SRY-box containing gene 9 (Sox9) and scleraxis (Scx) regulate cartilage and tendon formation, respectively. Here we report that murine Scx+/Sox9+ progenitors differentiate into chondrocytes and tenocytes/ligamentocytes to form the junction between cartilage and tendon/ligament. Sox9 lineage tracing in the Scx+ domain revealed that Scx+ progenitors can be subdivided into two distinct populations with regard to their Sox9 expression history: Scx+/Sox9+ and Scx+/Sox9− progenitors. Tenocytes are derived from Scx+/Sox9+ and Scx+/Sox9− progenitors. The closer the tendon is to the cartilaginous primordium, the more tenocytes arise from Scx+/Sox9+ progenitors. Ligamentocytes as well as the annulus fibrosus cells of the intervertebral discs are descendants of Scx+/Sox9+ progenitors. Conditional inactivation of Sox9 in Scx+/Sox9+ cells causes defective formation in the attachment sites of tendons/ligaments into the cartilage, and in the annulus fibrosus of the intervertebral discs. Thus, the Scx+/Sox9+ progenitor pool is a unique multipotent cell population that gives rise to tenocytes, ligamentocytes and chondrocytes for the establishment of the chondro-tendinous/ligamentous junction.
Scleraxis (Scx) is a basic helix-loop-helix transcription factor that is a marker for the tendon/ligament cell lineage. The ∼11 kb genomic region from the mouse Scx gene locus faithfully recapitulates the endogenous Scx expression pattern in ScxGFP transgenic (Tg) mice. We have established two Tg mouse lines expressing Cre-recombinase (Cre) using this regulatory region (ScxCre-L and ScxCre-H). The specificity and efficiency of Cre recombination in these Tg lines are evaluated by crossing with Rosa-CAG-LSL-tdTomato (Ai14) or ROSA26R (R26R) reporter mice. The recombination in ScxCre-H;Ai14 mice is efficiently achieved in the endogenous Scx expression domains including the branchial arches, the syndetome, and the lateral plate mesoderm. Further analysis of ScxCre-H;Ai14;ScxGFP embryos reveal that expression of the ScxGFP transgene largely overlaps with Cre activity detected by tdTomato at embryonic day 12.5 (E12.5). In ScxCre-L;R26R or ScxCre-H;R26R neonates, Cre activity is detected in tendons, ligaments, intervertebral discs, joints, and cartilage around the chondro-tendinous/ligamentous junction, the prospective enthesis. The present results suggest that ScxCre Tg lines are useful for targeting the gene specifically in the Scx-expressing domains.
In order to understand relationships between scanning behaviors, characteristics of visual stimuli and the clinical symptoms in schizophrenia, eye movements of 37 schizophrenic patients and 36 controls were recorded using an eye-mark recorder during a free-response period in a Rorschach test. Four cards (I, II, V and VIII) were used. Data were analyzed during 15 s from the presentation of each card. For all cards, the number of eye fixations and the number of eye fixation areas were fewer, and total scanning length and mean scanning length were shorter for schizophrenic patients than for controls. For card II, in the non-popular response group, eye fixation frequency upon area 5 + 6 (red) was higher for schizophrenic patients. For card VIII, in the popular response group, eye fixation frequency upon area 5 + 6 (pink) was lower for schizophrenic patients. For cards II and VIII, the number of eye fixations was inversely correlated with negative symptoms. For card II, total scanning length tended to be inversely correlated with negative symptoms, and mean eye fixation time was correlated with negative symptoms. The number of eye fixation areas was inversely correlated with positive symptoms. For card VIII, eye fixation frequency in a stimulative area tended to be correlated with positive symptoms. Scanning behaviors in schizophrenic patients are affected by characteristics of visual stimuli, and partially by clinical symptoms.
Abstract. Second harmonic electron cyclotron current drive (ECCD) has been applied in Heliotron J to stabilize magnetohydrodynamic (MHD) modes in Heliotron J. Localized EC current driven at central region modifies the rotational transform profile, , making a high magnetic shear. An energetic-ion-driven MHD mode of 80 kHz has been fully stabilized by co-ECCD, and another mode of 90 kHz has been stabilized by counter-ECCD when the EC current of a few kA is driven. Both co-and counter-ECCD is effective for the energetic-ion-driven MHD modes. An experiment of scanning the EC driven current shows that there is a threshold in magnetic shear to stabilize the energetic-ion-driven MHD mode.
Encapsulation of cytokines within protein microcrystals (polyhedra) is a promising approach for the stabilization and delivery of therapeutic proteins. Here, we investigate the influence of vascular endothelial growth factor (VEGF) microcrystals and endostatin microcrystals on angiogenesis. VEGF was successfully encapsulated into microcrystals derived from insect cypovirus with overexpression of protein disulfide bond isomerase. VEGF microcrystals were observed to increase the phosphorylation of p42/p44 MAP kinase and to stimulate the proliferation, migration, and network and tube formation of human umbilical vein endothelial cells (HUVECs). Endostatin was also successfully encapsulated into microcrystals. Endostatin microcrystals showed antiangiogenesis activities and inhibited the migration, and network and tube formation of HUVECs. Local administration of endostatin microcrystals in mice inhibited both angiogenesis and tumor growth with clear significant differences between treatment and control groups. Endostatin microcrystals only affected angiogenesis, but had no significant effect on lymphangiogenesis compared to controls. Local therapy using endostatin microcrystals offers a potential approach to achieve sustained therapeutic release of antiangiogenic molecules for cancer treatment.
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