scholarly journals Kearns Sayre Syndrome: A Mitochondrial Disorder

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Anali Cisneros ◽  
Jeffrey O. Henderson
Keyword(s):  
Nuclear Dna ◽  
Single Gene ◽  
Mitochondrial Disorder ◽  
Genetic Material ◽  
Cardiac Conduction ◽  
Cardiac Complications ◽  
Biochemical Pathway ◽  
Kearns Sayre Syndrome ◽  
Disease Modifying Therapies

Kearns–Sayre syndrome (KSS) is a pleiotropic disorder caused by non-specific spontaneous deletion of a large amount of genetic material from mitochondrial DNA (mtDNA). Aside from patients having mtDNA defects there are also autosomal mutations in nuclear DNA, indicating KSS is not caused by a single gene mutation, but is most likely the result of mutations in genes forming a common biochemical pathway. KSS is characterized by a wide array of symptoms including: ophthalmoplegia, pigmentary retinopathy, ataxia, cardiac conduction defects that later develop into cardiac complications, and brain abnormalities. This review considers the association of deletions in mtDNA with a decrease in mitochondrial function and the pathogenetic role of the dysfunctional mitochondria by analyzing different variants of the mitochondrial genome. Despite there being no curative treatment for these patients, some possible disease modifying therapies have been proposed such as folinic acid supplementation and intravenous arginine therapy.

scholarly journals Human model of IRX5 mutations reveals key role for this transcription factor in ventricular conduction

2020 ◽  
Author(s):  
Zeina R Al Sayed ◽  
Robin Canac ◽  
Bastien Cimarosti ◽  
Carine Bonnard ◽  
Jean-Baptiste Gourraud ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Electrical Conduction ◽  
Sodium Current ◽  
Single Gene ◽  
Gene Mutations ◽  
Cardiac Conduction ◽  
Human Model ◽  
Loss Of Function ◽  
Cardiac Electrical Activity

Abstract Aims Several inherited arrhythmic diseases have been linked to single gene mutations in cardiac ion channels and interacting proteins. However, the mechanisms underlying most arrhythmias, are thought to involve altered regulation of the expression of multiple effectors. In this study, we aimed to examine the role of a transcription factor (TF) belonging to the Iroquois homeobox family, IRX5, in cardiac electrical function. Methods and results Using human cardiac tissues, transcriptomic correlative analyses between IRX5 and genes involved in cardiac electrical activity showed that in human ventricular compartment, IRX5 expression strongly correlated to the expression of major actors of cardiac conduction, including the sodium channel, Nav1.5, and Connexin 40 (Cx40). We then generated human-induced pluripotent stem cells (hiPSCs) derived from two Hamamy syndrome-affected patients carrying distinct homozygous loss-of-function mutations in IRX5 gene. Cardiomyocytes derived from these hiPSCs showed impaired cardiac gene expression programme, including misregulation in the control of Nav1.5 and Cx40 expression. In accordance with the prolonged QRS interval observed in Hamamy syndrome patients, a slower ventricular action potential depolarization due to sodium current reduction was observed on electrophysiological analyses performed on patient-derived cardiomyocytes, confirming the functional role of IRX5 in electrical conduction. Finally, a cardiac TF complex was newly identified, composed by IRX5 and GATA4, in which IRX5 potentiated GATA4-induction of SCN5A expression. Conclusion Altogether, this work unveils a key role for IRX5 in the regulation of human ventricular depolarization and cardiac electrical conduction, providing therefore new insights into our understanding of cardiac diseases.

A Comparative Study of the Desoxyribonuclease Activity in Adult and Embryonic Tissue

Development ◽  
1957 ◽  
Vol 5 (4) ◽  
pp. 377-395
Author(s):  
Gertrude Blumenthal
Keyword(s):  
Enzyme Activity ◽  
Comparative Study ◽  
Recent Work ◽  
Nuclear Dna ◽  
Genetic Material ◽  
Biological Role ◽  
Dnase Activity ◽  
Embryonic Tissue ◽  
Essential Components

Recent work has pointed to DNA as either the genetic material of the cell or one of its most essential components. As yet the biological role of the desoxyribonucleases (DNases), the only enzymes known to attack polymerized DNA, has not been established. The distribution of these enzymes throughout the animal and plant kingdoms appears to be widespread, and it is now recognized that they fall into at least two general classes (Schmidt, 1955). If these enzymes are involved in chromosome reduplication or in the genetic or developmental controls which may be attributed to nuclear DNA, it might be expected that the pattern of enzyme activity in rapidly growing, undifferentiated tissue and adult differentiated tissues would differ. For these reasons it was decided to investigate the type of DNase activity found in a developing embryonic system as compared to the activity of adult organs of the same species.

scholarly journals Horizontal Gene Transfer Involving Chloroplasts

2021 ◽  
Vol 22 (9) ◽  
pp. 4484
Author(s):  
Ewa Filip ◽  
Lidia Skuza
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Driving Force ◽  
Genetic Material ◽  
Adaptive Significance ◽  
Chloroplast Genomes ◽  
Organelle Genomes ◽  
Number Of Genes ◽  
Cellular Compartments

Horizontal gene transfer (HGT)- is defined as the acquisition of genetic material from another organism. However, recent findings indicate a possible role of HGT in the acquisition of traits with adaptive significance, suggesting that HGT is an important driving force in the evolution of eukaryotes as well as prokaryotes. It has been noted that, in eukaryotes, HGT is more prevalent than originally thought. Mitochondria and chloroplasts lost a large number of genes after their respective endosymbiotic events occurred. Even after this major content loss, organelle genomes still continue to lose their own genes. Many of these are subsequently acquired by intracellular gene transfer from the original plastid. The aim of our review was to elucidate the role of chloroplasts in the transfer of genes. This review also explores gene transfer involving mitochondrial and nuclear genomes, though recent studies indicate that chloroplast genomes are far more active in HGT as compared to these other two DNA-containing cellular compartments.

scholarly journals Sperm Cryopreservation in American Flamingo (Phoenicopterus Ruber): Influence of Cryoprotectants and Seminal Plasma Removal

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 203
Author(s):  
María Gemma Millán de la Blanca ◽  
Eva Martínez-Nevado ◽  
Cristina Castaño ◽  
Juncal García ◽  
Berenice Bernal ◽  
...  
Keyword(s):  
Seminal Plasma ◽  
Genetic Material ◽  
First Year ◽  
Sperm Cryopreservation ◽  
Straight Line ◽  
The Family ◽  
Second Year ◽  
American Flamingo ◽  
Phoenicopterus Ruber

The American flamingo is a useful model for the development of successful semen cryopreservation procedures to be applied to threatened related species from the family Phoenicopteridae, and to permit genetic material banking. Current study sought to develop effective sperm cryopreservation protocols through examining the influences of two permeating cryoprotectants and the seminal plasma removal. During two consecutive years (April), semen samples were collected and frozen from American flamingos. In the first year, the effect of two permeating cryoprotectants, DMA (dimethylacetamide) (6%) or Me2SO (dimethylsulphoxide) (8%), on frozen–thawed sperm variables were compared in 21 males. No differences were seen between DMA and Me2SO for sperm motility, sperm viability, and DNA fragmentation after thawing. In the second year, the role of seminal plasma on sperm cryoresistance was investigated in 31 flamingos. Sperm samples were cryopreserved with and without seminal plasma, using Me2SO (8%) as a cryoprotectant. The results showed that samples with seminal plasma had higher values than samples without seminal plasma for the following sperm variables: Straight line velocity (22.40 µm/s vs. 16.64 µm/s), wobble (75.83% vs. 69.40%), (p < 0.05), linearity (62.73% vs. 52.01%) and straightness (82.38% vs. 73.79%) (p < 0.01); but acrosome integrity was lower (55.56% vs. 66.88%) (p < 0.05). The cryoresistance ratio (CR) was greater in samples frozen with seminal plasma than without seminal plasma for CR-progressive motility (138.72 vs. 54.59), CR-curvilinear velocity (105.98 vs. 89.32), CR-straight line velocity (152.77 vs. 112.58), CR-average path velocity (122.48 vs. 98.12), CR-wobble (111.75 vs. 102.04) (p < 0.05), CR-linearity (139.41 vs. 113.18), and CR-straightness (124.02 vs. 109.97) (p < 0.01). This research demonstrated that there were not differences between Me2SO and DMA to successful freezing sperm of flamingos; seminal plasma removal did not provide a benefit for sperm cryopreservation.

scholarly journals The Role of Mitochondria in Carcinogenesis

2021 ◽  
Vol 22 (10) ◽  
pp. 5100
Author(s):  
Paulina Kozakiewicz ◽  
Ludmiła Grzybowska-Szatkowska ◽  
Marzanna Ciesielka ◽  
Jolanta Rzymowska
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Dna ◽  
Nuclear Dna ◽  
Dna Polymorphisms ◽  
Gene Encoding ◽  
Dna Mutations ◽  
Nadh Ubiquinone Oxidoreductase ◽  
Gene Coi ◽  
The Impact

The mitochondria are essential for normal cell functioning. Changes in mitochondrial DNA (mtDNA) may affect the occurrence of some chronic diseases and cancer. This process is complex and not entirely understood. The assignment to a particular mitochondrial haplogroup may be a factor that either contributes to cancer development or reduces its likelihood. Mutations in mtDNA occurring via an increase in reactive oxygen species may favour the occurrence of further changes both in mitochondrial and nuclear DNA. Mitochondrial DNA mutations in postmitotic cells are not inherited, but may play a role both in initiation and progression of cancer. One of the first discovered polymorphisms associated with cancer was in the gene NADH-ubiquinone oxidoreductase chain 3 (mt-ND3) and it was typical of haplogroup N. In prostate cancer, these mutations and polymorphisms involve a gene encoding subunit I of respiratory complex IV cytochrome c oxidase subunit 1 gene (COI). At present, a growing number of studies also address the impact of mtDNA polymorphisms on prognosis in cancer patients. Some of the mitochondrial DNA polymorphisms occur in both chronic disease and cancer, for instance polymorphism G5913A characteristic of prostate cancer and hypertension.

scholarly journals Accelerating diagnosis of Parkinson’s disease through risk prediction

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
William Yuan ◽  
Brett Beaulieu-Jones ◽  
Richard Krolewski ◽  
Nathan Palmer ◽  
Christine Veyrat-Follet ◽  
...  
Keyword(s):  
Machine Learning ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Subsequent Development ◽  
Time Compression ◽  
Disease Modifying Therapies ◽  
Machine Learning Approach ◽  
Diagnostic Window

Abstract Background Characterization of prediagnostic Parkinson’s Disease (PD) and early prediction of subsequent development are critical for preventive interventions, risk stratification and understanding of disease pathology. This study aims to characterize the role of the prediagnostic period in PD and, using selected features from this period as novel interception points, construct a prediction model to accelerate the diagnosis in a real-world setting. Methods We constructed two sets of machine learning models: a retrospective approach highlighting exposures up to 5 years prior to PD diagnosis, and an alternative model that prospectively predicted future PD diagnosis from all individuals at their first diagnosis of a gait or tremor disorder, these being features that appeared to represent the initiation of a differential diagnostic window. Results We found many novel features captured by the retrospective models; however, the high accuracy was primarily driven from surrogate diagnoses for PD, such as gait and tremor disorders, suggesting the presence of a distinctive differential diagnostic period when the clinician already suspected PD. The model utilizing a gait/tremor diagnosis as the interception point, achieved a validation AUC of 0.874 with potential time compression to a future PD diagnosis of more than 300 days. Comparisons of predictive diagnoses between the prospective and prediagnostic cohorts suggest the presence of distinctive trajectories of PD progression based on comorbidity profiles. Conclusions Overall, our machine learning approach allows for both guiding clinical decisions such as the initiation of neuroprotective interventions and importantly, the possibility of earlier diagnosis for clinical trials for disease modifying therapies.

Platelets in cancer development and diagnosis

2018 ◽  
Vol 46 (6) ◽  
pp. 1517-1527 ◽  
Author(s):  
Annalisa Contursi ◽  
Rosalia Grande ◽  
Melania Dovizio ◽  
Annalisa Bruno ◽  
Rosa Fullone ◽  
...  
Keyword(s):  
Cancer Detection ◽  
Immune Escape ◽  
Genetic Material ◽  
Antiplatelet Agents ◽  
Therapeutic Drug ◽  
Target Cells ◽  
Tumor Immune Escape ◽  
New Strategy ◽  
Tumor Drugs

Platelets are involved in the development and progression of cancer through several mechanisms. Platelet activation at the site of tissue damage contributes to the initiation of a cascade of events which promote tumorigenesis. In fact, platelets release a wide array of proteins, including growth and angiogenic factors, lipids and extracellular vesicles rich in genetic material, which can mediate the induction of phenotypic changes in target cells, such as immune, stromal and tumor cells, and promote carcinogenesis and metastasis formation. Importantly, the role of platelets in tumor immune escape has been described. These lines of evidence open the way to novel strategies to fight cancer based on the use of antiplatelet agents. In addition to their ability to release factors, platelets are able of up-taking proteins and genetic material present in the bloodstream. Platelets are like ‘sentinels’ of the disease state. The evaluation of proteomics and transcriptomics signature of platelets and platelet-derived microparticles could represent a new strategy for the development of biomarkers for early cancer detection and/or therapeutic drug monitoring in cancer chemotherapy. Owing to the ability of platelets to interact with cancer cells and to deliver their cargo, platelets have been proposed as a ‘biomimetic drug delivery system’ for anti-tumor drugs to prevent the occurrence of off-target adverse events associated with the use of traditional chemotherapy.

Reaching Future Scientists, Consumers, & Citizens

2014 ◽  
Vol 76 (6) ◽  
pp. 379-383 ◽  
Author(s):  
Melissa A. Hicks ◽  
Rebecca J. Cline ◽  
Angela M. Trepanier
Keyword(s):  
Personalized Medicine ◽  
Genetic Basis ◽  
Genetic Disorders ◽  
Single Gene ◽  
Personal Health ◽  
Adult Onset ◽  
Biology Textbooks ◽  
Multifactorial Diseases ◽  
Single Gene Disorders

An understanding of how genomics information, including information about risk for common, multifactorial disease, can be used to promote personal health (personalized medicine) is becoming increasingly important for the American public. We undertook a quantitative content analysis of commonly used high school textbooks to assess how frequently the genetic basis of common multifactorial diseases was discussed compared with the “classic” chromosomal–single gene disorders historically used to teach the concepts of genetics and heredity. We also analyzed the types of conditions or traits that were discussed. We identified 3957 sentences across 11 textbooks that addressed multifactorial and “classic” genetic disorders. “Classic” gene disorders were discussed relatively more frequently than multifactorial diseases, as was their genetic basis, even after we enriched the sample to include five adult-onset conditions common in the general population. Discussions of the genetic or hereditary components of multifactorial diseases were limited, as were discussions of the environmental components of these conditions. Adult-onset multifactorial diseases are far more common in the population than chromosomal or single-gene disorders; many are potentially preventable or modifiable. As such, they are targets for personalized medical approaches. The limited discussion in biology textbooks of the genetic basis of multifactorial conditions and the role of environment in modifying genetic risk may limit the public’s understanding and use of personalized medicine.

scholarly journals Study of Staphylococcus aureusPathogenic Genes by Transfer and Expression in the Less Virulent Organism Streptococcus gordonii

2001 ◽  
Vol 69 (2) ◽  
pp. 657-664 ◽  
Author(s):  
P. Stutzmann Meier ◽  
J. M. Entenza ◽  
P. Vaudaux ◽  
P. Francioli ◽  
M. P. Glauser ◽  
...  
Keyword(s):  
Single Gene ◽  
Individual Factors ◽  
Gene Products ◽  
Streptococcus Gordonii ◽  
Pathogenic Role ◽  
Gain Of Function ◽  
Function Strategy

ABSTRACT Because Staphylococcus aureus strains contain multiple virulence factors, studying their pathogenic role by single-gene inactivation generated equivocal results. To circumvent this problem, we have expressed specific S. aureus genes in the less virulent organism Streptococcus gordonii and tested the recombinants for a gain of function both in vitro and in vivo. Clumping factor A (ClfA) and coagulase were investigated. Both gene products were expressed functionally and with similar kinetics during growth by streptococci and staphylococci. ClfA-positive S. gordoniiwas more adherent to platelet-fibrin clots mimicking cardiac vegetations in vitro and more infective in rats with experimental endocarditis (P < 0.05). Moreover, deletingclfA from clfA-positive streptococcal transformants restored both the low in vitro adherence and the low in vivo infectivity of the parent. Coagulase-positive transformants, on the other hand, were neither more adherent nor more infective than the parent. Furthermore, coagulase did not increase the pathogenicity ofclfA-positive streptococci when both clfA andcoa genes were simultaneously expressed in an artificial minioperon in streptococci. These results definitively attribute a role for ClfA, but not coagulase, in S. aureus endovascular infections. This gain-of-function strategy might help solve the role of individual factors in the complex the S. aureus-host relationship.

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