Analysis of TCR activation kinetics in primary human T cells upon focal or soluble stimulation.?

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LIME: A New Membrane Raft-associated Adaptor Protein Involved in CD4 and CD8 Coreceptor Signaling

Lymphocyte membrane rafts contain molecules critical for immunoreceptor signaling. Here, we report identification of a new raft-associated adaptor protein LIME (Lck-interacting molecule) expressed predominantly in T lymphocytes. LIME becomes tyrosine phosphorylated after cross-linking of the CD4 or CD8 coreceptors. Phospho-LIME associates with the Src family kinase Lck and its negative regulator, Csk. Ectopic expression of LIME in Jurkat T cells results in an increase of Csk in lipid rafts, increased phosphorylation of Lck and higher Ca2+ response to CD3 stimulation. Thus, LIME appears to be involved in regulation of T cell activation by coreceptors

A Logical Model Provides Insights into T Cell Receptor Signaling

Cellular decisions are determined by complex molecular interaction networks. Large-scale signaling networks are currently being reconstructed, but the kinetic parameters and quantitative data that would allow for dynamic modeling are still scarce. Therefore, computational studies based upon the structure of these networks are of great interest. Here, a methodology relying on a logical formalism is applied to the functional analysis of the complex signaling network governing the activation of T cells via the T cell receptor, the CD4/CD8 co-receptors, and the accessory signaling receptor CD28. Our large-scale Boolean model, which comprises 94 nodes and 123 interactions and is based upon well-established qualitative knowledge from primary T cells, reveals important structural features (e.g., feedback loops and network-wide dependencies) and recapitulates the global behavior of this network for an array of published data on T cell activation in wild-type and knock-out conditions. More importantly, the model predicted unexpected signaling events after antibody-mediated perturbation of CD28 and after genetic knockout of the kinase Fyn that were subsequently experimentally validated. Finally, we show that the logical model reveals key elements and potential failure modes in network functioning and provides candidates for missing links. In summary, our large-scale logical model for T cell activation proved to be a promising in silico tool, and it inspires immunologists to ask new questions. We think that it holds valuable potential in foreseeing the effects of drugs and network modifications

The art of video MashUp: supporting creative users with an innovative and smart application

In this paper, we describe the development of a new and innovative tool of video mashup. This application is an easy to use tool of video editing integrated in a cross-media platform; it works taking the information from a repository of videos and puts into action a process of semi-automatic editing supporting users in the production of video mashup. Doing so it gives vent to their creative side without them being forced to learn how to use a complicated and unlikely new technology. The users will be further helped in building their own editing by the intelligent system working behind the tool: it combines semantic annotation (tags and comments by users), low level features (gradient of color, texture and movements) and high level features (general data distinguishing a movie: actors, director, year of production, etc.) to furnish a pre-elaborated editing users can modify in a very simple way

Clinical characteristics and prognostic factors in COVID-19 patients aged ≥80 years

Aim: The aim of the present study was to describe the clinical presentation of patients aged ≥80 years with coronavirus disease 2019 (COVID-19), and provide insights regarding the prognostic factors and the risk stratification in this population. Methods: This was a single-center, retrospective, observational study, carried out in a referral center for COVID-19 in central Italy. We reviewed the clinical records of patients consecutively admitted for confirmed COVID-19 over a 1-month period (1-31 March 2020). We excluded asymptomatic discharged patients. We identified risk factors for death, by a uni- and multivariate Cox regression analysis. To improve model fitting and hazard estimation, continuous parameters where dichotomized by using Youden's index. Results: Overall, 69 patients, aged 80-98 years, met the inclusion criteria and were included in the study cohort. The median age was 84 years (82-89 years is interquartile range); 37 patients (53.6%) were men. Globally, 14 patients (20.3%) presented a mild, 30 (43.5%) a severe and 25 (36.2%) a critical COVID-19 disease. A total of 23 (33.3%) patients had died at 30 days' follow up. Multivariate Cox regression analysis showed that severe dementia, pO2 ≤90 at admission and lactate dehydrogenase >464 U/L were independent risk factors for death. Conclusions: The present data suggest that risk of death could be not age dependent in patients aged ≥80 years, whereas severe dementia emerged is a relevant risk factor in this population. Severe COVID-19, as expressed by elevated lactate dehydrogenase and low oxygen saturation at emergency department admission, is associated with a rapid progression to death in these patients