometric training in volleyball players caused a decrease in the differences in muscle stiffness between the left and right limbs, and in both limbs, adaptation trended towards an increase or a decrease in stiffness.

scholarly journals Novel Membrane Protein shrew-1 Targets to Cadherin-Mediated Junctions in Polarized Epithelial Cells

2004 ◽  
Vol 15 (1) ◽  
pp. 397-406 ◽  
Author(s):  
Sanita Bharti ◽  
Heike Handrow-Metzmacher ◽  
Silvia Zickenheiner ◽  
Andreas Zeitvogel ◽  
Rudolf Baumann ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Membrane Protein ◽  
Transmembrane Protein ◽  
Adherens Junctions ◽  
Direct Interaction ◽  
Potential Candidate ◽  
Putative Open Reading Frame ◽  
Polarized Epithelial Cells ◽  
E Cadherin

While searching for potential candidate molecules relevant for the pathogenesis of endometriosis, we discovered a 2910-base pair cDNA encoding a novel putative 411-amino acid integral membrane protein that we called shrew-1. The putative open-reading frame was confirmed with antibodies against shrew-1 peptides that labeled a protein of ∼48 kDa in extracts of shrew-1 mRNA-positive tissue and also detected ectopically expressed shrew-1. Expression of epitope-tagged shrew-1 in epithelial cells and analysis by surface biotinylation and immunoblots demonstrated that shrew-1 is indeed a transmembrane protein. Shrew-1 is able to target to E-cadherin-mediated adherens junctions and interact with the E-cadherin–catenin complex in polarized MCF7 and Madin-Darby canine kidney cells, but not with the N-cadherin–catenin complex in nonpolarized epithelial cells. Direct interaction of shrew-1 with β-catenin in in vitro pull-down assay suggests that β-catenin might be one of the proteins that targets and/or retains shrew-1 in the adherens junctions. Interestingly, shrew-1 was partially translocated in response to scatter factor (ligand of receptor tyrosine kinase c-met) from the plasma membrane to the cytoplasm where it still colocalized with endogenous E-cadherin. In summary, we introduce shrew-1 as a novel component of adherens junctions, interacting with E-cadherin–β-catenin complexes in polarized epithelial cells.

Effects of myostatin on the mechanical properties of muscles during repeated active lengthening in the mouse

2019 ◽  
Vol 44 (4) ◽  
pp. 381-388
Author(s):  
Danguole Satkunskiene ◽  
Aivaras Ratkevicius ◽  
Sigitas Kamandulis ◽  
Tomas Venckunas
Keyword(s):  
Mechanical Properties ◽  
Isometric Force ◽  
Muscle Stiffness ◽  
Repeated Loading ◽  
Relative Reduction ◽  
Muscle Type ◽  
Age Dependent ◽  
Exercise Induced ◽  
Edl Muscle ◽  
Early Phases

The aim of the present study was to investigate how myostatin dysfunction affects fast and slow muscle stiffness and viscosity during severe repeated loading. Isolated extensor digitorum longus (EDL) and soleus muscles of young adult female mice of the BEH (dysfunctional myostatin) and BEH+/+ (functional myostatin) strains were subjected to 100 contraction–stretching loading cycles during which contractile and mechanical properties were assessed. BEH mice exhibited greater exercise-induced muscle damage, although the effect was muscle- and age-dependent and limited to the early phases of simulated exercise. The relative reduction of the EDL muscle isometric force recorded during the initial 10–30 loading cycles was greater in BEH mice than in BEH+/+ mice and exceeded that of the soleus muscle of either strain. The induced damage was associated with lower muscle stiffness. The effects of myostatin on the mechanical properties of muscles depend on muscle type and maturity.

scholarly journals Improved method for the catheterization of the right ventricle in a rat model of pulmonary artery hypertension

2020 ◽  
Vol 30 (4) ◽  
pp. 535-537
Author(s):  
Marcello Tontodonati ◽  
Debbie Ridley ◽  
René Remie ◽  
Peter Clements
Keyword(s):  
Right Ventricle ◽  
Jugular Vein ◽  
Disease Model ◽  
Pulmonary Artery Hypertension ◽  
Animal Disease ◽  
Improved Method ◽  
Novel Approach ◽  
Catheter Tip ◽  
The Right

Abstract Ventricle catheterization in the rat is widely practiced in cardiopulmonary research. The catheters deployed are either fluid filled or solid tip pressure or pressure–volume catheters. The access to the right ventricle is through the right jugular vein, most commonly without direct visualization such as fluoroscopy. Advancement of the catheter tip is aided by visualizing the pressure signals of the monitoring/recording systems used. This approach may present challenges due to various reasons, including the stiffness of new catheters, their dimensions or anatomical changes associated with the animal disease model. In this article, we present a novel approach, which has been optimized, successfully validated surgically and adopted in current projects. It has been shown to improve both the overall quality of the signals recorded and the time to access the right ventricle, thus reducing the overall time of surgery. The method presented in this article is safe, easy to reproduce and does not require additional skills compared to a more ‘standard’ approach.

scholarly journals Noninvasive evaluation of pulmonary artery pressure during exercise: the importance of right atrial hypertension

2019 ◽  
Vol 55 (2) ◽  
pp. 1901617 ◽  
Author(s):  
Masaru Obokata ◽  
Garvan C. Kane ◽  
Hidemi Sorimachi ◽  
Yogesh N.V. Reddy ◽  
Thomas P. Olson ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Pressure Gradient ◽  
Systolic Pressure ◽  
Area Under The Curve ◽  
Right Atrial ◽  
Pulmonary Artery Systolic Pressure ◽  
Therapeutic Implications ◽  
Exercise Induced ◽  
The Right ◽  
Minimal Bias

IntroductionIdentification of elevated pulmonary artery pressures during exercise has important diagnostic, prognostic and therapeutic implications. Stress echocardiography is frequently used to estimate pulmonary artery pressures during exercise testing, but data supporting this practice are limited. This study examined the accuracy of Doppler echocardiography for the estimation of pulmonary artery pressures at rest and during exercise.MethodsSimultaneous cardiac catheterisation-echocardiographic studies were performed at rest and during exercise in 97 subjects with dyspnoea. Echocardiography-estimated pulmonary artery systolic pressure (ePASP) was calculated from the right ventricular (RV) to right atrial (RA) pressure gradient and estimated RA pressure (eRAP), and then compared with directly measured PASP and RAP.ResultsEstimated PASP was obtainable in 57% of subjects at rest, but feasibility decreased to 15–16% during exercise, due mainly to an inability to obtain eRAP during stress. Estimated PASP correlated well with direct PASP at rest (r=0.76, p<0.0001; bias −1 mmHg) and during exercise (r=0.76, p=0.001; bias +3 mmHg). When assuming eRAP of 10 mmHg, ePASP correlated with direct PASP (r=0.70, p<0.0001), but substantially underestimated true values (bias +9 mmHg), with the greatest underestimation among patients with severe exercise-induced pulmonary hypertension (EIPH). Estimation of eRAP during exercise from resting eRAP improved discrimination of patients with or without EIPH (area under the curve 0.81), with minimal bias (5 mmHg), but wide limits of agreement (−14–25 mmHg).ConclusionsThe RV–RA pressure gradient can be estimated with reasonable accuracy during exercise when measurable. However, RA hypertension frequently develops in patients with EIPH, and the inability to noninvasively account for this leads to substantial underestimation of exercise pulmonary artery pressures.

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