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We performed a whole genome QTL analysis to confirm the existence of QTL affecting fatty acid composition and to investigate the effects of additive, dominance, imprinting, and epistatic interactions between QTL in an [F.sub.2] resource population. The [F.sub.2] population, comprising 166 pigs, was obtained by crossing a Duroc boar and a Meishan sow. The [F.sub.2] population was measured for fatty acid composition and was used for whole genome QTL analysis, using a total of 180 microsatellite markers. The suggestive and significant thresholds were equivalent to likelihood ratio test statistics (LRT) of 13.7 and 20.5, respectively. For single QTL analysis, 2 suggestive QTL and 1 significant QTL were detected. Suggestive QTL for C14:0 and C16:1 were identified on chromosomes 12 and 7, respectively, and a significant QTL for C18:2 was detected on chromosome 5 with the greatest LRT of 22.9. For C14:0, a significant QTL with paternal imprinting effect was also detected on chromosome 12, where the locus was in the same region as an additive QTL effect, with a large LRT of 24.2. The suggestive QTL on chromosome 7 was not significant when correction for backfat thickness was included. For epistatic QTL analysis, a total of 5 epistatic pairs were located on chromosomes 4, 5, 9, and 16. The same epistatic pairs were significant when correction for backfat thickness was included. The individual QTL identified in the single QTL analysis and in the epistatic QTL analysis were not the same loci, except for C18:2. For C14:0, an epistatic QTL pair was detected on chromosome 16, with the least P-value of 4.9 x [10.sup.-12]. The present study constitutes one of the first reports on the mapping of imprinted QTL and epistatic pairs of QTL affecting fatty acid composition in a swine population. Key words: epistatic interaction, fatty acid composition, quantitative trait locus, swine doi: 10.2527/jas.2009-1917

Automated quantification of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) using whole slide imaging (WSI) is expected to eliminate subjectivity in visual assessment. However, the color intensity in WSI varies depending on the staining process and scanner device. Such variations affect the image analysis results. This paper presents methods to diminish the influence of color variation produced in the staining process using a calibrator slide consisting of peptide-coated microbeads. The calibrator slide is stained along with tissue sample slides, and the 3,3'-diaminobenzidine (DAB) color intensities of the microbeads are used for calibrating the color variation of the sample slides. An off-the-shelf image analysis tool is employed for the automated assessment, in which cells are classified by the thresholds for the membrane staining. We have adopted two methods for calibrating the color variation based on the DAB color intensities obtained from the calibrator slide: (1) thresholds for classifying the DAB membranous intensity are adjusted, and (2) the color intensity of WSI is corrected. In the experiment, the calibrator slides and tissue of breast cancer slides were stained together on different days and used to test our protocol. With the proposed protocol, the discordance in the HER2 evaluation was reduced to one slide out of 120 slides., Competing Interests: Conflict of Interest The authors declare that they have no competing interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Microscopy Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study aimed to determine whether there are associations between laughter, disease activity, frailty, and depression in rheumatoid arthritis (RA) patients., Methods: A total of 240 patients were included in this prospective cohort study on frailty in RA patients between March 2021 and June 2022. Patients were divided into the following four groups according to the frequency of laughter: "almost every day," "1-5 days per week," "1-3 days per month," and "never or almost never." Patient characteristics were compared among the four groups by analysis of variance. Factors associated with laughter were identified by multivariable logistic analysis., Results: The mean 28-joint Disease Activity Score using CRP was 1.91, with 70.7% of patients in remission and 12.6% in low disease activity. For the "almost every day" (42.5% of patients), "1-5 days per week" (40.0%), "1-3 days per month" (11.3%), and "never or almost never" (6.3%) groups, scores of the Kihon Checklist (KCL) for assessing frailty status were 3.5, 4.6, 7.3, and 8.1 (p < .001), respectively, and scores of the Beck Depression Inventory (BDI-II) were 8.4, 10.7, 15.1, and 16.5 (p < .001), respectively. Multivariable analysis revealed that KCL (OR: 0.81, 95% CI: 0.73-0.90) and BDI-II (OR: 0.91, 95% CI: 0.86-0.95) scores were independently associated with the frequency of laughter., Conclusion: Frailty and depression were associated with laughter in RA patients with controlled disease activity. Interventions aimed at not only disease activity control but also frailty prevention may lead to a life filled with laughter., (© 2024 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

In the evaluation of human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) - one of the standard biomarkers for breast cancer- visual assessment is laborious and subjective. Image analysis using whole slide image (WSI) could produce more consistent results; however, color variability in WSIs due to the choice of stain and scanning processes may impact image analysis. We therefore developed a calibration protocol to diminish the staining and scanning variations of WSI using two calibrator slides. The IHC calibrator slide (IHC-CS) contains peptide-coated microbeads with different concentrations. The color distribution obtained from the WSI of stained IHC-CS reflects the staining process and scanner characteristics. A color chart slide (CCS) is also useful for calibrating the color variation due to the scanner. The results of the automated HER2 assessment were compared to confirm the effectiveness of two calibration slides. The IHC-CS and HER2 breast cancer cases were stained on different days. All stained slides and CCS were digitized by two different WSI scanners. Results revealed 100% concordance between automated evaluation and the pathologist's assessment with both the scanner and staining calibration. The proposed method may enable consistent evaluation of HER2., (© 2023. Korean Society of Microscopy.)

We performed a plateau-linear regression model analysis of the average daily gain (ADG) of pigs on daily average temperature at the end of performance testing (T). Records for performance testing between 30 kg and 105 kg of 2268 purebred Duroc pigs raised at the National Livestock Breeding Center Miyazaki Station were used. Off-farm ambient temperatures were measured at the nearest Automated Meteorological Data Acquisition System station at Kobayashi, Miyazaki (Kobayashi station). A plateau-linear regression equation was obtained in which ADG decreased by 12.6 g for every 1°C when T > 21.1°C. We calculated the expected age in day at the end of testing (D105) using the regression equation obtained and T observed at the Kobayashi station in 2020. The number of days that D105 was prolonged due to higher T was 125 days, corresponding to approximately one third of the year. These results could contribute to planning and management of stable pork production in response to heat in Japan., (© 2022 Japanese Society of Animal Science.)

We investigated maternal effect on nine body measurement traits (body height, body length, front width (FW), chest width (CW), hind width (HW), chest depth, chest girth (CHG), front cannon circumference (FCC) and rear cannon circumference (RCC)) measured at the end of performance testing and five meat production traits (ages at the start and end of performance testing (D30 and D105), average daily gain (ADG), backfat thickness and loin muscle area) in purebred Duroc pigs. Genetic parameters for each trait were estimated by using six single-trait models with and without common litter environmental effect, maternal genetic effect and direct-maternal genetic correlation. The value of Akaike's information criterion was lowest with the model including direct additive genetic and common litter environmental effects for 10 traits. The estimated proportion of common litter environmental variance to phenotypic variance was approximately ≥0.1 for D30, D105, ADG, FW, CW, HW, CHG, FCC and RCC. Using a model without common litter environmental effect would overestimate the direct heritability of most traits. Standard errors of estimated genetic parameters tended to be larger in models including maternal genetic effect. The results indicate that a compromise could be made for accurate genetic parameter estimation for body measurement traits, as well as meat production traits, in pigs by considering common litter environmental effect., (© 2020 Wiley-VCH GmbH.)

The amount of intramuscular fat (IMF) present in the loin eye area is one of the most important characteristics of high-quality pork. IMF measurements are currently impractical without a labor-intensive process. Metabolomic profiling could be used as an IMF indicator to avoid this process; however, no studies have investigated their use during the fattening period of pigs. This study examined the metabolite profiles in the plasma of two groups of pigs derived from the same Duroc genetic line and fed the same diet. Five plasma samples were collected from each individual the day before slaughter. Capillary electrophoresis-time of flight mass spectrometry (CE-TOFMS) was used to analyze the purified plasma from each sample. Principle component analysis (PCA) and partial least squares (PLS) were used to find the semi-quantitative values of the compounds. The results indicate that branched-chain amino acids are significantly associated with high IMF content, while amino acids are associated with low IMF content. These differences were validated using the quantification analyses by high-performance liquid chromatograph, which supported our results. These results suggest that the concentration of branched-chain amino acids in plasma could be an indicative biomarker for the IMF content in the loin eye area.

Heritabilities of litter size traits at birth (total number born (TNB), number born alive (NBA), and number still born (NSB)) and their genetic correlations with body measurement (body height, body length, front width (FW), chest width (CW), hind width, chest depth, chest girth, front cannon circumference, and rear cannon circumference) and production traits (ages at the start and end of performance testing (D30 and D105), average daily gain (ADG), backfat thickness, and loin muscle area) in purebred Duroc pigs were estimated. Records of performance testing for 2,835 animals and farrowing records of 1,168 litters from 437 dams were used. Genetic parameters were estimated using single-trait and two-trait animal models. Permanent environment effect was considered for litter size traits and common litter environmental effect was considered for body measurement and production traits. The estimated heritability was 0.10 ± 0.06 for TNB, 0.16 ± 0.06 for NBA, and 0.08 ± 0.05 for NSB. Positive genetic correlation of NBA was estimated with D30, D105, and ADG (0.51, 0.11, and 0.39). The estimated genetic correlation of NBA was 0.47 ± 0.17 with FW and 0.55 ± 0.18 with CW, implying that FW and CW could be promising indicator traits for efficiently improving NBA., (© 2020 Japanese Society of Animal Science.)

Leg weakness in pigs is a serious problem in the pig industry. We performed a whole genome quantitative trait locus (QTL) analysis to find QTLs affecting leg weakness traits in the Landrace population. Half-sib progeny (n = 522) with five sires were measured for leg weakness traits. Whole genome QTL mapping was performed using a half-sib regression-based method using 190 microsatellite markers. No experiment-wide significant QTLs affecting leg weakness traits were detected. However, at the 5% chromosome-wide level, QTLs affecting leg weakness traits were detected on chromosomes 1, 3, 10 and 11 with QTL effects ranging from 0.07 to 0.11 of the phenotypic variance. At the 1% chromosome-wide level, QTLs affecting rear feet score and total leg score were detected on chromosomes 2 and 3 with QTL effects of 0.11 and 0.13 of the phenotypic variance, respectively. On chromosome 3 and 10, some QTLs found in this study were located at nearby positions. The present study is one of the first reports of QTLs affecting fitness related traits such as leg weakness traits, that segregate within the Landrace population. The study also provides useful information for studying QTLs in purebred populations.

At Nara Social Insurance Hospital, from January 2005 to September 2008, chemotherapy for older adult (>or=70) colorectal cancer patients was performed in 18 adjuvant cases and 10 advanced cases. In adjuvant cases, 18 out of 33 patients of >or= stage IIIa received chemotherapy, and 13 completed treatment safely. In advanced cases, all patients received FLOFOX or FOLFIRI, with or without bevacizumab as first-line treatment with a response rate of 50%. Although adverse events were relatively frequent in the older adult patients, there was no difference in the survival rate between elderly and younger patient groups. Cancer chemotherapy for older adults with a high comorbidity rate requires more skill and experience than for younger patients. It was possible even for a small-volume hospital, which plays an important role in regional medical service for elderly patients, to build up a system providing standard chemotherapy for colorectal cancer. However, considering the limited financial and human resources, it is essential to form a regional alliance of designated cancer care hospitals and other clinics in order to maintain the level of practice.

Unlabelled: Sepsis is an infection-induced syndrome with systemic inflammatory response leading to multiorgan failure and occasionally death. During this process, signal transducer and activator of transcription 3 (STAT3) is activated in the liver, but the significance of this molecule has not been established. We generated hepatocyte-specific STAT3-deficient mice (L-STAT3 KO) and examined the susceptibility of these mice to cecal ligation and puncture-induced peritonitis, a well-established septic model. L-STAT3 KO mice showed significantly higher mortality and produced lesser amounts of various acute phase proteins than control littermates. Although blood bacterial infection did not differ between L-STAT3 KO mice and control mice, the former showed deterioration of the systemic inflammatory response as evidenced by a significant increase in various cytokines such as tumor necrosis factor alpha, IFN-gamma, IL-6, IL-10, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1beta. A similar hyperinflammatory response was observed in another septic model caused by lipopolysaccharide (LPS) injection. In vitro analysis revealed that soluble substances derived from hepatocytes and dependent on STAT3 were critical for suppression of cytokine production from LPS-stimulated macrophage and splenocytes., Conclusion: STAT3 activation in hepatocytes can attenuate a systemic hyperinflammatory response and lethality in sepsis, in part by suppressing immune cell overactivation, implying a critical role of hepatocyte STAT3 signaling in maintaining host homeostasis.

Background/aims: Parenchymal hepatocytes (PHs) of rat contain colony-forming parenchymal hepatocytes (CF-PHs) as a small fraction. We aimed to demonstrate the presence of CF-PHs in humans and characterize them with respect to growth and differentiation potential., Methods: Human PHs were co-cultured with Swiss 3T3 cells in the medium containing human serum, EGF, nicontinamide, and ascorbic acid 2-phosphate. To examine differentiation potential hepatocytes were cultured on gels of Matrigel Matrix., Results: Few PHs formed colonies, the colony-forming efficiency being as low as 0.01-0.09%. The CF-PHs could be subcultured up to 7 passages. They showed a liver epithelial cell-like morphology, and immunocytochemically positive for albumin (ALB), cytokeratin (CK) 7, 8, 18, and 19 in a pre- and early phase-confluence, whereas they showed a typical differentiated hepatocyte-like morphology, and positive for alpha(1)-antitrypsin, but negative for CK7 and 19 in condensed regions at confluence. The CF-PHs at late confluence expressed mRNAs of ALB, HNF4, and isoforms of cytochrome P450 at low levels. However, when cultured on Matrigel, these cells expressed them at high levels comparable to those of original PHs., Conclusions: We concluded that the human liver contains highly replicative hepatic progenitor-like cells as a minute population that retain a normal differentiation potential.

We found a system of Na(+)-dependent uptake of fructose by rat renal brush-border membrane vesicles. It consisted of two saturable components, and was thought to involve at least two transporters. rNaGLT1, a novel glucose transporter in rat kidney, showed fructose uptake as well as alpha-methyl-D-glucopyranoside uptake by transfected HEK293 cells. The features of the lower affinity type of fructose transporter in the brush-border membranes, such as affinity and substrate recognition, were very comparable with those of rNaGLT1-transfected HEK293 cells. These results indicated that rNaGLT1 is a primary fructose transporter in rat renal brush-border membranes.

One of the chitinases secreted in the culture filtrate of a gram-negative bacteria, Burkholderia cepacia strain KH2, which was isolated from the bed log of Lentinus edodes, Shiitake mushrooms, was purified by DEAE Sepharose CL-6B chromatography, followed by Sephacryl S-100 HR gel filtration. The purified enzyme was homogenous, determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), with an estimated molecular weight of 34,000 and an isoelectric point (pI) of 5.9. The enzyme was stable at pH values of 4.0-6.0, and at temperatures up to 50 degrees C; the optimum pH and temperature were 4.5 and 50 degrees C, respectively. The enzyme exhibited higher activities toward chitosan 7B, a 62% deacetylated chitosan, than toward the highly deacetylated chitosan substrates. The enzyme was observed to drastically hydrolyze partially deacetylated chitin substrates, with the subsequent formation of N-acetylchitooligosaccharides [(GlcNAc) (n), n=2-7]. Separation and quantification of the hydrolysis products of (GlcNAc) (n), n52-6, by HPLC showed the splitting into (GlcNAc)(n), n=3-6. Activity toward N-acetylchitobiose was not detected. Oligomers with a higher number of units than the starting substrate were also detected, which indicate transglycosylation activity.

The effects of valproic acid (VPA) on pharmacokinetics of cyclophosphamide (CPM) alkylating metabolites were investigated in male BALB/c mice. The pharmacokinetics of CPM alkylating metabolites was found to be dose-dependent representing the decrease of formation and elimination rates of the metabolites. A nonlinear increase of area under blood concentration of CPM alkylating metabolites-time curve (AUC) occurred with increasing CPM dose of 100, 200, and 300 mg/kg body weight. The effects of VPA (100 mg/kg dose) coadministered with CPM were similar to those of the increase of the CPM dose in preventing the activation of CPM and the elimination of its alkylating metabolites. The delayed disposition of CPM alkylating metabolites resulted in a 1.5-fold increase (p less than 0.02) of AUC which was considered the most important pharmacokinetic parameter in the CPM therapy. VPA which was injected i.p. at a dose of 100, 200, or 300 mg/kg increased the pentobarbital induced-sleep time by 81, 138, or 192%, respectively. In order to assess the effect of VPA on drug metabolizing enzyme(s) activity in humans, the ratio of daily urinary 6-hydroxycortisol to 17-hydroxycorticosteroids, which can reflect cytochrome P-450 activity, was determined in 5 healthy volunteers. The ratio was rapidly and significantly decreased (p less than 0.05) and this reduction continued during VPA administration. These findings and those reported in the literature concerning CPM metabolism suggest that the delay of CPM alkylating metabolites elimination resulted in part from microsomal enzyme(s) inhibition by VPA.