The late endocytic Rab39a GTPase regulates the interaction between multivesicular bodies and chlamydial inclusions.

Given their obligate intracellular lifestyle, Chlamydia trachomatis ensure their access to multiple host sources of essential lipids by interfering vesicular transport. These bacteria hijack Rab6-, Rab11- and Rab14-controlled trafficking pathways to acquire sphingomyelin from the Golgi apparatus. Another important source of sphingolipids, phospholipids and cholesterol are multivesicular bodies (MVBs). Despite their participation in chlamydial inclusion development and bacterial replication, the molecular mechanisms mediating MVBs-inclusion interaction remain unknown. In the present study, we demonstrate that Rab39a labels a subset of late endocytic vesicles -mainly MVBs- that move along microtubules. Moreover, Rab39a is actively recruited to chlamydial inclusions throughout the pathogen life cycle by a bacterial-driven process and depending on its GTP/GDP binding state. Interestingly, Rab39a participates in the delivery of MVB and host sphingolipids to maturing chlamydial inclusions thereby promoting inclusion growth and bacterial development. Altogether, our findings indicate that Rab39a favours chlamydial replication and infectivity. This is the first report showing a late endocytic Rab GTPase involved in chlamydial infection development.Fil: Gambarte Tudela, Julian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Capmany, Anahi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Romao, Maryse. Institute Curie; FranciaFil: Quintero, Cristian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Miserey Lenkei, Stephanie. Institute Curie; FranciaFil: Raposo, Graça. Institute Curie; FranciaFil: Goud, Bruno. Institute Curie; FranciaFil: Damiani, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin

Rab39a and Rab39b display different intracellular distribution and function in sphingolipids and phospholipids transport

Rab GTPases define the identity and destiny of vesicles. Some of these small GTPases present isoforms that are expressed differentially along developmental stages or in a tissue-specific manner, hence comparative analysis is difficult to achieve. Here, we describe the intracellular distribution and function in lipid transport of the poorly characterized Rab39 isoforms using typical cell biology experimental tools and new ones developed in our laboratory. We show that, despite their amino acid sequence similarity, Rab39a and Rab39b display non-overlapping intracellular distribution. Rab39a localizes in the late endocytic pathway, mainly at multivesicular bodies. In contrast, Rab39b distributes in the secretory network, at the endoplasmic reticulum/cis-Golgi interface. Therefore, Rab39a controls trafficking of lipids (sphingomyelin and phospholipids) segregated at multivesicular bodies, whereas Rab39b transports sphingolipids biosynthesized at the endoplasmic reticulum-Golgi factory. Interestingly, lyso bis-phosphatidic acid is exclusively transported by Rab39a, indicating that both isoforms do not exert identical functions in lipid transport. Conveniently, the requirement of eukaryotic lipids by the intracellular pathogen Chlamydia trachomatis rendered useful for dissecting and distinguishing Rab39a-and Rab39b-controlled trafficking pathways. Our findings provide comparative insights about the different subcellular distribution and function in lipid transport of the two Rab39 isoforms.Fil: Gambarte Tudela, Julian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Buonfigli, Julio Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Luján, Lucas Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Alonso Bivou, Mariano Ángel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cebrián, José Ignacio. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mendoza. Instituto de Histologia y Embriologia de Mendoza Dr. Mario H. Burgos. Grupo Vinculado de Investigacion y Desarrollo Biotecnologico Aplicado Al Diagnostico Al Ihem | Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Instituto de Histologia y Embriologia de Mendoza Dr. Mario H. Burgos. Grupo Vinculado de Investigacion y Desarrollo Biotecnologico Aplicado Al Diagnostico Al Ihem.; ArgentinaFil: Capmany, Anahi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Damiani, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Heterologous prime-boost vaccination based on Polymorphic protein D protects against intravaginal Chlamydia trachomatis infection in mice

The control of the worldwide spread of sexually transmitted Chlamydia trachomatis (Ct) infection urgently demands the development of a preventive vaccine. In this work, we designed a vaccine based on a fragment of polymorphic protein D (FPmpD) that proved to be immunogenic enough to generate a robust systemic and mucosal IgG humoral immune response in two strains of mice. We used a heterologous prime-boost strategy, including simultaneous systemic and mucosal administration routes. The high titers of anti-PmpD antibodies elicited by this immunization scheme did not affect murine fertility. We tested the vaccine in a mouse model of Ct intravaginal infection. Anti-PmpD antibodies displayed potent neutralizing activity in vitro and protective effects in uterine tissues in vivo. Notably, the humoral immune response of PmpD-vaccinated mice was faster and stronger than the primary immune response of non-vaccinated mice when exposed to Ct. FPmpD-based vaccine effectively reduced Ct shedding into cervicovaginal fluids, bacterial burden at the genitourinary tract, and overall infectivity. Hence, the FPmpD-based vaccine might constitute an efficient tool to protect against Ct intravaginal infection and decrease the infection spreading.Fil: Russi, Romina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Inmunologia Experimental.; ArgentinaFil: del Balzo, Diego Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Lujan, Agustin Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Reidel, Ivana Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Inmunologia Experimental.; ArgentinaFil: García, María Inés. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Inmunologia Experimental.; ArgentinaFil: Veaute, Carolina Melania Isabel. Universidad Nacional del Litoral. Facultad de Bioquimica y Ciencias Biologicas. Laboratorio de Inmunologia Experimental.; ArgentinaFil: Damiani, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Knowledge and beliefs on vaccines among a sample of Italian pregnant women: results from the NAVIDAD study

BACKGROUND: Vaccine hesitancy is an emerging phenomenon in European countries and leads to decreasing trends in infant vaccine coverage. The aim of this study was to analyze the level of confidence and correct awareness about immunizations, which are crucial for the success of vaccination programmes. METHODS: As part of the NAVIDAD multicentre study, we examined vaccination confidence and complacency among a sample of 1820 pregnant women from 14 Italian cities. The questionnaire assessed the interviewee's knowledge, beliefs and misconceptions, as well as their socioeconomic status, information sources about vaccines and confidence in the Italian National Healthcare Service. RESULTS: Only 9% of women completely believed to the efficacy, necessity and safety of vaccinations. Almost 20% of them had misconceptions on most of the themes. There was a significant difference in the level of knowledge considering educational level: women with a high educational level have less probability of obtaining a low knowledge score (odds ratio (OR) 0.43 [95% confidence interval (CI) 0.34-0.54]). The level of knowledge was also influenced by the sources of information: women who received information from their general practitioner (GP) and from institutional websites had a significantly lower chance of having misconceptions (OR 0.74 [95% CI 0.58-0.96]; OR 0.59 [95% CI 0.46-0.74]). Finally, the results underlined the influence of trust in healthcare professional information on the likelihood of having misconceptions (OR 0.49 [95% CI 0.27-0.89]). CONCLUSIONS: The data suggest the efficacy of GPs and institutional websites as a source of information to contrast misconceptions and underline the importance of confidence in the healthcare system to increase complacency and confidence in vaccines

Cost-Effectiveness of Whole-Genome vs Whole-Exome Sequencing Among Children With Suspected Genetic Disorders

Importance The diagnosis of rare diseases and other genetic conditions can be daunting due to vague or poorly defined clinical features that are not recognized even by experienced clinicians. Next-generation sequencing technologies, such as whole-genome sequencing (WGS) and whole-exome sequencing (WES), have greatly enhanced the diagnosis of genetic diseases by expanding the ability to sequence a large part of the genome, rendering a cost-effectiveness comparison between them necessary. Objective To assess the cost-effectiveness of WGS compared with WES and conventional testing in children with suspected genetic disorders. Design, Setting, and Participants In this economic evaluation, a bayesian Markov model was implemented from January 1 to June 30, 2023. The model was developed using data from a cohort of 870 pediatric patients with suspected genetic disorders who were enrolled and underwent testing in the Ospedale Pediatrico Bambino Gesu, Rome, Italy, from January 1, 2015, to December 31, 2022. The robustness of the model was assessed through probabilistic sensitivity analysis and value of information analysis. Main Outcomes and Measures Overall costs, number of definitive diagnoses, and incremental cost-effectiveness ratios per diagnosis were measured. The cost-effectiveness analyses involved 4 comparisons: first-tier WGS with standard of care; first-tier WGS with first-tier WES; first-tier WGS with second-tier WES; and first-tier WGS with second-tier WGS. Results The ages of the 870 participants ranged from 0 to 18 years (539 [62%] girls). The results of the analysis suggested that adopting WGS as a first-tier strategy would be cost-effective compared with all other explored options. For all threshold levels above euro29 800 (US $32 408) per diagnosis that were tested up to euro50 000 (US$54 375) per diagnosis, first-line WGS vs second-line WES strategy (ie, 54.6%) had the highest probability of being cost-effective, followed by first-line vs second-line WGS (ie, 54.3%), first-line WGS vs the standard of care alternative (ie, 53.2%), and first-line WGS vs first-line WES (ie, 51.1%). Based on sensitivity analyses, these estimates remained robust to assumptions and parameter uncertainty. Conclusions and Relevance The findings of this economic evaluation encourage the development of policy changes at various levels (ie, macro, meso, and micro) of international health systems to ensure an efficient adoption of WGS in clinical practice and its equitable access

Does Clinical Governance influence the quality of medical records?

Background. Clinical Governance (CG) is a validated framework for continuous quality improvement in health care settings. Quality medical records may reflect the quality of care delivered and are a viable tool to implement CG skills. Aim. Aim of this study is to investigate the correlation between the level of implementation of CG dimensions and the quality of medical records. Material and methods. A cross-sectional study was carried out in an Italian Teaching Hospital. CG implementation levels were quantified through a systematic methodology (OPTIGOV©). The overall quality of medical records was measured through a revised version of a National-validated scale. A multiple linear regression model was used to test the likely influence of all the variables constituting the OPTIGOV evaluation on the quality of medical records. 47 hospital wards and 1458 medical records were assessed. Results. A significant and positive association between the quality of medical records and the accountability score (β = 0.15; p < 0.01) and the clinical audit score (b = 0.11; p = 0.02), was found. Conversely, the risk management score shown a negative and significant correlation (b = -0.17; p < 0.01). This study confirms that CG plays a central role in driving quality improvement and advocates a systematic implementation of such an approach within healthcare organizations.

Nuevas estrategias para el control de las infecciones clamidiales

Chlamydia trachomatis (Ctr) es la causa más frecuente de infecciones de transmisión sexual (ITS). La Organización Mundial de la Salud (OMS) estima que cada año se infectan 131 millones de personas, principalmente jóvenes en edad reproductiva. Ctr provoca en la mujer infecciones agudas como cervicitis, endometritis, salpingitis, que frecuentemente cronifican y generan complicaciones graves como enfermedad inflamatoria pélvica, abortos espontáneos e infertilidad. El recién nacido, al infectarse en el canal del parto, puede desarrollar conjuntivitis y neumonía. En el hombre causa uretritis, prostatitis y epididimitis. Es la causa más frecuente en el mundo de ceguera prevenible de naturaleza infecciosa o tracoma. El Ministerio de Salud de la Nación emitió una alerta epidemiológica en agosto de 2018 por la aparición de linfogranuloma venéreo. La falta de sintomatología dificulta el diagnóstico y el tratamiento; sumado a la falta de una vacuna preventiva para evitar el contagio y la aparición de resistencia a antibióticos. Por lo que se requiere el desarrollo de nuevas herramientas para la prevención y el control de las infecciones clamidiales. Ctr invade las células epiteliales cervicales a través de numerosos receptores, muchos de ellos glicosilados y sobrevive y se multiplica intracelularmente en una vesícula llamada inclusión. En el laboratorio hemos demostrado que las células cervicales inflamadas liberan una proteína unidora de glicanos, galectina 1 (Gal1); y que esta lectina es capaz de unirse a proteínas glicosiladas de la membrana externa de Ctr como MOMP (Major Outer Membrane Protein) y OmcB; y a receptores glicosilados de la célula epitelial cervical como PDGFR y varias integrinas. Demostramos que Gal1 facilita el acercamiento de la bacteria a la membrana plasmática y promueve la invasión celular, al actuar como un puente entre los glicanos bacterianos y eucariotas. Gal1 aumenta no sólo el número de células infectadas sino también el número de inclusiones por célula y el número de bacterias por inclusión. Nuestros resultados muestran que la interferencia de la interacción glicanos bacterianos-Gal1-receptores glicosilados con lactosa, glicanasas como PNGasa F o anticuerpos neutralizantes contra los receptores involucrados es efectiva para reducir el reconocimiento y la unión de Ctr a la superficie celular, disminuyendo la invasión, y en consecuencia la magnitud de la infección clamidial. Hemos comprobado in vivo en un modelo murino de infección genital, que los ratones KO para Gal1 o para enzimas formadoras de N-glicanos complejos son menos susceptibles a la infección clamidial. Se ha descripto que Gal1 favorece la infección por el virus de la inmunodeficiencia humana (VIH) y por Trichomonas vaginalis. Gal1 es uno de los mediadores que se libera en los tejidos inflamados y hemos demostrado que Ctr aumenta su expresión, lo que podría explicar al menos en parte, la mayor susceptibilidad del tejido genital femenino inflamado a la invasión por patógenos y la alta frecuencia de re- y co-infecciones en ITS. Nuestros hallazgos sugieren que la interferencia del puente glicanos bacterianos-Gal1-receptores celulares N-glicosilados podría ser una nueva herramienta preventiva para evitar la invasión celular y lograr el control de las infecciones clamidiales y otras ITS.Fil: Damiani, Maria Elena Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Lujan, Agustin Leonardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Croci Russo, Diego Omar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Gambarte Tudela, Julian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Losinno, Antonella Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaXXI Congreso de la Sociedad de Biología de Rosario; XXXIX Reunión Anual de la Sociedad de Biología de RosarioRosarioArgentinaSociedad de Biología de Rosari

VizieR Online Data Catalog: Gamma Vel cluster membership and IMF (Prisinzano+, 2016)

We derived a list as complete as possible of confirmed members of the young open cluster Gamma Velorum, with the aim of deriving general cluster properties such as the IMF. We used all available spectroscopic membership indicators within the Gaia-ESO public archive, based on spectra acquired with FLAMES a the VLT using the GIRAFFE intermediate-resolution spectrograph. In addition, we used literature photometry and X-ray data. For each membership criterion, we derived the most complete list of candidate cluster members. Then, we considered photometry, gravity, and radial velocities as necessary conditions for selecting a subsample of candidates whose membership was confirmed by using the lithium and Halpha lines and X-rays as youth indicators. Table 5 lists the fundamental parameters of the confirmed and possible members in Gamma Velorum, i.e. photometry, radial velocities, equivalent widths of the lithium line, the Halpha activity index, the X-ray flag, the gravity gamma index and the stellar masses. Finally the binarity and membership flags are given. (1 data file)

Analisi dei modelli organizzativi di risposta al COVID-19 in Italia: evidenze da 2 anni di ISTANT REPORT Altems

Sistematizzazione e pubblicazione settimanalmente un report per analizzare in modo sistemico e comparativo i modelli di risposta adottati dalle Regioni in risposta all'emergenza da COVID- 1