プロテアソーム阻害剤エポキソマイシンとMG262はヒト口腔扁平上皮癌細胞(HSC-3)によるウロキナーゼ型プラスミノーゲンアクチベータ発現を抑制する

プロテアソーム阻害剤のエポキソマイシンとMG262が、HSC-3細胞におけるウロキナーゼ型プラスミノーゲンアクチベータ(uPA)のmRNA発現とuPA産生に及ぼす影響について検討した。エポキソマイシンとMG262はuPA mRNA発現とuPA産生を用量依存性に抑制した。経時変化の検討では、エポキソマイシンまたはMG262への曝露から6時間程度で、uPA mRNA発現に顕著な減少が認められ、抑制効果は12および24時間後と同等またはやや強かった。エポキソマイシンとMG262は核性因子(NF)-κB-依存性プロモーターの転写活性を弱めた。uPA遺伝子の転写はNF-κB活性に依存することが知られており、これらのプロテアソーム阻害剤によるuPA遺伝子発現の抑制は、構成的NF-κB活性阻害の影響と考えられる。またエポキソマイシンとPG262はHSC-3細胞の浸潤活性を低下させた。プロテアソーム阻害剤による浸潤活性の減少はuPA産生抑制の影響を一部に受けていると考えられた

Importin-β and the small guanosine triphosphatase Ran mediate chromosome loading of the human chromokinesin Kid

Nucleocytoplasmic transport factors mediate various cellular processes, including nuclear transport, spindle assembly, and nuclear envelope/pore formation. In this paper, we identify the chromokinesin human kinesin-like DNA binding protein (hKid) as an import cargo of the importin-α/β transport pathway and determine its nuclear localization signals (NLSs). Upon the loss of its functional NLSs, hKid exhibited reduced interactions with the mitotic chromosomes of living cells. In digitonin-permeabilized mitotic cells, hKid was bound only to the spindle and not to the chromosomes themselves. Surprisingly, hKid bound to importin-α/β was efficiently targeted to mitotic chromosomes. The addition of Ran–guanosine diphosphate and an energy source, which generates Ran–guanosine triphosphate (GTP) locally at mitotic chromosomes, enhanced the importin-β–mediated chromosome loading of hKid. Our results indicate that the association of importin-β and -α with hKid triggers the initial targeting of hKid to mitotic chromosomes and that local Ran-GTP–mediated cargo release promotes the accumulation of hKid on chromosomes. Thus, this study demonstrates a novel nucleocytoplasmic transport factor–mediated mechanism for targeting proteins to mitotic chromosomes

Multicolor and multi-spot observations of Starlink's Visorsat

This study provides the results of simultaneous multicolor observations for the first Visorsat (STARLINK-1436) and the ordinary Starlink satellite, STARLINK-1113 in the $U$, $B$, $V$, $g'$, $r$, $i$, $R_{\rm C}$, $I_{\rm C}$, $z$, $J$, $H$, and $K_s$ bands to quantitatively investigate the extent to which Visorsat reduces its reflected light. Our results are as follows: (1) in most cases, Virorsat is fainter than STARLINK-1113, and the sunshade on Visorsat, therefore, contributes to the reduction of the reflected sunlight; (2) the magnitude at 550 km altitude (normalized magnitude) of both satellites often reaches the naked-eye limiting magnitude ($<$ 6.0); (3) from a blackbody radiation model of the reflected flux, the peak of the reflected components of both satellites is around the $z$ band; and (4) the albedo of the near infrared range is larger than that of the optical range. Under the assumption that Visorsat and STARLINK-1113 have the same reflectivity, we estimate the covering factor, $C_{\rm f}$, of the sunshade on Visorsat, using the blackbody radiation model: the covering factor ranges from $0.18 \leq C_{\rm f} \leq 0.92$. From the multivariable analysis of the solar phase angle (Sun-target-observer), the normalized magnitude, and the covering factor, the phase angle versus covering factor distribution presents a moderate anti-correlation between them, suggesting that the magnitudes of Visorsat depend not only on the phase angle but also on the orientation of the sunshade along our line of sight. However, the impact on astronomical observations from Visorsat-designed satellites remains serious. Thus, new countermeasures are necessary for the Starlink satellites to further reduce reflected sunlight.Comment: 31 pages, 9 figures, published in PAS

Synthesis of dihydro-1,4-thiazine from α-keto spiro-thiazolidine

1037-1041The reaction of &alpha;-bromocycloalkanone with 2-aminoethanthiol leads to the regioselective formation of spirothiazolidin-2-one with the oxo-group migrating to the original position occupied by the halogen atom. The reaction of 1-thia-4-azaspiro[4.5]alkan-6-one with bromine, iodine, copper (II) salts, acid or base gives dihydro-1,4-thiazine derivatives in moderate yields. Moreover, the treatment of the spiro-thiazolidine derivatives on silica gel under microwave gives the 1,4-thiazine compound