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Group 2 innate lymphoid cells (ILC2s) are highly heterogeneous tissue-resident lymphocytes that regulate inflammation and tissue homeostasis in health and disease. However, how these cells integrate into the tissue microenvironment to perform tissue-specific functions is unclear. Here, we show neuropilin-1 (Nrp1), which is induced postnatally and sustained by lung-derived transforming growth factor beta-1 (TGFß1), is a tissue-specific marker of lung ILC2s. Genetic ablation or pharmacological inhibition of Nrp1 suppresses IL-5 and IL-13 production by ILC2s and protects mice from the development of pulmonary fibrosis. Mechanistically, TGFß1-Nrp1 signaling enhances ILC2 function and type 2 immunity by upregulating IL-33 receptor ST2 expression. These findings identify Nrp1 as a tissue-specific regulator of lung-resident ILC2s and highlight Nrp1 as a potential therapeutic target for pulmonary fibrosis.
Assuntos
Imunidade Inata/imunologia , Pulmão/imunologia , Neuropilina-1/imunologia , Animais , Modelos Animais de Doenças , Inflamação/imunologia , Interleucina-33/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Endogâmicos ICR , Fibrose Pulmonar/imunologia , Transdução de Sinais/imunologiaRESUMO
Adipose tissue group 2 innate lymphoid cells (ILC2s) help maintain metabolic homeostasis by sustaining type 2 immunity and promoting adipose beiging. Although impairment of the ILC2 compartment contributes to obesity-associated insulin resistance, the underlying mechanisms have not been elucidated. Here, we found that ILC2s in obese mice and humans exhibited impaired liver kinase B1 (LKB1) activation. Genetic ablation of LKB1 disrupted ILC2 mitochondrial metabolism and suppressed ILC2 responses, resulting in exacerbated insulin resistance. Mechanistically, LKB1 deficiency induced aberrant PD-1 expression through activation of NFAT, which in turn enhanced mitophagy by suppressing Bcl-xL expression. Blockade of PD-1 restored the normal functions of ILC2s and reversed obesity-induced insulin resistance in mice. Collectively, these data present the LKB1-PD-1 axis as a promising therapeutic target for the treatment of metabolic disease.
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Tecido Adiposo , Homeostase , Resistência à Insulina , Linfócitos , Mitocôndrias , Obesidade , Receptor de Morte Celular Programada 1 , Proteínas Serina-Treonina Quinases , Animais , Resistência à Insulina/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Mitocôndrias/metabolismo , Humanos , Tecido Adiposo/metabolismo , Tecido Adiposo/imunologia , Obesidade/imunologia , Obesidade/metabolismo , Linfócitos/imunologia , Linfócitos/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Imunidade Inata , Masculino , Mitofagia/imunologia , Quinases Proteína-Quinases Ativadas por AMPRESUMO
Humoral immunity depends on the germinal center (GC) reaction where B cells are tightly controlled for class-switch recombination and somatic hypermutation and finally generated into plasma and memory B cells. However, how protein SUMOylation regulates the process of the GC reaction remains largely unknown. Here, we show that the expression of SUMO-specific protease 1 (SENP1) is up-regulated in GC B cells. Selective ablation of SENP1 in GC B cells results in impaired GC dark and light zone organization and reduced IgG1-switched GC B cells, leading to diminished production of class-switched antibodies with high-affinity in response to a TD antigen challenge. Mechanistically, SENP1 directly binds to Paired box protein 5 (PAX5) to mediate PAX5 deSUMOylation, sustaining PAX5 protein stability to promote the transcription of activation-induced cytidine deaminase. In summary, our study uncovers SUMOylation as an important posttranslational mechanism regulating GC B cell response.
Assuntos
Linfócitos B , Cisteína Endopeptidases , Centro Germinativo , Fator de Transcrição PAX5 , Sumoilação , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Fator de Transcrição PAX5/metabolismo , Fator de Transcrição PAX5/genética , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Cisteína Endopeptidases/metabolismo , Cisteína Endopeptidases/genética , Camundongos , Switching de Imunoglobulina , Humanos , Citidina Desaminase/metabolismo , Citidina Desaminase/genética , Imunidade Humoral , Camundongos Endogâmicos C57BLRESUMO
Electrochemical CO2 reduction provides a potential means for synthesizing value-added chemicals over the near equilibrium potential regime, i.e., formate production on Pd-based catalysts. However, the activity of Pd catalysts has been largely plagued by the potential-depended deactivation pathways (e.g., [Formula: see text]-PdH to [Formula: see text]-PdH phase transition, CO poisoning), limiting the formate production to a narrow potential window of 0 V to -0.25 V vs. reversible hydrogen electrode (RHE). Herein, we discovered that the Pd surface capped with polyvinylpyrrolidone (PVP) ligand exhibits effective resistance to the potential-depended deactivations and can catalyze formate production at a much extended potential window (beyond -0.7 V vs. RHE) with significantly improved activity (~14-times enhancement at -0.4 V vs. RHE) compared to that of the pristine Pd surface. Combined results from physical and electrochemical characterizations, kinetic analysis, and first-principle simulations suggest that the PVP capping ligand can effectively stabilize the high-valence-state Pd species (Pdδ+) resulted from the catalyst synthesis and pretreatments, and these Pdδ+ species are responsible for the inhibited phase transition from [Formula: see text]-PdH to [Formula: see text]-PdH, and the suppression of CO and H2 formation. The present study confers a desired catalyst design principle, introducing positive charges into Pd-based electrocatalyst to enable efficient and stable CO2 to formate conversion.
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The N6-methyladenosine (m6 A) RNA modification serves crucial functions in RNA metabolism; however, the molecular mechanisms underlying the regulation of m6 A are not well understood. Here, we establish arginine methylation of METTL14, a component of the m6 A methyltransferase complex, as a novel pathway that controls m6 A deposition in mammalian cells. Specifically, protein arginine methyltransferase 1 (PRMT1) interacts with, and methylates the intrinsically disordered C terminus of METTL14, which promotes its interaction with RNA substrates, enhances its RNA methylation activity, and is crucial for its interaction with RNA polymerase II (RNAPII). Mouse embryonic stem cells (mESCs) expressing arginine methylation-deficient METTL14 exhibit significantly reduced global m6 A levels. Transcriptome-wide m6 A analysis identified 1,701 METTL14 arginine methylation-dependent m6 A sites located in 1,290 genes involved in various cellular processes, including stem cell maintenance and DNA repair. These arginine methylation-dependent m6 A sites are associated with enhanced translation of genes essential for the repair of DNA interstrand crosslinks; thus, METTL14 arginine methylation-deficient mESCs are hypersensitive to DNA crosslinking agents. Collectively, these findings reveal important aspects of m6 A regulation and new functions of arginine methylation in RNA metabolism.
Assuntos
Adenosina/análogos & derivados , Arginina/química , Metiltransferases/metabolismo , Células-Tronco Embrionárias Murinas/metabolismo , Processamento de Proteína Pós-Traducional , Proteína-Arginina N-Metiltransferases/metabolismo , RNA Polimerase II/metabolismo , Adenosina/química , Animais , Citoplasma , Metiltransferases/química , Metiltransferases/genética , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Proteína-Arginina N-Metiltransferases/genética , RNA Polimerase II/genética , TranscriptomaRESUMO
ConspectusElectrides make up a fascinating group of materials with unique physical and chemical properties. In these materials, excess electrons do not behave like normal electrons in metals or form any chemical bonds with atoms. Instead, they "float" freely in the gaps within the material's structure, acting like negatively charged particles called anions (see the graph). Recently, there has been a surge of interest in van der Waals (vdW) electrides or electrenes in two dimensions. A typical example is layered lanthanum bromide (LaBr2), which can be taken as [La3+(Br1-)2]+â¢(e-). Each excess free electron is trapped within a hexagonal pore, forming dense dots of electron density. These anionic electrons are loosely bound, giving vdW electrides some unique properties such as ferromagnetism, superconductivity, topological features, and Dirac plasmons. The high density of the free electron makes electrides very promising for applications in thermionic emission, organic light-emitting diodes, and high-performance catalysts.In this Account, we first discuss the discovery of numerous vdW electrides through high-throughput computational screening of over 67,000 known inorganic crystals in Materials Project. A dozen of them have been newly discovered and have not been reported before. Importantly, they possess completely different structural prototypes and properties of anionic electrons compared to widely studied electrides such as Ca2N. Finding these new vdW electrides expands the variety of electrides that can be made in the experiment and opens up new possibilities for studying their unique properties and applications.Then, based on the screened vdW electrides, we delve into their various emerging properties. For example, we developed a new magnetic mechanism specific to atomic-orbital-free ferromagnetism in electrides. We uncover the dual localized and extended nature of the anionic electrons in such electrides and demonstrate the formation of the local moment by the localized feature and the ferromagnetic interaction by the direct overlapping of their extended states. We further show the effective tuning of the magnetic properties of vdW electrides by engineering their structural, electronic, and compositional properties. Besides, we show that the complex interaction between the multiple quantum orderings in vdW electrides leads to many interesting properties including valley polarization, charge density waves, a topological property, a superconducting property, and a thermoelectrical property.Moreover, we discuss strategies to leverage the unique intrinsic properties of vdW electrides for practical applications. We show that these properties make vdW electrides potential candidates for advanced applications such as spin-orbit torque memory devices, valleytronic devices, K-ion batteries, and thermoelectricity. Finally, we discuss the current challenges and future perspectives for research using these emerging materials.
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Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.
Assuntos
Mapeamento Encefálico , Indóis , Imageamento por Ressonância Magnética , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Odorantes , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Percepção Olfatória/fisiologia , Emoções/fisiologia , Olfato/fisiologiaRESUMO
Pepper (Capsicum annuum) responds differently to high temperature stress (HTS) and Ralstonia solanacearum infection (RSI) but employs some shared transcription factors (TFs), such as CabZIP63 and CaWRKY40, in both cases. How the plant activates and balances these distinct responses, however, was unclear. Here, we show that the protein CaSWC4 interacts with CaRUVBL2 and CaTAF14b and they all act positively in pepper response to RSI and thermotolerance. CaSWC4 activates chromatin of immunity or thermotolerance related target genes of CaWRKY40 or CabZIP63 by promoting deposition of H2A.Z, H3K9ac and H4K5ac, simultaneously recruits CabZIP63 and CaWRKY40 through physical interaction and brings them to their targets (immunity- or thermotolerance-related genes) via binding AT-rich DNA element. The above process relies on the recruitment of CaRUVBL2 and TAF14 by CaSWC4 via physical interaction, which occurs at loci of immunity related target genes only when the plants are challenged with RSI, and at loci of thermotolerance related target genes only upon HTS. Collectively, our data suggest that CaSWC4 regulates rapid, accurate responses to both RSI and HTS by modulating chromatin of specific target genes opening and recruiting the TFs, CaRUVBL2 and CaTAF14b to the specific target genes, thereby helping achieve the balance between immunity and thermotolerance.
Assuntos
Capsicum , Ralstonia solanacearum , Termotolerância , Capsicum/genética , Cromatina/genética , Cromatina/metabolismo , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Inativação Gênica , Doenças das Plantas/genética , Reguladores de Crescimento de Plantas/metabolismo , Imunidade Vegetal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ralstonia solanacearum/genética , Ralstonia solanacearum/metabolismoRESUMO
Vγ9Vδ2 T cells play an important role in the development and progression of psoriasis vulgaris (PV), but how they promote skin inflammation and the molecular mechanisms underlying Vγ9Vδ2 T cell dysfunction are poorly understood. Here, we show that circulating Vγ9Vδ2 T cells are decreased and exhibit enhanced proliferation and increased production of IFN-γ and TNF-α in PV patients. Monocytes from PV patients express higher levels of the phosphoantigen sensor butyrophilin 3A1 (BTN3A1) than monocytes from healthy controls. Blockade of BTN3A1 suppresses Vγ9Vδ2 T cell activation and abolishes the difference in Vγ9Vδ2 T cell activation between PV patients and healthy controls. The CD14+ cells in PV skin lesions highly express BTN3A1 and juxtapose to Vδ2 T cells. In addition, IFN-γ induces the up-regulation of BTN3A1 on monocytes. Collectively, our results demonstrate a crucial role of BTN3A1 on monocytes in regulating Vγ9Vδ2 T cell activation and highlight BTN3A1 as a potential therapeutic target for psoriasis.
Assuntos
Psoríase , Receptores de Antígenos de Linfócitos T gama-delta , Humanos , Butirofilinas/metabolismo , Regulação para Cima , Fator de Necrose Tumoral alfa , Antígenos , Antígenos CD , Ativação Linfocitária , Linfócitos TRESUMO
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19), which is most frequently mild yet can be severe and life-threatening. Virus-neutralizing monoclonal antibodies are predicted to reduce viral load, ameliorate symptoms, and prevent hospitalization. METHODS: In this ongoing phase 2 trial involving outpatients with recently diagnosed mild or moderate Covid-19, we randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes. The primary outcome was the change from baseline in the viral load at day 11. The results of a preplanned interim analysis as of September 5, 2020, are reported here. RESULTS: At the time of the interim analysis, the observed mean decrease from baseline in the log viral load for the entire population was -3.81, for an elimination of more than 99.97% of viral RNA. For patients who received the 2800-mg dose of LY-CoV555, the difference from placebo in the decrease from baseline was -0.53 (95% confidence interval [CI], -0.98 to -0.08; P = 0.02), for a viral load that was lower by a factor of 3.4. Smaller differences from placebo in the change from baseline were observed among the patients who received the 700-mg dose (-0.20; 95% CI, -0.66 to 0.25; P = 0.38) or the 7000-mg dose (0.09; 95% CI, -0.37 to 0.55; P = 0.70). On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo. The percentage of patients who had a Covid-19-related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group. CONCLUSIONS: In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.).
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Neutralizantes/administração & dosagem , Tratamento Farmacológico da COVID-19 , Fatores Imunológicos/administração & dosagem , SARS-CoV-2/isolamento & purificação , Carga Viral/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Neutralizantes/efeitos adversos , COVID-19/virologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , RNA Viral/sangue , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , Índice de Gravidade de Doença , Adulto JovemRESUMO
BACKGROUND: Patients with underlying medical conditions are at increased risk for severe coronavirus disease 2019 (Covid-19). Whereas vaccine-derived immunity develops over time, neutralizing monoclonal-antibody treatment provides immediate, passive immunity and may limit disease progression and complications. METHODS: In this phase 3 trial, we randomly assigned, in a 1:1 ratio, a cohort of ambulatory patients with mild or moderate Covid-19 who were at high risk for progression to severe disease to receive a single intravenous infusion of either a neutralizing monoclonal-antibody combination agent (2800 mg of bamlanivimab and 2800 mg of etesevimab, administered together) or placebo within 3 days after a laboratory diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The primary outcome was the overall clinical status of the patients, defined as Covid-19-related hospitalization or death from any cause by day 29. RESULTS: A total of 1035 patients underwent randomization and received an infusion of bamlanivimab-etesevimab or placebo. The mean (±SD) age of the patients was 53.8±16.8 years, and 52.0% were adolescent girls or women. By day 29, a total of 11 of 518 patients (2.1%) in the bamlanivimab-etesevimab group had a Covid-19-related hospitalization or death from any cause, as compared with 36 of 517 patients (7.0%) in the placebo group (absolute risk difference, -4.8 percentage points; 95% confidence interval [CI], -7.4 to -2.3; relative risk difference, 70%; P<0.001). No deaths occurred in the bamlanivimab-etesevimab group; in the placebo group, 10 deaths occurred, 9 of which were designated by the trial investigators as Covid-19-related. At day 7, a greater reduction from baseline in the log viral load was observed among patients who received bamlanivimab plus etesevimab than among those who received placebo (difference from placebo in the change from baseline, -1.20; 95% CI, -1.46 to -0.94; P<0.001). CONCLUSIONS: Among high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of Covid-19-related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.).
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , COVID-19/etnologia , COVID-19/virologia , Criança , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Carga Viral/efeitos dos fármacos , Adulto JovemRESUMO
As cost-effective catalysts, platinum (Pt) single-atom catalysts (SACs) have attracted substantial attention. However, most studies indicate that Pt SACs in acidic hydrogen evolution reaction (HER) follow the slow Volmer-Heyrovsky (VH) mechanism instead of the fast kinetic Volmer-Tafel (VT) pathway. Here, this work propose that the VH mechanism in Pt SACs can be switched to the faster VT pathway for efficient HER by correlating Pt single atoms (SAs) with Pt clusters (Cs). Our calculations reveal that the correlation between Pt SAs and Cs significantly impacts the electronic structure of exposed Pt atoms, lowering the adsorption barrier for atomic hydrogen and enabling a faster VT mechanism. To validate these findings, this work purposely synthesize three catalysts: l-Pt@MoS2, m-Pt@MoS2 and h-Pt@MoS2 with low, moderate, and high Pt-loading, having different distributions of Pt SAs and Cs. The m-Pt@MoS2 catalyst with properly correlating Pt SAs and Cs exhibits outstanding performance with an overpotential of 47 mV and Tafel slope of 32 mV dec-1. Further analysis of the Tafel values confirms that the m-Pt@MoS2 sample indeed follows the VT reaction mechanism, aligning with the theoretical findings. This study offers a deep understanding of the synergistic mechanism, paving a way for designing novel-advanced catalysts.
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Accurate construction of artificial nano-chaperones' structure is crucial for precise regulation of protein conformational transformation, facilitating effective treatment of proteopathy. However, how the ligand-anchors of nano-chaperones affect the spatial conformational changes in proteins remains unclear, limiting the development of efficient nano-chaperones. In this study, three types of gold nanoparticles (AuNPs) with different core/ligands interface anchor structures (AuâNHâR, AuâSâR, and AuâC≡CâR, R = benzoic acid) are synthesized as an ideal model to investigate the effect of interfacial anchors on Aß and amylin fibrillization. Computational results revealed that the distinct interfacial anchors imparted diverse distributions of electrostatic potential on the nanointerface and core/ligands bond strength of AuNPs, leading to differential interactions with amyloid peptides. Experimental results demonstrated that all three types of AuNPs exhibit site-specific inhibitory effects on Aß40 fibrillization due to preferential binding. For amylin, amino-anchored AuNPs demonstrate strong adsorption to multiple sites on amylin and effectively inhibit fibrillization. Conversely, thiol- and alkyne-anchored AuNPs adsorb at the head region of amylin, promoting folding and fibrillization. This study not only provided molecular insights into how core/ligands interfacial anchors of nanomaterials induce spatial conformational changes in amyloid peptides but also offered guidance for precisely engineering artificial-chaperones' nanointerfaces to regulate the conformational transformation of proteins.
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A rational design of sulfur host is the key to conquering the"polysulfide shuttle effects" by accelerating the polysulfide conversion. Since the process involves solid-liquid-solid multistep phase transitions, purposely-engineered heterostructure catalysts with various active regions for catalyzing conversion steps correspondingly are beneficial to promote the overall conversion process. However, the functionalities of the materials surface and interface in heterostructure catalysts remain unclear. In this work, an Mo2C/MoC catalyst with abundant Mo2C surface-interface-MoC surface tri-active-region is developed by in situ converting the MoZn-metal organic framework. The experimental and simulation studies demonstrate the interface can catch long-chain polysulfides and promote their conversion. Instead, the Mo2C and MoC tend to accommodate the short-chain polysulfide and accelerate their conversion and the Li2S dissociation. Benefitting from the high catalytic ability, the Li-S battery assembled with the Mo2C/MoC-S cathode shows more discrete redox reactions and delivers a high initial capacity of 1603.6 mAh g-1 at 1 C charging-discharging rate, which is over twofolds of the one assembled using individual hosts, and 80.4% capacity can be maintained after 1000 cycles at 3 C rate. This work has demonstrated a novel synergy between the interface and material surface, which will help the future design of high-performance Li-S batteries.
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Plant diseases tend to be more serious under conditions of high-temperature/high-humidity (HTHH) than under moderate conditions, and hence disease resistance under HTHH is an important determinant for plant survival. However, how plants cope with diseases under HTHH remains poorly understood. In this study, we used the pathosystem consisting of pepper (Capsicum annuum) and Ralstonia solanacearum (bacterial wilt) as a model to examine the functions of the protein mildew resistance locus O 1 (CaMLO1) and U-box domain-containing protein 21 (CaPUB21) under conditions of 80% humidity and either 28 °C or 37 °C. Expression profiling, loss- and gain-of-function assays involving virus-induced gene-silencing and overexpression in pepper plants, and protein-protein interaction assays were conducted, and the results showed that CaMLO1 acted negatively in pepper immunity against R. solanacearum at 28 °C but positively at 37 °C. In contrast, CaPUB21 acted positively in immunity at 28 °C but negatively at 37 °C. Importantly, CaPUB21 interacted with CaMLO1 under all of the tested conditions, but only the interaction in response to R. solanacearum at 37 °C or to exposure to 37 °C alone led to CaMLO1 degradation, thereby turning off defence responses against R. solanacearum at 37 °C and under high-temperature stress to conserve resources. Thus, we show that CaMLO1 and CaPUB21 interact with each other and function distinctly in pepper immunity against R. solanacearum in an environment-dependent manner.
Assuntos
Capsicum , Ralstonia solanacearum , Termotolerância , Imunidade Vegetal/fisiologia , Temperatura , Proteínas de Plantas/metabolismo , Resistência à Doença , Doenças das Plantas/microbiologia , Ralstonia solanacearum/fisiologia , Capsicum/metabolismo , Regulação da Expressão Gênica de PlantasRESUMO
In contrast to delayed-type hypersensitivity (DTH) and other hallmark reactions of cell-mediated immunity that correlate with vaccine-mediated protection against Mycobacterium tuberculosis, the contribution of vaccine dose on responses that emerge early after infection in the skin with Bacille Calmette-Guérin (BCG) is not well understood. We used a mouse model of BCG skin infection to study the effect of BCG dose on the relocation of skin Dendritic cells (DCs) to draining lymph node (DLN). Mycobacterium antigen 85B-specific CD4+ P25 T cell-receptor transgenic (P25 TCRTg) cells were used to probe priming to BCG in DLN. DC migration and T cell priming were studied across BCG inocula that varied up to 100-fold (104 to 106 Colony-forming units-CFUs). In line with earlier results in guinea pigs, DTH reaction in our model correlated with BCG dose. Importantly, priming of P25 TCRTg cells in DLN also escalated in a dose-dependent manner, peaking at day 6 after infection. Similar dose-escalation effects were seen for DC migration from infected skin and the accompanying transport of BCG to the DLN. BCG-triggered upregulation of co-stimulatory molecules on migratory DCs was restricted to the first 24 hour after infection and was independent of BCG dose over a 10-fold range (105 to 106 CFUs). The dose seemed to be a determinant of the number of total skin DCs that move to the DLN. In summary, our results support the use of higher BCG doses to detect robust DC migration and T cell priming.
Assuntos
Vacina BCG , Linfócitos T , Camundongos , Animais , Cobaias , Imunidade Celular , Células de Langerhans , LinfonodosRESUMO
Droughts have been implicated as the main driver behind recent vegetation die-off and are projected to drive greater mortality under future climate change. Understanding the coupling relationship between vegetation and drought has been of great global interest. Currently, the coupling relationship between vegetation and drought is mainly evaluated by correlation coefficients or regression slopes. However, the optimal drought timescale of vegetation response to drought, as a key indicator reflecting vegetation sensitivity to drought, has largely been ignored. Here, we apply the optimal drought timescale identification method to examine the change in coupling between vegetation and drought over the past three decades (1982-2015) with long-term satellite-derived Normalized Difference Vegetation Index and Standardized Precipitation-Evapotranspiration Index data. We find substantial increasing response of vegetation to drought timescales globally, and the correlation coefficient between vegetation and drought under optimal drought timescale overall declines between 1982 and 2015. This decrease in vegetation-drought coupling is mainly observed in regions with water deficit, although its initial correlation is relatively high. However, vegetation in water-surplus regions, with low coupling in earlier stages, is prone to show an increasing trend. The observed changes may be driven by the increasing trend of atmospheric CO2 . Our findings highlight more pressing drought risk in water-surplus regions than in water-deficit regions, which advances our understanding of the long-term vegetation-drought relationship and provides essential insights for mapping future vegetation sensitivity to drought under changing climate conditions.
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Mudança Climática , Secas , Água , Ecossistema , ChinaRESUMO
We experimentally realized a high-speed nested anti-resonant nodeless fiber (NANF) transmission with the assistance of the polarization division multiplexing (PDM) and probabilistic shaping (PS) technology. In this system, a low-complexity multiple-input multiple-output (MIMO) real-valued equalizer (RVE) is integrated with decision-directed carrier phase estimation (DDCPE), which is robust against the IQ cross talk and a tiny phase disturbance between PS symbols. By using the proposed MIMO-RVEDDCPE, the 60-Gbaud PDM-PS-256QAM signal has been delivered through 2-km NANF satisfying the soft-decision forward error correction (SD-FEC) threshold.
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Self-homodyne coherent transmission has recently received extensive investigation as a coherent lite candidate for high-speed short-reach optical networks. In this Letter, we propose a weakly coupled mode-division-multiplexing (MDM) self-homodyne coherent scheme using a multiple-ring-core few-mode fiber, in which one of the modes transmits a self-homodyne local oscillator (LO) and the rest are utilized for carrying signals. Multiple rings of index perturbations in the fiber core are applied to achieve low modal crosstalk, allowing the signals and the remote LO to be transmitted independently. We experimentally demonstrate a 7.2-Tb/s (5.64-Tb/s net rate) self-homodyne coherent transmission with an 800-Gb/s data rate for each of the nine information-bearing modes formatted in 80-GBaud probabilistic constellation-shaped 64-quadrature-amplitude modulation. To the best of our knowledge, this is the first experimental demonstration of an MDM self-homodyne coherent transmission with up to 10 spatial modes. The proposed scheme may pave the way for future high-capacity data center interconnections.
RESUMO
Weakly coupled mode-division-multiplexing (MDM) systems based on intensity modulation and direct detection (IM-DD) are a good candidate for further improving the capacity of short-reach optical interconnections. However, restrained by the modal crosstalk of the transmission link and the reception of degenerate mode groups (DMGs) utilizing bandwidth-limited multimode photodetectors (PDs), high-speed MDM IM-DD has encountered a capacity bottleneck. In this Letter, we investigate a high-speed weakly coupled MDM IM-DD transmission system utilizing a degenerate mode diversity receiver scheme adopting high-bandwidth single-mode PDs over a multiple-ring-core (MRC) few-mode fiber (FMF) and a low-crosstalk mode multiplexer/demultiplexer (MUX/DMUX). An MDM IM-DD transmission with four DMGs and eight wavelengths is experimentally demonstrated with 112-GBaud four-level pulse-amplitude modulation (PAM4) and probabilistically shaped PAM8 per lane over 200-m weakly coupled MRC-FMF. To the best of our knowledge, this is the first experimental demonstration of the MDM IM-DD transmission system with up to 112-GBaud baud rate and beyond 6.4-Tb/s net rate. Meanwhile, the experimental results show that the proposed MDM IM-DD transmission link has a superior performance only adopting a low-complexity feedforward equalizer, making it a promising candidate for high-speed optical interconnections.