Lineage-Specific Duplication and Loss of Pepsinogen Genes in Hominoid Evolution

Fourteen different pepsinogen-A cDNAs and one pepsinogen-C cDNA have been cloned from gastric mucosa of the orangutan, Pongo pygmaeus. Encoded pepsinogens A were classified into two groups, i.e., types A1 and A2, which are different in acidic character. The occurrence of 9 and 5 alleles of A1 and A2 genes (at least 5 and 3 loci), respectively was anticipated. Respective orthologous genes are present in the chimpanzee genome although their copy numbers are much smaller than those of the orangutan genes. Only A1 genes are present in the human probably due to the loss of the A2 gene. Molecular phylogenetic analyses showed that A1 and A2 genes diverged before the speciation of great hominoids. Further reduplications of respective genes occurred several times in the orangutan lineage, with much higher frequencies than those occurred in the chimpanzee and human lineages. The rates of non-synonymous substitutions were higher than those of synonymous ones in the lineage of A2 genes, implying the contribution of the positive selection on the encoded enzymes. Several sites of pepsin moieties were indeed found to be under positive selection, and most of them locate on the surface of the molecule, being involved in the conformational flexibility. Deduced from the known genomic structures of pepsinogen-A genes of primates and other mammals, the duplication/loss were frequent during their evolution. The extreme multiplication in the orangutan might be advantageous for digestion of herbaceous foods due to the increase in the level of enzymes in stomach and the diversification of enzyme specificit

A Possible Spin-Orbit Misalignment in the Transiting Eccentric Planet HD 17156b

We present simultaneous photometric and spectroscopic observations of HD 17156b spanning a transit on UT 2007 November 12. This system is of special interest because of its 21-day period (unusually long for a transiting planet) and its high orbital eccentricity of 0.67. By modeling the Rossiter-McLaughlin effect, we find the angle between the sky projections of the orbital axis and the stellar rotation axis to be $62^{\circ} \pm 25^{\circ}$. Such a large spin-orbit misalignment, as well as the large eccentricity, could be explained as the relic of a previous gravitational interaction with other planets.Comment: 5 pages, 2 figures, 3 tables. Accepted for publication in PASJ Letters (Vol. 60, No. 2

Separation of immature granules containing color dye from the rat parotid gland

Parotid acinar cell contains many secretory granules. Most of granules are mature, but only little immature granules are included. These immature granules are not enough for investigation of granule maturation. In this study, we show an easy method of separation of immature granules from the rat parotid gland. In addition, we succeeded in detection of color dye in the granules. These results suggest that secretory granules can be visualized through endocytosis

The thiol-oxidizing agent diamide reduces isoproterenolstimulated amylase release in rat parotid acinar cells

In parotid acinar cells, activation of β-adrenergic receptors provokes exocytotic amylase release via the accumulation of intracellular cAMP. Cellular redox status plays a pivotal role in the regulation of various cellular functions. Cellular redox imbalance caused by the oxidation of cellular antioxidants, as a result of oxidative stress, induces significant biological damages. In this study, we examined effect of diamide, a thioloxidizing reagent, on amylase release in rat parotid acinar cells. In the presence of diamide, isoproterenol (IPR)-induced cAMP formation and amylase release were partially reduced. Diamide had no effect on amylase release induced by forskolin and mastoparan, an adenylate cyclase activator and heterotrimeric GTP binding protein activator, respectively. In the cells pretreated with diamide, the binding affinity of [3H]dihydroalprenolol to β-receptors was reduced. These results suggest that oxidative stress results in reduction of binding affinity of ligand on β-receptor and consequently reduces protein secretory function in rat parotid acinar cells

Early aggressive intervention for infantile atopic dermatitis to prevent development of food allergy : a multicenter, investigator‑blinded, randomized, parallel group controlled trial (PACI Study) : protocol for a randomized controlled trial

Background: Atopic dermatitis is the first clinical manifestation of the atopic march, with the highest incidence in the first year of life. Those affected often go on to develop other allergic diseases including food allergy, asthma, and allergic rhinitis. Recent evidence suggests that sensitization to foods may occur through a defective skin barrier which is common in atopic dermatitis in early life. We hypothesize that therapeutic aggressive intervention to treat new onset atopic dermatitis may prevent the development of later allergen sensitization, and associated food allergy, asthma, and allergic rhinitis. Methods: This study is a multi-center, pragmatic, two-parallel group, assessor-blind, superiority, individually randomized controlled trial. Atopic dermatitis infants (N = 650) 7–13 weeks old who develop an itchy rash within the previous 28 days are randomly assigned to the aggressive treatment or the conventional treatment in a 1:1 ratio. The primary outcome is oral food challenge-proven IgE-mediated hen’s egg allergy at the age of 28 weeks. Discussion: This is a novel pragmatic RCT study to examine the efficacy of early aggressive treatment for atopic dermatitis to prevent later food allergy. If our hypothesis is correct, we hope that such a strategy might impact on disease prevention in countries where food allergy is common, and that our results might reduce the frequency and associated costs of all food allergies as well as hens egg food allergy. Long-term follow and other similar studies will help to determine whether such a strategy will reduce the burden of other allergic diseases such as asthma and allergic rhinitis

Cytotoxic T Lymphocytes Regenerated from iPS Cells Have Therapeutic Efficacy in a Patient-Derived Xenograft Solid Tumor Model

Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of the patient's T cells. To address these issues, we developed a strategy in which cytotoxic T lymphocytes (CTLs) are regenerated from iPSCs that were originally derived from T cells and succeeded in regenerating CTLs specific for the WT1 antigen, which exhibited therapeutic efficacy in a xenograft model of leukemia. In this study, we extended our strategy to solid tumors. The regenerated WT1-specific CTLs had a strong therapeutic effect in orthotopic xenograft model using a renal cell carcinoma (RCC) cell line. To make our method more generally applicable, we developed an allogeneic approach by transducing HLA-haplotype homozygous iPSCs with WT1-specific TCR α/β genes that had been tested clinically. The regenerated CTLs antigen-specifically suppressed tumor growth in a patient-derived xenograft model of RCC, demonstrating the feasibility of our strategy against solid tumors

Point source in a phononic grating: stop bands give rise to phonon-focusing caustics

We use locally-excited gigahertz surface phonon wavepackets in microscopic line structures of different pitches to reveal profound anisotropy in the radiation pattern of a point source in a grating. Time-domain data obtained by an ultrafast optical imaging technique and by numerical simulations are Fourier transformed to obtain frequency-filtered real-space acoustic field patterns and k-space phononic band structure. The numerically-obtained k-space images are processed to reveal an intriguing double-horn structure in the lowest-order group-velocity surface, which explains the observed non-propagation sectors bounded by caustics, noted at frequencies above the bottom of the first stop band. We account for these phonon-focusing effects, analogous to collimation effects previously observed in two- and three-dimensional lattices, with a simple analytical model of the band structure based on a plane wave expansion. As the frequency is increased, a transition to dominant waveguiding effects along the lines is also documented

TP53 codon 72 polymorphism is associated with FGFR3 and RAS mutation in non-muscle-invasive bladder cancer

ObjectiveTP53, a well-known tumor-suppressor gene in bladder carcinogenesis, has a functional single-nucleotide polymorphism on codon 72. The aim of this study was to elucidate the association between TP53 codon 72 polymorphism and somatic mutations in bladder cancer.Material and methodsGermline TP53 codon 72 polymorphism and somatic mutations of 50 cancer-associated genes were analyzed in 103 bladder cancer patients (59 non-muscle-invasive and 44 muscle-invasive), using Taqman genotyping assay and target sequencing, respectively. The expression of FGF-FGFR signaling pathway genes was analyzed by RNA sequencing of frozen tissue.ResultsThe allele frequency of TP53 codon 72 in our cohort was 37, 42, and 21% for Arg/Arg, Arg/Pro, and Pro/Pro, respectively. Interestingly, the prevalence of FGFR3 mutation was higher in patients with the Arg allele, whereas that of the RAS mutation was higher in patients without the Arg allele. The same association was seen in non-muscle-invasive bladder cancer (NMIBC) patients and no differences were observed in muscle-invasive bladder cancer patients. In NMIBC, FGFR1 expression was higher in patients without the Arg allele and FGFR3 expression was higher in patients with the Arg allele.ConclusionThe germline TP53 codon 72 polymorphism was associated with mutations of FGFR3 or RAS and expression of FGFR1 and FGFR3 in NMIBC. These findings provide new insight into the molecular mechanisms underlying the influence of the genetic background on carcinogenesis in bladder cancer

ダイ47ジ ナンキョク チイキ カンソクタイ キショウ ブモン ホウコク 2006

この報告は第47次南極地域観測隊気象部門が,2006年2月1日～2007年1月31日まで昭和基地において行った気象観測結果をまとめたものである.観測方法,測器,統計方法等は第46次隊とほぼ同様である.越冬期間中,特記される気象現象として,次のものがあげられる.1)地上気象観測において,7月の月平均気温が-24.1°Cを記録し,これまでの極値を更新(昨年までの月平均気温の記録は1997年9月の-23.6°C)した.2)昭和基地上空の下部成層圏の気温は,冬から春先にかけて平年より低めに推移した.特に,8-10月にかけ,70 hPa以下の多くの指定気圧面で,これまでの各月の極値を更新する低温を観測した.一方,対流圏においては,10月7～9日にかけてのA級ブリザードの影響で,850 hPa-350 hPaの指定気圧面で,00 UTC観測における10月の高温の極値を更新した.3)昭和基地上空のオゾン全量は,10月17日に114 m atm-cmと,これまでの過去最小を記録(昨年までの最小値は1995年10月6日の128 m atm-cm),月の平均でも10月に137 m atm-cmと,これまでの過去最小を記録し(昨年までの最小値は1996年10月の156 m atm-cm),オゾンホールが現れる前の1980年以前と比べて,半分以下の値となった.また,オゾン量の回復も例年より遅れ,2007年1月となった.This report describes the results of meteorological observations at Syowa Station from February 1st, 2006 to January 31st, 2007, carried out by the Meteorological Observation Team of the 47th Japanese Antarctic Research Expedition (JARE-47). The observation methods, instruments and statistical methods used by JARE-47 were almost the same as those used by the JARE-46 observation team.Remarkable weather phenomena observed during the period of JARE-47 are as follows.1)The monthly mean temperature in July in 2006 at Syowa Station was -24.1°C, which was the lowest record for Syowa Station.2)The temperature of the lower part of the stratosphere over Syowa Station was lower than normal from winter to early spring in 2006. Especially, the minimum temperature at many standard pressure levels under 70 hPa set the lowest record in each month from August to October. On the other hand, in the troposphere, due to the A-class blizzard on 7-10 October, the maximum temperature at the standard pressure level from 850-350 hPa set the highest record in October.3)The amount of total ozone over Syowa Station became lower than or equal to 220 m atm-cm from the end of August to mid-October. The monthly mean amount of total ozone in September was 173 m atm-cm, which was the 4th lowest value in the historical record. On 4th October, the amount of total ozone was 136 m atm-cm, which was the lowest value during JARE-46.The amount of total ozone over Syowa Station on October 17th, 2000 was 114 m atm-cm, which was the lowest record. The monthly mean amount of total ozone in October was 137 m atm-cm, which was the lowest record. It was below half compared with the value before 1980 when the ozone hole had not yet appeared. The recovery of the total amount of ozone was slower than usual, in January 2007