Comparative tracking of tetramer-positive and epitope-specific CD4 super(+) T cells in blood and other tissues from tuberculosis (TB) patients during TB development and treatment using control donor ...samples is not well characterized. In this study, a novel HLA-DR-restricted peptide E7 from the ESAT-6 protein of Mycobacterium tuberculosis (MTB) was used to prepare modified HLA-DR*08032/E7 tetramer (tetramer 1) and HLA-DR*0818/E7 tetramer (tetramer 2) to monitor a series of samples from TB patients and control donors. Tetramer staining showed that (1) by direct staining of single sample and flow cytometric analyses, detection of tetramer-positive CD4 super(+) T cells ranged from 0.1% to 8.8% (median 0.67% in tetramer 1 and 0.5% in tetramer 2), 0.1 to 10.7% (0.74% and 0.71%), 0.02 to 2.2% (0.25% and 0.25%), 0.02 to 0.48% (0.2% and 0.2%) and most at under 0-0.2% (0.2% and 0.16%) in the initial pulmonary TB (PTB) patients' blood, pleural fluid (PLF) of initial tuberculous pleuritis patients, non-TB patients' blood, healthy donors' blood and umbilical cord blood, respectively; significantly higher levels of CD4 super(+) T cells were detected in samples of TB patients than in three control donor groups; (2) by direct staining of time point TB samples and flow cytometric analyses, along with TB symptom amendment at day 60, tetramer-positive CD4 super(+) T cells began to decrease, until after 90-120 days, reached and kept at a relatively low even normal level about at 0.03-0.3%; (3) by enrichment approach, at least 10-fold increased memory tetramer-positive CD4 super(+) T cells were seen; (4) by in situ staining, tetramer-positive, IFN- gamma -producing and/or TNF- alpha -producing CD4 super(+) T cells in the lymph node and lung granuloma and cavernous tissues of TB patients could be determined. Therefore, by further increasing the sample size tested to confirm the specificity and sensitivity of tetrameric molecules, it should be possible to develop them for use as research and diagnostic reagents.
A soliton mode-locked lead selenide (PbSe) quantum-dot-doped fiber laser (QDFL) is proposed and investigated by numerical simulation for the first time. Buildup dynamics in time and spectral domains ...are studied. Output properties starting from Gaussian and noise-like signals are characterized. The optimum quantum-dot-doped fiber lengths are revealed under various PbSe quantum dot doping concentrations. The evolutions of the pulse and spectrum in the resonator at the steady state are discussed. The results obtained facilitate the understanding of the operating principle of QDFL for solving emission wavelength problem.
Although microbial (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) can activate primate Vgamma2Vdelta2 T cells, molecular mechanisms by which HMBPP interacts with Vgamma2Vdelta2 T cells ...remain poorly characterized. Here, we developed soluble, tetrameric Vgamma2Vdelta2 TCR of rhesus macaques to define HMBPP/APC interaction with Vgamma2Vdelta2 TCR. While exogenous HMBPP was associated with APC membrane in an appreciable affinity, the membrane-associated HMBPP readily bound to the Vgamma2Vdelta2 TCR tetramer. The Vgamma2Vdelta2 TCR tetramer was shown to bind stably to HMBPP presented on membrane by various APC cell lines from humans and nonhuman primates but not those from mouse, rat, or pig. The Vgamma2Vdelta2 TCR tetramer also bound to the membrane-associated HMBPP on primary monocytes, B cells and T cells. Consistently, endogenous phosphoantigen produced in Mycobacterium-infected dendritic cells was transported and presented on membrane, and bound stably to the Vgamma2Vdelta2 TCR tetramer. The capability of APC to present HMBPP for recognition by Vgamma2Vdelta2 TCR was diminished after protease treatment of APC. Thus, our studies elucidated an affinity HMBPP-APC association conferring stable binding to the Vgamma2Vdelta2 TCR tetramer and the protease-sensitive nature of phosphoantigen presentation. The findings defined APC presentation of phosphoantigen HMBPP to Vgamma2Vdelta2 TCR.
Adaptive immune responses of gammadelta T cells during active mycobacterial coinfection of human immunodeficiency virus-infected humans have not been studied. Macaques infected with the simian ...immunodeficiency virus (SIV) SIVmac were employed to determine the extent to which a coincident AIDS virus infection might compromise immune responses of mycobacterium-specific Vgamma2Vdelta2(+) T cells during active mycobacterial infection. Control SIVmac-negative macaques developed primary and recall expansions of phosphoantigen-specific Vgamma2Vdelta2(+) T cells after Mycobacterium bovis BCG infection and BCG reinfection, respectively. In contrast, SIVmac-infected macaques did not exhibit sound primary and recall expansions of Vgamma2Vdelta2(+) T cells in the blood and pulmonary alveoli following BCG infection and reinfection. The absence of adaptive Vgamma2Vdelta2(+) T-cell responses was associated with profound CD4(+) T-cell deficiency and subsequent development of SIVmac-related tuberculosis-like disease in the coinfected monkeys. Consistently, Vgamma2Vdelta2(+) T cells from coinfected monkeys displayed a reduced capacity to expand in vitro following stimulation with phosphoantigen. The reduced ability of Vgamma2Vdelta2(+) peripheral blood lymphocytes (PBL) to expand could be restored to some extent by coculture of these cells with CD4(+) T cells purified from PBL of SIV-negative monkeys. Furthermore, naïve monkeys inoculated simultaneously with SIVmac and BCG were unable to sustain expansion of Vgamma2Vdelta2(+) T cells at the time that the coinfected monkeys developed lymphoid depletion and a fatal tuberculosis-like disease. Nevertheless, no deletion in Vdelta2 T-cell receptor repertoire was identified in SIVmac-BCG-coinfected macaques, implicating an SIVmac-induced down-regulation rather than a clonal exhaustion of these cells. Thus, an SIVmac-induced compromise of the adaptive Vgamma2Vdelta2(+) T-cell responses may contribute to the immunopathogenesis of the SIV-related tuberculosis-like disease in macaques.
Atherosclerotic cardiovascular disease is the leading cause of death in the world which is resulted from complex interactions among multiple genetic and environmental factors （WHO）. Athero- sclerosis ...is a chronic inflammatory disease characterized by accumulation of lipids in the arterial wall （Gofman and Lindgren, 1950）. Tremendous clinical and experimental efforts have been made to reveal the pathogenesis of the disease. Nevertheless, the mechanism of atherosclerosis is still unclear. A suitable animal model to study metabolic disorders and subsequent atherosclerosis is a necessity. The traditional method by feeding high fat diet to establish animal models of atherosclerosis disease is time- consuming and laborious, and in many circumstances, the pheno- types are not consistent among the individual models.
rhml is a major recessive disease resistance locus for Southern corn leaf blight （SCLB）. To further narrow down its genetic position, F2 population and BCIFI population derived from the cross between ...resistant （H95rhm） and susceptible parents （H95） of maize （Zea mays） were constructed. Using newly developed markers, rhml was initially delimited within an interval of 2.5 Mb, and then finally mapped to a 8.56 kb interval between InDel marker IDP961-503 and simple sequence repeat （SSR） marker A194149--1. Three polymorphic markers IDP961-504, IDP B2-3 and A194149-2 were shown to be co-segregated with the rhml locus. Sequence analysis of the 8.56 kb DNA fragment revealed that it contained only one putative gene with a predicted amino acid sequence identical to lysine histidine transporter 1 （LHT1）. Comparative sequence analysis indicated that the LHT1 in H95rhrn harbors a 354 bp insertion in its third exon as compared with that of susceptible alleles in B73, H95 and Mo17. The 354 bp insertion resulted in a truncation of the predicted protein of candidate resistance allele （LHT1-H95rhm）. Our results strongly suggest LHTI as the candidate gene for rhml against SCLB. The tightly linked molecular markers developed in this study can be directly used for molecular breeding of resistance to Southern corn leaf blight in maize.
There have been many recent advances in wireless communication technologies, particularly in the area of wireless sensor networks, which have undergone rapid development and been successfully applied ...in the consumer electronics market. Therefore, wireless networks (WNs) have been attracting more attention from academic communities and other domains. From an industrial perspective, WNs present many advantages including flexibility, low cost, easy deployment and so on. Therefore, WNs can play a vital role in the Industry 4.0 framework, and can be used for smart factories and intelligent manufacturing systems. In this paper, we present an overview of industrial WNs (IWNs), discuss IWN features and related techniques, and then provide a new architecture based on quality of service and quality of data for IWNs. We also propose some applications for IWNs and IWN standards. Then, we will use a case from our previous achievements to explain how to design an IWN under Industry 4.0. Finally, we highlight some of the design challenges and open issues that still need to be addressed to make IWNs truly ubiquitous for a wide range of applications.
Allostery is the phenomenon in which a ligand binding at one site affects other sites in the same macromolecule. Allostery has important roles in many biological processes. Theoretically, all ...nonfibrous proteins are potentially allosteric. However, few allosteric proteins have been validated, and the identification of novel allosteric sites remains a challenge. The motion of residues and subunits underlies protein function; therefore, we hypothesized that the motions of allosteric and orthosteric sites are correlated. We utilized a data set of 24 known allosteric sites from 23 monomer proteins to calculate the correlations between potential ligand-binding sites and corresponding orthosteric sites using a Gaussian network model (GNM). Most of the known allosteric site motions showed high correlations with corresponding orthosteric site motions, whereas other surface cavities did not. These high correlations were robust when using different structural data for the same protein, such as structures for the apo state and the orthosteric effector-binding state, whereas the contributions of different frequency modes to motion correlations depend on the given protein. The high correlations between allosteric and orthosteric site motions were also observed in oligomeric allosteric proteins. We applied motion correlation analysis to predict potential allosteric sites in the 23 monomer proteins, and some of these predictions were in good agreement with published experimental data. We also performed motion correlation analysis to identify a novel allosteric site in 15-lipoxygenase (an enzyme in the arachidonic acid metabolic network) using recently reported activating compounds. Our analysis correctly identified this novel allosteric site along with two other sites that are currently under experimental investigation. Our study demonstrates that the motions of allosteric sites are highly correlated with the motions of orthosteric sites. Our correlation analysis method provides new tools for predicting potential allosteric sites.
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