Stromal cell–derived factor 1α increases polyploidization of megakaryocytes generated by human hematopoietic progenitor cells

AbstractThe alpha chemokine receptor CXCR4 has been shown to be expressed on human hematopoietic progenitor cells and during the megakaryocytic differentiation pathway. Stromal cell–derived factor 1 (SDF-1) is the ligand for CXCR4. In this study, the role of SDF-1α in megakaryocytopoiesis was investigated. CD34+ progenitors purified from peripheral blood were grown in serum-free liquid suspension culture supplemented with thrombopoietin to obtain a virtually pure megakaryocytic progeny. In this condition, the addition of SDF-1α gives rise to megakaryocytes (MKs) showing an increased DNA content and a rise of lobated nuclei, as compared with untreated cells: at day 5, approximately 20% of the cells already showed the presence of more than one nuclear lobe versus fewer than 5% in the control cells; at day 12, approximately 85% of the cells were of large size and markedly polyploid, whereas approximately 60% of the control cells were polyploid, showed fewer lobes, and were a smaller size. This effect was dose-dependent and did not affect the megakaryocytic proliferation. Experiments with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 suggested a role for MAPK pathway on SDF-1α–induced endomitosis. Furthermore, SDF-1α induced a significant increase in the number of proplatelet-bearing MKs and promoted the migration of megakaryocytic cells. Treatment with SDF-1α caused reduction in CXCR4 abundance on the plasma membrane, seemingly owing to receptor internalization. Furthermore, the presence of SDF-1α did not affect the expression of megakaryocytic markers, indicating that differentiation and polyploidization are independently regulated events

MRAP2 Inhibits β-Arrestin-2 Recruitment to the Prokineticin Receptor 2

Melanocortin receptor accessory protein 2 (MRAP2) is a membrane protein that binds multiple G protein-coupled receptors (GPCRs) involved in the control of energy homeostasis, including prokineticin receptors. These GPCRs are expressed both centrally and peripherally, and their endogenous ligands are prokineticin 1 (PK1) and prokineticin 2 (PK2). PKRs couple all G-protein subtypes, such as Gαq/11, Gαs, and Gαi, and recruit β-arrestins upon PK2 stimulation, although the interaction between PKR2 and β-arrestins does not trigger receptor internalisation. MRAP2 inhibits the anorexigenic effect of PK2 by binding PKR1 and PKR2. The aim of this work was to elucidate the role of MRAP2 in modulating PKR2-induced β-arrestin-2 recruitment and β-arrestin-mediated signalling. This study could allow the identification of new specific targets for potential new drugs useful for the treatment of the various pathologies correlated with prokineticin, in particular, obesity

Functional Interaction between Adenosine A_2A and mGlu₅ Receptors Mediates STEP Phosphatase Activation and Promotes STEP/mGlu₅R Binding in Mouse Hippocampus and Neuroblastoma Cell Line

(1) Background: Recently, we found that adenosine A2A receptor (A2AR) stimulation results in an increase in STEP phosphatase activity. In order to delve into the mechanism through which A2AR stimulation induced STEP activation, we investigated the involvement of mGlu5R since it is well documented that A2AR and mGlu5R physically and functionally interact in several brain areas. (2) Methods: In a neuroblastoma cell line (SH-SY5Y) and in mouse hippocampal slices, we evaluated the enzymatic activity of STEP by using a para-nitrophenyl phosphate colorimetric assay. A co-immunoprecipitation assay and a Western blot analysis were used to evaluate STEP/mGlu5R binding. (3) Results: We found that the A2AR-dependent activation of STEP was mediated by the mGlu5R. Indeed, the A2AR agonist CGS 21680 significantly increased STEP activity, and this effect was prevented not only by the A2AR antagonist ZM 241385, as expected, but also by the mGlu5R antagonist MPEP. In addition, we found that mGlu5R agonist DHPG-induced STEP activation was reversed not only by the mGlu5R antagonist MPEP but also by ZM 241385. Finally, via co-immunoprecipitation experiments, we found that mGlu5R and STEP physically interact when both receptors are activated (4) Conclusions: These results demonstrated a close functional interaction between mGlu5 and A2A receptors in the modulation of STEP activity

Evolução do comportamento auditivo após meningite bacteriana: relato de caso Auditory behaviour monitoring after bacterial meningitis: case report

A deficiência auditiva adquirida tem nas meningites bacterianas a sua principal etiologia e pouco tem-se dito a respeito da evolução para melhora ou piora do comportamento auditivo após a alta hospitalar. O presente estudo descreve o caso de um menino que teve meningite por Haemophilus influenzae aos 5 meses de vida e que entre outras complicações apresentou diminuição da acuidade auditiva detectada na evolução imediata, com melhora significativa posteriormente, confirmada por testes qualitativos e quantitativos. Discute-se a importância e a necessidade do seguimento fonoaudiológico de tais indivíduos para estabelecer orientação adequada.Bacterial meningitis is the main cause for acquired hearing loss. Nevertheless very little has been written about the development of the auditory behaviour either for improvement or for deterioration, after hospital release. The present study describes the case of a five month old boy with Haemophilus influenzae meningitis. Amongst various complications, a decrement in the auditory acuity was detected in the immediate evolution, with significant improvement later on by qualitative and quantitative tests

Catalysts based on Rh(III)-hexamolybdate/g-Al2O3 and their application in the selective hydrogenation of cinnamaldehyde to hydrocinnamaldehyde

Several catalysts based on [RhMo6O24H6]3− (RhMo6) heteropolyanion supported on -Al2O3 with different textural properties were prepared, characterized and tested in the liquid-phase hydrogenation of cinnamaldehyde. The characterization of pure and supported systems was carried out using several techniques including XRD, SEM-EDS microscopy, Raman microprobe, X-ray photoelectron spectroscopies and temperature programmed reduction (TPR). The catalytic performance was monitored by conversion of the starting cinnamaldehyde as a function of time: the initial activities represented as the turnover frequency (TOF), were measured considering the surface Rh atoms. The planar heteropolyanion RhMo6/(EI) based systems showed enhanced catalytic activity over the RhMo conventional catalyst obtained by successive impregnation of both transition metal ions (Rh(III) chloride and heptamolybdate). The selectivity for the RhMo6 systems was mainly toward HCAL unlike the conventional catalyst which showed selectivity toward CA. This study also showed a synergetic effect between Rh and Mo through which Rh promoted Mo reducibility.Fil: Bertolini, Guillermo Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Ciencias Aplicadas; ArgentinaFil: Cabello, Carmen Ines . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Ciencias Aplicadas; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Muñoz, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Ciencias Aplicadas; ArgentinaFil: Casella, Monica Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Centro de Investigación y Desarrollo En Ciencias Aplicadas; ArgentinaFil: Gazzoli, Delia. Dipartimento Di Chimica; ItaliaFil: Pettiti, Ida. Dipartimento Di Chimica; ItaliaFil: Ferraris, Giovani. Dipartimento Di Chimica; Itali

Sequelae from meningococcal meningitis in children: a critical analysis of dexamethasone therapy Seqüelas de meningite meningocócica em crianças: análise crítica da utilização da dexametasona

OBJECTIVE: To evaluate the effectiveness of dexamethasone as an adjunctive therapy to antibiotics in children with meningococcal meningitis. METHOD: A total of 81 children diagnosed with meningococcal meningitis hospitalized in sequence were studied at the University Hospital of São Paulo University, with the objective of evaluating the presence of sequelae in four different groups of patients, following the administration of dexamethasone: Group I - 25 patients who received the first dose at least 10 minutes before the introduction of the antibiotic therapy; Group II - 19 patients who received the corticosteroid concomitantly; Group III - 14 patients for which the dexamethasone was administered after beginning the antibiotic scheme; Group IV - 23 patients that did not receive dexamethasone. The groups were evaluated for homogeneity through the prognostic indexes and clinical and laboratory characteristics, based on the records obtained at hospitalization. RESULTS: Some degree of sequelae occurred in 16 (26.22%) of the survivors and 23 patients (28.39%) coursed with sequelae or died. The mean period of neurological attendance was 36.97 months and neurological alterations were detected in 16.17% of the patients. No significant difference was found between the four groups. There was also no statistical difference in the comparison of the neurological sequelae in the children from group IV with the children of groups I and II or even with groups I, II and III analyzed as a whole. The presence of hearing loss occurred in 11.11% of the patients, again there was no significant difference between the four groups. Psychological evaluation was performed using the WPSSI and WISC tests. A mild mental disability was detected in one patient from group I and another in group III. The overall analysis of the sequelae (neurological, auditory and intellectual level) also did not demonstrate any significant difference between the four groups. Comparing the children from groups I and II together and also groups I, II and III as a whole with the children in group IV also failed to detect a significant difference arising from the use or nonuse of the corticosteroid. CONCLUSION: Dexamethasone was not proven to be effective in decreasing the number of sequelae among patients with meningococcal meningitis.OBJETIVO: Avaliar a eficácia da dexametasona como uma terapia adjunta à antibioticoterapia em crianças com meningite meningocócica. MÉTODO: Foram avaliadas 81 crianças com diagnóstico de meningite meningocócica e hospitalizadas sequencialmente no Hospital Universitário da Universidade de São Paulo, com o objetivo de avaliar a presença de sequelas em 4 diferentes grupos de pacientes, segundo a administração da dexametasona: Grupo I - 25 pacientes, que receberam a primeira dose pelo menos 10 minutos antes da introdução da antibioticoterapia; Grupo II - 19 pacientes que receberam o corticosteróide de modo concomitante à antibioticoterapia; Grupo III - 14 pacientes, nos quais a dexametasona foi administrada após o início do esquema antibiótico; Grupo IV - 23 pacientes que não receberam dexametasona. A avaliação das características clínicas e laboratoriais no momento da internação demonstrou que os 4 grupos poderiam ser considerados homogêneos. RESULTADOS: Algum grau de sequela ocorreu em 16 (26,22%) dos sobreviventes e 23 pacientes (28,39%) apresentaram sequelas ou faleceram. O período médio de seguimento neurológico foi 36,97 meses e foram detectadas alterações neurológicas em 16,17% dos pacientes. Não se observaram diferenças significativas em relação a presença de seqüelas neurológicas entre os 4 grupos, não havendo também diferenças entre as crianças do grupo IV em relação ao agrupamento das crianças dos grupos I e II ou mesmo I, II e III. A presença de disacusia ocorreu em 11,11% dos pacientes, também não havendo diferenças entre os 4 grupos. A avaliação psicológica foi realizada através dos testes WPSSI and WISC. Foi detectada a presença de deficiência mental leve em um paciente do grupo I e em outro do grupo III. A avaliação global das sequelas (neurológicas, auditivas e cognitivas) também não mostrou haver diferenças significativas entre os 4 grupos. A comparação conjunta das crianças dos grupos I e II e também dos grupos I, II e III com as do grupo IV, também não permitiu a verificação da presença de diferenças significativas em relação a utilização ou não do corticosteróide. CONCLUSÃO: A dexametasona não foi efetiva na redução de sequelas em crianças com meningite meningocóccica

Milano Rogoredo. Innovation District. Riqualificazione del comparto urbano di Via Medici del Vascello a Milano

In coesione con gli obiettivi richiesti dal bando del Workshop di progettazione RE-LIVE 2019, volti a definire e a “fornire un apporto culturale, scientifico e di ricerca utile a supportare la definizione dei contenuti di un Progetto di Fattibilità Tecnico Economica per il comparto urbano di Via Medici del Vascello”, la ricerca progettuale proposta dal gruppo di lavoro MINA si è strutturata su tre diversi enunciati: - Il primo enunciato riguarda l’approccio metodologico adottato attraverso le relazioni dialogiche ed analogiche delle proposte progettuali con il contesto non solo contiguo e prossimo all’area di intervento, ma esteso ad un ambito più vasto in cui i caratteri tipo-morfologici, le preesistenze ambientali e il sistema infrastrutturale (di terra, di acqua e di ferro) hanno assunto lo sfondo fisico-spaziale oltre che culturale per la lettura interpretativa della città di Milano. - Il secondo enunciato riguarda il ruolo strategico del progetto del Giardino Metamorfico, inteso come nuovo spazio pubblico per eccellenza di ultima generazione inserito nell’area ARU – Ambito di rigenerazione ambientale - del comparto di Santa Giulia, oggetto, in questi ultimi anni, di un processo di trasformazione che investe l’intero quadrante urbano sud-est della città. Il nuovo parco definisce un nuovo assetto urbano grazie la realizzazione di nuovi spazi collettivi verdi aperti alla comunità e servizi. - Il terzo enunciato focalizza la sua attenzione sulla sperimentazione e l’individuazione di nuovi modelli dell’abitare secondo un processo ermeneutico del lotto gotico, volto a definire una mixitè urbana e funzionale capaci di accogliere processi innovativi in cui le residenze, le attività produttive e gli spazi dedicati al tempo libero e siano capaci di coesistere simultaneamente