Aplicación del Score de Riesgo de desarrollo de hipertensión arterial esencial a corto plazo de Framingham en Santo Tomé, Argentina.

Objetivo: Valorar la utilidad del Score de Framingham en el desarrollo de la enfermedad, la influencia de los factores de riesgo cardiovasculares valorados, y conocer la frecuencia de nuevos casos de hipertensión arterial a corto plazo en la ciudad de Santo Tomé.Material y Métodos: Se realizó un trabajo de seguimiento, en la ciudad argentina de Santo Tomé (Santa Fe) de 316 personas normotensos no diabéticos, de 20 a 69 años; valorando el grado de riesgo de desarrollo de HTAe mediante el Score de Framingham de Riesgo a corto plazo y la influencia de los factores de riesgo cardiovasculares que éste considera, en el desarrollo de la enfermedad.Resultados: La edad media fue de 39,4±12,8 años, siendo el 62,3% mujeres. En relación al riesgo de desarrollar HTA a 1 y 2 años fueron de bajo riesgo el 67,7% y 55,1%; de moderado riesgo el 11,1% y 9,8%; y de alto riesgo el 21,2% y 35,1% respectivamente. La incidencia a un año de HTA fue del 11,4% en comparación a 2 años que fue significativamente menor (5,7%, IC95 0,97%-10,4% p=0,02), y la variable de mayor influencia en el desarrollo de la enfermedad fue el índice de masa corporal elevado (OR=3; IC95 1,4-6,9; p=0,004).Conclusión: En nuestra muestra el score no fue útil como predictor de desarrollo de hipertensión arterial esencial a corto plazo, pudiendo deberse al hecho de que en el mismo se incluyen factores que en nuestra muestra no influyeron en la presencia de la enfermedad.Fil: Vicco, Miguel Hernán. Provincia de Santa Fe. Ministerio de Salud. Htal J. B. Iturraspe. Area de Clinica Medica; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: César, Lucia. Provincia de Santa Fe. Ministerio de Salud. Htal J. B. Iturraspe. Area de Clinica Medica; ArgentinaFil: Musacchio, Héctor Mario. Provincia de Santa Fe. Ministerio de Salud. Htal J. B. Iturraspe. Area de Clinica Medica; ArgentinaFil: Galluccio, Federico. Provincia de Santa Fe. Ministerio de Salud. Htal J. B. Iturraspe. Area de Clinica Medica; Argentin

SCIENZAPERTA: EARTH SCIENCE FOR EVERYONE... FINALLY IN MILAN!

ScienzAperta is an outreach science venue that the Istituto Nazionale di Geofisica e Vulcanologia started in 2011 as the spring of science: the doors of the headquarters of science were finally opened to public. A number of events, conferences, seminars, guided tours through the Institute and its laboratories are every year offered to general public. The venue is held in most of the cities where the Institute is located, priority to high seismic and/or volcanic risk regions. On May 2014 we held ScienzAperta for the first time in Milano and open up the doors to schools specifically dealing mostly with seismic hazard in a region where general public not necessarily think it might We offered students conferences, seminars and educational activities to highlight the fun of science and jet raise awareness on proper behaviours in case of earthquake shaking. We asked students and teachers, from elementary to high schools, to fill in a questionnaire that we use to evaluate the appreciation the venue had. One hundred years after Giuseppe Mercalli’s death we could not forget to celebrate his science the city where he was born.UnpublishedMilano3T. Pericolosità sismica e contributo alla definizione del rischiorestricte

A mutation in the pleckstrin homology (PH) domain of the FGD1 gene in an Italian family with faciogenital dysplasia (Aarskog–Scott syndrome)

AbstractAarskog–Scott Syndrome (AAS) is an X-linked disorder characterised by short stature and multiple facial, limb and genital abnormalities. A gene, FGD1, altered in a patient with AAS phenotype, has been identified and found to encode a protein with homology to Rho/Rac guanine nucleotide exchange factors (Rho/Rac GEF). However, since this original report on identification of a mutated FGD1 gene in an AAS patient, no additional mutations in the FGD1 gene have been described. We analysed 13 independent patients with clinical diagnosis of AAS. One patient presented a mutation that results in a nucleotide change in exon 10 of the FGD1 gene (G2559>A) substituting a Gln for Arg in position 610. The mutation was found to segregate with the AAS phenotype in affected males and carrier females in the family of this patient. Interestingly, Arg-610 is located within one of the two pleckstrin homology (PH) domains of the FGD1 gene and it corresponds to a highly conserved residue which has been involved in InsP binding in PH domains of other proteins. The same residue is often mutated in the Bruton’s tyrosine kinase (Btk) gene in patients with an X-linked agammaglobulinemia. The Arg610Gln mutation represents the first case of a mutation in the PH domain of the FGD1 gene and additional evidence that mutations in PH domains can be associated to human diseases

The Influence of Catalysis on Mad2 Activation Dynamics

Mad2 is a key component of the spindle assembly checkpoint, a safety device ensuring faithful sister chromatid separation in mitosis. The target of Mad2 is Cdc20, an activator of the anaphase-promoting complex/cyclosome (APC/C). Mad2 binding to Cdc20 is a complex reaction that entails the conformational conversion of Mad2 from an open (O-Mad2) to a closed (C-Mad2) conformer. Previously, it has been hypothesized that the conversion of O-Mad2 is accelerated by its conformational dimerization with C-Mad2. This hypothesis, known as the Mad2-template hypothesis, is based on the unproven assumption that the natural conversion of O-Mad2 required to bind Cdc20 is slow. Here, we provide evidence for this fundamental assumption and demonstrate that conformational dimerization of Mad2 accelerates the rate of Mad2 binding to Cdc20. On the basis of our measurements, we developed a set of rate equations that deliver excellent predictions of experimental binding curves under a variety of different conditions. Our results strongly suggest that the interaction of Mad2 with Cdc20 is rate limiting for activation of the spindle checkpoint. Conformational dimerization of Mad2 is essential to accelerate Cdc20 binding, but it does not modify the equilibrium of the Mad2:Cdc20 interaction, i.e., it is purely catalytic. These results surpass previously formulated objections to the Mad2-template model and predict that the release of Mad2 from Cdc20 is an energy-driven process

In Vitro FRAP Identifies the Minimal Requirements for Mad2 Kinetochore Dynamics

BACKGROUND: Mad1 and Mad2 are constituents of the spindle-assembly checkpoint, a device coupling the loss of sister-chromatid cohesion at anaphase to the completion of microtubule attachment of the sister chromatids at metaphase. Fluorescence recovery after photobleaching (FRAP) revealed that the interaction of cytosolic Mad2 with kinetochores is highly dynamic, suggesting a mechanism of catalytic activation of Mad2 at kinetochores followed by its release in a complex with Cdc20. The recruitment of cytosolic Mad2 to kinetochores has been attributed to a stable receptor composed of a distinct pool of Mad2 tightly bound to Mad1. Whether specifically this interaction accounts for the kinetochore dynamics of Mad2 is currently unknown. RESULTS: To gain a precise molecular understanding of the interaction of Mad2 with kinetochores, we reconstituted the putative Mad2 kinetochore receptor and developed a kinetochore recruitment assay with purified components. When analyzed by FRAP in vitro, this system faithfully reproduced the previously described in vivo dynamics of Mad2, providing an unequivocal molecular account of the interaction of Mad2 with kinetochores. Using the same approach, we dissected the mechanism of action of p31(comet), a spindle-assembly checkpoint inhibitor. CONCLUSIONS: In vitro FRAP is a widely applicable approach to dissecting the molecular bases of the interaction of a macromolecule with an insoluble cellular scaffold. The combination of in vitro fluorescence recovery after photobleaching with additional fluorescence-based assays in vitro can be used to unveil mechanism, stoichiometry, and kinetic parameters of a macromolecular interaction, all of which are important for modeling protein interaction networks

Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22)

BACKGROUND: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published.METHODS: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine (R)).RESULTS: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found.CONCLUSIONS: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics

The MIS12 complex is a protein interaction hub for outer kinetochore assembly

The NSL1 subunit structures interactions between the MIS12, NDC80, and KNL1 kinetochore complexes (see also a related paper by Maskell et al. in this issue)

Piovono idee! diventa progetto continuità

Piovono idee! (Cloudy with a Chance of ideas!) is the participative scientific dissemination initiative of the Istituto Nazionale di Geofisica e Vulcanologia on environmental education designed specifically for the last two primary school classes (ISCDE 1) and the first middle school class (ISCDE 2), so it was chosen by the “Don Milani” (ex ISA1) comprehensive institute of La Spezia as continuity project between the two different school orders for the school year 2017/2018. The aim was to promote scientific culture in Primary and Middle Schools emphasizing the importance of Science in everyday life in order to favor sustainable development of Society. To knowledge the mechanisms that regulate the environment is increasingly important and the educational dialogue between School and Research endorses reflection starting from the sharing of personal experiences on the flood phenomena that often affect the area of la Spezia with a participatory experimental approach. Piovono idee! is an interactive learning experience on hydrogeological risk and climate change. The active path is rich of experiments, educational-scientific laboratories and interactive exhibits to better understand the geological phenomena through manipulation. The team role-playing games reinforce and stimulate emotional intelligence instilling correct behaviour and best practices. Visitors spontaneously ask questions in the area of experience, and find answers in the area of knowledge, learn the key concepts through learning by doing activities and conclude with role playing to reflect on the sustainability of their daily behavior (area of action). The exploration of Geosciences becomes a mean of raising pupils’ awareness of environmental problems by understanding natural phenomena. They learn that, through active and responsible citizenship actions, coexistence with natural hazards is possible. We can all do something to prevent catastrophes if we respect Nature and our territory.Published62-682TM. Divulgazione ScientificaJCR Journa

Participatory Approach to Natural Hazard Education for Hydrological Risk Reduction

Modern Society needs interactive public discussion to provide an effective way of focusing on hydrological hazards and their consequences. Embracing a holistic Earth system Science approach, we experiment since 2004 different stimulating educational/communicative model which emotionally involves the participants to raise awareness on the social dimension of the disaster hydrogeological risk reduction, pointing out that human behavior is the crucial factor in the degree of vulnerability and the likelihood of disasters taking place. The implementation of strategies for risk mitigation must include educational aspects, as well as economical and societal ones. Education is the bridge between knowledge and understanding and the key to raise risk perception. Children’s involvement might trigger a chain reaction that reinforce and spread the culture of risk. No matter how heavy was the rain that hit our land in the past and recent seasons, we still are not prepared. If on one hand we need to fight against worsening Global Warming that trigger extreme meteorological events, we should also work on sustainable land use and promote landscape preservation. Since science can work on improving knowledge of phenomena, technology can provide modern tool to reduce the impact of disasters, children and adults education is the flywheel to provide the change. We present here two cases selected among the wide range of educational activities that we have tested and to which more than 2,000 students and adults have participated within a period of 12 years. They include learn-by-playing, hands-on, emotional-learning activities, open questions seminars, learning paths, curiosity-driven approaches, special venues and science outreach.Sendai Partnerships 2015-2025PublishedLjubljana (Slovenia)2TM. Divulgazione Scientific