Phylogenetic and biochemical analysis of calsequestrin structure and association of its variants with cardiac disorders

Abstract Calsequestrin is among the most abundant proteins in muscle sarcoplasmic reticulum and displays a high capacity but a low affinity for Ca2+ binding. In mammals, calsequestrin is encoded by two genes, CASQ1 and CASQ2, which are expressed almost exclusively in skeletal and cardiac muscles, respectively. Phylogenetic analysis indicates that calsequestrin is an ancient gene in metazoans, and that the duplication of the ancestral calsequestrin gene took place after the emergence of the lancelet. CASQ2 gene variants associated with catecholaminergic polymorphic ventricular tachycardia (CPVT) in humans are positively correlated with a high degree of evolutionary conservation across all calsequestrin homologues. The mutations are distributed in diverse locations of the calsequestrin protein and impart functional diversity but remarkably manifest in a similar phenotype in humans.

Download Full-text

Diagnosis of arrhythmia based on ECG analysis using CNN

Bulletin of Electrical Engineering and Informatics ◽

10.11591/eei.v9i3.2172 ◽

2020 ◽

Vol 9 (3) ◽

pp. 988-995

Author(s):

Muayed S. AL-Huseiny ◽

Noor Khudhair Abbas ◽

Ahmed S. Sajit

Keyword(s):

Neural Network ◽

Classification Accuracy ◽

Processing Time ◽

Image Data ◽

Training Phase ◽

Test Results ◽

Ecg Signals ◽

Thermal Paper ◽

Cardiac Disorders ◽

High Degree

Arrhythmia is the prime indicator of serious heart issues, and, hence, it is essential to be detected properly for early phase treatment. This article presents an approach for the diagnosis of cardiac disorders via the recognition of 17 types of arrhythmia. The proposed approach includes building a convolution neural network (2D-CNN) which is trained by using images of Electrocardiograph (ECG) signals collected from the MIH-BIH database. The ECGs are first converted into images. This step serves twofold: first, CNN is best suited for classifying image data and thus reduces preprocessing, and second, most ECG recordings are still being produced on thermal paper which can then be captured as image. Next, 2D-CNN is trained and validated. Test results show that the proposed method achieves classification accuracy of 96.67% and error of 0.004%. in addition to the superior accuracy achieved by this method compared to the previous literature, this approach enjoys reduced processing time and complexity apart from the training phase, also by dealing with images this method offers high degree of versatility and can be integrated as utility within other applications or wearables.

Download Full-text

Novel and nondetected human signaling protein polymorphisms

Physiological Genomics ◽

10.1152/physiolgenomics.00030.2002 ◽

2002 ◽

Vol 10 (3) ◽

pp. 159-168 ◽

Cited By ~ 10

Author(s):

Roy A. Lynch ◽

Lynne Wagoner ◽

Shunan Li ◽

Li Sparks ◽

Jeffery Molkentin ◽

...

Keyword(s):

Genomic Dna ◽

Evolutionary Conservation ◽

Nonsynonymous Snps ◽

Signaling Proteins ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Signaling Protein ◽

Downstream Signaling ◽

Small G Protein ◽

High Degree

The frequency of single nucleotide polymorphisms (SNPs) in downstream signaling proteins was determined by combination heteroduplex HPLC and double-stranded sequencing of genomic DNA from 96–144 congestive heart failure (CHF) patients. Analysis of 56 coding exons in 9 signaling genes revealed 17 novel and 8 previously reported synonymous (no change in amino acid) SNPs, as well as one novel nonsynonymous SNP in the Rad small G protein. Because this initial analysis failed to detect numerous SNPs reported in the NCBI and Celera databases, double-strand sequencing of relevant exons from 74–91 CHF patients was used to confirm the absence of 10 previously reported nonsynonymous SNPs. Our results show that synonymous SNPs are frequent in signaling protein genes, whereas nonsynonymous SNPs are rare, suggesting a high degree of evolutionary conservation among these downstream signaling molecules. Comparisons of our results to the NCBI and Celera databases indicates that 56% of their SNP entries are not detected in our cohort. Importantly, while 31% of database SNPs were verified, 69% of SNPs detected in our cohort are not included in these databases. These findings indicate that caution may be warranted in relying exclusively on SNP databases as catalogs for polymorphic signaling protein genes.

Download Full-text

Mouse Beta-Mannosidase: cDNA Cloning, Expression, and Chromosomal Localization

Bioscience Reports ◽

10.1023/a:1013286216030 ◽

2001 ◽

Vol 21 (3) ◽

pp. 315-323 ◽

Cited By ~ 7

Author(s):

Tommaso Beccari ◽

Lucia Bibi ◽

Sofia Stinchi ◽

John Laing Stirling ◽

Aldo Orlacchio

Keyword(s):

Chromosomal Localization ◽

Human Gene ◽

Evolutionary Conservation ◽

Northern Blotting ◽

Northern Analysis ◽

Gene Encoding ◽

Lysosomal Disorder ◽

Conservation Analysis ◽

High Degree ◽

Differential Tissue

β-mannosidase is an exoglycosidase involved in the degradation of N-linked oligosacharides moieties of glycoproteins. Lack of β-mannosidase activity leads to the lysosomal disorder β-mannosidosis (MIM 248510). We have isolated and sequenced the gene encoding the mouse β-mannosidase. Comparison of the deduced amino acid sequence of mouse, human, bovine, and goat β-mannosidase showed 64% identity, reflecting a high degree of evolutionary conservation. Analysis of a multiple tissue northern blotting revealed a major transcript of about 3.7 kb in all tissues examined. The northern analysis also demonstrates that there is differential tissue mRNA expression. The mouse β-mannosidase gene (Bmn) was mapped to the distal end of Chromosome (Chr) 3, in a region that is homologous with a segment of human Chr 4 containing the orthologous human gene.

Download Full-text

Evolutionary conservation of the transcribed spacer sequences of the rDNA repeat unit in three species of the genus Aspergillus.

Acta Biochimica Polonica ◽

10.18388/abp.1994_4776 ◽

1994 ◽

Vol 41 (1) ◽

pp. 73-77 ◽

Cited By ~ 2

Author(s):

P Borsuk ◽

M Gniadkowski ◽

R Kucharski ◽

M Bisko ◽

M Kanabus ◽

...

Keyword(s):

Repeat Unit ◽

Evolutionary Conservation ◽

Secondary Structures ◽

Aspergillus Species ◽

Rdna Repeat ◽

Rdna Repeat Unit ◽

High Degree

We have cloned and sequenced the two intervening transcribed spacers in the rDNA repeat unit of three Aspergillus species--A. nidulans, A. awamori and A. wentii. The A. wentii and A. awamori spacers are almost identical and share a high degree of homology with the A. nidulans spacers. All spacers have a high G-C content (66%-76%) and the potential of forming complex secondary structures, which may indicate that they play a role in the maturation of pre-rRNA molecules.

Download Full-text

Lueshite, pyrochlore and monazite-(Ce) from apatite-dolomite carbonatite, Lesnaya Varaka complex, Kola Peninsula, Russia

Mineralogical Magazine ◽

10.1180/002646198548151 ◽

1998 ◽

Vol 62 (6) ◽

pp. 769-782 ◽

Cited By ~ 51

Author(s):

A. R. Chakhmouradian ◽

R. H. Mitchell

Keyword(s):

Kola Peninsula ◽

Divalent Cations ◽

High Capacity ◽

Compositional Variation ◽

X Ray ◽

Degree Of Hydration ◽

Pyrochlore Group ◽

Primary Mineral ◽

High Degree

AbstractApatite-dolomite carbonatite at Lesnaya Varaka, Kola Peninsula, Russia, hosts intricate mineral intergrowths composed of lueshite in the core and pyrochlore-group minerals in the rim. Lueshite is a primary Nb-bearing phase in the carbonatite and ranges in composition from cerian lueshite to almost pure NaNbO3. For comparison, the compositional variation of lueshite from the Kovdor and Sallanlatvi carbonatites is described. At Lesnaya Varaka, lueshite is replaced by nearly stoichiometric Na-Ca pyrochlore due to late-stage re-equilibration in the carbonatite system. X-ray powder diffraction data for both minerals are presented. Barian strontiopyrochlore, occurring as replacement mantles on Na-Ca pyrochlore, contains up to 43% Sr and 8–18% Ba at the A-site, and shows a high degree of hydration and strong ionic deficiency at the A- and Y-sites. This mineral is metamict and, upon heating, recrystallises to an aeschynite-type structure. Monazite-(Ce) found as minute crystals in fractures, represents the solid solution between monazite-(Ce) CePO4, brabantite CaTh(PO4)2 and SrTh(PO4)2. Our data indicate the high capacity of the monazite structure for Th and accompanying divalent cations at low temperatures and pressures that has a direct relevance to solving the problem of long-term conservation of radioactive wastes. Monazite-(Ce) and barian strontiopyrochlore are products of low-temperature hydrothermal or secondary (hypergene) alteration of the primary mineral assemblage of the carbonatite.

Download Full-text

Calcium storage in nonmuscle tissues: is the retina special?

Biochemistry and Cell Biology ◽

10.1139/o92-141 ◽

1992 ◽

Vol 70 (10-11) ◽

pp. 972-979 ◽

Cited By ~ 5

Author(s):

Michal Opas ◽

Marek Michalak

Keyword(s):

Endoplasmic Reticulum ◽

Storage Systems ◽

High Capacity ◽

Retinal Neurons ◽

Active System ◽

Calcium Storage ◽

Neuronal Tissues ◽

Intracellular Ca ◽

Cardiac Muscles ◽

And Storage

It is now well established that calreticulin is a high capacity Ca2+-binding protein which is a major Ca2+ storage protein of the lumen of endoplasmic reticulum membranes in a wide variety of tissues with the exception of skeletal and cardiac muscles. However, in nervous tissue, confusion exists regarding the nature of the intracellular Ca2+ stores, as the organelle responsible for Ca2+ storage has been identified as the endoplasmic reticulum by some investigators and as the specialized organelle, calciosome by others. Calreticulin, calsequestrin, and calsequestrin-like proteins have all been, on different occasions, reported to be present in calciosomes. Cerebral and cerebellar tissues, moreover, have been shown to contain somewhat different systems of Ca2+-buffering proteins. In the present paper we discuss evidence that the Ca2+ storage systems of the retina may prove to be more complex than those of other neuronal tissues. Biochemical and immunocytochemical evidence indicates the presence of either an isoform of calreticulin or another protein that is antigenically similar to calreticulin, but of slightly higher molecular weight, in the endoplasmic reticulum of both neurons and Müller glia from rabbit neural retina. However, as retinal neurons express Purkinje cell markers, one may expect to observe the presence of calsequestrin in these cells as well. Secondly, antibodies against the onchocercal RAL-1 antigen recognize a protein sharing 62–65% amino acid sequence identity with calreticulin. The anti-RAL-1 antibodies show specificity for the retina. Whether or not the RAL-1 antigen is an active part of the Ca2+ storage systems of the retina remains to be verified. Finally, the retinal epithelial cells of the retina have an additional active system for Ca2+ uptake and storage associated with melanin-containing pigment granules. Thus, taking into account the differences in Ca2+ uptake, storage, and release systems noted for neuronal versus nonneuronal nonmuscle tissues, the retina might show yet another diversification of the intracellular Ca2+ management system.Key words: calcium, calreticulin, endoplasmic reticulum, retina.

Download Full-text

Health-related quality of life and physical activity in children with inherited cardiac arrhythmia or inherited cardiomyopathy: the prospective multicentre controlled QUALIMYORYTHM study rationale, design and methods

Health and Quality of Life Outcomes ◽

10.1186/s12955-021-01825-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Pascal Amedro ◽

Oscar Werner ◽

Hamouda Abassi ◽

Aymeric Boisson ◽

Luc Souilla ◽

...

Keyword(s):

Quality Of Life ◽

Physical Activity ◽

Cardiac Arrhythmia ◽

Polymorphic Ventricular Tachycardia ◽

Health Related Quality ◽

Inherited Cardiomyopathy ◽

Related Quality ◽

Health Related ◽

Cardiac Disorders

Abstract Background Advances in paediatric cardiology have improved the prognosis of children with inherited cardiac disorders. However, health-related quality of life (QoL) and physical activity have been scarcely analysed in children with inherited cardiac arrhythmia or inherited cardiomyopathy. Moreover, current guidelines on the eligibility of young athletes with inherited cardiac disorders for sports participation mainly rely on expert opinions and remain controversial. Methods The QUALIMYORYTHM trial is a multicentre observational controlled study. The main objective is to compare the QoL of children aged 6 to 17 years old with inherited cardiac arrhythmia (long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, or arrhythmogenic right ventricular dysplasia), or inherited cardiomyopathy (hypertrophic, dilated, or restrictive cardiomyopathy), to that of age and gender-matched healthy subjects. The secondary objective is to assess their QoL according to the disease’s clinical and genetic characteristics, the level of physical activity and motivation for sports, the exercise capacity, and the socio-demographic data. Participants will wear a fitness tracker (ActiGraph GT3X accelerometer) for 2 weeks. A total of 214 children are required to observe a significant difference of 7 ± 15 points in the PedsQL, with a power of 90% and an alpha risk of 5%. Discussion After focusing on the survival in children with inherited cardiac disorders, current research is expanding to patient-reported outcomes and secondary prevention. The QUALIMYORYTHM trial intends to improve the level of evidence for future guidelines on sports eligibility in this population. Trial registration ClinicalTrials.gov Identifier: NCT04712136, registered on January 15th, 2021 (https://clinicaltrials.gov/ct2/show/NCT04712136).

Download Full-text

Structural Characterization of Carbon Materials Prepared at Low Temperature

MRS Proceedings ◽

10.1557/proc-393-321 ◽

1995 ◽

Vol 393 ◽

Cited By ~ 4

Author(s):

Xiang-Yun Song ◽

Xi Chu ◽

Kimio Kinoshita

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

Phenol Formaldehyde ◽

High Capacity ◽

Lithium Ion ◽

X Ray Diffraction ◽

Transmission Electron ◽

High Degree

ABSTRACTHigh-capacity carbon electrodes for rechageable lithium-ion batteries were prepared by carbonization of thermosetting resins such as phenol-formaldehyde at temperatures between 500°C and 600°C. Their structures were characterized by high resolution transmission electron microscopy, in-situ transmission electron microscopy and x-ray diffraction analysis. These studies suggest that the carbons consist predominantly of disorganized (amorphous) phase. However evidence was found in carbon containing nickel cobalt oxide for the presence of organized graphite-like regions of parallel and curved layer planes. These graphitized structure usually appear as agglomerate particles which are composed of many smaller (100-nm diameter) particles. The high degree of graphitization is attributed to catalytic graphitization that occurs in the presence of the metal oxide.

Download Full-text

Molecular Mechanism and Current Therapies for Catecholaminergic Polymorphic Ventricular Tachycardia

10.5772/intechopen.98767 ◽

2021 ◽

Author(s):

Bin Liu ◽

Brian D. Tow ◽

Ingrid M. Bonilla

Keyword(s):

Ventricular Tachycardia ◽

Molecular Mechanisms ◽

Calcium Release ◽

Heart Diseases ◽

Catecholaminergic Polymorphic Ventricular Tachycardia ◽

Polymorphic Ventricular Tachycardia ◽

Release Channel ◽

Current Therapies ◽

Cardiac Disorders

The rhythmic contraction of the heart relies on tightly regulated calcium (Ca) release from the sarcoplasmic reticulum (SR) Ca release channel, Ryanodine receptor (RyR2). Genetic mutations in components of the calcium release unit such as RyR2, cardiac calsequestrin and other proteins have been shown to cause a genetic arrhythmic syndrome known as catecholaminergic polymorphic ventricular tachycardia (CPVT). This book chapter will focus on the following: (1) to describing CPVT as a stress-induced cardiac arrhythmia syndrome and its genetic causes. (2) Discussing the regulation of SR Ca release, and how dysregulation of Ca release contributes to arrhythmogenesis. (3) Discussing molecular mechanisms of CPVT with a focus on impaired Ca signaling refractoriness as a unifying mechanism underlying different genetic forms of CPVT. (4) Discussing pharmacological approaches as CPVT treatments as well as other potential future therapies. Since dysregulated SR Ca release has been implicated in multiple cardiac disorders including heart failure and metabolic heart diseases, knowledge obtained from CPVT studies will also shed light on the development of therapeutic approaches for these devastating cardiac dysfunctions as a whole.

Download Full-text

Calsequestrin 2 and arrhythmias

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00779.2011 ◽

2012 ◽

Vol 302 (6) ◽

pp. H1250-H1260 ◽

Cited By ~ 50

Author(s):

Michela Faggioni ◽

Björn C. Knollmann

Keyword(s):

Heart Diseases ◽

Cardiac Contractility ◽

Complex Function ◽

High Capacity ◽

Polymorphic Ventricular Tachycardia ◽

Pathophysiological Mechanism ◽

Functional Importance ◽

Gene Encoding ◽

Shed Light

Calsequestrin is the most abundant Ca-binding protein of the specialized endoplasmic reticulum found in muscle, the sarcoplasmic reticulum (SR). Calsequestrin binds Ca with high capacity and low affinity and importantly contributes to the mobilization of Ca during each contraction both in skeletal and cardiac muscle. Surprisingly, mutations in the gene encoding the cardiac isoform of calsequestrin (Casq2) have been associated with an inherited form of ventricular arrhythmia triggered by emotional or physical stress termed catecholaminergic polymorphic ventricular tachycardia (CPVT). Despite normal cardiac contractility and normal resting ECG, CPVT patients present with a high risk of sudden death at a young age. Here, we review recent new insights regarding the role of calsequestrin in genetic and acquired arrhythmia disorders. Mouse models of CPVT have shed light on the pathophysiological mechanism underlying CPVT. Casq2 is not only a Ca-storing protein as initially hypothesized, but it has a far more complex function in Ca handling and regulating SR Ca release channels. The functional importance of Casq2 interactions with other SR proteins and the importance of alterations in Casq2 trafficking are also being investigated. Reports of altered Casq2 trafficking in animal models of acquired heart diseases such as heart failure suggest that Casq2 may contribute to arrhythmia risk beyond genetic forms of Casq2 dysfunction.

Download Full-text