27 research outputs found

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

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    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

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    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

    An automated 3D-printed perfusion bioreactor combinable with pulsed electromagnetic field stimulators for bone tissue investigations

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    In bone tissue engineering research, bioreactors designed for replicating the main features of the complex native environment represent powerful investigation tools. Moreover, when equipped with automation, their use allows reducing user intervention and dependence, increasing reproducibility and the overall quality of the culture process. In this study, an automated uni-/bi-directional perfusion bioreactor combinable with pulsed electromagnetic field (PEMF) stimulation for culturing 3D bone tissue models is proposed. A user-friendly control unit automates the perfusion, minimizing the user dependency. Computational fluid dynamics simulations supported the culture chamber design and allowed the estimation of the shear stress values within the construct. Electromagnetic field simulations demonstrated that, in case of combination with a PEMF stimulator, the construct can be exposed to uniform magnetic fields. Preliminary biological tests on 3D bone tissue models showed that perfusion promotes the release of the early differentiation marker alkaline phosphatase. The histological analysis confirmed that perfusion favors cells to deposit more extracellular matrix (ECM) with respect to the static culture and revealed that bi-directional perfusion better promotes ECM deposition across the construct with respect to uni-directional perfusion. Lastly, the Real-time PCR results of 3D bone tissue models cultured under bi-directional perfusion without and with PEMF stimulation revealed that the only perfusion induced a similar to 40-fold up-regulation of the expression of the osteogenic gene collagen type I with respect to the static control, while a similar to 80-fold up-regulation was measured when perfusion was combined with PEMF stimulation, indicating a positive synergic proosteogenic effect of combined physical stimulations

    Extreme and long-term drought in the La Plata Basin: event evolution and impact assessment until September 2022

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    The current drought conditions across the Parana-La Plata Basin (LPB) in Brazil-Argentina have been the worst since 1944. While this area is characterized by a rainy season with a peak from October to April, the hydrological year 2020-2021 was very deficient in rainfall, and the situation extended into the 2021-2022 hydrological year. Below-normal rainfall was dominant in south-eastern Brazil, northern Argentina, Paraguay, and Uruguay, suggesting a late onset and weaker South American Monsoon and the continuation of drier conditions since 2021. In fact, in 2021 Brazilian south and south-east regions faced their worst droughts in nine decades, raising the spectre of possible power rationing given the grid dependence on hydroelectric plants. The Paraná-La Plata Basin drought induced damages to agriculture and reduced crop production, including soybeans and maize, with effects on global crop markets. The drought situation continued in 2022 in the Pantanal region. Dry meteorological conditions are still present in the region at the end of September 2022 with below-average precipitation anomalies. Soil moisture anomaly and vegetation conditions are worst in the lower part of the La Plata Basin, in the southern regions. Conversely, upper and central part of the basin show partial and temporary recovery

    Can we model cultural ecosystem services, and are we measuring the right things?

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    Abstract: Cultural ecosystem services (CES), a key aspect of nature's contributions to people, remain a challenge to incorporate into decision making. One contributing factor is the difficulty of defining and describing these, due partly to: ongoing poor understanding of what drives people to interact with nature, a lack of appropriate data to quantify these interactions, and basic difficulties in measuring and modelling the complex array of social, psychological and behavioural attributes which help explain people's actions. In this study we present a framework which develops the concepts of cultural capital, social capital and human capital as specific forms of human‐centred capital, in the context of their contribution to understanding CES. Each form of capital encompasses separate attributes of beneficiaries. Testing the framework with data from a separate trans‐disciplinary study illustrated that the framework was readily applicable to specific situations. A measure of cultural capital, EcoCentrism, explained more variation than a suite of seven demographic variables. Applying the framework also showed that despite using a wide range of explanatory variables, a large proportion of observed variation remained unaccounted for. This suggests that more work is needed to understand and to develop metrics which can measure additional factors which underlie peoples’ motivations to engage with nature. The framework is applicable to other types of ecosystem service, and may also be useful for exploring relational values. A free Plain Language Summary can be found within the Supporting Information of this article

    Heterogenous response to aging of astrocytes in murine Substantia Nigra pars compacta and pars reticulata

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    Currently, little is known about the impact of aging on astrocytes in substantia nigra pars compacta (SNpc), where dopaminergic neurons degenerate both in physiological aging and in Parkinson's disease, an age-related neurodegenerative disorder. We performed a morphometric analysis of GFAP+ astrocytes in SNpc and, for comparison, in the pars reticulata (SNpr) of young (4–6 months), middle-aged (14–17 months) and old (20–24 months) C57BL/6J male mice. We demonstrated an age-dependent increase of structural complexity only in astrocytes localized in SNpc, and not in SNpr. Astrocytic structural remodelling was not accompanied by changes in GFAP expression, while GFAP increased in SNpr of old compared to young mice. In parallel, transcript levels of selected astrocyte-enriched genes were evaluated. With aging, decreased GLT1 expression occurred only in SNpc, while xCT transcript increased both in SNpc and SNpr, suggesting a potential loss of homeostatic control of extracellular glutamate only in the subregion where age-dependent neurodegeneration occurs. Altogether, our results support an heterogenous morphological and biomolecular response to aging of GFAP+ astrocytes in SNpc and SNpr
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