Computational tools for viral metagenomics and their application in clinical research

AbstractThere are 100 times more virions than eukaryotic cells in a healthy human body. The characterization of human-associated viral communities in a non-pathological state and the detection of viral pathogens in cases of infection are essential for medical care and epidemic surveillance. Viral metagenomics, the sequenced-based analysis of the complete collection of viral genomes directly isolated from an organism or an ecosystem, bypasses the “single-organism-level” point of view of clinical diagnostics and thus the need to isolate and culture the targeted organism. The first part of this review is dedicated to a presentation of past research in viral metagenomics with an emphasis on human-associated viral communities (eukaryotic viruses and bacteriophages). In the second part, we review more precisely the computational challenges posed by the analysis of viral metagenomes, and we illustrate the problem of sequences that do not have homologs in public databases and the possible approaches to characterize them

A new management scheme to support reverse logistics processes in the agrifood distribution sector

During the last decades, reverse logistics and reuse of products have received growing attention as profitable and sustainable business strategies. Looking at the agrifood distribution sector, every day thousands of agrifood stores throw away large quantities of food product no longer suitable for sale. This "waste product", in the majority of cases, could still find new uses as animal feed or fertilizer. The return flow of food product is a typical problem of reverse logistics. This study proposes a new bi-modular scheme for managing the process of collection of "food waste" resulting from the agribusiness distribution sector and its subsequent distribution to livestock farms and collection centers located in the area of interest. The proposed management scheme consists of two modules: - module 1: to cluster the observed area into convenient collection sectors by means of clustering algorithms; - module 2: to identify optimal retrieval routes within each cluster by using Vehicle Routing models. The province of Cagliari in Sardinia (Italy) has been identified as test area. An extensive data collection process has been performed in order to collect the information necessary to portray the existing scenario. The following businesses have been recorded: grocery stores and supermarkets with at least 400 sqm of retail area, livestock farms with at least 200 heads of cattle, feed mills. A number of variables concerning location, type, size and demand data have been collected for each recorded unit.The management scheme has been implemented in a software platform and successfully applied in the test area. The outcome provides useful insights to stakeholders and suggests avenues for further research in the area in order to develop a more general and intuitive tool for managing reverse logistics processes in agrifood chains

From mining wastes to mineral sources - investigating the REE-bearing occurrences in the Arburèse District (SW Sardinia)

In recent years, the search for possible sources of REE minerals in Europe involved numerous old mine areas with high volumes of mining wastes that may offer significant amounts of Critical Raw Materials (CRMs). In some cases, strong evidence of CRMs anomalous concentrations arises from environmental characterization of wastes, so that an interesting problem is that of finding their sources, i.e., the original CRMs - rich mineral phases in the residual ore. An excellent example is provided by the Arburèse district of SW Sardinia, for about 150 years a major Pb-Zn source in Italy, now an area under study for remediation of its severe environmental problems, including >10 Mt of waste deposits. The district exploited a large system (>10 km) of low-temperature polymetallic veins hosted in Lower Paleozoic siliciclastic rocks belonging to the Variscan Nappe zone, arranged in two main geometrical trends relative to the late Variscan Arbus pluton: “peripheral” and “intersecting”. Recent investigations in the Montevecchio mine area discovered high Zn (up to 2.65 wt.%) and Pb (1.23 wt.%) grades in stratified tailing materials belonging to the Sanna old processing plant. Remarkably, ICP-MS analyses on the same materials revealed total REE+ Y contents attaining about 600 ppm. XRD studies confirmed a tailing composition essentially made of gangue minerals (quartz, siderite and micas) with goethite, baryte and traces of Zn carbonates and Pb sulfates. Chondrite-normalized REE patterns are coherent with the hydrothermal character of the source: however, both the REE mineralogical host(s) in tailings and in the Montevecchio ore are still undetermined. In the search of REE-bearing phases in the ores, some relevant insights are provided by studies on the southern branch of the Arburèse system, where the veins of “peripheral” system are hosted in late Ordovician-Silurian sedimentary sequences. In this part of the district the polymetallic veins assume the character of five-elements (Ni-Co-As-Bi-Ag) veins, with a rich Ni-Co-Fe arsenide – quartz association (1) overprinted by a Zn-Pb-Cu sulfide – siderite – quartz association (2), very similar to that dominating in Montevecchio. Investigations in the Pira Inferida mine sector highlighted the presence of LREE fluorocarbonates (synchysite-Ce and bastnaesite-Ce) and phosphates (monazite) associated with rutile and apatite. LREE minerals have been detected by SEM-EDS as tiny crystals in the quartz-sericitic gangue of the Montevecchio-type (2) mineral association. The same minerals are found in millimetric aggregates in the oxide zone of the veins, sporadically reported by mineral collectors in other mine sites of the same system. Overall, these occurrences, similar to those found in other low-temperature vein systems of Sardinia (e.g., Silius vein system), appear reliable mineral REE sources for Montevecchio mine wastes; they may be therefore used as proxies for REE exploration and assessment in the district

Mineralogy of the scheelite-bearing ores of Monte Tamara, SW Sardinia: insights for the evolution of a Late Variscan W–Sn skarn system

Southwestern Sardinia, Italy, hosts several skarn, W–Sn–Mo greisen and hydrothermal deposits related to a 289±1 Ma Late Variscan granite suite. Among them, the most representative scheelite-bearing skarns belong to the San Pietro and Sinibidraxiu localities, in the Monte Tamara area, Sulcis region. The San Pietro deposit is a typical calc-silicate skarn whereas Sinibidraxiu is a sharply bounded orebody hosted in a marble unit. Optical petrographic observations and compositional data of major and trace elements were obtained for samples from both localities. San Pietro data suggests evolution from an oxidising prograde skarn stage (andradite–diopside, hematite and scheelite), to progressively more reducing conditions from the early retrograde (magnetite–cassiterite) to the late sulfide stage (arsenopyrite, stannite, molybdenite, Bi sulfosalts and Zn–Cu–Pb–Fe sulfides); Sinibidraxiu has diffuse carbonate–quartz intergrowths pseudomorphic over an early mineral assemblage with fibrous habit, followed by abundant ore mineral precipitation under reducing conditions (scheelite, arsenopyrite and Pb–Zn–Cu–Fe sulfides). Geothermometers indicate a comprehensive temperature range of 460–270°C for the sulfide stages of both deposits. The differences between the two deposits might be controlled by the distance from the source intrusion coupled with the different reactivity of the host rocks. The San Pietro mineralogy represents a more proximal skarn, contrasting with more distal mineralogical and chemical features characterising the Sinibidraxiu orebody (lack of Mo–Sn–Bi phases; LREE–MREE–HREE signature of scheelite). This investigation contributes for the first time to the identification of a W–Sn skarn system in SW Sardinia, thereby suggesting the Monte Tamara area and its surroundings as favourable for further exploration

A Cocktail-Based Formula for the Design of Nanosized Cosmeceuticals as Skincare and Anti-Age Products

Nasco and Bovale grape pomace extracts, alone or in association, were loaded in nanoemulsions tailored for cosmetic application, using Kolliphor((R))RH40 (kolliphor) as the synthetic surfactant, Olivem((R))1000 (olivem) as the natural one, and lecithin as the cosurfactant. Pink transparent or milky dispersions, as a function of the used extract and surfactant, were obtained to be used as cosmeceutical serum or milk. The sizes of the nanoemulsion droplets were small ( approximate to 77 nm with kolliphor and approximate to 141 nm with olivem), homogenously dispersed (similar to 0.24 with kolliphor and similar to 0.16 with olivem), highly negatively charged ( similar to-43 mV irrespective of the used surfactant) and their stability either on storage or under stressing conditions was affected by the used extract and surfactant. Formulations protected the extracts from the degradation caused by UV exposition, were biocompatible against keratinocytes, protected them against oxidative damages induced using hydrogen peroxide and inhibited the release of nitrite induced in macrophages using the lipopolysaccharide inflammatory stimulus. The overall results underlined the key role played by the composition of the formula to achieve a suitable cosmeceutical for skin care but even for the prevention of premature aging and chronic damages caused by the stressing conditions

RPL5 on 1p22.1 is recurrently deleted in multiple myeloma and its expression is linked to bortezomib response

Chromosomal region 1p22 is deleted in 6520% of multiple myeloma (MM) patients, suggesting the presence of an unidentified tumor suppressor. Using high-resolution genomic profiling, we delimit a 58 kb minimal deleted region (MDR) on 1p22.1 encompassing two genes: ectopic viral integration site 5 (EVI5) and ribosomal protein L5 (RPL5). Low mRNA expression of EVI5 and RPL5 was associated with worse survival in diagnostic cases. Patients with 1p22 deletion had lower mRNA expression of EVI5 and RPL5, however, 1p22 deletion status is a bad predictor of RPL5 expression in some cases, suggesting that other mechanisms downregulate RPL5 expression. Interestingly, RPL5 but not EVI5 mRNA levels were significantly lower in relapsed patients responding to bortezomib and; both in newly diagnosed and relapsed patients, bortezomib treatment could overcome their bad prognosis by raising their progression-free survival to equal that of patients with high RPL5 expression. In conclusion, our genetic data restrict the MDR on 1p22 to EVI5 and RPL5 and although the role of these genes in promoting MM progression remains to be determined, we identify RPL5 mRNA expression as a biomarker for initial response to bortezomib in relapsed patients and subsequent survival benefit after long-term treatment in newly diagnosed and relapsed patients

Natural attenuation can lead to environmental resilience in mine environment

Four streams flowing in the Iglesiente and Arburese mine districts (SW Sardinia, Italy), exploited for zinc (Zn) and lead (Pb) extraction from sulphides and secondary non-sulphide mineralization (calamine ores), have been studied combining investigations from the macroscale (hydrologic tracer techniques) to the microscale (X-ray powder diffraction, scanning electron microscopy, X-ray absorption spectroscopy). In the investigated area, concerns arise from release of metals to water during weathering of ore minerals and mine-waste. Specifically, Zn is observed at extremely high concentrations (10s of mg/L or more) in waters in some of the investigated catchments. The results from synoptic sampling campaigns showed marked differences of Zn loads, from 6.3 kg/day (Rio San Giorgio) to 2000 kg/day (Rio Irvi). Moreover, natural attenuation of metals was found to occur i) through precipitation of Fe compounds (Fe oxy/hydroxides and “green rust”), ii) by means of the authigenic formation of metal sulphides promoted by microbial sulphate reduction, iii) by metal intake in roots and stems of plants (Phragmites australis and Juncus acutus) and by immobilization in the rhizosphere, and iv) by cyanobacterial biomineralization processes that lead to formation of Zn-rich phases (hydrozincite and amorphous Zn-silicate). The biologically mediated natural processes that lead to significant abatement and/or reduction of metal loads, are the response of environmental systems to perturbations caused from mine activities, and can be considered part of the resilience of the system itself. The aim of this study is to understand the effect of these processes on the evolution of the studied systems towards more stable and, likely, resilient conditions, e.g. by limiting metal mobility and favouring the improvement of the overall quality of water. The understanding of how ecosystems adapt and respond to contamination, and which chemical and physical factors control these natural biogeochemical barriers, can help to plan effective remediation actions

Antiproliferative and proapoptotic effects of Inula viscosa extract on Burkitt lymphoma cell line.

Burkitt lymphoma is a very aggressive B-cell non-Hodgkin lymphoma. Although remarkable progress has been made in the therapeutic scenario for patients with Burkitt lymphoma, search and development of new effective anticancer agents to improve patient outcome and minimize toxicity has become an urgent issue. In this study, the antitumoral activity of Inula viscosa, a traditional herb obtained from plants collected on the Asinara Island, Italy, was evaluated in order to explore potential antineoplastic effects of its metabolites on Burkitt lymphoma. Raji human cell line was treated with increasing Inula viscosa extract concentration for cytotoxicity screening and subsequent establishment of cell cycle arrest and apoptosis. Moreover, gene expression profiles were performed to identify molecular mechanisms involved in the anticancer activities of this medical plant. The Inula viscosa extract exhibited powerful antiproliferative and cytotoxic activities on Raji cell line, showing a dose- and time-dependent decrease in cell viability, obtained by cell cycle arrest in the G2/M phase and an increase in cell apoptosis. The treatment with Inula viscosa caused downregulation of genes involved in cell cycle and proliferation (c-MYC, CCND1) and inhibition of cell apoptosis (BCL2, BCL2L1, BCL11A). The Inula viscosa extract causes strong anticancer effects on Burkitt lymphoma cell line. The molecular mechanisms underlying such antineoplastic activity are based on targeting and downregulation of genes involved in cell cycle and apoptosis. Our data suggest that Inula viscosa natural metabolites should be further exploited as potential antineoplastic agents against Burkitt lymphoma

A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population

<p>Abstract</p> <p>Background</p> <p>In recent years, numerous studies have assessed the prevalence of germline mutations in <it>BRCA1 </it>and <it>BRCA2 </it>genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of <it>BRCA1-2 </it>mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of <it>BRCA1-2 </it>germline mutations was also evaluated.</p> <p>Methods</p> <p>Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for <it>BRCA1-2 </it>mutations by DHPLC analysis and DNA sequencing. Association of <it>BRCA1 </it>and <it>BRCA2 </it>mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test.</p> <p>Results and Conclusion</p> <p>Overall, 8 <it>BRCA1 </it>and 5 <it>BRCA2 </it>deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in <it>BRCA2 </it>gene. The geographical distribution of <it>BRCA1-2 </it>mutations was related to three specific large areas of Sardinia, reflecting its ancient history: <it>a</it>) the Northern area, linguistically different from the rest of the island (where a <it>BRCA2 c.8764_8765delAG </it>mutation with founder effect was predominant); <it>b</it>) the Middle area, land of the ancient Sardinian population (where <it>BRCA2 </it>mutations are still more common than <it>BRCA1 </it>mutations); and <it>c</it>) the South-Western area, with many Phoenician and Carthaginian locations (where <it>BRCA1 </it>mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of <it>BRCA1-2 </it>germline mutations.</p