scholarly journals Absence of a primary role for TTN missense variants in arrhythmogenic cardiomyopathy: From a clinical and pathological perspective

2018 ◽  
Vol 41 (5) ◽  
pp. 615-622 ◽  
Author(s):  
Kai Chen ◽  
Jiangping Song ◽  
Zhen Wang ◽  
Man Rao ◽  
Liang Chen ◽  
...  
Keyword(s):  
Primary Role ◽  
Arrhythmogenic Cardiomyopathy ◽  
Missense Variants

scholarly journals The Role of MicroRNAs in Arrhythmogenic Cardiomyopathy: Biomarkers or Innocent Bystanders of Disease Progression?

2020 ◽  
Vol 21 (17) ◽  
pp. 6434
Author(s):  
Maria Bueno Marinas ◽  
Rudy Celeghin ◽  
Marco Cason ◽  
Gaetano Thiene ◽  
Cristina Basso ◽  
...  
Keyword(s):  
Gene Expression Regulation ◽  
Phenotypic Variability ◽  
Incomplete Penetrance ◽  
Primary Role ◽  
Arrhythmogenic Cardiomyopathy ◽  
Small Noncoding Rnas ◽  
Early Disease Detection ◽  
Pathogenic Variants ◽  
Fatty Replacement ◽  
Genes Encoding

Arrhythmogenic cardiomyopathy (AC) is an inherited cardiac disease characterized by a progressive fibro-fatty replacement of the working myocardium and by life-threatening arrhythmias and risk of sudden cardiac death. Pathogenic variants are identified in nearly 50% of affected patients mostly in genes encoding for desmosomal proteins. AC incomplete penetrance and phenotypic variability advocate that other factors than genetics may modulate the disease, such as microRNAs (miRNAs). MiRNAs are small noncoding RNAs with a primary role in gene expression regulation and network of cellular processes. The implication of miRNAs in AC pathogenesis and their role as biomarkers for early disease detection or differential diagnosis has been the objective of multiple studies employing diverse designs and methodologies to detect miRNAs and measure their expression levels. Here we summarize experiments, evidence, and flaws of the different studies and hitherto knowledge of the implication of miRNAs in AC pathogenesis and diagnosis.

Missense variants in the spectrin repeat domain of DSP are associated with arrhythmogenic cardiomyopathy: A family report and systematic review

2020 ◽  
Vol 182 (10) ◽  
pp. 2359-2368
Author(s):  
Steffany Grondin ◽  
Avedis‐Christ Wazirian ◽  
Paloma Jorda ◽  
Donato G. Terrone ◽  
Johannie Gagnon ◽  
...  
Keyword(s):  
Systematic Review ◽  
Arrhythmogenic Cardiomyopathy ◽  
Spectrin Repeat ◽  
Missense Variants ◽  
Repeat Domain

scholarly journals Evaluating the relevance of sequence conservation in the prediction of pathogenic missense variants

2021 ◽  
Author(s):  
Emidio Capriotti ◽  
Piero Fariselli
Keyword(s):  
Protein Sequence ◽  
Prediction Models ◽  
Evolutionary Information ◽  
Large Set ◽  
Primary Role ◽  
Sequence Profile ◽  
Sequence Alignments ◽  
Multiple Sequence ◽  
Missense Variants ◽  
The Impact

Abstract Evolutionary information is the primary tool for detecting functional conservation in nucleic acid and protein. This information has been extensively used to predict structure, interactions and functions in macromolecules. Pathogenicity prediction models rely on multiple sequence alignment information at different levels. However, most accurate genome-wide variant deleteriousness ranking algorithms consider different features to assess the impact of variants. Here, we analyze three different ways of extracting evolutionary information from sequence alignments in the context of pathogenicity predictions at DNA and protein levels. We showed that protein sequence-based information is slightly more informative in the annotation of Clinvar missense variants than those obtained at the DNA level. Furthermore, to achieve the performance of state-of-the-art methods, such as CADD, the conservation of reference and variant, encoded as frequencies of reference/alternate alleles or wild-type/mutant residues, should be included. Our results on a large set of missense variants show that a basic method based on three input features derived from the protein sequence profile performs similarly to the CADD algorithm which uses hundreds of genomic features. This observation indicates that for missense variants, evolutionary information, when properly encoded, plays the primary role in ranking pathogenicity.

Structure of Myosin Subfragment-1 from Electron Microscopy and Crystallography

1988 ◽  
Vol 46 ◽  
pp. 156-157
Author(s):  
Donald A. Winkelmann
Keyword(s):  
Electron Microscopy ◽  
Molecular Weight ◽  
Actin Filaments ◽  
Light Chains ◽  
Myosin Filament ◽  
Primary Role ◽  
Heavy Chains ◽  
Myosin Subfragment ◽  
Myosin Subfragment 1 ◽  
Globular Head

The primary role of the interaction of actin and myosin is the generation of force and motion as a direct consequence of the cyclic interaction of myosin crossbridges with actin filaments. Myosin is composed of six polypeptides: two heavy chains of molecular weight 220,000 daltons and two pairs of light chains of molecular weight 17,000-23,000. The C-terminal portions of the myosin heavy chains associate to form an α-helical coiled-coil rod which is responsible for myosin filament formation. The N-terminal portion of each heavy chain associates with two different light chains to form a globular head that binds actin and hydrolyses ATP. Myosin can be fragmented by limited proteolysis into several structural and functional domains. It has recently been demonstrated using an in vitro movement assay that the globular head domain, subfragment-1, is sufficient to cause sliding movement of actin filaments.The discovery of conditions for crystallization of the myosin subfragment-1 (S1) has led to a systematic analysis of S1 structure by x-ray crystallography and electron microscopy. Image analysis of electron micrographs of thin sections of small S1 crystals has been used to determine the structure of S1 in the crystal lattice.

Immunogold localization of calmodulin in root caps of the maize Cultivar Merit

1990 ◽  
Vol 48 (3) ◽  
pp. 674-675
Author(s):  
P.T. Nguyen ◽  
C. Uphoff ◽  
C.L. Stinemetz
Keyword(s):  
Calcium Binding ◽  
Calcium Transport ◽  
Primary Role ◽  
Immunogold Localization ◽  
Root Tips ◽  
Electrical Currents ◽  
Considerable Evidence ◽  
Maize Cultivar ◽  
Gravity Response ◽  
Induced Changes

Considerable evidence suggest that the calcium-binding protein calmodulin (CaM) may mediate calcium action and/or transport important in the gravity response of plants. Calmodulin is present in both shoots and roots and is capable of regulating calcium transport in plant vesicles. In roots calmodulin is concentrated in the tip, the gravisensing region of the root; and is reported to be closely associated with amyloplasts, organelles suggested to play a primary role in gravi-perception. Inhibitors of CaM such as chlorpromazine, calmidazolium, and compound 48/80 interfere with the gravitropic response of both snoots and roots. The magnitude of the inhibition corresponded well with the extent to which the drug binds to endogenous CaM. Compound 48/80 and calmidazolium block gravi-induced changes in electrical currents across root tips, a phenomenon thought to be associated with the sensing of the gravity stimulus.In this study, we have investigated the subcellular distribution of CaM in graviresponsive and non-graviresponsive root caps of the maize cultivar Merit.

The Psychosocial Aspects of Feeding in the Neonatal Intensive Care Unit and Beyond

2019 ◽  
Vol 4 (6) ◽  
pp. 1507-1515
Author(s):  
Lauren L. Madhoun ◽  
Robert Dempster
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Neonatal Intensive Care Unit ◽  
Hospital Discharge ◽  
Neonatal Intensive Care ◽  
Oral Feeding ◽  
Medical Attention ◽  
Primary Role ◽  
Speech Language Pathologists ◽  
The Family

Purpose Feeding challenges are common for infants in the neonatal intensive care unit (NICU). While sufficient oral feeding is typically a goal during NICU admission, this can be a long and complicated process for both the infant and the family. Many of the stressors related to feeding persist long after hospital discharge, which results in the parents taking the primary role of navigating the infant's course to ensure continued feeding success. This is in addition to dealing with the psychological impact of having a child requiring increased medical attention and the need to continue to fulfill the demands at home. In this clinical focus article, we examine 3 main areas that impact psychosocial stress among parents with infants in the NICU and following discharge: parenting, feeding, and supports. Implications for speech-language pathologists working with these infants and their families are discussed. A case example is also included to describe the treatment course of an infant and her parents in the NICU and after graduation to demonstrate these points further. Conclusion Speech-language pathologists working with infants in the NICU and following hospital discharge must realize the family context and psychosocial considerations that impact feeding progression. Understanding these factors may improve parental engagement to more effectively tailor treatment approaches to meet the needs of the child and family.

Clues for Understanding the Structure and Function of a Prototypic Human Integrin: The Platelet Glycoprotein IIb/IIIa Complex

1994 ◽  
Vol 72 (01) ◽  
pp. 001-015 ◽  
Author(s):  
Juan J Calvete
Keyword(s):  
Structure Function ◽  
Thrombus Formation ◽  
Platelet Glycoprotein ◽  
Primary Role ◽  
Clot Retraction ◽  
Inhibitory Peptide ◽  
Rgd Sequence ◽  
Platelet Receptor ◽  
Adhesive Proteins ◽  
And Function

SummaryThe glycoprotein (GP) IIb/IIIa, a Ca2+-dependent heterodimer, is the major integrin on the platelet plasma membrane. On resting platelets GPIIb/IIIa is maintained in an inactive conformation and serves as a low affinity adhesion receptor for surface-coated fibrinogen, whereas upon platelet activation signals within the cytoplasma alter the receptor function of GPIIb/IIIa (inside-out signalling), which undergoes a measurable conformational change within its exoplasmic domains, and becomes a competent receptor for soluble fibrinogen and some other RGD sequence-containing plasma adhesive proteins. Upon ligand binding, further structural alterations trigger the association of receptor-occupied GPIIb/IIIa complexes with themselves within the plane of the membrane. The simultaneous binding of dimeric fibrinogen molecules to GPIIb/IIIa clusters on adjacent platelets leads to platelet aggregation, which promotes attachment of fibrinogen-GPIIb/IIIa clusters to the cytoskeleton (outside-in signalling). This, in turn, provides the necessary physical link for clot retraction to occur, and generates a cascade of intracellular biochemical reactions which result in the formation of a multiprotein signalling complex at the cytoplasmic domains of GPIIb/IIIa. Glycoprotein IMIIa, also called αIIbβ3 in the integrin nomenclature, plays thus a primary role in both platelet adhesion and thrombus formation at the site of vascular injury. In addition, the human glycoprotein Ilb/IIIa complex is the most thoroughly studied integrin receptor, its molecular biology and major features of its primary structure having been elucidated mainly during the last six years. Furthermore, localization of functionally relevant monoclonal antibody epitopes, determination of the cross-linking sites of inhibitory peptide ligands, proteolytic dissection of the isolated integrin, and analysis of natural and artificial GPIIb/IIIa mutants have recently provided a wealth of information regarding structure-function relationships of human GPIIb/IIIa. The aim of this review is to summarize these many structural and functional data in the perspective of an emerging model. Although most of the interpretations based on structural elements of this initial biochemical model require independent confirmation, they may help us to understand the structure-function relationship of this major platelet receptor, and of other members of the integrin superfamily, as well as to perform further investigations in order to test current hypotheses.

Blood Analysis Requests of Patients’ and Clinical Reflections in Primary Care

2020 ◽  
Vol 9 (2) ◽  
pp. 96-102
Author(s):  
Zerrin Gamsizkan ◽  
Mehmet Ali Sungur ◽  
Yasemin Çayır
Keyword(s):  
Chronic Disease ◽  
Blood Test ◽  
Family Health ◽  
Cross Sectional Study ◽  
Blood Analysis ◽  
Primary Role ◽  
Cross Sectional ◽  
High Expectations ◽  
Blood Tests ◽  
Study Results

Aim: The aim of the study is to determine the factors that may affect the demands of patients who come with the request to have a blood test without any chronic disease or a planned examination check. Methods: The data of this descriptive, cross-sectional study, were collected with a questionnaire that was prepared to examine the opinions of the patients who claim to have a blood test by coming to the family health center without any complaints. Patients over 18 years of age, who did not have any chronic disease and had no scheduled examination appointments were included in the study. Results: A total of 278 patients who wanted to have a blood test within the 6-months period were included in the study. Female patients who wanted to have a blood test were significantly more than male patients. When we look at the causes of patients who wanted to have a blood test; 61.2% (n=170) patients stated that they are concerned about their health and 6.1% (n=17) stated that they were affected by media warnings. There was no significant relationship between the frequency of blood test requests of patients and their age, gender, education, and general health status. Conclusion: Patients with high expectations and anxiety may be more willing to perform blood tests at inappropriate intervals. Family physicians, whose primary role is preventive medicine, have consultancy and information duties in order to protect their patients from the risk of over-examination and diagnosis. Keywords: blood tests, patient, screening, routine diagnostic tests

Sports Photography and Historical Development

2018 ◽  
Vol 5 (1) ◽  
pp. 93-115
Author(s):  
Miloš Stamenković
Keyword(s):  
Historical Development ◽  
Emotional Reaction ◽  
Main Role ◽  
Primary Role

SummarySports photography undoubtedly has a significant place in sports press and publicism. It’s main and primary role is to present sports to the readers as art, which it is. Sport is characterized by dynamic and varied movements, and the main role of sports photography is reflected in the fact that it is in this way that sport shows its essence. Having in mind that photography tells more than a thousand words it sends a clear message to the reader as well to people who are informed about events via sports portals. Sports photography is a multidimensional art for many reasons. When we say “multi”, it primarily refers to a wider range that sports photography has to offer, which means sports photography is not only directed at presenting athletes on the move and the main actors who contribute to achieving the results by their engagement – it also has the role of sports “psychophotography” which is an analysis and capture of the emotional reaction of an athlete after winning or losing from the opposing team.

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