ABSTRACT
Plasmacytoid dendritic cells (pDCs) are the main source of type I interferon (IFN-I) during viral infections. Their other functions are debated, due to a lack of tools to identify and target them in vivo without affecting pDC-like cells and transitional DCs (tDCs), which harbor overlapping phenotypes and transcriptomes but a higher efficacy for T cell activation. In the present report, we present a reporter mouse, pDC-Tom, designed through intersectional genetics based on unique Siglech and Pacsin1 coexpression in pDCs. The pDC-Tom mice specifically tagged pDCs and, on breeding with Zbtb46GFP mice, enabled transcriptomic profiling of all splenic DC types, unraveling diverging activation of pDC-like cells versus tDCs during a viral infection. The pDC-Tom mice also revealed initially similar but later divergent microanatomical relocation of splenic IFN+ versus IFN- pDCs during infection. The mouse models and specific gene modules we report here will be useful to delineate the physiological functions of pDCs versus other DC types.
Subject(s)
Dendritic Cells , Interferon Type I , Animals , Mice , Interferon Type I/metabolism , Gene Expression Profiling , Phenotype , TranscriptomeABSTRACT
Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN-I). What other functions pDCs exert in vivo during viral infections is controversial, and more studies are needed to understand their orchestration. In the present study, we characterize in depth and link pDC activation states in animals infected by mouse cytomegalovirus by combining Ifnb1 reporter mice with flow cytometry, single-cell RNA sequencing, confocal microscopy and a cognate CD4 T cell activation assay. We show that IFN-I production and T cell activation were performed by the same pDC, but these occurred sequentially in time and in different micro-anatomical locations. In addition, we show that pDC commitment to IFN-I production was marked early on by their downregulation of leukemia inhibitory factor receptor and was promoted by cell-intrinsic tumor necrosis factor signaling. We propose a new model for how individual pDCs are endowed to exert different functions in vivo during a viral infection, in a manner tightly orchestrated in time and space.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Dendritic Cells/immunology , Herpesviridae Infections/immunology , Muromegalovirus/physiology , Animals , Cells, Cultured , Interferon Type I/metabolism , Lymphocyte Activation , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Microscopy, Confocal , Sequence Analysis, RNA , Signal Transduction , Single-Cell Analysis , Tumor Necrosis Factor-alpha/metabolismABSTRACT
The classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127- and CD127+ early lymphoid progenitors (ELPs). Combining molecular analyses with in vitro and in vivo functional assays, we demonstrated that CD127- and CD127+ ELPs emerged independently from lympho-mono-dendritic progenitors, responded differently to Notch1 signals, underwent divergent modes of lineage restriction, and displayed both common and specific differentiation potentials. Whereas CD127- ELPs comprised precursors of T cells, marginal zone B cells, and natural killer (NK) and innate lymphoid cells (ILCs), CD127+ ELPs supported production of all NK cell, ILC, and B cell populations but lacked T potential. On the basis of these results, we propose a "two-family" model of human lymphoid development that differs from the prevailing model of hematopoiesis.
Subject(s)
B-Lymphocytes/metabolism , Killer Cells, Natural/metabolism , Lymphoid Progenitor Cells/metabolism , Lymphopoiesis/genetics , T-Lymphocytes/metabolism , Adolescent , Adult , Animals , B-Lymphocytes/cytology , Cell Differentiation/genetics , Cell Lineage/genetics , Cells, Cultured , Female , Gene Expression Profiling/methods , Humans , Interleukin Receptor Common gamma Subunit/deficiency , Interleukin Receptor Common gamma Subunit/genetics , Interleukin-7 Receptor alpha Subunit/genetics , Interleukin-7 Receptor alpha Subunit/metabolism , Killer Cells, Natural/cytology , Lymphoid Progenitor Cells/cytology , Lymphoid Progenitor Cells/transplantation , Male , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Middle Aged , Stem Cell Transplantation , T-Lymphocytes/cytology , Transplantation, Heterologous , Young AdultABSTRACT
BACKGROUND: Mental disorders are the leading global cause of health burden among adolescents. However, prevalence data for mental disorders among adolescents in low-income and middle-income countries are scarce with often limited generalisability. This study aimed to generate nationally representative prevalence estimates for mental disorders in adolescents in Kenya, Indonesia, and Viet Nam. METHODS: As part of the National Adolescent Mental Health Surveys (NAMHS), a multinational cross-sectional study, nationally representative household surveys were conducted in Kenya, Indonesia, and Viet Nam between March and December, 2021. Adolescents aged 10-17 years and their primary caregiver were interviewed from households selected randomly according to sampling frames specifically designed to elicit nationally representative results. Six mental disorders (social phobia, generalised anxiety disorder, major depressive disorder, post-traumatic stress disorder, conduct disorder, and attention-deficit hyperactivity disorder) were assessed with the Diagnostic Interview Schedule for Children, Version 5. Suicidal behaviours and self-harm in the past 12 months were also assessed. Prevalence in the past 12 months and past 4 weeks was calculated for each mental disorder and collectively for any mental disorder (ie, of the six mental disorders assessed). Prevalence of suicidal behaviours (ie, ideation, planning, and attempt) and self-harm in the past 12 months was calculated, along with adjusted odds ratios (aORs) to show the association with prevalence of any mental disorder in the past 12 months. Inverse probability weighting was applied to generate national estimates with corresponding 95% CIs. FINDINGS: Final samples consisted of 5155 households (ie, adolescent and primary caregiver pairs) from Kenya, 5664 households from Indonesia, and 5996 households from Viet Nam. In Kenya, 2416 (46·9%) adolescents were male and 2739 (53·1%) were female; in Indonesia, 2803 (49·5%) adolescents were male and 2861 (50·5%) were female; and in Viet Nam, 3151 (52·5%) were male and 2845 (47·4%) were female. Prevalence of any mental disorder in the past 12 months was 12·1% (95% CI 10·9-13·5) in Kenya, 5·5% (4·3-6·9) in Indonesia, and 3·3% (2·7-4·1) in Viet Nam. Prevalence in the past 4 weeks was 9·4% (8·3-10·6) in Kenya, 4·4% (3·4-5·6) in Indonesia, and 2·7% (2·2-3·3) in Viet Nam. The prevalence of suicidal behaviours in the past 12 months was low in all three countries, with suicide ideation ranging from 1·4% in Indonesia (1·0-2·0) and Viet Nam (1·0-1·9) to 4·6% (3·9-5·3) in Kenya, suicide planning ranging from 0·4% in Indonesia (0·3-0·8) and Viet Nam (0·2-0·6) to 2·4% (1·9-2·9) in Kenya, and suicide attempts ranging from 0·2% in Indonesia (0·1-0·4) and Viet Nam (0·1-0·3) to 1·0% (0·7-1·4) in Kenya. The prevalence of self-harm in the past 12 months was also low in all three countries, ranging from 0·9% (0·6-1·3) in Indonesia to 1·2% (0·9-1·7) in Kenya. However, the prevalence of suicidal behaviours and self-harm in the past 12 months was significantly higher among those with any mental disorder in the past 12 months than those without (eg, aORs for suicidal ideation ranged from 7·1 [3·1-15·9] in Indonesia to 14·7 [7·5-28·6] in Viet Nam). INTERPRETATION: NAMHS provides the first national adolescent mental disorders prevalence estimates for Kenya, Indonesia, and Viet Nam. These data can inform mental health and broader health policies in low-income and middle-income countries. FUNDING: The University of Queensland in America (TUQIA) through support from Pivotal Ventures, a Melinda French Gates company.
Subject(s)
Mental Disorders , Humans , Adolescent , Indonesia/epidemiology , Female , Cross-Sectional Studies , Male , Kenya/epidemiology , Prevalence , Vietnam/epidemiology , Child , Mental Disorders/epidemiology , Health SurveysABSTRACT
Dendritic cells (DCs) are instrumental in the initiation of T cell responses, but how thymic and peripheral tolerogenic DCs differ globally from Toll-like receptor (TLR)-induced immunogenic DCs remains unclear. Here, we show that thymic XCR1(+) DCs undergo a high rate of maturation, accompanied by profound gene-expression changes that are essential for central tolerance and also happen in germ-free mice. Those changes largely overlap those occurring during tolerogenic and, more unexpectedly, TLR-induced maturation of peripheral XCR1(+) DCs, arguing against the commonly held view that tolerogenic DCs undergo incomplete maturation. Interferon-stimulated gene (ISG) expression was among the few discriminators of immunogenic and tolerogenic XCR1(+) DCs. Tolerogenic XCR1(+) thymic DCs were, however, unique in expressing ISGs known to restrain virus replication. Therefore, a broad functional convergence characterizes tolerogenic and immunogenic XCR1(+) DC maturation in the thymus and periphery, maximizing antigen presentation and signal delivery to developing and to conventional and regulatory mature T cells.
Subject(s)
Central Tolerance , Dendritic Cells/immunology , Peripheral Tolerance , T-Lymphocytes, Regulatory/immunology , Thymus Gland/immunology , Animals , Antigen Presentation , Cell Differentiation , Cells, Cultured , Interferon Regulatory Factors/genetics , Lymphocyte Activation , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Chemokine/metabolism , Toll-Like Receptors/immunology , Transcriptome , Virus ReplicationABSTRACT
Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies.
Subject(s)
COVID-19 , Cytokines , Lung , Macrophages, Alveolar , Macrophages , SARS-CoV-2 , Humans , COVID-19/virology , COVID-19/immunology , SARS-CoV-2/physiology , Lung/virology , Lung/immunology , Lung/pathology , Macrophages/virology , Macrophages/metabolism , Macrophages/immunology , Macrophages, Alveolar/virology , Macrophages, Alveolar/immunology , Macrophages, Alveolar/metabolism , Cytokines/metabolism , Monocytes/virology , Monocytes/metabolism , Monocytes/immunology , Male , Female , Single-Cell Analysis , Middle AgedABSTRACT
BACKGROUND: Years of life lost (YLL) is recently used as a more insightful indicator to assess the mortality impact of COVID-19. However, this indicator still has methodological limits. This study aims to propose an alternative approach and new index, early-death weeks. METHODS: The natural mortality and social mortality laws were employed to support two essential assumptions: the sequential and translational early-mortality patterns of COVID-19. This approach was then used with the data related to COVID-19 to calculate early-death weeks associated with COVID-19 in France, the UK and the USA. RESULTS: As of week 20 of 2021, the rate of the total number of early-death weeks per the population of the USA is nearly two times compared to that of France and the UK, with 0.004% to 0.0021 and 0.0023%, respectively. The average numbers of early-death weeks after converting to units of years are 1.2, 1.0 and 1.3 years in France, the UK and the USA, respectively. CONCLUSIONS: The new approach is significantly different from death counts, excess deaths and YLL. The early-death week index provides more insights into COVID-19 and can be applied promptly at any time as well as anywhere once excess deaths have occurred.
Subject(s)
COVID-19 , Humans , France/epidemiology , United Kingdom/epidemiology , MortalityABSTRACT
The relationship between postures, sleep stages and eye state was established in two species of deer, the Indian sambar (Rusa unicolor) and sika deer (Cervus nippon), based on video recording. In both species, the state of rest or behavioral sleep was recorded in the sternal position, holding the head above the ground, and in the lateral position, with the head resting on the croup or on the ground. Rest accounted for at least 80% of the time in these positions. Based on behavior criteria a substantial portion of rest represented slow-wave sleep. Episodes of rapid eye movements (REM sleep) were recorded in the lateral position. They did not exceed 2 min. When the deer were in the sternal posture, they kept their eyes open most of the time: in average 96% of the time in sambars and 82% in sika deer. Episodes of the open eye in this posture lasted up to 8.4 min in sambars and up to 3.3 min in sika deer. In the lateral position, such episodes were 4 and 1.5 times shorter. Sleeping with open eyes in ungulates may be an important mechanism of maintaining vigilance.
Subject(s)
Deer , Animals , SleepABSTRACT
Background: The study was to evaluate the effectiveness of dose distribution of four-dimensional computed tomography (4DCT) simulation. Materials and methods: The gross tumor volume (GTV) and clinical target volume (CTV) were contoured in all 10 respiratory phases of 4DCT in 30 patients with non-small cell lung cancer (NSCLC). Both 3D and 4D treatment plans were made individually for each patient using the planning volume (PTV). The PTV3D was taken from a single CTV plus the recommended margin, and the PTV4D was taken from the 4D internal target volume, including all 10 CTVs plus the setup margins. Results: The mean PTV was 460 ± 179 (69-820) cm3 for 3DCT and 401 ± 167 (127-854) cm3 for 4DCT (p = 0.0018). The dose distribution (DD) of organs at risk, especially the lungs, was lower for the 4DCT simulation. The V5%, V10%, and V20% of the total lung dose for 4DCT were significantly lower for the 3DCT. However, lung V30% the heart, esophagus, and spinal cord were not significantly different. In addition, the conformity index and the dose heterogeneity index of the PTV were not significantly different. The normal tissue complication probability (NTCP) of the lung and heart was significantly lower for 4DCT than for 3DCT. Conclusions: The 4DCT simulation gives better results on the NTCP. The organs at risk, especially the lungs, receive a significantly lower DD compared with the 3DCT. The conformity index (CI), heterogeneity index (HI) and the DD to the heart, spinal cord, and esophagus were not significantly different between the two techniques.
ABSTRACT
Plasmacytoid dendritic cells (pDC) are the major source of type I interferons (IFN-I) during viral infections, in response to triggering of endosomal Toll-like receptors (TLRs) 7 or 9 by viral single-stranded RNA or unmethylated CpG DNA, respectively. Synthetic ligands have been used to disentangle the underlying signaling pathways. The adaptor protein AP3 is necessary to transport molecular complexes of TLRs, synthetic CpG DNA, and MyD88 into endosomal compartments allowing interferon regulatory factor 7 (IRF7) recruitment whose phosphorylation then initiates IFN-I production. High basal expression of IRF7 by pDC and its further enhancement by positive IFN-I feedback signaling appear to be necessary for robust cytokine production. In contrast, we show here that in vivo during mouse cytomegalovirus (MCMV) infection pDC produce high amounts of IFN-I downstream of the TLR9-to-MyD88-to-IRF7 signaling pathway without requiring IFN-I positive feedback, high IRF7 expression, or AP3-driven endosomal routing of TLRs. Hence, the current model of the molecular requirements for professional IFN-I production by pDC, established by using synthetic TLR ligands, does not strictly apply to a physiological viral infection.
Subject(s)
Dendritic Cells/immunology , Herpesviridae Infections/immunology , Interferon Type I/immunology , Muromegalovirus/immunology , Signal Transduction/immunology , Adaptor Protein Complex 3/genetics , Adaptor Protein Complex 3/immunology , Animals , Dendritic Cells/pathology , Endosomes/genetics , Endosomes/immunology , Herpesviridae Infections/genetics , Herpesviridae Infections/pathology , Interferon Regulatory Factor-7/genetics , Interferon Regulatory Factor-7/immunology , Interferon Type I/genetics , Membrane Glycoproteins/genetics , Membrane Glycoproteins/immunology , Mice , Mice, Knockout , Myeloid Differentiation Factor 88/genetics , Myeloid Differentiation Factor 88/immunology , Signal Transduction/genetics , Toll-Like Receptor 7/genetics , Toll-Like Receptor 7/immunology , Toll-Like Receptor 9/genetics , Toll-Like Receptor 9/immunologyABSTRACT
The Omics Discovery Index is an open source platform that can be used to access, discover and disseminate omics datasets. OmicsDI integrates proteomics, genomics, metabolomics, models and transcriptomics datasets. Using an efficient indexing system, OmicsDI integrates different biological entities including genes, transcripts, proteins, metabolites and the corresponding publications from PubMed. In addition, it implements a group of pipelines to estimate the impact of each dataset by tracing the number of citations, reanalysis and biological entities reported by each dataset. Here, we present the OmicsDI REST interface (www.omicsdi.org/ws/) to enable programmatic access to any dataset in OmicsDI or all the datasets for a specific provider (database). Clients can perform queries on the API using different metadata information such as sample details (species, tissues, etc), instrumentation (mass spectrometer, sequencer), keywords and other provided annotations. In addition, we present two different libraries in R and Python to facilitate the development of tools that can programmatically interact with the OmicsDI REST interface.
Subject(s)
Gene Expression Profiling/methods , Proteomics/methods , Software , Databases, Genetic , Datasets as Topic , Genomics/methods , Metabolomics/methods , User-Computer InterfaceABSTRACT
Computational modelling has become increasingly common in life science research. To provide a platform to support universal sharing, easy accessibility and model reproducibility, BioModels (https://www.ebi.ac.uk/biomodels/), a repository for mathematical models, was established in 2005. The current BioModels platform allows submission of models encoded in diverse modelling formats, including SBML, CellML, PharmML, COMBINE archive, MATLAB, Mathematica, R, Python or C++. The models submitted to BioModels are curated to verify the computational representation of the biological process and the reproducibility of the simulation results in the reference publication. The curation also involves encoding models in standard formats and annotation with controlled vocabularies following MIRIAM (minimal information required in the annotation of biochemical models) guidelines. BioModels now accepts large-scale submission of auto-generated computational models. With gradual growth in content over 15 years, BioModels currently hosts about 2000 models from the published literature. With about 800 curated models, BioModels has become the world's largest repository of curated models and emerged as the third most used data resource after PubMed and Google Scholar among the scientists who use modelling in their research. Thus, BioModels benefits modellers by providing access to reliable and semantically enriched curated models in standard formats that are easy to share, reproduce and reuse.
Subject(s)
Models, Biological , Biological Science Disciplines , Conflict of Interest , Programming Languages , Software , User-Computer InterfaceABSTRACT
White grub metacercariae were found in the livers and kidneys of diseased specimens of an introduced channel catfish, Ictalurus punctatus (Rafinesque), in Vietnam. Based on morphological features and 28S rDNA sequence analysis, the isolated metacercariae were identified as Dollfustrema bagarii (Digenea: Bucephalidae) Moravec & Sey. Histopathological examination shows that encysted metacercariae can change the tissue structure of the infected organs and is often accompanied by haemorrhaging and the presence of eosinophilic granular cell infiltration. Degenerative changes were also observed.
Subject(s)
Fish Diseases , Ictaluridae , Trematoda , Trematode Infections , Animals , Aquaculture , Metacercariae/genetics , Trematoda/genetics , Trematode Infections/veterinary , VietnamABSTRACT
In innate immune responses, induction of type-I interferons (IFNs) prevents virus spreading while viral replication is delayed by protein synthesis inhibition. We asked how cells perform these apparently contradictory activities. Using single fibroblast monitoring by flow cytometry and mathematical modeling, we demonstrate that type-I IFN production is linked to cell's ability to enter dsRNA-activated PKR-dependent translational arrest and then overcome this inhibition by decreasing eIF2α phosphorylation through phosphatase 1c cofactor GADD34 (Ppp1r15a) expression. GADD34 expression, shown here to be dependent on the IRF3 transcription factor, is responsible for a biochemical cycle permitting pulse of IFN synthesis to occur in cells undergoing protein synthesis inhibition. Translation arrest is further demonstrated to be key for anti-viral response by acting synergistically with MAVS activation to amplify TBK1 signaling and IFN-ß mRNA transcription, while GADD34-dependent protein synthesis recovery contributes to the heterogeneous expression of IFN observed in dsRNA-activated cells.
Subject(s)
Gene Expression Regulation , Interferon-beta/metabolism , Protein Biosynthesis , Protein Phosphatase 1/metabolism , RNA, Double-Stranded/immunology , RNA, Double-Stranded/metabolism , Animals , Cells, Cultured , Fibroblasts/immunology , Fibroblasts/virology , Flow Cytometry , Gene Expression Profiling , Immunity, Innate , Mice , Models, TheoreticalABSTRACT
BACKGROUND: The comorbid presence of tuberculosis and diabetes mellitus has become an increasingly important public health threat to the prevention and control of both diseases. Thus, household contact investigation may serve a dual purpose of screening for both tuberculosis and diabetes mellitus among household contacts. We therefore aimed to evaluate the coverage of screening for tuberculosis and diabetes mellitus among household contacts of tuberculosis index cases and to determine predictors of tuberculosis screening. METHODS: A household-based survey was conducted in February 2019 in Muang district of Phatthalung Province, Thailand where 95 index tuberculosis patients were newly diagnosed with pulmonary or pleural tuberculosis between October 2017 and September 2018. Household contacts of the index patients were interviewed using a structured questionnaire to ascertain their past-year history of tuberculosis screening and, if appropriate, diabetes mellitus screening. For children, the household head or an adult household member was interviewed as a proxy. Coverage of tuberculosis screening at the household level was regarded as households having all contacts screened for tuberculosis. Logistic regression and mixed-effects logistic regression models were used to determine predictors of tuberculosis screening at the household and individual levels, respectively, with the strengths of association presented as adjusted odds ratios (AOR) and 95% confidence intervals (CI). RESULTS: Of 61 responding households (64%), complete coverage of tuberculosis screening at the household level was 34.4% and among the 174 household contacts was 46.6%. About 20% of contacts did not receive any recommendation for tuberculosis screening. Households were more likely to have all members screened for tuberculosis if they were advised to be screened by a healthcare professional rather than someone else. At the individual level, contacts aged ≥35 years (AOR: 30.6, 95% CI: 2.0-466.0), being an employee (AOR: 0.1, 95% CI: 0.0-0.8) and those who had lived more than 5 years in the same household (AOR: 0.1, 95% CI: 0.0-0.8) were independent predictors for tuberculosis screening. Coverage of diabetes mellitus screening was 80.6% with lack of awareness being the main reason for not being screened. CONCLUSIONS: Compared to diabetes screening, the coverage of tuberculosis screening was low. A better strategy to improve coverage of tuberculosis contact screening is needed.
Subject(s)
Contact Tracing/statistics & numerical data , Diabetes Mellitus/diagnosis , Family Characteristics , Mass Screening/statistics & numerical data , Tuberculosis/diagnosis , Adolescent , Adult , Aged , Child , Cross-Sectional Studies , Diabetes Mellitus/prevention & control , Female , Humans , Infant , Logistic Models , Male , Odds Ratio , Outcome and Process Assessment, Health Care , Risk Factors , Surveys and Questionnaires , Thailand , Tuberculosis/prevention & controlABSTRACT
Immune response against pathogens is a tightly regulated process that must ensure microbial control while preserving integrity of the infected organs. Tuberculosis (TB) is a paramount example of a chronic infection in which antimicrobial immunity is protective in the vast majority of infected individuals but can become detrimental if not finely tuned. Here, we report that C-type lectin dendritic cell (DC) immunoreceptor (DCIR), a key component in DC homeostasis, is required to modulate lung inflammation and bacterial burden in TB. DCIR is abundantly expressed in pulmonary lesions in Mycobacterium tuberculosis-infected nonhuman primates during both latent and active disease. In mice, we found that DCIR deficiency impairs STAT1-mediated type I IFN signaling in DCs, leading to increased production of IL-12 and increased differentiation of T lymphocytes toward Th1 during infection. As a consequence, DCIR-deficient mice control M. tuberculosis better than WT animals but also develop more inflammation characterized by an increased production of TNF and inducible NOS (iNOS) in the lungs. Altogether, our results reveal a pathway by which a C-type lectin modulates the equilibrium between infection-driven inflammation and pathogen's control through sustaining type I IFN signaling in DCs.
Subject(s)
Dendritic Cells/immunology , Interferon Type I/immunology , Lectins, C-Type/immunology , Tuberculosis/immunology , Animals , Female , Lectins, C-Type/genetics , Macaca mulatta , Mice, Inbred C57BL , Mice, Knockout , Phosphorylation , STAT1 Transcription Factor/immunology , Signal TransductionABSTRACT
For decades, reports have suggested that photo-catalytic nitrogen fixation by titania in an aqueous environment is possible. Yet a consensus does not exist regarding how the reaction proceeds. Furthermore, the presence of an aqueous protonated solvent and the similarity between the redox potential for nitrogen and proton reduction suggest that ammonia production is unlikely. Here, we re-investigate photo-catalytic nitrogen fixation by titania in an aqueous environment through a series of photo-catalytic and electrocatalytic experiments. Photo-catalytic testing reveals that mineral phase and metal dopants play a marginal role in promoting nitrogen photofixation, with ammonia production increasing when the majority phase is rutile and with iron dopants. However, the presence of a trace amount of adsorbed carbonaceous species increased the rate of ammonia production by two times that observed without adsorbed carbon based species. This suggests that carbon species play a potential larger role in mediating the nitrogen fixation process over mineral phase and metal dopants. We also demonstrate an experimental approach aimed to detect low-level ammonia production from photo-catalysts using rotating ring disk electrode experiments conducted with and without illumination. Consistent with the photocatalysis, ammonia is only discernible at the ring with rutile phase titania, but not with mixed-phase titania. Rotating ring disk electrode experiments may also provide a new avenue to attain a higher degree of precision in detecting ammonia at low levels.
Subject(s)
Carbon/chemistry , Nitrogen Fixation , Titanium/chemistry , Catalysis , Electrochemical Techniques , Photochemical Processes , Surface Properties , Water/chemistryABSTRACT
This study aims to analyze compositions of fatty acids and phospholipid molecular species in the hard clams Meretrix lyrata (Sowerby, 1851) harvested from Cua Lo beach, Nghe An province, Viet Nam. Total lipid of hard clams Meretrix lyrata occupied 1.7 ± 0.2% of wet weight and contained six classes: hydrocarbon and wax (HW), triacylglycerol (TAG), free fatty acids (FFA), sterol (ST), polar lipid (PoL), and monoalkyl diacylglycerol (MADAG). Among the constituents, the proportion of PoL accounted was highest, at 45.7%. In contrast, the figures for MADAG were lowest, at 1.3%. Twenty-six fatty acids were identified with the ratios of USAFA/SAFA was 2. The percentage of n-3 PUFA (ω-3) and n-6 PUFA (ω-6) was high, occupying 38.4% of total FA. Among PUFAs, arachidonic acid (AA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid (DPA, 22:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) accounted for 3.8%, 7.8%, 2.2% and 12.0% of total lipid of the clam respectively. Phospholipid molecular species were identified in polar lipids of the clams consisting six types: phosphatidylethalnolamine (PE, with 28 molecular species), phosphatidylcholine (PC, with 26 molecular species), phosphatidylserine (PS, with 18 molecular species), phosphatidylinositol (PI, with 10 molecular species), phosphatidylglycerol (PG, with only one molecular species), and ceramide aminoethylphosphonate (CAEP, with 15 molecular species). This is the first time that the molecular species of sphingophospholipid were determined, in Meretrix lyrata in particular, and for clams in general. Phospholipid formula species of PE and PS were revealed to comprise two kinds: Alkenyl acyl glycerophosphoethanolamine and Alkenyl acyl glycerophosphoserine occupy 80.3% and 81.0% of total PE and PS species, respectively. In contrast, the percentage of diacyl glycero phosphatidylcholine was twice as high as that of PakCho in total PC, at 69.3, in comparison with 30.7%. In addition, phospholipid formula species of PI and PG comprised only diacyl glycoro phospholipids. PE 36:1 (p18:0/18:1), PC 38:6 (16:0/22:6), PS 38:1 (p18:0/20:1), PI 40:5 (20:1/20:4), PG 32:0 (16:0/16:0) and CAEP 34:2 (16:2/d18:0) were the major molecular species.
Subject(s)
Bivalvia/chemistry , Fatty Acids/analysis , Phospholipids/analysis , Animals , Chromatography, High Pressure Liquid , Molecular Structure , Principal Component Analysis , Tandem Mass Spectrometry , VietnamABSTRACT
Nickel supported CdIn2S4 (Ni-CIS) spongy-like spheres have been developed using alcoholysis followed by a sulfidation process. The formation of nanocrystalline-single phase CdIn2S4 was confirmed using X-ray diffraction studies. Electron microscopy images showed that the spongy-like spheres are composed of CdIn2S4 nanoparticles with average sizes of around 25 nm. X-ray photoelectron spectra indicated the presence of elements with their respective stable oxidation states that led to the formation of single phase CdIn2S4 with enhanced structural integrity and chemical composition. The absorption spectra indicated the visible light activity of the material and the band gap energy is deduced to be 2.23 eV. The photocatalytic efficiency of the synthesized Ni-CIS in relation to its ability to produce hydrogen under solar light irradiation is estimated to be 1060 µmol g-1 h-1, which is around 5.5 and 3.6 fold higher than that of Pt-CIS (180 µmol g-1 h-1) and Pd-CIS (290 µmol g-1 h-1), respectively, as obtained in this study. Accordingly, the mechanism of the observed efficiency of the Ni-CIS nanoparticles is also proposed. The recyclability test showed consistent hydrogen evolution efficiency over 3 cycles (9 h), which essentially revealed the excellent photo- and chemical-stability of the photocatalyst. The strategy to utilize non-noble metals such as Ni, rather than noble-metals, as a co-catalyst opens up a new possibility to develop low cost and high-performance sunlight-driven photocatalysts as achieved in this study.
ABSTRACT
The existence of conventional dendritic cells (cDCs) has not yet been demonstrated outside mammals. In this article, we identified bona fide cDCs in chicken spleen. Comparative profiling of global and of immune response gene expression, morphology, and T cell activation properties show that cDCs and macrophages (MPs) exist as distinct mononuclear phagocytes in the chicken, resembling their human and mouse cell counterparts. With computational analysis, core gene expression signatures for cDCs, MPs, and T and B cells across the chicken, human, and mouse were established, which will facilitate the identification of these subsets in other vertebrates. Overall, this study, by extending the newly uncovered cDC and MP paradigm to the chicken, suggests that these two phagocyte lineages were already in place in the common ancestor of reptiles (including birds) and mammals in evolution. It opens avenues for the design of new vaccines and nutraceuticals that are mandatory for the sustained supply of poultry products in the expanding human population.