America\u27s closet door: an investigation of television and its effects on perceptions of homosexuality

This study investigates the relationship between television and social perceptions. It uses the television shows Will&Grace, The L Word, Queer as Folk, and Modern Family for rhetorical analysis. Then, it uses the information gained from the analysis to hypothesize how and why these television shows both reflect and affect social perceptions of homosexuality

Importin-beta and CRM1 control a RANBP2 spatiotemporal switch essential for mitotic kinetochore function

Protein conjugation with small ubiquitin-related modifier (SUMO) is a post-translational modification that modulates protein interactions and localisation. RANBP2 is a large nucleoporin endowed with SUMO E3 ligase and SUMO-stabilising activity, and is implicated in some cancer types. RANBP2 is part of a larger complex, consisting of SUMO-modified RANGAP1, the GTP-hydrolysis activating factor for the GTPase RAN. During mitosis, the RANBP2–SUMO-RANGAP1 complex localises to the mitotic spindle and to kinetochores after microtubule attachment. Here, we address the mechanisms that regulate this localisation and how they affect kinetochore functions. Using proximity ligation assays, we find that nuclear transport receptors importin-β and CRM1 play essential roles in localising the RANBP2–SUMO-RANGAP1 complex away from, or at kinetochores, respectively. Using newly generated inducible cell lines, we show that overexpression of nuclear transport receptors affects the timing of RANBP2 localisation in opposite ways. Concomitantly, kinetochore functions are also affected, including the accumulation of SUMO- conjugated topoisomerase-IIα and stability of kinetochore fibres. These results delineate a novel mechanism through which nuclear transport receptors govern the functional state of kinetochores by regulating the timely deposition of RANBP2

Leveling Up Hydrogels:Hybrid Systems in Tissue Engineering

Hydrogels can mimic several features of the cell native microenvironment and have been widely used as synthetic extracellular matrices (ECMs) in tissue engineering and regenerative medicine (TERM). However, some applications have specifications that hydrogels cannot efficiently fulfill on their own. Incorporating reinforcing structures like fibrous scaffolds or particles into hydrogels, as hybrid systems, is a promising strategy to improve their functionality. We describe recent advances in the fabrication and application of these hybrid systems, where structural properties and stimuli responsiveness of hydrogels are enhanced while their ECM-like features are preserved. Furthermore, we discuss how these systems can contribute to the development of more complex tissue engineered structures in the rapidly evolving field of TERM

AI for Health and Well Being @SI Lab

This presentation was delivered in the framework of a bilateral meeting between CNR and IVI on September 5, 2023

Correction: Biofunctionalized pectin hydrogels as 3D cellular microenvironments

Correction for 'Biofunctionalized pectin hydrogels as 3D cellular microenvironments' by Sara C. Neves et al., J. Mater. Chem. B, 2015, 3, 2096–2108

Size effects in finite element modelling of 3D printed bone scaffolds using hydroxyapatite PEOT/PBT composites

Additive manufacturing (AM) of scaffolds enables the fabrication of customized patient-specific implants for tissue regeneration. Scaffold customization does not involve only the mac-roscale shape of the final implant, but also their microscopic pore geometry and material properties, which are dependent on optimizable topology. A good match between the experimental data of AM scaffolds and the models is obtained when there is just a few millimetres at least in one direction. Here, we describe a methodology to perform finite element modelling on AM scaffolds for bone tissue regeneration with clinically relevant dimensions (i.e., volume > 1 cm3). The simulation used an equivalent cubic eight node finite elements mesh, and the materials properties were derived both empirically and numerically, from bulk material direct testing and simulated tests on scaffolds. The experimental validation was performed using poly(ethylene oxide terephthalate)-poly(butylene ter-ephthalate) (PEOT/PBT) copolymers and 45 wt% nano hydroxyapatite fillers composites. By applying this methodology on three separate scaffold architectures with volumes larger than 1 cm3, the simulations overestimated the scaffold performance, resulting in 150–290% stiffer than average values obtained in the validation tests. The results mismatch highlighted the relevance of the lack of printing accuracy that is characteristic of the additive manufacturing process. Accordingly, a sensi-tivity analysis was performed on nine detected uncertainty sources, studying their influence. After the definition of acceptable execution tolerances and reliability levels, a design factor was defined to calibrate the methodology under expectable and conservative scenarios.This research was funded by the European Union, represented by the European Commission, grant number 685825-FAST-H2020-NMP-2014-2015/H2020-NMP-PILOTS-2015

Modulation of Methacrylated Hyaluronic Acid Hydrogels Enables Their Use as 3D Cultured Model

: Bioengineered hydrogels represent physiologically relevant platforms for cell behaviour studies in the tissue engineering and regenerative medicine fields, as well as in in vitro disease models. Hyaluronic acid (HA) is an ideal platform since it is a natural biocompatible polymer that is widely used to study cellular crosstalk, cell adhesion and cell proliferation, and is one of the major components of the extracellular matrix (ECM). We synthesised chemically modified HA with photo-crosslinkable methacrylated groups (HA-MA) in aqueous solutions and in strictly monitored pH and temperature conditions to obtain hydrogels with controlled bulk properties. The physical and chemical properties of the different HA-MA hydrogels were investigated via rheological studies, mechanical testing and scanning electron microscopy (SEM) imaging, which allowed us to determine the optimal biomechanical properties and develop a biocompatible scaffold. The morphological evolution processes and proliferation rates of glioblastoma cells (U251-MG) cultured on HA-MA surfaces were evaluated by comparing 2D structures with 3D structures, showing that the change in dimensionality impacted cell functions and interactions. The cell viability assays and evaluation of mitochondrial metabolism showed that the hydrogels did not interfere with cell survival. In addition, morphological studies provided evidence of cell-matrix interactions that promoted cell budding from the spheroids and the invasiveness in the surrounding environment

Staphylococcus aureus nosocomial infections: The role of a rapid and low-cost characterization for the establishment of a surveillance system

Continuous surveillance on resistance patterns and characterization of Staphylococcus aureus represent simple and low-cost techniques to understand and evaluate the effectiveness of infection control and antimicrobial prescribing measures. In this study we analyzed the antibiotic susceptibility and trends for S. aureus strains collected from bacteraemia cases in a five year period. Between 2004 and 2008 we noted a progressive decrease in the number of S. aureus isolates compared to all pathogens from clinical specimens and S. aureus bloodstream infections (BSI) reflected a similar trend. In particular we analyzed 185 isolates from blood cultures: 89 isolates were MSSA and 96 isolates were MRSA. Molecular SCCmec typing of these strains showed an absolute prevalence of types I and II, whereas five spa types from 96 isolates were obtained. Resistance pattern analysis allowed us to place MRSA strains into 12 antibiotypes and the major antibiotype was resistant to penicillin, gentamicin, erythromycin, clindamycin and ciprofloxacin. The predominant antibiotype among the MSSA isolates was resistant only to penicillin. In addition, 19.1% of MSSA are susceptible to all antibiotics tested. We also found a close association between antibiotyping 1 and genotyping t002/SCCmecI of MRSA strains, suggesting a nosocomial scenario dominated by a few particular clones

Activation of Hsp90 Enzymatic Activity and Conformational Dynamics through Rationally Designed Allosteric Ligands

Hsp90 is a molecular chaperone of pivotal importance for multiple cell pathways. ATP-regulated internal dynamics are critical for its function and current pharmacological approaches block the chaperone with ATP-competitive inhibitors. Herein, a general approach to perturb Hsp90 through design of new allosteric ligands aimed at modulating its functional dynamics is proposed. Based on the characterization of a first set of 2-phenylbenzofurans showing stimulatory effects on Hsp90 ATPase and conformational dynamics, new ligands were developed that activate Hsp90 by targeting an allosteric site, located 65 æ from the active site. Specifically, analysis of protein responses to first-generation activators was exploited to guide the design of novel derivatives with improved ability to stimulate ATP hydrolysis. The molecules’ effects on Hsp90 enzymatic, conformational, cochaperone and client-binding properties were characterized through biochemical, biophysical and cellular approaches. These designed probes act as allosteric activators of the chaperone and affect the viability of cancer cell lines for which proper functioning of Hsp90 is necessary