Challenges of Periodontal Tissue Engineering: Increasing Biomimicry through 3D Printing and Controlled Dynamic Environment

In recent years, tissue engineering studies have proposed several approaches to regenerate periodontium based on the use of three-dimensional (3D) tissue scaffolds alone or in association with periodontal ligament stem cells (PDLSCs). The rapid evolution of bioprinting has sped up classic regenerative medicine, making the fabrication of multilayered scaffolds—which are essential in targeting the periodontal ligament (PDL)—conceivable. Physiological mechanical loading is fundamental to generate this complex anatomical structure ex vivo. Indeed, loading induces the correct orientation of the fibers forming the PDL and maintains tissue homeostasis, whereas overloading or a failure to adapt to mechanical load can be at least in part responsible for a wrong tissue regeneration using PDLSCs. This review provides a brief overview of the most recent achievements in periodontal tissue engineering, with a particular focus on the use of PDLSCs, which are the best choice for regenerating PDL as well as alveolar bone and cementum. Different scaffolds associated with various manufacturing methods and data derived from the application of different mechanical loading protocols have been analyzed, demonstrating that periodontal tissue engineering represents a proof of concept with high potential for innovative therapies in the near future

Fragmentation and thresholds in hydrological flow‐based ecosystem services

Loss and fragmentation of natural land cover due to expansion of agricultural areas is a global issue. These changes alter the configuration and composition of the landscape, particularly affecting those ecosystem services (benefits people receive from ecosystems) that depend on interactions between landscape components. Hydrological mitigation describes the bundle of ecosystem services provided by landscape features such as woodland that interrupt the flow of runoff to rivers. These services include sediment retention, nutrient retention and mitigation of overland water flow. The position of woodland in the landscape and the landscape topography are both important for hydrological mitigation. Therefore, it is crucial to consider landscape configuration and flow pathways in a spatially explicit manner when examining the impacts of fragmentation. Here we test the effects of landscape configuration using a large number (>7,000) of virtual landscape configurations. We created virtual landscapes of woodland patches within grassland, superimposed onto real topography and stream networks. Woodland patches were generated with user‐defined combinations of patch number and total woodland area, placed randomly in the landscape. The Ecosystem Service model used hydrological routing to map the “mitigated area” upslope of each woodland patch. We found that more fragmented woodland mitigated a greater proportion of the catchment. Larger woodland area also increased mitigation, however, this increase was nonlinear, with a threshold at 50% coverage, above which there was a decline in service provision. This nonlinearity suggests that the benefit of any additional woodland depends on two factors: the level of fragmentation and the existing area of woodland. Edge density (total edge of patches divided by area of catchment) was the best single metric in predicting mitigated area. Distance from woodland to stream was not a significant predictor of mitigation, suggesting that agri‐environment schemes planting riparian woodland should consider additional controls such as the amount of fragmentation in the landscape. These findings highlight the potential benefits of fragmentation to hydrological mitigation services. However, benefits for hydrological services must be balanced against any negative effects of fragmentation or habitat loss on biodiversity and other services

Indicators of biodiversity in agroecosystems: insights from Article 17 of the Habitat Directive and IUCN Red List of Threatened Species

In the current decade, the main goals for biodiversity conservation and environmental protection at the level of the European Union are set in the EU Biodiversity Strategy to 2020: halting biodiversity loss and restoring ecosystem services. A key requirement for the implementation of the Strategy in terms of targeting measures and funds, and monitoring trends is the construction of a biodiversity knowledge base, including spatially explicit information on biodiversity distribution and ecosystem condition. The work presented in this report is based on the analysis of two primary datasets on biodiversity and habitat status. The first one is the Habitats assessment carried out by EU Members States under Art.17 of the Habitats and Birds Directive. Information reported by Member States is analysed to derive the links between pressures and conservation status, showing that agriculture-related habitats have, on average, a worse conservation status when compared to other habitats. Consequently, threats and pressures having most influenced the status of the agricultural-related habitats can be identified. The second one is the global dataset on species threat status elaborated by The International Union for Conservation of Nature (IUCN). Spatially explicit representations of species distribution, status and richness across the EU 28 are provided, and most importantly the identification of wide geographic variables linked to ecological theory is presented, that explain to a large extent the continental trend in species richness. Finally, an example is presented of how the two exploited datasets can be jointly used by cross-tabulating data on habitats assessments and species threat status in a spatially explicit way at 10 km resolution, aiming at identifying hotspots were policy intervention is needed

Monitoring and modeling the invasion of the fast spreading alien Senecio inaequidens DC. in an alpine region

We modeled the distribution of the South African alien Senecio inaequidens DC. in the Aosta Valley, Western Italian Alps, using data extracted from the Regional floristic database and from an intensive field survey carried out in years 2009-2010. The aims of the work were (1) to evaluate whether the species is in the introduction, colonization, or establishment stage of invasion, (2) to detect the environmental factors that drive the invasion process, and (3) to highlight the potential range of distribution of the alien species. The modeling framework was a stepwise generalized linear model (GLM), using gridded presence/absence data and environmental predictors such as topography, climate, land use, and anthropogenic and natural disturbances. GLM were fit both with and without an additional independent variable to take into account current dispersal limitations. S. inaequidens displayed a very fast spread in the Aosta Valley in the years 1990-2010. The species was positively associated with roads and rivers, southern slopes, and negatively with elevation. However, it was found at an elevation of 1600 m, showing the ability to reach higher elevations than those observed for other invasive alien species, and confirming to be pre-adapted to mountain conditions. The difference between the species distribution models, with and without dispersal constraints, suggested that the availability of seed sources still limits the potential distribution of the species, rather than the environmental variables, and that the realized regional niche differs to a great extent from the equilibrium niche. When limitations to the seed source cease (i.e., in the establishment stage), the species will likely invade large areas that are currently characterized by pastures and grasslands with native species of high agricultural importance. The invasion of S. inaequidens should therefore be considered a serious threat, due to its potential to invade mountain regions, and in particular to colonize habitats used for grazing and forage, thus leading to a high risk for cattle and human health. We discuss the relevance of the results both concerning communication with the public and to support local eradication and control activities. The inclusion of S. inaequidens in the "black list" of the regional law for the conservation of alpine flora (L.R. 45/2009) will help to transfer the information and support invasion control, in particular at medium elevations

Self-Test Libraries Analysis for Pipelined Processors Transition Fault Coverage Improvement

Testing digital integrated circuits is generally done using Design-for-Testability (DfT) solutions. Such solutions, however, introduce non-negligible area and timing overheads that can be overcome by adopting functional solutions. In particular, functional test of integrated circuits plays a key role when guaranteeing the device's safety is required during the operative lifetime (in-field test), as required by standards like ISO26262. This can be achieved via the execution of a Self-Test Library (STL) by the device under test (DUT). Nevertheless, developing such test programs requires a significant manual effort, and can be non-trivial when dealing with complex modules. This paper moves the first step in defining a generic and systematic methodology to improve transition delay faults' observability of existing STLs. To do so, we analyze previously devised STLs in order to highlight specific points within test programs to be improved, leading to an increase in the final fault coverage

Short high fat diet triggers reversible and region specific effects in DCX+ hippocampal immature neurons of adolescent male mice

Adolescence represents a crucial period for maturation of brain structures involved in cognition. Early in life unhealthy dietary patterns are associated with inferior cognitive outcomes at later ages; conversely, healthy diet is associated with better cognitive results. In this study we analyzed the effects of a short period of hypercaloric diet on newborn hippocampal doublecortin+ (DCX) immature neurons in adolescent mice. Male mice received high fat diet (HFD) or control low fat diet (LFD) from the 5th week of age for 1 or 2 weeks, or 1 week HFD followed by 1 week LFD. After diet supply, mice were either perfused for immunohistochemical (IHC) analysis or their hippocampi were dissected for biochemical assays. Detailed morphometric analysis was performed in DCX+ cells that displayed features of immature neurons. We report that 1 week-HFD was sufficient to dramatically reduce dendritic tree complexity of DCX+ cells. This effect occurred specifically in dorsal and not ventral hippocampus and correlated with reduced BDNF expression levels in dorsal hippocampus. Both structural and biochemical changes were reversed by a return to LFD. Altogether these studies increase our current knowledge on potential consequences of hypercaloric diet on brain and in particular on dorsal hippocampal neuroplasticity

The Human Metapneumovirus Small Hydrophobic Protein has Properties Consistent with Those of a Viroporin and Can Modulate Viral Fusogenic Activity

Human metapneumovirus (HMPV) encodes three glycoproteins: the glycoprotein, which plays a role in glycosaminoglycan binding, the fusion (F) protein, which is necessary and sufficient for both viral binding to the target cell and fusion between the cellular plasma membrane and the viral membrane, and the small hydrophobic (SH) protein, whose function is unclear. The SH protein of the closely related respiratory syncytial virus has been suggested to function as a viroporin, as it forms oligomeric structures consistent with a pore and alters membrane permeability. Our analysis indicates that both the full-length HMPV SH protein and the isolated SH protein transmembrane domain can associate into higher-order oligomers. In addition, HMPV SH expression resulted in increases in permeability to hygromycin B and alteration of subcellular localization of a fluorescent dye, indicating that SH affects membrane permeability. These results suggest that the HMPV SH protein has several characteristics consistent with a putative viroporin. Interestingly, we also report that expression of the HMPV SH protein can significantly decrease HMPV F protein-promoted membrane fusion activity, with the SH extracellular domain and transmembrane domain playing a key role in this inhibition. These results suggest that the HMPV SH protein could regulate both membrane permeability and fusion protein function during viral infection. IMPORTANCE: Human metapneumovirus (HMPV), first identified in 2001, is a causative agent of severe respiratory tract disease worldwide. The small hydrophobic (SH) protein is one of three glycoproteins encoded by all strains of HMPV, but the function of the HMPV SH protein is unknown. We have determined that the HMPV SH protein can alter the permeability of cellular membranes, suggesting that HMPV SH is a member of a class of proteins termed viroporins, which modulate membrane permeability to facilitate critical steps in a viral life cycle. We also demonstrated that HMPV SH can inhibit the membrane fusion function of the HMPV fusion protein. This work suggests that the HMPV SH protein has several functions, though the steps in the HMPV life cycle impacted by these functions remain to be clarified

2018 - Drought and Water Crisis in Southern Africa

The results presented in this short technical report are focused on the 2018 Water Crisis that affected the Western Cape Province in South Africa. In one side it includes an analysis carried out by the JRC´s "Disaster Risk Management" Unit and the Global Drought Observatory (GDO report), which periodically provides an overview of precipitation patterns and its anomalies, including also those related to vegetation greenness and soil moisture values respect to the long term average. In the other, it presents a complementary section carried out by the WEFE4DEV Work Package of the Water-Energy-Food-Ecosystems (WEFE) Project which contributes to the online African Atlas on WEFE Cooperation. The analysis is focused on the medium to long term spatio-temporal patterns and behaviour of precipitation and temperature patterns. Both help the community to better understand the exceptional character of these phonomena, their periodicity and the scale at which these events occur. The outcomes are helpful for policymakers to identify current and future issues that impact water management, food and energy security in Africa, as well as they providevaluable information to better define mitigation measures, resilience and adaptation policies.JRC.D.2-Water and Marine Resource

Anti-tumor activity of functionalized biomimetic magnetite nanoparticles produced in the presence of MamC protein of Magnetococcus marinus MC-1

Magnetite Nanoparticles (MNPs) find many applications, including biotechnology, as they can be manipulated by an external magnetic field and functionalized with different molecules. Magnetotactic bacteria bio-mineralize magnetosomes (membrane-enveloped magnetites), which are the ideal magnetic particle. However, scaling-up magnetosome production is still challenging, so bio-mimetics, i.e. in vitro magnetite synthesis mediated by magnetosome-associated proteins is being explored. Our group is working with MamC from Magnetococcus marinus MC-1 that controls the morphology and size of the crystals, producing well faceted Biomimetic Magnetic Nanoparticles (BMNPs) of ~40 nm, which are paramagnetic at room and body temperature while having a large magnetic moment per particle under an external magnetic field. These BMNPs were cytocompatible and biocompatible in vivo. BMNPs were functionalized (isothermal adsorption) with a monoclonal antibody (mAb) recognizing the ectodomain of the human Met/HGF receptor (overexpressed in many cancers) and the chemotherapeutic Doxorubicin (DOXO). The functionalized BMNPs present hyperthermia and were stable at physiological pH, while releasing the adsorbed DOXO at acidic pH. mAb functionalization of BMNPs favored their interaction with cells expressing the Met/HGFR and cellular DOXO uptake and toxicity, which was enhanced upon cell exposition to a continuous magnetic field. Real-time cytotoxicity of the BMNPs showed that DOXO-mAb-BMNPs were significantly more toxic than DOXO-BMNPs on Met/HGFR expressing cells, while no differential toxicity was observed on cells not expressing this receptor. When DOXO-BMNPs were injected intravenously in tumor bearing mice and an external magnetic field was applied there, a higher amount of BMNPs accumulated in the tumor and tumor growth was decreased in comparison to mice in which no magnetic field was applied. These BMNPs could thus represent effective nano-carriers for targeted drug delivery and might be combined with hyperthermia to increase efficiency, resulting in a targeted local treatment of tumors with a decrease in the deleterious systemic side effects