Temperature dependence of the electronic structure of the J(eff)=12 Mott insulator Sr2IrO4 studied by optical spectroscopy

We investigated the temperature-dependent evolution of the electronic structure of the J(eff)=1/2 Mott insulator Sr2IrO4 using optical spectroscopy. The optical conductivity spectra sigma(omega) of this compound has recently been found to exhibit two d-d transitions associated with the transition between the J(eff)=1/2 and J(eff)=3/2 bands due to the cooperation of the electron correlation and spin-orbit coupling. As the temperature increases, the two peaks show significant changes resulting in a decrease in the Mott gap. The experimental observations are compared with the results of first-principles calculation in consideration of increasing bandwidth. We discuss the effect of the temperature change in the electronic structure of Sr2IrO4 in terms of local lattice distortion, excitonic effect, electron-phonon coupling, and magnetic ordering.open69575

Magnetic Origin of Giant Magnetoelectricity in Doped Y-type Hexaferrite Ba0.5Sr1.5Zn2(Fe1-xAlx)(12)O-22

We investigated site-specific magnetic behaviors of multiferroic Ba0.5Sr1.5Zn2(Fe1-xAlx)(12)O-22 using Fe L-2,L-3-edge x-ray magnetic circular dichroism. The Al dopants mostly replace the Fe3+ ions at octahedral (O-h) sites, which contribute unquenched angular momenta through off-centering displacements. This replacement greatly reduces the magnetic anisotropy energy to change the magnetic order from a helical to a heliconical type with enhanced magnetoelectric susceptibility (alpha(ME)). The tetrahedral (T-d) Fe sites exhibit magnetic hysteresis distinguishable from that of the O-h sites, especially at low magnetic fields. These results provide essential clues for the heliconical order with a giant aME and multibit memory effects in the Al-doped Y-type hexaferrite.open1178sciescopu

A Novel Histone Deacetylase Inhibitor Exhibits Antitumor Activity via Apoptosis Induction, F-Actin Disruption and Gene Acetylation in Lung Cancer

BACKGROUND: Lung cancer is the leading cause of cancer mortality worldwide, yet the therapeutic strategy for advanced non-small cell lung cancer (NSCLC) is limitedly effective. In addition, validated histone deacetylase (HDAC) inhibitors for the treatment of solid tumors remain to be developed. Here, we propose a novel HDAC inhibitor, OSU-HDAC-44, as a chemotherapeutic drug for NSCLC. METHODOLOGY/PRINCIPAL FINDINGS: The cytotoxicity effect of OSU-HDAC-44 was examined in three human NSCLC cell lines including A549 (p53 wild-type), H1299 (p53 null), and CL1-1 (p53 mutant). The antiproliferative mechanisms of OSU-HDAC-44 were investigated by flow cytometric cell cycle analysis, apoptosis assays and genome-wide chromatin-immunoprecipitation-on-chip (ChIP-on-chip) analysis. Mice with established A549 tumor xenograft were treated with OSU-HDAC-44 or vehicle control and were used to evaluate effects on tumor growth, cytokinesis inhibition and apoptosis. OSU-HDAC-44 was a pan-HDAC inhibitor and exhibits 3-4 times more effectiveness than suberoylanilide hydroxamic acid (SAHA) in suppressing cell viability in various NSCLC cell lines. Upon OSU-HDAC-44 treatment, cytokinesis was inhibited and subsequently led to mitochondria-mediated apoptosis. The cytokinesis inhibition resulted from OSU-HDAC-44-mediated degradation of mitosis and cytokinesis regulators Auroroa B and survivin. The deregulation of F-actin dynamics induced by OSU-HDAC-44 was associated with reduction in RhoA activity resulting from srGAP1 induction. ChIP-on-chip analysis revealed that OSU-HDAC-44 induced chromatin loosening and facilitated transcription of genes involved in crucial signaling pathways such as apoptosis, axon guidance and protein ubiquitination. Finally, OSU-HDAC-44 efficiently inhibited A549 xenograft tumor growth and induced acetylation of histone and non-histone proteins and apoptosis in vivo. CONCLUSIONS/SIGNIFICANCE: OSU-HDAC-44 significantly suppresses tumor growth via induction of cytokinesis defect and intrinsic apoptosis in preclinical models of NSCLC. Our data provide compelling evidence that OSU-HDAC-44 is a potent HDAC targeted inhibitor and can be tested for NSCLC chemotherapy

Role of HDAC3 on p53 Expression and Apoptosis in T Cells of Patients with Multiple Sclerosis

Background: Histone deacetylase 3 (HDAC3) belongs to a family of proteins which plays an important role in protein acetylation, chromatin remodeling and transcription of genes, including those that are involved in cell proliferation and cell death. While increased expression of HDAC3 is seen in neoplastic cells, the role of HDAC3 in T cells and their role in autoimmune disease is not known. Methodology/Principal Findings: Applying Affymetrix GeneChip Human Gene 1.0 ST Array and the mixed effects model for gene set analysis, we compared gene expression profiles between multiple sclerosis (MS) patients and healthy controls (HC). Within the Apoptosis_GO gene set, the constitutive expression level of HDAC3 in peripheral blood mononuclear cell (PBMC) was significantly increased in MS patients when compared to controls. Following addition of trichostatin A (TSA), an inhibitor of HDAC3, we examined the expression of p53 by flow cytometry and p53 targeted genes by real time RT-PCR in MS and HC. Culture of PBMC with TSA resulted in increased expression of p53 in HC but not in MS patients. TSA treated T cells from MS patients also showed reduced sensitivity to apoptosis when compared to HC, which was independent of activation of p53 targeted pro-apoptotic genes. Conclusion/Significance: MS patients, when compared to controls, show an increased expression of HDAC3 and relative resistance to TSA induced apoptosis in T cells. Increased expression of HDAC3 in PBMC of MS patients may render putativ

Emergency department spirometric volume and base deficit delineate risk for torso injury in stable patients

BACKGROUND: We sought to determine torso injury rates and sensitivities associated with fluid-positive abdominal ultrasound, metabolic acidosis (increased base deficit and lactate), and impaired pulmonary physiology (decreased spirometric volume and PaO(2)/FiO(2)). METHODS: Level I trauma center prospective pilot and post-pilot study (2000–2001) of stable patients. Increased base deficit was < 0.0 in ethanol-negative and ≤ -3.0 in ethanol-positive patients. Increased lactate was > 2.5 mmol/L in ethanol-negative and ≥ 3.0 mmol/L in ethanol-positive patients. Decreased PaO(2)/FiO(2 )was < 350 and decreased spirometric volume was < 1.8 L. RESULTS: Of 215 patients, 66 (30.7%) had a torso injury (abdominal/pelvic injury n = 35 and/or thoracic injury n = 43). Glasgow Coma Scale score was 14.8 ± 0.5 (13–15). Torso injury rates and sensitivities were: abdominal ultrasound negative and normal base deficit, lactate, PaO(2)/FiO(2), and spirometric volume – 0.0% & 0.0%; normal base deficit and normal spirometric volume – 4.2% & 4.5%; chest/abdominal soft tissue injury – 37.8% & 47.0%; increased lactate – 39.7% & 47.0%; increased base deficit – 41.3% & 75.8%; increased base deficit and/or decreased spirometric volume – 43.8% & 95.5%; decreased PaO(2)/FiO(2 )– 48.9% & 33.3%; positive abdominal ultrasound – 62.5% & 7.6%; decreased spirometric volume – 73.4% & 71.2%; increased base deficit and decreased spirometric volume – 82.9% & 51.5%. CONCLUSIONS: Trauma patients with normal base deficit and spirometric volume are unlikely to have a torso injury. Patients with increased base deficit or lactate, decreased spirometric volume, decreased PaO(2)/FiO(2), or positive FAST have substantial risk for torso injury. Increased base deficit and/or decreased spirometric volume are highly sensitive for torso injury. Base deficit and spirometric volume values are readily available and increase or decrease the suspicion for torso injury

Vaccine responses in newborns.

Immunisation of the newborn represents a key global strategy in overcoming morbidity and mortality due to infection in early life. Potential limitations, however, include poor immunogenicity, safety concerns and the development of tolerogenicity or hypo-responsiveness to either the same antigen and/or concomitant antigens administered at birth or in the subsequent months. Furthermore, the neonatal immunological milieu is polarised towards Th2-type immunity with dampening of Th1-type responses and impaired humoral immunity, resulting in qualitatively and quantitatively poorer antibody responses compared to older infants. Innate immunity also shows functional deficiency in antigen-presenting cells: the expression and signalling of Toll-like receptors undergo maturational changes associated with distinct functional responses. Nevertheless, the effectiveness of BCG, hepatitis B and oral polio vaccines, the only immunisations currently in use in the neonatal period, is proof of concept that vaccines can be successfully administered to the newborn via different routes of delivery to induce a range of protective mechanisms for three different diseases. In this review paper, we discuss the rationale for and challenges to neonatal immunisation, summarising progress made in the field, including lessons learnt from newborn vaccines in the pipeline. Furthermore, we explore important maternal, infant and environmental co-factors that may impede the success of current and future neonatal immunisation strategies. A variety of approaches have been proposed to overcome the inherent regulatory constraints of the newborn innate and adaptive immune system, including alternative routes of delivery, novel vaccine configurations, improved innate receptor agonists and optimised antigen-adjuvant combinations. Crucially, a dual strategy may be employed whereby immunisation at birth is used to prime the immune system in order to improve immunogenicity to subsequent homologous or heterologous boosters in later infancy. Similarly, potent non-specific immunomodulatory effects may be elicited when challenged with unrelated antigens, with the potential to reduce the overall risk of infection and allergic disease in early life

Riluzole Attenuates L-DOPA-Induced Abnormal Involuntary Movements Through Decreasing CREB1 Activity

Chronic administration of L-DOPA, the first-line treatment of dystonic symptoms in childhood or in Parkinson's disease, often leads to the development of abnormal involuntary movements (AIMs), which represent an important clinical problem. Although it is known that Riluzole attenuates L-DOPA-induced AIMs, the molecular mechanisms underlying this effect are not understood. Therefore, we studied the behavior and performed RNA sequencing of the striatum in three groups of rats that all received a unilateral lesion with 6-hydroxydopamine in their medial forebrain bundle, followed by the administration of saline, L-DOPA, or L-DOPA combined with Riluzole. First, we provide evidence that Riluzole attenuates AIMs in this rat model. Subsequently, analysis of the transcriptomics data revealed that Riluzole is predicted to reduce the activity of CREB1, a transcription factor that regulates the expression of multiple proteins that interact in a molecular landscape involved in apoptosis. Although this mechanism underlying the beneficial effect of Riluzole on AIMs needs to be confirmed, it provides clues towards novel or existing compounds for the treatment of AIMs that modulate the activity of CREB1 and, hence, its downstream targets

HDAC 阻害剤は Diethylstilbestrol による性腺刺激ホルモン細胞からのプロラクチン細胞への分化転換を抑制する

Diethylstilbestrol (DES), an estrogen agonist, increases prolactin (PRL) cells through transdifferentiation of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) cells to PRL cells as well as proliferation of PRL cells in adult male mouse pituitary. Since hyperacetylation of histone H3 is implicated in the regulation of activation of various genes, we examined the effect of DES on the state of histone H3 acetylation. DES significantly reduced the immunohistochemical signal for acetylated histone H3 at lysine 9 (H3K9ac) in PRL, LH and FSH cells, but not for H3K18ac or H3K23ac. DES-treated mice were injected intraperitoneally with HDAC inhibitors (HDACi), sodium phenylbutyrate (NaPB) or valproic acid (VPA), to mimic the acetylation level of histone H3. As expected, HDACi treatment restored the level of H3K9ac expression in these cells, and also inhibited DES-induced increase in PRL cells. Furthermore, NaPB and VPA also abrogated the effects of DES on the population density of both LH and FSH cells. Similarly, the numbers of proliferating and apoptotic cells in the pituitary in NaPB- or VPA-treated mice were comparable to those of the control mice. Considered together, these results indicated that the acetylation level of histone H3 plays an important role in DES-induced transdifferentiation of LH to PRL cells as well as proliferation of PRL cells.長崎大学学位論文 学位記番号:博(医歯薬)甲第1128号 学位授与年月日:平成31年3月20日Author: Nandar Tun, Yasuaki Shibata, Myat Thu Soe, Myo Win Htun, Takehiko KojiCitation: Histochemistry and Cell Biology, 151(4), pp.291-303; 2018Nagasaki University (長崎大学)課程博

Progress on lead-free metal halide perovskites for photovoltaic applications: a review

ABSTRACT: Metal halide perovskites have revolutionized the field of solution-processable photovoltaics. Within just a few years, the power conversion efficiencies of perovskite-based solar cells have been improved significantly to over 20%, which makes them now already comparably efficient to silicon-based photovoltaics. This breakthrough in solution-based photovoltaics, however, has the drawback that these high efficiencies can only be obtained with lead-based perovskites and this will arguably be a substantial hurdle for various applications of perovskite-based photovoltaics and their acceptance in society, even though the amounts of lead in the solar cells are low. This fact opened up a new research field on lead-free metal halide perovskites, which is currently remarkably vivid. We took this as incentive to review this emerging research field and discuss possible alternative elements to replace lead in metal halide perovskites and the properties of the corresponding perovskite materials based on recent theoretical and experimental studies. Up to now, tin-based perovskites turned out to be most promising in terms of power conversion efficiency; however, also the toxicity of these tin-based perovskites is argued. In the focus of the research community are other elements as well including germanium, copper, antimony, or bismuth, and the corresponding perovskite compounds are already showing promising properties. GRAPHICAL ABSTRACT: [Image: see text