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1.
Annu Rev Immunol ; 29: 215-33, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21219172

RESUMO

The clonal selection theory first proposed by Macfarlane Burnet is a cornerstone of immunology (1). At the time, it revolutionized the thinking of immunologists because it provided a simple explanation for lymphocyte specificity, immunological memory, and elimination of self-reactive clones (2). The experimental demonstration by Nossal & Lederberg (3) that B lymphocytes bear receptors for a single antigen raised the central question of where B lymphocytes encounter antigen. This question has remained mostly unanswered until recently. Advances in techniques such as multiphoton intravital microscopy (4, 5) have provided new insights into the trafficking of B cells and their antigen. In this review, we summarize these advances in the context of our current view of B cell circulation and activation.


Assuntos
Antígenos/imunologia , Linfócitos B/citologia , Linfócitos B/imunologia , Linfonodos/citologia , Linfonodos/imunologia , Animais , Apresentação de Antígeno , Células Dendríticas/imunologia , Humanos
2.
Nature ; 601(7893): 415-421, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34987220

RESUMO

Transcriptional and proteomic profiling of individual cells have revolutionized interpretation of biological phenomena by providing cellular landscapes of healthy and diseased tissues1,2. These approaches, however, do not describe dynamic scenarios in which cells continuously change their biochemical properties and downstream 'behavioural' outputs3-5. Here we used 4D live imaging to record tens to hundreds of morpho-kinetic parameters describing the dynamics of individual leukocytes at sites of active inflammation. By analysing more than 100,000 reconstructions of cell shapes and tracks over time, we obtained behavioural descriptors of individual cells and used these high-dimensional datasets to build behavioural landscapes. These landscapes recognized leukocyte identities in the inflamed skin and trachea, and uncovered a continuum of neutrophil states inside blood vessels, including a large, sessile state that was embraced by the underlying endothelium and associated with pathogenic inflammation. Behavioural screening in 24 mouse mutants identified the kinase Fgr as a driver of this pathogenic state, and interference with Fgr protected mice from inflammatory injury. Thus, behavioural landscapes report distinct properties of dynamic environments at high cellular resolution.


Assuntos
Inflamação , Leucócitos , Proteômica , Animais , Forma Celular , Endotélio/imunologia , Inflamação/imunologia , Leucócitos/imunologia , Camundongos , Neutrófilos/imunologia , Proteínas Proto-Oncogênicas/imunologia , Quinases da Família src/imunologia
3.
PLoS Biol ; 21(2): e3001922, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36780432

RESUMO

A universal taxonomy of viruses is essential for a comprehensive view of the virus world and for communicating the complicated evolutionary relationships among viruses. However, there are major differences in the conceptualisation and approaches to virus classification and nomenclature among virologists, clinicians, agronomists, and other interested parties. Here, we provide recommendations to guide the construction of a coherent and comprehensive virus taxonomy, based on expert scientific consensus. Firstly, assignments of viruses should be congruent with the best attainable reconstruction of their evolutionary histories, i.e., taxa should be monophyletic. This fundamental principle for classification of viruses is currently included in the International Committee on Taxonomy of Viruses (ICTV) code only for the rank of species. Secondly, phenotypic and ecological properties of viruses may inform, but not override, evolutionary relatedness in the placement of ranks. Thirdly, alternative classifications that consider phenotypic attributes, such as being vector-borne (e.g., "arboviruses"), infecting a certain type of host (e.g., "mycoviruses," "bacteriophages") or displaying specific pathogenicity (e.g., "human immunodeficiency viruses"), may serve important clinical and regulatory purposes but often create polyphyletic categories that do not reflect evolutionary relationships. Nevertheless, such classifications ought to be maintained if they serve the needs of specific communities or play a practical clinical or regulatory role. However, they should not be considered or called taxonomies. Finally, while an evolution-based framework enables viruses discovered by metagenomics to be incorporated into the ICTV taxonomy, there are essential requirements for quality control of the sequence data used for these assignments. Combined, these four principles will enable future development and expansion of virus taxonomy as the true evolutionary diversity of viruses becomes apparent.


Assuntos
Bacteriófagos , Vírus , Humanos , Metagenômica , Filogenia , Vírus/genética
4.
J Immunol ; 212(8): 1307-1318, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38416036

RESUMO

Plitidepsin is a host-targeted compound known for inducing a strong anti-SARS-CoV-2 activity, as well as for having the capacity of reducing lung inflammation. Because IL-6 is one of the main cytokines involved in acute respiratory distress syndrome, the effect of plitidepsin in IL-6 secretion in different in vitro and in vivo experimental models was studied. A strong plitidepsin-mediated reduction of IL-6 was found in human monocyte-derived macrophages exposed to nonproductive SARS-CoV-2. In resiquimod (a ligand of TLR7/8)-stimulated THP1 human monocytes, plitidepsin-mediated reductions of IL-6 mRNA and IL-6 levels were also noticed. Additionally, although resiquimod-induced binding to DNA of NF-κB family members was unaffected by plitidepsin, a decrease in the regulated transcription by NF-κB (a key transcription factor involved in the inflammatory cascade) was observed. Furthermore, the phosphorylation of p65 that is required for full transcriptional NF-κB activity was significantly reduced by plitidepsin. Moreover, decreases of IL-6 levels and other proinflammatory cytokines were also seen in either SARS-CoV-2 or H1N1 influenza virus-infected mice, which were treated at low enough plitidepsin doses to not induce antiviral effects. In summary, plitidepsin is a promising therapeutic agent for the treatment of viral infections, not only because of its host-targeted antiviral effect, but also for its immunomodulatory effect, both of which were evidenced in vitro and in vivo by the decrease of proinflammatory cytokines.


Assuntos
Depsipeptídeos , Vírus da Influenza A Subtipo H1N1 , NF-kappa B , Humanos , Animais , Camundongos , NF-kappa B/metabolismo , Interleucina-6/farmacologia , Antivirais/farmacologia , Fatores Imunológicos/farmacologia , Citocinas/metabolismo , SARS-CoV-2/metabolismo
5.
J Biol Chem ; 300(5): 107218, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522515

RESUMO

Virus genomes may encode overlapping or nested open reading frames that increase their coding capacity. It is not known whether the constraints on spatial structures of the two encoded proteins limit the evolvability of nested genes. We examine the evolution of a pair of proteins, p22 and p19, encoded by nested genes in plant viruses from the genus Tombusvirus. The known structure of p19, a suppressor of RNA silencing, belongs to the RAGNYA fold from the alpha+beta class. The structure of p22, the cell-to-cell movement protein from the 30K family widespread in plant viruses, is predicted with the AlphaFold approach, suggesting a single jelly-roll fold core from the all-beta class, structurally similar to capsid proteins from plant and animal viruses. The nucleotide and codon preferences impose modest constraints on the types of secondary structures encoded in the alternative reading frames, nonetheless allowing for compact, well-ordered folds from different structural classes in two similarly-sized nested proteins. Tombusvirus p22 emerged through radiation of the widespread 30K family, which evolved by duplication of a virus capsid protein early in the evolution of plant viruses, whereas lineage-specific p19 may have emerged by a stepwise increase in the length of the overprinted gene and incremental acquisition of functionally active secondary structure elements by the protein product. This evolution of p19 toward the RAGNYA fold represents one of the first documented examples of protein structure convergence in naturally occurring proteins.


Assuntos
Tombusvirus , Evolução Molecular , Fases de Leitura Aberta , Dobramento de Proteína , Estrutura Secundária de Proteína , Tombusvirus/genética , Tombusvirus/metabolismo , Proteínas Virais/genética , Proteínas Virais/metabolismo , Proteínas Virais/química , Sequência de Aminoácidos , Homologia de Sequência de Aminoácidos , Modelos Psicológicos , Estrutura Terciária de Proteína
6.
BMC Plant Biol ; 24(1): 172, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443837

RESUMO

BACKGROUND: Plant responses to a wide range of stresses are known to be regulated by epigenetic mechanisms. Pathogen-related investigations, particularly against RNA viruses, are however scarce. It has been demonstrated that Arabidopsis thaliana plants defective in some members of the RNA-directed DNA methylation (RdDM) or histone modification pathways presented differential susceptibility to the turnip mosaic virus. In order to identify genes directly targeted by the RdDM-related RNA Polymerase V (POLV) complex and the histone demethylase protein JUMONJI14 (JMJ14) during infection, the transcriptomes of infected mutant and control plants were obtained and integrated with available chromatin occupancy data for various epigenetic proteins and marks. RESULTS: A comprehensive list of virus-responsive gene candidates to be regulated by the two proteins was obtained. Twelve genes were selected for further characterization, confirming their dynamic regulation during the course of infection. Several epigenetic marks on their promoter sequences were found using in silico data, raising confidence that the identified genes are actually regulated by epigenetic mechanisms. The altered expression of six of these genes in mutants of the methyltransferase gene CURLY LEAF and the histone deacetylase gene HISTONE DEACETYLASE 19 suggests that some virus-responsive genes may be regulated by multiple coordinated epigenetic complexes. A temporally separated multiple plant virus infection experiment in which plants were transiently infected with one virus and then infected by a second one was designed to investigate the possible roles of the identified POLV- and JMJ14-regulated genes in wild-type (WT) plants. Plants that had previously been stimulated with viruses were found to be more resistant to subsequent virus challenge than control plants. Several POLV- and JMJ14-regulated genes were found to be regulated in virus induced resistance in WT plants, with some of them poisoned to be expressed in early infection stages. CONCLUSIONS: A set of confident candidate genes directly regulated by the POLV and JMJ14 proteins during virus infection was identified, with indications that some of them may be regulated by multiple epigenetic modules. A subset of these genes may also play a role in the tolerance of WT plants to repeated, intermittent virus infections.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Vírus de Plantas , Viroses , Metilação de DNA , Arabidopsis/genética , Histona Desacetilases , Histona Desmetilases com o Domínio Jumonji
7.
Nat Immunol ; 13(5): 499-510, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22466668

RESUMO

Lymph node stromal cells (LNSCs) closely regulate immunity and self-tolerance, yet key aspects of their biology remain poorly elucidated. Here, comparative transcriptomic analyses of mouse LNSC subsets demonstrated the expression of important immune mediators, growth factors and previously unknown structural components. Pairwise analyses of ligands and cognate receptors across hematopoietic and stromal subsets suggested a complex web of crosstalk. Fibroblastic reticular cells (FRCs) showed enrichment for higher expression of genes relevant to cytokine signaling, relative to their expression in skin and thymic fibroblasts. LNSCs from inflamed lymph nodes upregulated expression of genes encoding chemokines and molecules involved in the acute-phase response and the antigen-processing and antigen-presentation machinery. Poorly studied podoplanin (gp38)-negative CD31(-) LNSCs showed similarities to FRCs but lacked expression of interleukin 7 (IL-7) and were identified as myofibroblastic pericytes that expressed integrin α(7). Together our data comprehensively describe the transcriptional characteristics of LNSC subsets.


Assuntos
Expressão Gênica/imunologia , Inflamação/imunologia , Linfonodos/imunologia , Células Estromais/imunologia , Células Estromais/metabolismo , Transcriptoma , Reação de Fase Aguda/imunologia , Animais , Apresentação de Antígeno/imunologia , Antígenos CD/imunologia , Antígenos CD/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Fibroblastos/imunologia , Fibroblastos/metabolismo , Homeostase/imunologia , Inflamação/genética , Cadeias alfa de Integrinas/imunologia , Cadeias alfa de Integrinas/metabolismo , Interleucina-7/imunologia , Interleucina-7/metabolismo , Linfonodos/citologia , Glicoproteínas de Membrana/imunologia , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pericitos/imunologia , Pericitos/metabolismo , Tolerância a Antígenos Próprios/imunologia , Análise Serial de Tecidos/métodos
8.
Curr Top Microbiol Immunol ; 439: 167-196, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36592246

RESUMO

Viruses are studied at each level of biological complexity: from within-cells to ecosystems. The same basic evolutionary forces and principles operate at each level: mutation and recombination, selection, genetic drift, migration, and adaptive trade-offs. Great efforts have been put into understanding each level in great detail, hoping to predict the dynamics of viral population, prevent virus emergence, and manage their spread and virulence. Unfortunately, we are still far from this. To achieve these ambitious goals, we advocate for an integrative perspective of virus evolution. Focusing in plant viruses, we illustrate the pervasiveness of the above-mentioned principles. Beginning at the within-cell level, we describe replication modes, infection bottlenecks, and cellular contagion rates. Next, we move up to the colonization of distal tissues, discussing the fundamental role of random events. Then, we jump beyond the individual host and discuss the link between transmission mode and virulence. Finally, at the community level, we discuss properties of virus-plant infection networks. To close this review we propose the multilayer network theory, in which elements at different layers are connected and submit to their own dynamics that feed across layers, resulting in new emerging properties, as a way to integrate information from the different levels.


Assuntos
Vírus de Plantas , Viroses , Humanos , Ecossistema , Vírus de Plantas/genética , Adaptação Fisiológica , Mutação
9.
Proc Natl Acad Sci U S A ; 118(6)2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33526695

RESUMO

Environmental conditions are an important factor driving pathogens' evolution. Here, we explore the effects of drought stress in plant virus evolution. We evolved turnip mosaic potyvirus in well-watered and drought conditions in Arabidopsis thaliana accessions that differ in their response to virus infection. Virus adaptation occurred in all accessions independently of watering status. Drought-evolved viruses conferred a significantly higher drought tolerance to infected plants. By contrast, nonsignificant increases in tolerance were observed in plants infected with viruses evolved under standard watering. The magnitude of this effect was dependent on the plant accessions. Differences in tolerance were correlated to alterations in the expression of host genes, some involved in regulation of the circadian clock, as well as in deep changes in the balance of phytohormones regulating defense and growth signaling pathways. Our results show that viruses can promote host survival in situations of abiotic stress, with the magnitude of such benefit being a selectable trait.


Assuntos
Arabidopsis/genética , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/genética , Vírus de Plantas/genética , Simbiose/genética , Adaptação Fisiológica , Arabidopsis/virologia , Brassica napus/genética , Brassica napus/virologia , Secas , Evolução Molecular , Regulação da Expressão Gênica de Plantas/genética , Doenças das Plantas/virologia , Reguladores de Crescimento de Plantas/genética , Vírus de Plantas/patogenicidade , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/virologia , Potyvirus/genética , Potyvirus/patogenicidade , Estresse Fisiológico/genética
10.
J Virol ; 96(22): e0098822, 2022 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-36314818

RESUMO

Although the coat protein (CP) has a relevant role in the long-distance movement of alfalfa mosaic virus (AMV) and brome mosaic virus (BMV), its precise function is not fully understood. Previous results showed that a specific interaction between the C termini of the movement protein (MP) and the cognate CP is required for systemic transport. Thus, we have performed a compensatory evolution experiment using an AMV RNA3 derivative defective in long-distance transport that carries a BMV MP lacking the C-terminal 48 residues and unable to interact with the AMV CP. After several passages, five independent evolution lineages were able to move long distance. The analysis of the viral RNA of these lineages showed the presence of three different modifications located exclusively at the 5' untranslated region (5' UTR). The three evolved 5' UTR variants accumulated comparable levels of viral RNA and CP but reduced the accumulation of virus particles and the affinity between the 5' UTR and the AMV CP. In addition, the evolved 5' UTR increased cell-to-cell transport for both the AMV RNA3 carrying the BMV MP and that carrying the AMV MP. Finally, the evolved 5' UTRs allowed the systemic transport of an AMV RNA3 carrying a CP mutant defective in virus particles and increased the systemic transport of several AMV RNA3 derivatives carrying different viral MPs associated with the 30K superfamily. Altogether, our findings indicate that virus particles are not required for the systemic transport of AMV but also that BMV MP is competent for the short- and long-distance transport without the interaction with the CP. IMPORTANCE The results obtained in the present work could challenge the view of the role of the virus particle in the systemic transport of plant viruses. In this sense, we show that two different MPs are competent to systemically transport the AMV genome without the requirement of the virus particles, as reported for viruses lacking a CP (e.g., Umbravirus). The incapability of the viral MP to interact with the CP triggered virus variants that evolved to reduce the formation of virus particles, probably to increase the accessibility of the MP to the viral progeny. Our results point to the idea that virus particles would not be necessary for the viral systemic transport but would be necessary for vector virus transmission. This idea is reinforced by the observation that heterologous MPs also increased the systemic transport of the AMV constructs that have reduced encapsidation capabilities.


Assuntos
Vírus do Mosaico da Alfafa , Bromovirus , Proteínas do Movimento Viral em Plantas , Transporte de RNA , Regiões 5' não Traduzidas , Vírus do Mosaico da Alfafa/genética , Bromovirus/genética , RNA Viral/genética , Proteínas do Movimento Viral em Plantas/genética
11.
PLoS Pathog ; 17(6): e1009583, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34081744

RESUMO

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic reveals a major gap in global biosecurity infrastructure: a lack of publicly available biological samples representative across space, time, and taxonomic diversity. The shortfall, in this case for vertebrates, prevents accurate and rapid identification and monitoring of emerging pathogens and their reservoir host(s) and precludes extended investigation of ecological, evolutionary, and environmental associations that lead to human infection or spillover. Natural history museum biorepositories form the backbone of a critically needed, decentralized, global network for zoonotic pathogen surveillance, yet this infrastructure remains marginally developed, underutilized, underfunded, and disconnected from public health initiatives. Proactive detection and mitigation for emerging infectious diseases (EIDs) requires expanded biodiversity infrastructure and training (particularly in biodiverse and lower income countries) and new communication pipelines that connect biorepositories and biomedical communities. To this end, we highlight a novel adaptation of Project ECHO's virtual community of practice model: Museums and Emerging Pathogens in the Americas (MEPA). MEPA is a virtual network aimed at fostering communication, coordination, and collaborative problem-solving among pathogen researchers, public health officials, and biorepositories in the Americas. MEPA now acts as a model of effective international, interdisciplinary collaboration that can and should be replicated in other biodiversity hotspots. We encourage deposition of wildlife specimens and associated data with public biorepositories, regardless of original collection purpose, and urge biorepositories to embrace new specimen sources, types, and uses to maximize strategic growth and utility for EID research. Taxonomically, geographically, and temporally deep biorepository archives serve as the foundation of a proactive and increasingly predictive approach to zoonotic spillover, risk assessment, and threat mitigation.


Assuntos
Bancos de Espécimes Biológicos/organização & administração , Controle de Doenças Transmissíveis , Doenças Transmissíveis Emergentes/prevenção & controle , Redes Comunitárias/organização & administração , Vigilância em Saúde Pública/métodos , Animais , Animais Selvagens , Biodiversidade , Bancos de Espécimes Biológicos/normas , Bancos de Espécimes Biológicos/provisão & distribuição , Bancos de Espécimes Biológicos/tendências , COVID-19/epidemiologia , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Controle de Doenças Transmissíveis/normas , Doenças Transmissíveis Emergentes/epidemiologia , Doenças Transmissíveis Emergentes/microbiologia , Doenças Transmissíveis Emergentes/virologia , Redes Comunitárias/normas , Redes Comunitárias/provisão & distribuição , Redes Comunitárias/tendências , Planejamento em Desastres/métodos , Planejamento em Desastres/organização & administração , Planejamento em Desastres/normas , Geografia , Saúde Global/normas , Saúde Global/tendências , Humanos , Contramedidas Médicas , Pandemias/prevenção & controle , Saúde Pública , Medição de Risco , SARS-CoV-2/fisiologia , Zoonoses/epidemiologia , Zoonoses/prevenção & controle
12.
Langmuir ; 39(12): 4207-4215, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36919825

RESUMO

Emulsions often act as carriers for water-insoluble solutes that are delivered to a specific target. The molecular transport of solutes in emulsions can be facilitated by surfactants and is often limited by diffusion through the continuous phase. We here investigate this transport on a molecular scale by using a lipophilic molecular rotor as a proxy for solutes. Using fluorescence lifetime microscopy we track the transport of these molecules from the continuous phase toward the dispersed phase in polydisperse oil-in-water emulsions. We show that this transport comprises two time scales, which vary significantly with droplet size and surfactant concentration, and, depending on the type of surfactant used, can be limited either by transport across the oil-water interface or by diffusion through the continuous phase. By studying the time-resolved fluorescence of the fluorophore, accompanied by molecular dynamics simulations, we demonstrate how the rate of transport observed on a macroscopic scale can be explained in terms of the local environment that the probe molecules are exposed to.

13.
Eur Radiol ; 33(5): 3103-3114, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36571605

RESUMO

OBJECTIVES: The pandemic caused by SARS-CoV-2 has led to the rapid publication of numerous radiology articles, primarily focused on disease diagnosis. The objective of this study is to analyze the intellectual structure of radiology research on COVID-19 using a citation and co-citation analysis. METHODS: We identified all documents about COVID-19 published in radiology journals included in the Web of Science in the period 2020-2021, conducting a citation analysis. Then we identified all bibliographic references that were cited by these documents, generating a co-citation matrix that was used to perform a co-citation network. RESULTS: Of the 3418 documents indexed in WoS, 857 were initially "Early Access," 2223 had citations, 393 had more than 20 citations, and 83 had more than 100 citations. The USA had the highest number of publications (32.62%) and China had the highest rate of funded studies (45.38%). The three authors with the most publications were affiliated with Italian institutions, while the five most cited authors were Chinese. A total of 647 publications were co-cited at least 12 times and were published in 206 different journals, with 49% of the documents found in radiology journals. The institutions with the greatest presence among these co-cited articles were Chinese and American. CONCLUSION: This co-citation analysis is the first to focus exclusively on radiology articles on COVID-19. Our study confirms the existence of interrelated thematic clusters with different specific weights. KEY POINTS: • As the pandemic caused by SARS-Cov-2 has led to the rapid publication of numerous radiology studies in a short time period, a bibliometric review based on citation and co-citation analysis has been conducted. • The co-citation analysis supported the identification of key themes in the study of COVID-19 in radiology publications. • Many of the most co-cited articles belong to a heterogeneous group of publications, with authors from countries that are far apart and even from different disciplines.


Assuntos
COVID-19 , Publicações Periódicas como Assunto , Radiologia , Humanos , Estados Unidos , SARS-CoV-2 , Bibliometria
14.
Soft Matter ; 19(10): 1941-1951, 2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36808176

RESUMO

What measurable physical properties allow one to distinguish surfactant-stabilised from Pickering emulsions? Whereas surfactants influence oil/water interfaces by lowering the oil/water interfacial tension, particles are assumed to have little effect on the interfacial tension. Here we perform interfacial tension (IFT) measurements on three different systems: (1) soybean oil and water with ethyl cellulose nanoparticles (ECNPs), (2) silicone oil and water with the globular protein bovine serum albumin (BSA), and (3) sodium dodecyl sulfate (SDS) solutions and air. The first two systems contain particles, while the third system contains surfactant molecules. We observe a significant decrease in interfacial tension with increasing particle/molecule concentration in all three systems. We analyse the surface tension data using the Gibbs adsorption isotherm and the Langmuir equation of state for the surface, resulting in surprisingly high adsorption densities for the particle-based systems. These seem to behave very much like the surfactant system: the decrease in tension is due to the presence of many particles at the interface, each with an adsorption energy of a few kBT. Dynamic interfacial tension measurements show that the systems are in equilibrium, and that the characteristic time scale for adsorption is much longer for particle-based systems than for surfactants, in line with their size difference. In addition, the particle-based emulsion is shown to be less stable against coalescence than the surfactant-stabilised emulsion. This leaves us with the conclusion that we are not able to make a clear distinction between the surfactant-stabilised and Pickering emulsions.

15.
Proc Natl Acad Sci U S A ; 117(50): 32005-32016, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33229588

RESUMO

Tumor-associated macrophages (TAMs) can have protumor properties, including suppressing immune responses, promoting vascularization and, consequently, augmenting tumor progression. To stop TAM-mediated immunosuppression, we use a novel treatment by injecting antibodies specific for scavenger receptor MARCO, which is expressed on a specific subpopulation of TAMs in the tumor. We now report the location of this TAM as well as the pleiotropic mechanism of action of anti-MARCO antibody treatment on tumor progression and further show that this is potentially relevant to humans. Using specific targeting, we observed decreased tumor vascularization, a switch in the metabolic program of MARCO-expressing macrophages, and activation of natural killer (NK) cell killing through TNF-related apoptosis-inducing ligand (TRAIL). This latter activity reverses the effect of melanoma cell-conditioned macrophages in blocking NK activation and synergizes with T cell-directed immunotherapy, such as antibodies to PD-1 or PD-L1, to enhance tumor killing. Our study thus reveals an approach to targeting the immunosuppressive tumor microenvironment with monoclonal antibodies to enhance NK cell activation and NK cell-mediated killing. This can complement existing T cell-directed immunotherapy, providing a promising approach to combinatorial immunotherapy for cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Células Matadoras Naturais/imunologia , Melanoma/tratamento farmacológico , Receptores Imunológicos/antagonistas & inibidores , Macrófagos Associados a Tumor/efeitos dos fármacos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Células Matadoras Naturais/metabolismo , Masculino , Melanoma/imunologia , Melanoma/patologia , Camundongos , Camundongos Knockout , Cultura Primária de Células , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
16.
J Gen Virol ; 103(11)2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36399124

RESUMO

Currently, many viruses are classified based on their genome organization and nucleotide/amino acid sequence identities of their capsid and replication-associated proteins. Although biological traits such as vector specificities and host range are also considered, this later information is scarce for the majority of recently identified viruses, characterized only from genomic sequences. Accordingly, genomic sequences and derived information are being frequently used as the major, if not only, criteria for virus classification and this calls for a full review of the process. Herein, we critically addressed current issues concerning classification of viruses in the family Betaflexiviridae in the era of high-throughput sequencing and propose an updated set of demarcation criteria based on a process involving pairwise identity analyses and phylogenetics. The proposed framework has been designed to solve the majority of current conundrums in taxonomy and to facilitate future virus classification. Finally, the analyses performed herein, alongside the proposed approaches, could be used as a blueprint for virus classification at-large.


Assuntos
Flexiviridae , Vírus , Flexiviridae/genética , Genoma Viral , Vírus/genética , Filogenia , Sequenciamento de Nucleotídeos em Larga Escala
17.
PLoS Pathog ; 16(6): e1008608, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32574227

RESUMO

Transmission is a crucial part of a viral life cycle and transmission mode can have an important impact on virus biology. It was demonstrated that transmission mode can influence the virulence and evolution of a virus; however, few empirical data are available to describe the direct underlying changes in virus population structure dynamics within the host. Potato virus Y (PVY) is an RNA virus and one of the most damaging pathogens of potato. It comprises several genetically variable strains that are transmitted between plants via different transmission modes. To investigate how transmission modes affect the within-plant viral population structure, we have used a deep sequencing approach to examine the changes in the genetic structure of populations (in leaves and tubers) of three PVY strains after successive passages by horizontal (aphid and mechanical) and vertical (via tubers) transmission modes. Nucleotide diversities of viral populations were significantly influenced by transmission modes; lineages transmitted by aphids were the least diverse, whereas lineages transmitted by tubers were the most diverse. Differences in nucleotide diversities of viral populations between leaves and tubers were transmission mode-dependent, with higher diversities in tubers than in leaves for aphid and mechanically transmitted lineages. Furthermore, aphid and tuber transmissions were shown to impose stronger genetic bottlenecks than mechanical transmission. To better understand the structure of virus populations within the host, transmission mode, movement of the virus within the host, and the number of replication cycles after transmission event need to be considered. Collectively, our results suggest a significant impact of virus transmission modes on the within-plant diversity of virus populations and provide quantitative fundamental data for understanding how transmission can shape virus diversity in the natural ecosystems, where different transmission modes are expected to affect virus population structure and consequently its evolution.


Assuntos
Modelos Biológicos , Doenças das Plantas/virologia , Folhas de Planta , Tubérculos , Potyvirus , Solanum tuberosum , Folhas de Planta/metabolismo , Folhas de Planta/virologia , Tubérculos/metabolismo , Tubérculos/virologia , Potyvirus/metabolismo , Potyvirus/patogenicidade , Solanum tuberosum/metabolismo , Solanum tuberosum/virologia
18.
Magn Reson Med ; 87(6): 2947-2956, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35076107

RESUMO

PURPOSE: 3D-printed porous metal scaffolds are a promising emerging technology in orthopedic implant design. Compared to solid metal implants, porous metal implants have lower magnetic susceptibility values, which have a direct impact on imaging time and image quality. The purpose of this study is to determine the relationship between porosity and effective susceptibility through quantitative estimates informed by comparing coregistered scanned and simulated field maps. METHODS: Five porous scaffold cylinders were designed and 3D-printed in titanium alloy (Ti-6Al-4V) with nominal porosities ranging from 60% to 90% using a cellular sheet-based gyroid design. The effective susceptibility of each cylinder was estimated by comparing acquired B0 field maps against simulations of a solid cylinder of varying assigned magnetic susceptibility, where the orientation and volume of interest of the simulations was informed by a custom alignment phantom. RESULTS: Magnitude images and field maps showed obvious decreases in artifact size and field inhomogeneity with increasing porosity. The effective susceptibility was found to be linearly correlated with porosity (R2  = 0.9993). The extrapolated 100% porous (no metal) magnetic susceptibility was -9.9 ppm, closely matching the expected value of pure water (-9 ppm), indicating a reliable estimation of susceptibility. CONCLUSION: Effective susceptibility of porous metal scaffolds is linearly correlated with porosity. Highly porous implants have sufficiently low effective susceptibilities to be more amenable to routine imaging with MRI.


Assuntos
Ligas , Titânio , Metais , Porosidade , Impressão Tridimensional
19.
Nat Immunol ; 11(5): 427-34, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20305659

RESUMO

A major pathway for B cell acquisition of lymph-borne particulate antigens relies on antigen capture by subcapsular sinus macrophages of the lymph node. Here we tested whether this mechanism is also important for humoral immunity to inactivated influenza virus. By multiple approaches, including multiphoton intravital imaging, we found that antigen capture by sinus-lining macrophages was important for limiting the systemic spread of virus but not for the generation of influenza-specific humoral immunity. Instead, we found that dendritic cells residing in the lymph node medulla use the lectin receptor SIGN-R1 to capture lymph-borne influenza virus and promote humoral immunity. Thus, our results have important implications for the generation of durable humoral immunity to viral pathogens through vaccination.


Assuntos
Moléculas de Adesão Celular/metabolismo , Células Dendríticas/metabolismo , Endocitose , Vírus da Influenza A/imunologia , Lectinas Tipo C/metabolismo , Macrófagos/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Anticorpos Antivirais/sangue , Apresentação de Antígeno , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/imunologia , Movimento Celular , Células Cultivadas , Ácido Clodrônico/administração & dosagem , Dendrímeros/administração & dosagem , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/patologia , Células Dendríticas/virologia , Endocitose/efeitos dos fármacos , Endocitose/genética , Imunidade Humoral/efeitos dos fármacos , Imunidade Humoral/genética , Cadeias Pesadas de Imunoglobulinas/genética , Imunoterapia Ativa , Vírus da Influenza A/patogenicidade , Vacinas contra Influenza/administração & dosagem , Lectinas Tipo C/genética , Lectinas Tipo C/imunologia , Linfonodos/patologia , Linfonodos/virologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Macrófagos/virologia , Lectina de Ligação a Manose/genética , Lectina de Ligação a Manose/metabolismo , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Microscopia de Fluorescência por Excitação Multifotônica , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/imunologia
20.
Phys Rev Lett ; 128(8): 080601, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35275654

RESUMO

Quantum matter at ultralow temperatures offers a test bed for analyzing and controlling desired properties in strongly correlated systems. Under typical conditions the nature of the atoms fixes the magnetic character of the system. Beyond classical light potentials leading to optical lattices and short-range interactions, high-Q cavities introduce novel dynamics into the system via the quantumness of light. Here we propose a theoretical model and we analyze it using exact diagonalization and density matrix renormalization group simulations. We explore the effects of cavity mediated long-range magnetic interactions and optical lattices in ultracold matter. We find that global interactions modify the underlying magnetic character of the system while introducing competition scenarios. Antiferromagnetic correlated bosonic matter emerges in conditions beyond what nature typically provides. These allow new alternatives toward the design of robust mechanisms for quantum information purposes, exploiting the properties of magnetic phases of strongly correlated quantum matter.

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