scholarly journals Clinical Diagnosis and Treatment of Leigh Syndrome Based on SURF1: Genotype and Phenotype

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1950
Author(s):  
Inn-Chi Lee ◽  
Kuo-Liang Chiang
Keyword(s):  
Basal Ganglia ◽  
Life Expectancy ◽  
Peripheral Nerves ◽  
Early Onset ◽  
Coenzyme Q ◽  
Leigh Syndrome ◽  
Early Mortality ◽  
C Terminus ◽  
Assembly Factor ◽  
The Relationship

SURF1 encodes the assembly factor for maintaining the antioxidant of cytochrome c oxidase (COX) stability in the human electron respiratory chain. Mutations in SURF1 can cause Leigh syndrome (LS), a subacute neurodegenerative encephalopathy, characterized by early onset (infancy), grave prognosis, and predominant symptoms presenting in the basal ganglia, thalamus, brainstem, cerebellum, and peripheral nerves. To date, more than sixty different SURF1 mutations have been found to cause SURF1-associated LS; however, the relationship between genotype and phenotype is still unclear. Most SURF1-associated LS courses present as typical LS and cause early mortality (before the age of ten years). However, 10% of the cases present with atypical courses with milder symptoms and increased life expectancy. One reason for this inconsistency may be due to specific duplications or mutations close to the C-terminus of the SURF1 protein appearing to cause less protein decay. Furthermore, the treatment for SURF1-associated LS is unsatisfactory. A ketogenic diet is most often prescribed and has proven to be effective. Supplementing with coenzyme Q and other cofactors is also a common treatment option; however, the results are inconsistent. Importantly, anti-epileptic drugs such as valproate—which cause mitochondrial dysfunction—should be avoided in patients with SURF1-associated LS presenting with seizures.

scholarly journals C Terminus of DJ-1 Determines Its Homodimerization, Deglycation Activity and Suppression of Ferroptosis

2020 ◽  
Author(s):  
Li Jiang ◽  
Xiaobing Chen ◽  
Qian Wu ◽  
Haiying Zhu ◽  
Chengyong Du ◽  
...  
Keyword(s):  
Amino Acids ◽  
Parkinson Disease ◽  
Enzymatic Activity ◽  
Early Onset ◽  
Wild Type ◽  
Functional Protein ◽  
Point Mutant ◽  
C Terminus ◽  
Antioxidative Stress ◽  
The Relationship

AbstractDJ-1 is a multi-functional protein related to cancer and autosomal early-onset Parkinson disease (PD). Besides the well-documented antioxidative stress activity, recent studies suggest that DJ-1 has the deglycation enzymatic activity and the anti-ferroptosis function. Although it has been demonstrated that DJ-1 forms the homodimerization, which dictates its antioxidative stress activity, the relationship between the dimeric structure and newly reported activities remains largely elusive. In this study, we find that the deletion mutation of the last 3 amino acids at C terminus of DJ-1 disrupts its homodimerization in both transfected and purified DJ-1 protein. Further study shows that hydrophobic L187 residue is of great importance for DJ-1 homodimerization. In addition, the ability in methylglyoxal detoxification is almost abolished in the mutation of deleting last 3 residues at C terminus (ΔC3) and point mutant L187E compared with wild type DJ-1 (DJ-1 WT). We also find that the suppression of ferroptosis is fully inhibited by ΔC3 and L187E while partially suppressed by V51C. Thus, our findings show that C terminus of DJ-1 is crucial for its homodimerization, deglycation activity and suppression of ferroptosis.

Biotin-responsive basal ganglia disease: a treatable differential diagnosis of Leigh syndrome

2013 ◽  
Vol 44 (02) ◽  
Author(s):  
F Distelmaier ◽  
P Huppke ◽  
J Schaper ◽  
E Morava ◽  
E Mayatepek ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Basal Ganglia ◽  
Leigh Syndrome ◽  
Basal Ganglia Disease

scholarly journals Dynamics of life expectancy and life span equality

2020 ◽  
Vol 117 (10) ◽  
pp. 5250-5259 ◽  
Author(s):  
José Manuel Aburto ◽  
Francisco Villavicencio ◽  
Ugofilippo Basellini ◽  
Søren Kjærgaard ◽  
James W. Vaupel
Keyword(s):  
Life Expectancy ◽  
Life Span ◽  
Health Policies ◽  
Public Health Policies ◽  
Dynamic Relationship ◽  
Mortality Increase ◽  
Long Time ◽  
Underlying Causes ◽  
The Relationship ◽  
Over Time

As people live longer, ages at death are becoming more similar. This dual advance over the last two centuries, a central aim of public health policies, is a major achievement of modern civilization. Some recent exceptions to the joint rise of life expectancy and life span equality, however, make it difficult to determine the underlying causes of this relationship. Here, we develop a unifying framework to study life expectancy and life span equality over time, relying on concepts about the pace and shape of aging. We study the dynamic relationship between life expectancy and life span equality with reliable data from the Human Mortality Database for 49 countries and regions with emphasis on the long time series from Sweden. Our results demonstrate that both changes in life expectancy and life span equality are weighted totals of rates of progress in reducing mortality. This finding holds for three different measures of the variability of life spans. The weights evolve over time and indicate the ages at which reductions in mortality increase life expectancy and life span equality: the more progress at the youngest ages, the tighter the relationship. The link between life expectancy and life span equality is especially strong when life expectancy is less than 70 y. In recent decades, life expectancy and life span equality have occasionally moved in opposite directions due to larger improvements in mortality at older ages or a slowdown in declines in midlife mortality. Saving lives at ages below life expectancy is the key to increasing both life expectancy and life span equality.

Nuclear fibroblast growth factor-2 interacts specifically with splicing factor SF3a66

2004 ◽  
Vol 385 (12) ◽  
pp. 1203-1208 ◽  
Author(s):  
Susanne Gringel ◽  
Jeroen van Bergeijk ◽  
Kirsten Haastert ◽  
Claudia Grothe ◽  
Peter Claus
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Splicing Factor ◽  
Fibroblast Growth Factor 2 ◽  
Interacting Proteins ◽  
Fibroblast Growth ◽  
Extracellular Signaling ◽  
C Terminus ◽  
Assembly Factor ◽  
Smn Protein

Abstract Fibroblast growth factor 2 (FGF-2) has a dual role as a classical extracellular signaling protein and as an intracellular factor. Isoforms of FGF-2, resulting from alternatively used start codons on one mRNA species, locate differentially to nuclear compartments. In this study we aimed to analyze functions of intracellular FGF-2 by identification of interacting proteins. We identified the 66-kDa subunit of splicing factor 3a (SF3a66) as a binding partner in a yeast two-hybrid screen and confirmed this interaction by pull-down assays. The splicing factor interacted with the 18-kDa (FGF-218) and with the 23-kDa (FGF-223) isoforms, indicating an interaction with a domain common to both isoforms. Moreover, FGF-2 interacted with the C-terminus of SF3a66, a sequence that has not previously been assigned a functional role. In a functional neurite outgrowth assay, SF3a66 enhanced neurite lengths similar to FGF-218. We have previously identified the spliceosomal assembly factor survival of motoneuron (SMN) protein as a protein interacting specifically with the FGF-223 isoform [Claus et al., J. Biol. Chem. 278 (2003), 479–485]. The identification of two FGF-2 interacting proteins from the same biochemical pathway suggests a novel intranuclear role of FGF-2.

THE RELATIONSHIP BETWEEN THE ONSET OF SEVERE PREECLAMPSIA AND PERINATAL COMPLICATIONS AT RUMKITAL Dr. RAMELAN IN SURABAYA

2021 ◽  
Vol 5 (2) ◽  
pp. 139
Author(s):  
Widya Retno ◽  
Ivon Diah Wittiarika ◽  
Muhammad Aldika Akbar
Keyword(s):  
Preterm Delivery ◽  
Early Onset ◽  
Late Onset ◽  
Previous History ◽  
Severe Preeclampsia ◽  
P Value ◽  
Chronic Hypertension ◽  
Perinatal Complications ◽  
Exact Test ◽  
The Relationship

 Abstract Background: Preeclampsia is one of the biggest causes of maternal-fetal morbidity and mortality. Based on the prognosis, the classification of Preeclampsia is early onset (<34 weeks) and late onset (> 34 weeks). Purpose: to investigate the relationship between the onset of severe Preeclampsia and perinatal complications. Method: This research is a quantitative study with a retrospective observational analytic study type and collected medical record data. The study population was severe Preeclampsia  patients who gave birth at RUMKITAL Dr. Ramelan Surabaya for the period January 2018 - June 2020 and has no previous history of chronic hypertension. The research sample was 79 subjects with 44 subjects early onset, and 35 subjects late onset. Perinatal complications  examined are preterm delivery, asphyxia, LBW, IUGR, stillbirth. The chi-square test or Fisher’s Exact Test was used to analyze relationships. Result: From the results of the study, the comparison of the percentage from early onset and late onset that experienced complications was 93.2% vs 48.6%, p-value = 0.000, OR = 14.5, CI = 3,764–55,635.  At preterm delivery, it was found that 75% vs 28.6%, p-value = 0.000,  OR = 7.5, CI = 2,754-20,422. . In asphyxia, it was found 41.7% vs 31.4%, p-value = 0.46. At LBW, it was found 72.7% vs 17.1%, p-value = 0,000, OR = 12.9, CI = 4,285-38,771. In IUGR, it was found that 15.9% vs 2.9%, p-value = 0.000. In stillbirth, it was found 18.2% vs 0% and p-value = 0.008. Conclusion: the onset of severe Preeclampsia is related with perinatal complications. Complications associated with the onset severe Preeclampsia are preterm, LBW, stillbirth. Meanwhile, complications that are not related with the onset severe Preeclampsia are asphyxia and IUGR  

scholarly journals The relationship of the age of onset of obesity to the success of its treatment in the adult

1975 ◽  
Vol 34 (2) ◽  
pp. 201-204 ◽  
Author(s):  
Margaret Ashwell
Keyword(s):  
Early Onset ◽  
Age Of Onset ◽  
Maximum Weight ◽  
Men And Women ◽  
Loss Of Weight ◽  
Relationship Of ◽  
The Relationship

1. A survey was done of 2333 men and women who claimed experience of slimming.2. Their loss of weight was determined from their maximum stated weight and their present weight. The loss of weight was calculated as the percentage of the maximum weight and was related to the stated age of onset of obesity.3. The results showed that those people in the survey who had been fat since childhood had lost just as much weight as those people who had become fat as adults.4. These results suggest that the treatment of early-onset obesity may not be an unrealistic objective.

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