Histological evaluation of nonsurgical periodontal treatment with and without the use of sodium hypochlorite / amino acids and cross-linked hyaluronic acid gels in dogs.

OBJECTIVES To evaluate periodontal wound healing following scaling and root planing (SRP) in conjunction with the application of sodium hypochlorite/amino acids and cross-linked hyaluronic acid (xHyA) gels in dogs. MATERIALS AND METHODS In four beagle dogs, 2-wall intrabony defects were created and metal strips were placed around the teeth. Clinical parameters were measured 4 weeks after plaque accumulation. The experimental root surfaces were subjected to SRP with either the subgingival application of a sodium hypochlorite/amino acid gel and a xHyA gel (test group) or SRP alone (control group) using a split-mouth design. Clinical parameters were re-evaluated at 6 weeks. The animals were sacrificed at 8 weeks for histological analysis. RESULTS The test group showed significant improvements in all clinical parameters compared to the control group. Histologically, the test group exhibited statistically significantly greater new bone formation [i.e., length of newly formed bone, new bone area] compared with the control group (p < 0.05). Furthermore, statistically significantly greater formation of new attachment [i.e., linear length of new cementum adjacently to newly formed bone with inserting collagen fibers] and new cementum was detected in the test group compared with the control group at 8 weeks (p < 0.05 and p < 0.01, respectively). CONCLUSION The adjunctive subgingival application of sodium hypochlorite/amino acid and xHyA gels to SRP offers an innovative novel approach to enhance periodontal wound healing/regeneration. CLINICAL RELEVANCE The present findings have for the first-time shown histologic evidence for periodontal regeneration in support of this novel treatment modality

Subaru Deep Survey V. A Census of Lyman Break Galaxies at z=4 and 5 in the Subaru Deep Fields: Photometric Properties

(abridged) We investigate photometric properties of Lyman Break Galaxies (LBGs) at z=3.5-5.2 based on large samples of 2,600 LBGs detected in deep (i'~27) and wide-field (1,200 arcmin^2) images taken in the Subaru Deep Field (SDF) and the Subaru/XMM Deep Field (SXDF). The selection criteria for the LBG samples are examined with 85 spectroscopically identified objects and by Monte Carlo simulations. We find in the luminosity functions of LBGs (i) that the number density of bright galaxies (M_{1700}<-22; corresponding to SFR_{corr}>100 Msolar yr^{-1}) decreases significantly from z=4 to 5 and (ii) that the faint-end slope of the luminosity function may become steeper towards higher redshifts. We estimate dust extinction of z=4 LBGs with M<M^* from UV slopes, and obtain E(B-V)=0.15+/-0.03 as the mean value. The dust extinction remains constant with apparent luminosity, but increases with intrinsic luminosity. We find no evolution in dust extinction between LBGs at z=3 and 4. We investigate the evolution of UV-luminosity density at 1700A, rho, and find that rho does not significantly change from z=3 to z=5, i.e., rho(z=4)/rho(z=3)=1.0+/-0.2 and rho(z=5)/rho(z=3)=0.8+/-0.4, thus the cosmic star-formation rate (SFR) density remains constant. We find that the stellar mass density estimated from the cosmic SFR is consistent with those derived directly from the stellar mass function at z=0-1, but exceeds those at z~3 by a factor of 3. We find that the ratio of the UV-luminosity density of Ly-a emitters (LAEs) to that of LBGs is ~60% at z=5, and thus about a half of the star formation at z=5 probably occurs in LAEs. We obtain a constraint on the escape fraction of UV-ionizing photons produced by LBGs, f_{esc}>~0.13.Comment: 41 pages, 22 figures, ApJ in press. Paper with high resolution figures is available at http://hikari.astron.s.u-tokyo.ac.jp/~ouchi/work/astroph/SDS_V_VI/SDS_V.pdf (PDF

PAI-1 mediates acquired resistance to MET-targeted therapy in non-small cell lung cancer

Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we investigated the possible mechanisms acquired for crizotinib in MET-amplified lung carcinoma cell lines. Two MET-amplified lung cancer cell lines, EBC-1 and H1993, were established for acquired resistance to MET-TKI crizotinib and were functionally elucidated. Genomic and transcriptomic data were used to assess the factors contributing to the resistance mechanism, and the alterations hypothesized to confer resistance were validated. Multiple mechanisms underlie acquired resistance to crizotinib in MET-amplified lung cancer cell lines. In EBC-1-derived resistant cells, the overexpression of SERPINE1, the gene encoding plasminogen activator inhibitor-1 (PAI-1), mediated the drug resistance mechanism. Crizotinib resistance was addressed by combination therapy with a PAI-1 inhibitor and PAI-1 knockdown. Another mechanism of resistance in different subline cells of EBC-1 was evaluated as epithelial-to-mesenchymal transition with the upregulation of antiapoptotic proteins. In H1993-derived resistant cells, MEK inhibitors could be a potential therapeutic strategy for overcoming resistance with downstream mitogen-activated protein kinase pathway activation. In this study, we revealed the different mechanisms of acquired resistance to the MET inhibitor crizotinib with potential therapeutic application in patients with MET-amplified lung carcinoma

Comparing serial X-ray crystallography and microcrystal electron diffraction (MicroED) as methods for routine structure determination from small macromolecular crystals.

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometre to micrometre scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges that are not encountered in traditional macromolecular crystallography experiments. Here, XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A are described. The results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample-preparation and delivery methods required for each type of experiment affect the crystal structure of the enzyme

Mapping protein dynamics at high spatial resolution with temperature-jump X-ray crystallography

温度による酵素の構造変化を分子動画撮影 様々な生体高分子のダイナミクスを決定する新たな方法論. 京都大学プレスリリース. 2023-09-19.Understanding and controlling protein motion at atomic resolution is a hallmark challenge for structural biologists and protein engineers because conformational dynamics are essential for complex functions such as enzyme catalysis and allosteric regulation. Time-resolved crystallography offers a window into protein motions, yet without a universal perturbation to initiate conformational changes the method has been limited in scope. Here we couple a solvent-based temperature jump with time-resolved crystallography to visualize structural motions in lysozyme, a dynamic enzyme. We observed widespread atomic vibrations on the nanosecond timescale, which evolve on the submillisecond timescale into localized structural fluctuations that are coupled to the active site. An orthogonal perturbation to the enzyme, inhibitor binding, altered these dynamics by blocking key motions that allow energy to dissipate from vibrations into functional movements linked to the catalytic cycle. Because temperature jump is a universal method for perturbing molecular motion, the method demonstrated here is broadly applicable for studying protein dynamics

First Data Release of the Hyper Suprime-Cam Subaru Strategic Program

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered imaging survey aimed at addressing some of the most outstanding questions in astronomy today, including the nature of dark matter and dark energy. The survey has been awarded 300 nights of observing time at the Subaru Telescope and it started in March 2014. This paper presents the first public data release of HSC-SSP. This release includes data taken in the first 1.7 years of observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and ~27.0 mag, respectively (5sigma for point sources). All the layers are observed in five broad bands (grizy), and the Deep and UltraDeep layers are observed in narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF photometry (rms) both internally and externally (against Pan-STARRS1), and ~10 mas and 40 mas internal and external astrometric accuracy, respectively. Both the calibrated images and catalogs are made available to the community through dedicated user interfaces and database servers. In addition to the pipeline products, we also provide value-added products such as photometric redshifts and a collection of public spectroscopic redshifts. Detailed descriptions of all the data can be found online. The data release website is https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for publication in PAS