SummaryTelomere homeostasis, a process that is essential for the maintenance of chromosome integrity, is regulated by telomerase and a collection of associated proteins. By mass spectrometry we have identified a new telomeric protein encoded by the AtWHY1 (Arabidopsis thaliana Whirly 1) gene in Arabidopsis. AtWHY1 specifically binds the single-stranded plant telomeric DNA sequences, but not double-stranded telomeric DNA. To gain insights into the function of AtWHY1 in telomere biogenesis, we have identified two Arabidopsis lines harboring T-DNA insertions in AtWHY1. These lines exhibit neither growth nor developmental defects. However, AtWHY1-deficient plants show a steady increase in the length of telomere tracts over generations. This telomere elongation is correlated with a significant increase in telomerase activity. On the contrary, transgenic plants expressing AtWHY1 show a decreased telomerase activity and shortened telomeres. The evidence presented here indicates that AtWHY1 is a new family of telomere end-binding proteins that plays a role in regulating telomere-length homeostasis in Arabidopsis.

SummaryHuman chromosome ends associate with shelterin, a sixprotein complex that protects telomeric DNA from being recognized as sites of DNA damage. The shelterin subunit TRF2 has been implicated in the protection of chromosome ends by facilitating their organization into the protective capping structure and by associating with several accessory proteins involved in various DNA transactions. Here we describe the characterization of DDX39 DEAD-box RNA helicase as a novel TRF2-interacting protein. DDX39 directly interacts with the telomeric repeat binding factor homology domain of TRF2 via the FXLXP motif (where X is any amino acid). DDX39 is also found in association with catalytically competent telomerase in cell lysates through an interaction with hTERT but has no effect on telomerase activity. Whereas overexpression of DDX39 in telomerasepositive human cancer cells led to progressive telomere elongation, depletion of endogenous DDX39 by small hairpin RNA (shRNA) resulted in telomere shortening. Furthermore, depletion of DDX39 induced DNA-damage response foci at internal genome as well as telomeres as evidenced by telomere dysfunction-induced foci. Some of the metaphase chromosomes showed no telomeric signal at chromatid ends, suggesting an aberrant telomere structure. Our findings suggest that DDX39, in addition to its role in mRNA splicing and nuclear export, is required for global genome integrity as well as telomere protection and represents a new pathway for telomere maintenance by modulating telomere length homeostasis.

BackgroundIt is known that nonsynostotic plagiocephaly does not spontaneously improve, and the craniofacial deformities that result from it. This study was conducted to analyze the effectiveness of helmet therapy for the nonsynostotic plagiocephaly patient, and to suggest a new treatment strategy based on this analysis.MethodsA total of 108 pediatric patients who had undergone helmet therapy after being diagnosed with nonsynostotic plagiocephaly were included in this study. The patients were classified according to the initiation age of the helmet therapy, severity, and helmet wearing time. The treatment effect was compared using cranial vault asymmetry (CVA) and the cranial vault asymmetry index (CVAI), which were obtained from diagonal measurements before and after therapy.ResultsThe discrepancy of CVA and CVAI of all the patients significantly decreased after helmet therapy. According to the initiation time of helmet therapy, the treatment effect was best at 5 months old or less. The helmet wearing time per day was proportional to the treatment effect up to 20 hours. In addition, the rate of the successful treatment (final CVA ≤5 mm) significantly decreased when the initiation age was 9.1 months or older and the treatment period was less than 7.83 months.ConclusionsThis study showed the effectiveness of the helmet therapy for nonsynostotic plagiocephaly patients. Based on analysis of this study, helmet therapy should be started at the age of 9 months or younger for 7.83 months or more, and the helmet wearing time should be more than 20 hours a day.

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Although prior research in Western societies has revealed an association between self-efficacy and both self-management behaviours and better health status, little is known about the applicability of this association in Korean populations. We examined the differences in self-management behaviours and health status among three groups according to the level of self-efficacy (high, moderate and low). We used a descriptive and correlational design, and administrated a questionnaire to 322 Korean patients with diabetes mellitus, hypertension or arthritis at three ambulatory clinics in a university medical centre. We performed the Pearson chi-square test to test for differences in proportions, and the Kruskall-Wallis and Mann-Whitney U-tests for non-parametric measures. The level of self-efficacy was associated with self-management behaviours (P < 0.05) and with better health status indices (P < 0.001) except fatigue (P < 0.277). The mean age (Mean ± standard deviation, 53.71 ± 12.60), the percentage of high level of education (62.4%) and the level of employment (51.4%) were significantly higher in high self-efficacy group than in low self-efficacy group or moderate self-efficacy group. Further study of the potential factors affecting any relationship between self-efficacy and fatigue is recommended. Self-efficacy-enhancing interventions can be beneficial for Korean chronic patients to improve their self-management behaviours and health status.

Background/Aims: Radiation-induced skin fibrosis is a common side effect of clinical radiotherapy. Our previous next-generation sequencing (NGS) study demonstrated the reduced expression of the regulatory α subunit of phosphatidylinositol 3-kinase (PIK3r1) in irradiated murine skin. Metformin has been reported to target the PIK3-FOXO3 pathway. In this study, we investigated the effects of metformin on radiation-induced skin fibrosis. Methods: Metformin was orally administered to irradiated mice. Skin fibrosis was analyzed by staining with H&E and Masson’s trichrome stain. The levels of cytokines and chemokines associated with fibrosis were analyzed by immunohistochemistry and quantitative RT-PCR. The roles of PIK3rl and FOXO3 in radiation-induced skin fibrosis were studied by overexpressing PIK3rl and transfecting FOXO3 siRNA in NIH3T3 cells and mouse-derived dermal fibroblasts (MDF). Results: The oral administration of metformin significantly reduced radiation-induced skin thickening and collagen accumulation and significantly reduced the radiation-induced expression of FOXO3 in murine skin. Additionally, the overexpression of PIK3r1 reduced the radiation-induced expression of FOXO3, while FOXO3 silencing decreased the radiation-induced expression of TGFβ in vitro. Conclusions: The results indicated that metformin suppresses radiation-induced skin injuries by modulating the expression of FOXO3 through PIK3r1. Collectively, the data obtained in this study suggested that metformin could be a potent therapeutic agent for alleviating radiation-induced skin fibrosis.

See editorial commentary page on 271 Background: Muscle strength has been suggested as a cardiovascular marker. The aim of this study was to examine the associations between hand grip strength and biomarkers of cardiovascular disease in the Korean population. Methods: A total of 9,083 participants aged 20-80 years from Korea National Health and Nutrition Examination Survey 2015-2016 were investigated. Results: Among men, both relative and dominant hand grip strength showed a positive association with diastolic blood pressure in those aged 65-80 years (95% confidence interval, P-value of dominant and relative hand grip strength: β=0.06, 0.01; P<0.05). Among women, relative and dominant hand grip strength showed a positive relationship to diastolic blood pressure in those aged 20-64 years (β=0.06, 0.01; P<0.001). Body mass index was positively associated with dominant hand grip strength in younger women (β=0.18, P<0.05), whereas it was positively associated with relative hand grip strength in all sex and age groups. High-sensitivity C-reactive protein showed a negative association with relative and dominant hand grip strength in all women, although the same association was observed only in younger men. Diabetes was inversely related to hand grip strength in younger women and men. Conclusion: Increased hand grip strength may be associated with lower C-reactive protein in women and with less risk of diabetes in the Korean adult population. Further prospective studies are needed for the determination of causality between cardiometabolic markers and hand grip strength.

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