Heterociclaciones con Tosilmetilisonitrilo (TosMIC) : síntesis total de la Mansouramicina B

Los isonitrilos son aquellos compuestos orgánicos que contienen el grupo funcional R-NC. Estos compuestos protagonizan una amplia gama de reacciones que han permitido acceder a la síntesis total de productos naturales y precursores de moléculas biológicamente activas. Dentro del amplio grupo que constituye la familia de los isonitrilos, cabe destacar el tosilmetilisonitrilo (TosMIC), descubierto en la década de los años 70 por van Leusen y que hoy en día se considera un reactivo de gran interés en la síntesis de sistemas heterocíclicos de cinco miembros. El interés de nuestro grupo de investigación por el TosMIC no es nuevo. Por ejemplo, en el año 1999 se observó que la reacción entre pirrolcarbaldehídos y TosMIC producía 3-tosilpirrolo[1,2-c]pirimidinas con buenos rendimientos. Aplicando esta estrategia sintética, nuestro grupo ha descrito la síntesis de diversos núcleos bicíclicos y tricíclicos. Alentados por estos resultados, el proyecto de Tesis Doctoral que ha dado lugar a esta memoria tuvo como objetivo principal el desarrollo de una nueva línea de investigación basada en el uso de TosMIC en la preparación de isoquinolinas sustituidas utilizando como sustratos de partida TosMIC y derivados de 2-bromometilbenceno. Estos estudios han generado los siguientes resultados: -La reacción de derivados de TosMIC bromoarilados en presencia de tBuLi produce un inesperado proceso en cascada en el que, por medio de una reacción de heterociclación, se forma un intermedio derivado de isoquinolina que en el propio medio de reacción evoluciona hasta obtener 2-iminoindanos. Estos, a su vez, reaccionan en presencia de tBuOK/tBuOH para dar 2-vinilbenzonitrilos con altos rendimientos. El proceso total puede contemplarse como una cianación de haloarenos que proporciona una amplia gama de nitrilos aromáticos con buenos rendimientos. -Se ha logrado desarrollar una nueva metodología para la síntesis de isoquinolinas a partir de isonitrilos. Las reacciones de heterociclación tienen lugar a través de una sustitución electrófila aromática, por lo cual resultan favorecidas por sustituyentes electrodonadores en el anillo aromático. Las isoquinolinas sustituidas se forman empleando cantidades catalíticas de CF3COOH o AlCl3, mientras que las isoquinolinas sustituidas en la posición C1, utilizando AlEt2Cl y diferentes electrófilos o únicamente NIS. -Aplicando la metodología desarrollada para la obtención de isoquinolinas, se ha realizado la primera síntesis total de la Mansouramicina B. Ésta consta de tres pasos a partir de TosMIC y se produce con un rendimiento global del 17%

Dendroclimatic analysis in the Adamello-Presanella Group (Central Italian Alps)

Inter annual or inter decadal climate reconstructions in the subarctic region and in high-mountain environments suffer from the absence of suitable long instrumental climate records. Annual tree-rings, along with other annually resolved natural archives, are widely used as proxies in high resolution paleoclimatology. A temperature signal-loss has been reported in tree-rings width and density records from several temperature-limited environments since the mid-20th century, revealing a decreasing attitude of tree-ring parameters in tracking increasing instrumental temperatures. In this study we carried out a dendroclimatic analysis on a data set of five European larch ring-width chronologies in the Adamello-Presanella Group, in the Italian Central Alps. We intended to evaluate the dendroclimatic potential of the high-elevation conifer vegetation to be used as a climate proxy, assessing the stability over time of the climate/tree-ring growth relationship. The dendroclimatic analysis was performed by means of correlation function and response function analysis, which allowed identifying climate parameters mainly involved in tree-rings growth. For capturing the dynamical variability of climate signal in the five tree-ring width chronologies, and to verify the stability over time of tree-rings/climate relationship, moving correlation function and moving response function analysis have been used. Moreover, to test the efficiency of the tree-rings dataset for climate reconstruction purposes, we conducted a reconstruction of JJ temperature for the 1596-2004 time period. The analysis of climate/tree ring growth relationships, producing results that are consistent with the more recent dendroclimatic studies in the Alpine Region, confirmed the presence of a common climatic signal for conifers living at the timberline ecotone. From the monthly climatic analysis a strong positive influence of early summer (JJ) temperatures on the tree growth emerged, with June mean temperature showing the highest positive correlation. Influence of mean monthly precipitation revealed to be quite irrelevant, although we found that the five chronologies are significantly negatively correlated to June mean precipitation. European larch confirms in this study to be a highly climate-sensitive species, with summer temperature representing the main limitig factor at the treeline. Nevertheless, a temporal instability in growth/climate response is noticeable, that means a general decreasing trend in tree-rings climate sensitivity. Non-stationary relationships with climatic parameters may cause some concerns in tree-ring based reconstructions, which usually presume a stable response of tree-rings to climate change. The reconstruction of 1595-2004 JJ mean temperatures we performed is statistically valuable, but shows higher proficiency in describing high frequency than low frequency early mean summer temperature changes. Overall, a decreasing skill of European larch at the treeline in the Adamello-Presanella Group in tracking increasing instrumental temperatures appears. We also found that extremely warm conditions, such as the heat wave of summer 2003, do not produce a linear response on larch tree-ring growth. Moreover, from the moving correlation analysis emerged a probable effect of a growing season lengthening on larch tree-ring growth

Heterociclaciones con Tosilmetilisonitrilo (TosMIC) : síntesis total de la Mansouramicina B

Los isonitrilos son aquellos compuestos orgánicos que contienen el grupo funcional R-NC. Estos compuestos protagonizan una amplia gama de reacciones que han permitido acceder a la síntesis total de productos naturales y precursores de moléculas biológicamente activas. Dentro del amplio grupo que constituye la familia de los isonitrilos, cabe destacar el tosilmetilisonitrilo (TosMIC), descubierto en la década de los años 70 por van Leusen y que hoy en día se considera un reactivo de gran interés en la síntesis de sistemas heterocíclicos de cinco miembros. El interés de nuestro grupo de investigación por el TosMIC no es nuevo. Por ejemplo, en el año 1999 se observó que la reacción entre pirrolcarbaldehídos y TosMIC producía 3-tosilpirrolo[1,2-c]pirimidinas con buenos rendimientos. Aplicando esta estrategia sintética, nuestro grupo ha descrito la síntesis de diversos núcleos bicíclicos y tricíclicos. Alentados por estos resultados, el proyecto de Tesis Doctoral que ha dado lugar a esta memoria tuvo como objetivo principal el desarrollo de una nueva línea de investigación basada en el uso de TosMIC en la preparación de isoquinolinas sustituidas utilizando como sustratos de partida TosMIC y derivados de 2-bromometilbenceno. Estos estudios han generado los siguientes resultados: -La reacción de derivados de TosMIC bromoarilados en presencia de tBuLi produce un inesperado proceso en cascada en el que, por medio de una reacción de heterociclación, se forma un intermedio derivado de isoquinolina que en el propio medio de reacción evoluciona hasta obtener 2-iminoindanos. Estos, a su vez, reaccionan en presencia de tBuOK/tBuOH para dar 2-vinilbenzonitrilos con altos rendimientos. El proceso total puede contemplarse como una cianación de haloarenos que proporciona una amplia gama de nitrilos aromáticos con buenos rendimientos. -Se ha logrado desarrollar una nueva metodología para la síntesis de isoquinolinas a partir de isonitrilos. Las reacciones de heterociclación tienen lugar a través de una sustitución electrófila aromática, por lo cual resultan favorecidas por sustituyentes electrodonadores en el anillo aromático. Las isoquinolinas sustituidas se forman empleando cantidades catalíticas de CF3COOH o AlCl3, mientras que las isoquinolinas sustituidas en la posición C1, utilizando AlEt2Cl y diferentes electrófilos o únicamente NIS. -Aplicando la metodología desarrollada para la obtención de isoquinolinas, se ha realizado la primera síntesis total de la Mansouramicina B. Ésta consta de tres pasos a partir de TosMIC y se produce con un rendimiento global del 17%

La gruppoanalisi soggettuale e la terapia di gruppo: introduzione alla teoria e alla prassi

rticle explains the theoretical foundations of the group-analysis approach, its main Italian developments, and its link with technique. In particular, after showing the hesitations of the original English model, it illustrates the Italian approach (Subjectual Groupanalysis), its evolution and dialogue with disciplines (complexity theory, cultural anthropology) that contributed to the foundation of its meta-psychological apparatus. Subsequently, it focuses on the relational foundation of psyche, on the therapeutic aspects linked to it, highlighting some key aspects of a classic group-analytic functioning, some of the main therapist’s responsibility, and some of the hardest troubles for the patients

Intermediate Alpha-1 Antitrypsin Deficiency Can Play a Role in Pulmonary Exacerbation?

Alpha-1 antitrypsin deficiency is generally suspected in young patients with pulmonary emphysema or chronic obstructive pulmonary disease (COPD). Patients often suffer from diagnostic delays or are misdiagnosed, for example, with COPD, asthma, or airway hyperresponsiveness because of the nonspecific nature of respiratory symptoms recognised with Alpha-1 antitrypsin deficiency (AATD). These pathologies develop in homozygous patients (both compromised alleles) with severely deficient protein; however, they are also frequently observed in heterozygous patients (only one compromised allele) for the gene mutation with a more or less deficient protein and functional anatomical damage of varying severity depending on the type of mutation and the exposure to environmental risk factors and/or professional that can trigger the repeated injurious inflammatory process. Case Description: We describe two cases of late diagnosis of alpha- 1 antitrypsin deficiency, with many exacerbations and intermediate level of alpha-1 antitrypsin. Due to the peculiar clinical history, and the PLowell rare mutation, although intermediate AATD, the patients were subjected to replacement therapy and they obtained clinical improvement. Discussion: Both the cases carried a heterozygous PLowell mutation representing two interesting and rare examples of clinical cases with double heterozygosity. The presence in the other AAT allele of the S- mutation in the first case and a concomitant presence of another mutation in the cystic fibrosis gene in the second case contributed to the protease-antiprotease imbalance and, despite intermediate AATD, was the probable cause of the numerous exacerbations. Conclusion: Alpha-1 antitrypsin deficiency should always be suspected in patients with respiratory disease and an unclear or complex clinical history. It may be useful to recognize and evaluate treatment even outside the established parameters, in selected cases

Lactic acid bacteria occurring during manufacture and ripening of Provolone del Monaco cheese: detection by different analytical approaches

Lactic acid bacteria occurring in Provolone del Monaco, an artisanal pasta filata cheese produced in Campania (Italy) from raw cows’ milk and without starter addition, were investigated by a combination of conventional and molecular approaches. The microbial community was monitored during a cheese-making process giving rise to a premium quality product. Streptococcus thermophilus and Streptococcus macedonicus prevailed during cheese manufacture and survived along nine months of ripening, together with enterococci and lactobacilli of the casei group, especially Lactobacillus rhamnosus. Phenotypic and genetic identification of 308 isolates largely reflected the results obtained by 16S rDNA sequencing analysis by polymerase chain reaction-denaturant gradient gel electrophoresis, with the significant exception of Lactobacillus fermentum and four Lactobacillus delbrueckii subspecies that were not detected by cultural methods. Each different analytical approach employed provided useful information. Their combination proved to be suitable to effectively describe the ecosystem of Provolone del Monaco cheese

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Abstract not availabl

Immunosuppressive effect and global dysregulation of blood transcriptome in response to psychosocial stress in vervet monkeys (Chlorocebus sabaeus).

Psychosocial stressors - life events that challenge social support and relationships - represent powerful risk factors for human disease; included amongst these events are relocation, isolation and displacement. To evaluate the impact of a controlled psychosocial stressor on physiology and underlying molecular pathways, we longitudinally studied the influence of a 28-day period of quarantine on biomarkers of immune signalling, microbial translocation, glycaemic health and blood transcriptome in the wild-born vervet monkey. This event caused a coordinated, mostly transient, reduction of circulating levels of nine immune signalling molecules. These were paralleled by a massive dysregulation of blood transcriptome, including genes implicated in chronic pathologies and immune functions. Immune and inflammatory functions were enriched among the genes downregulated in response to stress. An upregulation of genes involved in blood coagulation, platelet activation was characteristic of the rapid response to stress induction. Stress also decreased neutrophils and increased CD4 + T cell proportions in blood. This model of psychosocial stress, characterised by an immune dysregulation at the transcriptomic, molecular and cellular levels, creates opportunities to uncover the underlying mechanisms of stress-related diseases with an immune component, including cardiovascular diseases and susceptibility to infections