NOD‐like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. ...Previous reports have shown that NLRC3 is expressed in dendritic cells (DCs). However, the role of NLRC3 in DC activation and immunogenicity is unclear. In the present study, we find that NLRC3 attenuates the antigen‐presenting function of DCs and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets. Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced experimental autoimmune encephalomyelitis (EAE) development. NLRC3 negatively regulates the antigen‐presenting function of DCs via p38 signaling pathway. Vaccination with NLRC3‐overexpressed DCs reduces EAE progression. Our findings support that NLRC3 serves as a potential target for treating adaptive immune responses driving multiple sclerosis and other autoimmune disorders.
Synopsis
The innate immune sensor NLRC3 negatively regulates dendritic cell activation to affect Th1 and Th17 cell differentiation and experimental autoimmune encephalomyelitis.
NLRC3 attenuates the antigen‐presenting function of DCs and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets.
Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced EAE development.
NLRC3 negatively regulates the antigen‐presenting function of DCs via p38 signaling pathway.
The innate immune sensor NLRC3 negatively regulates dendritic cell activation to affect Th1 and Th17 cell differentiation and experimental autoimmune encephalomyelitis.
We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). ...Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
Rationale
In situ trace element analysis of melt inclusions by laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) provides important geochemistry information. However, the ...precision and accuracy of this technique are affected by many factors, such as matrix effect, laser conditions, and calibration method. In addition, many previous LA‐ICP‐MS studies ablated entire melt inclusions along with their host minerals and obtained trace element composition by deconvoluting the mixed ablation signal, which may induce much uncertainty.
Methods
A 193 nm ArF laser ablation system combined with inductively coupled plasma sector field mass spectrometry (ICP‐SF‐MS) was used to investigate matrix effect, laser conditions, choice of external calibration standards, and data reduction strategy for in situ analysis of 36 major and trace elements in six common silicate reference glasses. The validity of the protocol presented here was demonstrated by measuring trace elements in olivine‐hosted melt inclusions. Instead of ablating entire melt inclusions along with their host minerals, melt inclusions were polished to the surface to avoid laser ablating the mineral host.
Results
The calibration lines calculated from the calibration standards should cross the coordinate origin, especially for low‐concentration elements (<10 ppm). As the laser crater size increased from 17 to 33 μm, the precision was improved from <20% to <8% (2RSD), and accuracy was improved from ±20% to better than ±10%. Most measured trace elements in Dali melt inclusions are consistent with those in their host rocks. For mobile elements (Ba, Sr, Pb), melt inclusions display much smaller variations than their host rocks.
Conclusions
A simple but accurate approach for in situ analysis of trace elements in melt inclusions by LA‐ICP‐SF‐MS has been established, which should greatly facilitate the wider application of in situ trace element geochemistry to melt inclusion studies.
Mucosal-associated invariant T (MAIT) cells have important functions in immune responses against pathogens and in diseases, but mechanisms controlling MAIT cell development and effector lineage ...differentiation remain unclear. Here, we report that IL-2/IL-15 receptor β chain and inducible costimulatory (ICOS) not only serve as lineage-specific markers for IFN-γ-producing MAIT1 and IL-17A-producing MAIT17 cells, but are also important for their differentiation, respectively. Both IL-2 and IL-15 induce mTOR activation, T-bet upregulation, and subsequent MAIT cell, especially MAIT1 cell, expansion. By contrast, IL-1β induces more MAIT17 than MAIT1 cells, while IL-23 alone promotes MAIT17 cell proliferation and survival, but synergizes with IL-1β to induce strong MAIT17 cell expansion in an mTOR-dependent manner. Moreover, mTOR is dispensable for early MAIT cell development, yet pivotal for MAIT cell effector differentiation. Our results thus show that mTORC2 integrates signals from ICOS and IL-1βR/IL-23R to exert a crucial role for MAIT17 differentiation, while the IL-2/IL-15R-mTORC1-T-bet axis ensures MAIT1 differentiation.
With the growing demands of the early, accurate, and sensitive diagnosis for cancers, the development of new diagnostic technologies becomes increasingly important. In this study, we proposed a ...strategy for efficient capture and sensitive detection of circulating tumor cells (CTCs) using an array nanochannel-ion channel hybrid coupled with an electrochemical detection technique. The aptamer probe was immobilized on the ion channel surface to couple with the protein overexpressed on the CTCs membrane. Through this special molecular recognition, CTCs can be selectively captured. The trapped CTCs cover the ion channel entrance efficiently, which will dramatically block the ionic flow through channels, resulting in a varied mass-transfer property of the nanochannel-ion channel hybrid. On the basis of the changed mass-transfer properties, the captured CTCs can be sensitively detected using the electrochemical linear sweep voltammetry technique. Furthermore, due to the amplified response of array channels compared to that of a single channel, the detection sensitivity can be enhanced greatly. The results showed that acute leukemia CCRF-CEM (a type of CTC) concentration as low as 100 cells mL
can be successfully captured and detected. The present method provides a simple, sensitive, and label-free technique for CTCs capture, detection, and release, which would hold great potential in the early clinical diagnosis and treatment of cancers.
In recent years, person re-identification (ReID) has received much attention since it is a fundamental task in intelligent surveillance systems and has widespread application prospects in numerous ...fields. Given an image of a pedestrian captured from one camera, the task is to identify this pedestrian from the gallery set captured by other multiple cameras. It is a challenging issue since the appearance of a pedestrian may suffer great changes across different cameras. The task has been greatly boosted by deep learning technology. There are mainly six types of deep learning-based methods designed for this issue, i.e. identification deep model, verification deep model, distance metric-based deep model, part-based deep model, video-based deep model and data augmentation-based deep model. In this paper, we first give a comprehensive review of current six types of deep learning methods. Second, we present the detailed descriptions of existing person ReID datasets. Then, some state-of-the-art performances of methods over recent years on several representative ReID datasets are summarized. Finally, we conclude this paper and discuss the future directions of the person ReID.
The engagement of the T cell receptor (TCR) induces the generation of diacylglycerol (DAG), an important second messenger activating both the Ras/Erk and PKCθ/NFκB pathways. DAG kinases (DGKs) ...participate in the metabolism of DAG by converting it to phosphatidic acid. DGKζ has been demonstrated to be able to inhibit DAG signaling following TCR engagement. Deficiency of DGKζ increases the sensitivity of T cells to TCR stimulation, resulting in enhanced T cell activation ex vivo and in vivo. However, the mechanisms that control DGKζ expression are poorly understood. Here we demonstrate that DGKζ mRNA is a direct target of a cellular microRNA miR-34a. The DGKζ transcript is decreased, whereas the primary miR-34a is upregulated upon TCR stimulation. Ectopic miR-34a expression suppresses DGKζ protein expression through the seed match binding to both the 3' untranslated region and coding region of DGKζ mRNA, leading to increased ERK1/2 phosphorylation and surface expression of the T cell activation marker CD69 following TCR cross-linking. In contrast, overexpression of a miR-34a competitive inhibitor increases DGKζ expression and suppresses TCR-mediated T cell activation. Together, our data demonstrate that miR-34a is a negative regulator for DGKζ and may play an important role in regulating T cell activation.
PDF
