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

Preliminary Observations on the Ability to Adapt To Salinity Changes in Nursehound Scyliorhinus Stellaris (Linnaeus, 1758) and Small Spotted Catsharks Scyliorhinus Canicula

Nursehound Scyliorhinus stellaris and small spotted catsharks Scyliorhinus canicula are frequently hosted in public aquaria and their husbandry is improving. The reproduction of this species in captive conditions is not difficult and juveniles are easily maintained in laboratory or in thematic tanks showed to the public. Data on juveniles are easily acquired in order to understand different aspects of their natural life and physiology. In two stages, during 2006 and 2010, six S. stellaris and three S. canicula juveniles were tested at different salinity levels under controlled conditions in order to understand their responses in terms of respiration rate to this stress. In fact this is a benthic species living at constant water quality parameters at approximately 70-100 meters deep

Analysis of sightings of white sharks in Gansbaai (South Africa)

In Gansbaai (South Africa), at Dyer Island Nature Reserve, a large White shark population is present and can be observed due to the support of local ecotourism operators authorised to reach the field observation sites. Between 2009 and 2019, it was possible to create a database including information about each individual observed. In total, 423 white sharks were sighted during 462 direct observation hours from the boat, that included 220 hours from the diving "cage". The mean sighting rate was 0.91 (range 0.18-1.53) sharks per hour and sighting rates dramatically declined in the last three years of the study period. Ninety-nine unique Photo-Ids of the dorsal fin were collected and only five re-sightings occurred, which indicate a transient behaviour for the Gansbaai White shark population. The sex ratio showed that females were always prevalent over males throughout the duration of the observations: the ratios were 1:2.2:0.8 for males, females, and unsexed sharks, respectively, and showed the prevalence of immature female individuals (immature: 51 males, 201 females, and 40 unsexed; adults: 49 males, 14 females, and 1 unsexed; undefined maturity: 5 males, 19 females, and 43 unsexed sharks). The predominance of immatures only applies to the females; there were as many immature males (51) as mature (49). The total length for all the individuals was between 150 cm and 500 cm (mean 308 cm, n = 423) with few young-of-the-year and adults recorded, indicating that Gansbaai Area is not a nursery area nor an adult aggregation site, but a seasonal feeding ground. The interannual sighting trend showed a consistent long-term increasing peak (ca. 4-5 years) and this could confirm that, in Gansbaai, the White shark frequency is not affected by ecotourism but, since 2017, a consistent loss of sightings was also due to recorded transient killer whales' unusual fatal attacks

The impact of fixed triple therapy with beclometasone/formoterol/glycopyrronium on health status and adherence in chronic obstructive pulmonary disease (COPD) in an italian context of real life: The TRITRIAL study protocol

Background: The fixed triple combination Beclometasone dipropionate/Formoterol fuma- rate/Glycopyrronium (BDP/FF/G, Trimbow\uae), an extrafine formulation in a unique pressur- ized metered dose inhaler, is indicated for the maintenance treatment in adult patients with moderate to severe COPD, not adequately treated by ICS/LABA or LABA/LAMA. Besides the evidence from three randomized controlled trials, the impact of fixed triple therapy has not been extensively evaluated in a real-world population of COPD patients. TRITRIAL (TRIple Therapy in Real life: Impact on Adherence and HeaLth status) is a non- interventional study to assess the effect of BDP/FF/G in a real world setting in Italy. Design: TRITRIAL is a 12-month, multicenter, cohort, prospective, longitudinal observational study. Two follow-up visits will be performed at 6 and 12 months, respectively. The study includes the collection of anamnestic clinical and functional data before the start of BDP/FF/G. The study is built for digital conduction, from signature of the informed consent on a dedicated web platform, to the collection of questionnaires and clinical data on the eCRF. Population: A total of 800 patients with COPD ranging from Global Initiative for Obstructive Lung Disease (GOLD) stages 2 to 4, receiving therapy with BDP/FF/G accord- ing to the Summary of Product Characteristics and local clinical practice, will be recruited. All concomitant therapies will be permitted for the duration of the study. Evaluations: The primary endpoint is the change of CAT score at 12 months versus baseline. Secondary endpoints are adherence, health-related quality of life, sleep quality, disease-related outcomes (lung function and COPD exacerbations), device usability, eco- nomic resources consumption, and safety. Conclusion: TRITRIAL study is expected to give relevant information about effectiveness of BDP/FF/G fixed triple therapy in a real-life setting of patients with COPD, where adherence, usability of inhalers and patient\u2019s preference of the device are crucial factors for the success of the therapy

An unprecedented case of cranial surgery in Longobard Italy (6th–8th century) using a cruciform incision

The Longobard necropolis of Castel Trosino dates from the 6th to the 8th century CE. Among the tombs excavated, the skull of an older female shows the first evidence of a cross-shaped bone modification on a living subject. Macroscopic, microscopic, and CT scan analyses revealed signs of at least two sets of scraping marks. Specifically, SEM analysis shows that perimortem bone-scraping traces are present on the skull. Both healed and non-healed defects suggest that the woman has received at least twice intentional bone modifications to address her condition. This is the first evidence of a cross-shaped therapeutic intervention on a living subject

Adipogenesis of skeletal muscle fibro/adipogenic progenitors is affected by the WNT5a/GSK3/β-catenin axis

Fibro/Adipogenic Progenitors (FAPs) are muscle-interstitial progenitors mediating pro-myogenic signals that are critical for muscle homeostasis and regeneration. In myopathies, the autocrine/paracrine constraints controlling FAP adipogenesis are released causing fat infiltrates. Here, by combining pharmacological screening, high-dimensional mass cytometry and in silico network modeling with the integration of single-cell/bulk RNA sequencing data, we highlighted the canonical WNT/GSK/β-catenin signaling as a crucial pathway modulating FAP adipogenesis triggered by insulin signaling. Consistently, pharmacological blockade of GSK3, by the LY2090314 inhibitor, stabilizes β-catenin and represses PPARγ expression abrogating FAP adipogenesis ex vivo while limiting fatty degeneration in vivo. Furthermore, GSK3 inhibition improves the FAP pro-myogenic role by efficiently stimulating, via follistatin secretion, muscle satellite cell (MuSC) differentiation into mature myotubes. Combining, publicly available single-cell RNAseq datasets, we characterize FAPs as the main source of WNT ligands inferring their potential in mediating autocrine/paracrine responses in the muscle niche. Lastly, we identify WNT5a, whose expression is impaired in dystrophic FAPs, as a crucial WNT ligand able to restrain the detrimental adipogenic differentiation drift of these cells through the positive modulation of the β-catenin signaling

An updated checklist of chondrichthyans of Calabria (Central Mediterranean, southern Italy), with emphasis on rare species

In this contribution the checklist of chondrichthyans of Calabria (Central Mediterranean, southern Italy) is reported. Data presented is derived from twenty years of opportunistic and active surveys from 2000 to 2020. A total of 55 species of chondrichthyans is present in Calabrian seas: 33 sharks, 20 rays, and 2 chimaeras. These species represent approximately 62% of the total reported for the Mediterranean. Approximately 71% of Calabrian species have been reported in the Tyrrhenian Sea, 49% in the Ionian Sea, and 33% in the Strait of Messina. According to IUCN criteria, new records of Endangered and Critically Endangered species (i.e., Carcahrodon carcharias [Linnaeus, 1758], Lamna nasus [Bonnaterre, 1788], Cetorhinus maximus [Gunnerus, 1765], Mobula mobular [Bonnaterre, 1788], Sphyrna zygaena [Linnaeus, 1758]) are reported, together with the first record of Raya brachyura Lafont, 1873 for the Ionian coasts and probably third confirmed record of the rare chimaera Hydrolagus mirabilis (Collett, 1904) for the Mediterranean

Trace elements and isotopes analyses on historical samples of white sharks from the Mediterranean Sea

The white shark Carcharodon carcharias has been present in the Mediterranean Sea since 3.2 million years ago. Nevertheless, the current population shows a low genetic variability suggesting an endangered small population, on which there is scarce information regarding ecotoxicology or trophic ecology. Given that white shark's sightings are rare in the Mediterranean and the possibility of obtaining samples is highly limited, the aim of this research was to provide general information regarding the concentration of trace elements and stable isotopes (delta N-15 and delta C-13). Laboratory analyses were performed on 18 and 12 subsamples from two different white sharks' vertebrae obtained from two adult specimens caught in 1987, in Favignana Island, Italy. Perforations were made along the vertebrae to describe both trace elements and stable isotopes at different life stages. A total of 38 trace elements were analysed, in which the highest concentrations were found in Fe, Sr, U, Pb, and Zn. The fluctuations of these elements during the ontogeny of both individuals could have been related to changes in diet and environment, although the specific origin remains unknown. Regarding stable isotopes, the vertebrae from the male showed an isotopic range from 9.6 parts per thousand to 10.8 parts per thousand (delta N-15) and from -16.5 parts per thousand to -13.0 parts per thousand (delta C-13) with a mean +/- SD value of 10.3 +/- 0.4 parts per thousand for delta N-15 and -14.6 +/- 1.3 parts per thousand for delta C-13; whereas the female vertebrae had an isotopic range from 9.8 parts per thousand to 11.1 parts per thousand (delta N-15) and from -16.9 parts per thousand to -15.0 parts per thousand (delta C-13), with a mean +/- SD value of 10.8 +/- 0.6 parts per thousand for delta N-15 and -15.8 +/- 0.8 parts per thousand for delta C-13. There were no significant delta N-15 differences (U = 6, p = 0.07346) between the two individuals. However, there were just significant differences in delta C-13 (t = -1.8, p = 0.049256), which could suggest sexual segregation in terms of habitat use and feeding habits

Mast cells and acute coronary syndromes : Relationship between serum tryptase, clinical outcome and severity of coronary artery disease

Objective: To assess the relationship between serum tryptase and the occurrence of major cardiovascular and cerebrovascular events (MACCE) at 2-year followup in patients admitted with acute coronary syndrome (ACS). To compare serum tryptase to other validated prognostic markers (maximum high-sensitivity troponin (hs-Tn), C reactive protein (CRP) levels at admission, Synergy between percutaneous coronary intervention with Taxus and Cardiac Surgery (SYNTAX) score). Methods: We measured serum tryptase at admission in 140 consecutive patients with ACS and in 50 healthy controls. The patients' follow-up was maintained for 2 years after discharge. The predictive accuracy of serum tryptase for 2-year MACCE was assessed and compared with hs-Tn, CRP and SYNTAX score. Results: Serum tryptase levels at admission were significantly higher in patients with ACS compared with the control group (p=0.0351). 2 years after discharge, 28/140 patients (20%) experienced MACCE. Serum tryptase levels, maximum hs-Tn measurements and SYNTAX score were higher in patients who experienced MACCE compared with those without (p<0.0001). Conversely, we found no significant association between MACCE and CRP. The predictive accuracy of serum tryptase for MACCE was set at the cut-off point of 6.7 ng/mL (sensitivity 46%, specificity 84%). Conclusions: In patients with ACS, serum tryptase measured during index admission is significantly correlated to the development of MACCE up to 2 years, demonstrating a possible long-term prognostic role of this biomarker