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Aim: To assess the relationship between body mass index (BMI), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), epicardial adipose tissue (EAT), pericardial adipose tissue (PAT) and clinical outcomes in dilated cardiomyopathy (DCM) patients., Methods: Non-ischemic DCM patients were prospectively enrolled. Regional adipose tissue, cardiac function, and myocardial tissue characteristics were measured by cardiac magnetic resonance (CMR). The primary endpoint included all-cause mortality and heart transplantation (HTX)., Results: This study enrolled 1042 DCM patients (68% men, mean age 48 ± 15 years, mean BMI 23.9 ± 4.0 kg/m2). Underweight patients were more frequently women, had lower blood pressure, worse New York Heart Association (NYHA) class, reduced biventricular ejection fraction, and higher native T1 and extracellular volume fraction (ECV) value. Similarly, reduced regional adipose tissue was associated with adverse heart remodeling, worse cardiac function, and higher diffuse myocardial fibrosis. After a median follow-up of 41 months, primary endpoint occurred in 237 patients. BMI (HR: 0.94, 95% CI: 0.90 - 0.98, P = 0.006), VAT thickness (per 1 mm: HR 0.94, 95% CI: 0.91 - 0.97, P < 0.001), and EAT volume (per 1 mL: HR 0.96, 95% CI: 0.95 - 0.97, P < 0.001) were independent predictors of primary endpoint. EAT volume showed highest predictive value for heart failure death/HTX (C-index: 0.70). BMI was the best predictor of arrhythmia endpoint (C-index: 0.64)., Conclusions: Lower BMI and thinner regional adipose tissue represented the worse clinical phenotype and adverse remodeling, and were associated with worse clinical outcomes in patients with DCM., (© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: People with the human immunodeficiency virus (PWH) have microvascular disease. Because perivascular adipose tissue (PVAT) regulates microvascular function and adipose tissue is inflamed in PWH, we tested the hypothesis that PWH have inflamed PVAT that impairs the function of their small vessels., Methods: Subcutaneous small arteries were dissected with or without PVAT from a gluteal skin biopsy from 11 women with treated HIV (WWH) aged < 50 years and 10 matched women without HIV, and studied on isometric myographs. Nitric oxide (NO) and reactive oxygen species (ROS) were measured by fluorescence microscopy. Adipokines and markers of inflammation and ROS were assayed in PVAT., Results: PVAT surrounding the small arteries in control women significantly (P < .05) enhanced acetylcholine-induced endothelium-dependent relaxation and NO, and reduced contractions to thromboxane and endothelin-1. However, these effects of PVAT were reduced significantly (P < .05) in WWH whose PVAT released less adiponectin but more markers of ROS and inflammation. Moderation of contractions by PVAT were correlated positively with adipose adiponectin., Conclusions: PVAT from WWH has oxidative stress, inflammation, and reduced release of adiponectin, which may contribute to enhanced contractions and therefore could promote small-artery dysfunction., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Protein engineering is an emerging field in biotechnology that has the potential to revolutionize various areas, such as antibody design, drug discovery, food security, ecology, and more. However, the mutational space involved is too vast to be handled through experimental means alone. Leveraging accumulative protein databases, machine learning (ML) models, particularly those based on natural language processing (NLP), have considerably expedited protein engineering. Moreover, advances in topological data analysis (TDA) and artificial intelligence-based protein structure prediction, such as AlphaFold2, have made more powerful structure-based ML-assisted protein engineering strategies possible. This review aims to offer a comprehensive, systematic, and indispensable set of methodological components, including TDA and NLP, for protein engineering and to facilitate their future development., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Glycogen storage disease (GSD) type Ⅲa is a rare autosomal recessive disorder resulting in the accumulation of abnormally structured glycogen in the liver, skeletal muscle, and cardiac muscle. Cardiovascular magnetic resonance (CMR) tissue characteristics in GSD have rarely been reported., Case Summary: We report a 24-year-old male patient suffering from recurrent palpitation and atypical chest pain for 5 years with suspected hypertrophic cardiomyopathy. Laboratory tests revealed an elevated creatine kinase, and physical exam revealed hepatosplenomegaly. Cardiovascular magnetic resonance demonstrated asymmetrical massive left ventricular hypertrophy with a maximal thickness of 34.6 mm in the septum. In the regions with focal late gadolinium enhancement (LGE) in the anterior septum, both native T1 and extracellular volume (ECV) are elevated. However, in the LGE-negative regions of the myocardium, native T1 was elevated without elevation in ECV (septum, 22.7%; free wall, 20.9%). Whole exome sequencing revealed a novel pathogenic homozygous nonsense variant of the AGL gene (c.4284 T > G, p. Tyr1428*), confirming the diagnosis of the patients as GSD type Ⅲa., Discussion: This case showed increased diffuse native T1 but not ECV on CMR in LGE-negative myocardium in GSD, which indicates that the T1 value is increased with an accumulation of glycogen in the myocardium, but the ECV space was not expanded in this process. Genetic testing should be obtained in severe LV hypertrophy when multi-organ involvement is present, and myocardial tissue characterization is discrepant between T1 elevation and normal ECV to consider glycogen storage disorder., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To explore the prognosis of myocardial oedema measured by T2 mapping in hypertrophic cardiomyopathy (HCM)., Methods and Results: A total of 674 patients with HCM (age: 50 ± 15 years, 60.5% males) who underwent cardiovascular magnetic resonance were prospectively enrolled from 2011 to 2020. One hundred healthy controls (age: 48 ± 19 years, 58.0% males) were included for comparison. Myocardial oedema was quantitatively measured by T2 mapping in both global and segmental myocardium. The endpoints were defined as a combination of cardiovascular death and appropriate implantable cardioverter defibrillator discharge. During a median follow-up of 36 months (interquartile range: 24-60 months), 55 patients (8.2%) had cardiovascular events. Patients with cardiovascular events had a higher T2 max, T2 min, and T2 global values (all P < 0.001) than patients who remained event free. Survival analysis demonstrated that patients with HCM with late gadolinium enhancement [LGE(+)] and T2 max ≥44.9 ms had a higher risk of developing cardiovascular events (P < 0.001). A multivariate Cox regression analysis showed that T2 max, T2 min, and T2 global provided significant prognostic value to predict cardiovascular events (all P < 0.001). According to the C-index (0.825, 0.814), net reclassification index (0.612, 0.536, both P < 0.001), and integrative discrimination index (0.029, 0.029, both P < 0.05), T2 max or T2 min significantly increased the predictive performance of established risk factors, including extensive LGE., Conclusion: Patients with HCM with LGE(+) and higher T2 had worse prognosis than those with LGE(+) and lower T2., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The ability to suppress unwelcome memories is important for productivity and well-being. Successful memory suppression is associated with hippocampal deactivations and a concomitant disruption of this region's functionality. Much of the previous neuroimaging literature exploring such suppression-related hippocampal modulations has focused on the region's negative coupling with the prefrontal cortex. Task-based changes in functional connectivity between the hippocampus and other brain regions still need further exploration. In the present study, we utilize psychophysiological interactions and seed connectome-based predictive modeling to investigate the relationship between the hippocampus and the rest of the brain as 134 participants attempted to suppress unwanted memories during the Think/No-Think task. The results show that during retrieval suppression, the right hippocampus exhibited decreased functional connectivity with visual cortical areas (lingual and cuneus gyrus), left nucleus accumbens and the brain-stem that predicted superior forgetting of unwanted memories on later memory tests. Validation tests verified that prediction performance was not an artifact of head motion or prediction method and that the negative features remained consistent across different brain parcellations. These findings suggest that systemic memory suppression involves more than the modulation of hippocampal activity-it alters functional connectivity patterns between the hippocampus and visual cortex, leading to successful forgetting., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Aims: Post-infarct myocardium contains viable corridors traversing scar or lipomatous metaplasia (LM). Ventricular tachycardia (VT) circuitry has been separately reported to associate with corridors that traverse LM and with repolarization heterogeneity. We examined the association of corridor activation recovery interval (ARI) and ARI dispersion with surrounding tissue type., Methods and Results: The cohort included 33 post-infarct patients from the prospective Intra-Myocardial Fat Deposition and Ventricular Tachycardia in Cardiomyopathy (INFINITY) study. We co-registered scar and corridors from late gadolinium enhanced magnetic resonance, and LM from computed tomography with intracardiac electrogram locations. Activation recovery interval was calculated during sinus or ventricular pacing, as the time interval from the minimum derivative within the QRS to the maximum derivative within the T-wave on unipolar electrograms. Regional ARI dispersion was defined as the standard deviation (SD) of ARI per AHA segment (ARISD). Lipomatous metaplasia exhibited higher ARI than scar [325 (interquartile range 270-392) vs. 313 (255-374), P < 0.001]. Corridors critical to VT re-entry were more likely to traverse through or near LM and displayed prolonged ARI compared with non-critical corridors [355 (319-397) vs. 302 (279-333) ms, P < 0.001]. ARISD was more closely associated with LM than with scar (likelihood ratio χ2 50 vs. 12, and 4.2-unit vs. 0.9-unit increase in 0.01*Log(ARISD) per 1 cm2 increase per AHA segment). Additionally, LM and scar exhibited interaction (P < 0.001) in their association with ARISD., Conclusion: Lipomatous metaplasia is closely associated with prolonged local action potential duration of corridors and ARI dispersion, which may facilitate the propensity of VT circuit re-entry., Competing Interests: Conflict of interest: S.N. is a consultant for CardioSolv and Circle CVI; and principal investigator for research funding from Biosense Webster, ImriCor, Siemens, ADAS software, and the US NIH. F.E.M. has served as consultant for Abbott Medical, Biosense Webster, Biotronik, and Medtronic Inc. The University of Pennsylvania Conflict of Interest Committee manages all commercial arrangements. The remaining authors have declared no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: To evaluate the impact of a simplified, rapid cardiovascular magnetic resonance (CMR) protocol embedded in care and supported by a partner education programme on the management of cardiomyopathy (CMP) in low- and middle-income countries (LMICs)., Methods and Results: Rapid CMR focused particularly on CMP was implemented in 11 centres, 7 cities, 5 countries, and 3 continents linked to training courses for local professionals. Patients were followed up for 24 months to assess impact. The rate of subsequent adoption was tracked. Five CMR conferences were delivered (920 attendees-potential referrers, radiographers, reporting cardiologists, or radiologists) and five new centres starting CMR. Six hundred and one patients were scanned. Cardiovascular magnetic resonance indications were 24% non-contrast T2* scans [myocardial iron overload (MIO)] and 72% suspected/known cardiomyopathies (including ischaemic and viability). Ninety-eighty per cent of studies were of diagnostic quality. The average scan time was 22 ± 6 min (contrast) and 12 ± 4 min (non-contrast), a potential cost/throughput reduction of between 30 and 60%. Cardiovascular magnetic resonance findings impacted management in 62%, including a new diagnosis in 22% and MIO detected in 30% of non-contrast scans. Nine centres continued using rapid CMR 2 years later (typically 1-2 days per week, 30 min slots)., Conclusions: Rapid CMR of diagnostic quality can be delivered using available technology in LMICs. When embedded in care and a training programme, costs are lower, care is improved, and services can be sustained over time., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Aims: To evaluate the prognostic value of left ventricular (LV) remodelling index (RI) in idiopathic dilated cardiomyopathy (DCM) patients., Methods and Results: We prospectively enrolled 412 idiopathic DCM patients and 130 age- and sex-matched healthy volunteers who underwent cardiovascular magnetic resonance imaging between September 2013 and March 2018. RI was defined as the cubic root of the LV end-diastolic volume divided by the mean LV wall thickness on basal short-axis slice. The primary endpoint included all-cause mortality and heart transplantation. The secondary endpoint included the primary endpoint and heart failure (HF) readmission. During the median follow-up of 28.1 months (interquartile range: 19.3-43.0 months), 62 (15.0%) and 143 (34.7%) patients reached the primary and secondary endpoints, respectively. Stepwise multivariate Cox regression showed that RI [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.11-1.30, P < 0.001], late gadolinium enhancement (LGE) presence and log (N-terminal pro-B-type natriuretic peptide) were independent predictors of the primary endpoint, while RI (HR 1.15, 95% CI 1.08-1.23, P < 0.001) and extracellular volume were independent predictors of the secondary endpoint. The addition of RI to LV ejection fraction (EF) and LGE presence showed significantly improved global χ2 for predicting primary and secondary endpoints (both P < 0.001). Furthermore, RI derived from echocardiography also showed independent prognostic value for primary and secondary endpoints with clinical risk factors., Conclusions: RI is an independent predictor of all-cause mortality, heart transplantation, and HF readmission in DCM patients and provides incremental prognostic value to LVEF and LGE presence., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: The increasing number of working elderly people has enhanced the importance of workplace health promotion activities. We investigated the association between the health status of workers approximately 60 years of age and the risk of all-cause mortality after compulsory retirement in Japan., Methods: The 2026 participants (1299 males and 727 females) had retired from a metal-products factory at ≥60 years of age. Baseline health examinations were conducted at 60 years of age and included questions about medical history and lifestyle factors; the participants also underwent a physical examination. The participants were followed up annually by mail for an average of 7.4 years. The association between health status at age 60 years and the risk of all-cause mortality was assessed by Cox proportional hazards regression analysis., Results: During the study, 71 deaths were reported. The age- and sex-adjusted hazard ratio (HR [95% confidence interval]) for all-cause mortality was higher for males (HR, 3.41 [1.73-6.69]) compared with females, participants with a low body mass index (<18.5 kg/m 2 ; HR 3.84 [1.91-7.73]) compared with normal body weight, smokers (HR, 2.63 [1.51-4.58]) compared with nonsmokers, and those with three or more of four metabolic abnormalities (obesity, high blood pressure, dyslipidemia, and glucose intolerance) (HR 2.29 [1.04-5.02]) compared with no metabolic abnormalities. The associations were unaffected by adjustment for these factors., Conclusion: Maintenance of an appropriate body weight, smoking cessation, and elimination of metabolic syndrome are required for older workers to prevent early death after retirement., (© 2019 The Authors. Journal of Occupational Health published by John Wiley & Sons Australia, Ltd on behalf of The Japan Society for Occupational Health.)

Background: Lipomatous hypertrophy of the interatrial septum (LHIAS) is a common finding on transthoracic echocardiogram (TTE). Occasionally, the appearance of LHIAS is atypical and multimodality imaging is helpful to make the diagnosis. We present a case of atypical LHIAS to highlight the potential aetiologies for an interatrial septal mass and review features on multimodality imaging that help decrease uncertainty and establish a diagnosis., Case Summary: A 64-year-old man with a history of hypertension, diabetes mellitus, and coronary artery disease with multiple percutaneous coronary interventions presented to the emergency room with chest pain. Transthoracic echocardiogram showed a homogenous echo-dense, intracardiac mass present within the interatrial septum. Computed tomography (CT) angiogram of the chest showed a homogenous mass similar in radiodensity to extracardiac and pericardial fat. Cardiac magnetic resonance (CMR) confirmed LHIAS by homogenous signal that was nulled on fat suppression images., Discussion: This case highlights that while most LHIAS has the standard 'dumbbell' appearance on TTE, there are instances where it can appear more like an adherent mass prompting a wider differential. Unenhanced CT of the heart can be used to confirm LHIAS by the presence of low attenuation values for tissue. Alternatively, CMR can be used for tissue characterization and confirmation of LHIAS. Precontrast T2/T1-weighted CMR images with steady-state free precession show high signal intensity in the area of LHIAS and produce a black/hypointense boundary effect between fat and myocardium. A multimodality approach is crucial in arriving at the appropriate diagnosis using the tissue characterization capabilities of CT and CMR., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

MicroRNA-125b (miR-125b), which was previously proved to be a potential immunomodulator in various disease, attenuated mouse hepatic ischemia/reperfusion (I/R) injury in this study. miR-125b was decreased in RAW 264.7 cells exposed to hypoxia/reoxygenation (H/R). The expression of IL-1β, IL-6 and TNF-α in both serum and supernate were reduced in miR-125b over-expression groups. The hepatic histopathological changes were reduced in miR-125b agomir groups. In the miR-125b antagomir groups, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated compared with negative control (NC) groups. The protein expression of TNF receptor-associated factor 6 (TRAF6), IL-1β and the phosphorylation of p65 (p-p65) were suppressed by the up-regulation of miR-125b. Furthermore, the nuclear translocation of p-p65, measured by immunofluorescence, was enhanced by the miR-125b inhibitors. In conclusion, our study indicates that miR-125b protects liver from hepatic I/R injury via inhibiting TRAF6 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signal pathway.

In Mycobacterium tuberculosis-infected macrophages, cyclooxygenase-2 (COX-2) expression considerably increases to defend the body against mycobacteria by regulating adaptive immunity and restoring the mitochondrial inner membrane. Moreover, in cancer cells, COX-2 enhances the autophagy machinery, an important bactericidal mechanism. However, the association between M. tuberculosis-induced COX-2 and autophagy-mediated antimycobacterial response has not been explored. Here, COX-2 expression silencing reduced the autophagy and bactericidal activity against intracellular M. tuberculosis, while COX-2 overexpression reversed the above effects. In addition, enhancement of bactericidal activity was suppressed by inhibiting autophagy in COX-2-overexpressing cells, indicating that COX-2 accelerated mycobacterial elimination by promoting autophagy. Furthermore, the regulatory effects of COX-2 on autophagy were mediated by its catalytic products, which functioned through inhibiting the protein kinase B/mammalian target of rapamycin pathway. Thus, COX-2 contributes to host defense against mycobacterial infection by promoting autophagy, establishing the basis for development of novel therapeutic agents against tuberculosis by targeting COX-2.

Study Question: What are the features of FAM71D (Family with sequence similarity 71, member D) expression and is there an association between FAM71D expression and sperm motility?, Summary Answer: FAM71D, a novel protein exclusively expressed in the testis, is located in sperm flagella and is functionally involved in sperm motility., What Is Known Already: Some testis-specific proteins have been reported as potential diagnostic biomarkers to evaluate the spermatogenesis process and sperm quality. We have identified a novel testis-specific protein, FAM71D, through microarray data analysis, yet little is known about its expression and function., Study Design, Size, Duration: FAM71D mRNA and protein expression was quantified during mouse testis development. Its localization in germ cells was detected by dual-labeled immunostaining in testis sections and sperm smears. The clinical significance was assessed by comparing FAM71D expression in spermatozoa from normozoospermic controls and asthenozoospermic patients., Participants/materials, Setting, Methods: Testes were dissected from C57BL/6 J male mice at postnatal ages of 1, 2, 3, 4, 6, 8 weeks and 6 months, and sperm was collected from cauda epididymides of adult mice by the swim-up method. Human spermatozoa were isolated from 100 human semen samples by density gradient Percoll centrifugation. RT-qPCR and western blot were performed to semi-quantify the expression of FAM71D in mouse testis, and in the ejaculated spermatozoa of normozoospermic controls and asthenozoospermic patients. Immunofluorescence staining was used to detect the localization of FAM71D. Co-immunoprecipitation assay was performed to evaluate the interaction between FAM71D and calmodulin. An antibody blocking assay was employed to assess the role of FAM71D in sperm motility., Main Results and the Role of Chance: Our results showed that FAM71D was exclusively expressed in the testis in an age-dependent manner. FAM71D expression exhibited dynamic change in the cytoplasm of spermatids during spermiogenesis and was finally retained in sperm flagella. FAM71D could interact with calmodulin. Use of anti-FAM71D antibody on sperm significantly decreased sperm motility. Expression level of FAM71D was markedly reduced in the ejaculated spermataozoa of asthenozoospermic patients (P < 0.05), and this was correlated with sperm progressive motility (r = 0.7435, P < 0.0001)., Large Scale Data: N/A., Limitations, Reasons for Caution: The sample size was limited and it is necessary to verify the correlation of FAM71D expression with sperm motility in larger cohorts. Furthermore, our results were descriptive and follow-up studies would be needed to elucidate the detailed role of FAM71D in sperm motility., Wider Implications of the Findings: This is the first systematic study to document the expression of endogenous FAM71D and a function for FAM71D in sperm motility. It provides new insights into our understanding of sperm motility regulation and causes of male infertility., Study Funding/competing Interests: This study was funded by the National Natural Science Foundation of China, Guangdong Natural Science Foundation and the Shenzhen Project of Science and Technology. The authors have no competing interests., (© The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com)

Phenotype-driven mutagenesis is an unbiased method to identify novel genes involved in spermatogenesis and other reproductive processes. Male repro29/repro29 mice generated by the Reproductive Genomics Program at the Jackson Laboratory were infertile with deformed sperm and poor motility. Using selected exonic capture and massively parallel sequencing technologies, we identified a nonsense mutation in the exon 6 of coiled-coil domain-containing 62 gene (Ccdc62), which results in a formation of a premature stop codon and a truncated protein. Among the tissues examined, CCDC62 was found to be expressed at the highest level in mouse testis by reverse transcriptase-PCR (RT-PCR) and Western blot analysis. With immunofluorescent staining, we demonstrated that CCDC62 was expressed in the cytoplasm and the developing acrosome in the spematids of mouse testis, and was specifically localized at the acrosome in mature sperm. The complementation analysis by mating repro29/+ mice with Ccdc62 -/- mice (generated by CRISPR-Cas9 strategy) further provided genetic proof that the infertility of repro29/repro29 mice was caused by Ccdc62 mutation. Finally, it was found that intracellular colocalization and interaction of CCDC62 and Golgi-associated PDZ and coiled-coil motif-containing protein may be important for acrosome formation. Taken together, this study identified a nonsense mutation in Ccdc62, which directly results in male infertility in repro29/repro29 mice., (© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Teratozoospermia is generally associated with clinical infertility. Despite numerous studies, the molecular mechanisms underlying male infertility are still poorly understood. In the present study, we demonstrated that deletion of Spata46, a gene encoding a novel protein of unknown function found in mouse testis, was responsible for male subfertility, and the cause of subfertility was characterized as abnormal sperm head shape and a failure of sperm-egg fusion. We also demonstrated that SPATA46 was expressed predominantly in condensed spermatids, with a highly specific localization restricted to the subacrosomal area; the protein is located at the nuclear membrane due to a transmembrane region in the N-terminus of the protein. At the subcellular level, SPATA46-deficient condensed spermatids displayed structural defects consisting of a discontinuous nuclear envelope and a cavity in the nucleus associated with an abnormal nuclear shape. Additionally, in vitro, we determined that the absence of SPATA46 led to accumulation of sperm around the perivitelline space of eggs, and the same phenomenon was also observed for natural sperm incubated with an anti-SPATA46 antibody, suggesting functional relevance of SPATA46 for sperm-egg fusion. Taken together, these results indicated that SPATA46 is a novel protein involved in reshaping of the sperm head and sperm-egg fusion., (© 2016 by the Society for the Study of Reproduction, Inc.)

Plant 14-3-3 proteins are phosphoserine-binding proteins that regulate a wide array of targets via direct protein-protein interactions. In this study, the role of a 14-3-3 protein, GRF9, in plant response to water stress was investigated. Arabidopsis wild-type, GRF9-deficient mutant (grf9), and GRF9-overexpressing (OE) plants were treated with polyethylene glycol (PEG) to induce mild water stress. OE plant showed better whole-plant growth and root growth than the wild type under normal or water stress conditions while the grf9 mutant showed worse growth. In OE plants, GRF9 favours the allocation of shoot carbon to roots. In addition, GRF9 enhanced proton extrusion, mainly in the root elongation zone and root hair zone, and maintained root growth under mild water stress. Grafting among the wild type, OE, and grf9 plants showed that when OE plants were used as the scion and GRF9 was overexpressed in the shoot, it enhanced sucrose transport into the root, and when OE plants were used as rootstock and GRF9 was overexpressed in the root, it caused more release of protons into the root surface under water stress. Taken together, the results suggest that under PEG-induced water stress, GRF9 is involved in allocating more carbon from the shoot to the root and enhancing proton secretion in the root growing zone, and this process is important for root response to mild water stress., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

High-performance centrifugal partition chromatography (HPCPC) combined with ultraviolet detection was employed for the separation and purification of flavonoids from Glycyrrhiza. At the detection wavelength of 276 nm, two flavonoids, liquiritigenin-4'-apiosyl-glucoside and liquiritin, were successfully separated by HPCPC with an optimized two-phase solvent system composed of ethyl acetate-ethanol-water (1:0.1:1, v/v/v). The purity of these compounds was 95.0 and 97.1%, respectively, as determined by high-performance liquid chromatography. Their structures were identified by electrospray ion source mass spectroscopy (ESI-MS(n)) in the negative ion mode.

Aims: The aim of this study was to investigate age-related differences in the relationship between work-related factors and heavy drinking., Methods: This study in 3,398 male workers at a factory in Japan examined data on heavy drinking, defined as an alcohol consumption >40 g/day, and work-related factors including occupation, shift work, and job stress evaluated using the Japanese version of the Karasek's Job Content Questionnaire (JCQ). In the present cross-sectional study, alcohol consumption was assessed using a self-administered diet history questionnaire (DHQ)., Results: The prevalence of heavy drinkers in the study population was 15.5% and rose with increasing age. An increase in the odds ratio (OR) for heavy drinking was observed consistently in blue-collar workers compared with white-collar workers in all age groups. In subjects aged 20-29 years, shift work had also increased the OR for heavy drinking. In subjects aged 40-49 years, the two groups with a lower decision latitude had an increased OR compared with the highest group. In subjects aged 20-29 years, the age adjusted OR for individuals who received the lowest level of social support in the workplace was increased significantly compared with the highest group (4.22 [95%CI, 1.07-16.62] ). On the other hand, social support showed a positive association with heavy drinking in subjects aged 40-49 and 50-59 years. Job demand was not related to heavy drinking in any of the age groups., Conclusions: Our findings suggest that occupation and work schedule are related to alcohol use more apparently in a younger age group and that psychosocial factors are related to enhancement or prevention of alcohol use.

Aims: To investigate the effects of shift work on increased alcohol intake associated with poor sleep quality., Methods: This cross-sectional survey evaluated the correlation between work schedule, poor sleep quality and heavy drinking among 909 factory workers aged 35-54 years in Japan. Subjects included 530 day workers, 72 shift workers who did not work at night and 290 shift workers who engaged in night work. Heavy drinking was defined as a mean volume of alcohol consumption exceeding 60 g/day., Results: Compared with other workers, night-shift workers who suffered poor sleep quality exhibited the highest frequency of heavy drinking (17.6%). Multiple logistic regression analysis demonstrated that compared with day workers with good sleep, night-shift workers who experienced poor sleep had more than twice the odds of heavy alcohol consumption (odds ratio 2.17 [95% confidence interval (CI), 1.20-3.93]). Shift workers who did not work at night and day workers with poor sleep were not at increased odds of heavy drinking., Conclusion: Shift workers who engage in night work may try to modify their health behavior to cope with sleep problems. Such modification may be a risk factor for heavy drinking.

Background: Epidemiological studies have observed conflicting patterns as to whether overtime work increases blood pressure (BP), probably as a consequence of methodological issues., Methods: We conducted a prospective cohort study to investigate the relationship between overtime work hours and 1-year changes in BP in 1,235 normotensive Japanese male workers who carried out a variety of jobs in a manufacturing factory. Casual BP measurements were repeated at annual health examinations in 2004-2005, using an automatic manometer. An analysis of covariance that incorporated potential confounding factors including baseline age, body mass index (BMI), and lifestyle factors was used to calculate and compare the means of the 1-year change in systolic (SBP) and diastolic BP (DBP). The participants were grouped according to their average monthly overtime work hours obtained from timecard data between April and September 2004., Results: The multivariate-adjusted mean for 1-year change in DBP in 611 male assembly-line workers was 1.5 mm Hg (95% confidence interval (CI) 0.8-2.2) for <40.0 h/month, 2.3 mm Hg (95% CI 1.3-3.2) for 40.0-79.9 h/month, and 5.3 mm Hg (95% CI 2.7-7.9) for ≥ 80.0 h/month (P for heterogeneity = 0.02). A broadly similar pattern was observed for SBP. In contrast, there was no significant difference in means 1-year change for both SBP and DBP in 315 clerks and 309 engineers/special technicians, grouped according to overtime work hours., Conclusions: Extensive overtime work was associated with increased BP in normotensive male assembly-line workers, but not in clerks and engineers/special technicians.

In the practice of molecular dating, substitution saturation will bias the results if not properly modeled. Date estimates based on commonly used mitochondrial DNA sequences likely suffer from this problem because of their high substitution rate. Nevertheless, the patterns and extent of such expected bias remain unknown for many major evolutionary lineages, which often differ in ages, available calibrations, and substitution rates of their mitochondrial genome. In this case study of salamanders, we used estimates based on multiple nuclear exons to assess the effects of saturation on dating divergences using mitochondrial genome sequences on a timescale of ~200-300 My. The results indicated that, due to saturation for older divergences and in the absence of younger effective calibration points, dates derived from the mitochondrial data were considerably overestimated and systematically biased toward the calibration point for the ingroup root. The overestimate might be as great as 3-10 times (about 20 My) older than actual divergence dates for recent splitting events and 40 My older for events that are more ancient. For deep divergences, dates estimated were strongly compressed together. Furthermore, excluding the third codon positions of protein-coding genes or only using the RNA genes or second codon positions did not considerably improve the performance. In the order Caudata, slowly evolving markers such as nuclear exons are preferred for dating a phylogeny covering a relatively wide time span. Dates estimated from these markers can be used as secondary calibrations for dating recent events based on rapidly evolving markers for which mitochondrial DNA sequences are attractive candidates due to their short coalescent time. In other groups, similar evaluation should be performed to facilitate the choice of markers for molecular dating and making inferences from the results.

Objectives: The purpose of this longitudinal study was to investigate the effects of burnout on risk factors for arteriosclerotic disease., Methods: Baseline data were collected from 442 male middle managers working for a manufacturing company in Japan. All participants had a physical health check-up and completed the Japanese Maslach Burnout Inventory-General Survey. We calculated the Japanese-specific cut-off points of the MBI-GS and applied "exhaustion +1" criterion to define subjects as healthy or burnout at baseline. Follow-up measures were collected 4-5 yr later for 383 middle managers. Changes in the subjects' waist circumference, body weight, body mass index (BMI), blood pressure, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, fasting blood sugar, fasting insulin, HOMA-R, and HbA1c over a time period of 4 to 5 yr were compared between the healthy and burnout groups. New cases of large waist circumference, high BMI, metabolic syndrome, hypertension, hypercholesterolemia, high triglycerides, low HDL cholesterol, high LDL cholesterol, and impaired fasting glucose were detected at follow-up., Results: Changes in waist circumference, body weight, and BMI were significantly greater in burned-out managers than in healthy managers. Furthermore, compared to other variables (age and health behaviors such as smoking), burnout was a significant explanatory variable. The odds ratio of the burnout group was 2.80 for hypercholesterolemia with statistical significance after adjusting for age. After adjusting for age, health behaviors, and baseline total cholesterol, the results were similar., Conclusions: Burnout, which results from prolonged exposure to chronic work stress, may be associated with risk factors for arteriosclerotic disease.

The aim of this study was to investigate the effects of shift work on nutrient intakes, including macronutrient intake and micronutrient intake, in a large sample size. The study population included 2,254 male manual workers, 20-59 yr of age, employed in a factory. A self-administered diet history questionnaire was used. The subjects were classified into 3 groups according to their work schedule: (i) fixed day workers; (ii) shift workers without midnight shifts; and (iii) shift workers with midnight shifts. The nutrient intakes of the groups were compared by age group. There was a significant difference in nutrient intakes between subjects aged 20-29 yr and those aged 30 yr and over. Among subjects aged 20-29 yr, the energy density value for saturated fat and the energy adjusted intakes of calcium, potassium, vitamin A, and vitamin B1 were the lowest among shift workers with midnight shifts. Among subjects aged 30 yr and over, the total energy intake was the highest among shift workers with midnight shifts; the difference was significant compared to fixed day workers. Shift workers with midnight shifts had the highest intake of cereals among subjects 30 yr of age and older. In conclusion, there were no significant differences in nutrient intakes between fixed day workers and shift workers without midnight shift. Shift work, particularly midnight shift work, affected nutrient intake. The impact of shift work on nutrient intakes differed by age and the type of shift work.