L'attentato a Mussolini: un esempio di drammaturgia anarchica durante il ventennio

L’attentato a Mussolini ovvero il segreto di Pulcinella del 1926 di Carlo Tresca (1879-1943) è esempio di come, tra la fine dell’Ottocento e gli inizi del Novecento, il movimento socialista e anarchico vedesse il Teatro come fondamentale strumento di educazione e propaganda per le masse.The play L’attentato a Mussolini ovvero il segreto di Pulcinella (1926) of Carlo Tresca (1879-1943) it is an example of how, between the end of the 19th Century and the beginning of the 20th Century, the socialist and anarchical movement concerned the Theatre as a fundamental instrument of education and propaganda for the masses

Hyperglycemia triggers HIPK2 protein degradation

Homeodomain interacting protein kinase-2 (HIPK2) is an evolutionary conserved kinase that modulates several key molecular pathways to restrain tumor growth and induce p53-depending apoptotic cell-death in response to anticancer therapies. HIPK2 silencing in cancer cells leads to chemoresistance and cancer progression, in part due to p53 inhibition. Recently, hyperglycemia has been shown to reduce p53 phosphorylation at serine 46 (Ser46), the target residue of HIPK2, thus impairing p53 apoptotic function. Here we asked whether hyperglycemia could, upstream of p53, target HIPK2. We focused on the effect of high glucose (HG) on HIPK2 protein stability and the underlying mechanisms. We found that HG reduced HIPK2 protein levels, therefore impairing HIPK2-induced p53 apoptotic activity. HG-triggered HIPK2 protein downregulation was rescued by both proteasome inhibitor MG132 and by protein phosphatase inhibitors Calyculin A (CL-A) and Okadaic Acid (OA). Looking for the phosphatase involved, we found that protein phosphatase 2A (PP2A) induced HIPK2 degradation, as evidenced by directly activating PP2A with FTY720 or by silencing PP2A with siRNA in HG condition. The effect of PP2A on HIPK2 protein degradation could be in part due to hypoxia-inducible factor-1 (HIF-1) activity which has been previously shown to induce HIPK2 proteasomal degradation through several ubiquitin ligases. Validation analysed performed with HIF-1α dominant negative or with silencing of Siah2 ubiquitin ligase clearly showed rescue of HG-induced HIPK2 degradation. These findings demonstrate how hyperglycemia, through a complex protein cascade, induced HIPK2 downregulation and consequently impaired p53 apoptotic activity, revealing a novel link between diabetes/obesity and tumor resistance to therapies

Orchestration of Immunological Synapse Assembly by Vesicular Trafficking

Ligation of the T-cell antigen receptor (TCR) by cognate peptide bound to the Major Histocompatibility Complex on the surface of an antigen-presenting cell (APC) leads to the spatial reorganization of the TCR and accessory receptors to form a specialized area of intimate contact between T cell and APC, known as the immunological synapse (IS), where signals are deciphered, coordinated, and integrated to promote T cell activation. With the discovery that an endosomal TCR pool contributes to IS assembly and function by undergoing polarized recycling to the IS, recent years have witnessed a shift from a plasma membrane-centric view of the IS to the vesicular trafficking events that occur at this location following the TCR-dependent translocation of the centrosome toward the synaptic membrane. Here we will summarize our current understanding of the trafficking pathways that are responsible for the steady delivery of endosomal TCRs, kinases, and adapters to the IS to sustain signaling, as well as of the endocytic pathways responsible for signal termination. We will also discuss recent evidence highlighting a role for endosomes in sustaining TCR signaling after its internalization at the IS and identifying the IS as a site of formation and release of extracellular vesicles that allow for transcellular communication with the APC

A Ciliary View of the Immunological Synapse

The primary cilium has gone from being a vestigial organelle to a crucial signaling hub of growing interest given the association between a group of human disorders, collectively known as ciliopathies, and defects in its structure or function. In recent years many ciliogenesis proteins have been observed at extraciliary sites in cells and likely perform cilium-independent functions ranging from regulation of the cytoskeleton to vesicular trafficking. Perhaps the most striking example is the non-ciliated T lymphocyte, in which components of the ciliary machinery are repurposed for the assembly and function of the immunological synapse even in the absence of a primary cilium. Furthermore, the specialization traits described at the immunological synapse are similar to those seen in the primary cilium. Here, we review common regulators and features shared by the immunological synapse and the primary cilium that document the remarkable homology between these structures

The immunological synapse: an emerging target for immune evasion by bacterial pathogens

Similar to other pathogens, bacteria have developed during their evolution a variety of mechanisms to overcome both innate and acquired immunity, accounting for their ability to cause disease or chronic infections. The mechanisms exploited for this critical function act by targeting conserved structures or pathways that regulate the host immune response. A strategic potential target is the immunological synapse (IS), a highly specialized structure that forms at the interface between antigen presenting cells (APC) and T lymphocytes and is required for the establishment of an effective T cell response to the infectious agent and for the development of long-lasting T cell memory. While a variety of bacterial pathogens are known to impair or subvert cellular processes essential for antigen processing and presentation, on which IS assembly depends, it is only recently that the possibility that IS may be a direct target of bacterial virulence factors has been considered. Emerging evidence strongly supports this notion, highlighting IS targeting as a powerful, novel means of immune evasion by bacterial pathogens. In this review we will present a brief overview of the mechanisms used by bacteria to affect IS assembly by targeting APCs. We will then summarize what has emerged from the current handful of studies that have addressed the direct impact of bacterial virulence factors on IS assembly in T cells and, based on the strategic cellular processes targeted by these factors in other cell types, highlight potential IS-related vulnerabilities that could be exploited by these pathogens to evade T cell mediated immunity

MEASURING ENERGY EXPENDITURE IN SWIMMING TO ASSESS GROSSMECHANICAL EFFICIENCY

When swimming at submaximal speeds the rate of energy expenditure can be estimated from respiratory analysis. Over the past decades many methods for stationary non-aqueous evaluation of respiratory and ventilatory parameters in swimmers has emerged. Recently there have been advances in portable telemetric systems (Cosmed K4 b2, Italy) that can measure these variables from rest to maximal activity while swimming without the need to stop the exercise. Preliminary data show that the last modified snorkel system can be considered as a valid device for collecting expired gas for BxB analysis, comparable to the standard facemask, with the advantage of being suitable for measurements during swimming

Calcium dependent activation of the NF-AT transcription factor by p59fyn

AbstractA reporter gene under the control of a T-cell antigen receptor response element was activated in Jurkat cells by antigen receptor triggering or by a combination of phorbol myristate acetate, which activates protein kinase C, and a calcium ionophore. Both these signals were necessary for expression of the reporter gene. When co-transfected with a construct capable of overexpressing the tyrosine kinase p59fyn, the reporter gene was activated by PMA alone. Thus p59fyn could replace the calcium ionophore but not activation of protein kinase C. The activation by p59fyn plus PMA was blocked by EGTA and by the immunosuppressant drug cyclosporin A

Interleukin (IL)-9 Supports the Tumor-Promoting Environment of Chronic Lymphocytic Leukemia

Interleukin (IL)-9 is a soluble factor secreted by immune cells into the microenvironment. Originally identified as a mediator of allergic responses, IL-9 has been detected in recent years in several tumor niches. In solid tumors, it mainly promotes anti-tumor immune responses, while in hematologic malignancies, it sustains the growth and survival of neoplastic cells. IL-9 has been recently implicated in the pathogenesis of chronic lymphocytic leukemia; however, the molecular mechanisms underlying its contribution to this complex neoplasia are still unclear. Here, we summarize the current knowledge of IL-9 in the tumor microenvironment, with a focus on its role in the pathogenesis of chronic lymphocytic leukemia