Association between healthy lifestyle practices and life purpose among a highly health-literate cohort: a cross-sectional study.

BACKGROUND: The national health promotion program in the twenty-first century Japan (HJ21) correlates life purpose with disease prevention, facilitating the adoption of healthy lifestyles. However, the influence of clustered healthy lifestyle practices on life purpose, within the context of this national health campaign remains uninvestigated. This study assessed the association between such practices and life purpose, in line with the HJ21. METHODS: We performed a nationwide cross-sectional survey on certified specialists in health management. Participants' demographic information, lifestyle, and purpose in life were measured using a validated tool. The cohort was median-split into two groups based on their clustered health-related lifestyle score. The values for health-related lifestyle and purpose were compared between the two groups and the correlation between health-related lifestyle and purpose in life was measured. RESULTS: Data from 4820 participants were analyzed. The higher-scoring health-related lifestyle group showed a significantly higher life purpose than the lower group (35.3 vs 31.4; t = 23.6, p < 0.001). There was a significant association between the scores of clustered healthy lifestyle practices and life purpose (r = 0.401, p < 0.001). The higher-scoring health-related lifestyle group achieved a higher life purpose than the lower-scoring group. This association between healthy lifestyle practices and life purpose denotes a positive and linear relationship. CONCLUSIONS: Our results suggest that individuals who have a better health-related lifestyle gain a higher sense of life purpose. In other words, a healthy lifestyle predicts a purpose in life. Our findings posit that examining the causal relationship between healthy lifestyle and purpose in life may be a more efficient approach toward health promotion.

OsIDD2, a zinc finger and INDETERMINATE DOMAIN protein, regulates secondary cell wall formation.

Previously, we found 123 transcription factors (TFs) as candidate regulators of secondary cell wall (SCW) formation in rice by using phylogenetic and co-expression network analyses. Among them, we examined in this work the role of OsIDD2, a zinc finger and indeterminate domain (IDD) family TF. Its overexpressors showed dwarfism, fragile leaves, and decreased lignin content, which are typical phenotypes of plants defective in SCW formation, whereas its knockout plants showed slightly increased lignin content. The RNA-seq and quantitative reverse transcription polymerase chain reaction analyses confirmed that some lignin biosynthetic genes were downregulated in the OsIDD2-overexpressing plants, and revealed the same case for other genes involved in cellulose synthesis and sucrose metabolism. The transient expression assay using rice protoplasts revealed that OsIDD2 negatively regulates the transcription of genes involved in lignin biosynthesis, cinnamyl alcohol dehydrogenase 2 and 3 (CAD2 and 3), and sucrose metabolism, sucrose synthase 5 (SUS5), whereas an AlphaScreen assay, which can detect the interaction between TFs and their target DNA sequences, directly confirmed the interaction between OsIDD2 and the target sequences located in the promoter regions of CAD2 and CAD3. Based on these observations, we conclude that OsIDD2 is negatively involved in SCW formation and other biological events by downregulating its target genes.

Evaluation of the R2* value in invasive ductal carcinoma with respect to hypoxic-related prognostic factors using iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL).

OBJECTIVE: To correlate the R2* value obtained by iterative decomposition of water and fat with echo asymmetry and least-squares emission (IDEAL) with fibrotic focus (FF), microvessel density and hypoxic biomarker (HIF-1α) in breast carcinoma. METHODS: Forty-two patients who were diagnosed with invasive ductal carcinoma (IDC) of the breast underwent breast MRI including IDEAL before surgery. The entire region of interest (ROI) was delineated on the R2* map, and average tumour R2* value was calculated for each ROI. Histological specimens were evaluated for the presence of FF, the microvessel density (the average microvessel density and the ratio of peripheral to central microvessel density), and the grading of HIF-1α. RESULTS: FF was identified in 47.6% (20/42) of IDCs. Average R2* value for IDC with FF (42.4±13.2 Hz) was significantly higher than that without FF (28.5±13.9 Hz) (P = 0.01). Spearman rank correlation suggested that the average R2* value correlated with the grade of HIF-1α and the ratio of peripheral to central microvessel density for IDCs (P < 0.001). CONCLUSION: Quantification of tumour R2* using IDEAL is associated with the presence of FF and the overexpression of HIF-1α, and may therefore be useful in predicting hypoxia of breast carcinoma. KEY POINTS: • R2* value obtained by IDEAL correlates with the overexpression of HIF-1α. • R2* value obtained by IDEAL is associated with fibrotic focus. • R2* quantification may be useful in predicting hypoxia of breast carcinoma.

Prediction of Femoral Neck Strength in Patients with Diabetes Mellitus with Trabecular Bone Analysis and Tomosynthesis Images.

Purpose To determine trabecular bone analysis values by using tomosynthesis images in determining femoral neck strength in patients with diabetes mellitus and compare its parameters between vertebral compression fracture and nonfracture groups. Materials and Methods The institutional review board approved this study, and written informed consent was obtained from all patients. Forty-nine patients with diabetes mellitus were included. Within 1 week, patients underwent dual x-ray absorptiometry (DXA), tomosynthesis, and computed tomography (CT) covering the T10 vertebral body to the hip joints. The trabecular patterns of tomosynthesis images were extracted, and the total strut length, bone volume per tissue volume, and five textural features (homogeneity, entropy, correlation, contrast, and variance) were obtained as the indices of tomosynthesis images. Failure load of the femoral neck, which was determined with the CT-based finite-element method (FEM), was used as the reference standard for bone strength. A forward stepwise multiple regression analysis for evaluating the availability of the tomosynthesis image indices was performed. The bone mineral density (BMD) at DXA and tomosynthesis image indices were compared between the vertebral compression fracture (n = 16) and nonfracture groups (n = 33) according to Genant semiquantitative morphometry methods by using one-way analysis of variance. Results The combination of BMD with the bone volume per tissue volume at the principal tensile group and the correlation at the principal compressive group showed the highest correlation to the failure load at CT FEM, and the correlation (r2 = 0.83) was higher than that between the failure load and the BMD alone (r2 = 0.76; P < .001). The averages of the bone volume per tissue volume and entropy at the principal tensile group in the vertebral compression fracture group were lower than those in the nonfracture group (P = .017 and P = .029, respectively), but there was no difference in BMD. Conclusion Tomosynthesis-based trabecular bone analysis is technically feasible and, in combination with BMD measurements, can potentially be used to determine bone strength in patients with diabetes mellitus. © RSNA, 2016 Online supplemental material is available for this article.

Pleomorphic Carcinoma of the Lung: Relationship Between CT Findings and Prognosis.

OBJECTIVE: The objective of our study was to assess the radiologic and clinical findings of pleomorphic carcinoma (PC) of the lung and to evaluate whether there are any characteristic features that can be used to predict prognosis. MATERIALS AND METHODS: Forty-four consecutive patients whose diagnosis of PC was histologically confirmed through resection of the lung tumor were included in this study. The clinical and CT findings of these patients were retrospectively reviewed. Two thoracic radiologists evaluated the CT findings including the size, location, internal characteristics, and margin characteristics of the tumors and the presence of chest wall invasion, mediastinal invasion, and surrounding lung abnormalities. A multivariate analysis by the Cox proportional hazards regression model was used to identify variables that can be used to predict overall survival and disease-free survival. RESULTS: In the patients with PC, a central low-attenuation area or cavity (40/44, 91%), chest wall invasion (19/44, 43%), and pulmonary emphysema (30/44, 68%) were frequently observed on CT. On multivariate analysis, a massive central low-attenuation area or cavity (> 25% of the lesion) on CT indicating necrosis was the only significant independent factor for overall survival and disease-free survival (p < 0.05). Clinical findings, the presence of lymph node metastasis at surgery, and postoperative pathologic stage were not significant predictors of overall survival and disease-free survival. CONCLUSION: A massive central low-attenuation area or cavity on CT was the only predictor of overall survival and disease-free survival in patients with lung PC.

Evaluation of the Differences in the Effects of Antihypertensive Drugs on Blood Pressure Variability by 24-Hour Ambulatory Blood Pressure Monitoring in Chronic Cerebrovascular Disease.

BACKGROUND: It has been suggested that antihypertensive drug therapy is attributable to the lower blood pressure variability, we investigated the effects of 4 classes of antihypertensives on the blood pressure variability; in addition, we also compared the effects among 4 calcium channel blockers. METHODS: We measured the 24-hour blood pressure variability in 309 patients with a history of cerebrovascular disease treated with angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, ß blocker, or calcium channel blocker. RESULTS: The daytime blood pressure variability treated with ß blockers (14.3 ± 3.1) was higher than that treated with an angiotensin receptor blockers (11.5 ± 3.1) or calcium channel blockers (12.6 ± 3.4) in patients with cerebrovascular disease (P < .05). In the analysis of the patient distribution of blood pressure variability, patients receiving ß blockers occurred more frequently in the higher blood pressure variability (P = .0023). Treatment with angiotensin receptor blockers and cilnidipine, which blocks N-type calcium channels, was shown to be more frequently associated with the lower blood pressure variability (P = .0202 and .0467). The mean blood pressure of patients grouped by distribution of blood pressure variability was found to be independent to blood pressure variability, for any of the antihypertensive drugs or calcium channel blockers examined. CONCLUSIONS: From the results, it is suggested that angiotensin receptor blocker and calcium channel blockers rather than ß blockers may be more favorable for blood pressure management in patients with cerebrovascular disease. Among the calcium channel blockers, cilnidipine may be more favorable than other calcium channel blockers.

High-resolution MRI predicts steroid injection response in carpal tunnel syndrome patients.

OBJECTIVES: To correlate median nerve T2 signal and shape at the carpal tunnel with steroid injection (SI) response in carpal tunnel syndrome (CTS) patients. METHODS: One hundred and sixty-three CTS wrists of 92 consecutive patients who were scheduled to undergo SI were prospectively evaluated with 3-T magnetic resonance imaging (MRI) and a nerve conduction study. All patients underwent axial high-resolution T2-weighted MRI (in-plane resolution of 0.25 × 0.25 mm). The CTS wrists were classified into three groups according to the nerve T2 signal and the flattening ratio at the hook of hamate level: group 1, high and oval; group 2, high and flat; group 3, low and flat. Clinical response to SI was evaluated at 6 months after injection. RESULTS: One hundred and thirteen of the 163 wrists (69.3%) responded well to SI. The percentage of improvement was 81.7% (49/60) in group 1, 69.9% (51/73) in group 2, and 43.3% (13/30) in group 3 (P < 0.01). On stepwise logistic regression analysis high-resolution MRI was the only significant independent factor for SI response in CTS patients (P < 0.01). CONCLUSIONS: High-resolution MRI correlates well with SI response in CTS patients and seems useful for predicting SI response. KEY POINTS: • MRI may help determine appropriate care in carpal tunnel syndrome. • MRI helps in therapeutic decision-making whenever steroid injection is considered. • T2 signal decrease of the median nerve correlates with poor outcome. • T2 signal decrease of median nerve may reflect fibrosis and amyloid deposition.

Effectiveness of using long-acting angiotensin II type 1 receptor blocker in Japanese obese patients with metabolic syndrome on morning hypertension monitoring by using telemedicine system (FUJIYAMA study).

AIM: Recently, obesity patients have been diagnosed as metabolic syndrome. The aim of this study was to evaluate which angiotensin type 1 receptor blockers (ARBs), telmisartan or candesartan, is superior for the control of home blood pressure (BP) in the morning when the outpatient clinic BP was well controlled in the patients with metabolic syndrome. METHODS: The patients with metabolic syndrome were enrolled. Home BP was monitored by using a telemedicine system. After a 2- to 4-week control period to establish baseline home BP values, these patients were randomly divided into telmisartan (20-80 mg) and candesartan (4-12 mg) groups. These end points were evaluated by using the telemedicine system during steady-state active therapy. A total of 356 patients attending 60 outpatient Japanese centers were recruited. RESULTS: On a day of active therapy, telmisartan significantly lowered both systolic and diastolic home BP in the morning to a greater extent compared to candesartan. At the end of the study, reductions in systolic and diastolic home BP in the morning, in telmisartan group were significantly larger compared to the changes in the candesartan group (systolic; Tel: 12.0 ± 8.9 versus Can: 8.1 ± 17.1 mmHg, p = 0.0292, diastolic; Tel: 7.4 ± 6.1 versus Can: 3.7 ± 6.8 mmHg, p = 0.0053). Additionally in the telmisartan treated group, LDL-cholesterol showed significant reduction (p = 0.037), but candesartan did not. CONCLUSION: The present study by using the telemedicine system clearly demonstrated that telmisartan has a strong effect on reducing morning home BP, and a good effect on lipid metabolism in patients with metabolic syndrome.

Does health literacy influence health-related lifestyle behaviors among specialists of health management? A cross-sectional study.

BACKGROUND: Noncommunicable diseases (NCDs), such as health-related lifestyle diseases, are the leading cause of mortality and societal and economic burdens. Poor lifestyle behaviors, which are modifiable to improve health, can cause diseases, including NCDs. Health literacy has been recognized as an important determinant of health, and studies have shown that higher health literacy is associated with better health outcomes and positive health-related behaviors. However, few studies have investigated the association between health literacy and health-related lifestyle behaviors to understand the mechanistic link between them. Thus, this study investigated the extent to which health literacy at different levels influences health-related lifestyle behaviors. METHODS: A cross-sectional study was conducted among Japanese health management specialists (N = 1,920). Functional, critical, and communicative health literacy were measured. Lifestyle behaviors (exercise, diet and nutrition, sleep, rest, smoking, and alcohol intake), in line with the Japanese National Health Promotion Program, were assessed and calculated into a total cumulative score of health-related lifestyle behaviors. Moreover, we analyzed the associations between the three levels of health literacy and lifestyle behaviors using regression analyses by adjusting for socio-psycho-demographic factors. RESULTS: Multiple linear regression analyses showed a significant association between the Japanese version of the European Health Literacy Survey Questionnaire and total health-related lifestyle scores (standardized ß = 0.160, p < 0.001, R2 = 0.136) after adjusting for sociodemographic factors. Similarly, the association between communicative and critical health literacy and the total health-related lifestyle scores was significant (standardized ß = 0.122, p < 0.001, R2 = 0.125). The analysis indicated that individuals who had higher level of health literacy (critical and communicative) than functional health literacy (Japanese version of the Newest Vital Sign score) had higher health-related lifestyle behaviors. CONCLUSIONS: A higher level of health literacy is associated with health-related lifestyle behaviors. Health literacy can be a target for interventions to achieve the national goal of lifestyle-related disease prevention and control.

Association of Health Literacy With the Prevalence of Cardiovascular Diseases and Their Risk Factors Among Older Japanese Health Management Specialists.

In this study, we aimed to determine the association between health literacy and the development of cardiovascular diseases (CVDs), among an older population. This cross-sectional study was conducted among Japanese health management specialists (N = 593). Higher levels (communicative and critical) of health literacy and CVD risk factors (diabetes mellitus, hypertension, dyslipidemia, and obesity) were measured. The mean patient age was 71.3 years. Logistic regression analyses showed statistically significant associations between higher levels of health literacy and the prevalence of CVDs (ß coefficient = -.091, p < .05) and metabolic risk factors (ß coefficient = -.084, p < .01). There was a statistically significant association between health literacy and the count of CVDs (and its risk factors) (ß coefficients of Poisson regression = -.036, p < .05). The results show health literacy to be fundamentally related to low prevalence of cardiovascular diseases and their associated metabolic risk factors.

Association between health literacy and purpose in life and life satisfaction among health management specialists: a cross-sectional study.

Purpose in life is anchored as a goal in national health promotion plans in several countries. Health literacy is the ability to find, understand, use, and evaluate health-related information; this ability has been investigated in terms of its effect on health outcomes and is said to play a critical role in health promotion. In the context of national health promotion, the effect of health literacy on purpose in life and life satisfaction remains unclear; therefore, this study aims to determine the effect of health literacy. A cross-sectional study was conducted on Japanese health management specialists (N = 1920). Health literacy was measured using the Communicative and Critical Health Literacy scale. Purpose in life and life satisfaction were measured using the Ikigai-9 scale and a Likert scale, respectively. We analyzed the associations between health literacy and purpose in life and life satisfaction with regression analyses. Age, sex, income, education, marital status, psychological stress, and diseases as present illness were adjusted in the statistical models. Our multiple linear regressions indicated that health literacy was significantly associated with purpose in life (ß = 0.199, p < 0.001), after adjusting for covariates (age, sex, income, education, marital status, psychological factor, and disease status). Life satisfaction was also significantly associated with health literacy (ß = 0.126, p < 0.001). Health literacy is associated with purpose in life and life satisfaction among specialists in health management. Health literacy plays a critical role in lifestyle-related disease prevention and health promotion. Interventions to improve health literacy may be warranted in the context of national health promotion.

Influence of Perceived Stress and Stress Coping Adequacy on Multiple Health-Related Lifestyle Behaviors.

Stress is a primary target of national health promotion efforts such as Healthy Japan in the 21st century (HJ21). However, little is known about how the combination of perceived stress and coping adequacy influence health-related lifestyle behaviors in line with national health promotion. This study assessed the association between combined perceived stress and coping adequacy and multiple health-related lifestyle behaviors in HJ21 practices. This cross-sectional survey that included specialists in health management comprehensively assessed multiple health-related lifestyle behaviors in accordance with HJ21. Total health-related lifestyle behavior scores were calculated and perceived stress and coping adequacy were recorded and categorized into four groups with group 1 to 4 being high to none, and highly adequate to not at all, respectively. The average total lifestyle behavior scores (standard deviation [SD]) were 35.1 (3.5), 33.7 (3.6), 31.8 (3.8), and 30.5 (4.9) for groups 1 to 4 of coping adequacy (p < 0.001). Further, individuals who had higher stress coping adequacy had better multiple health-related lifestyle behaviors after adjusting for demographic factors and perceived stress in the linear trend among the groups. Stress coping skills might be an essential target for stress reduction, ultimately leading to health promotion for disease prevention and longevity.

Does Improvement in Health-Related Lifestyle Habits Increase Purpose in Life among a Health Literate Cohort?

A growing number of studies have revealed the association between health-related lifestyle habits and purpose in life. However, the mechanism linking the two has not been adequately understood. This study aims to examine the effect of changes in health-related lifestyle habits on purpose in life. A retrospective cohort study was conducted on certified professional specialists of health management. We analyzed the cohort's demographic information, health-related lifestyle behaviors, reported changes in health-related lifestyle habits (exercise, diet, sleep, and other habits), and purpose in life using a validated tool (Ikigai-9). The cohort was divided into four groups based on the number of reported changes in health-related lifestyles. The purpose in life score was compared among the four groups with and without adjusting for lifestyle. In total, there were 4820 participants. The means (and SD) of the Ikigai-9 score for groups 1, 2, 3, and 4 were 31.4 (6.6), 32.2 (5.6), 32.8 (5.8), and 34.9 (5.4), respectively. There was a statistically significant difference in the Ikigai-9 score among the groups. Healthier changes in lifestyle habits increased perceptions of purpose in life. Both purpose in life and health-related lifestyle habits might be the target factors for disease prevention and health promotion.

Mediastinal and axillar lymphadenopathy in patients with rheumatoid arthritis: prevalence and clinical significance.

BACKGROUND: With recent advances of biological disease-modifying antirheumatic drugs, chest CT has been increasingly performed in rheumatoid arthritis (RA) patients, and mediastinal/axillar lymphadenopathy is being detected. PURPOSE: To determine the prevalence of mediastinal and axillar lymph node enlargements on chest CT in RA patients at the initial diagnosis, and to assess its clinical significance. MATERIAL AND METHODS: We retrospectively reviewed the medical records and chest CT findings of 78 consecutive RA patients. The short axis of the most enlarged lymph nodes (SLN) on CT was measured for the mediastinal and axillar regions separately. The SLN was classified into two groups: Group 1, 10 mm or less; and Group 2, larger than 10 mm. RESULTS: Group 2 was observed in 13 of 78 patients (17%) for the mediastinum, and in 29 (37%) for the axilla; 11 patients (14%) showed Group 2 for both regions. The Group 2 patients (n = 31), either mediastinum or axilla, showed significantly higher simple disease activity index (SDAI) (mean, 36.0) than the patients of Group 1 (n = 47; mean SDAI, 23.0) (p < 0.001). For the mediastinal SLN, the RA-related lung disease was more frequently observed in the Group 2 patients than in the Group 1 (p = 0.036). CONCLUSION: The mediastinal and/or axillar lymphadenopathy on chest CT may reflect the activity of RA. The mediastinal lymphadenopathy also seems to relate to the RA-related lung disease.

[POEMS syndrome presenting with transient immunoglobulin isotype switching after successful treatment with autologous peripheral blood stem cell transplantation].

A 60-year-old man was admitted with muscle weakness and numbness in the extremities. Based on the existence of monoclonal gammopathy of the IgG-lamda type, a slight increase of plasma cells in the bone marrow, and an elevated level of serum vascular endothelial growth factor (VEGF), the diagnosis of POEMS syndrome was made. After peripheral blood stem cell collection by etoposide and G-CSF, the patient received high dose melphalan (200 mg/m2) therapy supported by autologous peripheral blood stem cell transplantation (autoPBSCT). After high-dose chemotherapy with autoPBSCT, the serum VEGF level normalized and the monoclonal IgG-lamda, disappeared. The patient gradually recovered from a bedridden state and at the time of writing has no impairment in his activities of daily life. After the autoPBSCT, monoclonal IgG-kappa, protein was detected transiently in serum. The new monoclonal immunoglobulin was considered to be due to normal immune reconstitution after myeloablation rather than alteration of the abnormal plasma cell clone, similarly as oligoclonal immunoglobulins occur in multiple myeloma after autoPBSCT. AutoPBSCT with high-dose chemotherapy should be considered among the treatments of choice for POEMS syndrome.

Stereoselective synthesis of axially chiral N-C bonds in N-aryl indoles.

[reaction: see text] N-Aryl indoles with axially chiral N-C bonds were synthesized by stereoselective nucleophilic aromatic substitution reactions of planar chiral arene chromium complexes. Stereoselective chromium tricarbonyl migration was achieved in the sterically hindered N-aryl indole chromium complex by refluxing in toluene.

Quantification of bone marrow fat content using iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL): reproducibility, site variation and correlation with age and menopause.

OBJECTIVE: To determine the reproducibility of the quantitative chemical shift-based water-fat separation method with a multiecho gradient echo sequence [iteraterative decomposition of water and fat with echo asymmetry and least-squares estimation quantitation sequence (IDEAL-IQ)] for assessing bone marrow fat fraction (FF); to evaluate variation of FF at different bone sites; and to investigate its association with age and menopause. METHODS: 31 consecutive females who underwent pelvic iterative decomposition of water and fat with echo asymmetry and least-squares estimation at 3-T MRI were included in this study. Quantitative FF using IDEAL-IQ of four bone sites were analyzed. The coefficients of variance (CV) on each site were evaluated repeatedly 10 times to assess the reproducibility. Correlations between FF and age were evaluated on each site, and the FFs between pre- and post-menopausal groups were compared. RESULTS: The CV in the quantification of marrow FF ranged from 0.69% to 1.70%. A statistically significant correlation was established between the FF and the age in lumbar vertebral body, ilium and intertrochanteric region of the femur (p < 0.001). The average FF of post-menopausal females was significantly higher than that of pre-menopausal females in these sites (p < 0.05). In the greater trochanter of the femur, there was no significant correlation between FF and age. CONCLUSION: In vivo IDEAL-IQ would provide reliable quantification of bone marrow fat. ADVANCES IN KNOWLEDGE: IDEAL-IQ is simple to perform in a short time and may be practical for providing information on bone quality in clinical settings.

Thin-section chest CT findings in polymyalgia rheumatica: a comparison between with and without rheumatoid arthritis.

We retrospectively compared the thin-section chest computed tomography (CT) findings between 25 patients of polymyalgia rheumatica (PMR) with rheumatoid arthritis (RA) and 29 patients of PMR without RA. PMR patients showed high-frequency CT abnormalities (68.5%) regardless of the association with RA. Ground-glass opacity (56% vs. 24%), traction bronchiectasis (44% vs. 3%), architectural distortion (32% vs. 0%), centrilobular nodules (32% vs. 7%), and honeycombing (20% vs. 0%) were significantly more common in the PMR with RA group than in the PMR without RA group (P<.01). PMR patients with RA have more increased prevalence of chest CT abnormalities than those without RA.

Evolutionary evidence of tumor necrosis factor super family members in the Japanese pufferfish (Takifugu rubripes): Comprehensive genomic identification and expression analysis.

Tumor necrosis factor (TNF) and its superfamily (TNFSF) members are important inflammatory cytokines. Although fish have fourteen TNFSF genes, their genomic location and existence are yet to be described and confirmed in the Japanese pufferfish (Fugu) (Takifugu rubripes). Therefore, we conducted in silico identification, synteny analysis of TNFSF genes from Fugu with that of zebrafish and human TNFSF loci and their expression analysis in various tissues. We identified ten novel TNFSF genes, viz. TNFSF5 (CD40L), TNFSF6 (FasL), three TNFSF10 (TRAIL) (-1, 2 and 3), TNFSF11 (RANKlg), TNFSF12 (TWEAK), two TNFSF13B (BAFF) (1 and 2) and TNFSF14 (LIGHT) belonging to seven TNFSFs in Fugu. Several features such as existence of TNF family signature, conservation of genes in TNF loci with human and zebrafish chromosomes and phylogenetic clustering with other teleost TNFSF orthologs confirmed their identity. Fugu TNFSF genes were constitutively expressed in all eight different tissues with most of them expressed highly in liver. Fugu TNFSF10 gene has three homologs present on chromosomes 10 (TNFSF10-1), 8 (TNFSF10-2) and 2 (TNFSF10-3). Moreover, a phylogenetic analysis containing all available vertebrate (mammals, birds, reptiles, amphibians and fish) TNFSF10 orthologs showed that Fugu TNFSF10-1 and 10-3 are present in all vertebrates, whereas TNFSF10-2 was not related to any mammalian and avian orthologs. Viral double-stranded RNA mimic poly (I:C) caused an elevated expression of three Fugu TNFSF10 genes in head kidney cells at 4h indicating probable role of these genes to induce apoptosis in virus-infected cells. In conclusion, Fugu possesses genes belonging to nine TNFSFs including the newly identified seven and previously reported two, TNFSF New (TNF-N) and TNFSF2 (TNF-α). Our findings would add up information to TNFSF evolution among vertebrates.

Presence of two tumor necrosis factor (tnf)-α homologs on different chromosomes of zebrafish (Danio rerio) and medaka (Oryzias latipes).

Two or more isoforms of several cytokines including tumor necrosis factors (tnfs) have been reported from teleost fish. Although zebrafish (Danio rerio) and medaka (Oryzias latipes) possess two tnf-α genes, their genomic location and existence are yet to be described and confirmed. Therefore, we conducted in silico identification, synteny analysis of tnf-α and tnf-n from both the fish with that of human TNF/lymphotoxin loci and their expression analysis in zebrafish. We identified two homologs of tnf-α (named as tnf-α1 and tnf-α2) and a tnf-n gene from zebrafish and medaka. Genomic location of these genes was found to be as: tnf-α1, and tnf-n and tnf-α2 genes on zebrafish chromosome 19 and 15 and medaka chromosome 11 and 16, respectively. Several features such as existence of TNF family signature, conservation of genes in TNF loci with human chromosome, phylogenetic clustering and amino acid similarity with other teleost TNFs confirmed their identity as tnf-α and tnf-n. There were a constitutive expression of all three genes in different tissues, and an increased expression of tnf-α1 and -α2 and a varied expression of tnf-n ligand in zebrafish head kidney cells induced with 20 µg mL(-1) LPS in vitro. Our results suggest the presence of two tnf-α homologs on different chromosomes of zebrafish and medaka and correlate this incidence arising from the fish whole genome duplication event.