Two Distinct Pathways Mediated by PA28 and hsp90 in Major Histocompatibility Complex Class I Antigen Processing

Major histocompatibility complex (MHC) class I ligands are mainly produced by the proteasome. Herein, we show that the processing of antigens is regulated by two distinct pathways, one requiring PA28 and the other hsp90. Both hsp90 and PA28 enhanced the antigen processing of ovalbumin (OVA). Geldanamycin, an inhibitor of hsp90, almost completely suppressed OVA antigen presentation in PA28α−/−/β−/− lipopolysaccharide blasts, but not in wild-type cells, indicating that hsp90 compensates for the loss of PA28 and is essential in the PA28-independent pathway. In contrast, treatment of cells with interferon (IFN)-γ, which induces PA28 expression, abrogated the requirement of hsp90, suggesting that IFN-γ enhances the PA28-dependent pathway, whereas it diminishes hsp90-dependent pathway. Importantly, IFN-γ did not induce MHC class I expressions in PA28-deficient cells, indicating a prominent role for PA28 in IFN-γ–stimulated peptide supply. Thus, these two pathways operate either redundantly or specifically, depending on antigen species and cell type

Search for a stochastic background of 100-MHz gravitational waves with laser interferometers

This letter reports the results of a search for a stochastic background of gravitational waves (GW) at 100 MHz by laser interferometry. We have developed a GW detector, which is a pair of 75-cm baseline synchronous recycling (resonant recycling) interferometers. Each interferometer has a strain sensitivity of ~ 10^{-16} Hz^{-1/2} at 100 MHz. By cross-correlating the outputs of the two interferometers within 1000 seconds, we found h_{100}^2 Omega_{gw} < 6 times 10^{25} to be an upper limit on the energy density spectrum of the GW background in a 2-kHz bandwidth around 100 MHz, where a flat spectrum is assumed.Comment: Accepted by Phys.Rev.Lett.; 10 pages, 4 figure

Genome editing in the mushroom-forming basidiomycete Coprinopsis cinerea, optimized by a high-throughput transformation system

Mushroom-forming basidiomycetes produce a wide range of metabolites and have great value not only as food but also as an important global natural resource. Here, we demonstrate CRISPR/Cas9-based genome editing in the model species Coprinopsis cinerea. Using a high-throughput reporter assay with cryopreserved protoplasts, we identified a novel promoter, CcDED1pro, with seven times stronger activity in this assay than the conventional promoter GPD2. To develop highly efficient genome editing using CRISPR/Cas9 in C. cinerea, we used the CcDED1pro to express Cas9 and a U6-snRNA promoter from C. cinerea to express gRNA. Finally, CRISPR/Cas9-mediated GFP mutagenesis was performed in a stable GFP expression line. Individual genome-edited lines were isolated, and loss of GFP function was detected in hyphae and fruiting body primordia. This novel method of high-throughput CRISPR/Cas9-based genome editing using cryopreserved protoplasts should be a powerful tool in the study of edible mushrooms

Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice

Autophagy is a membrane-trafficking mechanism that delivers cytoplasmic constituents into the lysosome/vacuole for bulk protein degradation. This mechanism is involved in the preservation of nutrients under starvation condition as well as the normal turnover of cytoplasmic component. Aberrant autophagy has been reported in several neurodegenerative disorders, hepatitis, and myopathies. Here, we generated conditional knockout mice of Atg7, an essential gene for autophagy in yeast. Atg7 was essential for ATG conjugation systems and autophagosome formation, amino acid supply in neonates, and starvation-induced bulk degradation of proteins and organelles in mice. Furthermore, Atg7 deficiency led to multiple cellular abnormalities, such as appearance of concentric membranous structure and deformed mitochondria, and accumulation of ubiquitin-positive aggregates. Our results indicate the important role of autophagy in starvation response and the quality control of proteins and organelles in quiescent cells

Efficacy and Safety of Switching Prostaglandin Analog Monotherapy to Tafluprost/Timolol Fixed-Combination Therapy

Purpose. To assess the efficacy and safety of switching from prostaglandin analog (PGA) monotherapy to tafluprost/timolol fixed-combination (Taf/Tim) therapy. Subjects and Methods. Patients with primary open-angle glaucoma, normal-tension glaucoma, or ocular hypertension who had received PGA monotherapy for at least 3 months were enrolled. Patients were examined at 1, 2, and 3 months after changing therapies. Subsequently, the patients were returned to PGA monotherapy. The examined parameters included intraocular pressure (IOP) and adverse events. A questionnaire survey was conducted after the switch to Taf/Tim therapy. Results. Forty patients with a mean age of 66.5 ± 10.3 years were enrolled; 39 of these patients completed the study protocol. Switching to Taf/Tim significantly reduced the IOP from 18.2 ± 2.6 mmHg at baseline to 14.8 ± 2.5 mmHg at 1 month, 15.2 ± 2.8 mmHg at 2 months, and 14.9 ± 2.5 mmHg at 3 months (P<0.001). Switching back to the original PGA monotherapy returned the IOP values to baseline levels. Taf/Tim reduced the pulse rate insignificantly. No significant differences were observed in blood pressure, conjunctival hyperemia, or corneal adverse events. A questionnaire showed that the introduction of Taf/Tim did not significantly influence symptoms. Conclusions. Compared with PGA monotherapy, Taf/Tim fixed-combination therapy significantly reduced IOP without severe adverse events

The Japanese space gravitational wave antenna; DECIGO

DECi-hertz Interferometer Gravitational wave Observatory (DECIGO) is the future Japanese space gravitational wave antenna. DECIGO is expected to open a new window of observation for gravitational wave astronomy especially between 0.1 Hz and 10 Hz, revealing various mysteries of the universe such as dark energy, formation mechanism of supermassive black holes, and inflation of the universe. The pre-conceptual design of DECIGO consists of three drag-free spacecraft, whose relative displacements are measured by a differential Fabry– Perot Michelson interferometer. We plan to launch two missions, DECIGO pathfinder and pre- DECIGO first and finally DECIGO in 2024

DECIGO pathfinder

DECIGO pathfinder (DPF) is a milestone satellite mission for DECIGO (DECi-hertz Interferometer Gravitational wave Observatory) which is a future space gravitational wave antenna. DECIGO is expected to provide us fruitful insights into the universe, in particular about dark energy, a formation mechanism of supermassive black holes, and the inflation of the universe. Since DECIGO will be an extremely large mission which will formed by three drag-free spacecraft with 1000m separation, it is significant to gain the technical feasibility of DECIGO before its planned launch in 2024. Thus, we are planning to launch two milestone missions: DPF and pre-DECIGO. The conceptual design and current status of the first milestone mission, DPF, are reviewed in this article

STUDIES ON THE PRODUCTIVITY OF SOIL ANIMALS IN PASOH FOREST RESERVE, WEST MALAYSIA : V. SEASONAL CHANGE IN THE DENSITY AND BIOMASS OF SOIL MACROFAUNA: OLIGOCHAETA, HIRUDINEA AND ARTHROPODA(Natural science)

本報は,IBP(国際生物学事業計画)のひとつとして,マレーシア・日本・イギリスが共同で研究した熱帯多雨林の研究のひとつで,土壌動物に関する一連の報告のひとつである。1971年4月から1972年8月までの間に,毎月5個,計68個の土壌塊を検査し,次の結果を得た。検査された土壌塊は,面積50cm×50cm,深さ20cmを単位とするものである。1.個体数が最も多いのは,アリを含む膜翅類の動物で全体の85.4%を占め,第2位は鞘翅類の幼虫の4.1%であった。現存量では膜翅類の26.6%,鞘翅類の成虫19.4%となった。2.全土壌大形動物の平均密度は1903個体/m^2,同現存量は3.1g/m^2であった。3.季節変化はすべての生物群について見られる共通点は明瞭ではないが,密度は6～8月に高く,現存量はむしろ7月に高くなっていた。4.Iδ-indexを用いた検討によると,ヒル類・サソリ類が少いが均等に分布し,貧毛類・半翅類・直翅類・鱗翅類・ヤスデ類・ムカデ類・ゴキブリ類についてはいくぶんかたまり気味であったが,かなり分散していることがわかった。アジを含む膜翅類とシロアリ(等翅類)はともに強い集合性を示していた。5.落葉が堆積している場所と,落葉がない場所との密度や現存量を比較してみたが,直翅類や鱗翅類幼虫については差が認められ難く,メクラグモ類・貧毛類・鞘翅類の幼虫と成虫・クモ類は集合性には差がなかったが,落葉のある土壌の方が高密度であった。双翅類の幼虫やアリを含む膜翅類は落葉の多い土壌の方が高い集合性を示した。6.これらの資料とA_(1979)のシロアリの密度や現存量の資料を加えて,この地域の土壌大形動物の密度は5000～5700個体/m^2同現存量は11.8～13.2g/m^2(湿重量)と推定することができる。ここに推定された密度は,今迄の報告にくらべて大きい値をとっているが,アリ・シロアリ以外の動物群のみを比較するとW_ et al. (1966)のタイにおける値とほぼ同様になる

Current status of space gravitational wave antenna DECIGO and B-DECIGO

Deci-hertz Interferometer Gravitational Wave Observatory (DECIGO) is the future Japanese space mission with a frequency band of 0.1 Hz to 10 Hz. DECIGO aims at the detection of primordial gravitational waves, which could be produced during the inflationary period right after the birth of the universe. There are many other scientific objectives of DECIGO, including the direct measurement of the acceleration of the expansion of the universe, and reliable and accurate predictions of the timing and locations of neutron star/black hole binary coalescences. DECIGO consists of four clusters of observatories placed in the heliocentric orbit. Each cluster consists of three spacecraft, which form three Fabry-Perot Michelson interferometers with an arm length of 1,000 km. Three clusters of DECIGO will be placed far from each other, and the fourth cluster will be placed in the same position as one of the three clusters to obtain the correlation signals for the detection of the primordial gravitational waves. We plan to launch B-DECIGO, which is a scientific pathfinder of DECIGO, before DECIGO in the 2030s to demonstrate the technologies required for DECIGO, as well as to obtain fruitful scientific results to further expand the multi-messenger astronomy.Comment: 10 pages, 3 figure