Intronic elements in the Na+/I- symporter gene (NIS) interact with retinoic acid receptors and mediate initiation of transcription

Activity of the sodium/iodide symporter (NIS) in lactating breast is essential for iodide (I–) accumulation in milk. Significant NIS upregulation was also reported in breast cancer, indicating a potential use of radioiodide treatment. All-trans-retinoic acid (tRA) is a potent ligand that enhances NIS expression in a subset of breast cancer cell lines and in experimental breast cancer models. Indirect tRA stimulation of NIS in breast cancer cells is very well documented; however, direct upregulation by tRA-activated nuclear receptors has not been identified yet. Aiming to uncover cis-acting elements directly regulating NIS expression, we screened evolutionary-conserved non-coding genomic sequences for responsiveness to tRA in MCF-7. Here, we report that a potent enhancer in the first intron of NIS mediates direct regulation by tRA-stimulated nuclear receptors. In vitro as well as in vivo DNA–protein interaction assays revealed direct association between retinoic acid receptor-α (RARα) and retinoid-X-receptor (RXR) with this enhancer. Moreover, using chromatin immunoprecipitation (ChIP) we uncovered early events of NIS transcription in response to tRA, which require the interaction of several novel intronic tRA responsive elements. These findings indicate a complex interplay between nuclear receptors, RNA Pol-II and multiple intronic RAREs in NIS gene, and they establish a novel mechanistic model for tRA-induced gene transcription

Raman spectroscopic studies on the ferroelectric soft mode in SnxSr1-xTiO3

The Raman spectra of novel ferroelectric ceramics SnxSr1-xTiO3 (x = 0.1, 0.05 and 0.02) were obtained to clarify the mechanism of their ferroelectric phase transitions. Two transverse-optic modes in the ferroelectric phase showed softening toward the ferroelectric transition temperature. A comparison of the spectra obtained for SnxSr1-xTiO3 with the spectrum of PbxSr1-xTiO3 facilitated the assignment of the observed modes under the assumption of the ferroelectric phase in C4v1 symmetry. However, several peaks violating the Raman selection rules were observed, suggesting the emergence and growth of polar regions even in the paraelectric phase

Study of the cement systems reactivity modified with mineral additives

The influence of mineral fillers on the hydration of cement systems and the curing of concrete during their partial replacement of cement has been studied. A comprehensive approach based on a combination of isothermal calorimetry method and compressive strength tests was used in this work. The results obtained allowed to draw conclusions about the reactive pozzolanic activity of silica fume and metakaolin, the microreinforcing function of wollastonite, and the effect of the zeolite filler

A Novel Role for Niemann-Pick Disease Type 2C Protein in Papillae Formation

BACKGROUND: Despite the presence of papillary structures and papillary tumors in humans, the mechanism of papillae formation is unknown. We describe herein a novel role for Niemann-Pick disease type 2C (NPC2) protein, a cholesterol binding protein in the lysosome, in papillae formation. METHODOLOGY/PRINCIPAL FINDING: We examined NPC2 protein expression in surgical samples of papillary tissues by immunohistochemical stain, and all papillary tissues expressed NPC2 protein in the epithelium. To examine our hypothesis of NPC2 protein-mediated papillae formation, we carried out xenograft experiments using wild H460 cells (large cell lung carcinoma cell line) that constitutively expressed abundant NPC2 protein and NPC2 protein-depleted H460 cells by NPC2 shRNA. The xenografts of wild H460 cells and empty shRNA vector cells showed distinct papillae formation, whereas NPC2 protein-depleted H460 cells displayed markedly reduced or no papillae. Since all papillary tissues have open spaces we examined whether NPC2 protein might also contribute to the creation of open spaces. The TUNEL assay in the xenografts of wild and empty shRNA vector H460 cells showed massive cell death, and NPC2 protein-depleted cells displayed minimal cell death. Measurement of caspase 3/7 activities in cultured H460 cells supported NPC2 protein-mediated apoptotic cell death. The presence of excess NPC2 protein, however, did not always produce papillae as seen in the xenografts of CHO cells that were stably transfected with NPC2. CONCLUSIONS/SIGNIFICANCE: The NPC2 protein of certain cells forms papillae coupled with apoptosis that creates open space. This protein may have future applications to modulate papillae formation and papillary growth in tumor tissues

細胞接着分子CADM1の新規Dependence Receptorとしての機能の解析

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 村上 善則, 東京大学教授 渡辺 俊樹, 東京大学教授 井上 純一郎, 東京大学教授 山梨 裕司, 東京大学准教授 池上 恒雄University of Tokyo(東京大学

Novel nano-hydroxyapatite coating of additively manufactured three-dimensional porous implants improves bone ingrowth and initial fixation

Electron beam melting (EBM) has been used to fabricate three-dimensional (3D) porous Ti-6Al-4V surfaces for acetabular cups in total hip arthroplasty. However, there are radiographic concerns regarding poor implant fixation and bone ingrowth around electron beam melted (EBMed) 3D porous cups. We hypothesize that nano-hydroxyapatite (nHA) coating can promote bone ingrowth and thus decrease the occurrence of radiolucent lines around EBMed 3D porous cups. This study aimed to investigate the effect of a novel nHA coating on the biological performance of EBMed 3D porous implants in a beagle transcortical model. Low-porosity (control) and high-porosity 3D porous Ti-6Al-4V implants were manufactured using EBM. Half of the high-porosity implants were coated with nHA without clogging the 3D pores. Implants were inserted into the femoral diaphysis of the beagles. The beagles were euthanized at 4, 8, and 12 weeks postoperatively, and push-out testing was performed. Bone ingrowth was evaluated by histological analysis. Although the increase in porosity alone had no effect on biological behavior, the addition of nHA to high-porosity 3D implants significantly improved early bone fixation and bone ingrowth into the deep region of porous structures compared to low-porosity implants. This is the first report of a novel nHA coating that improved bone ingrowth into the deeper regions of 3D porous implants, which can prevent the occurrence of radiolucent lines around EBMed 3D porous cups.Watanabe R., Takahashi H., Matsugaki A., et al. Novel nano-hydroxyapatite coating of additively manufactured three-dimensional porous implants improves bone ingrowth and initial fixation. Journal of Biomedical Materials Research - Part B Applied Biomaterials. https://doi.org/10.1002/jbm.b.35165

Is there Initial Upper Palaeolithic in Western Tian Shan? Example of an open-air site Katta Sai 2 (Uzbekistan)

The paper presents the results of multidisciplinary studies on the open-air loess site Katta Sai 2 located in thewestern piedmonts of Tian Shan in Uzbekistan. Two archaeological horizons contain features associated with theInitial Upper Palaeolithic (IUP) - both Levallois and blade/bladelet volumetric technology, together with anUpper Palaeolithic toolkit. The cultural traits observed in Katta Sai 2 might have local roots dating back to MIS 5aand can be found in so-called Obirakhmatian technocomplex determined in several archaeological sites in theregion. Thus, the obtained results question the hypothesis of non-local origins of IUP complexes associated withthe early modern human migration from the Near East to Mongolia along the piedmonts of Pamir and Tian Shan.Until reliable anthropological and genetic data are obtained, it seems to be too early to conclude about therelationship between modern human migration and the appearance of IUP assemblages, at least across thewestern parts of Central Asia