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1.
Plant Dis ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442047

RESUMO

A probe-based quantitative PCR (qPCR) protocol was developed for detection and evaluation of the wheat bacterial leaf streak pathogen Xanthomonas translucens pathovar (pv.) undulosa. The protocol can also detect X. translucens pv. translucens and X. translucens pv. secalis, but can't differentiate the three pathovars. When tested on non-target DNA, i.e. from plant, bacteria other than X. translucens pv. undulosa, X. translucens pv. translucens and X. translucens pv. secalis, and culture of microorganisms from wheat grains, the qPCR showed a high specificity. On purified X. translucens pv. undulosa DNA, the qPCR was more sensitive than a loop-mediated isothermal amplification (LAMP) assay. When DNA samples from a set of serial dilutions of X. translucens pv. undulosa cells were tested, the qPCR method could repeatedly generate quantification cycle (Cq) values from the dilutions containing ≥1,000 cells. Since 2 µL of the total of 50 µL DNA was used in one reaction, one qPCR reaction could detect the presence of the bacteria in samples containing as few as 40 bacterial cells. The qPCR could detect the bacteria from both infected grain and leaf tissues. For seed testing, a protocol for template preparation was standardized, which allowed one qPCR reaction to test DNA from the surface of one wheat grain. Thus, the qPCR system could detect X. translucens pv. undulosa, X. translucens pv. translucens and/or X. translucens pv. secalis in samples where the bacteria had an average concentration ≥40 cells per grain.

2.
Materials (Basel) ; 15(6)2022 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-35329488

RESUMO

In this paper, the traditional, silicate-based Portland cement (PC) was employed as the control to explore the impact of adding varying amounts of metakaolin (MK) on the mechanical properties of cement mortar. In fact, as a mineral admixture, metakaolin (MK) has the ability to significantly improve the early strength and sulfate resistance of cement mortar in traditional, silicate-based Portland cement (PC). In addition to this, the performance of Portland cement mortar is greatly affected by the curing mode. The previous research mainly stays in the intermittent curing and alkaline excitation mode, and there are few studies on the influence of relatively humidity on it. Moreover, the paper investigated the impact of four different curing methods about humidity on the mechanical properties and sulfate resistance. The results show that the best content of metakaolin in Portland cement is 10% (M10), and the best curing method is 95% humidity in the first three days followed by 60% humidity in the later period (3#). Based on previous literature that suggests that adding MK thickens water film layer on the surface of mortar, the mechanism of MK increasing the early strength of cement was analyzed. The compressive strength of the Portland cement containing 10% MK (M10) after 1 day curing is 3.18 times that of pristine PC mortar, and is comparable if PC is cured for three days under the same curing conditions. The traditional PC mortar is highly dependent on the wet curing time, and normally requires a curing time of at least seven days. However, the incorporation of MK can greatly reduce the sensitivity of Portland cement to water; MK cement mortar with only three days wet curing (3#M10) can reach 49.12 MPa after 28 days, which can greatly shorten the otherwise lengthy wet curing time. Lastly, the cement specimens with MK also demonstrated excellent resistance against sulfate corrosion. The work will provide a strong theoretical basis for the early demolding of cement products in construction projects. At the same time, this study can also provide a theoretical reference for the construction of climate drought and saline land areas, which has great reference value.

3.
J Inflamm Res ; 15: 735-746, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35153498

RESUMO

BACKGROUND: As deubiquitinases (DUBs), ubiquitin C-terminal hydrolase (UCH)-L1 has been shown to play a crucial role in regulating diverse biological processes. However, its function in macrophage polarization remains unclear. METHODS: We performed in vivo and in vitro experiments to investigate the role of ubiquitin carboxyl-terminal hydrolase L1 (UCHL1), a kind of DUBs, in macrophage differentiation by using UCHL1-deficiency mice. RESULTS: We demonstrated that LPS stimulation induced UCHL1 expression in macrophages. The deficiency of UCHL1 expression decreased the expression of CD80 and CD86 but increased the expression of CD206. The expression of TNF-α, IL-6, iNOS, and IL-10 was downregulated, while that of Arg1, Ym1, and Fizz1 was upregulated in UCHL1 deficient macrophages. Moreover, we observed that UCHL1 promoted the degradation of p110α through autophagy, but paradoxically increased the activity of AKT, thereby promoting polarization of macrophages into pro-inflammatory states. CONCLUSION: In this study, we identified UCHL1 as a positive regulator of M1 macrophage polarization. Our findings may help in developing therapeutic interventions for the treatment of inflammatory diseases and pathogenic infections.

4.
Cancer Med ; 11(5): 1371-1395, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35037412

RESUMO

BACKGROUND: Breast cancer (BC) is the leading malignancy among women worldwide. AIM: This work aimed to present a comprehensively bioinformatic analysis of gene expression profiles and to identify the hub genes during BC tumorigenesis, providing potential biomarkers and targets for the diagnosis and therapy of BC. MATERIALS & METHODS: In this study, multiple public databases, bioinformatics approaches, and online analytical tools were employed and the real-time reverse transcription polymerase chain reaction was implemented. RESULTS: First, we identified 10, 107, and 3869 differentially expressed genes (DEGs) from three gene expression datasets (GSE9574, GSE15852, and GSE42568, covering normal, para-cancerous, and BC samples, respectively), and investigated different biological functions and pathways involved. Then, we screened out 8, 16, and 29 module genes from these DEGs, respectively. Next, 10 candidate genes were determined through expression and survival analyses. We noted that seven candidate genes JUN, FOS, FOSB, EGR1, ZFP36, CFD, and PPARG were downregulated in BC compared to normal tissues and lower expressed in aggressive types of BC (basal, HER2+ , and luminal B), TP53 mutation group, younger patients, higher stage BC, and lymph node metastasis BC, while CD27, PSMB9, and SELL were upregulated. The present study discovered that the expression levels of these candidate genes were correlated with the infiltration of immune cells (CD8+ T cell, macrophage, natural killer [NK] cell, and cancer-associated fibroblast) in BC, as well as biomarkers of immune cells and immune checkpoints. We also revealed that promoter methylation, amplification, and deep deletion might contribute to the abnormal expressions of candidate genes. Moreover, we illustrated downstream-targeted genes of JUN, FOS, FOSB, EGR1, and ZFP36 and demonstrated that these targeted genes were involved in "positive regulation of cell death", "pathways in cancer", "PI3K-Akt signaling pathway", and so on. DISCUSSION & CONCLUSION: We presented differential gene expression profiles among normal, para-cancerous, and BC tissues and further identified candidate genes that might contribute to tumorigenesis and progression of BC, as potential diagnostic and prognostic targets for BC patients.


Assuntos
Neoplasias da Mama , Biologia Computacional , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Carcinogênese/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Fatores de Transcrição/genética
5.
Medicine (Baltimore) ; 101(1): e28511, 2022 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-35029909

RESUMO

INTRODUCTION: Reconstruction of the medial patellofemoral ligament (MPFL) is an effective surgical method for the treatment of lateral patellar instability. At present, there is not much controversies regarding the femoral attachment, however, the controversies regarding patellar attachment versus attachment, number of graft strands, tension, isometry and so on. The following electronic databases will be searched: PubMed, the Cochrane Library, Embase, Web of Science, Medline. We will consider articles published between database initiation and March 2021. MPFL in the subject heading will be included in the study. Language is limited to English. Research selection, data extraction, and research quality assessment were independently completed by 2 researchers. CONCLUSIONS: MPFL reconstruction is a reliable technique for the treatment of patellofemoral instability. The Schöttle point is still the mainstream method for locating the femoral attachment, the patellar attachment for single-bundle is located at the junction of the proximal one third and the distal two third of the longitudinal axis of the patella. For double-bundles, one is located in the proximal one third of the medial patellar edge and another is in the center of the patellar edge. Meanwhile, the adjustment of graft tension during operation is very important.


Assuntos
Instabilidade Articular/cirurgia , Ligamentos Articulares/cirurgia , Luxação Patelar/cirurgia , Articulação Patelofemoral/cirurgia , Humanos , Articulação do Joelho , Patela
6.
Artigo em Inglês | MEDLINE | ID: mdl-34882554

RESUMO

Augmented Reality (AR) embeds digital information into objects of the physical world. Data can be shown in-situ, thereby enabling real-time visual comparisons and object search in real-life user tasks, such as comparing products and looking up scores in a sports game. While there have been studies on designing AR interfaces for situated information retrieval, there has only been limited research on AR object labeling for visual search tasks in the spatial environment. In this paper, we identify and categorize different design aspects in AR label design and report on a formal user study on labels for out-of-view objects to support visual search tasks in AR. We design three visualization techniques for out-of-view object labeling in AR, which respectively encode the relative physical position (height-encoded), the rotational direction (angle-encoded), and the label values (value-encoded) of the objects. We further implement two traditional in-view object labeling techniques, where labels are placed either next to the respective objects (situated) or at the edge of the AR FoV (boundary). We evaluate these ve different label conditions in three visual search tasks for static objects. Our study shows that out-of-view object labels are benecial when searching for objects outside the FoV, spatial orientation, and when comparing multiple spatially sparse objects. Angle-encoded labels with directional cues of the surrounding objects have the overall best performance with the highest user satisfaction. We discuss the implications of our ndings for future immersive AR interface design.

7.
Front Genet ; 12: 768140, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966410

RESUMO

Cell migration-inducing hyaluronidase 1 (CEMIP), a Wnt-related protein and also known as KIAA1199, is implicated in the process of metastatic colonization in a variety of malignant tumors, including breast cancer (BC), which is one of the most frequently diagnosed tumors in women worldwide. In this study, multiple public databases, online analytical tools, and bioinformatics approaches were applied to explore the expression levels, regulatory mechanisms, and biological functions of CEMIP in BC. We illustrated that CEMIP was highly expressed in various kinds of carcinomas, including BC, especially advanced subtypes, and predicted less favorable prognosis (negatively associated with overall survival) in BC patients, which might be an independent prognostic factor. Then, we revealed that the mutation and high expression of CEMIP might lead to it as an oncogene. We also demonstrated that TP53 mutation, DNA hypo-methylation, and the expression changes of three potential upstream transcription factors (EZH2, EGR1, and JUN) of CEMIP were likely to cause the hyperexpression of CEMIP in BC. Moreover, our findings suggested that CEMIP might exert its carcinogenic roles in the tumor microenvironment via participation in the extracellular matrix formation, increasing cancer-associated fibroblast (CAF), M2 macrophage, and neutrophil infiltration and decreasing CD8+ T cell infiltration. In summary, our study provided more solid evidence for CEMIP as a prognostic and metastatic biomarker and a potential therapeutic target in BC. Of course, these findings also need more confirmations of basic experiments and further clinical trials in the future.

8.
IEEE Comput Graph Appl ; 41(6): 37-47, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34559644

RESUMO

We present how to integrate Design Sprints and project-based learning into introductory visualization courses. A design sprint is a unique process based on rapid prototyping and user testing to define goals and validate ideas before starting costly development. The well-defined, interactive, and time-constrained design cycle makes design sprints a promising option for teaching project-based and active-learning-centered courses to increase student engagement and hands-on experience. Over the past five years, we have adjusted the design sprint methodology for teaching a range of visualization courses. We present a detailed guide on incorporating design sprints into large undergraduate and small professional development courses in both online and on-campus settings. Design sprint results, including quantitative and qualitative student feedback, show that design sprints engage students and help practice and apply visualization and design skills. We provide design sprint teaching materials, show examples of student-created work, and discuss limitations and lessons learned.


Assuntos
Aprendizagem Baseada em Problemas , Estudantes , Humanos , Materiais de Ensino
9.
Cell Death Differ ; 28(10): 2857-2870, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33941870

RESUMO

Deubiquitinases (DUBs) regulate diverse biological processes and represent a novel class of drug targets. However, the biological function of only a small fraction of DUBs, especially in adaptive immune response regulation, is well-defined. In this study, we identified DUB ubiquitin-specific peptidase 12 (USP12) as a critical regulator of CD4+ T cell activation. USP12 plays an intrinsic role in promoting the CD4+ T cell phenotype, including differentiation, activation, and proliferation. Although USP12-deficient CD4+ T cells protected mice from autoimmune diseases, the immune response against bacterial infection was subdued. USP12 stabilized B cell lymphoma/leukemia 10 (BCL10) by deubiquitinating, and thereby activated the NF-κB signaling pathway. Interestingly, this USP12 regulatory mechanism was identified in CD4+ T cells, but not in CD8+ T cells. Our study results showed that USP12 activated CD4+ T cell signaling, and targeting USP12 might help develop therapeutic interventions for treating inflammatory diseases or pathogen infections.


Assuntos
Proteína 10 de Linfoma CCL de Células B/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Enzimas Desubiquitinantes/metabolismo , Linfócitos T/metabolismo , Ubiquitina Tiolesterase/metabolismo , Animais , Proliferação de Células , Camundongos
10.
Phytopathology ; 111(10): 1743-1750, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33656354

RESUMO

Clubroot caused by Plasmodiophora brassicae is an important disease on cruciferous crops worldwide. Management of clubroot is challenging, largely because of the millions of resting spores produced within an infected root that can survive dormant in the soil for many years. This study was conducted to investigate some of the environmental conditions that may affect the survival of resting spores in the soil. Soil samples containing clubroot resting spores (1 × 107 spores/g soil) were stored at various temperatures for 2 years. Additionally, other samples were buried in soil or kept on the soil surface in the field. The content of P. brassicae DNA and the numbers of viable spores in the samples were assessed by quantitative PCR (qPCR) and pathogenicity bioassays, respectively. The results indicated that 4°C, 20°C, and being buried in the soil were more conductive conditions for spore survival than -20°C, 30°C, and at the soil surface. Most (99.99%) of the spores kept on the soil surface were nonviable, suggesting a negative effect of light on spore viability. Additional experiments confirmed the negative effect of ultraviolet light on spore viability because spores receiving 2 and 3 h ultraviolet light exhibited lower disease potential and contained less DNA content than the nontreated control. Finally, this work confirmed that DNA-based quantification methods such as qPCR can be poor predictors of P. brassicae disease potential because of the presence and persistence of DNA from dead spores.


Assuntos
Plasmodioforídeos , Doenças das Plantas , Solo , Esporos , Temperatura
11.
IEEE Trans Vis Comput Graph ; 27(12): 4507-4519, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32746267

RESUMO

We introduce Tilt Map, a novel interaction technique for intuitively transitioning between 2D and 3D map visualisations in immersive environments. Our focus is visualising data associated with areal features on maps, for example, population density by state. Tilt Map transitions from 2D choropleth maps to 3D prism maps to 2D bar charts to overcome the limitations of each. Our article includes two user studies. The first study compares subjects' task performance interpreting population density data using 2D choropleth maps and 3D prism maps in virtual reality (VR). We observed greater task accuracy with prism maps, but faster response times with choropleth maps. The complementarity of these views inspired our hybrid Tilt Map design. Our second study compares Tilt Map to: a side-by-side arrangement of the various views; and interactive toggling between views. The results indicate benefits for Tilt Map in user preference; and accuracy (versus side-by-side) and time (versus toggle).

12.
IEEE Trans Vis Comput Graph ; 27(2): 1214-1224, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33048730

RESUMO

data has no natural scale and so interactive data visualizations must provide techniques to allow the user to choose their viewpoint and scale. Such techniques are well established in desktop visualization tools. The two most common techniques are zoom+pan and overview+detail. However, how best to enable the analyst to navigate and view abstract data at different levels of scale in immersive environments has not previously been studied. We report the findings of the first systematic study of immersive navigation techniques for 3D scatterplots. We tested four conditions that represent our best attempt to adapt standard 2D navigation techniques to data visualization in an immersive environment while still providing standard immersive navigation techniques through physical movement and teleportation. We compared room-sized visualization versus a zooming interface, each with and without an overview. We find significant differences in participants' response times and accuracy for a number of standard visual analysis tasks. Both zoom and overview provide benefits over standard locomotion support alone (i.e., physical movement and pointer teleportation). However, which variation is superior, depends on the task. We obtain a more nuanced understanding of the results by analyzing them in terms of a time-cost model for the different components of navigation: way-finding, travel, number of travel steps, and context switching.

13.
IEEE Trans Vis Comput Graph ; 27(2): 1677-1687, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33301404

RESUMO

Node-link diagrams are widely used to visualise networks. However, even the best network layout algorithms ultimately result in 'hairball' visualisations when the graph reaches a certain degree of complexity, requiring simplification through aggregation or interaction (such as filtering) to remain usable. Until now, there has been little data to indicate at what level of complexity node-link diagrams become ineffective or how visual complexity affects cognitive load. To this end, we conducted a controlled study to understand workload limits for a task that requires a detailed understanding of the network topology-finding the shortest path between two nodes. We tested performance on graphs with 25 to 175 nodes with varying density. We collected performance measures (accuracy and response time), subjective feedback, and physiological measures (EEG, pupil dilation, and heart rate variability). To the best of our knowledge this is the first network visualisation study to include physiological measures. Our results show that people have significant difficulty finding the shortest path in high density node-link diagrams with more than 50 nodes and even low density graphs with more than 100 nodes. From our collected EEG data we observe functional differences in brain activity between hard and easy tasks. We found that cognitive load increased up to certain level of difficulty after which it decreased, likely because participants had given up. We also explored the effects of global network layout features such as size or number of crossings, and features of the shortest path such as length or straightness on task difficulty. We found that global features generally had a greater impact than those of the shortest path.


Assuntos
Algoritmos , Gráficos por Computador , Cognição , Humanos
14.
Proc Natl Acad Sci U S A ; 118(1)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33372158

RESUMO

Macrophages are the principal immune cells of the epididymis and testis, but their origins, heterogeneity, development, and maintenance are not well understood. Here, we describe distinct populations of epididymal and testicular macrophages that display an organ-specific cellular identity. Combining in vivo fate-mapping, chimeric and parabiotic mouse models with in-depth cellular analyses, we found that CD64hiMHCIIlo and CD64loMHCIIhi macrophage populations of epididymis and testis arise sequentially from yolk sac erythro-myeloid progenitors, embryonic hematopoiesis, and nascent neonatal monocytes. While monocytes were the major developmental source of both epididymal and testicular macrophages, both populations self-maintain in the steady-state independent of bone marrow hematopoietic precursors. However, after radiation-induced macrophage ablation or during infection, bone marrow-derived circulating monocytes are recruited to the epididymis and testis, giving rise to inflammatory macrophages that promote tissue damage. These results define the layered ontogeny, maintenance and inflammatory response of macrophage populations in the male reproductive organs.


Assuntos
Infertilidade Masculina/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Animais , Diferenciação Celular , Linhagem da Célula , Epididimo/imunologia , Epididimo/metabolismo , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/imunologia , Testículo/imunologia , Testículo/metabolismo
15.
J Cell Mol Med ; 24(22): 13129-13138, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32967056

RESUMO

Vitamin B6 is necessary to maintain normal metabolism and immune response, especially the anti-inflammatory immune response. However, the exact mechanism by which vitamin B6 plays the anti-inflammatory role is still unclear. Here, we report a novel mechanism of preventing excessive inflammation by vitamin B6 via reduction in the accumulation of sphingosine-1-phosphate (S1P) in a S1P lyase (SPL)-dependent manner in macrophages. Vitamin B6 supplementation decreased the expression of pro-inflammatory cytokines by suppressing nuclear factor-κB and mitogen-activated protein kinases signalling pathways. Furthermore, vitamin B6-reduced accumulation of S1P by promoting SPL activity. The anti-inflammatory effects of vitamin B6 were inhibited by S1P supplementation or SPL deficiency. Importantly, vitamin B6 supplementation protected mice from lethal endotoxic shock and attenuated experimental autoimmune encephalomyelitis progression. Collectively, these findings revealed a novel anti-inflammatory mechanism of vitamin B6 and provided guidance on its clinical use.


Assuntos
Aldeído Liases/metabolismo , Inflamação/metabolismo , Lisofosfolipídeos/metabolismo , Macrófagos/metabolismo , Esfingosina/análogos & derivados , Vitamina B 6/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Progressão da Doença , Encefalomielite Autoimune Experimental/metabolismo , Lipopolissacarídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Choque/metabolismo , Transdução de Sinais , Esfingosina/metabolismo
16.
Artigo em Inglês | MEDLINE | ID: mdl-32276306

RESUMO

Lighting condition is essential to human performance. With the widespread use of computer-based learning, the performance measurements become difficult, and the effects of artificial lighting conditions towards the new learning forms are not investigated extensively. The current study conducts a subject-within experiment with a 45-min-long online learning along with electroencephalogram (EEG)-based measurements, and a post-interview under five lighting setups respectively (300 lx, 3000 K; 300 lx, 4000 K; 300 lx, 6500 K; 500 lx, 4000 K; 1000 lx, 4000 K). Attention is chosen as the key factor to represent the learning performance. The results show that the attention of people aged in the 20s is not affected by the experimental lighting conditions. The results also demonstrate that people in high illumination at 1000 lx are more inclined to sustain attention despite the discomfort and dissatisfaction. Taking the EEG-based attention measurements and post-interview answers into consideration, lighting conditions at 300 lx, 4000 K are the recommended set points for university architectures among the investigated conditions, providing a practical basis when adjusting the lighting standard for its advantage in energy saving.


Assuntos
Atenção , Aprendizagem , Iluminação , Cognição , Meio Ambiente , Humanos , Estimulação Luminosa
17.
Plant Dis ; 104(1): 116-120, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31644392

RESUMO

Clubroot, caused by Plasmodiophora brassicae, is an important disease on canola in Alberta, Canada. The pathogen is grouped into pathotypes according to their virulence reaction on differential hosts. Multiple pathotypes or strains are known exist in one field, one plant, or even one gall. This study was conducted with the objective of testing the prevalence of the coexistence of multiple strains in a single gall. In all, 79 canola clubroot galls were collected from 22 fields across Northern Alberta in 2018. Genomic DNA extracted from these single galls was analyzed using RNase H-dependent PCR (rhPCR). The rhPCR primers were designed to amplify a partial sequence of a dimorphic gene, with one primer pair specific to one sequence and the other primer pair specific to the alternative sequence. The amplification of both sequences from DNA obtained from a single gall would indicate that it contains two different P. brassicae strains. The rhPCR analyses indicated that the P. brassicae populations in 50 of the 79 galls consisted of more than one strain. This result emphasizes the need for cautious interpretation of results when a single-gall population is subject to pathotyping or being used as inoculum in plant pathology research. It also confirms that the maintenance of pathotype diversity within single root galls is a common occurrence which has implications for the durability, and stewardship, of single-gene host resistance.


Assuntos
Brassica napus , Plasmodioforídeos , Alberta , Doenças das Plantas/microbiologia , Raízes de Plantas/microbiologia , Tumores de Planta/microbiologia , Plasmodioforídeos/classificação , Plasmodioforídeos/genética , Plasmodioforídeos/patogenicidade , Virulência
18.
EMBO J ; 38(16): e101397, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31290162

RESUMO

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.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Células Dendríticas/imunologia , Encefalomielite Autoimune Experimental/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Animais , Apresentação do Antígeno , Autoimunidade , Linfócitos T CD4-Positivos/transplante , Polaridade Celular , Células Cultivadas , Células Dendríticas/citologia , Encefalomielite Autoimune Experimental/terapia , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos , Transdução de Sinais , Células Th1/citologia , Células Th1/metabolismo , Células Th17/citologia , Células Th17/metabolismo , Vacinação
19.
Front Immunol ; 9: 1778, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30166982

RESUMO

It is known that vitamin B1 (VB1) has a protective effect against oxidative retinal damage induced by anti-tuberculosis drugs. However, it remains unclear whether VB1 regulates immune responses during Mycobacterium tuberculosis (MTB) infection. We report here that VB1 promotes the protective immune response to limit the survival of MTB within macrophages and in vivo through regulation of peroxisome proliferator-activated receptor γ (PPAR-γ). VB1 promotes macrophage polarization into classically activated phenotypes with strong microbicidal activity and enhanced tumor necrosis factor-α and interleukin-6 expression at least in part by promoting nuclear factor-κB signaling. In addition, VB1 increases mitochondrial respiration and lipid metabolism and PPAR-γ integrates the metabolic and inflammatory signals regulated by VB1. Using both PPAR-γ agonists and deficient mice, we demonstrate that VB1 enhances anti-MTB activities in macrophages and in vivo by down-regulating PPAR-γ activity. Our data demonstrate important functions of VB1 in regulating innate immune responses against MTB and reveal novel mechanisms by which VB1 exerts its function in macrophages.


Assuntos
Imunidade Inata , Mycobacterium tuberculosis/imunologia , PPAR gama/metabolismo , Tiamina/metabolismo , Tuberculose/imunologia , Tuberculose/metabolismo , Animais , Biomarcadores , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata/efeitos dos fármacos , Imunofenotipagem , Metabolismo dos Lipídeos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Camundongos Transgênicos , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Tiamina/farmacologia , Tuberculose/microbiologia
20.
Artigo em Inglês | MEDLINE | ID: mdl-30136995

RESUMO

Immersive virtual- and augmented-reality headsets can overlay a flat image against any surface or hang virtual objects in the space around the user. The technology is rapidly improving and may, in the long term, replace traditional flat panel displays in many situations. When displays are no longer intrinsically flat, how should we use the space around the user for abstract data visualisation? In this paper, we ask this question with respect to origin-destination flow data in a global geographic context. We report on the findings of three studies exploring different spatial encodings for flow maps. The first experiment focuses on different 2D and 3D encodings for flows on flat maps. We find that participants are significantly more accurate with raised flow paths whose height is proportional to flow distance but fastest with traditional straight line 2D flows. In our second and third experiment we compared flat maps, 3D globes and a novel interactive design we call MapsLink, involving a pair of linked flat maps. We find that participants took significantly more time with MapsLink than other flow maps while the 3D globe with raised flows was the fastest, most accurate, and most preferred method. Our work suggests that careful use of the third spatial dimension can resolve visual clutter in complex flow maps.

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