Scleroderma and scleroderma-like syndromes.
Systemic sclerosis is a systemic connective tissue disease whose main pathophysiological mechanism is a progressive fibrosis of internal organs and skin leading to thickening and induration. Blood ves...
Protéines mitochondriales : Questions médicales fréquentes
Questions fréquentes et termes MeSH associés
Diagnostic 5
#1
Comment diagnostiquer une dysfonction mitochondriale ?
Un diagnostic peut inclure des tests génétiques, des biopsies musculaires et des analyses biochimiques.
#2
Quels tests sanguins sont utilisés pour évaluer les protéines mitochondriales ?
Des tests de lactate, pyruvate et des enzymes spécifiques peuvent être effectués.
#3
Quels symptômes indiquent une maladie mitochondriale ?
Fatigue, faiblesse musculaire, troubles neurologiques et problèmes cardiaques peuvent indiquer une maladie.
#4
Les tests génétiques sont-ils fiables pour les maladies mitochondriales ?
Oui, les tests génétiques peuvent identifier des mutations spécifiques liées aux maladies mitochondriales.
#5
Quel rôle joue l'imagerie dans le diagnostic mitochondrial ?
L'imagerie par résonance magnétique (IRM) peut aider à visualiser des anomalies cérébrales.
Symptômes 5
#1
Quels sont les symptômes courants des maladies mitochondriales ?
Les symptômes incluent fatigue, douleurs musculaires, troubles de la vision et épilepsie.
#2
Les troubles cognitifs sont-ils liés aux protéines mitochondriales ?
Oui, des troubles cognitifs peuvent survenir en raison de dysfonctionnements mitochondriaux.
#3
Comment la myopathie mitochondriale se manifeste-t-elle ?
Elle se manifeste par une faiblesse musculaire, des crampes et une intolérance à l'exercice.
#4
Les troubles cardiaques sont-ils fréquents dans les maladies mitochondriales ?
Oui, des cardiomyopathies peuvent se développer en raison de dysfonctionnements mitochondriaux.
#5
Les symptômes varient-ils selon l'âge d'apparition ?
Oui, les symptômes peuvent varier considérablement selon l'âge d'apparition de la maladie.
Prévention 5
#1
Peut-on prévenir les maladies mitochondriales ?
Certaines maladies génétiques ne peuvent pas être prévenues, mais un mode de vie sain aide.
#2
L'exercice physique peut-il réduire les risques ?
Oui, l'exercice régulier peut améliorer la santé mitochondriale et réduire les risques.
#3
Les antioxydants jouent-ils un rôle préventif ?
Oui, les antioxydants peuvent protéger les mitochondries des dommages oxydatifs.
#4
Une alimentation équilibrée est-elle importante ?
Oui, une alimentation riche en nutriments soutient la santé mitochondriale.
#5
Les dépistages précoces sont-ils recommandés ?
Oui, le dépistage précoce peut aider à identifier les risques et à intervenir rapidement.
Traitements 5
#1
Quels traitements sont disponibles pour les maladies mitochondriales ?
Les traitements incluent des suppléments, des thérapies symptomatiques et des approches nutritionnelles.
#2
Les coenzymes Q10 sont-elles bénéfiques ?
Oui, le coenzyme Q10 peut améliorer la fonction mitochondriale et réduire les symptômes.
#3
La thérapie génique est-elle une option pour ces maladies ?
La thérapie génique est en recherche, mais elle pourrait offrir des solutions futures.
#4
Les régimes alimentaires peuvent-ils aider ?
Oui, des régimes spécifiques peuvent soutenir la fonction mitochondriale et améliorer les symptômes.
#5
Les traitements varient-ils selon le type de maladie mitochondriale ?
Oui, les traitements doivent être adaptés au type spécifique de maladie mitochondriale.
Complications 5
#1
Quelles complications peuvent survenir avec les maladies mitochondriales ?
Les complications incluent des troubles neurologiques, cardiaques et endocriniens.
#2
Les maladies mitochondriales peuvent-elles affecter la fertilité ?
Oui, certaines maladies mitochondriales peuvent entraîner des problèmes de fertilité.
#3
Les complications peuvent-elles être gérées ?
Certaines complications peuvent être gérées avec des traitements symptomatiques appropriés.
#4
Les maladies mitochondriales augmentent-elles le risque de cancer ?
Certaines études suggèrent un lien entre dysfonction mitochondriale et risque accru de cancer.
#5
Les complications cardiovasculaires sont-elles fréquentes ?
Oui, les maladies mitochondriales peuvent entraîner des cardiomyopathies et d'autres complications.
Facteurs de risque 5
#1
Quels sont les facteurs de risque pour les maladies mitochondriales ?
Les facteurs incluent des antécédents familiaux, des mutations génétiques et des expositions environnementales.
#2
L'âge est-il un facteur de risque ?
Oui, certaines maladies mitochondriales se manifestent plus fréquemment avec l'âge.
#3
Les facteurs environnementaux influencent-ils les maladies mitochondriales ?
Oui, l'exposition à des toxines peut augmenter le risque de dysfonction mitochondriale.
#4
Le stress oxydatif est-il un facteur de risque ?
Oui, le stress oxydatif peut endommager les mitochondries et contribuer à des maladies.
#5
Les habitudes alimentaires peuvent-elles influencer le risque ?
Oui, une alimentation pauvre en nutriments peut augmenter le risque de dysfonction mitochondriale.
Contenu validé par Dr Olivier Menir
Expert en Médecine, Optimisation des Parcours de Soins et Révision Médicale
Validation scientifique effectuée le 07/04/2025
Contenu vérifié selon les dernières recommandations médicales
Sous-catégories
25 au total
└─
Aldehyde dehydrogenase, mitochondrial
Aldehyde Dehydrogenase, MitochondrialD000071396 -
D12.776.575.093
└─
Mitochondrial creatine kinase
Creatine Kinase, Mitochondrial FormD052281 -
D12.776.575.186
└─
DNA Polymerase gamma
DNA Polymerase gammaD000074002 -
D12.776.575.280
└─
Ferrochelatase
FerrochelataseD005294 -
D12.776.575.562
└─
Protéines de transport de la membrane mitochondriale
Mitochondrial Membrane Transport ProteinsD033681 -
D12.776.575.750
└─
Protéine trifonctionnelle mitochondriale
Mitochondrial Trifunctional ProteinD063991 -
D12.776.575.765
└─
Nucleoside diphosphate kinase D
Nucleoside Diphosphate Kinase DD061107 -
D12.776.575.781
└─
Peroxiredoxin III
Peroxiredoxin IIID061105 -
D12.776.575.812
└─
Prohibitines
ProhibitinsD000091402 -
D12.776.575.844
└─
Sirtuine-3
Sirtuin 3D056566 -
D12.776.575.875
└─└─
Mitochondrial ADP, ATP Translocases
Mitochondrial ADP, ATP TranslocasesD000226 -
D12.776.575.750.500
└─└─
Pore de transition de perméabilité mitochondriale
Mitochondrial Permeability Transition PoreD000083162 -
D12.776.575.750.563
└─└─
Protéines du complexe d'import des protéines précurseurs mitochondriales
Mitochondrial Precursor Protein Import Complex ProteinsD000090622 -
D12.776.575.750.594
└─└─
Mitochondrial Proton-Translocating ATPases
Mitochondrial Proton-Translocating ATPasesD025261 -
D12.776.575.750.625
└─└─
Protéines de découplage mitochondrial
Mitochondrial Uncoupling ProteinsD000071245 -
D12.776.575.750.688
└─└─
Canal anionique-1 voltage-dépendant
Voltage-Dependent Anion Channel 1D050995 -
D12.776.575.750.750
└─└─
Canal anionique-2 voltage-dépendant
Voltage-Dependent Anion Channel 2D050996 -
D12.776.575.750.875
└─└─
Sous-unité alpha de la protéine trifonctionnelle mitochondriale
Mitochondrial Trifunctional Protein, alpha SubunitD063992 -
D12.776.575.765.200
└─└─
Sous-unité bêta de la protéine trifonctionnelle mitochondriale
Mitochondrial Trifunctional Protein, beta SubunitD063993 -
D12.776.575.765.500
└─└─└─
Translocateur-1 de nucléotides adényliques
Adenine Nucleotide Translocator 1D033741 -
D12.776.575.750.500.100
└─└─└─
Translocateur-2 de nucléotides adényliques
Adenine Nucleotide Translocator 2D033742 -
D12.776.575.750.500.200
└─└─└─
Translocateur-3 de nucléotides adényliques
Adenine Nucleotide Translocator 3D033781 -
D12.776.575.750.500.300
└─└─└─
Protéine-1 de découplage
Uncoupling Protein 1D000071256 -
D12.776.575.750.688.500
└─└─└─
Protéine-2 de découplage
Uncoupling Protein 2D000071246 -
D12.776.575.750.688.750
└─└─└─
Protéine-3 de découplage
Uncoupling Protein 3D000071247 -
D12.776.575.750.688.875
Auteurs principaux
Thomas Becker
3 publications dans cette catégorie
Affiliations :
- Institute of Biochemistry und Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
- CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
Publications dans "Protéines mitochondriales" :
-
Porins as helpers in mitochondrial protein translocation.
Biological chemistry
-
Protein Quality Control at the Mitochondrial Surface.
Frontiers in cell and developmental biology 2021-12-03
-
Mitochondrial protein translocation-associated degradation.
Nature 2019-05-22
Johannes M Herrmann
3 publications dans cette catégorie
Affiliations :
- Cell Biology, University of Kaiserslautern, Kaiserslautern, Germany. Electronic address: hannes.herrmann@biologie.uni-kl.de.
Publications dans "Protéines mitochondriales" :
-
Cytosolic Events in the Biogenesis of Mitochondrial Proteins.
Trends in biochemical sciences 2020-05-11
-
The ER protein Ema19 facilitates the degradation of nonimported mitochondrial precursor proteins.
Molecular biology of the cell 2021-02-17
-
The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis.
The Journal of cell biology 2023-09-08
Timothy E Shutt
2 publications dans cette catégorie
Affiliations :
- Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
- Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB T2N 4N1, Canada.
- Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
- Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial Protein Homeostasis and Cardiomyopathy.
International journal of molecular sciences 2022-03-20
-
Mitochondrial quality control pathways sense mitochondrial protein import.
Trends in endocrinology and metabolism: TEM 2023-12-15
Cole M Haynes
2 publications dans cette catégorie
Affiliations :
- Molecular, Cell and Cancer Biology, UMass-Chan Medical School, Worcester, MA 01655, USA.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial dysfunction, aging, and the mitochondrial unfolded protein response in Caenorhabditis elegans.
Genetics
-
Signaling and Regulation of the Mitochondrial Unfolded Protein Response.
Cold Spring Harbor perspectives in biology 2019-06-03
Yang Yang
2 publications dans cette catégorie
Affiliations :
- Stem Cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland.
- School of Life and Health Sciences, Faculty of Science, The Chinese University of Hong Kong, 518172 Shenzhen, China.
Publications dans "Protéines mitochondriales" :
-
Small mitochondrial protein NERCLIN regulates cardiolipin homeostasis and mitochondrial ultrastructure.
Proceedings of the National Academy of Sciences of the United States of America 2023-07-18
-
Unfolded proteins in the mitochondria activate HRI and inhibit mitochondrial protein translation.
Cellular signalling 2024-08-19
Yury S Bykov
2 publications dans cette catégorie
Affiliations :
- Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.
Publications dans "Protéines mitochondriales" :
-
Cytosolic Events in the Biogenesis of Mitochondrial Proteins.
Trends in biochemical sciences 2020-05-11
-
The ER protein Ema19 facilitates the degradation of nonimported mitochondrial precursor proteins.
Molecular biology of the cell 2021-02-17
Maya Schuldiner
2 publications dans cette catégorie
Affiliations :
- Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. Electronic address: maya.schuldiner@weizmann.ac.il.
Publications dans "Protéines mitochondriales" :
-
Cytosolic Events in the Biogenesis of Mitochondrial Proteins.
Trends in biochemical sciences 2020-05-11
-
The ER protein Ema19 facilitates the degradation of nonimported mitochondrial precursor proteins.
Molecular biology of the cell 2021-02-17
Süleyman Bozkurt
2 publications dans cette catégorie
Affiliations :
- Institute of Molecular Systems Medicine, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.
Publications dans "Protéines mitochondriales" :
-
Quantifying mitochondrial protein import by mePROD
Methods in enzymology 2024-08-26
-
Monitoring Mitochondrial Protein Import Using Mitochondrial Targeting Sequence (MTS)-eGFP.
Bio-protocol 2022-12-20
Christian Münch
2 publications dans cette catégorie
Affiliations :
- Institute of Molecular Systems Medicine, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany; Cardio-Pulmonary Institute, Frankfurt am Main, Germany. Electronic address: ch.muench@em.uni-frankfurt.de.
Publications dans "Protéines mitochondriales" :
-
Quantifying mitochondrial protein import by mePROD
Methods in enzymology 2024-08-26
-
Monitoring Mitochondrial Protein Import Using Mitochondrial Targeting Sequence (MTS)-eGFP.
Bio-protocol 2022-12-20
Bettina Warscheid
2 publications dans cette catégorie
Affiliations :
- Institute of Biology II, Biochemistry and Functional Proteomics, Faculty of Biology, University of Freiburg, Freiburg, Germany.
- Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial protein translocation-associated degradation.
Nature 2019-05-22
-
Mitochondrial proteins: from biogenesis to functional networks.
Nature reviews. Molecular cell biology
Sarah Gerlich
2 publications dans cette catégorie
Affiliations :
- Institute of Molecular Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, University Avenue, Glasgow, G12 8QQ Scotland, UK.
- Department for Chemistry, Institute for Biochemistry, University of Cologne, 50674 Cologne, Germany.
Publications dans "Protéines mitochondriales" :
-
The biogenesis of mitochondrial intermembrane space proteins.
Biological chemistry
-
The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis.
The Journal of cell biology 2023-09-08
Markus Räschle
2 publications dans cette catégorie
Affiliations :
- Molecular Genetics, University of Kaiserslautern, 67663 Kaiserslautern, Germany.
Publications dans "Protéines mitochondriales" :
-
The ER protein Ema19 facilitates the degradation of nonimported mitochondrial precursor proteins.
Molecular biology of the cell 2021-02-17
-
The Orf9b protein of SARS-CoV-2 modulates mitochondrial protein biogenesis.
The Journal of cell biology 2023-09-08
Nikolaus Pfanner
2 publications dans cette catégorie
Affiliations :
- Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. Electronic address: nikolaus.pfanner@biochemie.uni-freiburg.de.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial protein transport: Versatility of translocases and mechanisms.
Molecular cell
-
Mitochondrial proteins: from biogenesis to functional networks.
Nature reviews. Molecular cell biology
Nils Wiedemann
2 publications dans cette catégorie
Affiliations :
- Institute of Biochemistry and Molecular Biology, ZBMZ, Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany; BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany. Electronic address: nils.wiedemann@biochemie.uni-freiburg.de.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial protein transport: Versatility of translocases and mechanisms.
Molecular cell
-
Mitochondrial proteins: from biogenesis to functional networks.
Nature reviews. Molecular cell biology
Sahebgowda Sidramagowda Patil
1 publication dans cette catégorie
Affiliations :
- University of South Florida, Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, Tampa, FL, United States.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial Protein
Frontiers in pharmacology 2022-03-14
Ramani Soundararajan
1 publication dans cette catégorie
Affiliations :
- University of South Florida, Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, Tampa, FL, United States.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial Protein
Frontiers in pharmacology 2022-03-14
Jutaro Fukumoto
1 publication dans cette catégorie
Affiliations :
- University of South Florida, Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, Tampa, FL, United States.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial Protein
Frontiers in pharmacology 2022-03-14
Mason Breitzig
1 publication dans cette catégorie
Affiliations :
- University of South Florida, Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, Tampa, FL, United States.
- Washington University in St. Louis, Brown School, St. Louis, MO, United States.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial Protein
Frontiers in pharmacology 2022-03-14
Helena Hernández-Cuervo
1 publication dans cette catégorie
Affiliations :
- University of South Florida, Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, Tampa, FL, United States.
- University of South Florida, Department of Molecular Medicine, College of Medicine, Tampa, FL, United States.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial Protein
Frontiers in pharmacology 2022-03-14
Matthew Alleyn
1 publication dans cette catégorie
Affiliations :
- University of South Florida, Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, Tampa, FL, United States.
Publications dans "Protéines mitochondriales" :
-
Mitochondrial Protein
Frontiers in pharmacology 2022-03-14
Sources (10000 au total)
Renal Disease and Systemic Sclerosis: an Update on Scleroderma Renal Crisis.
Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis (SSc) with a mortality of 20% at 6 months. Once the leading cause of mortality in scleroderma (SSc), it remains ...
Scleroderma cardiac crisis: A-life-threatening but reversible complication of systemic sclerosis.
To describe systemic sclerosis (SSc) heart involvement in the ICU.... We retrospectively studied patients with previous diagnosis of SSc admitted to the ICU for acute cardiac dysfunction between 2012 and mid-2021.... 9 female patients were included, mainly with diffuse SSc (n = 7, 78%). Six (67%) had digital ulcers. All but one patient complained about physical cardiac symptoms (n = 8, 89%), 5 (56%) had electrocar... We report an uncommon and specific severe acute life-threatening cardiac dysfunction in SSc patients, which can be reversible but remains associated with a poor long-term prognosis, which can be rever...
Acute limb ischemia in an adolescent with COVID-19 and systemic scleroderma: a case report.
Juvenile Scleroderma is a rare autoimmune disease of the connective tissue. Its concurrence with COVID-19 can lead to limb ischemia as both disease entities are pro-inflammatory and pro-thrombotic. To... An adolescent with acute limb ischemia presented with a history of generalized hypo-and-hyperpigmented skin lesions and mild, non-productive cough. She tested positive for SARS-CoV-2 on nasopharyngeal... There is evolving knowledge about the interplay of COVID-19 hyperinflammatory state and rheumatologic disorders. COVID-19 is thought to exacerbate cutaneous manifestations of autoimmune disorders via ...
Association of Race and Risk of Future Scleroderma Renal Crisis at Systemic Sclerosis Diagnosis.
Scleroderma renal crisis (SRC) is a rare and severe manifestation of systemic sclerosis (SSc). Although it is well documented that Black patients with SSc have worse morbidity and mortality than non-B... Using the electronic health record of the US Military Health System, we conducted a comprehensive chart review of each patient with SSc from 2005 to 2016. The final study cohort was comprised of 31 SR... Of 353 patients, 294 had identifiable race (79 Black, 215 non-Black). Thirteen of 79 Black patients (16.5%) versus 16 of 215 (7.4%) non-Black patients developed SRC (P = 0.02). On adjusted analysis, B... Black race was independently associated with a higher risk of future SRC. Further studies are needed to elucidate the mechanisms that underlie this important association....
Paclitaxel-induced diffuse scleroderma with possible scleroderma-renal crisis: a case report and literature review of taxanes-induced scleroderma.
Scleroderma is a rare complication in taxanes therapy. Although individual cases of taxanes-induced scleroderma have been reported, the clinical manifestation and treatment outcomes were reviewed and ... A PubMed literature review on published cases of taxanes-induced scleroderma up until April 2022 was included for analysis.... The search identified 27 patients with adequate information for analysis. Of the 28 patients, including the one presented here, 22 were female. Peripheral edema was the most common symptom in all but ... Taxanes-induced scleroderma is different from idiopathic scleroderma. Physicians should be aware of this condition in order to provide early diagnosis and apply appropriate management in order to avoi...
Barriers to care in juvenile localized and systemic scleroderma: an exploratory survey study of caregivers' perspectives.
Juvenile localized scleroderma (LS) and systemic sclerosis (SSc) are rare pediatric conditions often associated with severe morbidities. Delays in diagnosis are common, increasing the risk for permane... In this cross-sectional study, caregivers of juvenile LS or SSc patients were recruited from a virtual family scleroderma educational conference and a juvenile scleroderma online interest group. The s... The response rate was 61% (73/120), with 38 parents of LS patients and 31 parents of SSc patients. Most patients were female (80%) and over half were non-Hispanic white (55%). Most families had at lea... Caregivers of children with LS or SSc reported numerous common barriers to the diagnosis, treatment, and ongoing care of juvenile scleroderma. The major problem highlighted was the lack of knowledge o...
Assessment of the skin with 2D-shear wave elastography in the systemic scleroderma and its correlation with pulmonary involvement.
The purpose of this study was to assess the skin involvement in systemic scleroderma patients (SSc) with 2D-Shear Wave Elastography (2D-SWE) and to review the corelation between skin elasticity and pu... Thirty SSc patients and 30 controls were examined using 2D-SWE. The demographics matched both groups. B-mode ultrasound (US) and 2D-SWE assessed skin thickness and elastography from the ventral side o... US parameter values (skin thickness, median kPa, median m/s) were higher in the SSc patient group (1.78 ± 0.36 mm, 22.15 ± 16.26, 2.60 ± 0.82, respectively) compared to the control group (1.55 ± 0.2 m... 2D-SWE is a promising non-invasive method to evaluate skin involvement in SSc patient group. For pulmonary involvement we need more data with bigger patient groups....
Assessment of kidney involvement in systemic sclerosis: From scleroderma renal crisis to subclinical renal vasculopathy.
The spectrum of kidney involvement in systemic sclerosis (SSc) includes scleroderma renal crisis, widely recognized as the most severe renal-vascular complication, but also several forms of chronic re...
Systemic sclerosis following COVID-19 infection with recurrent corticosteroid-induced scleroderma renal crisis.
Systemic sclerosis is a complex multisystem connective tissue disease resulting in fibrosis of the skin and internal organs. Exposure to corticosteroids can trigger scleroderma renal crisis, a life-th...