1,029 research outputs found
2-Chloro-7-methyl-12-phenyldibenzo[b,g][1,8]naphthyridin-11(6H)-one
In the title compound, C23H15ClN2O, the fused ring system is planar: the deviation of all the non-H atoms from the plane through all four fused rings is less than 0.31 Å. The plane of the phenyl ring is inclined at 71.78 (5)° to the mean plane of the 1,8-naphthrydine ring system. The crystal structure is devoid of any classical hydrogen bonds but π–π interactions are present
Requirement of Interaction between Mast Cells and Skin Dendritic Cells to Establish Contact Hypersensitivity
The role of mast cells (MCs) in contact hypersensitivity (CHS) remains controversial. This is due in part to the use of the MC-deficient Kit W/Wv mouse model, since Kit W/Wv mice congenitally lack other types of cells as a result of a point mutation in c-kit. A recent study indicated that the intronic enhancer (IE) for Il4 gene transcription is essential for MCs but not in other cell types. The aim of this study is to re-evaluate the roles of MCs in CHS using mice in which MCs can be conditionally and specifically depleted. Transgenic Mas-TRECK mice in which MCs are depleted conditionally were newly generated using cell-type specific gene regulation by IE. Using this mouse, CHS and FITC-induced cutaneous DC migration were analyzed. Chemotaxis assay and cytoplasmic Ca2+ imaging were performed by co-culture of bone marrow-derived MCs (BMMCs) and bone marrow-derived dendritic cells (BMDCs). In Mas-TRECK mice, CHS was attenuated when MCs were depleted during the sensitization phase. In addition, both maturation and migration of skin DCs were abrogated by MC depletion. Consistently, BMMCs enhanced maturation and chemotaxis of BMDC in ICAM-1 and TNF-α dependent manners Furthermore, stimulated BMDCs increased intracellular Ca2+ of MC upon direct interaction and up-regulated membrane-bound TNF-α on BMMCs. These results suggest that MCs enhance DC functions by interacting with DCs in the skin to establish the sensitization phase of CHS
Lineage Diversion of T Cell Receptor Transgenic Thymocytes Revealed by Lineage Fate Mapping
Background: The binding of the T cell receptor (TCR) to major histocompatibility complex (MHC) molecules in the thymus determines fates of lymphocytes that subsequently home to secondary lymphoid tissue. TCR transgenic models have been used to study thymic selection and lineage commitment. Most TCR transgenic mice express the rearranged prematurely at the double negative stage and abnormal TCRαβ populations of T cells that are not easily detected in non-transgenic mice have been found in secondary lymphoid tissue of TCR transgenic mice. Methodology and Principal Findings: To determine developmental pathways of TCR-transgenic thymocytes, we used Cre-LoxP-mediated fate mapping and show here that premature expression of a transgenic diverts some developing thymocytes to a developmental pathway which resembles that of gamma delta cells. We found that most peripheral T cells with the HY-TCR in male mice have bypassed the RORγt-positive (double positive, DP) stage to accumulate either as (double negative, DN) or as T cells in lymph nodes or gut epithelium. Likewise, DN cells in lymphoid tissue of female mice were not derived from DP thymocytes. Conclusion: The results further support the hypothesis that the premature expression of the can divert DN thymocytes into gamma delta lineage cells
Oropouche orthobunyavirus infection is mediated by the cellular host factor Lrp1
Oropouche orthobunyavirus (OROV
Heme-Mediated SPI-C Induction Promotes Monocyte Differentiation into Iron-Recycling Macrophages
Splenic red pulp macrophages (RPM) degrade senescent erythrocytes and recycle heme-associated iron. The transcription factor SPI-C is selectively expressed by RPM and is required for their development, but the physiologic stimulus inducing Spic is unknown. Here, we report that Spic also regulated the development of F4/80^+VCAM1^+ bone marrow macrophages (BMM) and that Spic expression in BMM and RPM development was induced by heme, a metabolite of erythrocyte degradation. Pathologic hemolysis induced loss of RPM and BMM due to excess heme but induced Spic in monocytes to generate new RPM and BMM. Spic expression in monocytes was constitutively inhibited by the transcriptional repressor BACH1. Heme induced proteasome-dependent BACH1 degradation and rapid Spic derepression. Furthermore, cysteine-proline dipeptide motifs in BACH1 that mediate heme-dependent degradation were necessary for Spic induction by heme. These findings are the first example of metabolite-driven differentiation of a tissue-resident macrophage subset and provide new insights into iron homeostasis
Discrete approaches to quantum gravity in four dimensions
The construction of a consistent theory of quantum gravity is a problem in
theoretical physics that has so far defied all attempts at resolution. One
ansatz to try to obtain a non-trivial quantum theory proceeds via a
discretization of space-time and the Einstein action. I review here three major
areas of research: gauge-theoretic approaches, both in a path-integral and a
Hamiltonian formulation, quantum Regge calculus, and the method of dynamical
triangulations, confining attention to work that is strictly four-dimensional,
strictly discrete, and strictly quantum in nature.Comment: 33 pages, invited contribution to Living Reviews in Relativity; the
author welcomes any comments and suggestion
Pion photoproduction on the nucleon in the quark model
We present a detailed quark-model study of pion photoproduction within the
effective Lagrangian approach. Cross sections and single-polarization
observables are investigated for the four charge channels, , , , and .
Leaving the coupling strength to be a free parameter, we obtain a
reasonably consistent description of these four channels from threshold to the
first resonance region. Within this effective Lagrangian approach, strongly
constrainted by the quark model, we consider the issue of double-counting which
may occur if additional {\it t}-channel contributions are included.Comment: Revtex, 35 pages, 16 eps figures; version to appear on PR
Lrp1 is essential for lethal Rift Valley fever hepatic disease in mice
Rift Valley fever virus (RVFV) is an emerging arbovirus found in Africa. While RVFV is pantropic and infects many cells and tissues, viral replication and necrosis within the liver play a critical role in mediating severe disease. The low-density lipoprotein receptor-related protein 1 (Lrp1) is a recently identified host factor for cellular entry and infection by RVFV. The biological significance of Lrp1, including its role in hepatic disease in vivo, however, remains to be determined. Because Lrp1 has a high expression level in hepatocytes, we developed a mouse model in which Lrp1 is specifically deleted in hepatocytes to test how the absence of liver Lrp1 expression affects RVF pathogenesis. Mice lacking Lrp1 expression in hepatocytes showed minimal RVFV replication in the liver, longer time to death, and altered clinical signs toward neurological disease. In contrast, RVFV infection levels in other tissues showed no difference between the two genotypes. Therefore, Lrp1 is essential for RVF hepatic disease in mice
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