NCR+ ILC3 maintain larger STAT4 reservoir via T-BET to regulate type 1 features upon IL-23 stimulation in mice

Innate lymphoid cells (ILCs) producing IL-22 and/or IL-17, designated as ILC3, comprise a heterogeneous subset of cells involved in regulation of gut barrier homeostasis and inflammation. Exogenous environmental cues in conjunction with regulated expression of endogenous factors are key determinants of plasticity of ILC3 towards the type 1 fate. Herein, by using mouse models and transcriptomic approaches, we defined at the molecular level, initial events driving ILC3 expressing natural cytotoxicity receptors (NCR+ ILC3) to acquire type 1 features. We observed that NCR+ ILC3 exhibited high basal expression of the signal-dependent transcription factor STAT4 due to T-BET, leading to predisposed potential for the type 1 response. We found that the prototypical inducer of type 3 response, IL-23, played a predominant role over IL-12 by accessing STAT4 and preferentially inducing its phosphorylation in ILC3 expressing T-BET. The early effector program driven by IL-23 was characterized by the expression of IL-22, followed by a production of IFN-γ, which relies on STAT4, T-BET and required chromatin remodeling of the Ifng locus. Altogether, our findings shed light on a feed-forward mechanism involving STAT4 and T-BET that modulates the outcome of IL-23 signaling in ILC3. This article is protected by copyright. All rights reserved

2,2′-(Biphenyl-4,4′-diyldi­oxy)diacetic acid N,N-dimethyl­formamide solvate

In the crystal struture of the title compound, C16H14O6·C3H7NO, the two crystallographically independent benzene rings are coplanar [dihedral angle = 1.00 (2)°]. The crystal structure is stabilized by O—H⋯O hydrogen bonds between the diacid and the solvate dimethylformamide mol­ecule, resulting in the formation of a zigzag chain structure extending parallel to [001]

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

Tumor necrosis factor superfamily member 14 (TNFSF14; LIGHT)による気道系上皮細胞からのCXCL8の産生と上皮間葉転換の誘導

学位の種別:課程博士University of Tokyo(東京大学

Developmental Acquisition of Regulomes Underlies Innate Lymphoid Cell Functionality

Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis and mirror adaptive CD4(+) T helper (Th) cell subtypes in both usage of effector molecules and transcription factors. To better understand the relationship between ILC subsets and their Th cell counterparts, we measured genome-wide chromatin accessibility. We find that chromatin in proximity to effector genes is selectively accessible in ILCs prior to high-level transcription upon activation. Accessibility of these regions is acquired in a stepwise manner during development and changes little after in vitro or in vivo activation. Conversely, dramatic chromatin remodeling occurs in naive CD4(+) T cells during Th cell differentiation using a type-2-infection model. This alteration results in a substantial convergence of Th2 cells toward ILC2 regulomes. Our data indicate extensive sharing of regulatory circuitry across the innate and adaptive compartments of the immune system, in spite of their divergent developing pathways

Detection of multipartite entanglement in the vicinity of symmetric Dicke states

We present methods for detecting entanglement around symmetric Dicke states. In particular, we consider N-qubit symmetric Dicke states with N/2 excitations. In the first part of the paper we show that for large N these states have the smallest overlap possible with states without genuine multi-partite entanglement. Thus these states are particulary well suited for the experimental examination of multi-partite entanglement. We present fidelity-based entanglement witness operators for detecting multipartite entanglement around these states. In the second part of the paper we consider entanglement criteria, somewhat similar to the spin squeezing criterion, based on the moments or variances of the collective spin operators. Surprisingly, these criteria are based on an upper bound for variances for separable states. We present both criteria detecting entanglement in general and criteria detecting only genuine multi-partite entanglement. The collective operator measured for our criteria is an important physical quantity: Its expectation value essentially gives the intensity of the radiation when a coherent atomic cloud emits light.Comment: 8 pages, no figures, revtex4; typos corrected, presentation improved, part about connection to superradiance added; published version; J. Opt. Soc. Am. B, Feature issue on optical quantum information science, Eds. B. Sanders, A. Zeilinger, and Y. Yamamot

Inhibition of Hsp90 Leads to Cell Cycle Arrest and Apoptosis in Human Malignant Pleural Mesothelioma

IntroductionHeat shock protein 90 (Hsp90) is an abundant molecular chaperone that mediates the maturation and stability of a variety of proteins associated with the promotion of cell growth and survival. Inhibition of Hsp90 function leads to proteasomal degradation of its mis-folded client proteins. Recently, Hsp90 has emerged as being of prime importance to the growth and survival of cancer cells and its inhibitors have already been used in phase I and II clinical trials.MethodsWe investigated how 17-allylamino-17-demethoxygeldanamycin (17-AAG), a small molecule inhibitor of Hsp90, is implicated in human malignant pleural mesothelioma (MM).ResultsWe found that 17-AAG led to significant G1 or G2/M cell cycle arrest, inhibition of cell proliferation, and decrease of AKT, AKT1, and survivin expression in all human malignant pleural mesothelioma cell lines examined. We also observed significant apoptosis induction in all MM cell lines treated with 17-AAG. Furthermore, 17-AAG induced apoptosis in freshly cultured primary MM cells and caused signaling changes identical to those in 17-AAG treated MM cell lines.ConclusionThese results suggest that Hsp90 is strongly associated with the growth and survival of MM and that inhibition of Hsp90 may have therapeutic potential in the treatment of MM

Comparative assessment of fully laparoscopic Duhamel-Z with minimal rectorectal dissection vs. laparoscopy-assisted Duhamel-Z with blunt manual rectorectal dissection for total colonic aganglionosis

AimsEarly postoperative outcome (EPO) was compared between fully laparoscopic Duhamel-Z (F-Dz) and laparoscopy-assisted Duhamel-Z (A-Dz) anastomoses performed for total colonic aganglionosis (TCA).MethodsEPO was assessed quarterly for the first year after F-Dz/A-Dz using a continence evaluation score (CES) based on stool frequency (motions/day) and stool consistency (0 = liquid, 1 = soft, 2 = formed), presence of anal erosion (0 = severe, 1 = moderate, 2 = mild), and incidence of enterocolitis.Surgical technique involved taking the ileostomy down, dissecting the colon laparoscopically, and preparing the pull-through ileum through the stoma wound. In F-Dz (n = 3), a working port (SILS trocar) was inserted, and laparoscopic retrorectal dissection with forceps used to create a retrorectal tunnel from the peritoneal reflection extending downward as narrow as possible along the posterior wall of the rectum to prevent lateral nerve injury and preserve vascularity. After completing the tunnel, the ileum was pulled-through from an incision on the anorectal line and a Z-shaped ileorectal side-to-side anastomosis performed without a blind pouch. In A-Dz (n = 11), the retrorectal pull-through route was created through a Pfannenstiel incision using blunt manual (finger) dissection along the anterior surface of the sacrum.ResultsSubject backgrounds were similar. Mean quarterly data were: frequency (F-Dz: 4.67, 4.67, 4.67, 3.33) vs. (A-Dz: 7.27, 7.09, 6.18, 5.36) p < .05; consistency (F-Dz: 0.33, 0.67, 0.67, 0.67) vs. (A-Dz: 0.27, 0.45, 0.70, 0.73) p = ns; anal erosion (F-Dz: 0.33, 0.33, 0.33, 0.67) vs. (A-Dz: 0.18, 0.36, 0.45, 0.64) p = ns; and enterocolitis (F-Dz: 1 episode in 1/3 cases or 33.3%) vs. (A-Dz: 7 episodes in 6/11 cases or 54.5%) p = ns.ConclusionsOverall, EPO after F-Dz was better than after A-Dz