195 research outputs found
Dating of Hydrothermal Mineralization in Active Hydrothermal Fields in the Southern Mariana Trough
The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.
Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex
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Epithelial damage and tissue ฮณฮด T cells promote a unique tumor-protective IgE response
IgE is an ancient and conserved immunoglobulin isotype with potent immunological function. Nevertheless, the regulation of IgE responses remains an enigma, and evidence of a role for IgE in host defense is limited. Here we report that topical exposure to a common environmental DNA-damaging xenobiotic initiated stress surveillance by ฮณฮดTCR+ intraepithelial lymphocytes that resulted in class switching to IgE in B cells and the accumulation of autoreactive IgE. High-throughput antibody sequencing revealed that ฮณฮด T cells shaped the IgE repertoire by supporting specific variable-diversity-joining (VDJ) rearrangements with unique characteristics of the complementarity-determining region CDRH3. This endogenous IgE response, via the IgE receptor FcฮตRI, provided protection against epithelial carcinogenesis, and expression of the gene encoding FcฮตRI in human squamous-cell carcinoma correlated with good disease prognosis. These data indicate a joint role for immunosurveillance by T cells and by B cells in epithelial tissues and suggest that IgE is part of the host defense against epithelial damage and tumor development
The Mass Distribution and Rotation Curve in the Galaxy
The mass distribution in the Galaxy is determined by dynamical and
photometric methods. Rotation curves are the major tool for determining the
dynamical mass distribution in the Milky Way and spiral galaxies. The
photometric (statistical) method utilizes luminosity profiles from optical and
infrared observations, and assumes empirical values of the mass-to-luminosity
(M/L) ratio to convert the luminosity to mass. In this chapter the dynamical
method is described in detail, and rotation curves and mass distribution in the
Milky Way and nearby spiral galaxies are presented. The dynamical method is
categorized into two methods: the decomposition method and direct method. The
former fits the rotation curve by calculated curve assuming several mass
components such as a bulge, disk and halo, and adjust the dynamical parameters
of each component. Explanations are given of the mass profiles as the de
Vaucouleurs law, exponential disk, and dark halo profiles inferred from
numerical simulations. Another method is the direct method, with which the mass
distribution can be directly calculated from the data of rotation velocities
without employing any mass models. Some results from both methods are
presented, and the Galactic structure is discussed in terms of the mass.
Rotation curves and mass distributions in external galaxies are also discussed,
and the fundamental mass structures are shown to be universal.Comment: 54 pages, 25 figures, in 'Planets, Stars and Stellar Systems',
Springer, Vol. 5, ed. G. Gilmore, Chap. 19. Note: Preprint with full figures
is available from http://www.ioa.s.u-tokyo.ac.jp/~sofue/htdocs/2013psss
Application of the bacteriophage Mu-driven system for the integration/amplification of target genes in the chromosomes of engineered Gram-negative bacteriaโmini review
The advantages of phage Mu transposition-based systems for the chromosomal editing of plasmid-less strains are reviewed. The cis and trans requirements for Mu phage-mediated transposition, which include the L/R ends of the Mu DNA, the transposition factors MuA and MuB, and the cis/trans functioning of the E element as an enhancer, are presented. Mini-Mu(LR)/(LER) units are Mu derivatives that lack most of the Mu genes but contain the L/R ends or a properly arranged E element in cis to the L/R ends. The dual-component system, which consists of an integrative plasmid with a mini-Mu and an easily eliminated helper plasmid encoding inducible transposition factors, is described in detail as a tool for the integration/amplification of recombinant DNAs. This chromosomal editing method is based on replicative transposition through the formation of a cointegrate that can be resolved in a recombination-dependent manner. (E-plus)- or (E-minus)-helpers that differ in the presence of the trans-acting E element are used to achieve the proper mini-Mu transposition intensity. The systems that have been developed for the construction of stably maintained mini-Mu multi-integrant strains of Escherichia coli and Methylophilus methylotrophus are described. A novel integration/amplification/fixation strategy is proposed for consecutive independent replicative transpositions of different mini-Mu(LER) units with โexcisableโ E elements in methylotrophic cells
Mouse Transgenesis Identifies Conserved Functional Enhancers and cis-Regulatory Motif in the Vertebrate LIM Homeobox Gene Lhx2 Locus
The vertebrate Lhx2 is a member of the LIM homeobox family of
transcription factors. It is essential for the normal development of the
forebrain, eye, olfactory system and liver as well for the differentiation of
lymphoid cells. However, despite the highly restricted spatio-temporal
expression pattern of Lhx2, nothing is known about its
transcriptional regulation. In mammals and chicken, Crb2,
Dennd1a and Lhx2 constitute a conserved
linkage block, while the intervening Dennd1a is lost in the
fugu Lhx2 locus. To identify functional enhancers of
Lhx2, we predicted conserved noncoding elements (CNEs) in
the human, mouse and fugu Crb2-Lhx2 loci and
assayed their function in transgenic mouse at E11.5. Four of the eight CNE
constructs tested functioned as tissue-specific enhancers in specific regions of
the central nervous system and the dorsal root ganglia (DRG), recapitulating
partial and overlapping expression patterns of Lhx2 and
Crb2 genes. There was considerable overlap in the
expression domains of the CNEs, which suggests that the CNEs are either
redundant enhancers or regulating different genes in the locus. Using a large
set of CNEs (810 CNEs) associated with transcription factor-encoding genes that
express predominantly in the central nervous system, we predicted four
over-represented 8-mer motifs that are likely to be associated with expression
in the central nervous system. Mutation of one of them in a CNE that drove
reporter expression in the neural tube and DRG abolished expression in both
domains indicating that this motif is essential for expression in these domains.
The failure of the four functional enhancers to recapitulate the complete
expression pattern of Lhx2 at E11.5 indicates that there must
be other Lhx2 enhancers that are either located outside the
region investigated or divergent in mammals and fishes. Other approaches such as
sequence comparison between multiple mammals are required to identify and
characterize such enhancers
Coronavirus Gene 7 Counteracts Host Defenses and Modulates Virus Virulence
Transmissible gastroenteritis virus (TGEV) genome contains three accessory genes: 3a, 3b and 7. Gene 7 is only present in members of coronavirus genus a1, and encodes a hydrophobic protein of 78 aa. To study gene 7 function, a recombinant TGEV virus lacking gene 7 was engineered (rTGEV-ฮ7). Both the mutant and the parental (rTGEV-wt) viruses showed the same growth and viral RNA accumulation kinetics in tissue cultures. Nevertheless, cells infected with rTGEV-ฮ7 virus showed an increased cytopathic effect caused by an enhanced apoptosis mediated by caspase activation. Macromolecular synthesis analysis showed that rTGEV-ฮ7 virus infection led to host translational shut-off and increased cellular RNA degradation compared with rTGEV-wt infection. An increase of eukaryotic translation initiation factor 2 (eIF2ฮฑ) phosphorylation and an enhanced nuclease, most likely RNase L, activity were observed in rTGEV-ฮ7 virus infected cells. These results suggested that the removal of gene 7 promoted an intensified dsRNA-activated host antiviral response. In protein 7 a conserved sequence motif that potentially mediates binding to protein phosphatase 1 catalytic subunit (PP1c), a key regulator of the cell antiviral defenses, was identified. We postulated that TGEV protein 7 may counteract host antiviral response by its association with PP1c. In fact, pull-down assays demonstrated the interaction between TGEV protein 7, but not a protein 7 mutant lacking PP1c binding motif, with PP1. Moreover, the interaction between protein 7 and PP1 was required, during the infection, for eIF2ฮฑ dephosphorylation and inhibition of cell RNA degradation. Inoculation of newborn piglets with rTGEV-ฮ7 and rTGEV-wt viruses showed that rTGEV-ฮ7 virus presented accelerated growth kinetics and pathology compared with the parental virus. Overall, the results indicated that gene 7 counteracted host cell defenses, and modified TGEV persistence increasing TGEV survival. Therefore, the acquisition of gene 7 by the TGEV genome most likely has provided a selective advantage to the virus
Boundedness of fractional oscillatory integral operators and their commutators on generalized Morrey spaces
A potent chemotherapeutic strategy in prostate cancer: S-(methoxytrityl)-L-cysteine, a novel Eg5 inhibitor
Docetaxel-based combination chemotherapy remains the predominant treatment for castration-resistant prostate cancer. However, taxane-related drug resistance and neurotoxicity have prompted us to develop substitute treatment strategies. Eg5 (kinesin spindle protein), which is crucial for bipolar spindle formation and duplicated chromosome separation during the early phase of mitosis, has emerged as an attractive target for cancer chemotherapy. The aim of this study was to investigate the anticancer efficacy of S-(methoxytrityl)-โ-cysteine (S(MeO)TLC), a novel Eg5 inhibitor in prostate cancer. Eg5 expression was examined in human prostate cancer cell lines and tissue microarrays were constructed from clinical specimens. Antiproliferative activity of S(MeO)TLC in prostate cancer cells was assessed by a cell viability assay. The anticancer effect and inhibitory mechanism of S(MeO)TLC in prostate cancer cells was further explored by Hoechst staining, flow cytometry and immunofluorescence. In addition, the antitumor effect of S(MeO)TLC on subcutaneous xenograft models was assessed. Eg5 expression was identified in PC3, DU145 and LNCaP cells. More than half of prostate cancer clinical specimens displayed Eg5 expression. S(MeO)TLC exhibited more powerful anticancer activity in prostate cancer cells compared with the other four Eg5 inhibitors tested. S(MeO)TLC induced cell death after arresting dividing cells at mitosis with distinct monopolar spindle formation. S(MeO)TLC exhibited its significant inhibitory activity (P<0.05) on subcutaneous xenograft models also through induction of mitotic arrest. We conclude that Eg5 is a good target for prostate cancer chemotherapy, and S(MeO)TLC is a potent promising anticancer agent in prostate cancer
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