Relationship Between High-Density Lipoprotein Cholesterol and Mortality in Elderly Hemodialysis Patients: Data From the Korean Society of Geriatric Nephrology Retrospective Cohort.

OBJECTIVES: The association between high-density lipoprotein (HDL) cholesterol levels and mortality in elderly patients undergoing hemodialysis is not well established. Thus, this study investigated HDL levels and mortality in elderly Korean patients undergoing hemodialysis. METHODS: We recruited 1860 incident hemodialysis patients aged greater than 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology. The primary outcome measure was all-cause mortality. RESULTS: The mean age of the cohort was 77.8 years, and 1049 (56.4%) were men. When we grouped the patients into HDL cholesterol tertiles, the T1 group (HDL level <30 mg/dL in men and <33 mg/dL in women) had a higher proportion of patients with end-stage kidney disease due to diabetic nephropathy. During the median follow-up period of 3.1 years, 1109 (59.7%) deaths occurred. In a multivariable Cox regression model, the T1 group had a significantly higher risk of mortality (hazard ratio [HR], 1.28; 95% confidence interval, 1.10-1.50; P = .002) compared to the T3 group. A nonlinear analysis using a restrictive spline curve showed that low HDL cholesterol levels were associated with increased HR when HDL cholesterol levels were <40 mg/dL; however, there was no association between HDL cholesterol and mortality when HDL cholesterol levels were >40 mg/dL. Triglyceride/HDL ratio was not significantly associated with the risk of mortality (HR per 1 log increase, 1.08; 95% confidence interval, 0.99-1.18; P = .069). CONCLUSIONS: Low HDL cholesterol levels are associated with an increased risk of mortality in elderly patients undergoing hemodialysis. However, there was no significant relationship between HDL cholesterol levels and mortality when levels were below 40 mg/dL. Therefore, low HDL cholesterol levels may be a useful risk factor for predicting mortality in elderly patients undergoing hemodialysis.

Association between food insecurity and risk of chronic diseases affecting the kidney in older Korean patients.

AIMS: This study aimed to examine the association between food insecurity and the prevalence of chronic diseases among older adults in South Korea and to compare the findings with data from the United States (US). MATERIALS AND METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey (KNHANES) V (2010 - 2012) and VI (2013 - 2015) and 4 years (2012 - 2015) of food security questionnaire data. The data of 46,189 National Health and Nutrition Examination Survey participants (1999 - 2016) were subjected to propensity score-matched (PSM) analysis. RESULTS: We included 7,914 individuals from the KNHANES. In the older group (age > 65 years), no differences were observed in the prevalence of hypertension, diabetes, chronic kidney disease (CKD), and metabolic syndrome across the income groups. Income, education, and food security had no impact on hypertension, diabetes, and CKD prevalence in the multivariate logistic analysis after PSM. CKD was not associated with food insecurity (odds ratio (OR), 1.26; 95% confidence interval (CI), 0.94 - 1.26) in the final model using the KNHANES data; however, the U.S. NHANES data showed that an increased risk of hypertension was associated with food insecurity (OR, 1.27; 95% CI, 1.04 - 1.55). CONCLUSION: As per the U.S. NHANES data, food insecurity was associated with a high prevalence of hypertension, while as per the South Korean KNHANES data, food insecurity was not found to be associated with CKD, indicating divergent relationships between food insecurity and chronic diseases in the two countries. Further research is needed to explore these differences.

Effect of low-density lipoprotein level and mortality in older incident statin-naïve hemodialysis patients.

BACKGROUND: This study aimed to analyze low-density lipoprotein cholesterol (LDL-C) levels and their relationship with mortality in order to identify the appropriate lipid profile for older Korean hemodialysis patients. METHODS: We enrolled a total of 2,732 incident hemodialysis patients aged > 70 years from a retrospective cohort of the Korean Society of Geriatric Nephrology from 2010 Jan to 2017 Dec, which included 17 academic hospitals in South Korea. Of these patients, 1,709 were statin-naïve, and 1,014 were analyzed after excluding those with missing LDL-C level data. We used multivariate Cox regression analysis to select risk factors from 20 clinical variables among the LDL-C groups. RESULTS: The mean age of the entire patient population was 78 years, with no significant differences in age between quartiles Q1 to Q4. However, the proportion of males decreased as the quartiles progressed towards Q4 (p < 0.001). The multivariate Cox regression analysis, which included all participants, showed that low LDL-C levels were associated with all-cause mortality. In the final model, compared to Q1, the hazard ratios (95% confidence interval) were 0.77 (0.620-0.972; p = 0.027), 0.85 (0.676-1.069; p = 0.166), and 0.65 (0.519-0.824; p < 0.001) for Q2, Q3, and Q4, respectively, after adjusting for covariates, such as conventional and age-specific risk factors. The final model demonstrated that all-cause mortality increased as LDL-C levels decreased, as confirmed by a restrictive cubic spline plot. CONCLUSIONS: In older hemodialysis patients who had not previously received dyslipidemia treatment, elevated LDL-C levels were not associated with increased all-cause mortality. Intriguingly, lower LDL-C levels appear to be associated with an unfavorable effect on all-cause mortality among high-risk hemodialysis patients.

The role of collectivism and moderating effect of IT proficiency on intention to disclose protected health information.

This paper aims to identify and understand factors affecting insiders' intention to disclose patients' medical information and to investigate how these factors affect the intention to disclose. Based on the literature review on deterrence theory and health information security awareness (HISA), we identify relevant factors and develop a research model explaining insiders' intention to disclose patients' health information. We collect data (N = 105) through scenario-based experiments. Results show that two personal factors, collectivism, and IT proficiency, play a significant role in the model. While collectivism affects two components (health information security regulation awareness and punishment severity awareness) of HISA which influences intention to disclose, IT proficiency moderates the relationship between HISA and intention to disclose. In addition, HISA negatively affects reporting assessment and intention to disclose. This paper aims to fill a research gap in understanding factors affecting insiders' intentions to disclose protected health information. We identify and investigate factors (e.g., collectivism, HISA, reporting assessment, and IT proficiency) that may affect insiders' disclosing intentions. We find that collectivism affects two components of HISA which influence reporting assessment and disclosing intention. We also discover that IT proficiency moderates the relationship between HISA and intention to disclose. Our findings suggest that we need to carefully consider personal factors such as collectivistic nature and IT proficiency in managing insiders' security breaches.

Comamonas fluminis sp. nov., isolated from the Han River, Republic of Korea.

A Gram-stain-negative, aerobic and motile bacterial strain, designated CJ34T, was isolated from Han River water in the Republic of Korea. Strain CJ34T grew optimally on tryptic soy agar at 30 °C and pH 7.0 in the absence of NaCl. Results of phylogenetic analysis based on 16S rRNA gene sequence showed that strain CJ34T belonged to the genus Comamonas within the family Comamonadaceae and was most closely related to Comamonas testosteroni ATCC 11996T and Comamonas thiooxydans DSM 17888T (both 98.63 % similarity). The average nucleotide identity values between strain CJ34T and two closely related type strains C. testosteroni ATCC 11996T and C. thiooxydans DSM 17888T were 82.77 and 82.73 %, respectively. The major isoprenoid quinone of strain CJ34T was ubiquinone Q-8. The major cellular fatty acids of strain CJ34T were C16 : 0, C16 : 1 ω6c and/or C16 : 1 ω7c and C18 : 1 ω6c and/or C18 : 1 ω7c. The predominant polar lipids of strain CJ34T were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified aminophospholipid. Whole genome sequencing revealed that strain CJ34T had a genome of 4.9 Mbp and the G+C content of the genomic DNA was 59.73 mol%. On the basis of the results of this polyphasic taxonomy study, strain CJ34T represents a novel species in the genus Comamonas, for which the name Comamonas fluminis sp. nov. is proposed. The type strain is CJ34T (=KACC 22237T=JCM 34454T).

Developing a structural equation model from Grandey's emotional regulation model to measure nurses' emotional labor, job satisfaction, and job performance.

AIMS: This study constructed and tested a structural equation model on clinical nurses' emotional labor, job satisfaction, and job performance based on Grandey's emotion regulation model. DESIGN: We performed a correlational study to predict the relationship between the following variables: emotional labor (surface and deep acting), job satisfaction, job performance, self-efficacy, emotional intelligence, display rules, job autonomy, social support, and job stress. METHODS: Our hypothetical model was based on Grandey's emotional regulation model and on a literature review of emotional labor, job satisfaction, and job performance. Structured questionnaires were distributed to participants who worked in seven general hospitals with no less than 300 beds in a province, South Korea. We analyzed 424 questionnaires and used AMOS 23 to explore the relationships between the constructs. RESULTS: Our model fit the data well (χ2 = 96.420, GFI = 0.966, CFI = 0.956, RMSEA = 0.084). Display rules, self-efficacy, job autonomy, and job stress accounted for 20.5% of variance in surface acting. Self-efficacy, emotional intelligence, job autonomy, and job stress accounted for 23.3% of variance in deep acting. Job stress, self-efficacy, job autonomy, surface acting, and deep acting accounted for 45.0% of variance in job satisfaction. Self-efficacy, job autonomy, emotional intelligence, and deep acting accounted for 43.3% of variance in job performance. CONCLUSION: We confirmed that display rules, emotional intelligence, job stress, self-efficacy, and job autonomy are important factors that could decrease nurses' emotional labor and increase their job satisfaction and performance. These findings support the development and application of various interventions to decrease emotional labor and increase job satisfaction and job performance among nurses. IMPLEMENTATION: This study filled the need for an integrated structural equation model of emotional labor. With this model, we found that emotional labor operates differently in nursing practice than in other service fields. As such, this model can help hospital management to adjust their customer service guidelines to improve nurses' job satisfaction and performance.

Development of novel antimicrobial peptides derived from anti-lipopolysaccharide factor of the swimming crab, Portunus trituberculatus.

Anti-lipopolysaccharide factors (ALFs) are a representative host defense protein in crustaceans. In this study, we successfully developed two novel antimicrobial peptides (AMPs), named crab-ALF2A and crab-ALF6A, which contain changes to the amino acid sequences of the lipopolysaccharide binding domain and signal peptide, respectively, of the ALF of the swimming crab Portunus trituberculatus. The crab-ALF2A peptide showed potent antimicrobial activity against the Gram-positive bacteria Bacillus cereus, Staphylococcus aureus, and Streptococcus iniae (minimal effective concentration [MEC] 1.51-1.93 µg/mL) and the Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli (MEC 1.87-1.98 µg/mL), with maximal bactericidal activity at a peptide concentration of 5 µg/mL. The crab-ALF6A peptide also showed potent antimicrobial activity against B. cereus, S. aureus, and S. iniae (MEC 1.49-2.3 µg/mL) and P. aeruginosa and E. coli (MEC 1.72-1.19 µg/mL) at a peptide concentration of 5 µg/mL. Notably, the crab-ALF2A and crab-ALF6A peptides exhibited strong activity against Candida albicans (MECs of 2.11 and 1.95 µg/mL, respectively). These activities were stable following heat treatment. Moreover, the effect of crab-ALF2A and crab-ALF6A peptide treatment on microbe cell morphology was confirmed by scanning electron microscopy. Membrane disruption and damage, and the leakage of cytoplasmic content were clearly observed. A downsizing peptide approach illustrated that the hexapeptide ALF6A8 (RVLLRL) was the shortest peptide showing significant antimicrobial activity. Our approach allows for the generation of novel antimicrobial peptides in a cost effective manner as potential next-generation antibiotics.

The 5'-7-methylguanosine cap on eukaryotic mRNAs serves both to stimulate canonical translation initiation and to block an alternative pathway.

Translational control is frequently exerted at the stage of mRNA recruitment to the initiating ribosome. We have reconstituted mRNA recruitment to the 43S preinitiation complex (PIC) using purified S. cerevisiae components. We show that eIF3 and the eIF4 factors not only stabilize binding of mRNA to the PIC, they also dramatically increase the rate of recruitment. Although capped mRNAs require eIF3 and the eIF4 factors for efficient recruitment to the PIC, uncapped mRNAs can be recruited in the presence of eIF3 alone. The cap strongly inhibits this alternative recruitment pathway, imposing a requirement for the eIF4 factors for rapid and stable binding of natural mRNA. Our data suggest that the 5' cap serves as both a positive and negative element in mRNA recruitment, promoting initiation in the presence of the canonical group of mRNA handling factors while preventing binding to the ribosome via an aberrant, alternative pathway requiring only eIF3.

DISTRIBUTION OF VIRULENCE GENES IN ENVIRONMENTAL AND CLINICAL ISOLATES OF LEGIONELLA PNEUMOPHILA IN BUSAN, SOUTH KOREA.

Legionella pneumophila is the major causative agent of Legionnaires' disease. The distribution of L. pneumophila in environmental water systems of public facilities in Busan, South Korea was previously reported; however, the distribution of virulence genes in environmental and clinical isolates in Busan is unknown. Here, we investigated using PCR the distribution of three virulence loci (dot/icm, lvh, and rtxA) in isolates from Busan. A high prevalence of environmental (127/254) and clinical (3/4) isolates were observed for the simultaneous presence of all three genes, while environmental harboring dot/icm + rtxA, dot/icm + lvh, rtxA + lvh, and only one gene were 21%, 11%, 9% and <1-4%, respectively, The remaining clinical isolate carried dot/icm + rtxA. In addition, 68% of isolates from serogroup 1, the main cause of legionellosis, possessed all three virulence genes compared with 40% of isolates from serogroups 2 to 15. Prevalence of isolates with two genes was 5-14% and 6-29% in serogroup 1 and serogroups 2 to 15, respectively, whereas that of isolates with one gene was 1-2% and 0-6%, respectively. These results provide valuable information for epidemiological investigations of the relationship between environmental and clinical isolates in legionellosis outbreaks in Busan.

Past suicidal ideation as an independent risk factor for suicide behaviours in patients with depression.

OBJECTIVES: As South Korea has the highest incidence of completed suicides, the present study aimed to investigate the predictive power of the variables that have been associated with suicide attempts in Korean patients diagnosed with depression. METHODS: Hundred participants were divided into two groups: suicide attempters (31%) and suicide non-attempters (69%). Participants with a history of more than one suicidal attempt were assigned to the suicide attempter group. A hierarchical logistic regression analysis was performed to determine the predictive strengths of the variables that were likely to be associated with suicide attempts. RESULTS: After controlling for the effects of such variables as the severity of depressive symptoms, life stress events and impulsivity, the severity of past suicidal ideation was the most important predictive factor for discriminating suicide attempters from suicide non-attempters. The odds ratio for attempting suicide relative to not attempting suicide increased by a factor of 4.408 for each unit of increase in suicidal ideation. CONCLUSIONS: The present study suggests that the most severe suicidal ideation throughout one's entire life should not be overlooked and may be a major predictor of the risk of suicide.

Antimicrobial and Antitumor Activities of Novel Peptides Derived from the Lipopolysaccharide- and ß-1,3-Glucan Binding Protein of the Pacific Abalone Haliotis discus hannai.

Antimicrobial peptides are a pivotal component of the invertebrate innate immune system. In this study, we identified a lipopolysaccharide- and ß-1,3-glucan-binding protein (LGBP) gene from the pacific abalone Haliotis discus hannai (HDH), which is involved in the pattern recognition mechanism and plays avital role in the defense mechanism of invertebrates immune system. The HDH-LGBP cDNA consisted of a 1263-bp open reading frame (ORF) encoding a polypeptide of 420 amino acids, with a 20-amino-acid signal sequence. The molecular mass of the protein portion was 45.5 kDa, and the predicted isoelectric point of the mature protein was 4.93. Characteristic potential polysaccharide binding motif, glucanase motif, and ß-glucan recognition motif were identified in the LGBP of HDH. We used its polysaccharide-binding motif sequence to design two novel antimicrobial peptide analogs (HDH-LGBP-A1 and HDH-LGBP-A2). By substituting a positively charged amino acid and amidation at the C-terminus, the pI and net charge of the HDH-LGBP increased, and the proteins formed an α-helical structure. The HDH-LGBP analogs exhibited antibacterial and antifungal activity, with minimal effective concentrations ranging from 0.008 to 2.2 µg/mL. Additionally, both were toxic against human cervix (HeLa), lung (A549), and colon (HCT 116) carcinoma cell lines but not much on human umbilical vein cell (HUVEC). Fluorescence-activated cell sorter (FACS) analysis showed that HDH-LGBP analogs disturb the cancer cell membrane and cause apoptotic cell death. These results suggest the use of HDH-LGBP analogs as multifunctional drugs.

DISTRIBUTION OF LEGIONELLA PNEUMOPHILA SEROGROUPS ISOLATED FROM WATER SYSTEMS OF PUBLIC FACILITIES IN BUSAN, SOUTH KOREA.

Legionella pneumophila is the major causes of legionellosis worldwide. The distribution of L. pneumophila was investigated in water systems of public facilities in Busan, South Korea during 2007 and 2013-2014. L. pneumophila was isolated from 8.3% of 3,055 samples, of which the highest isolation rate (49%) was from ships and the lowest 4% from fountains. Serogroups of L. pneumophila isolated in 2007 were distributed among serogroups (sgs) 1-7 with the exception of sg 4, while those of isolates during 2013 and 2014 included also 11 sgs ( 1, 2, 3, 4, 5, 6, 7, 8, 12, 13, 15). L. pneumophila sg 1 was predominated among isolates from fountains (75%), hotels (60%), buildings (44%), hospitals (38%), and public baths (37%), whereas sg 3 and sg 7 was the most prevalent from ships (46%) and factories (40%), respectively. The predominated serogroup of L. pneumophila isolates from hot and cooling tower water was sg 1 (35% and 46%, respectively), while from cold water was sg 3 (29%). These results should be useful for epidemiological surveys to identify sources of outbreaks of legionellosis in Busan, South Korea.

Multiple elements in the eIF4G1 N-terminus promote assembly of eIF4G1•PABP mRNPs in vivo.

eIF4G is the scaffold subunit of the eIF4F complex, whose binding domains for eIF4E and poly(A)-binding protein (PABP) are thought to enhance formation of activated eIF4F•mRNA•PABP complexes competent to recruit 43S pre-initiation complexes. We found that the RNA-binding region (RNA1) in the N-terminal domain (NTD) of yeast eIF4G1 can functionally substitute for the PABP-binding segment to rescue the function of an eIF4G1-459 mutant impaired for eIF4E binding. Assaying RNA-dependent PABP-eIF4G association in cell extracts suggests that RNA1, the PABP-binding domain, and two conserved elements (Box1 and Box2) between these segments have overlapping functions in forming native eIF4G•mRNA•PABP complexes. In vitro experiments confirm the role of RNA1 in stabilizing eIF4G-mRNA association, and further indicate that RNA1 and Box1 promote PABP binding, in addition to RNA binding, by the eIF4G1 NTD. Our findings indicate that PABP-eIF4G association is only one of several interactions that stabilize eIF4F•mRNA complexes, and emphasize that closed-loop mRNP formation via PABP-eIF4G interaction is non-essential in vivo. Interestingly, two other RNA-binding regions in eIF4G1 have critical functions downstream of eIF4F•mRNA assembly.

Yeast eukaryotic initiation factor 4B (eIF4B) enhances complex assembly between eIF4A and eIF4G in vivo.

Translation initiation factor eIF4F (eukaryotic initiation factor 4F), composed of eIF4E, eIF4G, and eIF4A, binds to the m(7)G cap structure of mRNA and stimulates recruitment of the 43S preinitiation complex and subsequent scanning to the initiation codon. The HEAT domain of eIF4G stabilizes the active conformation of eIF4A required for its RNA helicase activity. Mammalian eIF4B also stimulates eIF4A activity, but this function appears to be lacking in yeast, making it unclear how yeast eIF4B (yeIF4B/Tif3) stimulates translation. We identified Ts(-) mutations in the HEAT domains of yeast eIF4G1 and eIF4G2 that are suppressed by overexpressing either yeIF4B or eIF4A, whereas others are suppressed only by eIF4A overexpression. Importantly, suppression of HEAT domain substitutions by yeIF4B overexpression was correlated with the restoration of native eIF4A·eIF4G complexes in vivo, and the rescue of specific mutant eIF4A·eIF4G complexes by yeIF4B was reconstituted in vitro. Association of eIF4A with WT eIF4G in vivo also was enhanced by yeIF4B overexpression and was impaired in cells lacking yeIF4B. Furthermore, we detected native complexes containing eIF4G and yeIF4B but lacking eIF4A. These and other findings lead us to propose that yeIF4B acts in vivo to promote eIF4F assembly by enhancing a conformation of the HEAT domain of yeast eIF4G conducive for stable binding to eIF4A.

Helicobacter pylori γ-glutamyl transpeptidase-induced Ca(2+) release via PLC-IP3 receptors in AGS cells.

In our previous study, γ-glutamyl transpeptidase (GGT) isolated from Helicobacter pylori induced apoptosis of AGS cells. Here, we investigate Ca(2+) effects on GGT-induced apoptosis. The GGT transiently and significantly increased intracellular Ca(2+) concentration ([Ca(2+)]i) in AGS cells in a dose-dependent manner (P < 0.05). The GGT-induced Ca(2+) increase resulted from Ca(2+) influx and release through the phospholipase C - inositol 1,4,5-trisphosphate (PLC-IP3) pathway. The GGT-induced apoptosis was significantly reduced by treatment with U73122 (a PLC inhibitor) and xestospongin (an IP3 receptor antagonist) (P < 0.05). These results indicate that GGT could induce apoptosis of AGS cells by high levels of [Ca(2+)]i.

Antimicrobial activity of peptides derived from olive flounder lipopolysaccharide binding protein/bactericidal permeability-increasing protein (LBP/BPI).

We describe the antimicrobial function of peptides derived from the C-terminus of the olive flounder LBP BPI precursor protein. The investigated peptides, namely, ofLBP1N, ofLBP2A, ofLBP4N, ofLBP5A, and ofLBP6A, formed α-helical structures, showing significant antimicrobial activity against several Gram-negative bacteria, Gram-positive bacteria, and the yeast Candida albicans, but very limited hemolytic activities. The biological activities of these five analogs were evaluated against biomembranes or artificial membranes for the development of candidate therapeutic agents. Gel retardation studies revealed that peptides bound to DNA and inhibited migration on an agarose gel. In addition, we demonstrated that ofLBP6A inhibited polymerase chain reaction. These results suggested that the ofLBP-derived peptide bactericidal mechanism may be related to the interaction with intracellular components such as DNA or polymerase.

Isolation of a Potential Probiotic Levilactobacillus brevis and Evaluation of Its Exopolysaccharide for Antioxidant and α-Glucosidase Inhibitory Activities.

The probiotic properties of ten lactic acid bacteria and antioxidant and α-glucosidase inhibitory activities of the exopolysaccharide (EPS) of the selected strain were investigated in this study. Levilactobacillus brevis L010 was one of the most active strains across all the in vitro tests. The cell-free supernatant (50 g/l) of L. brevis L010 showed high levels of both α-glucosidase inhibitory activity (98.73 ± 1.32%) and 2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity (32.29 ± 3.86%). The EPS isolated from cell-free supernatant of L. brevis L010 showed 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical-scavenging activity (80.27 ± 2.51%) at 80 g/l, DPPH radical-scavenging activity (38.19 ± 9.61%) at 40 g/l, and ferric reducing antioxidant power (17.35 ± 0.20 mg/l) at 80 g/l. Further, EPS exhibited inhibitory activities against α-glucosidase at different substrate concentrations. Kinetic analysis suggests that the mode of inhibition was competitive, with a kinetic constant of Km = 2.87 ± 0.88 mM and Vmax = 0.39 ± 0.06 µmole/min. It was concluded that the EPS might be one of the plausible candidates for possible antioxidant and α-glucosidase activities of the L. brevis L010 strain.

Enhancing Diabetes Care through a Mobile Application: A Randomized Clinical Trial on Integrating Physical and Mental Health among Disadvantaged Individuals.

BACKGRUOUND: This study examines integrating physical and mental healthcare for disadvantaged persons with type 2 diabetes mellitus and mild-to-moderate depression in the community, using a mobile application within a public-private-academic partnership. METHODS: The Korean Diabetes Association has developed a mobile application combining behavioral activation for psychological well-being and diabetes self-management, with conventional medical therapy. Participants were randomly assigned to receive the application with usual care or only usual care. Primary outcomes measured changes in psychological status and diabetes selfmanagement through questionnaires at week 12 from the baseline. Secondary outcomes assessed glycemic and lipid control, with psychological assessments at week 16. RESULTS: Thirty-nine of 73 participants completed the study (20 and 19 in the intervention and control groups, respectively) and were included in the analysis. At week 12, the intervention group showed significant reductions in depression severity and perceived stress compared to the control group. Additionally, they reported increased perceived social support and demonstrated improved diabetes self-care behavior. These positive effects persisted through week 16, with the added benefit of reduced anxiety. While fasting glucose levels in the intervention group tended to improve, no other significant differences were observed in laboratory assessments between the groups. CONCLUSION: This study provides compelling evidence for the potential efficacy of a mobile application that integrates physical and mental health components to address depressive symptoms and enhance diabetes self-management in disadvantaged individuals with type 2 diabetes mellitus and depression. Further research involving larger and more diverse populations is warranted to validate these findings and solidify their implications.

Specific domains in yeast translation initiation factor eIF4G strongly bias RNA unwinding activity of the eIF4F complex toward duplexes with 5'-overhangs.

During eukaryotic translation initiation, the 43 S ribosomal pre-initiation complex is recruited to the 5'-end of an mRNA through its interaction with the 7-methylguanosine cap, and it subsequently scans along the mRNA to locate the start codon. Both mRNA recruitment and scanning require the removal of secondary structure within the mRNA. Eukaryotic translation initiation factor 4A is an essential component of the translational machinery thought to participate in the clearing of secondary structural elements in the 5'-untranslated regions of mRNAs. eIF4A is part of the 5'-7-methylguanosine cap-binding complex, eIF4F, along with eIF4E, the cap-binding protein, and the scaffolding protein eIF4G. Here, we show that Saccharomyces cerevisiae eIF4F has a strong preference for unwinding an RNA duplex with a single-stranded 5'-overhang versus the same duplex with a 3'-overhang or without an overhang. In contrast, eIF4A on its own has little RNA substrate specificity. Using a series of deletion constructs of eIF4G, we demonstrate that its three previously elucidated RNA binding domains work together to provide eIF4F with its 5'-end specificity, both by promoting unwinding of substrates with 5'-overhangs and inhibiting unwinding of substrates with 3'-overhangs. Our data suggest that the RNA binding domains of eIF4G provide the S. cerevisiae eIF4F complex with a second mechanism, in addition to the eIF4E-cap interaction, for directing the binding of pre-initiation complexes to the 5'-ends of mRNAs and for biasing scanning in the 5' to 3' direction.

Control of total GFP expression by alterations to the 3' region nucleotide sequence.

BACKGROUND: Previously, we distinguished the Escherichia coli type II cytoplasmic membrane translocation pathways of Tat, Yid, and Sec for unfolded and folded soluble target proteins. The translocation of folded protein to the periplasm for soluble expression via the Tat pathway was controlled by an N-terminal hydrophilic leader sequence. In this study, we investigated the effect of the hydrophilic C-terminal end and its nucleotide sequence on total and soluble protein expression. RESULTS: The native hydrophilic C-terminal end of GFP was obtained by deleting the C-terminal peptide LeuGlu-6×His, derived from pET22b(+). The corresponding clones induced total and soluble GFP expression that was either slightly increased or dramatically reduced, apparently through reconstruction of the nucleotide sequence around the stop codon in the 3' region. In the expression-induced clones, the hydrophilic C-terminus showed increased Tat pathway specificity for soluble expression. However, in the expression-reduced clone, after analyzing the role of the 5' poly(A) coding sequence with a substituted synonymous codon, we proved that the longer 5' poly(A) coding sequence interacted with the reconstructed 3' region nucleotide sequence to create a new mRNA tertiary structure between the 5' and 3' regions, which resulted in reduced total GFP expression. Further, to recover the reduced expression by changing the 3' nucleotide sequence, after replacing selected C-terminal 5' codons and the stop codon in the ORF with synonymous codons, total GFP expression in most of the clones was recovered to the undeleted control level. The insertion of trinucleotides after the stop codon in the 3'-UTR recovered or reduced total GFP expression. RT-PCR revealed that the level of total protein expression was controlled by changes in translational or transcriptional regulation, which were induced or reduced by the substitution or insertion of 3' region nucleotides. CONCLUSIONS: We found that the hydrophilic C-terminal end of GFP increased Tat pathway specificity and that the 3' nucleotide sequence played an important role in total protein expression through translational and transcriptional regulation. These findings may be useful for efficiently producing recombinant proteins as well as for potentially controlling the expression level of specific genes in the body for therapeutic purposes.