RESUMO
VDAC1 is a critical substrate of Parkin responsible for the regulation of mitophagy and apoptosis. Here, we demonstrate that VDAC1 can be either mono- or polyubiquitinated by Parkin in a PINK1-dependent manner. VDAC1 deficient with polyubiquitination (VDAC1 Poly-KR) hampers mitophagy, but VDAC1 deficient with monoubiquitination (VDAC1 K274R) promotes apoptosis by augmenting the mitochondrial calcium uptake through the mitochondrial calcium uniporter (MCU) channel. The transgenic flies expressing Drosophila Porin K273R, corresponding to human VDAC1 K274R, show Parkinson disease (PD)-related phenotypes including locomotive dysfunction and degenerated dopaminergic neurons, which are relieved by suppressing MCU and mitochondrial calcium uptake. To further confirm the relevance of our findings in PD, we identify a missense mutation of Parkin discovered in PD patients, T415N, which lacks the ability to induce VDAC1 monoubiquitination but still maintains polyubiquitination. Interestingly, Drosophila Parkin T433N, corresponding to human Parkin T415N, fails to rescue the PD-related phenotypes of Parkin-null flies. Taken together, our results suggest that VDAC1 monoubiquitination plays important roles in the pathologies of PD by controlling apoptosis.
Assuntos
Apoptose , Mitofagia , Ubiquitina-Proteína Ligases/metabolismo , Canal de Ânion 1 Dependente de Voltagem/metabolismo , Animais , Cálcio/fisiologia , Drosophila/genética , Drosophila/metabolismo , Feminino , Humanos , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Doença de Parkinson/enzimologia , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação , Canal de Ânion 1 Dependente de Voltagem/genéticaRESUMO
The aim of this study is to compare the muscle strength, balance ability, thickness, and stiffness of the tibialis anterior and gastrocnemius muscle in the elderly, with (fallers) and without (non-fallers) fall experience, and confirmed the correlation between the variables mentioned above and muscle stiffness in the faller. We selected 122 elderly participants, comprising 40 fallers and 82 non-fallers, and measured the muscle strength of the tibialis anterior (TA) and the gastrocnemius (GA). Balance ability was measured by the functional reach test (FRT), timed up and go test (TUG), short physical performance battery (SPPB), and gait speed (GS). We used shear wave elastography (SWE) to determine the thickness of the TA and the medial (GAmed) and lateral head (GAlat) of the gastrocnemius and the stiffness during relaxation and contraction. Balance ability, except muscle strength, was significantly lower in fallers compared with non-fallers. The GAmed and GAlat thickness were significantly lower in fallers than that in non-fallers. In fallers, the thickness, rest, and contractive stiffness of GAmed were correlated with the FRT, GS, SPPB. Low rest and GAmed contractive stiffness were related to lower balance ability in fallers. The muscle stiffness measurement using SWE was a novel method to assess potential fall risk.
RESUMO
PURPOSE: This study aimed at developing a happiness assessment scale for middle-aged women (HAS-MW) in Korea. METHODS: Preliminary items for the scale were drafted from the results of literature review and personal interviews and open-ended questions with women in the community. The interviews were based on the theory of existence, relatedness, and growth. After validating a preliminary scale, we analyzed the validity and reliability of the new scale items, and model fit. We surveyed 600 women aged 40 years to 64 years for exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). Valid data were divided into 352 for EFA and 174 for CFA by multiplies of number 1 to 3. RESULTS: Using exploratory and confirmatory factor analyses, we extracted four primary factors-self-value, positive thinking, self-care, and family relationship-and with a total of 24 items for HAS-MW. The fit of the final model was evaluated as good showing χ2/df = 2.10, goodness of fit index = .80, comparative fit index = .85, root mean square error of approximation = .08, standardized root mean residual = .05. The HAS-MW had a significant positive correlation with the Oxford Happiness scale and showed a significant negative correlation with the Hwa-Byeong Scale. Cronbach's α for the new scale was .91, and the Spearman-Brown half coefficient was .93. The new scale used a five-point Likert scale with higher scores indicating greater happiness. CONCLUSION: The HAS-MW is a reliable and valid one. It can be used to measure the level of happiness for middle-aged women. In addition, it might be applied to find low women and to evaluate the effect of intervention program related to happiness in woman of middle age.
Assuntos
Felicidade , Análise Fatorial , Feminino , Humanos , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Korea has been divided into South Korea and North Korea for over 70 years. DNA profiles of the North Korean population have never been reported in the Y-chromosome STR Haplotype Reference Database (YHRD; https://yhrd.org ). To investigate genetic features of Y-chromosome STR haplotypes of the North Korean population for the first time. Genomic DNA was isolated from 838 cigarette butts assumed to have been smoked by North Korean men and amplified with PowerPlex Y23 (PPY23) kit. Statistical parameters were calculated using Nei's formula and analysis of molecular variance (AMOVA). Multidimensional scaling (MDS) plot was constructed by the AMOVA tool and neighbor-joining (NJ) tree was constructed by MEGA 6.06. A total of 121 haplotypes were analyzed for PPY23 loci from a sample population. Haplotype diversity and discrimination capacity were 0.9992 and 0.9837, respectively. Genetic diversities ranged from 0.2981 to 0.9716. For the 16 Y-filer loci and eight minimal loci, respectively 90.9 and 82.6% of the matched haplotypes were estimated to belong to haplogroup O, representing the Southeast and East Asian type. The MDS plot and NJ tree indicated that the samples are most closely related to South Korean. In addition, p-value in the pairwise comparison to the South Korean was slightly above statistical significance (p = 0.0534). The Y-STR haplotypes of the samples were unique and highly genetically polymorphic. Despite the separation between North and South Korea for 70 years, they can still be considered a single genetic population, based on Y-STR haplotypes.
Assuntos
Cromossomos Humanos Y/genética , Genética Populacional , Repetições de Microssatélites/genética , República Democrática Popular da Coreia/epidemiologia , Etnicidade/genética , Variação Genética , Haplótipos/genética , Humanos , Masculino , República da Coreia/epidemiologia , Produtos do Tabaco/análiseRESUMO
Members of the Mongol imperial family (designated the Golden family) are buried in a secret necropolis; therefore, none of their burial grounds have been found. In 2004, we first discovered 5 graves belonging to the Golden family in Tavan Tolgoi, Eastern Mongolia. To define the genealogy of the 5 bodies and the kinship among them, SNP and/or STR profiles of mitochondria, autosomes, and Y chromosomes were analyzed. Four of the 5 bodies were determined to carry the mitochondrial DNA haplogroup D4, while the fifth carried haplogroup CZ, indicating that this individual had no kinship with the others. Meanwhile, Y-SNP and Y-STR profiles indicate that the males examined belonged to the R1b-M343 haplogroup. Thus, their East Asian D4 or CZ matrilineal and West Eurasian R1b-M343 patrilineal origins reveal genealogical admixture between Caucasoid and Mongoloid ethnic groups, despite a Mongoloid physical appearance. In addition, Y chromosomal and autosomal STR profiles revealed that the four D4-carrying bodies bore the relationship of either mother and three sons or four full siblings with almost the same probability. Moreover, the geographical distribution of R1b-M343-carrying modern-day individuals demonstrates that descendants of Tavan Tolgoi bodies today live mainly in Western Eurasia, with a high frequency in the territories of the past Mongol khanates. Here, we propose that Genghis Khan and his family carried Y-haplogroup R1b-M343, which is prevalent in West Eurasia, rather than the Y-haplogroup C3c-M48, which is prevalent in Asia and which is widely accepted to be present in the family members of Genghis Khan. Additionally, Tavan Tolgoi bodies may have been the product of marriages between the lineage of Genghis Khan's Borjigin clan and the lineage of either the Ongud or Hongirad clans, indicating that these individuals were members of Genghis Khan's immediate family or his close relatives.