A two-amino-acid substitution in the transcription factor RORγt disrupts its function in T_H17 differentiation but not in thymocyte development

The transcription factor RORγt regulates differentiation of the T_H17 subset of helper T cells, thymic T cell development and lymph-node genesis. Although elimination of RORγt prevents T_H17 cell–mediated experimental autoimmune encephalomyelitis (EAE), it also disrupts thymocyte development, which could lead to lethal thymic lymphoma. Here we identified a two-amino-acid substitution in RORγt (RORγt^M) that 'preferentially' disrupted T_H17 differentiation but not thymocyte development. Mice expressing RORγt^M were resistant to EAE associated with defective T_H17 differentiation but maintained normal thymocyte development and normal lymph-node genesis, except for Peyer's patches. RORγt^M showed less ubiquitination at Lys69 that was selectively required for T_H17 differentiation but not T cell development. This study will inform the development of treatments that selectively target T_H17 cell–mediated autoimmunity but do not affect thymocyte development or induce lymphoma

A two-amino-acid substitution in the transcription factor RORγt disrupts its function in T_H17 differentiation but not in thymocyte development

The transcription factor RORγt regulates differentiation of the T_H17 subset of helper T cells, thymic T cell development and lymph-node genesis. Although elimination of RORγt prevents T_H17 cell–mediated experimental autoimmune encephalomyelitis (EAE), it also disrupts thymocyte development, which could lead to lethal thymic lymphoma. Here we identified a two-amino-acid substitution in RORγt (RORγt^M) that 'preferentially' disrupted T_H17 differentiation but not thymocyte development. Mice expressing RORγt^M were resistant to EAE associated with defective T_H17 differentiation but maintained normal thymocyte development and normal lymph-node genesis, except for Peyer's patches. RORγt^M showed less ubiquitination at Lys69 that was selectively required for T_H17 differentiation but not T cell development. This study will inform the development of treatments that selectively target T_H17 cell–mediated autoimmunity but do not affect thymocyte development or induce lymphoma

Advances in non-thermal treatment techniques to control yogurt post-acidification

Post-acidification is one of the most important factors affecting the sensory quality, flavor characteristics and stability of yogurt during shelf-life. Non-thermal treatments are novel methods to control post-acidification, which can maintain the original nutritional properties and sensory quality of food to the maximum extent. In this paper, the mechanism of post-acidification of lactic acid bacteria was reviewed. The mechanism and recent research progress of non-heat treatment processes such as ultra-high pressure, ultrasound, pulsed electric field, CO2 treatment, irradiation were analyzed and provided theoretical guidance for the development and industrial application of non-heat acid control technology

A simulation study on the measurement of D0-D0bar mixing parameter y at BES-III

We established a method on measuring the \dzdzb mixing parameter $y$ for BESIII experiment at the BEPCII $e^+e^-$ collider. In this method, the doubly tagged $\psi(3770) \to D^0 \overline{D^0}$ events, with one $D$ decays to CP-eigenstates and the other $D$ decays semileptonically, are used to reconstruct the signals. Since this analysis requires good $e/\pi$ separation, a likelihood approach, which combines the $dE/dx$, time of flight and the electromagnetic shower detectors information, is used for particle identification. We estimate the sensitivity of the measurement of $y$ to be 0.007 based on a $20fb^{-1}$ fully simulated MC sample.Comment: 6 pages, 7 figure

Design & Optimization of the HV divider for JUNO 20-inch PMT

The Jiangmen Underground Observatory (JUNO) is a 20-kton liquid scintillator detector that employs 20,000 20-inch photomultiplier tubes (PMTs) as photon sensors, with 5,000 dynode-PMTs from HAMAMATSU Photonics K.K. (HPK), and 15,000 MCP-PMTs from North Night Vision Technology (NNVT) installed in pure water. JUNO aims to provide long-lasting and the best performance operation by utilizing a high-transparency liquid scintillator, high detection efficiency PMTs, and specially designed electronics including water-proof potting for the high voltage (HV) dividers of PMTs. In this paper, we present a summary of the design and optimization of HV dividers for both types of 20-inch PMTs, which includes collection efficiency, charge resolution, HV divider current, pulse shape, and maximum amplitude restriction. We have developed and finalized four schemes of the HV divider for different scenarios, including the final version selected by JUNO. All 20,000 20-inch PMTs have successfully undergone production and burning tests.Comment: 14pages,28figure

Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae