表皮角化細胞による血小板由来増殖因子産生機構の研究

金沢大学医薬保健研究域医学系表皮角化細胞は,通常は無血清増殖培地で培養されるが,この培養系では増殖した表皮角化細胞の抽出蛋白・培養上清ともウエスタンブロットではPDGFは検出されず,培地にEGFないしbasicFGFを添加したときに培養上清のみからPDGFのバンドが検出された。さらに抗PGDF-AA抗体,抗PDGF-BB抗体を用いて,検出されるPDGFのアイソフォームを検討したところ,表皮角化細胞は主としてPGDF-AAを産生していることが明らかとなった。次に,モルモットの皮膚欠損モデルを用いて,免疫組織化学とin situ hybridizationによって,表皮角化細胞のPDGFの発現とそのアイソフォームを検討したところ,創辺縁部と再生表皮に限局してPDGF-AAの蛋白およびmRNAが発現しており,前述の培養系と一致する結果が得られた。以上の結果から,表皮角化細胞は通常PDGFを発現していないが,サイトカインなどの刺激により増殖期に入ると主としてPDGF-AAを発現するようになり,産生されたPDGF-AAは速やかに分泌されるものと考えられた。創傷治癒過程においては,サイトカインなどにより刺激された表皮角化細胞がPDGFを産生し,分泌されたPDGFが創傷治癒を促進することが示唆された。このような,PDGFを介したサイトカインネットワークが皮膚において,様々な生理的意義を有するものと推測される。研究課題/領域番号:10770396, 研究期間(年度):1998 – 1999出典：「表皮角化細胞による血小板由来増殖因子産生機構の研究」研究成果報告書　課題番号10770396（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-10770396/)を加工して作

線維化組織の形成と維持における結合組織増殖因子と形質転換増殖因子βの役割と相互作用: マウス線維化モデルの作成

取得学位：博士(医学), 学位授与番号：医博乙第1506号，学位授与年月日：平成11年12月1日,学位授与年：199

シリヤケイカの繁殖行動

The reproductive behavior of the Japanese spineless cuttlefish Sepiella japonica was observed in a tank. The males competed for females before egg-laying and then formed pairs with females. The male then initiated mating by pouncing on the female head, and maintained the male superior head-to-head position during the mating. Before ejaculation, the male moved his right (non-hectocotylized) arm IV under the ventral portion of the female buccal membrane, resulting in the dropping of parts of spermatangia placed there during previous matings. After the sperm removal behavior, the male held spermatophores ejected through his funnel with the base of hectocotylized left arm IV and transferred them to the female buccal area. The spermatophore transfer occurred only once during each mating. The female laid an egg capsule at average intervals of 1.5 min and produced from 36 to more than 408 egg capsules in succession during a single egg-laying bout. Our results also suggested one female produced nearly 200 fertilized eggs without additional mating, implying that the female have potential capacity to store and use active sperm properly. The male continued to guard the spawning female after mating (range=41.8-430.1 min), and repeated matings occurred at an average interval of 70.8 min during the mate guarding. Although the time spent on the sperm removal in S. japonica was shorter than in other sperm-removing cuttlefishes, the shorter sperm removal duration may be compensated by the post-copulatory mate guarding and repeated matings in this species.水槽内でのシリヤケイカSepiella japonicaの繁殖行動を観察した。シリヤケイカの雄は雌が産卵を開始する前に雌をめぐって闘争し,ペアを形成した。ペア雄は雌の頭部に覆い被さる形で交接を始め,雄上位のままで雌雄の頭部が向き合う交接体勢を維持した。雄は自らの精莢を射出する前に,雌の口球周口腹下部で右第IV腕を動かすことによって,過去の交接によってそこに付着させられていた精子塊の一部を落下させた。その精子除去行動後,雄は交接腕である左第IV腕の根元で漏斗から吐き出した精莢をつかみ,雌の口球下部に渡した。この精莢輸送は各交接で1回だけであった。雌は平均1.5分の間隔で産卵基質に卵嚢を1つずつ産みつけ,一連の産卵行動で36から408個以上の卵嚢を産出した。また,本研究では1個体の雌が追加の交接なして200個近くの受精卵を産出することが示され,シリヤケイカの雌は過去の交接によって貯えられた精子を必要な時に受精に使う能力を持つと考えられた。それに対して雄は交接後も産卵雌を他雄からガードし続け(交接後ガード時間の範囲=41.8〜430.1分),そのガード行動中に平均70.8分の間隔で繰り返し交接を行った。シリヤケイカの雄が精子除去に費やす時間は他のコウイカ類のそれらと比べて短かったが,永続的な交接後ガード行動と繰り返し交接が短時間の精子除去から推測された本種の低い精子置換率を補償しているかもしれない

Sperm removal, ejaculation and their behavioural interaction in male cuttlefish in response to female mating history

The removal of previously stored rival sperm and increased ejaculate expenditure are effective male sperm competition tactics to ensure paternity. We examined both behaviours and their interaction for male cuttlefish, Sepia lycidas, as a strategic investment. Males increased the duration of sperm removal and the number of ejaculations per mating when they were not the last male who had mated with the current partner. These responses would decrease the number of rival sperm and increase the male\u27s own sperm in the fertilization area. Recognition of the female\u27s mating history appeared to result from close mate guarding during successive matings. Moreover, when the last mate of the current partner was different from the current mate, there was a significant negative relationship between sperm removal duration and the number of subsequent ejaculations. This interaction suggests both strategic investment allocation and constraints on each mating investment as possible results of mating interruption by other males and spermatophore depletion, respectively. In addition, larger males with high competitive ability prolonged sperm removal when the last mate of the current partner was different from the current mate, whereas smaller males with relatively larger testes ejaculated more times during a mating. Male S. lycidas might adjust the duration of sperm removal at the risk of failing to achieve ejaculation and allocate their finite ejaculate expenditures based on the results (i.e. the increasing proportion of their own sperm)

Dual Functions of Yeast tRNA Ligase in the Unfolded Protein Response: Unconventional Cytoplasmic Splicing of HAC1 Pre-mRNA Is Not Sufficient to Release Translational Attenuation

Unconventional cytoplasmic splicing of HAC1 mRNA is essential for the yeast unfolded protein response (UPR). The UPR requires translational regulation of unspliced and spliced forms of HAC1 mRNAs. Here we report that tRNA ligase, Rlg1p, which ligates HAC1 exons in its splicing, has another face as a translational regulator of HAC1 mRNA

Mohawk promotes the maintenance and regeneration of the outer annulus fibrosus of intervertebral discs.

The main pathogenesis of intervertebral disc (IVD) herniation involves disruption of the annulus fibrosus (AF) caused by ageing or excessive mechanical stress and the resulting prolapse of the nucleus pulposus. Owing to the avascular nature of the IVD and lack of understanding the mechanisms that maintain the IVD, current therapies do not lead to tissue regeneration. Here we show that homeobox protein Mohawk (Mkx) is a key transcription factor that regulates AF development, maintenance and regeneration. Mkx is mainly expressed in the outer AF (OAF) of humans and mice. In Mkx(-/-) mice, the OAF displays a deficiency of multiple tendon/ligament-related genes, a smaller OAF collagen fibril diameter and a more rapid progression of IVD degeneration compared with the wild type. Mesenchymal stem cells overexpressing Mkx promote functional AF regeneration in a mouse AF defect model, with abundant collagen fibril formation. Our results indicate a therapeutic strategy for AF regeneration

Localized Right Cerebral Hemisphere Dysfunction, Bereavement and Secondary Mania.

The authors report on a fully right-handed man without prior psychiatric history who developed mania secondary to vascular lesion in the right hemisphere immediately after bereavement of his wife. From literature consideration, it is suggested that bereavement is an effective trigger of mania and that right hemisphere dysfunction provides vulnerability for this effect. This case raises important question for both organic and psychological theories of causation of bipolar affective illness