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

Stochastic synchronization in globally coupled phase oscillators

Cooperative effects of periodic force and noise in globally Cooperative effects of periodic force and noise in globally coupled systems are studied using a nonlinear diffusion equation for the number density. The amplitude of the order parameter oscillation is enhanced in an intermediate range of noise strength for a globally coupled bistable system, and the order parameter oscillation is entrained to the external periodic force in an intermediate range of noise strength. These enhancement phenomena of the response of the order parameter in the deterministic equations are interpreted as stochastic resonance and stochastic synchronization in globally coupled systems.Comment: 5 figure

Structure of the dopamine D2 receptor in complex with the antipsychotic drug spiperone

統合失調症に関わるドパミン受容体の構造解明 --副作用を抑えた薬の迅速な探索・設計が可能に--. 京都大学プレスリリース. 2020-12-24.In addition to the serotonin 5-HT2A receptor (5-HT2AR), the dopamine D2 receptor (D2R) is a key therapeutic target of antipsychotics for the treatment of schizophrenia. The inactive state structures of D2R have been described in complex with the inverse agonists risperidone (D2Rris) and haloperidol (D2Rhal). Here we describe the structure of human D2R in complex with spiperone (D2Rspi). In D2Rspi, the conformation of the extracellular loop (ECL) 2, which composes the ligand-binding pocket, was substantially different from those in D2Rris and D2Rhal, demonstrating that ECL2 in D2R is highly dynamic. Moreover, D2Rspi exhibited an extended binding pocket to accommodate spiperone’s phenyl ring, which probably contributes to the selectivity of spiperone to D2R and 5-HT2AR. Together with D2Rris and D2Rhal, the structural information of D2Rspi should be of value for designing novel antipsychotics with improved safety and efficacy

Electrical conductivity of V₂O₅-SnO-TeO₂ glasses

Electrical conductivity of glasses in the system V₂O₅-SnO-TeO₂ prepared by press quenching is measured and the mechanism of conduction related to glass composition is discussed. The glass forming region was found in the composition range (in mol%): 0 to 70 V₂O₅, 0 to 30 SnO and 30 to 100 TeO₂. Dc conductivities ranged from 2.1 * 10⁻⁵ to 5.4- 10⁻⁴ S/cm at 473 K for V₂O₅ concentrations of 20 to 60 mol%. The glass 20V₂O₅ * 20SnO * 60TeO₂ was more conductive (σ = 2.6 * 10⁻⁴ S/cm at 473 K) than the glasses V₂O₅ * 20SnO * (80 - X)TeO₂ with X=30 and 40 mol% (σ = -1.0 to 1.4 * 10⁻⁴ S/cm at 473 K). The electric conduction was attributed to adiabatic small-polaron hopping for V₂O₅ ≥ 50 mol% and non-adiabatic small-polaron hopping for V₂O₅ ≤ 50 mol%. The SnO content is contributed to increase basicity and decrease activation energy. The polaron bandwidth / ranged from 0.02 to 0.07 eV depending on the V-V ion spacing. The estimated carrier mobilities were remarkably small: 1.3 * 10⁻⁶ to 4.5 * 10⁻⁵ cm²/(Vs) at 473 K. This small mobility confirmed the small-polaron hopping conduction mechanism. The carrier density was evaluated to be 2.1 * 10¹⁹ to 2.1 * 10²¹/cm³ for V₂O₅ concentrations of 20 to 60mol%

A new histological evaluation method to detect residual ophthalmic viscosurgical devices for cataract surgery

Purpose: To establish a new evaluation method to quantify residual ophthalmic viscosurgical device (OVD) volume and corneal endothelium adhesion properties for phacoemulsification surgery. Methods: We compared the performance of four OVDs (Viscoat®, Healon5®, Healon® and DisCoVisc®) using porcine eyes. First, OVDs were mixed with fluorescent-conjugated dextrans to render them visible under the microscope. A corneal side port was opened, followed by a continuous curvilinear capsulorhexis, and a corneal tunnel incision was made. OVDs were injected, then the lens was removed using one-handed phacoemulsification. After this procedure, the anterior segment of the eye was isolated via an equatorial incision and the tissue was immediately frozen in shimmering liquid nitrogen. Sagittal slices (20 μm) were cut with a Cryostat from limbus to limbus. Every tenth slide was imaged using a fluorescent microscope with a CCD camera. We evaluated the percentage of the corneal endothelium covered by each OVD as the OVD adhesion to corneal endothelium ratio (OAE ratio) and the volume of residual OVD in the anterior chamber. Results: Viscoat® showed significantly higher endothelium coverage compared with both Healon® and DisCoVisc®. A statistically larger volume of Healon5® remained in the anterior chamber compared with Healon® and DisCoVisc®. Conclusion: The new evaluation methods used here provide precise quantitative analysis of OAE ratio and residual OVD volume. These results show that Viscoat® and Healon5® have a high potential for coating the corneal endothelium during phacoemulsification and aspiration surgery

沿岸域生態系評価における非線形波動の流体力学的考察

研究期間:平成10-11年度 ; 研究種目:基盤研究B2 ; 課題番号: 10450385原著には既発表論文の別刷を含む

Expression of WISP-1 (ccn4), WISP-2 (ccn5) and WISP-3 (ccn6) in Rheumatoid Arthritic Synovium Evaluated by DNA Microarrays

Abstract : Rheumatoid disease (RA) is one of the complex diseases that showed multiple progression stages. At first inflammatory response is occurred by self antibodies, and then the proliferation of synoviocytes is abnormally promoted. These synoviocytes invade into articular structures and finally articular cartilage is destroyed. In order to analyze growth-promoting factors in synovial cells from articular tissues of RA, we performed DNA microarray analysis and compared the expression patterns of their mRNA to that of synoviocytes from osteoarthritis (OA). The results showed that the expression of many genes was up-regulated in RA synoviocytes comparing with OA synoviocytes. Among these genes, RT-PCR analysis revealed that Wnt-1-induced secreted protein 2 (WISP-2, CCN5) and protein 3 (WISP-3, CCN6) which are belong to the novel gene family, CCN, were highly up-regulated in RA synoviocytes. In addition, one truncated isoform of WISP-3 which may be related to the ongoing of some type of RA, was detected in RA synoviocytes. Furthermore, immunohistochemical analysis showed that the products of both CCN genes were highly distributed in active synoviocytes of articular tissues of RA. These results indicate that both CCN genes and their products play some roles in the progression of RA

Inter-grader reliability (A-D) and a Brand-Altman plot (E-H) of the area measurements from OCTA and immunolabeling.

<p>(A and E) CNV lesion by OCTA. (B and F) dark halo comprising CNV lesion by OCTA. (C and G) CD31+ CNV lesion by immunolabeling. (D and H) PDGFRβ+ pericyte-like scaffold by immunolabeling. The <i>r</i>²value was 0.97 (A: CNV lesion by OCTA), 0.94 (B: dark halo comprising CNV lesion by OCTA), 0.95 (C: CD31+ CNV lesion by immunolabeling) and 0.98 (D: PDGFRβ+ pericyte-like scaffold by immunolabeling). A Bland-Altman plot showed agreement between the measurements of the two graders (E-H). No particular trend was found in this plot suggesting that there was no systematic bias.</p

Alternative method for laser-induced CNV irradiation.

<p>(A) Near-infrared reflectance (NIR) image obtained immediately after laser photocoagulation of one spot. (B) Enface OCTA image at 5 days post-laser photocoagulation (area measuring 900×900 μm). (A) and (B) are the same eye. (C) NIR image obtained immediately after laser photocoagulation of three spots. (D) Enface OCTA image at 5 days post-laser photocoagulation (area measuring 900×900 μm). (C) and (D) are the same eye. Note that in the three-spot laser photocoagulation irradiation, the spots overlapped each other to create a larger disruption of the choroid/Bruch’s membrane/RPE complex, resulting in a larger CNV lesion that is easier to observe and evaluate in detail by enface OCTA (D) than one-spot laser photocoagulation.</p