The spontaneous immortalization probability of mammalian cell culture strains, as their proliferative capacity, correlates with species body mass, not longevity

Background: The Peto's paradox consists in the observation that individuals from long-lived and large animal species do not experience a higher cancer incidence, despite being exposed for longer time to the possibility of accumulating mutations and having more target cells exposed to the phenomenon. The existence of this paradox has been recently confirmed (Vincze et al., 2022). Concurrently, robust evidence has been published that longevity involves a convergent evolution of cellular mechanisms that prevent the accu-mulation of mutations (Cagan et al., 2022). It remains unclear which cellular mechanisms are critical to allow the evolution of a large body mass while keeping cancer at bay.Methods: Adding to existing data linking cellular replicative potential and species body mass (Lorenzini et al., 2005), we have grown a total of 84 skin fibroblast cell strains from 40 donors of 17 mammalian species and analyzed their Hayflick's limit, i.e., their senescent plateau, and eventual spontaneous immortalization escape. The correlation of immortal-ization and replicative capacity of the species with their longevity, body mass and meta-bolism has been assessed through phylogenetic multiple linear regression (MLR).Results: The immortalization probability is negatively related to species body mass. The new evaluation and additional data about replicative potential strengthen our previous observation, confirming that stable and extended proliferation is strongly correlated with the evolution of a large body mass rather than lifespan.Conclusion: The relation between immortalization and body mass suggests a need to evolve stringent mechanisms that control genetic stability during the evolution of a large body mass

Prvi nalaz školjkaša Tellimya tenella (Lovén, 1846) u talijanskom dijelu Jadranskog mora

Alive specimens belonging to Tellimya tenella (Lovén, 1846) were recorded for the first time in Adriatic Sea. Up to date, only few pleistocene fossils or empty valves of this species had been reported in Italian waters.Žive jedinke Tellimya tenella (Lovén, 1846.) prvi su puta zabilježeni u Jadranskom moru. Do danas je u talijanskim vodama zabilježeno svega nekoliko pleistocenskih fosila ili praznih ljuski ove vrste

Prvi nalaz vrste Paradiopatra bihanica (Polychaeta, onuphidae) u Jadranskom moru

Paradiopatra bihanica (Intes & Le Loeuff, 1975) (Polychaeta, Onuphidae) is reported for the first time in the Adriatic Sea. In this study the morphological characters of the observed individuals are provided, as well as the extension of its hitherto geographical distribution.Paradiopatra bihanica (Intes & Le Loeuff, 1975) (Polychaeta, Onuphidae) je po prvi put pronađena u Jadranskom moru. U ovom radu su prikazane morfološke karakteristike istraživanih jedinki, te su priloženi podaci o njezinoj geografskoj raspodjeli

Incremental Peritoneal Dialysis Favourably Compares with Hemodialysis as a Bridge to Renal Transplantation

Background. The value of incremental peritoneal dialysis (PD) as a bridge to renal transplantation (Tx) has not been specifically addressed. Methods. All consecutive Stage 5 CKD patients with at least 1 year predialysis followup, starting incremental PD or HD under our care and subsequently receiving their first renal Tx were included in this observational cohort study. Age, gender, BMI, underlying nephropathy, residual renal function (RRF) loss rate before dialysis and RRF at RRT start, comorbidity, RRT schedules and adequacy measures, dialysis-related morbidity, Tx waiting time, RRF at Tx, incidence of delayed graft function (DGF), in-hospital stay for Tx, serum creatinine at discharge and one year later were collected and compared between patients on incremental PD or HD before Tx. Results. Seventeen patients on incremental PD and 24 on HD received their first renal Tx during the study period. Age, underlying nephropathy, RRF loss rate in predialysis, RRF at the start of RRT and comorbidity did not differ significantly. While on dialysis, patients on PD had significantly lower epoetin requirements, serum phosphate, calciumxphosphate product and better RRF preservation. Delayed graft function (DGF) occurred in 12 patients (29%), 1 on incremental PD and 11 on HD. Serum creatinine at discharge and 1 year later was significantly higher in patients who had been on HD. Conclusions. In patients receiving their first renal Tx, previous incremental PD was associated with low morbidity, excellent preservation of RRF, easier attainment of adequacy targets and significantly better immediate and 1-year graft function than those observed in otherwise well-matched patients previously treated with HD

Multi-benthic size approach to unveil different environmental conditions in a Mediterranean harbor area (Ancona, Adriatic Sea, Italy)

Harbors are hubs of human activity and are subject to the continuous discharge and release of industrial, agricultural, and municipal waste and contaminants. Benthic organisms are largely known to reflect environmental conditions they live in. Despite meio- and macrofauna interacting within the benthic system, they are ecologically distinct components of the benthos and as such may not necessarily respond to environmental conditions and/or disturbances in the same way. However, in a few field studies the spatial patterns of meio- and macrofauna have been simultaneously compared. In the present study, we assess the response and patterns in the abundance, diversity, and distribution of the two benthic size classes to the different environmental conditions they live in (i.e., sediment concentrations of selected trace metals and polycyclic aromatic hydrocarbons (PAHs); organic matter contents and grain size) characterizing the Ancona Harbor (Adriatic Sea). Meio- and macrofauna provided partially similar types of information depending on the indices used (univariate measures or community structure/species composition) and the different ‘response-to-stress’. The community structure (i.e., taxa composition) of both benthic size components clearly showed differences among sampling stations located from inside to outside the harbor, reflecting the marked environmental heterogeneity and disturbance typically characterizing these systems. Notwithstanding, the univariate measures (i.e., meio- and macrofauna total abundance, diversity indices and equitability) didn’t show similar spatial patterns. Meiofauna were likely to be more sensitive to the effects of environmental features and contaminants than macrofauna. Overall, trace metals and PAHs affected the community composition of the two benthic components, but only the meiofauna abundance and diversity were related to the environmental variables considered (i.e., quantity and quality oforganic matter). Our results pinpoint the importance of studying both meio- and macrofauna communities, which could provide greater insight into the processes affecting the investigated area and reveal different aspects of the benthic ecosystems in response to harbor conditions

Anadara kagoshimensis (Mollusca: Bivalvia: Arcidae) in Adriatic Sea: morphological analysis, molecular taxonomy, spatial distribution, and prediction

Morphological analysis, molecular characterization, and information on distribution and density of Anadara kagoshimensis (Tokunaga, 1906) specimens collected in the Adriatic Sea were here carried out as based on various material and data from five surveys conducted from 2010 to 2014, for a total of 329 bottom trawl hauls. The morphological and molecular analyses allowed to clarify the confused taxonomy regarding the biggest ark clam alien species invading the Italian waters and the Mediterranean Sea. The analysis on distribution and density revealed that A. kagoshimensis mostly occurs along the Italian coast at depths from 8 to 50 m, with a catch frequency of more than 98% in all hauls performed on silty-clay sediment at 8-30 m depth. The hotspot map clearly shows a reduction of its distribution area from 2010 to 2012

A genome search for primary vesicoureteral reflux shows further evidence for genetic heterogeneity

Vesicoureteral reflux (VUR) is the most common disease of the urinary tract in children. In order to identify gene(s) involved in this complex disorder, we performed a genome-wide search in a selected sample of 31 patients with primary VUR from eight families originating from southern Italy. Sixteen additional families with 41 patients were included in a second stage. Nonparametric, affected-only linkage analysis identified four genomic areas on chromosomes 1, 3, and 4 (p < 0.05); the best result corresponded to the D3S3681-D3S1569 interval on chromosome 3 (nonparametric linkage score, NPL = 2.75, p = 0.008). This region was then saturated with 26 additional markers, tested in the complete group of 72 patients from 24 families (NPL = 2.01, p = 0.01). We identified a genomic area on 3q22.2-23, where 26 patients from six multiplex families shared overlapping haplotypes. However, we did not find evidence for a common ancestral haplotype. The region on chromosome 1 was delimited to 1p36.2-34.3 (D1S228-D1S255, max. NPL = 1.70, p = 0.03), after additional fine typing. Furthermore, on chromosome 22q11.22-12.3, patients from a single family showed excess allele sharing (NPL = 3.35, p = 0.015). Only the chromosome 3q region has been previously reported in the single genome-wide screening available for primary VUR. Our results suggest the presence of several novel loci for primary VUR, giving further evidence for the genetic heterogeneity of this disorder

Fermentation of Vaccinium floribundum Berries with Lactiplantibacillus plantarum Reduces Oxidative Stress in Endothelial Cells and Modulates Macrophages Function

Accumulating evidence suggests that high consumption of natural antioxidants promotes health by reducing oxidative stress and, thus, the risk of developing cardiovascular diseases. Similarly, fermentation of natural compounds with lactic acid bacteria (LAB), such as Lactiplantibacillus plantarum, enhances their beneficial properties as regulators of the immune, digestive, and cardiovascular system. We investigated the effects of fermentation with Lactiplantibacillus plantarum on the antioxidant and immunomodulatory effects of Pushgay berries (Vaccinium floribundum, Ericaceae family) in human umbilical vein endothelial cells (HUVECs) and macrophage cell line RAW264.7. Polyphenol content was assayed by Folin-Ciocalteu and HPLC-MS/MS analysis. The effects of berries solutions on cell viability or proliferation were assessed by WST8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt and Lactate dehydrogenase (LDH) release, Trypan blue exclusion test, and Alamar blue assay. Antioxidant activity was evaluated by a cell-based chemiluminescent probe for the detection of intracellular H2O2 production in HUVECs. Heme oxygenase-1 (HO-1) expression levels were investigated by RT-qPCR. Glutathione reductase (GR), glutathione peroxidase (Gpx), superoxide dismutase (SOD), and catalase (CAT) activities, as markers of intracellular antioxidant defense, were evaluated by spectrophotometric analysis. The immunomodulatory activity was examined in RAW 264.7 by quantification of inducible nitric oxide synthase (iNOS) and Tumor Necrosis Factor-alpha (TNF alpha) by RT-qPCR. Data showed that fermentation of Pushgay berries (i) enhances the content of quercetin aglycone, and (ii) increases their intracellular antioxidant activity, as indicated by the reduction in H2O2-induced cell death and the decrease in H2O2-induced HO-1 gene expression in HUVECs treated for 24 h with fermented berries solution (10 mu g/mL). Moreover, treatment with Pushgay berries for 72 h (10 mu g/mL) promotes cells growth in RAW 264.7, and only fermented Pushgay berries increase the expression of iNOS in the same cell line. Taken together, our results show that LAB fermentation of Pushgay berries enhances their antioxidant and immunomodulatory properties

Development of effect-based bio-chemiluminescent cell bioassays for nutraceutical and biomedical applications

The final goal of the bioassay developed during the first two years of my Ph.D. was its application for the screening of antioxidant activity of nutraceuticals and for monitoring the intracellular H2O2 production in peripheral blood mononuclear cells (PBMCs) from hypercholesterolemic subjects before and after two months treatment with Evolocumab, a new generation LDL-cholesterol lowering drug. Moreover, a recombinant bioluminescent protein was developed during the last year using the Baculovirus expression system in insect cells. In particular, the protein combines the extracellular domain (ECD) of the Notch high affinity mutated form of one of the selective Notch ligands defined as Jagged 1 (Jag1) with a red emitting firefly luciferase since a pivotal role of “aberrant” Notch signaling activation in colorectal cancer (CRC) was reported. The probe was validated and characterized in terms of analytical performance and through imaging experiments, in order to understand if Jagged1-FLuc binding correlates with a Notch signaling overexpression and activation in CRC progression