1,721,035 research outputs found

    Bias in the use of a SSClow/CCR3pos gate to capture basophils in chronic urticaria?

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    A comment on D'Auria E., De Amici M., Licari A., Caimmi S., Mantegazza C., Zuccotti G. and Marseglia G., Basophil activation test in children with autoimmune chronic spontaneous urticaria: Iis it ready for clinical practice?, Immunobiology 224 (1), 2019, 30-33

    The extra-lymphoid compartment of breast milk: Not a simple transfer of passive immunization

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    Discussion on how breast milk shows similarity to the immune gut micro-environment, creating a sort of immune "extended gut" between mother and child; helps advance the newborn's immune endowment by further tuning mucosal immunity and CD8 memory cells in the early life intestine

    Molecules, information and the origin of life: what is next?

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    How life did originate and what is life, in its deepest foundation? The texture of life is known to be held by molecules and their chemical-physical laws, yet a thorough elucidation of the aforementioned questions still stands as a puzzling challenge for science. Focusing solely on molecules and their laws has indirectly consolidated, in the scientific knowledge, a mechanistic (reductionist) perspective of biology and medicine. This occurred throughout the long historical path of experimental science, affecting subsequently the onset of the many theses and speculations about the origin of life and its maintenance. Actually, defining what is life, asks for a novel epistemology, a ground on which living systems' organization, whose origin is still questioned via chemistry, physics and even philosophy, may provide a new key to focus onto the complex nature of the human being. In this scenario, many issues, such as the role of information and water structure, have been long time neglected from the theoretical basis on the origin of life and marginalized as a kind of scenic backstage. On the contrary, applied science and technology went ahead on considering molecules as the sole leading components in the scenery. Water physics and information dynamics may have a role in living systems much more fundamental than ever expected. Can an organism be simply explained by a mechanistic view of its nature or we need "something else"? Probably, we can earn sound foundations about life by simply changing our prejudicial view about living systems simply as complex, highly ordered machines. In this manuscript we would like to reappraise many fundamental aspects of molecular and chemical biology and reading them through a new paradigm, which includes Prigogine's dissipative structures and informational dissipation (Shannon dissipation). This would provide readers with insightful clues about how biology and chemistry may be thoroughly revised, referring to new models, such as informational dissipation. We trust they are enabled to address a straightforward contribution in elucidating what life is for science. This overview is not simply a philosophical speculation, but it would like to affect deeply our way to conceive and describe the foundations of organisms' life, providing intriguing suggestions for readers in the field

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Further Insights into the Hematological Disorders Observed in Shwachman-Diamond Syndrome: mTOR and STAT3 Hyper-Phosphorylation in CD4+ and CD8+ T Cells and Efficacy of Rapamycin Treatment

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    Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disease which affects 1/168,000 newborns in Italy with a mean of 3.0 new cases/year. SDS is caused by mutations in the Shwachman-Bodian-Diamond syndrome (SBDS) gene, which encodes for the homonymous protein SBDS, whose exact function is still unknown. SBDS protein has been reported to play a role in eukaryotic ribosome biogenesis. Thus, SDS is considered a ribosomopathy. The pathology is characterized by multiple-organ impairment involving bone marrow failure, exocrine pancreatic insufficiency, skeletal malformations, hepatic and cognitive disorders. Neutropenia and impaired neutrophil chemotaxis, which in turn cause recurrent infections, are reported in young children. Furthermore, 15-20% of SDS patients develop myelodysplastic syndrome (MDS), with increased risk of acute myeloid leukemia (AML) progression, which represent the main cause of mortality. However, the exact pathologic mechanism whereby loss of SDBS function could lead to the specific SDS hematological issues remains unclear. We recently reported, for the first time to the best of our knowledge, that the mammalian Target of Rapamycin (mTOR) and Signal Transducer and Activator of Transcription (STAT)-3 pathways are hyper-activated in B cells, PMNs and, mostly, in monocytes obtained from SDS patients (Bezzerri V et al, Sci Rep 2016, in press). Since mTOR and STAT3 activation are associated with neutrophil development and AML, this finding could at least partially explain the onset of the hematological issues. Here we show a further Phospho flow analysis of mTOR and STAT3 pathways activation in otherlymphocytes subsets,in particular in CD8+/CD4+ T cells and NK cells obtained from five SDS patients. We found that STAT3 S727 is the most phosphorylated site in CD8+ and CD4+ T cells (more than twice than the healthy control cells, each). Furthermore, mTOR (S2448) is hyper-phosphorylated in CD8+ and CD4+ T cells derived from SDS patients. Median fluorescence intensity shifted from 220 ± 25 (healthy controls) to 405 ± 29 (SDS patients) in CD8+ T cells and from 350 ± 132 (healthy controls) to 590 ± 150 (SDS patients) in CD4+ T cells, similarly to results obtained from Monocytes and B cells. NK seems to be less responsive to mTOR/STAT3 activation than B and T cells. Importantly, mTOR inhibitor rapamycin is able to reduce both mTOR and STAT3 activation, with different efficacy, in a cell type-dependent manner. In particular, rapamycin strongly reduces both mTOR and STAT3 S727 phosphorylation in CD8+ and CD4+ T cells. Thus, these results suggest a role of mTOR/STAT3 pathways in both myeloid and lymphoid lineages of SDS blood cells. Since several drugs approved by FDA and EMA targeting the JAK-STAT and mTOR pathways have been currently evaluated for the treatment of different forms of hematological malignancies, this work could open a wider scenario into the current SDS therapeutic approaches

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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