Pharmacoeconomic study of biologics for psoriasis treatment based on real-world drug survival.

The efficacy of biologics in psoriasis treatment is clinically proven; however, biologics are expensive. In this study, we assessed the real-world cost-effectiveness of biologics for psoriasis treatment by evaluating the relationship between biologic drug survival (DS) and total medical-treatment costs from a pharmacoeconomic viewpoint. Furthermore, the effects of patient factors on cost-effectiveness were investigated. We retrospectively reviewed the medical records of 135 cases who received either a tumor necrosis factor-alpha (TNF-α) monoclonal antibody (TNF-mab), interleukin (IL)-17 mab, or IL23p19-mab for psoriasis from January 2010 to June 2020 at Yamaguchi University Hospital. We compared the monthly medical-treatment costs according to biologic classification and found that costs of medical services, tests, and external preparations required for the treatment process were significantly higher in the TNF-mab group than in the other groups, and the total medical costs associated with TNF-mab treatment were significantly higher than those of IL17-mab treatment. The total monthly cost of medical care was lower in the long-term DS group than in the short-term group. The number of prescriptions for external preparations, comprising Vitamin D3 and corticosteroid, was significantly higher in the long-term DS group than in the short-term group; in the TNF-mab group, the proportion of patients without smoking habits was significantly higher in the long-term group as well. Our study indicated that when costly biologics are used for psoriasis treatment, the maintenance of long-term DS and appropriate patient guidance might improve the quality of medical care, thus allowing cost-effective medical care.

Construction of genetic linkage map and identification of a novel major locus for resistance to pine wood nematode in Japanese black pine (Pinus thunbergii).

BACKGROUND: Pine wilt disease (PWD), which is caused by the pine wood nematode (PWN) Bursaphelenchus xylophilus, is currently the greatest threat to pine forests in Europe and East Asian countries including Japan. Constructing a detailed linkage map of DNA markers and identifying PWD resistance genes/loci lead to improved resistance in Pinus thunbergii, as well as other Pinus species that are also susceptible to PWD. RESULTS: A total F1 mapping population of 188 individuals derived from a cross between the PWD-resistant P. thunbergii varieties 'Tanabe 54' (resistant rank 2 to PWD) and 'Tosashimizu 63' (resistant rank 4 to PWD) was inoculated with PWN, and was evaluated for disease symptoms. To perform linkage analysis for PWN resistance, a set of three maps was constructed; two parental maps generated using the integrated two-way pseudo-testcross method, and a consensus map with population-type cross-pollination. The linkage map of 'Tanabe 54' consisted of 167 loci, and covered 14 linkage groups (LGs), with a total genetic distance of 1214.6 cM. The linkage map of 'Tosashimizu 63' consisted of 252 loci, and covered 14 LGs, with a total genetic distance of 1422.1 cM. The integrated consensus map comprised 12 LGs with the basic chromosome number of P. thunbergii, and a total genetic distance of 1403.6 cM. Results from quantitative trait loci (QTL) analysis using phenotype data and linkage maps indicated that PWN resistance is controlled by a single dominant allele, which was derived from the 'Tanabe 54' female parent. This major QTL was located on linkage group 3 and was designated PWD1 for PINE WILT DISEASE 1. CONCLUSIONS: The PWD1 locus is a major resistance QTL located on the Pinus consensus LG03 that acts in a dominant manner to confer pine wood nematode resistance. Information from the present study will be useful for P. thunbergii breeding programs to improve resistance to PWD, and also to help identify susceptibility genes in Pinus species.

Identification of novel putative causative genes and genetic marker for male sterility in Japanese cedar (Cryptomeria japonica D.Don).

BACKGROUND: Japanese cedar (Cryptomeria japonica) is an important tree for Japanese forestry. Male-sterile marker development in Japanese cedar would facilitate selection of male-sterile plus trees, addressing the widespread social problem of pollinosis and facilitating the identification of heterozygotes, which are useful for breeding. RESULTS: This study used next-generation sequencing for single-nucleotide polymorphism discovery in libraries constructed from several organs, including male-sterile and male-fertile strobili. The single-nucleotide polymorphisms obtained were used to construct a high-density linkage map, which enabled identification of a locus on linkage group 9 strongly correlated with male-sterile trait. Expressed sequence tags corresponding to 11 marker loci from 5 isotigs were associated with this locus within 33.4-34.5 cM. These marker loci explained 100% of the phenotypic variation. Several homologs of these sequences are associated with male sterility in rice or Arabidopsis, including a pre-mRNA splicing factor, a DEAD-box protein, a glycosyl hydrolase, and a galactosyltransferase. These proteins are thus candidates for the causal male-sterile gene at the ms-1 locus. After we used a SNaPshot assay to develop markers for marker-assisted selection (MAS), we tested F2 progeny between male-sterile and wild-type plus trees to validate the markers and extrapolated the testing to a larger plus-tree population. We found that two developed from one of the candidates for the causal gene were suitable for MAS. CONCLUSIONS: More than half of the ESTs and SNPs we collected were new, enlarging the genomic basis for genetic research on Japanese cedar. We developed two SNP markers aimed at MAS that distinguished individuals carrying the male-sterile trait with 100% accuracy, as well as individuals heterozygous at the male-sterile locus, even outside the mapping population. These markers should enable practical MAS for conifer breeding.

Analysis of the prognostic value of BMI and the difference in its impact according to age and sex in DLBCL patients.

Studies that have evaluated the prognostic value of body mass index (BMI) in patients with diffuse large B-cell lymphoma have recently been reported. However, the impact of BMI on survival outcomes remains controversial. We retrospectively analyzed the data of 406 diffuse large B-cell lymphoma patients treated with R-CHOP or R-CHOP-like regimens. The number (%) of patients that were categorized into 1 of 4 groups according to BMI were underweight (<18.5 kg/m2 ), 58 (14.3%); normal weight (≥18.5 to <25 kg/m2 ), 262 (64.5%); overweight (≥25 to <30 kg/m2 ), 75 (18.5%); and obese (≥30.0 kg/m2 ), 11 (2.7%). While the prognosis of overweight patients was good, being similar to that of normal weight, underweight, and obese patients had a worse prognosis (5-y overall survival [OS] was 57.9%, 74.3%, 73.4%, and 40.9% for underweight, normal weight, overweight, and obese patients, respectively; P = .004). In multivariate analysis, underweight and obesity were independent prognostic factors for OS compared with normal weight (hazard ratios 2.90 and 5.17, respectively). In elderly female patients (≥70 y), patients with a low BMI (<25 kg/m2 ) had significantly inferior OS than those with a high BMI (≥25 kg/m2 ) (5-y OS, 61.5% vs 85.7%; P = .039). In contrast, in young female patients (<70 years), patients with a low BMI had significantly better OS than those with a high BMI (5-y OS, 88.6% vs 46.4%; P < .001). In male patients, there were no differences in the effect of BMI on OS between young and elderly patients. In this study, we demonstrated that being underweight and obese were independent prognostic factors compared with being normal weight. In female patients, BMI had a different impact on the prognosis of young and elderly patients, whereas in male patients, there was no difference in the effect of BMI on prognosis according to age.

Chemotherapy for alpha-fetoprotein producing gastric cancers expressing human epidermal growth factor receptor 2.

Although, gastric cancer is one of the most common cancers worldwide, alpha-fetoprotein (AFP) producing human epidermal growth factor receptor 2 (HER2) positive gastric cancers are rare. AFP producing gastric cancer has a poor prognosis and an appropriate treatment option has not been established to date. A 75-year-old woman with AFP- producing gastric cancer was treated with S-1, an oral fluoropyrimidine derivative, chemotherapy after distal gastrectomy. Recurrence of gastric cancer was observed after 18 months and immunohistochemistry analysis showed AFP and HER2 positive gastric cancer. The patient received combination therapy containing capecitabine, cisplatin, and trastuzumab. Computed tomography scans showed regression of the lymph node metastasis. The patient's quality of life substantially improved after the treatment. Thus, the present case suggests that AFP and HER2 positive gastric cancer can be effectively treated with, capecitabine, cisplatin, and trastuzumab combination therapy.

Expression analysis of transporter genes for screening candidate monolignol transporters using Arabidopsis thaliana cell suspensions during tracheary element differentiation.

The mechanism of monolignol transportation from the cytosol to the apoplast is still unclear despite being an essential step of lignification. Recently, ATP-binding cassette (ABC) transporters were suggested to be involved in monolignol transport. However, there are no reliable clues to the transporters of the major lignin monomers coniferyl and synapyl alcohol. In this study, the lignification progress of Arabidopsis cultured cells during tracheary element differentiation was monitored. The expression of selected transporter genes, as well as lignification and cell-wall formation related genes as references, in differentiating cultured cell samples harvested at 2-day intervals was analyzed by real-time PCR and the data were statistically processed. The cell wall formation transcription factor MYB46, programmed-cell death related gene XCP1 and lignin polymerization peroxidase AtPrx25 were classified into the same cluster. Furthermore, the cluster closest to the abovementioned cluster contained the lignin synthesis transcription factor MYB58 and the Arabidopsis ABC transporters ABCG11, ABCG22, ABCG36 and ABCG29. This result suggested that these four ABC transporters may be involved in lignification. In the expression analysis, unexpectedly, the lignification-related genes CAD5 and C4H were not included in the same cluster as MYB58 and AtPrx25. The expression data also suggested that the lignification of tracheary elements in the culture, where lignification ratio finally reached to around 40%, continued after cell death because lignification actively progressed after programmed cell death-related gene started to be expressed.

Beta-2 microglobulin as a significant prognostic factor and a new risk model for patients with diffuse large B-cell lymphoma.

Previous reports have evaluated the prognostic value of serum beta-2 microglobulin (B2MG) level in patients with non-Hodgkin lymphoma. However, its role in predicting clinical outcome of patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era has not been extensively investigated. Here, we evaluated the prognostic value of B2MG and proposed a new prognostic model including B2MG for patients with DLBCL. A total of 274 patients with newly diagnosed de novo DLBCL were retrospectively analyzed. We defined the best cutoff value as 3.2 mg/L by using a receiver operating characteristic curve. Patients with a B2MG level ≥3.2 mg/L had significantly lower overall survival (OS) and progression-free survival than those with a B2MG level <3.2 mg/L (3-year OS, 50.9% vs. 89.4%, p < 0.001; 3-year progression-free survival, 45.3% vs. 79.7%, p < 0.001). Multivariate analysis showed that B2MG, age, performance status, and Ann Arbor stage were independent prognostic factors for OS. We developed a new prognostic model consisting of these four significant factors. We stratified patients into four-risk groups: low (L, 0 factor), low-intermediate (LI, 1-2 factors), high-intermediate (HI, 3 factors), high (H, 4 factors). This new prognostic model showed better risk discrimination compared with the National Comprehensive Cancer Network-International Prognostic Index (5-year OS: 100% and 23.4% vs. 100% and 27.1%, in L and H risk groups, respectively). Our study suggested that B2MG level is a significant prognostic factor in patients with DLBCL. A new prognostic index composed of age, performance status, stage, and B2MG could stratify the outcomes of patients with DLBCL effectively and appears to be a valuable risk model for these patients. Copyright © 2016 John Wiley & Sons, Ltd.

Central nervous system relapse in patients with diffuse large B cell lymphoma: analysis of the risk factors and proposal of a new prognostic model.

Central nervous system (CNS) relapse in patients with diffuse large B cell lymphoma (DLBCL) is an uncommon event, and the outcome of patients with CNS relapse is poor. However, no reliable prediction models for CNS relapse have been developed. We retrospectively analyzed consecutive de novo DLBCL patients referred to our department between September 2004 and August 2015 and treated with R-CHOP or R-CHOP-like regimens. Of 413 patients analyzed in this study, a total of 27 patients (6.5 %) eventually developed CNS relapse. The 5-year probability of CNS relapse was 8.4 %. The median time from diagnosis of DLBCL to CNS relapse was 15 months, and the median survival after CNS relapse was 7 months. In univariate analysis, the risk factors significantly associated with CNS relapse were Ann Arbor stage 3 or 4, albumin level <3.2 mg/L, number of extranodal sites >1, and involvement of retroperitoneal lymph node. We developed a new prognostic model consisting of these four factors. The 5-year probability of CNS relapse was significantly higher in patients with at least three of these four factors than in those with two or fewer factors (26.4 vs. 3.0 %, P < 0.001). Using this model, we evaluated the incidence and the risk factors of CNS relapse in DLBCL patients. The new risk model consisting of the four factors demonstrated good risk stratification for CNS relapse, and could help to identify high-risk patients for whom CNS prophylaxis is warranted.

Efficacy of scallop shell powders and slaked lime for inactivating avian influenza virus under harsh conditions.

The efficacy and stability of scallop shell powder (SSP) were investigated, in terms of its capacity to inactivate avian influenza virus (AIV), and compared with slaked lime (SL). An environmental simulation was conducted by emulating sunlight and wet-dry conditions. The powders were collected at consecutive 2-week intervals under sunlight and upon every resuspension. These materials were tested by mixing them with AIV and incubating the mixture for 3 min or 20 h, followed by AIV titration. At the same time, a pH buffering test was conducted by neutralization with Tris-HCl. The results revealed that SSP and SL have high alkalinity and excellent ability to inactivate AIV. In a simulated harsh environment, SSP and SL retained a satisfactory ability to inactivate AIV within 20 h throughout the experimental procedure. However, SSP was able to inactivate AIV during a short contact period (3 min), even under harsh conditions, and it was more resistant than SL to neutralization.

Early measurement of urinary N-acetyl-ß-glucosaminidase helps predict severe hyponatremia associated with cisplatin-containing chemotherapy.

BACKGROUND: Although cisplatin is a widely used anticancer drug for treating various types of cancer, its clinical application is limited by severe systemic toxicities, such as nephropathy, hematologic toxicity, and gastrointestinal toxicity. There are no reliable and validated biomarkers to predict adverse events caused by cisplatin. METHODS: Sixty-six patients who underwent cisplatin-containing first-line chemotherapy between June 2010 and November 2013 were retrospectively analyzed. Data on urinary N-acetyl-ß-glucosaminidase activities measured 24-48 h after cisplatin infusion were retrieved, and adverse events during the first course of chemotherapy were recorded according to the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Patient characteristics were: male/female 60/6, median age 65 (range 36-78) years, esophageal/gastric/other cancer 60/4/2, chemotherapy regimen docetaxel-cisplatin-fluorouracil/fluorouracil-cisplatin/S-1-cisplatin 54/8/4, cisplatin dose (mg/sm) 60/70/80 16/43/7. Grade 3/4 adverse events were leukopenia (40.9%), neutropenia (54.4%), febrile neutropenia (37.9%), hyponatremia (28.8%), and acute kidney injury (37.9%). Patients with 20 units/gram creatinine or higher urinary N-acetyl-ß-glucosaminidase developed statistically lower minimum serum sodium concentration (median 126 vs. 134 mEq/L, p = 0.0053). There were no significant correlations between urinary N-acetyl-ß-glucosaminidase and the development of other severe adverse events. CONCLUSION: Early significant increase in urinary N-acetyl-ß-glucosaminidase predicts subsequent development of severe hyponatremia after cisplatin-containing chemotherapy.

Transcriptome sequencing and profiling of expressed genes in cambial zone and differentiating xylem of Japanese cedar (Cryptomeria japonica).

BACKGROUND: Forest trees have ecological and economic importance, and Japanese cedar has highly valued wood attributes. Thus, studies of molecular aspects of wood formation offer practical information that may be used for screening and forward genetics approaches to improving wood quality. RESULTS: After identifying expressed sequence tags in Japanese cedar tissue undergoing xylogenesis, we designed a custom cDNA microarray to compare expression of highly regulated genes throughout a growing season. This led to identification of candidate genes involved both in wood formation and later cessation of growth and dormancy. Based on homology to orthologous protein groups, the genes were assigned to functional classes. A high proportion of sequences fell into functional classes related to posttranscriptional modification and signal transduction, while transcription factors and genes involved in the metabolism of sugars, cell-wall synthesis and lignification, and cold hardiness were among other classes of genes identified as having a potential role in xylem formation and seasonal wood formation. CONCLUSIONS: We obtained 55,051 unique sequences by next-generation sequencing of a cDNA library prepared from cambial meristem and derivative cells. Previous studies on conifers have identified unique sequences expressed in developing xylem, but this is the first comprehensive study utilizing a collection of expressed sequence tags for expression studies related to xylem formation in Japanese cedar, which belongs to a different lineage than the Pinaceae. Our characterization of these sequences should allow comparative studies of genome evolution and functional genetics of wood species.

Influence of oral supplementation with sesamin on longevity of Caenorhabditis elegans and the host defense.

PURPOSE: Nutritional control has been proposed as a potential therapy for slowing the senescence of immune function and decreasing mortality. This study investigated whether sesamin could modify host defense systems and extend the lifespan of the nematode Caenorhabditis elegans. METHODS: Nematodes were fed standard food (the bacterium Escherichia coli strain OP50) supplemented with various doses of sesamin/γ-cyclodextrin inclusion compounds starting from young adulthood. The mean lifespan, muscle function, lipofuscin accumulation, protein carbonyl content, and stress resistance of the worms were examined. Then, C. elegans mutants harboring loss-of-function lesions in longevity- and host defense-related signaling pathways were supplemented with sesamin to identify the genes involved in the longevity effects. RESULTS: Worms supplemented with sesamin displayed higher locomotion and prolongevity and produced offspring at levels similar to unsupplemented control animals. The growth curves of nematodes were similar to those of controls, suggesting that sesamin did not induce prolongevity effects through dietary restriction. Notably, sesamin made the worms more resistant to infection by Legionella pneumophila and more resistant to oxidative stressors such as paraquat and hydrogen peroxide and prolonged the lifespan of a mev-1 mutant that produces abundant superoxide anions. However, the accumulation of protein carbonyls and lipofuscin was similar in sesamin-exposed and control worms, suggesting that sesamin is unlikely to work simply as an antioxidant. Sesamin supplementation failed to extend the lifespan of loss-of-function mutants of daf-2, daf-16, pmk-1, and skn-1. CONCLUSIONS: Sesamin enhances the host defense of C. elegans and increases the average lifespan via activation of both skn-1 (encoding a component of the p38 MAPK pathway) and daf-16 (encoding a component of the IGF-1 pathway).

Relationship between prolonged gestation and nifedipine pharmacokinetics in long-term tocolysis.

In this study, we examined the pharmacokinetics of nifedipine and investigated the maternal and foetal background factors that prolong pregnancy in pregnant women undergoing long-term tocolysis. This prospective observational study included 38 pregnant women hospitalised for threatened preterm labour and treated with nifedipine extended-release tablets in combination with an intravenous ritodrine infusion. Maternal plasma nifedipine concentrations were determined using high-performance liquid chromatography. All patients were administered 20 or 40 mg/dose of nifedipine every 6 h at the time of blood sampling. The plasma trough concentration (Ctrough ) was 22.6 ± 17.3 ng/mL, the maximum plasma concentration (Cmax ) was 30.9 ± 15.3 ng/mL and the time to maximum concentration (Tmax ) was 1.70 ± 1.10 h, as determined using noncompartmental analysis (NCA). The area under the curve for drug concentration (AUCtau ) was 152.3 ± 91.8 mg/L・h, and oral clearance (CL/F) was 0.17 ± 0.08 L/h. Using logistic regression analyses, we identified the factors that predicted term delivery from 37 weeks to <42 weeks of gestation. Gestational age at admission and the AUCtau of nifedipine can predict term delivery. The AUCtau of nifedipine is a valuable regulatory predictor of term delivery in pregnant women undergoing long-term tocolysis.

Evolution of the number of LRRs in plant disease resistance genes.

The largest group of plant resistance (R) genes contain the regions that encode the nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains (NBS-LRR genes). To gain new resistance, amino acid substitutions and changes in number of the LRRs that recognize the presence of pathogens are considered important. In this study, we focus on the evolution of the number of LRRs and analyze the genome data of five plant species, Arabidopsis thaliana, Oryza sativa, Medicago truncatula, Lotus japonicus and Populus trichocarpa. We first categorized the NBS-LRR genes in each species into groups and subgroups based on the phylogenetic relationships of their NBS domain sequences. Then we estimated the evolutionary rate of the number of LRRs relative to the synonymous divergence in the NBS domain sequences by a maximum likelihood method assuming the single stepwise mutation model. The estimates ranged from 4.5 to 600 and differed between groups in the same species or between species. This indicated different roles played by different groups of the NBS-LRR genes within a species or the effects of various life history characteristics, such as generation time, of the species. We also tested the fit of the model to the data using the variance of number of LRRs in each subgroup. In some subgroups in some plants (16 out of 174 subgroups), the results of simulation using the estimated rates significantly deviated from the observed data. Those subgroups may have undergone different modes of selection from the other subgroups.

Identification and Total Synthesis of an Unstable Anticancer Macrolide Presaccharothriolide Z Produced by Saccharothrix sp. A1506.

Saccharothriolides A-F are 10-membered microbial macrolides proposed to be generated from their precursors presaccharothriolides X-Z. Previously, we isolated presaccharothriolide X, and its unique natural prodrug-like properties have intrigued us. However, the other congeners were not detected. Herein, we detected presaccharothriolide Z using our highly sensitive labeling reagent. Moreover, chemical synthesis of presaccharothriolide Z, the first total synthesis of saccharothriolide-class macrolides, was achieved, and the structure and biological activity of presaccharothriolide Z were determined.

A Retrospective Analysis of Perioperative Chemotherapy and Coronavirus Disease in Patients With Breast Cancer.

BACKGROUND/AIM: Since January 2020, coronavirus disease (COVID-19) cases have been confirmed in Japan, and the number of patients with COVID-19 has been increasing. Two emergency declarations have been made previously and one is currently in effect. Based on our experience of a situation that could affect cancer treatment, this study retrospectively examined the correlation between perioperative anticancer therapy and COVID-19 incidence in patients with breast cancer. PATIENTS AND METHODS: Patients who underwent perioperative anticancer therapy for breast cancer at our hospital from February 2020 to February 2021 were included in this study. The presence or absence of COVID-19, timing of anticancer drug initiation, and clinical data were collected. RESULTS: No cases of COVID-19 were diagnosed in patients receiving perioperative anticancer therapy at our hospital. CONCLUSION: Regimen modification, active use of supportive care, and patient lifestyle were factors reducing the incidence of COVID-19.

Long-term outcomes of oligometastatic breast cancer patients treated with curative intent: an updated report.

BACKGROUND: Oligometastatic breast cancer (OMBC) is characterized by limited metastatic tumor numbers and sites. We have reported a 20-year overall survival (OS) rate and relapse-free rate (RFR) of 34.1% and 27.4%, respectively, in a retrospective analysis of OMBC patients treated with curative intent including a multidisciplinary approach. Metastatic breast cancer (MBC) is generally incurable; however, OMBC might be a potentially curable subset. The previous analysis included isolated locoregional recurrence (ILRR) cases, which differs from distant metastasis in treatment strategies. Therefore, in this study, we excluded ILRR cases and provided an update on clinical outcomes. We also performed a detailed subgroup analysis of OMBC patients by introducing new prognostic variables. METHODS: Data of 73 OMBC patients, including 10 ILRR cases, treated in our institution between 1980 and 2010 were retrospectively analyzed. OMBC was defined as the presence of metastatic lesions in 1-2 organs, < 5 lesions per metastasized organ, and lesion diameter < 5 cm. RESULTS: The median follow-up duration was 151 (range 12-350) months. Twenty-eight (44%) patients received local therapy. Excluding ILRR cases, the OS rates were 28.3% and 18.9% and RFRs were 26.7% at 20 and 25 years, respectively. In multivariate analysis, single-organ involvement and three or fewer metastatic lesions per organ were associated with a longer progression-free and relapse-free interval (RFI). CONCLUSIONS: Relapse-free interval reached a plateau after 20 years at approximately 25% probability. Patients with long-term survival without disease relapse are considered cured. Curative-intent therapy should be considered for OMBC patients, especially those with low tumor volume.

Effects of day length- and temperature-regulated genes on annual transcriptome dynamics in Japanese cedar (Cryptomeria japonica D. Don), a gymnosperm indeterminate species.

Seasonal phenomena in plants are primarily affected by day length and temperature. The shoot transcriptomes of trees grown in the field and a controlled-environment chamber were compared to characterize genes that control annual rhythms and the effects of day length- and temperature-regulated genes in the gymnosperm Japanese cedar (Cryptomeria japonica D. Don), which exhibits seasonally indeterminate growth. Annual transcriptome dynamics were clearly demonstrated by principal component analysis using microarray data obtained under field-grown conditions. Analysis of microarray data from trees grown in a controlled chamber identified 2,314 targets exhibiting significantly different expression patterns under short-day (SD) and long-day conditions, and 2,045 targets exhibited significantly different expression patterns at 15°C (LT; low temperature) versus 25°C. Interestingly, although growth was suppressed under both SD and LT conditions, approximately 80% of the SD- and LT-regulated targets differed, suggesting that each factor plays a unique role in the annual cycle. The top 1,000 up-regulated targets in the growth/dormant period in the field coincided with more than 50% of the SD- and LT-regulated targets, and gene co-expression network analysis of the annual transcriptome indicated a close relationship between the SD- and LT-regulated targets. These results indicate that the respective effects of day length and temperature interact to control annual transcriptome dynamics. Well-known upstream genes of signaling pathways responsive to environmental conditions, such as the core clock (LHY/CjLHYb and CCA1/CjLHYa) and PEBP family (MFT) genes, exhibited unique expression patterns in Japanese cedar compared with previous reports in other species, suggesting that these genes control differences in seasonal regulation mechanisms between species. The results of this study provide new insights into seasonal regulation of transcription in Japanese cedar.

Potential of Genome-Wide Studies in Unrelated Plus Trees of a Coniferous Species, Cryptomeria japonica (Japanese Cedar).

A genome-wide association study (GWAS) was conducted on more than 30,000 single nucleotide polymorphisms (SNPs) in unrelated first-generation plus tree genotypes from three populations of Japanese cedar Cryptomeria japonica D. Don with genomic prediction for traits of growth, wood properties and male fecundity. Among the assessed populations, genetic characteristics including the extent of linkage disequilibrium (LD) and genetic structure differed and these differences are considered to be due to differences in genetic background. Through population-independent GWAS, several significant SNPs found close to the regions associated with each of these traits and shared in common across the populations were identified. The accuracies of genomic predictions were dependent on the traits and populations and reflected the genetic architecture of traits and genetic characteristics. Prediction accuracies using SNPs selected based on GWAS results were similar to those using all SNPs for several combinations of traits and populations. We discussed the application of genome-wide studies for C. japonica improvement.