Distribution of allele frequencies at TTN g.231054C > T, RPL27A g.3109537C > T and AKIRIN2 c.*188G > A between Japanese Black and four other cattle breeds with differing historical selection for marbling

<p>Abstract</p> <p>Background</p> <p>Marbling defined by the amount and distribution of intramuscular fat, so-called <it>Shimofuri</it>, is an economically important trait of beef cattle in Japan. Our previous study detected 3 single nucleotide polymorphisms (SNPs), <it>g.231054C > T</it>, <it>g.3109537C > T </it>and <it>c.*188G > A</it>, respectively, in the 5' flanking region of the <it>titin </it>(<it>TTN</it>), the 5' flanking region of the <it>ribosomal protein L27a </it>(<it>RPL27A</it>) and the 3' untranslated region of the <it>akirin 2 </it>genes (<it>AKIRIN2</it>), which have been considered as positional functional candidates for the genes responsible for marbling, and showed association of these SNPs with marbling in Japanese Black beef cattle. In the present study, we investigated the allele frequency distribution of the 3 SNPs among the 5 cattle breeds, Japanese Black, Japanese Brown, Japanese Shorthorn, Holstein and Brown Swiss breeds.</p> <p>Findings</p> <p>We genotyped the <it>TTN g.231054C > T</it>, <it>RPL27A g.3109537C > T </it>and <it>AKIRIN2 c.*188G > A </it>SNPs by polymerase chain reaction-restriction fragment length polymorphism method, using 101 sires and 1,705 paternal half sib progeny steers from 8 sires for Japanese Black, 86 sires and 27 paternal half sib progeny steers from 3 sires for Japanese Brown, 79 sires and 264 paternal half sib progeny steers from 14 sires for Japanese Shorthorn, 119 unrelated cows for Holstein, and 118 unrelated cows for Brown Swiss breeds. As compared to the frequencies of the <it>g.231054C > T T</it>, <it>g.3109537C > T T </it>and <it>c.*188G > A A </it>alleles, associated with high marbling, in Japanese Black breed that has been subjected to a strong selection for high marbling, those in the breeds, Japanese Shorthorn, Holstein and Brown Swiss breeds, that have not been selected for high marbling were null or lower. The Japanese Brown breed selected slightly for high marbling showed lower frequency than Japanese Black breed in the <it>g.3109537C > T T </it>allele, whereas no differences were detected between the 2 breeds in the frequencies of the <it>g.231054C > T T </it>and <it>c.*188G > A A </it>alleles.</p> <p>Conclusions</p> <p>Based on this finding, we hypothesized that the pressure of the strong selection for high marbling in Japanese Black breed has increased the frequencies of the <it>T</it>, <it>T </it>and <it>A </it>alleles at the <it>TTN g.231054C > T</it>, <it>RPL27A g.3109537C > T </it>and <it>AKIRIN2 c.*188G > A </it>SNPs, respectively. This study, together with the previous association studies, suggested that the 3 SNPs may be useful for effective marker-assisted selection to increase the levels of marbling.</p

Multicenter Phase II Study of Intravenous and Intraperitoneal Paclitaxel With S-1 for Pancreatic Ductal Adenocarcinoma Patients With Peritoneal Metastasis

OBJECTIVE:To evaluate the clinical efficacy and tolerability of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel combined with S-1, "an oral fluoropyrimidine derivative containing tegafur, gimestat, and otastat potassium" in chemotherapy-naive pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis.BACKGROUND:PDAC patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis. An effective treatment strategy remains elusive.METHODS:Paclitaxel was administered i.v. at 50 mg/m and i.p. at 20 mg/m on days 1 and 8. S-1 was administered at 80 mg/m/d for 14 consecutive days, followed by 7 days of rest. The primary endpoint was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect and safety (UMIN000009446).RESULTS:Thirty-three patients who were pathologically diagnosed with the presence of peritoneal dissemination (n = 22) and/or positive peritoneal cytology (n = 11) without other organ metastasis were enrolled. The tumor was located at the pancreatic head in 7 patients and the body/tail in 26 patients. The median survival time was 16.3 (11.47-22.57) months, and the 1-year survival rate was 62%. The response rate and disease control rate in assessable patients were 36% and 82%, respectively. OS in 8 patients who underwent conversion surgery was significantly higher than that of nonsurgical patients (n = 25, P = 0.0062). Grade 3/4 hematologic toxicities occurred in 42% of the patients and nonhematologic adverse events in 18%. One patient died of thrombosis in the superior mesenteric artery.CONCLUSIONS:This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis

Inhibitory Effects of Chlorella Extract on Airway Hyperresponsiveness and Airway Remodeling in a Murine Model of Asthma

Chlorella extract （CE） has been shown to induce production of T helper-1 cytokines, and regulate serum IgE levels in animal models of asthma. We aimed to evaluate whether CE could inhibit ovalbumin （OVA）-induced airway hyperresponsiveness （AHR） and airway remodeling in a murine model of asthma. Balb/c mice were allocated to four groups: a control group （no OVA exposure, not given CE）, a CE group （no OVA exposure, given CE）, an asthma group （sensitized/challenged with OVA, not given CE） and a CE＋asthma group （sensitized/challenged with OVA, given CE）. In the asthma and CE＋asthma groups, mice were sensitized with OVA on day 0 and day 12, and then challenged with OVA on three consecutive days. In the CE and CE＋asthma groups, the mice were given feed containing 2％ CE. We assessed AHR to methacholine, and analyzed bronchoalveolar lavage fluid （BALF）, serum, lung tissue and spleen cells. Administration of CE was associated with significantly lower AHR in OVA-sensitized and challenged mice. CE administration was also associated with marked reduction of total cells, eosinophils and T helper-2 cytokines （IL-4, IL-5 and IL-13） in BALF. In addition, administration of CE significantly decreased the numbers of periodic acid-Schiff （PAS）-positive cells in OVA-sensitized and challenged mice. Administration of CE also directly suppressed IL-4, IL-5 and IL-13 production in spleen cells of OVA-sensitized and challenged mice. These results indicate that CE can partly prevent AHR and airway remodeling in a murine model of asthma

Human iPS cell-derived dopaminergic neurons function in a primate Parkinson's disease model

Induced pluripotent stem cells (iPS cells) are a promising source for a cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminergic neurons progressively degenerate. However, long-term analysis of human iPS cell-derived dopaminergic neurons in primate PD models has never been performed to our knowledge. Here we show that human iPS cell-derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons in a primate model of PD (Macaca fascicularis) treated with the neurotoxin MPTP. Score-based and video-recording analyses revealed an increase in spontaneous movement of the monkeys after transplantation. Histological studies showed that the mature dopaminergic neurons extended dense neurites into the host striatum; this effect was consistent regardless of whether the cells were derived from patients with PD or from healthy individuals. Cells sorted by the floor plate marker CORIN did not form any tumours in the brains for at least two years. Finally, magnetic resonance imaging and positron emission tomography were used to monitor the survival, expansion and function of the grafted cells as well as the immune response in the host brain. Thus, this preclinical study using a primate model indicates that human iPS cell-derived dopaminergic progenitors are clinically applicable for the treatment of patients with PD