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Commun Biol ; 5(1): 1351, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494499


T cells play a pivotal role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. We studied 50 COVID-19 convalescent patients and found that T cell response was induced more frequently and persisted longer than circulating antibodies. We identified 756 clonotypes specific to nine CD8+ T cell epitopes. Some epitopes were recognized by highly similar public clonotypes. Receptors for other epitopes were extremely diverse, suggesting alternative modes of recognition. We tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the studied epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence.

COVID-19 , SARS-CoV-2 , Humanos , Epitopos de Linfócito T , Linfócitos T CD8-Positivos , Células Clonais
JCI Insight ; 7(9)2022 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-35389886


The ongoing COVID-19 pandemic calls for more effective diagnostic tools. T cell response assessment serves as an independent indicator of prior COVID-19 exposure while also contributing to a more comprehensive characterization of SARS-CoV-2 immunity. In this study, we systematically assessed the immunogenicity of 118 epitopes with immune cells collected from multiple cohorts of vaccinated, convalescent, healthy unexposed, and SARS-CoV-2-exposed donors. We identified 75 immunogenic epitopes, 24 of which were immunodominant. We further confirmed HLA restriction for 49 epitopes and described association with more than 1 HLA allele for 14 of these. Exclusion of 2 cross-reactive epitopes that generated a response in prepandemic samples left us with a 73-epitope set that offered excellent diagnostic specificity without losing sensitivity compared with full-length antigens, and this evoked a robust cross-reactive response. We subsequently incorporated this set of epitopes into an in vitro diagnostic Corona-T-test, which achieved a diagnostic accuracy of 95% in a clinical trial. In a cohort of asymptomatic seronegative individuals with a history of prolonged SARS-CoV-2 exposure, we observed a complete absence of T cell response to our epitope panel. In combination with strong reactivity to full-length antigens, this suggests that a cross-reactive response might protect these individuals.

COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Epitopos de Linfócito T , Humanos , Pandemias , Linfócitos T
Front Psychol ; 9: 92, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29479326


Recently, two forms of virtue-related humor, benevolent and corrective, have been introduced. Benevolent humor treats human weaknesses and wrongdoings benevolently, while corrective humor aims at correcting and bettering them. Twelve marker items for benevolent and corrective humor (the BenCor) were developed, and it was demonstrated that they fill the gap between humor as temperament and virtue. The present study investigates responses to the BenCor from 25 samples in 22 countries (overall N = 7,226). The psychometric properties of the BenCor were found to be sufficient in most of the samples, including internal consistency, unidimensionality, and factorial validity. Importantly, benevolent and corrective humor were clearly established as two positively related, yet distinct dimensions of virtue-related humor. Metric measurement invariance was supported across the 25 samples, and scalar invariance was supported across six age groups (from 18 to 50+ years) and across gender. Comparisons of samples within and between four countries (Malaysia, Switzerland, Turkey, and the UK) showed that the item profiles were more similar within than between countries, though some evidence for regional differences was also found. This study thus supported, for the first time, the suitability of the 12 marker items of benevolent and corrective humor in different countries, enabling a cumulative cross-cultural research and eventually applications of humor aiming at the good.

ACS Nano ; 7(1): 286-93, 2013 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-23241017


We have investigated superlattices consisting of up to 30 epitaxial nanomultilayers (3-7 nm thick) of ferromagnetic La(2/3)Ca(1/3)MnO(3) (LCMO) and insulating SrTiO(3) (STO) hybrids. The superlattices demonstrate dramatic shifts of Curie temperature, indicating the possibility of its tunability. The metal-insulator transition (MIT) has been observed around 140 K. Below the MIT temperature, the superlattices have shown sharp drops of resistivity, facilitating the largest and sharpest magnetoresistance peaks (>2000%) ever observed in LCMO films and superlattices at low temperatures. The observed experimental results can be explained in the frame of the phase separation model in manganites with well-organized structures. The results of magnetic and transport measurements of such hybrid structures are discussed, indicating a magnetodielectric effect in STO interlayers. The magnetic and transport properties of the superlattices are shown to be technology-dependent, experiencing dimensional transitions, which enables the creation of structures with prescribed magnetoresistance characteristics for a broad range of applications.

Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Impedância Elétrica , Campos Magnéticos , Teste de Materiais , Tamanho da Partícula
Biochem J ; 429(2): 291-302, 2010 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-20459395


KRP (kinase-related protein), also known as telokin, has been proposed to inhibit smooth muscle contractility by inhibiting the phosphorylation of the rMLC (regulatory myosin light chain) by the Ca2+-activated MLCK (myosin light chain kinase). Using the phosphatase inhibitor microcystin, we show in the present study that KRP also inhibits Ca2+-independent rMLC phosphorylation and smooth muscle contraction mediated by novel Ca2+-independent rMLC kinases. Incubating KRP-depleted Triton-skinned taenia coli with microcystin at pCa>8 induced a slow contraction reaching 90% of maximal force (Fmax) at pCa 4.5 after approximately 25 min. Loading the fibres with KRP significantly slowed down the force development, i.e. the time to reach 50% of Fmax was increased from 8 min to 35 min. KRP similarly inhibited rMLC phosphorylation of HMM (heavy meromyosin) in vitro by MLCK or by the constitutively active MLCK fragment (61K-MLCK) lacking the myosin-docking KRP domain. A C-terminally truncated KRP defective in myosin binding inhibited neither force nor HMM phosphorylation. Phosphorylated KRP inhibited the rMLC phosphorylation of HMM in vitro and Ca2+-insensitive contractions in fibres similar to unphosphorylated KRP, whereby the phosphorylation state of KRP was not altered in the fibres. We conclude that (i) KRP inhibits not only MLCK-induced contractions, but also those elicited by Ca2+-independent rMLC kinases; (ii) phosphorylation of KRP does not modulate this effect; (iii) binding of KRP to myosin is essential for this inhibition; and (iv) KRP inhibition of rMLC phosphorylation is most probably due to the shielding of the phosphorylation site on the rMLC.

Colo/fisiologia , Contração Muscular/fisiologia , Quinase de Cadeia Leve de Miosina/metabolismo , Fragmentos de Peptídeos/metabolismo , Animais , Sequência de Bases , Sítios de Ligação , Cálcio/metabolismo , Cálcio/farmacologia , Proteínas de Ligação ao Cálcio/química , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/farmacologia , Galinhas , Colo/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Primers do DNA/genética , Feminino , Cobaias , Humanos , Técnicas In Vitro , Masculino , Toxinas Marinhas , Microcistinas/farmacologia , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Modelos Biológicos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/fisiologia , Cadeias Leves de Miosina/química , Cadeias Leves de Miosina/metabolismo , Subfragmentos de Miosina/química , Subfragmentos de Miosina/metabolismo , Quinase de Cadeia Leve de Miosina/química , Quinase de Cadeia Leve de Miosina/genética , Quinase de Cadeia Leve de Miosina/farmacologia , Octoxinol , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/farmacologia , Fosforilação , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia