The October 2000 flooding in Valle d'Aosta (Italy): Event description and land planning measures for the risk mitigation

On October 13-16th, 2000 heavy rainfalls in the Northwestern Italian Alps caused huge flooding and landslides with significant damages to houses and infrastructures and several life losses. In this paper a description of the main events that affected Valle d’Aosta’s region and the subsequent land planning measures adopted for the risk mitigation are presented. After a first meteorological and hydrological framing, based on the data of the regional monitoring system (that pointed out rainfalls up to 236 mm in 24 h also in high‐altitude zones, because of the rise of the isotherm 0°C around 3000 m above sea level), the main effects of the event (extensive flooding, landslides, soil slips and debris flows) in the regional catchment of the Dora Baltea river are described. Through aerial and direct surveys those effects have been transferred into a thematic cartography within two months from the event, in order to have detailed elements for the technical, administrative and political land planning decisions, and, on this basis, a new regional directive containing detailed measures for the hydro‐geological risk mitigation and land safety has been adopted. © 2003 by Taylor nad Francis Group, LLC

Habitat Preferences of Italian Freshwater Fish: A Systematic Review of Data Availability for Applications of the MesoHABSIM Model

The MesoHABitat SImulation Model (MesoHABSIM) is the preferred method to calculate spatio-temporal variation in the fish habitat availability in Italian rivers. With the aim of improving the applicability of the MesoHABSIM approach in the Italian territory, we carried out a systematic review of physical habitat preferences for 31 freshwater fish species and three freshwater lampreys, representing 75% of the total indigenous freshwater fish community of Italy. Information related to suitable ranges of depth, flow velocity, biotic/abiotic substrates, covers/shelters was collected and summarized for two critical life stages (adult and juvenile) and two bioperiods (rearing/growth and spawning). Overall, 250 publications were reviewed, classified as 206 peer-reviewed papers, 20 books, 7 PhD thesis, and 17 grey literature sources. Our analysis revealed substantial deficits of information about habitat requirements for more than 30% of Italian freshwater fish species. This information is particularly scarce for the most threatened endemic species, especially for their most critical bioperiod (i.e., spawning). With the aim of preserving freshwater fish biodiversity as required in the EU Biodiversity Strategy for 2030 (European Commission, 2020), accurate information on physical habitat requirements for spawning is crucial. As an example application of MesoHABSIM, the collected habitat preference information was used to define and apply mesohabitat suitability criteria for one fish species (Telestes muticellus) in a regulated river reach of Argentina Creek (Province of Imperia, Italy). This analysis demonstrates the potential for applying information from the current review to other fish species

p190 Rho-GTPase activating protein associates with plexins and it is required for semaphorin signalling

Plexins are transmembrane receptors for semaphorins, guiding cell migration and axon extension. Plexin activation leads to the disassembly of integrin-based focal adhesive structures and to actin cytoskeleton remodelling and inhibition of cell migration; however, the underlying molecular mechanisms are unclear. We consistently observe a transient decrease of cellular RhoA-GTP levels upon plexin activation in adherent cells. One of the main effectors of RhoA downregulation is p190, a ubiquitously expressed GTPase activating protein (GAP). We show that, in p190-deficient fibroblasts, the typical functional activities mediated by plexins (such as cell collapse and inhibition of integrin-based adhesion) are blocked or greatly impaired. Notably, the functional response can be rescued in these cells by re-expressing exogenous p190, but not a mutant form specifically lacking RhoGAP activity. We furthermore demonstrate that semaphorin function is blocked in epithelial cells, primary endothelial cells and neuroblasts upon treatment with small interfering RNAs that knockdown p190 expression. Finally, we show that p190 transiently associates with plexins, and its RhoGAP activity is increased in response to semaphorin stimulation. We conclude that p190-RhoGAP is crucially involved in semaphorin signalling to the actin cytoskeleton, via interaction with plexins

Thromopoietin signaling to chromatin elicits rapid and pervasive epigenome remodeling within poised chromatin architectures.

Thrombopoietin (TPO) is a critical cytokine regulating hematopoietic stem cell maintenance and differentiation into the megakaryocytic lineage. However, the transcriptional and chromatin dynamics elicited by TPO signaling are poorly understood. Here, we study the immediate early transcriptional and cis-regulatory responses to TPO in hematopoietic stem/progenitor cells (HSPCs) and use this paradigm of cytokine signaling to chromatin to dissect the relation between cis- regulatory activity and chromatin architecture. We show that TPO profoundly alters the transcriptome of HSPCs, with key hematopoietic regulators being transcriptionally repressed within 30 minutes of TPO. By examining cis-regulatory dynamics and chromatin architectures, we demonstrate that these changes are accompanied by rapid and extensive epigenome remodeling of cis-regulatory landscapes that is spatially coordinated within topologically associating domains (TADs). Moreover, TPO-responsive enhancers are spatially clustered and engage in preferential homotypic intra- and inter-TAD interactions that are largely refractory to TPO signaling. By further examining the link between cis-regulatory dynamics and chromatin looping, we show that rapid modulation of cis-regulatory activity is largely independent of chromatin looping dynamics. Finally, we show that, although activated and repressed cis-regulatory elements share remarkably similar DNA sequence compositions, transcription factor binding patterns accurately predict rapid cis-regulatory responses to TPO

Tumor cell-derived Timp-1 is necessary for maintaining metastasis-promoting Met-signaling via inhibition of Adam-10.

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The long-lasting protective effect of HGF in cardiomyoblasts exposed to doxorubicin requires a positive feed-forward loop mediated by ERK1,2-TIMP1-STAT3

Previous studies showed that the hepatocyte growth factor (HGF)–Met receptor axis plays long-lasting cardioprotection against doxorubicin anti-cancer therapy. Here, we explored the mechanism(s) underlying the HGF protective effect. DNA damage was monitored by histone H2AX phosphorylation and apoptosis by proteolytic cleavage of caspase 3. In doxorubicin-treated H9c2 cardiomyoblasts, the long-lasting cardioprotection is mediated by activation of the Ras/Raf/Mek/Erk (extracellular signal-regulated kinase 1,2) signaling pathway and requires Stat3 (signal transducer and activator of transcription 3) activation. The HGF protection was abrogated by the Erk1,2 inhibitor, PD98059. This translated into reduced Y705 phosphorylation and impaired nuclear translocation of Stat3, showing crosstalk between Erk1,2 and Stat3 signaling. An array of 29 cytokines, known to activate Stat3, was interrogated to identify the molecule(s) linking the two pathways. The analysis showed a selective increase in expression of the tissue inhibitor of metalloproteinases-1 (Timp1). Consistently, inhibition in cardiomyoblasts of Timp1 translation by siRNAs blunted both Stat3 activation and the cardioprotective effect of HGF. Thus, Timp1 is responsible for the generation of a feed-forward loop of Stat3 activation and helps cardiomyocytes to survive during the genotoxic stress induced by anthracyclines

met overexpression turns human primary osteoblasts into osteosarcomas

The MET oncogene was causally involved in the pathogenesis of a rare tumor, i.e., the papillary renal cell carcinoma, in which activating mutations, either germline or somatic, were identified. MET activating mutations are rarely found in other human tumors, whereas at higher frequencies, MET is amplified and/or overexpressed in sporadic tumors of specific histotypes, including osteosarcoma. In this work, we provide experimental evidence that overexpression of the MET oncogene causes and sustains the full-blown transformation of osteoblasts. Overexpression of MET , obtained by lentiviral vector–mediated gene transfer, resulted in the conversion of primary human osteoblasts into osteosarcoma cells, displaying the transformed phenotype in vitro and the distinguishing features of human osteosarcomas in vivo . These included atypical nuclei, aberrant mitoses, production of alkaline phosphatase, secretion of osteoid extracellular matrix, and striking neovascularization. Although with a lower tumorigenicity, this phenotype was superimposable to that observed after transfer of the MET gene activated by mutation. Both transformation and tumorigenesis were fully abrogated when MET expression was quenched by short-hairpin RNA or when signaling was impaired by a dominant-negative MET receptor. These data show that MET overexpression is oncogenic and that it is essential for the maintenance of the cancer phenotype. (Cancer Res 2006; 66(9): 4750-7

Plexin A Is a Neuronal Semaphorin Receptor that Controls Axon Guidance

AbstractThe Semaphorins comprise a large family of secreted and transmembrane proteins, some of which function as repellents during axon guidance. Semaphorins fall into seven subclasses. Neuropilins are neuronal receptors for class III Semaphorins. In the immune system, VESPR, a member of the Plexin family, is a receptor for a viral-encoded Semaphorin. Here, we identify two Drosophila Plexins, both of which are expressed in the developing nervous system. We present evidence that Plexin A is a neuronal receptor for class I Semaphorins (Sema 1a and Sema 1b) and show that Plexin A controls motor and CNS axon guidance. Plexins, which themselves contain complete Semaphorin domains, may be both the ancestors of classical Semaphorins and binding partners for Semaphorins