Role of nitric oxide in the maturation process of human dendritic cells

Nitric oxide (NO) generated by phagocytes at inflammation sites contributes to regulate immune responses through both autocrine and paracrine actions on bystander cells. Among the latter are dendritic cells (DCs). Little is known about regulation of DC function by NO, especially in the human system. In this thesis I report about the role of NO in two specific aspects of human DC maturation: i.e. endocytosis and ability to induce T cell activation. At variance with rodents, human DCs express the inducible isoform of the NO synthase neither when immature, nor after various treatment which induce DC maturation, indicating that regulation of these cells may occur only through exogenous NO. Exposure of DCs to NO, released by either bystander phagocytes or NO donors, reversed the inhibition of endocytosis induced by TNF-a. The intracellular accumulation of ceramide induced by TNF-a was also inhibited by NO. In addition, NO was found to exert an inhibitory effect downstream of the TNF-a-triggered ceramide accumulation, since NO donors reversed the inhibition of endocytosis induced by the cell-permeant C2-ceramide. I then studied the role of NO on DC ability of triggering T cell activation. DCs were exposed to the NO donor DETA-NO during their maturation process induced by treatment with TNF-a or lipopolysaccharide, or by CD40 activation. After exposure to DETA-NO, DCs exhibit a significantly increased ability to activate T lymphocytes stimulated by mycobacterial antigens, Staphylococcus aureus Cowen strain B, allo-antigens, or cross-linking of the CD3-T cell receptor complex. This effect persists after removal of DETA-NO and is due to enhanced release by DCs of soluble factors, in particular IL-12. All the effects described above were mimicked by the membrane-permeant cyclic GMP analogue, 8-Br cyclic GMP, and prevented by inhibition of the soluble guanyly 1-cyclase. The cGMP dependent modulation of DC function reported here is due to a synergism between NO and the various maturation stimuli since neither the changes in endocytic function nor the enhanced T cell activation and IL-12 release were observed after DC exposure to DETA-NO only. These results provide the first evidence that NO acts as a co-signalling molecule regulating human DC response to maturation stimuli

Narrative and orthographic writing abilities in Elementary School students: characteristics and correlations

PURPOSE: To characterize, according to the school grade and the type of school (private or public), the performance on orthographic and narrative text production in the writing of Elementary School students with good academic performance, and to investigate the relationships between these variables. METHODS: Participants were 160 children with ages between 8 and 12 years, enrolled in 4th to 7th grades Elementary School. Their written production was assessed using words and pseudowords dictation, and autonomous writing of a narrative text. RESULTS: Public school students had a higher number of errors in the words and pseudowords dictation, improving with education level. The occurrence of complete and incomplete utterances was similar in both public and private schools. However, 4th graders presented more incomplete statements than the other students. A higher number of overall microstructure and macrostructure productions occurred among private school students. The essential macrostructures were most frequently found in the later school grades. The higher the total number of words in the autonomous written production, the higher the occurrence of linguistic variables and the better the narrative competence. There was a weak negative correlation between the number of wrong words and the total of events in text production. Positive and negative correlations (from weak to good) were observed between different orthographic, linguistic and narrative production variables in both private and public schools. CONCLUSION: Private school students present better orthographic and narrative performance than public school students. Schooling progression influences the performance in tasks of words' writing and text production, and the orthographic abilities influence the quality of textual production. Different writing abilities, such as orthographic performance and use of linguistic elements and narrative structures, are mutually influenced in writing production.OBJETIVO: Caracterizar, de acordo com o ano escolar e a rede de ensino, o desempenho ortográfico e de produção textual da escrita de escolares do Ensino Fundamental, com bom aproveitamento acadêmico, e investigar as relações entre essas variáveis. MÉTODOS: Participaram 160 crianças, entre 8 e 12 anos de idade, alunos do 4º ao 7º anos do Ensino Fundamental. Todos foram avaliados quanto à produção escrita, por meio de ditado de palavras e pseudopalavras e da escrita autônoma de texto narrativo. Computaram-se os erros ortográficos, os números de palavras, por classe gramatical, e os elementos de narrativa textual utilizados nas produções. RESULTADOS: Escolares da rede pública apresentaram mais erros no ditado de palavras e pseudopalavras, com melhora de desempenho com o avanço da escolaridade. No entanto, a ocorrência de enunciados completos e incompletos mostrou-se semelhante quando comparadas as redes de ensino. Escolares do 4º ano apresentaram mais enunciados incompletos que os demais. Quanto às produções de microestruturas e macroestruturas gerais, maior número destas foi apresentado pelos escolares da rede particular. As macroestruturas essenciais foram mais frequentes nos anos mais avançados. Quanto maior o número de palavras escritas na produção autônoma, maior a ocorrência das variáveis linguísticas e melhor a competência narrativa. Houve correlação negativa e fraca entre o número de palavras erradas e o total de eventos na produção textual. Foram observadas correlações positivas e negativas (de fracas a boas) entre diferentes variáveis ortográficas, linguísticas e de produção narrativa em ambas as redes. CONCLUSÃO: Os escolares da rede particular apresentam melhor desempenho ortográfico e narrativo que os da rede pública. A progressão da escolaridade influencia o desempenho nas tarefas de escrita de palavras e produção textual e as capacidades ortográficas influenciam a qualidade da produção textual. Diferentes habilidades de escrita como desempenho ortográfico e uso de elementos linguísticos e de estruturas narrativas influenciam-se mutuamente na produção escrita.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

The p75NTR-induced Apoptotic Program Develops through a Ceramide-Caspase Pathway Negatively Regulated by Nitric Oxide

SK-N-BE neuroblastoma cell clones transfected with p75(NTR) and lacking Trk neurotrophin receptors, previously reported to undergo extensive spontaneous apoptosis and to be protected by nerve growth factor (NGF) (Bunone, G., Mariotti, A., Compagni, A., Morandi, E., and Della Valle, G. (1997) Oncogene 14, 1463-1470), are shown to exhibit (i) increased levels of the pro-apoptotic lipid metabolite ceramide and (ii) high activity of caspases, the proteases of the cell death cascade. In the p75(NTR)-expressing cells, these parameters were partially normalized by prolonged NGF treatment, which, in addition, decreased apoptosis, similar to caspase blockers. Conversely, exogenous ceramide increased caspase activity and apoptosis in both wild-type and p75(NTR)-expressing cells. A new p75(NTR)-expressing clone characterized by low spontaneous apoptosis exhibited high endogenous ceramide and low caspase levels. A marked difference between the apoptotic and resistant clones concerned the very low and high activities of nitric-oxide (NO) synthase, respectively. Protection from apoptosis by NO was confirmed by results with the NO donor S-nitrosoacetylpenicillamine and the NO-trapping agent hemoglobin. We conclude that the p75(NTR) receptor, while free of NGF, triggers a cascade leading to apoptosis; the cascade includes generation of ceramide and increased caspase activity; and the protective role of NO occurs at step(s) in between the latter events

Reading errors typology of Brazilian students considered good readers

BACKGROUND: assessment of oral reading. AIM: to characterize, according to the variables of public or private school and literacy, the types of errors in word reading presented by typical elementary/middle school students considered competent readers by their teachers. METHOD: participants of this study were 151 students with ages ranging between 8 and 12 years, from the 4th to the 7th grade of public and private schools. The students read a list of 38 words. The oral readings were transcribed and the errors analyzed according to their frequency. The frequency of errors was calculated based on the possibilities of errors presented by the used word list. RESULTS: the obtained results gave evidence to the errors presented by typical students of both public and private schools from all of the tested grades. There was a statistically significant progressive reduction in errors of orthographic decoding according to literacy (p<0.0001). Considering the groups, students from private schools presented fewer errors of global orthographic decoding when compared to students from public schools (p < 0.0001). CONCLUSION: the results suggest that reading errors are part of the learning process of orthographic decoding rules. These errors are progressively overcome with literacy. The domain of orthographic decoding independent of the context occurred more prematurely than that which is dependent of the grapheme context.TEMA: avaliação da leitura oral. OBJETIVO: caracterizar, segundo as variáveis rede de ensino e escolaridade, os tipos de erro na leitura de palavras isoladas, apresentados por escolares típicos do ensino fundamental, considerados competentes por seus professores. MÉTODO: participaram da pesquisa 151 escolares com idade entre oito e doze anos, matriculados do quarto ao sétimo ano do ensino fundamental das redes pública e particular. Os escolares leram uma lista com 38 palavras. As leituras orais foram transcritas e os erros analisados, segundo a freqüência de erros cometidos calculada com base na possibilidade de erros oferecida pela lista apresentada. RESULTADOS: os resultados encontrados evidenciaram a presença de erros quando analisadas as leituras dos escolares típicos de ambas as redes de ensino e de todas as séries estudadas. Houve redução progressiva e estatisticamente significante dos erros de decodificação ortográfica em função da progressão da escolaridade (p < 0,0001). Considerando a rede de ensino, os escolares da rede particular apresentaram menor número de erros que os de escola pública quando comparado o desempenho na decodificação ortográfica global na prova de leitura de palavras (p < 0,0001). CONCLUSÃO: os resultados demonstraram que os erros de leitura fazem parte do aprendizado das regras de decodificação ortográfica e são superados, progressivamente, com o aumento da escolaridade. O domínio da decodificação da ortografia independente do contexto ocorreu mais precocemente que o da dependente do contexto grafêmico.UNIFESP Departamento de FonoaudiologiaUNIFESPUNIFESP, Depto. de FonoaudiologiaUNIFESPSciEL

Síndrome de Young: Young's Syndrome

Introdução: A Síndrome de Young refere-se à condição rara e hereditária, de etiologia desconhecida, que acomete homens de meia idade causando-lhes a tríade rinossinusite, bronquiectasias e azoospermia obstrutiva. Apresentação do caso: paciente do sexo masculino, 36 anos, encaminhado ao ambulatório de urologia por dificuldade para engravidar. Apresenta tosse crônica e rinossinusite de repetição desde a infância. Exames complementares possibilitaram o diagnóstico de Síndrome de Young. Discussão: A ocorrência de azoospermia persistente com espermatogênese normal, associada a episódios recorrentes de infecções pulmonares, além da exclusão de fibrose cística ou discinesia ciliar primária caracterizam a Síndrome de Young, que não tem cura, contudo é passível a tratamento individualizado e dependente da sintomatologia do paciente. Conclusão: Apesar de ser um distúrbio raro, o diagnóstico precoce é capaz de prevenir complicações associadas, entre elas a infertilidade. No entanto, a escassez de estudos acerca deste distúrbio pode afetar negativamente a qualidade de vida e a morbimortalidade dos pacientes, portanto ressalta-se a importância da produção de evidências científicas

Síndrome de Trotter: Trotter's Syndrome

Introdução: A Síndrome de Trotter refere-se ao quadro clínico característico de neoplasias da nasofaringe, principalmente quando os tumores são encontrados em estágios mais avançados. Apresentação do caso: paciente do sexo masculino, 55 anos, com dor mandibular à esquerda, que iniciou- se com otalgia, zumbido, hipoacusia e cefaléia fronto-temporal à esquerda, evoluindo para dor em região de mandíbula e trismo. Foi solicitado tomografia de base de crânio e nasofaringe, com sinais sugestivos da Síndrome de Trotter. Discussão: O caso trata- se de uma síndrome pouco conhecida devido apresentar sinais e sintomas muitas vezes banalizados, sendo que, a maioria das neoplasias são descobertas em casos bastantes avançados&nbsp; e com um prognóstico muito reservado. Conclusão: Se descoberta precocemente, aumentaria então, as chances de sucesso no tratamento. Ademais, cabe aos profissionais odontólogos e médicos se atentar e buscar conhecimento acerca da clínica desta síndrome a fim de corroborar no diagnóstico precoce

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio