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Prognostic role of ΔNp63 expression in canine transitional cell carcinoma of the urinary bladder
ArticleBackground: Decreased p63 protein expression in canine transitional cell carcinoma (TCC) of the urinary bladder is associated with vascular invasion of the tumor, metastasis, and shortened survival. ΔNp63, an isoform of p63, is downregulated in high-grade invasive urothelial carcinoma in humans. However, the clinical significance of ΔNp63 expression in canine urinary bladder tumors is unknown. Therefore, it is essential to investigate ΔNp63 expression patterns in TCC, the most common urinary bladder tumor in dogs. Aim: This study aimed to evaluate the expression and role of ΔNp63 in canine TCC of the urinary bladder. Methods: ΔNp63 expression was compared between the normal canine urinary bladder, polypoid cystitis, and TCC. The correlation of ΔNp63 expression with histopathological and clinical findings were further evaluated, and its usefulness as a prognostic factor was examined. Results: We observed that ΔNp63 was highly expressed in dogs’ normal urinary bladder and polypoid cystitis, and its expression levels were low in TCC. Furthermore, low levels of ΔNp63 expression were associated with vascular invasion, metastasis, and shortened survival in dogs with TCC. Conclusion: These results indicate that ΔNp63 expression could serve as a valuable biomarker for invasion, metastasis, and prognosis of canine TCC of the urinary bladder.journal articl
5-アミノレブリン酸投与によるホルスタイン種哺育牛の血液性状に及ぼす影響
BulletinDuring the suckling period, calves are prone to physiological anemia. Anemic calves often develop respiratory and digestive problems that lead to poor growth. As a precursor of hemoglobin, aminolevulinic acid has an oxygencarrying function in red blood cells in the body, and is expected to prevent anemia. In this study, we examined the effects of feeding aminolevulinic acid to calves on their growth and analyzed whether it had anemia-preventing effects. Our subject calves were six suckling calves, three of which were orally administered an aminolevulinic acid preparation (5 g/day for 60 days; test group), and three of which received no aminolevulinic acid (controls). At 0, 1, and 3 months of age, body weight, height, daily gain, and blood parameters (red blood cell count, hemoglobin, iron, hematocrit, white blood cell count, total protein, and total cholesterol) were measured, and the number of respiratory and digestive diseases and number of days of treatment were investigated. In the test group, body height was significantly higher at 1 month of age, and daily body mass also tended to be higher at 1-3 months of age. In blood tests, the red blood cell count and hemoglobin were below standard values at birth and at 2 months of age in both the test and control groups. Iron and total cholesterol tended to be higher in the test group at 1 and 3 months of age, while white blood cell count and total protein tended to be higher in the control group. In terms of disease status, the number of days of treatment was small in the test group, and no calves were diagnosed with anemia. These results suggest that aminolevulinic acid may improve the nutritional status of calves and be effective in promoting growth and preventing anemia.departmental bulletin pape
草地型酪農における草地更新後の収益性格差と意思決定
Bulletin本研究の課題は草地更新の経営にとっての経済効果が生じる要因を示すことにある。このため29の酪農場の調査を実施した。これらを過去10年間の合計草地更新率の高さと過去5年間平均の収益性の高さにより4つのグループに分けた。管理行動と意識の差を比較分析した。第1に,高更新率階層のうち低収益性グループと比べて高収益性グループでは以下の特徴が示された。草地更新に牧草の質的向上によるコスト低下を期待していたこと。経営面積を拡大し草地更新による牧草収量の減少リスクを回避したこと。完全更新だけでなく簡易更新を実施して牧草の質を高めたこと。第2に,低更新率階層の中の高収益性グループでは,以下の特徴が示された。広い視点で経営収支を管理していた。放牧の積極的な活用により,草地更新をせずに草地を維持し,少ない労働時間で高い収益性をえた。以上の結果草地更新で高い収益性を得るためには,明確なコスト削減意識と,草地の分析・観察・維持管理作業などの実施,そして更新による減収リスクを回避するために十分な経営面積の確保などの条件が必要と考えられた。さらに長期的な視点に立ち,労働時間を短縮すること,農薬使用のリスクを考慮すると,収益性を高めるためにすべての農場にとって草地更新が必要であるとは言えないことを示した。The objective of this study was to determine the factors that contribute to the economic benefits of pasture renovation for dairy management. To this end, 29 dairy farms were surveyed. These were divided into four groups according to their total pasture renovation rate over the past 10 years and their average profitability over the past 5 years. Differences in management behavior and awareness were analyzed comparatively. First, compared to the low profitability group in the high renovation rate hierarchy, the high profitability group showed the following characteristics. They expected pasture renovation to reduce costs by improving pasture quality. They expanded their area of operation and avoided the risk of a decrease in pasture yield due to pasture renovation. The quality of grass was improved not only by complete renovation but also by simple renovation. Second, the highly profitable group in the low renovation rate group showed the following characteristics. They managed their management balance from a broad perspective. They maintained grassland without pasture renovation through active use of grazing, and achieved high profitability with fewer labor hours. As results of the above, it was considered that in order to obtain high profitability through pasture renovation, the following conditions were necessary: a clear awareness of cost reduction, analysis, observation, and maintenance of the grassland, and a sufficient area of land for management to avoid the risk of reduced income due to renovation. Furthermore, taking a long-term perspective, reducing labor hours, and considering the risks of pesticide use indicated that pasture renovation is not necessary for all farms to increase profitability.departmental bulletin pape
R package DCchoice for dichotomous choice contingent valuation : a contribution to open scientific software and its impact
journal articleThe R package DCchoice is designed to mitigate programing-related barriers to the application of dichotomous choice contingent valuation (DCCV) methods in empirical studies. Since its release in 2014, DCchoice has been updated. This paper introduces the current version of DCchoice which supports single-, one-and-one-half-, and double-bounded DCCVs, with and without a spike. Additionally, the willingness-to-pay and its confidence intervals can be calculated for a representative respondent as well as for a user-defined specific respondent using the current version. The associated web tutorial and R Commander plug-in for basic usage of DCchoice are also available. DCchoice has advanced DCCV applications in various fields.journal articl
Stability of enveloped and nonenveloped viruses in hydrolyzed gelatin liquid formulation
journal article[Background The thermal stability of viruses in gelatin liquid formulations for medical research and application is poorly understood and this study aimed to examine the thermal stability of 4 enveloped and nonenveloped DNA and RNA viruses in hydrolyzed gelatin liquid formulations. [Methods] Bovine herpesvirus (BHV) was used as a model virus to examine the molecular weight (MW), concentration and gelatin type and to optimize virus stability in liquid formulations at 25 °C and 4 °C. Using the model virus liquid formulation, the stability of multiple enveloped and nonenveloped RNA and DNA viruses, including parainfluenza virus, reovirus (RV), BHV, and adenovirus (AdV), was monitored over up to a 30-week storage period. [Results] The BHV model virus was considered stable after 3 weeks in hydrolyzed gelatin (MW: 4000) with a 0.8 LRV (log10 reduction value) at 25 °C or a 0.2 LRV at 4 °C, compared to the stabilities observed in higher MW gelatin (60,000 and 160,000) with an LRV above 1. Based on the gelatin type, BHV in alkaline-treated hydrolyzed gelatin samples were unexpectantly more stable than in acid-treated hydrolyzed gelatin sample. All four viruses exhibited stability at 4 °C for at least 8 weeks, BHV or AdV remained stable for over 30 weeks of storage, and at 25 °C, AdV and RV remained stable for 8 weeks. [Conclusion] The results demonstrated that 5% of 4000 MW hydrolyzed gelatin formulation can act as a relevant stabilizer for the thermal stability of viruses in medical research and application.journal articl
Effect of the locational relationship between the 1st wave dominant follicle and the corpus luteum on conception rate after embryo transfer : data analysis of 297 embryo transfers from a commercial embryo production program
journal articleThe ovarian structures identified at the time of ET are important for the selection of recipients. In previous report, the first-wave dominant follicle, located ipsilateral to the corpus luteum on the ovary, was associated with reduced conception rate after artificial insemination. Thus, a similar locational relationship may affect conception rate during embryo transfer. Data from 297 transfers of fresh embryos to virgin heifers were analyzed aiming to check the effect of first-wave dominant follicle location in relation to the corpus luteum on conception rate using a multivariable logistic regression model with six confounders.The location of the first-wave dominant follicle in relation to the corpus luteum location had no significant effect on conception rate, suggesting that it is not necessary to consider the firstwave dominant follicle size and location in the ovaries for recipient selection.journal articl
Is single-step genomic REML with the algorithm for proven and young more computationally efficient when less generations of data are present?
journal articleEfficient computing techniques allow the estimation of variance components for virtually any traditional dataset. When genomic information is available, variance components can be estimated using genomic REML (GREML). If only a portion of the animals have genotypes, single-step GREML (ssGREML) is the method of choice. The genomic relationship matrix (G) used in both cases is dense, limiting computations depending on the number of genotyped animals. The algorithm for proven and young (APY) can be used to create a sparse inverse of G (G^_) with close to linear memory and computing requirements. In ssGREML, the inverse of the realized relationship matrix (H−1) also includes the inverse of the pedigree relationship matrix, which can be dense with a long pedigree, but sparser with short. The main purpose of this study was to investigate whether costs of ssGREML can be reduced using APY with truncated pedigree and phenotypes. We also investigated the impact of truncation on variance components estimation when different numbers of core animals are used in APY. Simulations included 150K animals from 10 generations, with selection. Phenotypes (h2 = 0.3) were available for all animals in generations 1–9. A total of 30K animals in generations 8 and 9, and 15K validation animals in generation 10 were genotyped for 52,890 SNP. Average information REML and ssGREML with G−1 and G^_ using 1K, 5K, 9K, and 14K core animals were compared. Variance components are impacted when the core group in APY represents the number of eigenvalues explaining a small fraction of the total variation in G. The most time-consuming operation was the inversion of G, with more than 50% of the total time. Next, numerical factorization consumed nearly 30% of the total computing time. On average, a 7% decrease in the computing time for ordering was observed by removing each generation of data. APY can be successfully applied to create the inverse of the genomic relationship matrix used in ssGREML for estimating variance components. To ensure reliable variance component estimation, it is important to use a core size that corresponds to the number of largest eigenvalues explaining around 98% of total variation in G. When APY is used, pedigrees can be truncated to increase the sparsity of H and slightly reduce computing time for ordering and symbolic factorization, with no impact on the estimates.journal articl
Case Report : Rotavirus Vaccination and Severe Combined Immunodeficiency in Japan
journal articleSevere combined immunodeficiency (SCID) is an inborn error of immunity that occurs in approximately 1 in 50,000 births, mainly due to impaired lymphocyte differentiation. Without curative treatment, such as hematopoietic cell transplantation (HCT) or gene therapy, severe infection in the first year of life could make this condition fatal. The results of HCT are poor when patients have active infections, thus requiring early diagnosis before onset of infection. In five cases of SCID diagnosed in Japan, the oral rotavirus vaccine had been administered before diagnosis. In this study, we demonstrated that the rotavirus from their stools was a vaccine-derived strain. In some cases, severe gastroenteritis triggered the diagnosis of SCID. However, newborn screening for SCID is available before the first rotavirus vaccination using assays for the detection of T-cell receptor excision circles (TRECs). Therefore, to improve the prognosis of patients with SCID in Japan, we should establish a screening system of TRECs for newborns throughout Japan.journal articl
Association of lithocholic acid with skeletal muscle hypertrophy through TGR5-IGF-1 and skeletal muscle mass in cultured mouse myotubes, chronic liver disease rats and humans
journal articleBackground: Hepatic sarcopenia is one of many complications associated with chronic liver disease (CLD) and has a high mortality rate; however, the liver-muscle axis is not fully understood. Therefore, few effective treatments exist for hepatic sarcopenia, the best of which being branched-chain amino acid (BCAA) supplementation to help increase muscle mass. Our aim was to investigate the molecular mechanism(s) of hepatic sarcopenia focused on bile acid (BA) composition. Methods: The correlation between serum BA levels and psoas muscle mass index (PMI) was examined in 73 CLD patients. Gastrocnemius muscle phenotype and serum BA levels were assessed in CLD rats treated with BCAA. Mouse skeletal muscle cells (C2C12) were incubated with lithocholic acid (LCA), G-protein-coupled receptor 5 (TGR5) agonist or TGR5 antagonist to assess skeletal muscle hypertrophy. Results: In human CLD, serum LCA levels were the sole factor positively correlated with PMI and were significantly decreased in both the low muscle mass group and the deceased group. Serum LCA levels were also shown to predict patient survival. Gastrocnemius muscle weight significantly increased in CLD rats treated with BCAA via suppression of protein degradation pathways, coupled with a significant increase in serum LCA levels. LCA treated C2C12 hypertrophy occurred in a concentration-dependent manner linked with TGR5-Akt pathways based upon inhibition results via a TGR5 antagonist. Conclusions: Our results indicate LCA-mediated skeletal muscle hypertrophy via activation of TGR5-IGF1-Akt signaling pathways. In addition, serum LCA levels were associated with skeletal muscle mass in cirrhotic rats, as well as CLD patients, and predicted overall patient survival. Funding: This research was supported by JSPS KAKENHI Grant Number 22K08011 and 21H02892, and AMED under Grant Number JP21fk0210090 and JP22fk0210115. Maintaining cirrhotic rats were partially supported by Otsuka Pharmaceutical Company.journal articl