Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells

Human mesenchymal stem cells (hMSCs) are adult multipotent stem cells located in various tissues, including the bone marrow. In contrast to terminally differentiated somatic cells, adult stem cells must persist and function throughout life to ensure tissue homeostasis and repair. For this reason, they must be equipped with DNA damage responses able to maintain genomic integrity while ensuring their lifelong persistence. Evaluation of hMSC response to genotoxic insults is of great interest considering both their therapeutic potential and their physiological functions. This study aimed to investigate the response of human bone marrow MSCs to the genotoxic agent Actinomycin D (ActD), a well-known anti-tumour drug. We report that hMSCs react by undergoing premature senescence driven by a persistent DNA damage response activation, as hallmarked by inhibition of DNA synthesis, p21 and p16 protein expression, marked Senescent Associated β-galactosidase activity and enlarged γH2AX foci co-localizing with 53BP1 protein. Senescent hMSCs overexpress several senescence-associated secretory phenotype (SASP) genes and promote motility of lung tumour and osteosarcoma cell lines in vitro. Our findings disclose a multifaceted consequence of ActD treatment on hMSCs that on the one hand helps to preserve this stem cell pool and prevents damaged cells from undergoing neoplastic transformation, and on the other hand alters their functional effects on the surrounding tissue microenvironment in a way that might worsen their tumour-promoting behaviour

Arcobacter spp. in raw milk from vending machines in Piedmont and occurrence of virulence genes in isolates

Arcobacter spp. has been recognized as an emerging foodborne pathogen and a hazard to human health. In the dairy chain, it has been isolated from different sources, nevertheless data on Arcobacter occurrence in raw milk provided by vending machines are few. This study aimed to identify potentially pathogenic Arcobacter spp. in raw milk intended for human consumption sold through vending machines located in Piedmont. In an 8-month period, 37 raw milk samples were collected from 24 dairy farms: 12 (32,4%) were collected directly in farm from bulk tank milk and 25 (67,6%) from vending machines. Eight (21,6%) out of the 37 milk samples and 7 (29,2%) out of the 24 dairy farms were positive for Arcobacter spp. by culture examination. Four (16%) out of the 25 samples from vending machines and 4 (33,3%) out of the 12 samples from bulk tank milk were positive. All 8 isolates were identified as A. butzleri both by MALDI-TOF MS and multiplex end-point PCR. According to the detection of virulence genes, a total of four Patho-types were highlighted: 5 isolates in P-type 1 and only one isolate for each of the P-types 2-3-4. A. butzleri isolates carrying encoding virulence factors genes were isolated from raw milk intended for human consumption: these findings strengthen the compulsory consumption after boiling as required by current legislation and suggest the need of enlarging the analytical investigations to other microorganisms not yet included in the food safety criteria

Identification of New Hematopoietic Cell Subsets with a Polyclonal Antibody Library Specific for Neglected Proteins

The identification of new markers, the expression of which defines new phenotipically and functionally distinct cell subsets, is a main objective in cell biology. We have addressed the issue of identifying new cell specific markers with a reverse proteomic approach whereby approximately 1700 human open reading frames encoding proteins predicted to be transmembrane or secreted have been selected in silico for being poorly known, cloned and expressed in bacteria. These proteins have been purified and used to immunize mice with the aim of obtaining polyclonal antisera mostly specific for linear epitopes. Such a library, made of about 1600 different polyclonal antisera, has been obtained and screened by flow cytometry on cord blood derived CD34+CD45dim cells and on peripheral blood derived mature lymphocytes (PBLs). We identified three new proteins expressed by fractions of CD34+CD45dim cells and eight new proteins expressed by fractions of PBLs. Remarkably, we identified proteins the presence of which had not been demonstrated previously by transcriptomic analysis. From the functional point of view, looking at new proteins expressed on CD34+CD45dim cells, we identified one cell surface protein (MOSC-1) the expression of which on a minority of CD34+ progenitors marks those CD34+CD45dim cells that will go toward monocyte/granulocyte differentiation. In conclusion, we show a new way of looking at the membranome by assessing expression of generally neglected proteins with a library of polyclonal antisera, and in so doing we have identified new potential subsets of hematopoietic progenitors and of mature PBLs

Contrasted Patterns of Molecular Evolution in Dominant and Recessive Self-Incompatibility Haplotypes in Arabidopsis

Self-incompatibility has been considered by geneticists a model system for reproductive biology and balancing selection, but our understanding of the genetic basis and evolution of this molecular lock-and-key system has remained limited by the extreme level of sequence divergence among haplotypes, resulting in a lack of appropriate genomic sequences. In this study, we report and analyze the full sequence of eleven distinct haplotypes of the self-incompatibility locus (S-locus) in two closely related Arabidopsis species, obtained from individual BAC libraries. We use this extensive dataset to highlight sharply contrasted patterns of molecular evolution of each of the two genes controlling self-incompatibility themselves, as well as of the genomic region surrounding them. We find strong collinearity of the flanking regions among haplotypes on each side of the S-locus together with high levels of sequence similarity. In contrast, the S-locus region itself shows spectacularly deep gene genealogies, high variability in size and gene organization, as well as complete absence of sequence similarity in intergenic sequences and striking accumulation of transposable elements. Of particular interest, we demonstrate that dominant and recessive S-haplotypes experience sharply contrasted patterns of molecular evolution. Indeed, dominant haplotypes exhibit larger size and a much higher density of transposable elements, being matched only by that in the centromere. Overall, these properties highlight that the S-locus presents many striking similarities with other regions involved in the determination of mating-types, such as sex chromosomes in animals or in plants, or the mating-type locus in fungi and green algae

Selenium and Vitamin E Concentrations in a Healthy Donkey Population in Central Italy.

Selenium and vitamin E protect the body against oxidative stress. Clinical manifestations of their deficiency in equids include neurologic and muscular symptoms. Despite the importance of donkeys as working and production animals, there is a dearth of scientific data on selenium and vitamin E normal values. Therefore, the aim of this study was to investigate the plasma concentrations of selenium and vitamin E in healthy donkeys belonging to different ages, sexes, and productive phases. Animals were divided into five groups including foals (group A: n = 7, n = 4 males and n = 3 females), weanlings and yearlings (group B: n = 7, n = 2 males and n = 5 females), nonpregnant nonlactating jennies (group C: n = 5), pregnant nonlactating jennies (group D: n = 9), and adult males (group E: n = 9). Plasma samples obtained from each animal were tested for vitamin E and selenium concentration. One-way analysis of variance showed significant differences in selenium concentrations (P = .001) between group A and group E. In this study, we found the selenium range for donkeys to be 0.02-0.14 μg/mL, which is lower than the recommended range for horses. The results suggest that donkeys may have a lower selenium requirement than horses. Plasma vitamin E levels were 3.29-12.99 μmol/L, with foals having lower concentrations than adults. Knowing specific reference ranges for vitamin E and selenium in healthy donkeys can help improve our understanding of how to prevent deficiencies that could compromise their overall health and well-being

Selenium and Vitamin E Concentrations in a Healthy Donkey Population in Central Italy.

Selenium and vitamin E protect the body against oxidative stress. Clinical manifestations of their deficiency in equids include neurologic and muscular symptoms. Despite the importance of donkeys as working and production animals, there is a dearth of scientific data on selenium and vitamin E normal values. Therefore, the aim of this study was to investigate the plasma concentrations of selenium and vitamin E in healthy donkeys belonging to different ages, sexes, and productive phases. Animals were divided into five groups including foals (group A: n = 7, n = 4 males and n = 3 females), weanlings and yearlings (group B: n = 7, n = 2 males and n = 5 females), nonpregnant nonlactating jennies (group C: n = 5), pregnant nonlactating jennies (group D: n = 9), and adult males (group E: n = 9). Plasma samples obtained from each animal were tested for vitamin E and selenium concentration. One-way analysis of variance showed significant differences in selenium concentrations (P = .001) between group A and group E. In this study, we found the selenium range for donkeys to be 0.02-0.14 μg/mL, which is lower than the recommended range for horses. The results suggest that donkeys may have a lower selenium requirement than horses. Plasma vitamin E levels were 3.29-12.99 μmol/L, with foals having lower concentrations than adults. Knowing specific reference ranges for vitamin E and selenium in healthy donkeys can help improve our understanding of how to prevent deficiencies that could compromise their overall health and well-being

Zeus, Aesculapius, Amalthea and the proteome of goat milk

he goat whey proteome has been explored in depth via capture with combinatorial peptide ligand libraries (CPLLs) at three different pH values. A total of 452 unique species have been tabulated, a proteome discovery so far unmatched in any single other investigation of milk from any mammalian species. This massive discovery is probably related to: i) the extraordinary load of proteins onto the CPLL beads (i.e. 2g for each different pH captures) vs. barely 100μL of beads; ii) the high resolution/high mass accuracy of mass spectral data; and iii) the use of two complementary tools, Mascot and PEAKS, each one contributing to a set of unique protein IDs. Due to the relative paucity of available protein annotations for goat, only 10% of the identified proteins belong to the capra, whereas 52% are specific of sheep and 37% are homologous to that of bovine milk. This work reports the largest description so far of the goat milk proteome, which has been compared with cow's milk proteome and would thus help to understand the importance of low-abundance proteins with respect to the unique biological properties of this nutrient

Does the COVID-19 external shock matter on household food waste? The impact of social distancing measures during the lockdown

The COVID-19 outbreak forced national governments to the adoption of social distancing and movement limitation measures aimed to reduce the diffusion of the virus and to mitigate its highly disruptive impact on the healthcare systems. Reduced income, job insecurity, distribution system interruptions, product shortages, localized price hikes, and time availability resulted in changes in food-related behaviors of households, including food waste generation. Although the significant progress achieved in the understanding of the multidimensional determinants of food losses and waste, no study has been considering the role of uncertainty generated by exogenous generalized shocks on consumer behavior. Building on an original and nationally representative survey, this work aims to investigate the impact of the measures introduced to contain the outbreak of COVID-19 on the main behavioral factors underpinning household food waste generation. The study develops a theoretical model introducing uncertainty validated through a Structural Equations Modelling approach. Results showed that during the quarantine period declared household food waste decreased, with more than half of the respondents reporting to waste less. The model suggested that the amount of material and non-material resources that consumers can dedicate to food-related activities represents the most influential factor for the generation of household food waste and that uncertainty is significantly affecting the drivers and indirectly influencing the self-declared values of food waste. Results suggest several potential policy implications, of which the most relevant being related to the importance of stimulating improvements in food management opportunities at home