Estudio de los alcaloides presentes en la Bocconia Pearcei Hutchinson (Papaveraceae)

1- Se ha hecho una revisión de los alcaloides aisladosde las especies de Bocconia y Macleaya que han sido investigadas,así como de la química y la biogénesis de los alcaloides benzefenantridínicos. 2- Se investigaron las bases presentes en la raíz y eltallo de la Bocconia pearcei Hutch., única especie de este géneroexistente en nuestro país. De raíz y tallo de la misma se aislarony caracterizaron siete alcaloides, los cuales pertenecen a tres gruposquímicos diferentes: benzofenantridínicos (queleritrina, sanguinarinay quelirrubina), protopínicos (protopina y alocriptopina) yberberínicos (berberina y coptisina). Cuatro de estos alcaloides (sanguinarina, quelirrubina,berberina y coptisina) no habían sido descriptos anteriormente paraesta planta. Es este el primer caso de aislamiento de quelirrubina enespecies de este género, así como de alcaloides del grupo de la berberina,los cuales se han aislado en cambio, de las especies del género Macleaya el cual está estrechamente relacionado con el género Bocconia. Del tallo de B. pearcei Hutch. pudo aislarse además, encantidad muy pequeña otra base que da sales coloreadas, cuyo comportamiento es muy semejante al de un alcaloide aislado por Slavík (1963) de Platystemon californicus Benth. 3- Todos los alcaloides aislados (con excepción de la quelirrubinacuya estructura es desconocida), poseen la misma distribución de los sustituyentes oxigenados y los grupos metilo y metilenose encuentran siempre unidos a oxígenos colocados en la mismaposición del esqueleto carbonado, dando lugar, de esta manera, ados grupos de bases cuyo tipo de sustitución es idéntico: queleritrina,alocriptopina y barberina por un lado, y sanguinarina, protopinay coptisina por otro. (Al agruparlas en esta forma se hatenido presente el reordenamiento sufrido por los alcaloides benzofenantridínicos). 4- Se han determinado los espectros de resonancia magnéticanuclear de los cloruros de queleritrina y sanguinarina asícomo el del pseudo cianuro de queleritrina. Mediante el cálculo delos índices de carga para la molécula del cloruro de sanguinarinase realizó una asignación de señales para todos los protones aromáticosde los cloruros cuaternarios y para los protones pertenecientesa los sustituyentes.Fil: Labriola, Rafael A.. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

A method for generating a quasi-linear convective system suitable for observing system simulation experiments

To understand the impact of different assimilated observations on convection-allowing model forecast skill, a diverse range of observing system simulation experiment (OSSE) case studies are required (different storm modes and environments). Many previous convection-allowing OSSEs predicted the evolution of an isolated supercell generated via a warm air perturbation in a horizontally homogenous environment. This study introduces a new methodology in which a quasi-linear convective system is generated in a highly sheared and modestly unstable environment. Wind, temperature, and moisture perturbations superimposed on a horizontally homogeneous environment simulate a cold front that initiates an organized storm system that spawns multiple mesovortices. Mature boundary layer turbulence is also superimposed onto the initial environment to account for typical convective-scale uncertainties. Creating an initial forecast ensemble remains a challenge for convection-allowing OSSEs because mesoscale uncertainties are difficult to quantify and represent. The generation of the forecast ensemble is described in detail. The forecast ensemble is initialized by 24 h full-physics simulations (e.g., radiative forcing, surface friction, and microphysics). The simulations assume different surface conditions to alter surface moisture and heat fluxes and modify the effects of friction. The subsequent forecast ensemble contains robust non-Gaussian errors that persist until corrected by the data assimilation system. This purposely degraded initial forecast ensemble provides an opportunity to assess whether assimilated environmental observations can improve, e.g., the wind profile. An example OSSE suggests that a combination of radar and conventional (surface and soundings) observations are required to produce a skilled quasi-linear convective system forecast, which is consistent with real-world case studies. The OSSE framework introduced in this study will be used to understand the impact of assimilated environmental observations on forecast skill.</p

Transient plasma cell dyscrasia in COVID-19 patients linked to IL-6 triggering

An unusual clonal gammopathy was reported in COVID-19 patient but whether this anomaly is related or not to the disease has not yet been clarified. To this aim, we selected a cohort of 35 COVID-19 patients swab positive and investigated serological levels of IL-6, immune response to major viral antigens and electrophoretic profile. Elevated levels of IL-6 were accompanied by a significative humoral response to viral Spike protein, revealing an altered electrophoretic profile in the gamma region. We can conclude that elevated levels of IL-6 triggers humoral response inducing a transient plasma cell dyscrasia in severe COVID-19 patients

Identification of levothyroxine antichagasic activity through computer-aided drug repurposing

Cruzipain (Cz) is the major cysteine protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. A conformation-independent classifier capable of identifying Cz inhibitors was derived from a 163-compound dataset and later applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 3 of which were acquired and tested on Cz and T. cruzi epimastigotes proliferation. Among them, levothyroxine, traditionally used in hormone replacement therapy in patients with hypothyroidism, showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.Facultad de Ciencias Exacta

Labour market trajectories following sickness absence due to self-reported all cause morbidity—a longitudinal study

Abstract Background To investigate differences in return to work (RTW) and employment trajectories in individuals on sick leave for either mental health reasons or other health related reasons. Methods This study was based on 2036 new sickness absence cases who completed a questionnaire on social characteristics, expectations for RTW and reasons for sickness absence. They were divided into two exposure groups according to their self-reported sickness absence reason: mental health reasons or other health reasons. The outcome was employment status during the following 51 weeks and was measured both as time-to-event analysis and with sequence analysis. Results Individuals with mental health reasons for sickness absence had a higher risk of not having returned to work (RR 0.87 (0.80;0.93)). Adjusting for gender, age, education and employment did not change the estimate, however, after adding RTW expectations to the model, the excess risk was no longer present (RR 1.01 (0.95;1.08)). In relation to the sequence analysis, individuals with mental health related absence had significantly higher odds of being in the sickness absence cluster and significantly lower odds for being in the fast RTW cluster, but when adjusting for RTW expectations, the odds were somewhat attenuated and no longer significant. Conclusions Employees on sick leave due to self-reported mental health problems spent more weeks in sickness absence and temporary benefits and had a higher risk of not having returned to work within a year compared to employees on sick leave due to other health reasons. The difference could be explained by their lower RTW expectations at baseline. This emphasises the need to develop suitable and specific interventions to facilitate RTW for this group of sickness absentees

Endoplasmic Reticulum Calcium Regulates the Retrotranslocation of Trypanosoma Cruzi Calreticulin to the Cytosol

For most secretory pathway proteins, crossing the endoplasmic reticulum (ER) membrane is an irreversible process. However, in some cases this flow can be reversed. For instance, misfolded proteins retained in the ER are retrotranslocated to the cytosol to be degraded by the proteasome. This mechanism, known as ER associated degradation (ERAD), is exploited by several bacterial toxins to gain access to the cytosol. Interestingly, some ER resident proteins can also be detected in the cytosol or nucleus, calreticulin (CRT) being the most studied. Here we show that in Trypanosoma cruzi a minor fraction of CRT localized to the cytosol. ER calcium depletion, but not increasing cytosolic calcium, triggered the retrotranslocation of CRT in a relatively short period of time. Cytosolic CRT was subsequently degraded by the proteasome. Interestingly, the single disulfide bridge of CRT is reduced when the protein is located in the cytosol. The effect exerted by ER calcium was strictly dependent on the C-terminal domain (CRT-C), since a CRT lacking it was totally retained in the ER, whereas the localization of an unrelated protein fused to CRT-C mirrored that of endogenous CRT. This finding expands the regulatory mechanisms of protein sorting and may represent a new crossroad between diverse physiological processes