Burden of illness in Japanese patients with paroxysmal nocturnal hemoglobinuria receiving C5 inhibitors.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening blood disorder characterized by hemolysis and resulting in anemia and fatigue. Current therapies for PNH in Japan rely on complement inhibitors targeting the C5 component of the complement. However, the disease burden of Japanese patients with PNH treated with C5 inhibitors (C5i) remains unclear. To investigate this topic, we conducted a cross-sectional survey study that included 59 Japanese patients with PNH treated with C5i. Although many participants received C5i for 1 year or longer, the mean hemoglobin (Hb) level was 10.2 g/dL. Fatigue and shortness of breath were the most common symptoms at the time of diagnosis and survey. In addition, patients with Hb levels ≥ 10.5 g/dL also reported fatigue, depression and reduced quality of life, albeit to a lesser extent. These results suggest that a substantial burden of illness remains in patients with C5i-treated PNH, likely resulting in low quality of life and effects of symptoms on daily life. This study contributes to understanding the unmet needs of the current therapies for PNH, highlighting the need for novel therapeutics.

Enrichment of halotolerant hydrogen-oxidizing bacteria and production of high-value-added chemical hydroxyectoine using a hybrid biological-inorganic system.

Hybrid biological-inorganic (HBI) systems show great promise as CO2 conversion platforms combining CO2 fixation by hydrogen-oxidizing bacteria (HOB) with water splitting. Herein, halotolerant HOB were enriched using an HBI system with a high-ionic-strength medium containing 180 mM phosphate buffer to identify new biocatalysts. The reactors were inoculated with samples from saline environments and applied with a voltage of 2.0 V. Once an increase in biomass was observed with CO2 consumption, an aliquot of the medium was transferred to a new reactor. After two successive subcultures, Achromobacter xylosoxidans strain H1_3_1 and Mycolicibacterium mageritense strain H4_3_1 were isolated from the reactor media. Genome sequencing indicated the presence of genes for aerobic hydrogen-oxidizing chemolithoautotrophy and synthesis of the compatible solute hydroxyectoine in both strains. Furthermore, both strains produced hydroxyectoine in the reactors under the high-ionic-strength condition, suggesting the potential for new HBI systems using halotolerant HOB to produce high-value-added chemicals.

COVID-19 and Listeria Meningitis Treated by Ampicillin, Sulfamethoxazole/Trimethoprim and Meropenem.

Background: Secondary bacterial infection was initially rare in SARS-CoV-2 infectious disease (COVID-19) patients, but COVID-19-associated bacterial infectious diseases have recently been increasing. Furthermore, it might be difficult to distinguish COVID-19 from bacterial meningitis by the symptoms, and one might be uncertain about antibiotic therapy for Listeria meningitis infection-typically caused by eating contaminated food-in elderly persons and pregnant women. Case Report: A 96-year-old woman who had been living alone was found to have SARS-CoV-2 infection in February 2023. She was admitted to our hospital with high fever and disturbance of consciousness and was started on treatment with remdesivir. Two days later, her consciousness was still disturbed, and she was found to have a stiff neck. In addition, increased white blood cell counts and C-reactive protein suggested bacterial infection. Therefore, a lumbar puncture was done, and Listeria monocytogenes was ultimately isolated from blood cultures and its genetic material was detected in cerebrospinal fluid. She had previously eaten refrigerated food and cheese products. Intravenous ampicillin 1.0 g 6×/day was started, but one week later, loss of consciousness continued, and the cerebrospinal findings were not improved, although nasal swab became negative for SARS-CoV-2. Intravenous sulfamethoxazole/trimethoprim (ST) 80/400 mg 3×/day was added, and her consciousness and fever improved by one week later. A drug rash appeared after ST was started, and she was switched to meropenem. Her condition finally improved. Conclusion: COVID-19-associated secondary listeria infection was found in an elderly woman. She was treated with not only ampicillin, but also ST and meropenem. Meningitis caused by Listeria monocytogenes should be considered as a secondary complication and carefully treated with antibiotics during the period of the COVID-19 pandemic.

Basic assessment on adding platelet measurement to legal health checkup in Japan: A cross-sectional and 20-year longitudinal study.

Background: In Japan, health checkups for workers are legally compulsory. Considering legal health checkup items are important for Japanese workers' health problems. To date, the legal health checkup items for blood cell counts include only red blood cell counts and hemoglobin but not platelet counts. This study aimed to investigate the significance of measuring platelets in workers by showing the association between the FIB-4 index (FIB-4), which can be easily calculated from factors including platelet counts and viral hepatitis infection. Method: Both cross-sectional and longitudinal analyses were conducted on the comprehensive medical examinations of male workers. In fiscal year (FY) 2019, a logistic regression model was applied to 12,918 examinees. For 13,459 examinees (mean age = 47.5 ± 9.3 SD), FY2000 was set to be followed until FY2019. A total of 149,956 records between FY2000 and FY2019 were analyzed cross-sectionally, and 8,038 men who were consecutively examined to FY2019 at the longest were analyzed longitudinally. Receiver operating characteristic (ROC) curve-area under the ROC curve (ROC-AUC) and Cox proportional methods were used to examine the association between platelet-related indices and viral hepatitis infection. Results: Logistic regression showed that the risk of FIB-4 ≥ 2.67 was mostly associated with hepatitis C virus antibody (HCVAb) positivity [odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.08-5.86], while negatively associated with body mass index (BMI) (OR = 0.54, 95% CI = 0.30-0.97), and not associated with the presence of fatty liver. To detect HVC Ab positivity, ROC-AUC showed more effectiveness in FIB-4 than in the AST/ALT ratio (0.776, 95% CI = 0.747-0.773 vs. 0.552; 95% CI = 0.543-0.561). The Cox analysis showed that the risk of FIB-4 ≥ 2.67 was closely associated with hepatitis B virus surface antigen (HBsAg) [hazard ratio (HR) = 3.1, 95% CI = 2.0-4.6] and HCV Ab positivity (HR = 3.2, 95% CI = 2.0-5.0). Conclusion: Our results suggest that it might be worth considering that usage of information on platelets in legal health checkups could be some help not to overlook workers with hepatitis virus carriers as a complementary countermeasure, although further investigations are needed into its practical application.

Significance of Fib4 index as an indicator of alcoholic hepatotoxicity in health examinations among Japanese male workers: a cross-sectional and retrospectively longitudinal study.

BACKGROUND: Fib4 index (Fib4) is clinically used as a noninvasive marker of liver fibrosis. In this study, we aimed to preliminarily investigate whether Fib4 can be used to detect individuals who need assessment for alcoholic liver disease (ALD) in the general population by clarifying the detailed association of Fib4 with alcohol consumption and gamma-glutamyl transferase (GGT) among male workers. METHODS: We analyzed data sets on the comprehensive medical examinations of male workers as cross-sectional and retrospectively longitudinal studies. We enrolled 10 782 males (mean age: 52.2 ± 10.2 years) in FY2019 and 7845 males (mean follow-up: 12.6 ± 6.7 years) who could be consecutively followed up for 20 years from FY2000 to FY2019. Data were evaluated using logistic regression and COX proportional analysis. RESULTS: In the cross-sectional setting, the rate of Fib4 ≥ 2.67 in heavy drinkers (≥ 40 g of ethanol/day) was increased dose dependently in those over 65 years old, and that of body mass index ≥ 30 kg/m2 was increased in those over 60 years old, but not in those with fatty liver. The odds ratio (OR) (95% confidence interval [CI]) for heavy drinking was 4.30 (95% CI = 1.90-9.72), and GGT ≥ 200 IU/L was considerably high (OR = 29.05 [95% CI = 17.03-49.56]). In the longitudinal setting, heavy drinkers and those with GGT ≥ 200 IU/L at 10 years after the baseline showed an increased risk for Fib4 ≥ 2.67 (hazard ratio = 2.17 [95% CI = 1.58-2.98] and 7.65 [95% CI 5.26-11.12], respectively). CONCLUSIONS: The development of Fib4 ≥ 2.67 after 10 years was associated with heavy alcohol drinking and GGT level ≥ 200 IU/L. Therefore, Fib4 combined with GGT could indicate high risk of ALD. However, clinical examinations and course observations are essentially needed.

Mechanisms of mineralocorticoid receptor-associated hypertension in diabetes mellitus: the role of O-GlcNAc modification.

This study investigated the mechanism underlying the beneficial effects of mineralocorticoid receptor (MR) antagonists in patients with resistant hypertension and diabetic nephropathy by examining post-translational modification of the MR by O-linked-N-acetylglucosamine (O-GlcNAc), which is strongly associated with type 2 diabetes. Coimmunoprecipitation assays in HEK293T cells showed that MR is a target of O-GlcNAc modification (O-GlcNAcylation). The expression levels and transcriptional activities of the receptor increased in parallel with its O-GlcNAcylation under high-glucose conditions. Liquid chromatography-tandem mass spectrometry revealed O-GlcNAcylation of the MR at amino acids 295-307. Point mutations in those residues decreased O-GlcNAcylation, and both the protein levels and transcriptional activities of MR. In db/db mouse kidneys, MR protein levels increased in parallel with overall O-GlcNAc levels of the tissue, accompanied by increased SGK1 mRNA levels. The administration of 6-diazo-5-oxo-L-norleucin, an inhibitor of O-GlcNAcylation, reduced tissue O-GlcNAc levels and MR protein levels in db/db mice. Thus, our study showed that O-GlcNAcylation of the MR directly increases protein levels and transcriptional activities of the receptor under high-glucose conditions in vitro and in vivo. These findings provide a novel mechanism of MR as a target for prevention of complications associated with diabetes mellitus.

Real-Time Risk Score for Glaucoma Mass Screening by Spectral Domain Optical Coherence Tomography: Development and Validation.

Purpose: To develop and validate a risk score assessable in real-time using only retinal thickness-related values measured by spectral domain optical coherence tomography alone for use in population-based glaucoma mass screenings. Methods: A total of 7572 participants (aged 35-74 years) underwent spectral domain optical coherence tomography examination annually between 2016 to 2021 in a population-based setting. We selected 284 glaucoma cases and 284 controls, matched by age and sex, from 11,487 scans in 2016. We conducted multivariable logistic regression with backward stepwise selection of retinal thickness-related variables to develop the diagnostic models. The developed risk scores were applied to all participants in 2018 (9720 eyes), and we randomly selected 723 scans for validation. Additional validation using the Humphrey field analyzer was conducted on 129 eyes in 2020. We assessed the models using sensitivity, specificity, the area under the receiver operating characteristic curve and positive and negative predictive values. Results: The best-predicting model achieved an area under the receiver operating characteristic curve of 0.97 (95% confidence interval, 0.96-0.98) with a sensitivity of 0.93 and specificity of 0.91. The validation dataset showed a positive predictive value of 90.8% for high-risk scorers, corresponding to 6.2% of the population, and negative predictive value of 88.2% for low-risk scorers, corresponding to 85.2%. Sensitivity and specificity for glaucoma diagnosis were 0.85 and 0.91, when we set the risk score cut-off at 90 points out of 100. Conclusions: This risk score could be used as a valid index for glaucoma screening in a population-based setting. Translational Relevance: The score is feasible by installing a simple computer application on an existing spectral domain optical coherence tomography and will help to improve the accuracy and efficiency of glaucoma screening.

Predicting of molecules mediating an interaction between bovine embryos and uterine epithelial cells.

Embryo-maternal reproductive tract interactions are pivotal for successful pregnancy. The present study predicted the molecules modulating embryo-uterine communication by comparing two sets of differentially expressed genes (DEGs): DEGs in uterine epithelial cells (UECs) collected from the uterus with and without blastocysts and DEGs between blastocysts developed in vivo and in vitro. Cows were subjected to super ovulation (SOV), followed by insemination or non-insemination at estrus (SOV + AI and SOV cows). Seven days after estrus, the uterus was flushed to collect UECs, and the presence of blastocysts in the uterus was confirmed. UECs were subjected to RNA-Sequencing (RNA-Seq) to identify DEGs. Publicly available RNA-Seq data of in vivo and in vitro developed bovine blastocysts were used to determine DEGs. Then, using ingenuity pathway analysis, activated- and inhibited-upstream regulators (USRs) for UECs in blastocysts were compared with those for blastocysts developed in vivo. RNA-Seq of UECs revealed that the DEGs were associated with immune response and cell adhesion pathways. The activated and inhibited USRs of UECs derived from SOV+ AI cows overlapped with the activated and inhibited USRs of blastocysts developed in vivo. Overlapping activated USRs include leukemia inhibitory factor, interleukin 6, fibroblast growth factor-2, transforming growth factor beta-1, and epidermal growth factor. In conclusion, the present study predicted the molecules that potentially mediate communication between the developing embryo and the uterus in vivo and prepare the uterus for pregnancy.

The mineralocorticoid receptor signal could be a new molecular target for the treatment of diabetic retinal complication.

BACKGROUND: Activation of the mineralocorticoid receptor (MR) is involved in the pathophysiology of diabetic vascular complications. In recent years, it has been indicated that the MR expressed in retinal Müller cells plays an important role in regulating the potassium and water balance in the retina. Therefore, it has also been speculated that abnormal MR signaling contributes to edematous diseases of the retina. RESEARCH DESIGN AND METHODS: We examined the effect of high-glucose conditions on MR protein and mRNA levels in human retinal Müller cells and changes in cell size in vitro. We also investigated MR transcriptional activity and signaling in high-glucose conditions. RESULTS: The MR protein increased by 2.2-fold with high-glucose treatment. Additionally, high-glucose treatment induced Müller cell swelling. Aldosterone-induced MR transcriptional activity was enhanced in high-glucose conditions, resulting in the upregulation of αENaC, AQP4, and Kir4.1 mRNA. Treatment with an MR antagonist led to the suppression of aldosterone-induced cell swelling, MR transcriptional activity, and upregulation of the target genes in high-glucose conditions. CONCLUSIONS: High glucose induces Müller cell swelling through activation of MR signaling, which could be associated with aggravation of macular edema. Thus, Müller cell swelling and diabetic macular edema may represent a target for treatment with MR antagonists.

Descriptive study of chest x-ray examination in mandatory annual health examinations at the workplace in Japan.

The utility of chest x-ray examination (CXR) in mandatory annual health examinations for occupational health is debatable in Japan. This study aimed to provide basic data to consider future policies for mandatory annual health examinations in the workplace. A nationwide descriptive survey was performed to determine the rate of detection of tuberculosis, lung cancer, and other diseases through CXR in organizations associated with National Federation of Industrial Health Association. The rate of finding on CXR conducted during annual health examinations in FY2016 was evaluated. Data regarding diagnosis based on follow-up examination findings were obtained and compared with the national statistics. In addition, CXR findings were compared with the results of low-dose lung computed tomography performed at the Hitachi Health Care Center. From 121 surveyed institutions, 88 institutions with 8,669,403 workers were included. For all ages, 1.0% of examinees required follow-up examination. Among 4,764,985 workers with diagnosis data, the tuberculosis detection rate was 1.8-5.3 per 100,000 persons. For Lung cancer, 3,688,396 workers were surveyed, and 334 positive cases were detected. The lung cancer detection rate using CXR was 9.1-24.4 per 100,000 persons. From 164 cases with information regarding the clinical stage, 72 (43.9%) had Stage I lung cancer. From 40,045 workers who underwent low-dose computed tomography multiple times, 31 lung cancer cases, all with Stage I disease, were detected (detection rate: 77.4 per 100,000 persons). Our findings suggest that CXR plays a little role in the detection of active tuberculosis. With regard to LC screening, the detection rate of LC by CXR was lower, approximately 50%, than the expected rate (41.0 per 100,000 persons) of LC morbidity based on the age-sex distribution of this study population. However, the role of CXR for LC screening cannot be mentioned based on this result, because assessment of mortality reduction is essential to evaluate the role.

Improving and maintaining healthy lifestyles are associated with a lower risk of diabetes: A large cohort study.

AIMS: It is well known that healthy lifestyles measured at one time-point are inversely associated with diabetes risk. The impact of transitions in combined lifestyles in real settings remains unknown. MATERIALS AND METHODS: The trajectory patterns of combined lifestyles over three years were identified using group-based trajectory modeling in 26,647 adults in Japan. Two types of indices (not having the unhealthy lifestyle [easy goal] and having healthiest lifestyles [challenging goal]) were developed using five lifestyle factors: smoking, alcohol consumption, exercise, sleep duration, and body weight control. This index was calculated using the yearly total score (0-5; higher score indicated healthier lifestyles). Diabetes was defined by high plasma glucose level, high hemoglobin A1c level, and self-report. RESULTS: Five trajectory patterns were identified for each index and it was shown that healthier patterns are associated with a lower risk of type 2 diabetes during 6.6 years of average follow-up. For example, with a challenging-goal, compared with a persistently very unhealthy pattern, the adjusted hazard ratios (95% confidence intervals) were 0.65 (0.59, 0.73), 0.50 (0.39, 0.64), 0.43 (0.38, 0.48), and 0.33 (0.27, 0.41) for 'persistently unhealthy', 'improved from unhealthy to moderately healthy', 'persistently moderately healthy', and 'persistently mostly healthy' patterns, respectively. CONCLUSIONS: Our data reinforce the importance of improving and maintaining health-related lifestyles to prevent diabetes.

Status of Acute Stroke Practice in Patients with a Cardiac Implantable Electronic Device.

Although diagnostic and therapeutic strategies for acute stroke patients in Japan depend largely on magnetic resonance imaging (MRI), patients with cardiac implantable electronic devices (CIED) must still rely on com-puted tomography (CT). We retrospectively analyzed clinical and neuroimaging data of ischemic stroke patients with CIED treated at our hospital. Forty-five patients were enrolled in the study. Patients were divided into two groups according to whether corresponding lesions were detected (group A, n = 21) or not detected (group B, n = 24) by the first brain CT. We also evaluated in detail the clinical courses of patients who arrived at hospital within therapeutic time windows for recanalization therapy. Negative fresh infarct in the first CT was associated, though not significantly, with early onset-to-arrival time and subcortical white matter infarction. Five patients did not undergo recanalization therapy because their families did not agree to the procedure. The reasons for their lack of consent included inadequate information about the safety and efficacy of recanalization therapy because MRI could not be performed. Our study confirmed delayed detection of the corresponding lesion and undertreatment for acute stroke in patients with CIED.

A cross-sectional study of relationships between periodontal disease and general health: The Hitachi Oral Healthcare Survey.

BACKGROUND: This cross-sectional study performed to clarify the relationship between periodontal disease and non-communicable diseases (NCDs), such as obesity, diabetes mellitus, impaired glucose tolerance (IGT), chronic obstructive pulmonary disease (COPD), and atherosclerotic cardiovascular disease (ASCVD) by introducing dental examinations into the annual health examinations conducted by Japanese companies, and to highlights the importance of a medical system that connects dental and medical professionals. METHODS: A total of 1.022 Hitachi Ltd. employees were enrolled in this cross-sectional study. We examined correlations and odds ratios (ORs) between the dental and overall health of employees using stratification and multiple logistic regression analyses based on the periodontal health indicators, general health indicators, and occlusal force. RESULTS: The adjusted OR of PPD for obesity (OR, 1.42; 95% confidence interval [CI], 1.09-1.84; p = 0.009), IGT (OR, 1.48; 95% CI, 1.00-2.20; p = 0.049), and COPD (OR, 1.38; 95% CI, 1.02-1.88; p = 0.038) significantly differed. The adjusted OR of body mass index (OR, 1.28; 95% CI 1.15-1.42; p < 0.001), haemoglobin A1C (HbA1c) (OR, 4.34; 95% CI, 1.89-9.98; p < 0.001), fasting blood glucose (FBG) levels (OR, 1.08; 95% CI 1.04-1.11; p < 0.001), postbronchodilator forced expiratory volume in one second/forced vital capacity ratio (%FEV1) (OR, 0.95; 95% CI 0.91-1.00; p = 0.031) and smoking (OR, 2.32; 95% CI 1.62-3.33; p < 0.001) for severe periodontal disease also significantly differed. Occlusal force was significantly reduced in employees aged 50-59 years compared to those aged 40-49 years. Both PPD, HbA1c, FBG levels were significantly associated with occlusal force among employees with moderate/severe periodontitis. PPD was significantly associated with occlusal force among employees with and moderate COPD, and ASCVD. %FEV1 was significantly associated with occlusal force among employees with IGT. CONCLUSIONS: This cross-sectional study revealed mutual relationships among periodontal disease, NCDs, and occlusal force on Japanese corporate workers. We demonstrated that a comprehensive, regional healthcare system centred on annual integrated dental and physical health examinations in the workplace will benefit employees and positively impact corporate health insurance.

Longitudinal study of risk factors for decreased cross-sectional area of psoas major and paraspinal muscle in 1849 individuals.

This 10-year retrospective observational study investigated longitudinal losses in psoas major and paraspinal muscle area in 1849 healthy individuals (1690 male, 159 female) screened using computed tomography. Logistic regression analysis revealed significant decreases in psoas major and paraspinal muscle area at 10 years relative to the baseline area regardless of age or sex, starting at 30 years of age. Only aging [≥ 50 s (odds ratio [OR]: 1.72; 95% confidence interval [CI] 1.05-2.84; p = 0.03) and ≥ 60 s (OR: 2.67; 95% CI 1.55-4.60; p < 0.001)] was a risk factor for decreases in psoas major area. Age ≥ 60 years (OR: 2.05; 95% CI 1.24-3.39; p = 0.005), body mass index ≥ 25 kg/m2 (OR: 1.32; 95% CI 1.01-1.73; p = 0.04), and visceral fat ≥ 100 cm2 (OR: 1.61; 95% CI 1.20-2.15; p = 0.001) were risk factors for decreases in paraspinal muscle area. Physical activity ≥ 900 kcal/week (OR: 0.68; 95% CI 0.50-0.94; p = 0.02) attenuated paraspinal muscle area loss in male. Our study demonstrated that walking > 45 min daily (Calories = METs (walking: 3.0) × duration of time (h) × weight (60 kg) × 1.05) can reduce paraspinal muscle loss, which may in turn decrease the risk of falls, low-back pain, and sarcopenia.

Analysis of the Segregation Distortion of FcRAN1 Genotypes Based on Whole-Genome Resequencing of Fig (Ficus carica L.) Breeding Parents.

The common fig (Ficus carica L.) has a gynodioecious breeding system, and its sex phenotype is an important trait for breeding because only female plant fruits are edible. During breeding to select for female plants, we analyzed the FcRAN1 genotype, which is strongly associated with the sex phenotype. In 12 F1 populations derived from 13 cross combinations, the FcRAN1 genotype segregation ratio was 1:1, whereas the M119-226 × H238-107 hybridization resulted in an extremely male-biased segregation ratio (178:7 = male:female). This finding suggests that the segregation distortion was caused by some genetic factor(s). A whole-genome resequencing of breeding parents (paternal and maternal lines) identified 9,061 high-impact SNPs in the parents. A genome-wide linkage analysis exploring the gene(s) responsible for the distortion revealed 194 high-impact SNPs specific to Caprifig6085 (i.e., seed parent ancestor) and 215 high-impact SNPs specific to H238-107 (i.e., pollen parent) in 201 annotated genes. A comparison between the annotated genes and the genes required for normal embryo or gametophyte development and function identified several candidate genes possibly responsible for the segregation distortion. This is the first report describing segregation distortion in F. carica.

Genome-wide association study of individual sugar content in fruit of Japanese pear (Pyrus spp.).

BACKGROUND: Understanding mechanisms of sugar accumulation and composition is essential to determining fruit quality and maintaining a desirable balance of sugars in plant storage organs. The major sugars in mature Rosaceae fruits are sucrose, fructose, glucose, and sorbitol. Among these, sucrose and fructose have high sweetness, whereas glucose and sorbitol have low sweetness. Japanese pear has extensive variation in individual sugar contents in mature fruit. Increasing total sugar content and that of individual high-sweetness sugars is a major target of breeding programs. The objective of this study was to identify quantitative trait loci (QTLs) associated with fruit traits including individual sugar accumulation, to infer the candidate genes underlying the QTLs, and to assess the potential of genomic selection for breeding pear fruit traits. RESULTS: We evaluated 10 fruit traits and conducted genome-wide association studies (GWAS) for 106 cultivars and 17 breeding populations (1112 F1 individuals) using 3484 tag single-nucleotide polymorphisms (SNPs). By implementing a mixed linear model and a Bayesian multiple-QTL model in GWAS, 56 SNPs associated with fruit traits were identified. In particular, a SNP located close to acid invertase gene PPAIV3 on chromosome 7 and a newly identified SNP on chromosome 11 had quite large effects on accumulation of sucrose and glucose, respectively. We used 'Golden Delicious' doubled haploid 13 (GDDH13), an apple reference genome, to infer the candidate genes for the identified SNPs. In the region flanking the SNP on chromosome 11, there is a tandem repeat of early responsive to dehydration (ERD6)-like sugar transporter genes that might play a role in the phenotypes observed. CONCLUSIONS: SNPs associated with individual sugar accumulation were newly identified at several loci, and candidate genes underlying QTLs were inferred using advanced apple genome information. The candidate genes for the QTLs are conserved across Pyrinae genomes, which will be useful for further fruit quality studies in Rosaceae. The accuracies of genomic selection for sucrose, fructose, and glucose with genomic best linear unbiased prediction (GBLUP) were relatively high (0.67-0.75), suggesting that it would be possible to select individuals having high-sweetness fruit with high sucrose and fructose contents and low glucose content.

Structure-dependent receptor subtype selectivity and G protein subtype preference of heterocyclic agonists in heterologously expressed silkworm octopamine receptors.

(R)-Octopamine (OA), a major invertebrate biogenic amine, plays an important role in a wide variety of physiological processes as a neurohormone, neuromodulator, and neurotransmitter in insects. OA receptors (OARs) are class A G protein-coupled receptors that specifically bind OA to activate downstream signaling cascades by coupling to G proteins and presumably other regulatory proteins. These receptors are broadly classified as α- and ß-adrenergic-like OARs (α- and ß-ALOARs). OARs are considered important targets of insecticides and acaricides. In the present study, we examined the actions of an array of 13 heterocyclic OAR agonists with the moieties that correspond to the phenyl group and the basic nitrogen atom of OA on α- and ß-ALOARs from the silkworm (Bombyx mori) and the signaling pathways activated through these actions. The results indicated that these compounds display structure-dependent receptor subtype selectivity and G protein subtype preference, underscoring the need to determine which subtype and signaling pathway mediates toxicologically relevant effects for the efficient discovery of novel pest control chemicals. The results of insecticidal assays using B. mori larvae suggested that the activation of signal transduction pathways via α-ALOARs might be mainly responsible for the toxicological effects of the heterocycles.

Hamiltonian Monte Carlo method for estimating variance components.

A Hamiltonian Monte Carlo algorithm is a Markov chain Monte Carlo method, and the method has a potential to improve estimating parameters effectively. Hamiltonian Monte Carlo is based on Hamiltonian dynamics, and it follows Hamilton's equations, which are expressed as two differential equations. In the sampling process of Hamiltonian Monte Carlo, a numerical integration method called leapfrog integration is used to approximately solve Hamilton's equations, and the integration is required to set the number of discrete time steps and the integration stepsize. These two parameters require some amount of tuning and calibration for effective sampling. In this study, we applied the Hamiltonian Monte Carlo method to animal breeding data and identified the optimal tunings of leapfrog integration for normal and inverse chi-square distributions. Then, using real pig data, we revealed the properties of the Hamiltonian Monte Carlo method with the optimal tuning by applying models including variance explained by pedigree information or genomic information. Compared with the Gibbs sampling method, the Hamiltonian Monte Carlo method had superior performance in both models. We have provided the source codes of this method written in the Fortran language at https://github.com/A-ARAKAWA/HMC.