L'impianto, la gestione e la valorizzazione multifunzionale dei boschi periurbani

I boschi periurbani, come tutti gli spazi verdi prossimi agli agglomerati urbani, migliorano le condizioni ambientali e la qualit\ue0 dell'aria, contribuiscono alla conservazione della biodiversit\ue0, possono favorire l'aggregazione sociale. I boschi prossimi ai centri urbani rivestono inoltre un ruolo importante dal punto di vista paesaggistico e turistico e contribuiscono a contrastare i cambiamenti climatici. Questa pubblicazione, redatta con il supporto tecnico-scientifico dell'Accademia italiana di scienze forestali di Firenze, si propone di fornire linee guida per la progettazione, la realizzazione e la gestione dei boschi periurbani e delle fasce verdi nelle aree prossime agli agglomerati urbani ed agli insediamenti industriali

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

Impaired Heat Shock Response in Cells Expressing Full-Length Polyglutamine-Expanded Huntingtin

The molecular mechanisms by which polyglutamine (polyQ)-expanded huntingtin (Htt) causes neurodegeneration in Huntington's disease (HD) remain unclear. The malfunction of cellular proteostasis has been suggested as central in HD pathogenesis and also as a target of therapeutic interventions for the treatment of HD. We present results that offer a previously unexplored perspective regarding impaired proteostasis in HD. We find that, under non-stress conditions, the proteostatic capacity of cells expressing full length polyQ-expanded Htt is adequate. Yet, under stress conditions, the presence of polyQ-expanded Htt impairs the heat shock response, a key component of cellular proteostasis. This impaired heat shock response results in a reduced capacity to withstand the damage caused by cellular stress. We demonstrate that in cells expressing polyQ-expanded Htt the levels of heat shock transcription factor 1 (HSF1) are reduced, and, as a consequence, these cells have an impaired a heat shock response. Also, we found reduced HSF1 and HSP70 levels in the striata of HD knock-in mice when compared to wild-type mice. Our results suggests that full length, non-aggregated polyQ-expanded Htt blocks the effective induction of the heat shock response under stress conditions and may thus trigger the accumulation of cellular damage during the course of HD pathogenesis

Resveratrol Enhances Antitumor Activity of TRAIL in Prostate Cancer Xenografts through Activation of FOXO Transcription Factor

Resveratrol (3, 4', 5 tri-hydroxystilbene), a naturally occurring polyphenol, exhibits anti-inflammatory, antioxidant, cardioprotective and antitumor activities. We have recently shown that resveratrol can enhance the apoptosis-inducing potential of TRAIL in prostate cancer cells through multiple mechanisms in vitro. Therefore, the present study was designed to validate whether resveratrol can enhance the apoptosis-inducing potential of TRAIL in a xenograft model of prostate cancer.Resveratrol and TRAIL alone inhibited growth of PC-3 xenografts in nude mice by inhibiting tumor cell proliferation (PCNA and Ki67 staining) and inducing apoptosis (TUNEL staining). The combination of resveratrol and TRAIL was more effective in inhibiting tumor growth than single agent alone. In xenografted tumors, resveratrol upregulated the expressions of TRAIL-R1/DR4, TRAIL-R2/DR5, Bax and p27(/KIP1), and inhibited the expression of Bcl-2 and cyclin D1. Treatment of mice with resveratrol and TRAIL alone inhibited angiogenesis (as demonstrated by reduced number of blood vessels, and VEGF and VEGFR2 positive cells) and markers of metastasis (MMP-2 and MMP-9). The combination of resveratrol with TRAIL further inhibited number of blood vessels in tumors, and circulating endothelial growth factor receptor 2-positive endothelial cells than single agent alone. Furthermore, resveratrol inhibited the cytoplasmic phosphorylation of FKHRL1 resulting in its enhanced activation as demonstrated by increased DNA binding activity.These data suggest that resveratrol can enhance the apoptosis-inducing potential of TRAIL by activating FKHRL1 and its target genes. The ability of resveratrol to inhibit tumor growth, metastasis and angiogenesis, and enhance the therapeutic potential of TRAIL suggests that resveratrol alone or in combination with TRAIL can be used for the management of prostate cancer

A Chaperone Trap Contributes to the Onset of Cystic Fibrosis

Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine the success or failure of the folding reaction in the cell. We now address how the Phe508 deletion in the NBD1 domain of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for cystic fibrosis (CF) impacts the binding of CFTR with cellular chaperones. We applied single ion reaction monitoring mass spectrometry (SRM-MS) to quantitatively characterize the stoichiometry of the heat shock proteins (Hsps) in CFTR folding intermediates in vivo and mapped the sites of interaction of the NBD1 domain of CFTR with Hsp90 in vitro. Unlike folding of WT-CFTR, we now demonstrate the presence of ΔF508-CFTR in a stalled folding intermediate in stoichiometric association with the core Hsps 40, 70 and 90, referred to as a ‘chaperone trap’. Culturing cells at 30 C resulted in correction of ΔF508-CFTR trafficking and function, restoring the sub-stoichiometric association of core Hsps observed for WT-CFTR. These results support the interpretation that ΔF508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation. We propose that stalled folding intermediates could define a critical proteostasis pathway branch-point(s) responsible for the loss of function in misfolding diseases as observed in CF

Structure and dynamics of a beech forest in a fully protected area in the northern Apennines (Sasso Fratino, Italy)

Sasso Fratino Nature Reserve (National Park of Casentino Forests, northern Apennines) is a quite rare example of natural Apennine forest. The Reserve was established in 1959, aiming to protect a forest, although not a virgin one, low-intensively disturbed in the past by comparison with other neighbouring stands. Causes of such a low disturbance are the very limited accessibility of the area due to the very steep slopes characterising the site morphology, as well as historical features. The forest is a pure beech stand from 1250 m a.s.l. upwards, below this altitude is a mixed beech and silver fir forest. The study focuses on the understanding of the processes driving the evolution of the forest in the absence of human activities. To achieve this goal, 9 permanent, long-term research plots were established at different altitudes, in order to investigate on forest dynamics and regeneration processes. Simplified (single-layer) stand structures are more frequent where canopy gaps are absent. Two-layered structures are the result of the occurrence of canopy gaps, which allow the settlement, and subsequently the establishment, of a lower regeneration layer. Where the gap dimensions allow canopy closure, this kind of structure persists. When the gaps are quite large, the regeneration layer reaches the top layer and the structure stand tends, once more, toward a single-layer. Multilayered structures are extremely rare at plot level and become evident only at a wider scale. Our surveys indicate also a high variability of tree diameter distribution patterns in the forest stands. Such variability could be strictly related to the heterogeneity of site characteristics as well as to the effects of disturbance factors (both natural and anthropic). Concerning altitude, we observed an increase both of site index (dominant height) and species diversity in the regeneration layer, moving from higher (1500 m) to lower (900 m) altitudes. As a whole, our observations show that the dynamics of forest vegetation in the reserve is mostly affected by the interruption of tree canopy continuity. This implies substantial local variations of PAR in space and in time, which determine favourable ecological conditions for: (a) survival and growth of beech seedlings, or release of advanced beech regeneration; and (b) release of advanced silver fir regeneration (fir, more shade tolerant than beech, regenerates mainly in locations and conditions where the broadleaf saplings cannot survive for lack of light). The knowledge of the mechanisms of vegetation dynamics in the Reserve can be used to form the basis of close-to-nature silvicultural choices in similar stands in order to increase functionality and stability. Periodical monitoring of RNI will allow the investigation of the evolutionary trends of the forest stands