Voluntary exercise normalizes the proteomic landscape in muscle and brain and improves the phenotype of progeroid mice.

The accumulation of mitochondrial DNA (mtDNA) mutations is a suspected driver of aging and age-related diseases, but forestalling these changes has been a major challenge. One of the best-studied models is the prematurely aging mtDNA mutator mouse, which carries a homozygous knock-in of a proofreading deficient version of the catalytic subunit of mtDNA polymerase-γ (PolgA). We investigated how voluntary exercise affects the progression of aging phenotypes in this mouse, focusing on mitochondrial and protein homeostasis in both brain and peripheral tissues. Voluntary exercise significantly ameliorated several aspects of the premature aging phenotype, including decreased locomotor activity, alopecia, and kyphosis, but did not have major effects on the decreased lifespan of mtDNA mutator mice. Exercise also decreased the mtDNA mutation load. In-depth tissue proteomics revealed that exercise normalized the levels of about half the proteins, with the majority involved in mitochondrial function and nuclear-mitochondrial crosstalk. There was also a specific increase in the nuclear-encoded proteins needed for the tricarboxylic acid cycle and complex II, but not in mitochondrial-encoded oxidative phosphorylation proteins, as well as normalization of enzymes involved in coenzyme Q biosynthesis. Furthermore, we found tissue-specific alterations, with brain coping better as compared to muscle and with motor cortex being better protected than striatum, in response to mitochondrial dysfunction. We conclude that voluntary exercise counteracts aging in mtDNA mutator mice by counteracting protein dysregulation in muscle and brain, decreasing the mtDNA mutation burden in muscle, and delaying overt aging phenotypes.

Infection-control knowledge, attitude, practice, and risk perception of occupational exposure to Zika virus among nursing students in Korea: A cross-sectional survey.

BACKGROUND: As the number of patients with Zika virus infection increases worldwide, nursing students who conduct clinical practice in hospitals tend to at risk of Zika virus infection. Therefore, this study was conducted to identify nursing students' knowledge, attitudes, practices, and risk perceptions of infection prevention related to occupational exposure to Zika virus infection, and to identify correlations among the related variables. METHODS: This cross-sectional study included 249 nursing students from 3 nursing colleges located in 3 Korean cities, with experience in hospital clinical practice. A questionnaire to assess the knowledge, attitudes, practices, and risk perceptions of Zika virus infection was developed through a literature review and was subjected to pilot testing and validation. RESULTS: The level of infection-control knowledge for Zika virus was 54.5 of 100 points, and that of practice was 4.5 of 5 points. The infection-prevention attitude score was 4.4 of 5 points, and the risk-perception score was 2.3 of 5 points. Significant differences emerged in infection-prevention attitude toward Zika virus based on Zika virus vaccination intention. Additionally, practice and risk-perception scores differed significantly based on gender and Zika virus vaccination intention. Knowledge significantly correlated with attitude and attitude toward preventive behavior. CONCLUSION: Improvement in infection-control knowledge for Zika virus can help improve nurses' related attitudes, which in turn could promote effective practice. Considering the characteristics of nursing students, it is necessary to develop and apply an effective and viable education program related to the prevention of Zika virus infection.

Korean infection control nurses' knowledge and awareness of infection control against Ebola virus disease.

AIM: To assess the level of knowledge and awareness of Ebola virus disease infection control among infection control nurses and to identify a correlation between these factors. METHODS: The data were collected from 125 infection control nurses by using a self-report questionnaire. The data were collected on sociodemographic and hospital characteristics, as well as the level of knowledge and awareness of Ebola virus disease infection control. RESULTS: The respondents' mean level of knowledge (correct-answer rate) was 87.7% and their mean level of awareness was 3.86 (1 = "not important at all" to 4 = "very important"). Knowledge of Ebola virus disease infection control was significantly higher among those nurses who had received some Ebola virus disease education. There was a significant positive correlation between the level of knowledge and the level of awareness. CONCLUSION: The development of effective education and training systems is necessary to improve infection control nurses' knowledge and awareness of Ebola virus disease infection control. Moreover, each hospital should build effective and systematic Ebola virus disease infection control strategies.

TLR2 signaling in tubular epithelial cells regulates NK cell recruitment in kidney ischemia-reperfusion injury.

Damage-associated molecular patterns released from damaged kidney cells initiate postischemic inflammation, an essential step in the progression of kidney ischemia-reperfusion injury (IRI). However, the mechanism that coordinates this highly specific process in ischemic kidneys remains to be clarified. Previously, we demonstrated that CD137 from NK cells specifically stimulates CD137 ligand (CD137L) on tubular epithelial cells (TECs) such that TECs produced the high CXCR2 chemokine levels required for neutrophil chemotaxis. We report in the present study that endogenous TLR2 ligands released from ischemic TECs induce CCR5 chemokine expression, which is critical to promoting NK cell recruitment. By implanting CD137L(-/-) TECs into the kidney capsule of TLR2(-/-) mice, we further showed that TLR2-mediated NK cell recruitment is an uncoupled event that can occur independently of CD137L signaling in TECs, which is responsible for recruiting neutrophils. Therefore, our findings identify TECs as both a target for kidney damage and also as a master regulator that actively modulates stepwise signaling, leading to the initiation and amplification of acute sterile inflammation that inflicts kidney IRI. Being clinically important, the signaling pathway of innate receptors in epithelial cells may therefore be a good target to block acute sterile inflammation resulting from tissue damage, including kidney IRI.

Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson's disease cohort.

INTRODUCTION AND AIMS: Wide phenotypic and genotypic heterogeneities in Wilson's disease (WD) have been reported, hampering the study of their correlations. The goal of this study was to identify the factors related to these diversities. METHODS: Clinical courses and molecular genetic characteristics were analysed in 237 unrelated Korean WD families. The average follow-up period was 8.2 ± 5.8 years. RESULTS: Presenting phenotypes were classified as H1 (12.2%), H2 (42.4%), N1 (21.6%), N2 (0.4%), NX (0.4%), presymptomatic (22.4%) and other (0.4%), modifying the guidelines by Ferenci and colleagues. Age at presentation was youngest and cirrhosis was rarest in the presymptomatic group. Decompensated cirrhosis was the highest in the H1 group. Favourable outcome was rarest in the N1 group. Forty-seven (11 novel) ATP7B mutations were identified in 85% of the 474 alleles. Multiplex ligation-dependent probe amplification assays in ATP7B and analyses of ATOX1 and COMMD1 genes identified no additional mutations. Yeast complementation assays demonstrated functional perturbation of the seven novel missense mutants. Five major mutations, p.Arg778Leu, p.Ala874Val, p.Asn1270Ser, p.Lys838SerfsX35 and p.Leu1083Phe, accounted for 63% of the alleles. H1 was more common, age at presentation was younger and N1+N2+NX tended to be less common in patients with nonsense, frame shifting or splicing mutations than in those with missense mutations alone. Patients with both mutations in the transduction (Td) or the ATP hinge domain showed presymptomatic or hepatic manifestations but no neurological manifestation. CONCLUSIONS: The presenting phenotype strongly affects the clinical outcome of WD, and is related to the ATP7B mutation type and location, providing an evidence for genotype-phenotype correlations in WD.