The r-process in supernova explosions from the collapse of O-Ne-Mg cores

We examine r-process nucleosynthesis in a "prompt supernova explosion" from an 8-10 Msun progenitor star, as an alternative scenario to the "neutrino wind" mechanism. In the present model, the progenitor star has formed an oxygen-neon-magnesium core at its center. The core-collapse simulations are performed with a one-dimension, Newtonian hydrodynamic code. We obtain a very weak prompt explosion, in which no r-processing occurs. We further simulate energetic prompt explosions by enhancement of the shock-heating energy, in order to investigate conditions necessary for the production of r-process nuclei in such events. The highly neutronized ejecta (Ye = 0.14-0.20) leads to robust production of r-process nuclei; their relative abundances are in excellent agreement with the solar r-process pattern. Our results suggest that prompt explosions of 8-10 Msun stars with oxygen-neon-magnesium cores can be a promising site of r-process nuclei.Comment: 32 pages, 9 figures, accepted for publication in Ap

Potential for Tumorigenesis and Repair of Osteochondral Defects by iPS Cell Transplantation in Rat

Abstract Articular cartilage repair remains a challenge in the field of orthopedic medicine. Cell-based therapy for cartilage repair, such as autologous chondrocyte implantation, was established in the 1990s. However, the issue of the source from which the lesion-targeting cells are harvested remains a limitation of this approach as larger lesions require more cells for repair, and thus, more healthy tissue must be damaged to harvest the needed cells. Reprogramming of induced pluripotent stem (iPS) cells is a promising tool for cell-based regenerative therapy because of their proliferative capacity and pluripotency; however, these characteristics also create a risk of tumorigenesis. This study aimed to determine the probability of iPS cell-derived tumor occurrence as a function of injection or transplantation site, and to assess whether transplanted iPS cells can promote cartilage defect repair. Pluripotent mouse iPS cells (5x10 6 cells/ml) were subcutaneously injected or transplanted into experimentally induced lesions in the knee cartilage of immunodeficient rats. Subcutaneous teratoma formation was observed in 30% of animals (3 of 10) at 4weeks, and 41% of animals (7 of 17) at 12 weeks after iPS cell injection. Cartilage repair as indicated by modified Wakitani's score was similar in the cell-free group and in the iPS cell implantation group at 4 weeks [11.8 ± 1.8 (n = 8) vs. 10.3 ± 2.8 (n = 18)]. iPS cell implantation yielded a score of 7.8 ± 2.0 (n = 10) at 12 weeks, significantly better than the cell-free group [10.5 ± 0.6 (n = 4)]. There was no macro-or microscopic evidence of tumor formation at the cartilage repair site after iPS cell implantation. Although we could not use the iPS cells directly for cartilage repair, the results of our study indicate the potential for a new therapy for cartilage repair by developing iPS reprogramming technology

Localization of oxytalan fiber, type III collagen and BMP family in conventional and desmoplastic ameloblastoma

The histologic hallmark distinguishing desmoplastic ameloblastoma (DA) from conventional ameloblastoma (CA) is its pronounced stromal desmoplasia, and this formed the basis of this investigation. To elucidate the stromal characteristics, localization patterns of oxytalan fibers, type III collagen and BMP family in DA (n=8) was compared with CA (n=24), and periodontal ligament (PL) (n=8). Oxytalan fibers formed apico-occlusal bundles in PL, thick radial bundles around tumor nests in DA, and as scanty fibers in CA. Type III collagen was identified in PL, strongly expressed in DA stroma, but weakly in CA. BMP-2, -3, -4 and -7 expression patterns in tumor epithelium and stroma were more pronounced in DA (including sites of bone formation), than CA. No immunoreactivity for BMP-5 and -6 were detected. Current findings suggest that the stroma in DA is neoplastic and derived from odontogenic ectomesenchyme, and recommends its reclassification as an odontogenic epithelial-ectomesenchymal neoplasm

Influence of palaeoweathering on trace metal concentrations and environmental proxies in black shales

The mineralogical and chemical compositions of Lower Carboniferous (Tournaisian) marine black shale from the Kowala quarry, the Holy Cross Mountains, Poland, were investigated. This study focuses on disturbances in palaeoenvironmental proxies caused by palaeoweathering, which progressively changed the major and trace element abundances. Palaeomagnetic investigations reveal that the Devonian – Carboniferous succession was weathered during the Permian-Triassic by the infiltration of oxidizing fluids related to karstification following post-Variscan exhumation. The weathering process led to vermiculitization of chlorite, partial dissolution of calcite and replacement of pyrite by hematite and goethite. Moreover, the concentrations of some trace metals, including Co, Cu, Pb, Mo, Ni, As and U, significantly decreased. Consequently, some elemental abundance ratios that are used as environmental proxies, including U/Th, Ni/Co and V/Cr, were altered. Elements that are bound to iron sulphides (e.g., Mo) appear to be especially prone to mobilization by even a lightly weathered black shale. The documented weathering, including changes in elemental concentrations, can potentially create misinterpretations of the original palaeoenvironmental conditions. In addition, the palaeoweathering of the studied samples appears to have substantially changed the carbon, oxygen, nitrogen and molybdenum stable isotope values. The nitrogen and molybdenum stable isotope ratios, in particular, appear to be most sensitive to the effects of weathering and therefore are good indicators of (palaeo)weathering processes. The major cause of these changes is the decay of organic matter and pyrite. For the organic carbon stable isotopes ratios, the main factor that controlls this process appears to be the preferential degradation of labile organic matter. A combination of the total organic carbon (TOC), total sulphur (TS) content, Mo concentration and stable isotope compositions seems to be the most useful for identify (palaeo)weathering. Our results suggest that reductions in TS and Mo in tandem with diminished Mo stable isotope values in the absence of obvious changes to the TOC content provide the most compelling evidence of (palaeo)weathering

Crosstalk between Chemokine Receptor CXCR4 and Cannabinoid Receptor CB2 in Modulating Breast Cancer Growth and Invasion

Cannabinoids bind to cannabinoid receptors CB(1) and CB(2) and have been reported to possess anti-tumorigenic activity in various cancers. However, the mechanisms through which cannabinoids modulate tumor growth are not well known. In this study, we report that a synthetic non-psychoactive cannabinoid that specifically binds to cannabinoid receptor CB(2) may modulate breast tumor growth and metastasis by inhibiting signaling of the chemokine receptor CXCR4 and its ligand CXCL12. This signaling pathway has been shown to play an important role in regulating breast cancer progression and metastasis.We observed high expression of both CB(2) and CXCR4 receptors in breast cancer patient tissues by immunohistochemical analysis. We further found that CB(2)-specific agonist JWH-015 inhibits the CXCL12-induced chemotaxis and wound healing of MCF7 overexpressing CXCR4 (MCF7/CXCR4), highly metastatic clone of MDA-MB-231 (SCP2) and NT 2.5 cells (derived from MMTV-neu) by using chemotactic and wound healing assays. Elucidation of the molecular mechanisms using various biochemical techniques and confocal microscopy revealed that JWH-015 treatment inhibited CXCL12-induced P44/P42 ERK activation, cytoskeletal focal adhesion and stress fiber formation, which play a critical role in breast cancer invasion and metastasis. In addition, we have shown that JWH-015 significantly inhibits orthotopic tumor growth in syngenic mice in vivo using NT 2.5 cells. Furthermore, our studies have revealed that JWH-015 significantly inhibits phosphorylation of CXCR4 and its downstream signaling in vivo in orthotopic and spontaneous breast cancer MMTV-PyMT mouse model systems.This study provides novel insights into the crosstalk between CB(2) and CXCR4/CXCL12-signaling pathways in the modulation of breast tumor growth and metastasis. Furthermore, these studies indicate that CB(2) receptors could be used for developing innovative therapeutic strategies against breast cancer

A pigmented calcifying cystic odontogenic tumor associated with compound odontoma: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Pigmented intraosseous odontogenic lesions are rare with only 47 reported cases in the English literature. Among them, pigmented calcifying cystic odontogenic tumor, formerly known as calcifying odontogenic cyst, is the most common lesion with 20 reported cases.</p> <p>Methods</p> <p>A case of pigmented calcifying cystic odontogenic tumor associated with odontoma occurring at the mandibular canine-premolar region of a young Japanese boy is presented with radiographic, and histological findings. Special staining, electron microscopic study and immunohistochemical staining were also done to characterize the pigmentation.</p> <p>Results</p> <p>The pigments in the lesion were confirmed to be melanin by Masson-Fontana staining and by transmission electron microscopy. The presence of dendritic melanocytes within the lesion was also demonstrated by S-100 immunostaining.</p> <p>Conclusion</p> <p>The present case report of pigmented calcifying cystic odontogenic tumor associated with odontoma features a comprehensive study on melanin and melanocytes, including histochemical, immunohistochemical and transmission electron microscopic findings.</p

Effect of the chemokine receptor CXCR7 on proliferation of carcinoma cells in vitro and in vivo

The chemokine CXCL12/SDF-1 and its receptor CXCR4 have been implicated in invasion, survival and proliferation of carcinoma cells. Recently, CXCR7 was identified as a second receptor for CXCL12. We observed that CXCL12 promoted proliferation of CT26 colon and KEP1 mammary carcinoma cells, and this was blocked when CXCR7 was downregulated by ‘intrakines' or RNAi, but not by CXCR4 inhibitors. The K1R mutant of CXCL12, which acts as a CXCR4 antagonist, also promoted proliferation through CXCR7 and is therefore a selective CXCR7 agonist. The effect of CXCR7 was not due to reduced apoptosis, and CXCR7 mediated chemotaxis of the carcinoma cells towards CXCL12. These results differ from those in a previous report on other carcinoma cells. We conclude that CXCL12 can be a potent growth factor for carcinoma cells by acting on CXCR7. Nevertheless, we observed no effect of complete and stable CXCR7 suppression on the growth of s.c. tumours or lung metastases of KEP1 and CT26 cells. A CXCR7 inhibitor has been reported to reduce growth of other tumours. Our results indicate that this inhibitor may not be applicable to therapy of all carcinomas

A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

CCN3 and bone marrow cells

CCN3 expression was observed in a broad variety of tissues from the early stage of development. However, a kind of loss of function in mice (CCN3 del VWC domain -/-) demonstrated mild abnormality, which indicates that CCN3 may not be critical for the normal embryogenesis as a single gene. The importance of CCN3 in bone marrow environment becomes to be recognized by the studies of hematopoietic stem cells and Chronic Myeloid Leukemia cells. CCN3 expression in bone marrow has been denied by several investigations, but we found CCN3 positive stromal and hematopoietic cells at bone extremities with a new antibody although they are a very few populations. We investigated the expression pattern of CCN3 in the cultured bone marrow derived mesenchymal stem cells and found its preference for osteogenic differentiation. From the analyses of in vitro experiment using an osteogenic mesenchymal stem cell line, Kusa-A1, we found that CCN3 downregulates osteogenesis by two different pathways; suppression of BMP and stimulation of Notch. Secreted CCN3 from Kusa cells inhibited the differentiation of osteoblasts in separate culture, which indicates the paracrine manner of CCN3 activity. CCN3 may also affect the extracellular environment of the niche for hematopoietic stem cells