SMYD5 methylation of rpL40 links ribosomal output to gastric cancer.

Dysregulated transcription due to disruption in histone lysine methylation dynamics is an established contributor to tumorigenesis1,2. However, whether analogous pathologic epigenetic mechanisms act directly on the ribosome to advance oncogenesis is unclear. Here we find that trimethylation of the core ribosomal protein L40 (rpL40) at lysine 22 (rpL40K22me3) by the lysine methyltransferase SMYD5 regulates mRNA translation output to promote malignant progression of gastric adenocarcinoma (GAC) with lethal peritoneal ascites. A biochemical-proteomics strategy identifies the monoubiquitin fusion protein partner rpL40 (ref. 3) as the principal physiological substrate of SMYD5 across diverse samples. Inhibiting the SMYD5-rpL40K22me3 axis in GAC cell lines reprogrammes protein synthesis to attenuate oncogenic gene expression signatures. SMYD5 and rpL40K22me3 are upregulated in samples from patients with GAC and negatively correlate with clinical outcomes. SMYD5 ablation in vivo in familial and sporadic mouse models of malignant GAC blocks metastatic disease, including peritoneal carcinomatosis. Suppressing SMYD5 methylation of rpL40 inhibits human cancer cell and patient-derived GAC xenograft growth and renders them hypersensitive to inhibitors of PI3K and mTOR. Finally, combining SMYD5 depletion with PI3K-mTOR inhibition and chimeric antigen receptor T cell administration cures an otherwise lethal in vivo mouse model of aggressive GAC-derived peritoneal carcinomatosis. Together, our work uncovers a ribosome-based epigenetic mechanism that facilitates the evolution of malignant GAC and proposes SMYD5 targeting as part of a potential combination therapy to treat this cancer.

Antibody toolkit to investigate eEF1A methylation dynamics in mRNA translation elongation.

Protein synthesis is a fundamental step in gene expression, with modulation of mRNA translation at the elongation step emerging as an important regulatory node in shaping cellular proteomes. In this context, five distinct lysine methylation events on eukaryotic elongation factor 1A (eEF1A), a fundamental nonribosomal elongation factor, are proposed to influence mRNA translation elongation dynamics. However, a lack of affinity tools has hindered progress in fully understanding how eEF1A lysine methylation impacts protein synthesis. Here we develop and characterize a suite of selective antibodies to investigate eEF1A methylation and provide evidence that methylation levels decline in aged tissue. Determination of the methyl state and stoichiometry on eEF1A in various cell lines by mass spectrometry shows modest cell-to-cell variability. We also find by Western blot analysis that knockdown of individual eEF1A-specific lysine methyltransferases leads to depletion of the cognate lysine methylation event and indicates active crosstalk between different sites. Further, we find that the antibodies are specific in immunohistochemistry applications. Finally, application of the antibody toolkit suggests that several eEF1A methylation events decrease in aged muscle tissue. Together, our study provides a roadmap for leveraging methyl state and sequence-selective antibody reagents to accelerate discovery of eEF1A methylation-related functions and suggests a role for eEF1A methylation, via protein synthesis regulation, in aging biology.

DeepResp: Deep learning solution for respiration-induced B0 fluctuation artifacts in multi-slice GRE.

Respiration-induced B0 fluctuation corrupts MRI images by inducing phase errors in k-space. A few approaches such as navigator have been proposed to correct for the artifacts at the expense of sequence modification. In this study, a new deep learning method, which is referred to as DeepResp, is proposed for reducing the respiration-artifacts in multi-slice gradient echo (GRE) images. DeepResp is designed to extract the respiration-induced phase errors from a complex image using deep neural networks. Then, the network-generated phase errors are applied to the k-space data, creating an artifact-corrected image. For network training, the computer-simulated images were generated using artifact-free images and respiration data. When evaluated, both simulated images and in-vivo images of two different breathing conditions (deep breathing and natural breathing) show improvements (simulation: normalized root-mean-square error (NRMSE) from 7.8 ± 5.2% to 1.3 ± 0.6%; structural similarity (SSIM) from 0.88 ± 0.08 to 0.99 ± 0.01; ghost-to-signal-ratio (GSR) from 7.9 ± 7.2% to 0.6 ± 0.6%; deep breathing: NRMSE from 13.9 ± 4.6% to 5.8 ± 1.4%; SSIM from 0.86 ± 0.03 to 0.95 ± 0.01; GSR 20.2 ± 10.2% to 5.7 ± 2.3%; natural breathing: NRMSE from 5.2 ± 3.3% to 4.0 ± 2.5%; SSIM from 0.94 ± 0.04 to 0.97 ± 0.02; GSR 5.7 ± 5.0% to 2.8 ± 1.1%). Our approach does not require any modification of the sequence or additional hardware, and may therefore find useful applications. Furthermore, the deep neural networks extract respiration-induced phase errors, which is more interpretable and reliable than results of end-to-end trained networks.

The effects of time-use intervention on the quality of life of outpatients with chronic stroke.

[Purpose] The purpose of this study was to examine the effects of time-use intervention on the quality of life of outpatients with chronic stroke. [Participants and Methods] This study randomly allocated 31 chronic stroke outpatients into an experimental group (n=16) and a control group (n=15). The experiment group was given general rehabilitative therapy three times per week for eight weeks, and time-use intervention through counselling once per week for eight weeks. The control group was given general rehabilitative therapy only for three times per week for eight weeks. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) was used to measure the changes in the quality of life of the participants. [Results] After the intervention, the experimental group showed a significant improvement in the overall quality of life in comparison with the control group. Looking at specific categories, the experimental group showed significant improvements in the physical, spiritual, and environmental areas in contrast to the control group. [Conclusion] The findings of this study demonstrated the positive effects of time-use intervention on an improvement in the quality of life of outpatients with chronic stroke.

A study on the sleep quality, pain, and instrumental activities of daily living of outpatients with chronic stroke.

[Purpose] The purpose of this study is to examine the sleep quality, pain, and instrumental activities of daily living (IADL) of outpatients with chronic stroke, and to examine their correlation. [Participants and Methods] This study was conducted on 42 outpatients with chronic stroke, and data on their sleep quality, pain, and instrumental activities of daily living were collected and analyzed using the survey measurement tools. [Results] The analysis shows significant correlations among the sleep quality, pain, and instrumental activities of daily living of the outpatients with chronic stroke. [Conclusion] The findings of this study confirmed that the sleep quality and pain of outpatients with chronic stroke was related with their capacities of instrumental activities of daily living.

The influences of client-centered therapy on the level of performance, the level of satisfaction of activity of daily living, and the quality of life of the chronic stroke patients.

[Purpose] The purpose of this research is to take a look at the influences of client-centered therapy on the level of everyday life performance, the level of satisfaction, and the quality of life of the chronic stroke patients. [Subjects and Methods] This research used client-centered therapy with two chronic stroke and hemiplegia patients as subjects. The therapy was carried out once a day, five times a week, for thirty minutes at a time for four weeks. Also, five kinds of training were included in the medical treatment programs which were organized after the initial Canadian occupational performance measure (COPM) evaluations. Evaluations were carried out before and after the mediation. Changes in the level of everyday life performance level of satisfaction were measured using the COPM, and changes in quality of life were measured using the Stroke Specific Quality of Life Scale (SS-QOL). [Results] After the application of medical treatment, both subjects showed positive changes in terms of the level of everyday life performance, level of satisfaction, and quality of life. [Conclusion] Both subjects demonstrated improvements in all aspects of both outcome measurements which implied that a short client-centered therapy program could help chronic stroke patients improve some aspects of their life.

Assessing the quality of reports about randomized controlled trials of scalp acupuncture combined with another treatment for stroke.

BACKGROUND: This study was designed to assess the quality of reporting on randomized controlled trials (RCTs) of scalp acupuncture for the treatment of stroke. METHODS: The following 8 databases were systematically investigated from their inception to December 2015: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, National Institute of Informatics Scholarly and Academic Information Navigator, National Digital Science Library, Korean Traditional Knowledge Portal, and Korean Studies Information Service System. RCTs utilizing scalp acupuncture as an intervention for stroke were selected, and the quality of reports was assessed based on the Consolidated Standards of Reporting Trials 2010 statement (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture 2010 (STRICTA). For each study, the overall quality score (OQS) of 13 CONSORT items, a combined key methodological index score (MIS) of 5 CONSORT items, and the OQS of 17 STRICTA items were measured. RESULTS: The original reports of 63 RCTs were ultimately obtained, and the median CONSORT OQS was 7 (minimum 2, maximum 11). Particularly, the items 'trial design', 'sample size', 'ancillary analyses', and 'harms' had a positive rate of less than 10%. The median MIS was 1 (minimum 0, maximum 5), with 'allocation concealment and implementation' and 'intent-to-treat analysis (ITT) analysis' having a positive rate of less than 10%. The median STRICTA OQS was 11 (minimum 6, maximum 14), and only the items 'sample size' and 'intent-to-treat analysis' were reported, with a positive rate of less than 10%. The mean CONSORT OQS increased by approximately 0.81 for each 5-year period in which manuscripts were published (95% confidence interval: 0.43 to 1.19; p < 0.001). No variable was significantly associated with MIS in the ordinal regression model. CONCLUSION: The quality of reports on RCTs investigating scalp acupuncture treatment for stroke was moderate to low. Furthermore, reporting of some items was either insufficient or inadequate in the majority of studies. In order to improve and standardize the quality of RCTs investigating scalp acupuncture for stroke, CONSORT and STRICTA guidelines should be utilized more frequently.

Dual task training effects on balance and hand functions of stroke patients.

[Purpose] The purpose of this research is to take a look at the influences of the dual task training on the hand function and the balance ability of the stroke patients. [Subjects and Methods] The dual task training was applied to 2 stroke hemiplegia patients. The dual task training had been carried out for 30 minutes by each session for 5 days a week for 3 weeks. The evaluations had been carried out 5 times for 3 weeks before and after the intervention. And the changes of the hand function had been measured by using the box and block test. And, for the changes of the balancing ability, the Berg Balance Scale was used. [Results] Both the hand function and the balancing ability of the subjects were improved after the dual task training. [Conclusion] Through the results of the research, it was able to confirm that the dual task training is effective for the enhancements of the hand function and the balancing ability of the stroke patients.

The influences of the mental practice on the quality of life of the stroke patients.

[Purpose] The purpose of this research is to take a look at the influences of the mental practice on the quality of life of stroke patients. [Subjects and Methods] Through a randomization of 32 stroke patients, this research allocated the experimental group (n=15) and the control group (n=17). Regarding the experimental group, the imagination practice intervention and the ordinary rehabilitation therapy had been applied 1 time a day and 5 times a week for 4 weeks. Regarding the control group, the ordinary rehabilitation therapy had been provided during the same session as that of the experimental group. In order to measure the quality of life, the SS-QOL was used. [Results] The mental practice and CON groups showed significant differences with the SS-QOL scores. [Conclusion] Through the result of this research, we were able to find out that the mental practice intervention is effective with regard to the improvement of the quality of life of the stroke patients. Regarding the researches that will take place later on, the researches which achieved the securing of even more experiment subjects and the control of the diverse variables of the quality of life will be needed.

The cold signaling attenuator HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 activates FLOWERING LOCUS C transcription via chromatin remodeling under short-term cold stress in Arabidopsis.

Exposure to short-term cold stress delays flowering by activating the floral repressor FLOWERING LOCUS C (FLC) in Arabidopsis thaliana. The cold signaling attenuator HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE1 (HOS1) negatively regulates cold responses. Notably, HOS1-deficient mutants exhibit early flowering, and FLC expression is suppressed in the mutants. However, it remains unknown how HOS1 regulates FLC expression. Here, we show that HOS1 induces FLC expression by antagonizing the actions of FVE and its interacting partner histone deacetylase 6 (HDA6) under short-term cold stress. HOS1 binds to FLC chromatin in an FVE-dependent manner, and FVE is essential for the HOS1-mediated activation of FLC transcription. HOS1 also interacts with HDA6 and inhibits the binding of HDA6 to FLC chromatin. Intermittent cold treatments induce FLC expression by activating HOS1, which attenuates the activity of HDA6 in silencing FLC chromatin, and the effects of intermittent cold are diminished in hos1 and fve mutants. These observations indicate that HOS1 acts as a chromatin remodeling factor for FLC regulation under short-term cold stress.

Dependency of Experimental Autoimmune Encephalomyelitis Induction on MOG35-55 Properties Modulating Matrix Metalloproteinase-9 and Interleukin-6.

Experimental autoimmune encephalomyelitis (EAE) is commonly induced with myelin oligodendrocyte glycoprotein (MOG)35-55; occasionally, EAE is not well induced despite MOG35-55 immunization. To confirm that EAE induction varies with difference in MOG35-55 properties, we compared three MOG35-55 from different commercial sources, which are MOG-A, MOG-B, and MOG-C. The peptides induced EAE disease with 100, 40, and 20 % incidence, respectively. Compared with others, MOG-A showed higher peptide purity (99.2 %) and content (92.2 %) and presented a sheet shape with additional sodium and chloride chemical elements. In MOG-A-treated group, MMP-9 activity and IL-6 levels were considerably higher than the other groups in CNS tissues, and significantly increased VCAM-1, IFN-γ, and decreased IL-4 were also shown compared to MOG-B- and/or MOG-C-treated group. In conclusion, the immunological and toxicological changes by the difference in MOG35-55 properties modulate EAE induction, and MOG35-55 which affects MMP-9 activity and IL-6 levels may be the most effective EAE-inducing antigen. This study can be potentially applied by researchers using MOG35-55 peptide and manufacturers for MOG35-55 synthesis.

The effect of task-oriented training on the muscle activation of the upper extremity in chronic stroke patients.

[Purpose] The aim of this study was to determine the effects of task-oriented training on upper extremity muscle activation in daily activities performed by chronic stoke patients. [Subjects and Methods] In this research, task-oriented training was conducted by 2 chronic hemiplegic stroke patients. Task-oriented training was conducted 5 times a week, 30 minutes per day, for 2 weeks. Evaluation was conducted 3 times before and after the intervention. The Change of muscle activation in the upper extremity was measured using a BTS FreeEMG 300. [Results] The subjects' root mean square values for agonistic muscles for the reaching activity increased after the intervention. All subjects' co-coordination ratios decreased after the intervention in all movements of reaching activity. [Conclusion] Through this research, task-oriented training was proven to be effective in improving the muscle activation of the upper extremity in chronic hemiplegic stroke patients.

Influence of mental practice on upper limb muscle activity and activities of daily living in chronic stroke patients.

[Purpose] The aim of this study was to determine the effects of mental practice on muscle activity of the upper extremity and performance of daily activities in chronic stroke patients. [Subjects and Methods] In this research, mental practice was conducted by 2 chronic hemiplegic stroke patients. Mental practice was conducted 30 minutes a day, 5 times a week, for 2 weeks. Evaluation was conducted 4 times before and after intervention. Muscle activity was measured using a surface electromyogram test, and the Modified Barthel Index was used to measure changes in the ability to carry out daily activities. [Results] Both the muscle activity of the upper extremity and capability to perform daily activities showed improved outcomes after mental practice was conducted. [Conclusion] Through this research, mental practice was proven to be effective in improving the muscle activity of upper extremity and capability to perform daily activities in chronic hemiplegic stroke patients.

Effects of task-oriented training on upper extremity function and performance of daily activities in chronic stroke patients with impaired cognition.

[Purpose] This study aimed to determine the effects of task-oriented training on upper extremity function and performance of daily activities in chronic stroke patients with impaired cognition. [Subjects and Methods] In this study, 2 chronic hemiplegic stroke patients underwent task-oriented training. The training was conducted once a day for 30 minutes, 5 times/week, for 2 weeks. The patients were evaluated 3 times before and after the task-oriented training. Changes in upper extremity function were assessed using the manual function test, and changes in the ability to carry out daily activities were assessed using the functional independence measure. [Results] The patients showed improvement in both the upper extremity function and ability to perform daily activities after task-oriented training. [Conclusion] Task-oriented training was proven effective in improving upper extremity function and ability to perform daily activities in chronic hemiplegic stroke patients with impaired cognition.

Zerumbone, Sesquiterpene Photochemical from Ginger, Inhibits Angiogenesis.

Here, we investigated the role of zerumbone, a natural cyclic sesquiterpene of Zingiber zerumbet Smith, on angiogenesis using human umbilical vein endothelial cells (HUVECs). Zerumbone inhibited HUVECs proliferation, migration and tubule formation, as well as angiogenic activity by rat aorta explants. In particular, zerumbone inhibited phosphorylation of vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1, which are key regulators of endothelial cell function and angiogenesis. In vivo matrigel plug assay in mice demonstrated significant decrease in vascularization and hemoglobin content in the plugs from zerumbone-treated mice, compared with control mice. Overall, these results suggest that zerumbone inhibits various attributes of angiogenesis, which might contribute to its reported antitumor effects.

Work-related musculoskeletal disorders among occupational therapists in Korea.

[Purpose] The purpose of the study was to identify general characteristics of occupational therapists in Korea and to investigate the present conditions of their work-related musculoskeletal disorders (WRMD) in order to present preliminary data for its prevention and directions for improvement. [Subjects and Methods] This study was conducted by performing a survey about WRMD among 95 occupational therapists working in Korea. Frequency analysis was conducted for the work-related general characteristics of subjects and for parts of the body with musculoskeletal disorder, and a χ(2) test was used to analyze the association between the presence of WRMD characteristics and each general characteristic. [Results] The parts of the body involved the most were the shoulders, hands, and neck (in decreasing order), and the work-related general characteristics shown to be associated with WRMD were the gender and the mean length of employment period. [Conclusion] The results of this study revealed that occupational therapists in Korea were extremely vulnerable to WRMD, and that realistic measures should be prepared swiftly for its prevention and treatment.

Impact of task-oriented training on hand function and activities of daily living after stroke.

Purpose] We examined the improvement of hand function and activities of daily living in stroke patients after carrying out task-oriented training. [Subjects] Thirty-two patients who had been diagnosed with stroke and underwent rehabilitation therapy participated in the task-oriented training. [Methods] The participants carried out task-oriented training for 30 min per day for 4 weeks. Their hand function and activities of daily living were evaluated before and after the training. [Results] The task-oriented training had a significant impact in terms of improving hand function and activities of daily living. [Conclusion] According to the results of this study, task-oriented training resulted in improved hand function and activities of daily living in stroke patients.

Effects of task-oriented training on upper extremity function and performance of daily activities by chronic stroke patients.

[Purpose] The aim of this study was to determine the effects that task-oriented training has on upper extremity function and performance of daily activities by chronic stroke patients. [Subjects and Methods] Task-oriented training was applied to two chronic hemiplegic patients in this research. The training was provided to each patient for 30 minutes a day, five times a week for two weeks. The treatment program included six different types of training that could be performed by the patients themselves. Evaluation was performed four times, that is, once a week for three weeks before the intervention and once after the intervention. The change in upper extremity function was measured with the Manual Function Test, and the change in performance of daily activity was measured with the Functional Independence Measure. [Results] The upper extremity function of both subjects was improved after application of task-oriented training. However, in the performance of daily activities, subject one showed improvement compared to with before the intervention, whereas subject two showed the same results. [Conclusion] This research confirmed that two weeks of task-oriented training for chronic stroke patients is effective for improvement of upper extremity function and performance of daily activities by chronic stroke patients.

Effects of mental practice on stroke patients' upper extremity function and daily activity performance.

[Purpose] The purpose of this study was to evaluate the effects of mental practice on stroke patients' upper extremity function and activities of daily living (ADL). [Subjects and Methods] In this study, 29 stroke patients were randomly assigned to two groups: an experimental group (n=14) and a control group (n=15). The experimental group performed 10 minutes of mental practice once a day, 5 days a week for 2 weeks in combination with conventional rehabilitation therapy. For the control group, general rehabilitation therapy was provided during the same sessions as the experimental group. The Action Research Arm Test (ARAT) and the Fugl-Myer assessment (FMA) were used to measure upper extremity function, and the Modified Bathel Index (MBI) was used to measure daily activity performance. [Results] After the intervention, the mental practice group showed significant improvements in upper extremity function on the affected side and ADL scores compared to the control group. [Conclusion] The results of this study demonstrate mental practice intervention is effective at improving stroke patients' upper extremity function and daily activity performance. In follow-up studies, securing a greater number of experimental subjects, and evaluation of the intervention's therapeutic durability are required.

Modified constraint-induced movement therapy for clients with chronic stroke: interrupted time series (ITS) design.

[Purpose] The purpose of this study was to investigate the impact that modified constraint-induced movement therapy has on upper extremity function and the daily life of chronic stroke patients. [Subjects and Methods] Modified constraint-induced movement therapy was conduct for 2 stroke patients with hemiplegia. It was performed 5 days a week for 2 weeks, and the participants performed their daily living activities wearing mittens for 6 hours a day, including the 2 hours of the therapy program. The assessment was conducted 5 times in 3 weeks before and after intervention. The upper extremity function was measured using the box and block test and a dynamometer, and performance daily of living activities was assessed using the modified Barthel index. The results were analyzed using a scatterplot and linear regression. [Results] All the upper extremity functions of the participants all improved after the modified constraint-induced movement therapy. Performance of daily living activities by participant 1 showed no change, but the results of participant 2 had improved after the intervention. [Conclusion] Through the results of this research, it was identified that modified constraint-induced movement therapy is effective at improving the upper extremity functions and the performance of daily living activities of chronic stroke patients.