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Brown algae are multicellular photosynthetic organisms that have evolved independently of plants and other algae. Here, we have studied the determinism of body axis formation in the kelp Saccharina latissima. After microdissection of the embryo, we show that the stalk, an empty cell that retains the embryo on the maternal tissue, represses longitudinal cell divisions in the early embryo, thereby reinforcing the establishment of the initial apico-basal axis. In addition, it promotes cell growth and controls cell shape and arrangement in the flat oblong embryo composed of cells aligned in rows and columns. Although the stalk persists for several weeks until the embryo reaches at least 500 cells, proper embryogenesis requires connection to maternal tissue only during the first 4â days after fertilisation, i.e. before the embryo reaches the 8-cell stage. Transplantation experiments indicate that the maternal signal is not diffused in seawater, but requires contact between the embryo and the maternal tissue. This first global quantitative study of brown algal embryogenesis highlights the role of MUM, an unknown maternal message, in the control of growth axes and tissue patterning in kelp embryos.
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Kelp , Padronização Corporal/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Phaeophyceae , Proteínas de Algas/metabolismo , Algas Comestíveis , LaminariaRESUMO
In most organisms, 3D growth takes place at the onset of embryogenesis. In some brown algae, 3D growth occurs later in development, when the organism consists of several hundred cells. We studied the cellular events that take place when 3D growth is established in the embryo of the brown alga Saccharina, a kelp species. Semi-thin sections, taken from where growth shifts from 2D to 3D, show that 3D growth first initiates from symmetrical cell division in the monolayered lamina, and then is enhanced through a series of asymmetrical cell divisions in a peripheral monolayer of cells called the meristoderm. Then, daughter cells rapidly differentiate into cortical and medullary cells, characterised by their position, size and shape. In essence, 3D growth in kelps is based on a series of differentiation steps that occur rapidly after the initiation of a bilayered lamina, followed by further growth of the established differentiated tissues. Our study depicts the cellular landscape necessary to study cell-fate programming in the context of a novel mode of 3D growth in an organism phylogenetically distant from plants and animals.
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Besouros , Kelp , Phaeophyceae , Animais , Divisão Celular , Diferenciação Celular , Desenvolvimento EmbrionárioRESUMO
Non-Hodgkin lymphomas (NHL) commonly occur in immune-deficient (ID) patients, both HIV-infected and transplanted, and are often EBV-driven with cerebral localization, raising the question of tumor immunogenicity, a critical issue for treatment responses. We investigated the immunogenomics of 68 lymphoproliferative disorders from 51 ID (34 posttransplant, 17 HIV+) and 17 immunocompetent patients. Overall, 72% were Large B Cells Lymphoma (LBCL) and 25% were primary central-nervous-system lymphoma (PCNSL) while 40% were EBV-positive. Tumor whole-exome and RNA sequencing, along with a bioinformatics pipeline allowed analysis of tumor mutational burden (TMB), tumor landscape and microenvironment (TME) and prediction of tumor neoepitopes. Both TMB (2.2 vs 3.4/Mb, p=0.001) and neoepitopes numbers (40 vs 200, p=0.00019) were lower in EBVpositive than in EBV-negative NHL, regardless of the immune status. In contrast both EBV and the immune status influenced the tumor mutational profile, with HNRNPF and STAT3 mutations exclusively observed in EBV-positive and ID NHL, respectively. Peripheral blood T-cell responses against tumor neoepitopes were detected in all EBV-negative cases but in only half EBV-positive ones, including responses against IgH-derived MHC-class-II restricted neoepitopes. The TME analysis showed higher CD8 T cell infiltrates in EBVpositive vs EBV-negative NHL, together with a more tolerogenic profile composed of Tregs, type-M2 macrophages and an increased expression of negative immune-regulators. Our results highlight that the immunogenomics of NHL in patients with immunodeficiency primarily relies on the tumor EBV status, while T cell recognition of tumor- and IgH-specific neoepitopes is conserved in EBV-negative patients, offering potential opportunities for future T cell-based immune therapies.
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Human immunodeficiency virus (HIV) infection is associated with an increased risk of non-Hodgkin lymphoma (NHL). Even in the era of suppressive antiretroviral treatment, HIV-infected individuals remain at higher risk of developing NHL compared to the general population. To identify potential genetic risk loci, we performed case-control genome-wide association studies and a meta-analysis across three cohorts of HIV+ patients of European ancestry, including a total of 278 cases and 1924 matched controls. We observed a significant association with NHL susceptibility in the C-X-C motif chemokine ligand 12 (CXCL12) region on chromosome 10. A fine mapping analysis identified rs7919208 as the most likely causal variant (P = 4.77e-11), with the G>A polymorphism creating a new transcription factor binding site for BATF and JUND. These results suggest a modulatory role of CXCL12 regulation in the increased susceptibility to NHL observed in the HIV-infected population.
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Infecções por HIV , Linfoma Relacionado a AIDS , Linfoma não Hodgkin , Antirretrovirais/uso terapêutico , Estudos de Casos e Controles , Quimiocina CXCL12 , Estudo de Associação Genômica Ampla , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Humanos , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/genética , Polimorfismo GenéticoRESUMO
There are no methods sensitive enough to detect enzymes within cells, without the use of analyte labeling. Here we show that it is possible to detect protein ion signals of three different H2S-synthesizing enzymes inside microglia after pretreatment with silver nanowires (AgNW) using time-of-flight secondary ion mass spectrometry (TOF-SIMS). Protein fragment ions, including the fragment of amino acid (C4H8N+ = 70 amu), fragments of the sulfur-producing cystathionine-containing enzymes, and the Ag+ ion signal could be detected without the use of any labels; the cells were mapped using the C4H8N+ amino acid fragment. Scanning electron microscopy imaging and energy-dispersive X-ray chemical analysis showed that the AgNWs were inside the same cells imaged by TOF-SIMS and transformed chemically into crystalline Ag2S within cells in which the sulfur-producing proteins were detected. The presence of these sulfur-producing cystathionine-containing enzymes within the cells was confirmed by Western blots and confocal microscopy images of fluorescently labeled antibodies against the sulfur-producing enzymes. Label-free TOF-SIMS is very promising for the label-free identification of H2S-contributing enzymes and their cellular localization in biological systems. The technique could in the future be used to identify which of these enzymes are most contributory.
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Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Microglia/enzimologia , Prata/farmacologia , Enxofre/química , Sulfurtransferases/metabolismo , Animais , Transporte Biológico , Linhagem Celular Transformada , Camundongos , Microglia/efeitos dos fármacos , Microglia/ultraestrutura , Microscopia Eletrônica de Varredura , Imagem Molecular/instrumentação , Imagem Molecular/métodos , Nanofios/química , Prata/química , Espectrometria de Massa de Íon Secundário , Enxofre/metabolismoRESUMO
It is widely assumed that CD4(+) T cells recognize antigenic peptides (epitopes) derived solely from incoming, exogenous, viral particles or proteins. However, alternative sources of MHC class II (MHC-II)-restricted Ags have been described, in particular epitopes derived from newly synthesized proteins (so-called endogenous). In this study, we show that HIV-infected dendritic cells (DC) present MHC-II-restricted endogenous viral Ags to HIV-specific (HS) CD4(+) T cells. This endogenous pathway functions independently of the exogenous route for HIV Ag presentation and offers a distinct possibility for the immune system to activate HS CD4(+) T cells. We examined the implication of autophagy, which plays a crucial role in endogenous viral Ag presentation and thymic selection of CD4(+) T cells, in HIV endogenous presentation. We show that infected DC do not use autophagy to process MHC-II-restricted HIV Ags. This is unlikely to correspond to a viral escape from autophagic degradation, as infecting DC with Nef- or Env-deficient HIV strains did not impact HS T cell activation. However, we demonstrate that, in DC, specific targeting of HIV Ags to autophagosomes using a microtubule-associated protein L chain 3 (LC3) fusion protein effectively enhances and broadens HS CD4(+) T cell responses, thus favoring an endogenous MHC-II-restricted presentation. In summary, in DC, multiple endogenous presentation pathways lead to the activation of HS CD4(+) T cell responses. These findings will help in designing novel strategies to activate HS CD4(+) T cells that are required for CTL activation/maintenance and B cell maturation.
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Apresentação de Antígeno/imunologia , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Infecções por HIV/imunologia , Ativação Linfocitária/imunologia , Autofagia/imunologia , Western Blotting , Células Dendríticas/virologia , HIV-1/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Microscopia ConfocalRESUMO
Previous genome-wide association studies (GWAS) of HIV-1-infected populations have been underpowered to detect common variants with moderate impact on disease outcome and have not assessed the phenotypic variance explained by genome-wide additive effects. By combining the majority of available genome-wide genotyping data in HIV-infected populations, we tested for association between â¼8 million variants and viral load (HIV RNA copies per milliliter of plasma) in 6,315 individuals of European ancestry. The strongest signal of association was observed in the HLA class I region that was fully explained by independent effects mapping to five variable amino acid positions in the peptide binding grooves of the HLA-B and HLA-A proteins. We observed a second genome-wide significant association signal in the chemokine (C-C motif) receptor (CCR) gene cluster on chromosome 3. Conditional analysis showed that this signal could not be fully attributed to the known protective CCR5Δ32 allele and the risk P1 haplotype, suggesting further causal variants in this region. Heritability analysis demonstrated that common human genetic variation-mostly in the HLA and CCR5 regions-explains 25% of the variability in viral load. This study suggests that analyses in non-European populations and of variant classes not assessed by GWAS should be priorities for the field going forward.
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Predisposição Genética para Doença , HIV-1/genética , Interações Hospedeiro-Patógeno/genética , Polimorfismo de Nucleotídeo Único/genética , Carga Viral/genética , Adulto , Alelos , Aminoácidos/genética , Cromossomos Humanos Par 3/genética , Estudo de Associação Genômica Ampla , Antígenos HLA-B/genética , Humanos , Padrões de Herança/genética , Mapeamento Físico do Cromossomo , Receptores CCR5/genéticaRESUMO
BACKGROUND: Familial Mediterranean fever (FMF) is an IL-1ß-dependent autoinflammatory disease caused by mutations of Mediterranean fever (MEFV) encoding pyrin and characterized by inflammatory attacks induced by physical or psychological stress. OBJECTIVE: We investigated the underlying mechanism that links stress-induced inflammatory attacks with neutrophil activation and release of IL-1ß-bearing neutrophil extracellular traps (NETs) in patients with FMF. METHODS: RNA sequencing was performed in peripheral neutrophils from 3 patients with FMF isolated both during attacks and remission, 8 patients in remission, and 8 healthy subjects. NET formation and proteins were analyzed by using confocal immunofluorescence microscopy, immunoblotting, myeloperoxidase-DNA complex ELISA, and flow cytometry. Samples from patients with Still's disease and bacterial infections were used also. RESULTS: The stress-related protein regulated in development and DNA damage responses 1 (REDD1) is significantly overexpressed during FMF attacks. Neutrophils from patients with FMF during remission are resistant to autophagy-mediated NET release, which can be overcome through REDD1 induction. Stress-related mediators (eg, epinephrine) decrease this threshold, leading to autophagy-driven NET release, whereas the synchronous inflammatory environment of FMF attack leads to intracellular production of IL-1ß and its release through NETs. REDD1 in autolysosomes colocalizes with pyrin and nucleotide-binding domain, leucine-rich repeat/pyrin domain-containing 3. Mutated pyrin prohibits this colocalization, leading to higher IL-1ß levels on NETs. CONCLUSIONS: This study provides a link between stress and initiation of inflammatory attacks in patients with FMF. REDD1 emerges as a regulator of neutrophil function upstream to pyrin, is involved in NET release and regulation of IL-1ß, and might constitute an important piece in the IL-1ß-mediated inflammation puzzle.
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Febre Familiar do Mediterrâneo/imunologia , Inflamação/imunologia , Neutrófilos/imunologia , Estresse Psicológico/imunologia , Fatores de Transcrição/metabolismo , Adulto , Autofagia , Progressão da Doença , Armadilhas Extracelulares/metabolismo , Febre Familiar do Mediterrâneo/genética , Feminino , Humanos , Interleucina-1beta/metabolismo , Masculino , Pirina/genética , Remissão Espontânea , Estresse Fisiológico/imunologia , Adulto JovemRESUMO
There is growing evidence that human genetic variants contribute to liver fibrosis in subjects with hepatitis C virus (HCV) monoinfection, but this aspect has been little investigated in patients coinfected with HCV and human immunodeficiency virus (HIV). We performed the first genome-wide association study of liver fibrosis progression in patients coinfected with HCV and HIV, using the well-characterized French National Agency for Research on AIDS and Viral Hepatitis CO13 HEPAVIH cohort. Liver fibrosis was assessed by elastography (FibroScan), providing a quantitative fibrosis score. After quality control, a genome-wide association study was conducted on 289 Caucasian patients, for a total of 8,426,597 genotyped (Illumina Omni2.5 BeadChip) or reliably imputed single-nucleotide polymorphisms. Single-nucleotide polymorphisms with P values <10-6 were investigated in two independent replication cohorts of European patients infected with HCV alone. Two signals of genome-wide significance (P < 5 × 10-8 ) were obtained. The first, on chromosome 3p25 and corresponding to rs61183828 (P = 3.8 × 10-9 ), was replicated in the two independent cohorts of patients with HCV monoinfection. The cluster of single-nucleotide polymorphisms in linkage disequilibrium with rs61183828 was located close to two genes involved in mechanisms affecting both cell signaling and cell structure (CAV3) or HCV replication (RAD18). The second signal, obtained with rs11790131 (P = 9.3 × 10-9 ) on chromosome region 9p22, was not replicated. CONCLUSION: This genome-wide association study identified a new locus associated with liver fibrosis severity in patients with HIV/HCV coinfection, on chromosome 3p25, a finding that was replicated in patients with HCV monoinfection; these results provide new relevant hypotheses for the pathogenesis of liver fibrosis in patients with HIV/HCV coinfection that may help define new targets for drug development or new prognostic tests, to improve patient care. (Hepatology 2016;64:1462-1472).
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Loci Gênicos , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Cirrose Hepática/genética , Cirrose Hepática/virologia , Coinfecção , Progressão da Doença , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Efficient enhancement of photoluminescence in rare-earth activated upconversion materials is of great significance for their practical applications in various fields. In this work, three-dimensional mesoporous gold films were fabricated by a low-cost and facile dealloying approach to improve the upconversion photoluminescence efficiency. The mesoporous Au films exhibit good chemical stability, large-area uniformity and abundant distribution of porous nanospaces. Varying the time of the dealloying process leads to modification of the pore size distribution, surface roughness and residual Ag content, resulting in effective tuning of the wavelength of the broadband localized surface plasmon resonance (LSPR). Enhancement factors were identified to be a function of the dealloying time. With the optimized upconversion photoluminescence enhancement, a 41-fold increase was achieved with the mesoporous gold substrate which had been dealloyed for 8 days. These results pave the way to overcome the limitation of poor upconversion efficiency for widespread practical applications in life science and energy fields.
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BACKGROUND: CD8+ T cells recognize HIV-1 epitopes translated from a gene's primary reading frame (F1) and any one of its five alternative reading frames (ARFs) in the forward (F2, F3) or reverse (R1-3) directions. The 3' end of HIV-1's proviral coding strand contains a conserved sequence that is directly overlapping but antiparallel to the env gene (ARF R2) and encodes for a putative antisense HIV-1 protein called ASP. ASP expression has been demonstrated in vitro using HIV-transfected cell lines or infected cells. Although antibodies to ASP were previously detected in patient sera, T cell recognition of ASP-derived epitopes has not been evaluated. We therefore investigated the ex vivo and in vitro induction of ASP-specific T cell responses as a measure of immune recognition and protein expression during HIV-1 infection. RESULTS: A panel of overlapping peptides was initially designed from the full-length ASP sequence to perform a global assessment of T cell responses. Recognition of ASP-derived antigens was evaluated in an IFN-γELISpot assay using PBMCs from HIV-1 seropositive and seronegative individuals. Eight of 25 patients had positive responses to ASP antigens and none of the seronegative donors responded. As a complimentary approach, a second set of antigens was designed using HLA-I binding motifs and affinities. Two ASP-derived peptides with high predicted binding affinities for HLA-A*02 (ASP-YL9) and HLA-B*07 (ASP-TL10) were tested using PBMCs from HIV-1 seropositive and seronegative individuals who expressed the matching HLA-I-restricting allele. We found that HLA-I-restricted ASP peptides were only recognized by CD8+ T cells from patients with the relevant HLA-I and did not induce responses in any of the seronegative donors or patients who do not express the restrictive HLA alleles. Further, ASP-YL9-specific CD8+ T cells had functional profiles that were similar to a previously described HLA-A*02-restricted epitope (Gag-SL9). Specific recognition of ASP-YL9 by CD8+ T cells was also demonstrated by tetramer staining using cells from an HLA-A*02 HIV-infected patient. CONCLUSION: Our results provide the first description of CD8+ T cell-mediated immune responses to ASP in HIV-1-infected patients, demonstrating that ASP is expressed during infection. Our identification of epitopes within ASP has implications for designing HIV vaccines.
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Linfócitos T CD8-Positivos/imunologia , Expressão Gênica , Antígenos HIV/imunologia , HIV-1/imunologia , HIV-1/fisiologia , Proteínas Virais/imunologia , Replicação Viral , Adulto , Idoso , Células Cultivadas , Estudos de Coortes , ELISPOT , Feminino , Antígenos HIV/biossíntese , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Proteínas Virais/biossínteseRESUMO
Multiple genome-wide association studies (GWAS) have been performed in HIV-1 infected individuals, identifying common genetic influences on viral control and disease course. Similarly, common genetic correlates of acquisition of HIV-1 after exposure have been interrogated using GWAS, although in generally small samples. Under the auspices of the International Collaboration for the Genomics of HIV, we have combined the genome-wide single nucleotide polymorphism (SNP) data collected by 25 cohorts, studies, or institutions on HIV-1 infected individuals and compared them to carefully matched population-level data sets (a list of all collaborators appears in Note S1 in Text S1). After imputation using the 1,000 Genomes Project reference panel, we tested approximately 8 million common DNA variants (SNPs and indels) for association with HIV-1 acquisition in 6,334 infected patients and 7,247 population samples of European ancestry. Initial association testing identified the SNP rs4418214, the C allele of which is known to tag the HLA-B*57:01 and B*27:05 alleles, as genome-wide significant (p = 3.6 × 10⻹¹). However, restricting analysis to individuals with a known date of seroconversion suggested that this association was due to the frailty bias in studies of lethal diseases. Further analyses including testing recessive genetic models, testing for bulk effects of non-genome-wide significant variants, stratifying by sexual or parenteral transmission risk and testing previously reported associations showed no evidence for genetic influence on HIV-1 acquisition (with the exception of CCR5Δ32 homozygosity). Thus, these data suggest that genetic influences on HIV acquisition are either rare or have smaller effects than can be detected by this sample size.
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Infecções por HIV/genética , HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Estudos de Coortes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Infecções por HIV/virologia , Humanos , População BrancaRESUMO
BACKGROUND & AIMS: Chronic infection with HCV remains a public health problem with approximately 150 million people infected worldwide. HCV intersects with lipid metabolism for replication and entry; and plasma concentrations of apolipoproteins have been identified as predictors for response to therapy. Herein, we conducted a screen of plasma proteins, including all apolipoproteins, to identify correlates of response to pegylated-interferon/ribavirin (PR) and HCV non-structural protein 3 (NS3) inhibitors (i.e., telaprevir/boceprevir) therapy in treatment-experienced cirrhotic patients from the ANRS CUPIC cohort. METHODS: We analysed 220 baseline plasma protein concentrations in 189 patients using Luminex technology and analyzed results. RESULTS: We identified baseline levels of apolipoprotein H (apoH) as a surrogate marker for sustained virological response (SVR). Notably, increased plasma concentration of apoH, used in combination with known clinical parameters, established a robust model with improved classification of patients as likely to achieve SVR (AUC = 0.77, Se = 66%, Sp = 72%, NRI = 39%). Moreover, we provide mechanistic information that indicates a previously unidentified role for apoH during viral entry. Using a human liver slices HCV infection model, we demonstrate that apoH limits replication. CONCLUSION: These data support testing of new biomarker strategies for the management of cirrhotic HCV patients and expand our understanding of how apoH may intersect with HCV infection.
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Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Inibidores de Proteases/uso terapêutico , Proteínas não Estruturais Virais/antagonistas & inibidores , Replicação Viral/efeitos dos fármacos , beta 2-Glicoproteína I/sangue , Idoso , Área Sob a Curva , Biomarcadores/sangue , Quimioterapia Combinada , Feminino , França , Hepacivirus/enzimologia , Hepacivirus/genética , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Valor Preditivo dos Testes , Prolina/análogos & derivados , Prolina/uso terapêutico , Estudos Prospectivos , RNA Viral/sangue , Curva ROC , Proteínas Recombinantes/uso terapêutico , Ribavirina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Proteínas não Estruturais Virais/metabolismoRESUMO
The increase of production volumes of silver nanowires (AgNWs) and of consumer products incorporating them may lead to increased health risks from occupational and public exposures. There is currently limited information about the putative toxicity of AgNWs upon inhalation and incomplete understanding of the properties that control their bioreactivity. The lung lining fluid (LLF), which contains phospholipids and surfactant proteins, represents a first contact site with the respiratory system. In this work, the impact of dipalmitoylphosphatidylcholine (DPPC), Curosurf, and murine LLF on the stability of AgNWs was examined. Both the phospholipid and protein components of the LLF modified the dissolution kinetics of AgNWs, due to the formation of a lipid corona or aggregation of the AgNWs. Moreover, the hydrophilic proteins, but neither the hydrophobic surfactant proteins nor the phospholipids, induced agglomeration of the AgNWs. Finally, the generation of a secondary population of nanosilver was observed and attributed to the reduction of Ag(+) ions by the surface capping of the AgNWs. Our findings highlight that combinations of spatially resolved dynamic and static techniques are required to develop a holistic understanding of which parameters govern AgNW behavior at the point of exposure and to accurately predict their risks on human health and the environment.
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1,2-Dipalmitoilfosfatidilcolina/química , Produtos Biológicos/química , Nanofios/química , Fosfolipídeos/química , Surfactantes Pulmonares/química , Prata/química , Animais , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Microscopia/métodosRESUMO
Demand for silver engineered nanomaterials (ENMs) is increasing rapidly in optoelectronic and in health and medical applications due to their antibacterial, thermal, electrical conductive, and other properties. The continued commercial up-scaling of ENM production and application needs to be accompanied by an understanding of the occupational health, public safety and environmental implications of these materials. There have been numerous in vitro studies and some in vivo studies of ENM toxicity but their results are frequently inconclusive. Some of the variability between studies has arisen due to a lack of consistency between experimental models, since small differences between test materials can markedly alter their behaviour. In addition, the propensity for the physicochemistry of silver ENMs to alter, sometimes quite radically, depending on the environment they encounter, can profoundly alter their bioreactivity. Consequently, it is important to accurately characterise the materials before use, at the point of exposure and at the nanomaterial-tissue, or "nanobio", interface, to be able to appreciate their environmental impact. This paper reviews current literature on the pulmonary effects of silver nanomaterials. We focus our review on describing whether, and by which mechanisms, the chemistry and structure of these materials can be linked to their bioreactivity in the respiratory system. In particular, the mechanisms by which the physicochemical properties (e.g., aggregation state, morphology and chemistry) of silver nanomaterials change in various biological milieu (i.e., relevant proteins, lipids and other molecules, and biofluids, such as lung surfactant) and affect subsequent interactions with and within cells will be discussed, in the context not only of what is measured but also of what can be visualized.
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Exposição por Inalação/efeitos adversos , Nanoestruturas , Prata , Animais , Ecotoxicologia/métodos , Humanos , Pneumopatias/etiologia , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Risco , Prata/químicaRESUMO
BACKGROUND: Since the consensus of ISAPP on the definition of the term "postbiotic" there has been an enthusiasm for publications in review form-their number being disproportionate to the primary research. The aim of this bibliometry is to analyze the bibliometric trends of this newfound interest in the field. METHODS: Search of the PubMed database for review articles on postbiotics, published between November 2021 and June 2024. RESULTS: Analysis was performed on 92 review articles, the number corresponding to 2.9 reviews per month. China, Poland, Italy, Iran and India had the maximum productivity among the 32 countries involved; 21 articles were published in 13 journals with the highest impact factor, while 45 were in 16 journals with an IF between 4.0 and 4.9. The authors were mainly affiliated to universities with specialization in both basic research and technology, as well as food science. The top five publications regarding the citations received, published in Foods (2), EBioMedicine, Biomolecules, and Front. Nutr., have collected between 138 and 109 citations. CONCLUSIONS: The ever-growing number of reviews regarding postbiotics is perhaps disproportionate to the actual original research in the field. Further clinical trials would extend and deepen the subject and facilitate the drowning of more robust conclusions in relation to their effects.
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Bibliometria , Humanos , Probióticos , Fator de Impacto de RevistasRESUMO
During SARS-CoV-2 pandemic, the assessment of immune protection of people at risk of severe infection was an important goal. The appearance of VOCs (Variant of Concern) highlighted the limits of evaluating immune protection through the humoral response. While the humoral response partly loses its neutralizing activity, the anti-SARS-CoV-2 memory T cell response strongly cross protects against VOCs becoming an indispensable tool to assess immune protection. We compared two techniques available in laboratory to evaluate anti-SARS-CoV-2 memory T cell response in a cohort of infected or vaccinated patients with different levels of risk to develop a severe disease: the ELISpot assay and the T-Cell Lymphocyte Proliferation Assay respectively exploring IFNγ production and cell proliferation. We showed that the ELISpot assay detected more anti-Spike memory T cell response than the Lymphocyte Proliferation Assay. We next observed that the use of two different suppliers as antigenic source in the ELISpot assay did not affect the detection of anti-Spike memory T cell response. Finally, we explored a new approach for defining the positivity threshold, using unsupervised mixed Gaussian modeling, challenging the traditional ROC curve used by the supplier. That will be helpful in endemic situation where it could be difficult to recruit "negative" patients.
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COVID-19 , ELISPOT , Células T de Memória , SARS-CoV-2 , Humanos , COVID-19/imunologia , COVID-19/epidemiologia , SARS-CoV-2/imunologia , Células T de Memória/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Proliferação de Células , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Adulto , Idoso , Interferon gama/imunologia , Interferon gama/metabolismo , Glicoproteína da Espícula de Coronavírus/imunologia , Memória ImunológicaRESUMO
The skin serves as a critical barrier against external threats-dehydration, ultraviolet exposure, and infections-playing a significant role in internal homeostasis and moisture retention. Additionally, and equally importantly, it interacts dynamically with the complex microbiome resident in it, which is essential for maintaining skin health. Recent interest has focused on the use of probiotics and postbiotics, besides their ability to modulate the skin microbiome, to enhance barrier function, and exhibit anti-inflammatory properties, to be involved in skincare, by having the potential to improve skin hydration, elasticity, and overall appearance, as well as in reducing signs of aging, such as wrinkles and fine lines. The products-being a combination of a cosmetic regime plus probiotic[s] or postbiotic[s]-are named cosmeceuticals. However, to comply with the regulations for the characterization of a microorganism as a specific probiotic strain, the pro- or postbiotics incorporated into the cosmetic regime should be both genetically and phenotypically defined. Thus, in this review, we present 14 published clinical trials using such cosmetic products with specific, well-characterized strains of probiotics or postbiotics applied to volunteers with healthy skin. Looking at the results of these studies collectively, we can say that these genetically and phenotypically defined strains of either live or inanimate bacteria and/or their components seem to keep the treated skin at least fully hydrated, with intact epithelial tone, increased radiance, and with decreased wrinkle depth, while normalizing the commensal skin microbiota. Future advancements in personalized skin care may lead to genomic sequencing and metabolomics to tailor probiotic and postbiotic treatments to individual skin microbiomes, promising a new frontier in cosmeceuticals.
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Cosmecêuticos , Probióticos , Envelhecimento da Pele , Pele , Probióticos/farmacologia , Humanos , Pele/microbiologia , Envelhecimento da Pele/efeitos dos fármacos , Microbiota , Ensaios Clínicos como AssuntoRESUMO
The key attributes of CD8+ T cell protective immunity in human immunodeficiency virus (HIV) infection remain unclear. We report that CD8+ T cell responses specific for Gag and, in particular, the immunodominant p24 epitope KK10 correlate with control of HIV-1 replication in human histocompatibility leukocyte antigen (HLA)-B27 patients. To understand further the nature of CD8+ T cell-mediated antiviral efficacy, we performed a comprehensive study of CD8+ T cells specific for the HLA-B27-restricted epitope KK10 in chronic HIV-1 infection based on the use of multiparametric flow cytometry together with molecular clonotypic analysis and viral sequencing. We show that B27-KK10-specific CD8+ T cells are characterized by polyfunctional capabilities, increased clonal turnover, and superior functional avidity. Such attributes are interlinked and constitute the basis for effective control of HIV-1 replication. These data on the features of effective CD8+ T cells in HIV infection may aid in the development of successful T cell vaccines.