Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Nanoparticles-cell association predicted by protein corona fingerprints

In a physiological environment (e.g., blood and interstitial fluids) nanoparticles (NPs) will bind proteins shaping a "protein corona" layer. The long-lived protein layer tightly bound to the NP surface is referred to as the hard corona (HC) and encodes information that controls NP bioactivity (e.g. cellular association, cellular signaling pathways, biodistribution, and toxicity). Decrypting this complex code has become a priority to predict the NP biological outcomes. Here, we use a library of 16 lipid NPs of varying size (Ø ≈ 100-250 nm) and surface chemistry (unmodified and PEGylated) to investigate the relationships between NP physicochemical properties (nanoparticle size, aggregation state and surface charge), protein corona fingerprints (PCFs), and NP-cell association. We found out that none of the NPs' physicochemical properties alone was exclusively able to account for association with human cervical cancer cell line (HeLa). For the entire library of NPs, a total of 436 distinct serum proteins were detected. We developed a predictive-validation modeling that provides a means of assessing the relative significance of the identified corona proteins. Interestingly, a minor fraction of the HC, which consists of only 8 PCFs were identified as main promoters of NP association with HeLa cells. Remarkably, identified PCFs have several receptors with high level of expression on the plasma membrane of HeLa cells

Finite element analysis applied to redesign of submerged entry nozzles for steelmaking

The production of steel by continuous casting is facilitated by the use of refractory hollow-ware components. A critical component in this process is the submerged entry nozzle (SEN). The normal operating conditions of the SEN are arduous, involving large temperature gradients and exposure to mechanical forces arising from the flow of molten steel; experimental development of the components is challenging in so hazardous an environment. The effects of the thermal stress conditions in relation to a well-tried design were therefore simulated using a finite element analysis approach. It was concluded from analyses that failures of the type being experienced are caused by the large temperature gradient within the nozzle. The analyses pointed towards a supported shoulder area of the nozzle being most vulnerable to failure and practical in-service experience confirmed this. As a direct consequence of the investigation, design modifications, incorporating changes to both the internal geometry and to the nature of the intermediate support material, were implemented, thereby substantially reducing the stresses within the Al2O3/graphite ceramic liner. Industrial trials of this modified design established that the component reliability would be significantly improved and the design has now been implemented in series production

Inflammation, neurodegeneration and protein aggregation in the retina as ocular biomarkers for Alzheimer’s Disease in the 3xTg-AD mouse model

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. In the pathogenesis of AD a pivotal role is played by two neurotoxic proteins that aggregate and accumulate in the central nervous system: amyloid beta and hyper-phosphorylated tau. Accumulation of extracellular amyloid beta plaques and intracellular hyper-phosphorylated tau tangles, and consequent neuronal loss begins 10-15 years before any cognitive impairment. In addition to cognitive and behavioral deficits, sensorial abnormalities have been described in AD patients and in some AD transgenic mouse models. Retina can be considered a simple model of the brain, as some pathological changes and therapeutic strategies from the brain may be observed or applicable to the retina. Here we propose new retinal biomarkers that could anticipate the AD diagnosis and help the beginning and the follow-up of possible future treatments. We analyzed retinal tissue of triple-transgenic AD mouse model (3xTg-AD) for the presence of pathological hallmarks during disease progression. We found the presence of amyloid beta plaques, tau tangles, neurodegeneration, and astrogliosis in the retinal ganglion cell layer of 3xTg-AD mice, already at pre-symptomatic stage. Moreover, retinal microglia in pre-symptomatic mice showed a ramified, anti-inflammatory phenotype which, during disease progression, switches to a pro-inflammatory, less ramified one, becoming neurotoxic. We hypothesize retina as a window through which monitor AD-related neurodegeneration process

Epidemiology of legionnaires’ disease in italy, 2004–2019: A summary of available evidence

Legionnaires’ disease (LD) incidence has been increasing in several European countries since 2011. Currently, Italy is experiencing high notification rates for LD, whose cause still remains scarcely understood. We sought to summarize the available evidence on the epidemiology of LD in Italy (2004–2019), characterizing the risk of LD by region, sex, age group, and settings of the case (i.e., community, healthcare, or travel-associated cases). Environmental factors (e.g., average air temperatures and relative humidity) were also included in a Poisson regression model in order to assess their potential role on the annual incidence of new LD cases. National surveillance data included a total of 23554 LD cases occurring between 2004 and 2019 (70.4% of them were of male gender, 94.1% were aged 40 years and older), with age-adjusted incidence rates increasing from 1.053 cases per 100,000 in 2004 to 4.559 per 100,000 in 2019. The majority of incident cases came from northern Italy (43.2% from northwestern Italy, 25.6% from northeastern Italy). Of these, 5.9% were healthcare-related, and 21.1% were travel-associated. A case-fatality ratio of 5.2% was calculated for the whole of the assessed timeframe, with a pooled estimate for mortality of 0.122 events per 100,000 population per year. Poisson regression analysis was associated with conflicting results, as any increase in average air temperature resulted in reduced risk for LD cases (Incidence Rate Ratio [IRR] 0.807, 95% Confidence Interval [95% CI] 0.744–0.874), while higher annual income in older individ-uals was associated with an increased IRR (1.238, 95% CI 1.134–1.351). The relative differences in incidence between Italian regions could not be explained by demographic factors (i.e., age and sex distribution of the population), and also a critical reappraisal of environmental factors failed to sub-stantiate both the varying incidence across the country and the decennial trend we were able to identify

The Origanum Collection of Gaetano Savi (1769-1844) in the Herbarium Horti Pisani (PI)

The Origanum Collection of Gaetano Savi (1769-1844) in the Herbarium Horti Pisani (PI). The collection of exsiccata of the genus Origanum, studied by Gaetano Savi and kept in the Herbarium Horti Pisani (PI) represents a valuable document of Savi's work as a taxonomist. It provides useful news for researchers of systematics and history of botany. The collection is enriched by some original drawings and includes the lectotypes of Origanum confertum Savi and O. fortuitum Savi

Hantaviruses in agricultural and forestry workers: Knowledge, attitudes and practices in Italian physicians

Hantaviruses are viral pathogens usually endemic in rodent populations. Human exposure follows inhalation of dusts contaminated with rodent excreta, and most individuals have been in-fected in occupational settings heavily contaminated with rodent droppings, such as agricultural and forestry. To date, knowledge, attitudes and practices of medical professionals, especially occupational physicians (OP), regarding hantavirus disease in at-risk workers have been scarcely investigated. We investigated these topics through a structured questionnaire administered through an online survey of 223 medical professionals (42.2% of them working as OP). Adequate general knowledge of hantavirus disease was found in 48.9% of respondents, with OP exhibiting a better understanding of clinical features of human hantavirus infections. OP aware of the endemic status of hantavirus in North-Eastern Italy exhibited higher risk perception for agricultural workers (odds ratio 21,193, 95% confidence interval 3.666–122.505). On the contrary, a better knowledge of hantaviruses was association with acknowledging an increased risk of hantavirus infection in forestry workers (odds ratio 5.880, 95% confidence interval 1.620–21.343). Hantavirus in Italy represent an often-overlooked biological risk in occupational settings. The lack of preventive immunization, the inappropriate risk perception and the unsatisfying awareness of hantavirus issues collectively stress the importance of appropriate information campaigns among health care providers

Lectotypification of two Origanum names (Lamiaceae) described by Gaetano Savi

Origanum confertum Savi and O. fortuitum Savi are typified on herbarium specimens kept in PI. These taxa are identifiable, as heterotypic synonyms, with O. majorana L. and O. xpaniculatum W.D.J.Koch, respectively

Genetic diversity in the threatened Bellevalia webbiana (Asparagaceae) parallels functional and reproductive traits

Amongst the numerous Italian narrow endemic plants, the Webb’s hyacinth (Bellevalia webbiana Parl., Asparagaceae) is one of the most evolutionarily relevant, and threatened. The range of this bulbous perennial herb is restricted to an area of pre-Apennines (100–700 m a.s.l.) in Tuscany, and Emilia-Romagna (Central Italy), with two disjunct population groups. Typical habitats for Webb’s hyacinth are open fields, and meadows, wood margins, olive groves, and vineyards. During the last century, Webb’s hyacinth disappeared from several historical localities due to the development of human settlements. For these reasons, this species is currently listed in The IUCN Red List of Threatened Species as Endangered (EN A2c). Despite contributions providing important information on the species’ reproductive and functional traits, no population genetic information was available so far. In this study, a DNA fingerprinting approach was applied to study the five richest populations of this species (each with N > 50 individuals): three in Tuscany (Pratolino, Uccellatoio, Tavarnuzze), and two in Emilia-Romagna (Casola Valsenio and Faenza)