Cell membrane lipid rafts mediate caveolar endocytosis of HIV-1 Tat fusion proteins.

The transactivator protein of human immunodeficiency virus type 1 Tat has the unique property of mediating the delivery of large protein cargoes into the cells when present in the extracellular milieu. Here we show that Tat fusion proteins are internalized by the cells through a temperature-dependent endocytic pathway that originates from cell membrane lipid rafts and follows caveolar endocytosis. These conclusions are supported by the study of the slow kinetics of the internalization of Tat endosomes, by their resistance to nonionic detergents, the colocalization of internalized Tat with markers of caveolar endocytosis, and the impairment of the internalization process by drugs that disrupt lipid rafts or disturb caveolar trafficking. These results are of interest for all those who exploit Tat as a vehicle for transcellular protein delivery

Caveolae-Mediated internalization of extracellular HIV-1 tat fusion proteins visualized in real time

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Learning from the past to improve the future-vaccine hesitancy determinants in the italian population: a systematic review

: WHO identifies vaccine hesitancy (VH) as one of the ten threats to global health. The authors bring to the international scientific community an Italian episode that offers the opportunity to renew the discussion on the extent of the VH matter. The purpose of this systematic review is to analyze the factors determining vaccine hesitancy in the Italian population, to understand its roots, and suggest potential strategies to mitigate it. A systematic review of the literature according to the PRISMA guidelines was carried out using the SCOPUS and Medline (via PubMed) databases, using the following strategy: (COVID-19 vaccines) AND (vaccination hesitancy) AND (Italy). After the selection process, 36 articles were included in this systematic review. The most frequently detected factors associated with VH in the Italian population can be grouped as vaccine-related factors, socio-cultural factors, and demographic factors. Currently, we are facing a gap between the population and science, governments, and institutions. To heal this breach, it is necessary to strengthen the trust of the population through the implementation of health communication and public education strategies, while scientific literacy must continue to support families and individuals in discerning evidence from opinions to recognize the real risks and balance them with the benefits

The conformational state of hERG1 channels determines integrin association, downstream signaling, and cancer progression

Ion channels regulate cell proliferation, differentiation, and migration in normal and neoplastic cells through cell-cell and cell-extracellular matrix (ECM) transmembrane receptors called integrins. K+ flux through the human ether-\ue0-gogo- related gene 1 (hERG1) channel shapes action potential firing in excitable cells such as cardiomyocytes. Its abundance is often aberrantly high in tumors, where it modulates integrin-mediated signaling. We found that hERG1 interacted with the \u3b21 integrin subunit at the plasma membrane of human cancer cells. This interaction was not detected in cardiomyocytes because of the presence of the hERG1 auxiliary subunit KCNE1 (potassium voltage-gated channel subfamily E regulatory subunit 1), which blocked the \u3b21 integrin-hERG1 interaction. Although open hERG1 channels did not interact as strongly with \u3b21 integrins as did closed channels, current flow through hERG1 channelswas necessary to activate the integrin-dependent phosphorylation of Tyr397 in focal adhesion kinase (FAK) in both normal and cancer cells. In immunodeficient mice, proliferation was inhibited in breast cancer cells expressing forms of hERG1 with impaired K+ flow, whereas metastasis of breast cancer cells was reduced when the hERG1/\u3b21 integrin interaction was disrupted. We conclude that the interaction of \u3b21 integrins with hERG1 channels in cancer cells stimulated distinct signaling pathways that depended on the conformational state of hERG1 and affected different aspects of tumor progression

Design and advancement status of the Beam Expander Testing X-ray facility (BEaTriX)

The BEaTriX (Beam Expander Testing X-ray facility) project is an X-ray apparatus under construction at INAF/OAB to generate a broad (200́60 mm2), uniform and low-divergent X-ray beam within a small lab (6́15 m2). BEaTriX will consist of an X-ray source in the focus a grazing incidence paraboloidal mirror to obtain a parallel beam, followed by a crystal monochromation system and by an asymmetrically-cut diffracting crystal to perform the beam expansion to the desired size. Once completed, BEaTriX will be used to directly perform the quality control of focusing modules of large X-ray optics such as those for the ATHENA X-ray observatory, based on either Silicon Pore Optics (baseline) or Slumped Glass Optics (alternative), and will thereby enable a direct quality control of angular resolution and effective area on a number of mirror modules in a short time, in full X-ray illumination and without being affected by the finite distance of the X-ray source. However, since the individual mirror modules for ATHENA will have an optical quality of 3-4 arcsec HEW or better, BEaTriX is required to produce a broad beam with divergence below 1-2 arcsec, and sufficient flux to quickly characterize the PSF of the module without being significantly affected by statistical uncertainties. Therefore, the optical components of BEaTriX have to be selected and/or manufactured with excellent optical properties in order to guarantee the final performance of the system. In this paper we report the final design of the facility and a detailed performance simulation

Management of the corpse with suspect, probable or confirmed COVID-19 respiratory infection \u2013 Italian interim recommendations for personnel potentially exposed to material from corpses, including body fluids, in morgue structures and during autopsy practice.

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