An Updated Review of Bioactive Peptides from Mushrooms in a Well-Defined Molecular Weight Range

Here, we report the current status of the bioactive peptides isolated and characterized from mushrooms during the last 20 years, considering ‘peptide’ a succession from to 2 to 100 amino acid residues. According to this accepted biochemical definition, we adopt ~10 kDa as the upper limit of molecular weight for a peptide. In light of this, a careful revision of data reported in the literature was carried out. The search revealed that in the works describing the characterization of bioactive peptides from mushrooms, not all the peptides have been correctly classified according to their molecular weight, considering that some fungal proteins (>10 kDa MW) have been improperly classified as ‘peptides’. Moreover, the biological action of each of these peptides, the principles of their isolation as well as the source/mushroom species were summarized. Finally, this review highlighted that these peptides possess antihypertensive, antifungal, antibiotic and antimicrobial, anticancer, antiviral, antioxidant and ACE inhibitory properties

La Ricerca-Azione Partecipativa come pedagogia della con-vers-azione. Un percorso di co-progettazione per la costruzione di una comunità educante

This paper shows the early results of a Participatory Action-Research (PAR) in which University, School, and Third Sector of the city of Palermo dialogue with each other to design new educational systems’ architectures. Within the theoretical framework provided by Universal Design for Learning, Outdoor Education and the Capability Approach, the chosen methodology is the informal conversation of the World Cafè. The working tables reflected on the implications of the intertwining among educational agencies, technological innovations, and territorial fabric. From these significant exchanges emerged perspectives of emancipation and co-construction of inclusive contexts for learning and social innovation

Relationship between bone cross-sectional area and indices of peripheral artery disease

Most studies on the relationship between bone mineral density and atherosclerosis have used dual-energy X-ray absorptiometry, but this method is relatively insensitive to bone geometry. The aim of this study was to investigate the relationship between bone area and indices of carotid and peripheral atherosclerosis. We studied 841 persons aged 65 years or older (women = 444, mean age 73.8 years; men = 397, mean age = 75.3 years) enrolled in the InCHIANTI study and free from active malignancies, chronic use of bisphosphonates or steroids, and estrogen replacement therapy. The tibial cortical and total cross-sectional area (CSA) were measured by peripheral quantitative computed tomography and their ratio was calculated (cortical/total cross-sectional area ratio, cCSA/tCSA); carotid plaques were screened by echography, and peripheral artery disease (PAD) was defined as an ankle/brachial index <0.9 or presence of intermittent claudication. No association between cCSA/tCSA and atherosclerosis was observed in men. In women, lower cCSA/tCSA was associated with both carotid plaques [odds ratio (OR) for lowest vs. best quartile = 2.09, 95 % confidence interval (CI) 1.2-3.68] and PAD (OR = 3.43, 95 % CI 1.58-8.12). After correction for potential confounders (age since menopause, body mass index, Parathyroid hormone, vitamin D, leptin, DHEA-S, testosterone, physical activity, chronic obstructive pulmonary disease, and reduced renal function), the association was not confirmed. According to partial logistic regression, the carotid plaque-cCSA/tCSA association, but not the PAD-cCSA/tCSA association, was mostly dependent on years since menopause. In women the association between osteoporosis and carotid plaques likely reflects hormonal deprivation, whereas that between osteoporosis and PAD seems multifactorial in origin. © 2013 Springer Science+Business Media New York

Ageritin from pioppino mushroom: The prototype of ribotoxin-like proteins, a novel family of specific ribonucleases in edible mushrooms

Ageritin is a specific ribonuclease, extracted from the edible mushroom Cyclocybe aegerita (synonym Agrocybe aegerita), which cleaves a single phosphodiester bond located within the uni-versally conserved alpha-sarcin loop (SRL) of 23–28S rRNAs. This cleavage leads to the inhibition of protein biosynthesis, followed by cellular death through apoptosis. The structural and enzy-matic properties show that Ageritin is the prototype of a novel specific ribonucleases family named ‘ribotoxin-like proteins’, recently found in fruiting bodies of other edible basidiomycetes mushrooms (e.g., Ostreatin from Pleurotus ostreatus, Edulitins from Boletus edulis, and Gambositin from Calocybe gambosa). Although the putative role of this toxin, present in high amount in fruiting body (>2.5 mg per 100 g) of C. aegerita, is unknown, its antifungal and insecticidal actions strongly support a role in defense mechanisms. Thus, in this review, we focus on structural, biological, antipathogenic, and enzymatic characteristics of this ribotoxin-like protein. We also highlight its biological relevance and potential biotechnological applications in agriculture as a bio-pesticide and in biomedicine as a therapeutic and diagnostic agent

Cytotoxicity effect of quinoin, type 1 ribosome-inactivating protein from quinoa seeds, on glioblastoma cells

Ribosome-inactivating proteins (RIPs) are found in several edible plants and are well characterized. Many studies highlight their use in cancer therapy, alone or as immunoconjugates, linked to monoclonal antibodies directed against target cancer cells. In this context, we investigate the cytotoxicity of quinoin, a novel type 1 RIP from quinoa seeds, on human continuous and primary glioblastoma cell lines. The cytotoxic effect of quinoin was assayed on human continuous glioblas-toma U87Mg cells. Moreover, considering that common conventional glioblastoma multiforme (GBM) cell lines are genetically different from the tumors from which they derive, the cytotoxicity of quinoin was subsequently tested towards primary cells NULU and ZAR (two cell lines established from patients’ gliomas), also in combination with the chemotherapeutic agent temozolomide (TMZ), cur-rently used in glioblastoma treatment. The present study demonstrated that quinoin (2.5 and 5.0 nM) strongly reduced glioblastoma cells’ growth. The mechanisms responsible for the inhibitory action of quinoin are different in the tested primary cell lines, reproducing the heterogeneous response of glioblastoma cells. Interestingly, primary cells treated with quinoin in combination with TMZ were more sensitive to the treatment. Overall, our data highlight that quinoin could represent a novel tool for glioblastoma therapy and a possible adjuvant for the treatment of the disease in combination with TMZ, alone or as possible immunoconjugates/nanoconstructs

Ageritin—The Ribotoxin-like Protein from Poplar Mushroom (Cyclocybe aegerita) Sensitizes Primary Glioblastoma Cells to Conventional Temozolomide Chemotherapy

Here, we propose Ageritin, the prototype of the ribotoxin-like protein family, as an adjuvant treatment to control the growth of NULU and ZAR, two primary human glioblastoma cell lines, which exhibit a pharmacoresistance phenotype. Ageritin is able to inhibit NULU and ZAR growth with an IC50 of 0.53 ± 0.29 µM and 0.42 ± 0.49 µM, respectively. In this study, Ageritin treatment highlighted a macroscopic genotoxic response through the formation of micronuclei, which represents the morphological manifestation of genomic chaos induced by this toxin. DNA damage was not associated with either the deregulation of DNA repair enzymes (i.e., ATM and DNA-PK), as demonstrated by quantitative PCR, or reactive oxygen species. Indeed, the pretreatment of the most responsive cell line ZAR with the ROS scavenger N-acetylcysteine (NAC) did not follow the reverse cytotoxic effect of Ageritin, suggesting that this protein is not involved in cellular oxidative stress. Vice versa, Ageritin pretreatment strongly enhanced the sensitivity to temozolomide (TMZ) and inhibited MGMT protein expression, restoring the sensitivity to temozolomide. Overall, Ageritin could be considered as a possible innovative glioblastoma treatment, directly damaging DNA and downregulating the MGMT DNA repair protein. Finally, we verified the proteolysis susceptibility of Ageritin using an in vitro digestion system, and considered the future perspective use of this toxin as a bioconjugate in biomedicine

The case for in-network computing on demand

Programmable network hardware can run services traditionally deployed on servers, resulting in orders-of-magnitude improvements in performance. Yet, despite these performance improvements, network operators remain skeptical of in-network computing. The conventional wisdom is that the operational costs from increased power consumption outweigh any performance benefits. Unless in-network computing can justify its costs, it will be disregarded as yet another academic exercise. In this paper, we challenge that assumption, by providing a detailed power analysis of several in-network computing use cases. Our experiments show that in-network computing can be extremely power-efficient. In fact, for a single watt, a software system on commodity CPU can be improved by a factor of x100 using FPGA, and a factor of x1000 utilizing ASIC implementations. However, this efficiency depends on the system load. To address changing workloads, we propose In-Network Computing On Demand, where services can be dynamically moved between servers and the network. By shifting the placement of services on-demand, data centers can optimize for both performance and power efficiency

Decentralised Commitment for Optimistic Semantic Replication

International audienceWe study large-scale distributed cooperative systems that use optimistic replication. We represent a system as a graph of actions (operations) connected by edges that reify semantic constraints between actions. Constraint types include conflict, execution order, dependence, and atomicity. The local state is some schedule that conforms to the constraints; because of conflicts, client state is only tentative. For consistency, site schedules should converge; we designed a decentralised, asynchronous commitment protocol. Each client makes a proposal, reflecting its tentative and/or preferred schedules. Our protocol distributes the proposals, which it decomposes into semantically-meaningful units called candidates, and runs an election between comparable candidates. A candidate wins when it receives a majority or a plurality. The protocol is fully asynchronous: each site executes its tentative schedule independently, and determines locally when a candidate has won an election. The committed schedule is as close as possible to the preferences expressed by clients

Transcription factor decoy molecules based on a peptide nucleic acid (PNA)-DNA chimera mimicking Sp1 binding sites

Peptide nucleic acids (PNAs) are DNA-mimicking molecules in which the sugar-phosphate backbone is replaced by a pseudopeptide backbone composed of N-(2-aminoethyl)glycine units. We determined whether double-stranded molecules based on PNAs and PNA-DNA-PNA (PDP) chimeras could be capable of stable interactions with nuclear proteins belonging to the Sp1 transcription factor family and, therefore, could act as decoy reagents able to inhibit molecular interactions between Sp1 and DNA. Since the structure of PNA/PNA hybrids is very different from that of the DNA/DNA double helix, they could theoretically alter the molecular structure of the double-stranded PNA-DNA-PNA chimeras, perturbing interactions with specific transcription factors. We found that PNA-based hybrids do not inhibit Sp1/DNA interactions. In contrast, hybrid molecules based on PNA-DNA-PNA chimeras are very effective decoy molecules, encouraging further experiments focused on the possible use of these molecules for the development of potential agents for a decoy approach in gene therapy. In this respect, the finding that PDP-based decoy molecules are more resistant than DNA/DNA hybrids to enzymatic degradation appears to be of great interest. Furthermore, their resistance can even be improved after complexation with cationic liposomes to which PDP/PDP chimeras are able to bind by virtue of their internal DNA structure