RESUMO
Using magnetization, dielectric constant, and neutron diffraction measurements on a high quality single crystal of YBaCuFeO5 (YBCFO), we demonstrate that the crystal shows two antiferromagnetic transitions at [Formula: see text] K and [Formula: see text] K, and displays a giant dielectric constant with a characteristic of the dielectric relaxation at T N2. It does not show the evidence of the electric polarization for the crystal used for this study. The transition at T N1 corresponds with a paramagnetic to antiferromagnetic transition with a magnetic propagation vector doubling the unit cell along three crystallographic axes. Upon cooling, at T N2, the commensurate spin ordering transforms to a spiral magnetic structure with a propagation vector of ([Formula: see text] [Formula: see text] [Formula: see text]), where [Formula: see text], [Formula: see text], and [Formula: see text] are odd, and the incommensurability δ is temperature dependent. Around the transition boundary at T N2, both commensurate and incommensurate spin ordering coexist.
RESUMO
The T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) is selectively expressed on terminally differentiated T helper 1 (Th1) cells and acts as a negative regulator that terminates Th1 responses. The dysregulation of TIM-3 expression on T cells is associated with several autoimmune phenotypes and with chronic viral infections; however, the mechanism of this regulation is unclear. In this study, we investigated the effect of DNA methylation on the expression of TIM-3. By analyzing the sequences of TIM-3 promoter regions in human and mouse, we identified a CpG island within the TIM-3 promoter and demonstrated that the promoter activity was controlled by DNA methylation. Furthermore, treatment with 5-aza-2'-deoxycytidine enhanced TIM-3 expression on mouse primary CD4(+) T cells under Th0-, Th1- or Th2-polarizing conditions. Finally, pyrosequencing analysis revealed that the methylation level of the TIM-3 promoter gradually decreased after each round of T-cell polarization, and this decrease was inversely correlated with TIM-3 expression. These data suggest that the DNA methylation of the TIM-3 promoter cooperates with lineage-specific transcription factors in the control of Th-cell development. In conclusion, DNA methylation-based regulation of TIM-3 may provide novel insights into understanding the dysregulation of TIM-3 expression under pathogenic conditions.
Assuntos
Metilação de DNA , Receptor Celular 2 do Vírus da Hepatite A/genética , Regiões Promotoras Genéticas , Linfócitos T Auxiliares-Indutores/metabolismo , Animais , Linhagem da Célula , Ilhas de CpG , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Humanos , Células Jurkat , Camundongos , Linfócitos T Auxiliares-Indutores/citologia , Fatores de Transcrição/metabolismoRESUMO
AIMS/HYPOTHESIS: Recent reports indicate that B lymphocyte-induced maturation protein 1 (BLIMP-1), encoded by the Prdm1 gene, expands its control over T cells and is associated with susceptibility to colitis in mice with T cell-specific BLIMP-1 deficiency. In this study, we aimed to investigate the potential role of BLIMP-1 in regulating autoimmune diabetes and T helper type 17 (Th17) cells. METHODS: We generated T cell-specific Blimp1 (also known as Prdm1) transgenic (Tg) or conditional knockout (CKO) NOD mice, in which Blimp1 is overexpressed or deleted in T cells, respectively. By side-by-side analysing these Tg or CKO mice, we further dissected the potential mechanisms of BLIMP-1-mediated modulation on autoimmune diabetes. RESULTS: Overproduction of BLIMP-1 in T cells significantly attenuated insulitis and the incidence of diabetes in NOD mice. Consistent with these results, the diabetogenic effect of splenocytes was remarkably impaired in Blimp1 Tg mice. Moreover, overproduction of BLIMP-1 repressed the proliferation and activation of lymphocytes and enhanced the function of regulatory T cells (Tregs) in NOD mice. In contrast, mice lacking BLIMP-1 in T cells markedly increased Th1 and Th17 cells, and developed highly proliferative and activated lymphocytes. Strikingly, overexpansion of Th1 and Th17 cells in CKO mice was significantly reduced by introducing a Blimp1 transgene, reinforcing the emerging role of BLIMP-1 in autoimmunity. CONCLUSIONS/INTERPRETATION: We conclude that BLIMP-1 orchestrates a T cell-specific modulation of autoimmunity by affecting lymphocyte proliferation and activation, Th1 and Th17 cell differentiation, and Treg function. Our results provide a theoretical basis for developing BLIMP-1-manipulated therapies for autoimmune diabetes.
Assuntos
Autoimunidade , Diabetes Mellitus Tipo 1/prevenção & controle , Terapia de Imunossupressão , Pâncreas/imunologia , Células Th1/imunologia , Células Th17/imunologia , Fatores de Transcrição/biossíntese , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Cruzamentos Genéticos , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Feminino , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Camundongos Transgênicos , Pâncreas/patologia , Fator 1 de Ligação ao Domínio I Regulador Positivo , Organismos Livres de Patógenos Específicos , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologia , Células Th1/patologia , Células Th17/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
UNLABELLED: Legionella pneumophila, aerosolized from numerous indoor facilities (e.g., shower heads, hot tubs, spas), may cause Pontiac fever (PF) and lethal pneumonia named Legionnaires' disease (LD) in humans. Reliable methods on quantitative exposure assessment of this bioaerosol are essential for the prevention of PF and LD. Coupled with culture, ethidium monoazide with qPCR, and qPCR assays, the collection efficiency for culturable, viable, and total L. pneumophila was assessed by means of filtration sampling (IOM with gelatin filter and cassette with polycarbonate filter) and liquid-based sampling methods (BioSampler, AGI-30, MAS-100 sampler with Tween mixture and deionized water (DW)). Results show IOM/gelatin filter was comparable to cassette/polycarbonate filter (P = 0.33) and performed greater than all of tested liquid-based methods for total cell collection. On the other hand, IOM/gelatin filter obtained greater efficiencies than cassette/polycarbonate filter by a factor of 3.8-8.6 for viable cells (P = 0.0006) and two orders of magnitude for culturable cells (P = 0.00002). Further comparison between liquid impingement and filtration methods indicates the sampling by IOM/gelatin filter, AGI-30, and BioSampler with DW were the most appropriate for viable cells, while culturable cells were collected most efficiently by BioSampler/DW with periodical replenishment during the sampling. PRACTICAL IMPLICATIONS: This study recommends the most suitable methodologies for quantifying culturable, viable, and total Legionella pneumophila in indoor air. By using appropriate sampling and analytical methods, the residents and building owners are able to obtain the reliable data and further characterize the exposure risk and/or intervention efficacy against L. pneumophila. Moreover, the adoption of suitable monitoring methods also assists the investigators to explore the sources linked to PF and LD during the outbreaks. Considering reliable microbial monitoring is fundamental for epidemiological survey and risk assessment, the present information should be taken into account in assessing L. pneumophila indoors.
Assuntos
Microbiologia do Ar , Poluição do Ar em Ambientes Fechados/análise , Monitoramento Ambiental/métodos , Legionella pneumophila/isolamento & purificação , Doença dos Legionários/diagnóstico , Aerossóis/análise , Azidas/química , Técnicas Bacteriológicas/métodos , Monitoramento Epidemiológico , Filtração/métodos , Gelatina/química , Humanos , Legionella pneumophila/crescimento & desenvolvimento , Doença dos Legionários/epidemiologia , Doença dos Legionários/etiologia , Reação em Cadeia da Polimerase/métodos , Medição de Risco/métodosRESUMO
We report herein the identification of a new HLA-C allele using sequence-based typing (SBT). This novel allele, HLA-Cw*08012, was found in an Aboriginal individual from the Puyuma tribe in the southern part of Taiwan. This individual was typed by the SBT method as having an HLA genotype of HLA-A*2402/2402, HLA-B*1502/4801, HLA-Cw*08011/08012, HLA-DRB1*15011/08032, HLA-DRB5*01011, and DPB1*0501/1401. This new allele differs from HLA-Cw*08011 in one of the nucleotides of the polymorphic exon 3 at codon 99 [TAT-->TAC; both code for tyrosine]. This residue is located in the beta sheet of the HLA-C alpha2 domain. This new allele was detected in a few individuals of the Puyuma tribe in Taiwan, but has not yet been observed in other populations in Taiwan.
Assuntos
Alelos , Antígenos HLA-C/genética , Havaiano Nativo ou Outro Ilhéu do Pacífico/genética , Mutação Puntual , Sequência de Bases , Éxons , Antígenos HLA-C/química , Teste de Histocompatibilidade , Humanos , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo Genético , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Grupos Raciais , Taiwan/etnologiaRESUMO
We report herein the identification of a new HLA-C allele using sequence-based typing (SBT). This novel allele, HLA-Cw*0106, was found in a Han Chinese individual from Taiwan. This individual was typed using SBT as having a class I HLA genotype of HLA-A*0206/0207, HLA-B*4601/5601, and HLA-Cw*0102/0106. This new allele differs from HLA-Cw*0102 in one of the nucleotides of the polymorphic exon 3 at codon 152 (GAG-->GTG; E152V). This residue is located in the alpha helix of the HLA-C alpha2 domain and may have the potential to affect the binding of HLA-C molecules with antigenic peptides and/or the interactions with the T cell receptor. This new allele was detected in a few individuals of Han Chinese in Taiwan, but has not yet been observed in the aboriginal populations in Taiwan.
Assuntos
Povo Asiático/genética , Antígenos HLA-C/química , Antígenos HLA-C/genética , Mutação Puntual , Sequência de Bases , Humanos , Dados de Sequência Molecular , Estrutura Secundária de Proteína , TaiwanRESUMO
We probed spin-spin correlations up to 725 K with 63Cu nuclear quadrupole resonance in the S = 1 / 2 three-leg ladder Sr2Cu3O5. We present experimental evidence that below 300 K weak interladder coupling causes dimensional crossover of the spin-spin correlation length xi from the quasi-1D (xi approximately 1 / T) to the anisotropic 2D regime ( xi approximately exp2pirho(s) / T, where 2pirho(s) = 290+/-30 K is the effective spin stiffness).