Genetic parameters were estimated for six reproductive traits related to farrowing events in Landrace and Large White pigs; total number born (TNB), number born alive (NBA), number stillborn (NSB), total litter weight at birth (LWB), mean litter weight at birth (MWB), and gestation length (GL). We analyzed 62,534 farrowing records for 10,637 Landrace dams and 49,817 farrowing records for 8,649 Large White dams. Estimated heritabilities of TNB, NBA, NSB, LWB, MWB, and GL by single‐trait repeatability model analyses were 0.12, 0.12, 0.08, 0.18, 0.19, and 0.29, respectively, in Landrace, and 0.12, 0.10, 0.08, 0.18, 0.16, and 0.34, respectively, in Large White. Genetic correlation between NBA and NSB was unfavorable: 0.20 in Landrace and 0.33 in Large White. Genetic correlations of GL with the other five traits were weak: from −0.18 with NSB to −0.03 with NBA in Landrace, and from −0.22 with NSB to −0.07 with NBA in Large White. LWB had a highly favorable genetic correlation with NBA (0.74 in both breeds), indicating the possibility of using LWB for the genetic improvement of NBA.

The purpose of this study was to gain a better understanding of the transport mechanism of pitavastatin, a novel synthetic HMG-CoA reductase inhibitor. Experiments were performed using oocytes of Xenopus laevis expressing several solute carrier (SLC) transporters and recombinant membrane vesicles expressing several human ABC transporters. The acid form of pitavastatin was shown to be a substrate for human OATP1, OATP2, OATP8, OAT3 and NTCP, and for rat Oatp1 and Oatp4 with relatively low K(m) values. In contrast, these SLC transporters were not involved in the uptake of the lactone form. A significant stimulatory effect was exhibited by pitavastatin lactone, while the acid form did not exhibit ATPase hydrolysis of P-glycoprotein. In the case of breast cancer resistant protein (BCRP), the acid form of pitavastatin is a substrate, whereas the lactone form is not. Taking these results into consideration, several SLC and ABC transporters were identified as critical to the distribution and excretion of pitavastatin in the body. This study showed, for the first time, that acid and lactone forms of pitavastatin differ in substrate activity towards uptake and efflux transporters. These results will potentially contribute to the differences in the pharmacokinetic profiles of pitavastatin.

Genetic parameters for 13 body measurement traits (body length, body height, front width, chest width, hind width, chest depth, chest girth, front and rear cannon circumferences, front and rear pastern postures, body mass index, and body density) and six production traits (age at start and end of test, average daily gain (DG), backfat thickness (BF), loin muscle area (LMA), and intramuscular fat content (IMF)) were estimated in Duroc pigs. Data on 2,835 individual pigs were collected from 2009 through 2017. Heritability estimates for body measurement traits ranged from moderate to high. The largest absolute values of estimated genetic correlations between each production traits (DG, BF, LMA, and IMF) and body measurement traits were chest girth (0.42), chest girth (0.68), front pastern postures (-0.28), and chest width (0.38), respectively. Our results suggest that these body measurement traits can be used as indicator traits for improving production traits. We also recommend taking leg conformation traits into consideration due to the estimated negative genetic correlations between cannon circumference and BF, front pastern posture and LMA, and the positive genetic correlation between front pastern posture and DG.

Accumulating evidence suggests that viruses play an important role in the development of diabetes. Although the diabetogenic encephalomyocarditis strain D virus induces diabetes in restricted lines of inbred mice, the susceptibility genes to virus-induced diabetes have not been identified. We report here that novel Tyrosine kinase 2 (Tyk2) gene mutations are present in virus-induced diabetes-sensitive SJL and SWR mice. Mice carrying the mutant Tyk2 gene on the virus-resistant C57BL/6 background are highly sensitive to virus-induced diabetes. Tyk2 gene expression is strongly reduced in Tyk2-mutant mice, associated with low Tyk2 promoter activity, and leads to decreased expression of interferon-inducible genes, resulting in significantly compromised antiviral response. Tyk2-mutant pancreatic β-cells are unresponsive even to high dose of Type I interferon. Reversal of virus-induced diabetes could be achieved by β-cell-specific Tyk2 gene expression. Thus, reduced Tyk2 gene expression in pancreatic β-cells due to natural mutation is responsible for susceptibility to virus-induced diabetes.

We estimated genetic parameters in Landrace and Large White pig populations for litter traits at farrowing (total number born, number born alive, number stillborn, total litter weight at birth (LWB), and mean litter weight at birth) and those at weaning (litter size at weaning (LSW), total litter weight at weaning (LWW), mean litter weight at weaning (MWW), and survival rate from farrowing to weaning). We analyzed 65,579 records at farrowing and 6,306 at weaning for Landrace, and 52,557 and 5,360, respectively, for Large White. Single‐trait and two‐trait repeatability animal models were exploited to estimate heritability and genetic correlation respectively. Heritability estimates of LSW were 0.09 for Landrace and 0.08 for Large White. Genetic correlations of LSW with MWW were –0.43 for Landrace and –0.24 for Large White. Genetic correlations of LSW with LWW and LWB ranged from 0.5 to 0.6. The genetic correlation of MWW with LWW was positive, but that with LWB was negligible. The results indicate that utilizing LWW or LWB could improve LSW efficiently, despite the antagonistic genetic correlation between LSW and MWW.

Extracellular matrix (ECM) is known to play several important roles in vascular development, although the molecular mechanisms behind these remain largely unknown. RECK, a tumor suppressor downregulated in a wide variety of cancers, encodes a membrane-anchored matrix-metalloproteinase-regulator. Mice lacking functional Reck die in utero, demonstrating its importance for mammalian embryogenesis; however, the underlying causes of mid-gestation lethality remain unclear. Using Reck conditional knockout mice, we have now demonstrated that the lack of Reck in vascular mural cells is largely responsible for mid-gestation lethality. Experiments using cultured aortic explants further revealed that Reck is essential for at least two events in sprouting angiogenesis; (1) correct association of mural and endothelial tip cells to the microvessels and (2) maintenance of fibronectin matrix surrounding the vessels. These findings demonstrate the importance of appropriate cell-cell interactions and ECM maintenance for angiogenesis and the involvement of Reck as a critical regulator of these events.

We estimated heritabilities of semen production traits and their genetic correlations with litter traits and pork production traits in purebred Duroc pigs. Semen production traits were semen volume, sperm concentration, proportion of morphologically normal sperms, total number of sperm, and total number of morphologically normal sperm. Litter traits at farrowing were total number born, number born alive, number stillborn, total litter weight at birth, mean litter weight at birth, and piglet survival rate at birth. Litter traits at weaning were litter size at weaning, total litter weight at weaning, mean litter weight at weaning, and piglet survival rate from birth to weaning. Pork production traits were average daily gain, backfat thickness, and loin muscle area. We analyzed 45,913 semen collection records of 896 boars, 6,950 farrowing performance records of 1,400 sows, 2,237 weaning performance records of 586 sows, and individual growth performance records of 9,550 animals measured at approximately 5 months of age. Heritabilities were estimated using a single-trait animal model. Genetic correlations were estimated using a two-trait animal model. Estimated heritabilities of semen production traits ranged from 0.20 for sperm concentration to 0.29 for semen volume and were equal to or higher than those of litter traits, ranging from 0.06 for number stillborn and piglet survival rate at birth to 0.25 for mean litter weight at birth, but lower than those of pork production traits, ranging from 0.50 for average daily gain to 0.63 for backfat thickness. In many cases, the absolute values of estimated genetic correlations between semen production traits and other traits were smaller than 0.3. These estimated genetic parameters provide useful information for establishing a comprehensive pig breeding scheme.

Matrix-assisted laser desorption ionization image mass spectrometry (MALDI-IMS) has been developed for the identification of peptides in various tissues. The MALDI-IMS signal distribution patterns and quantification of the signal intensities of the regions of interest (ROI) with healthy regions were compared for identification of the disease specific biomarkers. We performed a new ROI analysis using the conventional t-test and data number independent Cohen’s d-value analysis. Using these techniques, we analysed heart tissues after acute myocardial infarction (AMI). As a result, IMS signals of mitochondrial adenosine triphosphate synthase alpha subunit (ATP5A), myosin-6/7(MYH6/7), aortic actin, and the myosin light chain 3 (MYL3) were identified in the infarcted region. In particular, the signals of MYH7 are significantly greater in the infarcted region using ROI analysis. ROI analysis using MALDI-IMS may be a promising technique for the identification of biomarkers for pathological studies that involve the comparison of diseased and control areas.