Albumin biofunctionalization to minimize the Staphylococcus aureus adhesion on solid substrates

Staphylococcus aureus has become the most common opportunistic microorganism related to nosocomial infections due to the bacteria capacity to form biofilms on biomedical devices and implants. Since bacterial adhesion is the first step in this pathogenesis, it is evident that inhibiting such a process will reduce the opportunity for bacterial colonization on the devices. This work is aimed at optimizing a surface biofunctionalization strategy to inhibit the adhesion of S. aureus on solid substrates. The first part of the work deals with the albumin adsorption-desorption process, studied by a factorial design of experiments to explore a wide range of experimental factors (protein concentration, pH, flow rate and adsorption time) and responses (initial adsorption rate, adsorbed amount, desorbed extent) for hydrophilic and hydrophobic substrates, with a reduced number of experiments. This approach allows the simultaneous evaluation of the factors affecting the albumin adsorption-desorption process to find a qualitative correlation with the amount of alive S. aureus adhered on albumin biofunctionalized substrates. The results of this work point to a relationship between bacterial adhesion and the degree of albumin relaxation on the solid substrate. In fact, the inhibition of bacterial adhesion on albumin biofunctionalized substrates is due to the surface perturbation on the native structure of the protein. On this base, a biofunctionalization strategy was designed using a solution of thermally treated albumin molecules (higher β-sheet or unordered secondary structure elements) to biofunctionalize solid substrates by dipping. With these albumin biofunctionalized substrates S. aureus adhesion was minimized.Fil: Martín, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Pfaffen, Maria Valeria del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Valenti, Laura Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Giacomelli, Carla Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

Original antifouling strategy: Polypropylene films modified with chitosan-coated silver nanoparticles

A new coating strategy of polypropylene (PP) films with silver nanoparticles (AgNPs) is proposed to obtain surfaces with antifouling properties. As a first step, the photograft polymerization is used to produce polyacrylic acid-grafted PP (PAA-grafted PP) films. A green AgNP synthesis is used by thermal reduction of AgNO3 with amino groups of chitosan (CS), which controls ion diffusion and stabilizes nanoparticles. AgNP/CS complexes are adsorbed on PAA-grafted PP by electrostatic interactions, yielding AgNP/CS-coated PP films. These films show an excellent antimicrobial activity, even for AgNP contents as low as 0.08 wt %, reducing more than 4 log units in the viable Staphylococcus aureus concentration or inducing Escherichia coli death. This trend is consistent with an adequate amount of small AgNP adsorbed in an organized manner within a thin surface layer. Therefore, the antimicrobial activity of this film seems to be more than promising, used as an active surface for a wide range of applications.Fil: Mosconi, Giuliana. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Stragliotto, María Fernanda. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Slenk, Walte. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Valenti, Laura Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Fisicoquímica; ArgentinaFil: Giacomelli, Carla Eugenia. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Strumia, Miriam Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; ArgentinaFil: Gomez, Cesar Gerardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentin

MiR-494 induces metabolic changes through G6pc targeting and modulates sorafenib response in hepatocellular carcinoma

BackgroundMetabolic reprogramming is a well-known marker of cancer, and it represents an early event during hepatocellular carcinoma (HCC) development. The recent approval of several molecular targeted agents has revolutionized the management of advanced HCC patients. Nevertheless, the lack of circulating biomarkers still affects patient stratification to tailored treatments. In this context, there is an urgent need for biomarkers to aid treatment choice and for novel and more effective therapeutic combinations to avoid the development of drug-resistant phenotypes. This study aims to prove the involvement of miR-494 in metabolic reprogramming of HCC, to identify novel miRNA-based therapeutic combinations and to evaluate miR-494 potential as a circulating biomarker.MethodsBioinformatics analysis identified miR-494 metabolic targets. QPCR analysis of glucose 6-phosphatase catalytic subunit (G6pc) was performed in HCC patients and preclinical models. Functional analysis and metabolic assays assessed G6pc targeting and miR-494 involvement in metabolic changes, mitochondrial dysfunction, and ROS production in HCC cells. Live-imaging analysis evaluated the effects of miR-494/G6pc axis in cell growth of HCC cells under stressful conditions. Circulating miR-494 levels were assayed in sorafenib-treated HCC patients and DEN-HCC rats.ResultsMiR-494 induced the metabolic shift of HCC cells toward a glycolytic phenotype through G6pc targeting and HIF-1A pathway activation. MiR-494/G6pc axis played an active role in metabolic plasticity of cancer cells, leading to glycogen and lipid droplets accumulation that favored cell survival under harsh environmental conditions. High miR-494 serum levels associated with sorafenib resistance in preclinical models and in a preliminary cohort of HCC patients. An enhanced anticancer effect was observed for treatment combinations between antagomiR-494 and sorafenib or 2-deoxy-glucose in HCC cells.ConclusionsMiR-494/G6pc axis is critical for the metabolic rewiring of cancer cells and associates with poor prognosis. MiR-494 deserves attention as a candidate biomarker of likelihood of response to sorafenib to be tested in future validation studies. MiR-494 represents a promising therapeutic target for combination strategies with sorafenib or metabolic interference molecules for the treatment of HCC patients who are ineligible for immunotherapy

A Framework for Prioritizing the TESS Planetary Candidates Most Amenable to Atmospheric Characterization

A key legacy of the recently launched TESS mission will be to provide the astronomical community with many of the best transiting exoplanet targets for atmospheric characterization. However, time is of the essence to take full advantage of this opportunity. JWST, although delayed, will still complete its nominal five year mission on a timeline that motivates rapid identification, confirmation, and mass measurement of the top atmospheric characterization targets from TESS. Beyond JWST, future dedicated missions for atmospheric studies such as ARIEL require the discovery and confirmation of several hundred additional sub-Jovian size planets (R_p < 10 R_Earth) orbiting bright stars, beyond those known today, to ensure a successful statistical census of exoplanet atmospheres. Ground-based ELTs will also contribute to surveying the atmospheres of the transiting planets discovered by TESS. Here we present a set of two straightforward analytic metrics, quantifying the expected signal-to-noise in transmission and thermal emission spectroscopy for a given planet, that will allow the top atmospheric characterization targets to be readily identified among the TESS planet candidates. Targets that meet our proposed threshold values for these metrics would be encouraged for rapid follow-up and confirmation via radial velocity mass measurements. Based on the catalog of simulated TESS detections by Sullivan et al. (2015), we determine appropriate cutoff values of the metrics, such that the TESS mission will ultimately yield a sample of $\sim300$ high-quality atmospheric characterization targets across a range of planet size bins, extending down to Earth-size, potentially habitable worlds.Comment: accepted to PAS

The Beaker phenomenon and the genomic transformation of northwest Europe

From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

Towards a Muon Collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work.Comment: 118 pages, 103 figure

Towards a muon collider

A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p &lt; 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription