Drug resistance in Medulloblastoma is driven by YB-1, ABCB1 and a seven-gene drug signature

Therapy resistance represents an unmet challenge in the treatment of medulloblastoma. Accordingly, the identification of targets that mark drug-resistant cell populations, or drive the proliferation of resistant cells, may improve treatment strategies. To address this, we undertook a targeted approach focused on the multi-functional transcription factor YB-1. Genetic knockdown of YB-1 in Group 3 medulloblastoma cell lines diminished cell invasion in 3D in vitro assays and increased sensitivity to standard-of-care chemotherapeutic vincristine and anti-cancer agents panobinostat and JQ1. For vincristine, this occurred in part by YB-1-mediated transcriptional regulation of multi-drug resistance gene ABCB1, as determined by chromatin immunoprecipitation. Whole transcriptome sequencing of YB-1 knockdown cells identified a role for YB-1 in the regulation of tumourigenic processes, including lipid metabolism, cell death and survival and MYC and mTOR pathways. Stable cisplatin- and vincristine-tolerant Group 3 and SHH cell lines were generated to identify additional mechanisms driving resistance to standard-of-care medulloblastoma therapy. Next-generation sequencing revealed a vastly different transcriptomic landscape following chronic drug exposure, including a drug-tolerant seven-gene expression signature, common to all sequenced drug-tolerant cell lines, representing therapeutically targetable genes implicated in the acquisition of drug tolerance. Our findings provide significant insight into mechanisms and genes underlying therapy resistance in medulloblastoma

Climate impact on Italian fisheries (Mediterranean Sea)

Global warming is increasingly affecting marine ecosystems and ecological services they provide. One of the major consequences is a shift in species geographical distribution, which may affect resources availability to fisheries. We computed the mean temperature of the catch (MTC) for Italian catches from 1972 to 2012 to test if an increase of warmer-water species against colder-water ones was observed. We further analysed the relationship among MTC, landings, fishing effort and climatic factors through a Linear Mixed Models approach. Global MTC increased at a rate of 0.12 _C per decade. Though, by considering the influence of sea surface temperature (SST), a strongest increase (0.31 _C) was estimated in southernmost areas, while in the northernmost basin (Northern Adriatic Sea) a decrease of 0.14 _C was observed. SST resulted the most relevant driver, and the relationship between MTC and SST showed a high spatial variability both in terms of strength and sign, being positively stronger in southernmost areas while negative in the northernmost basin. The result is probably underestimated since several psychrophilous and thermophilous species were not included in the analysis. However, it seems that a change towards warmer-water species has already occurred in Italian marine ecosystems. Conversely, total landings temporal dynamics seem mostly driven by changes in fishing effort rather than by MTC and climatic factors. Consequently, fishery management strategies need to focalize primarily on fishing effort reduction, in order to reduce the pressure on the stocks while increasing their resilience to other stressors, among which global warmingGlobal warming is increasingly affecting marine ecosystems and ecological services they provide. One of the major consequences is a shift in species geographical distribution, which may affect resources availability to fisheries. We computed the mean temperature of the catch (MTC) for Italian catches from 1972 to 2012 to test if an increase of warmer-water species against colder-water ones was observed. We further analysed the relationship among MTC, landings, fishing effort and climatic factors through a Linear Mixed Models approach. Global MTC increased at a rate of 0.12 A degrees C per decade. Though, by considering the influence of sea surface temperature (SST), a strongest increase (0.31 A degrees C) was estimated in southernmost areas, while in the northernmost basin (Northern Adriatic Sea) a decrease of 0.14 A degrees C was observed. SST resulted the most relevant driver, and the relationship between MTC and SST showed a high spatial variability both in terms of strength and sign, being positively stronger in southernmost areas while negative in the northernmost basin. The result is probably underestimated since several psychrophilous and thermophilous species were not included in the analysis. However, it seems that a change towards warmer-water species has already occurred in Italian marine ecosystems. Conversely, total landings temporal dynamics seem mostly driven by changes in fishing effort rather than by MTC and climatic factors. Consequently, fishery management strategies need to focalize primarily on fishing effort reduction, in order to reduce the pressure on the stocks while increasing their resilience to other stressors, among which global warming

The geochemistry of outcropping rocks as the starting point for the knowledge of a territory (the Valchiavenna area)

Knowledge of rock chemical composition is very important for the evaluation of soil chemistry, particularly as for the trace element content of residual soil corresponds to the characteristics of the parental rock. These elemental concentrations are known as "background values" and their contents can vary by some orders of magnitude in relation to rock chemistry composition. The evaluation of the most recent literature has allowed us to look at the geochemistry of rocks regarding those trace elements which are particularly significant from the environmental point of view, as Cr, V, Ni, Zn , Pb. The distribution of these elements in some zones of the Valchiavenna area clearly shows the relationship with the different rock types. In particular, the ophiolitic complex of Chiavenna, characterised by mafic and ultramafic rocks, shows high values of Cr (>900 ppm) and Ni (>600). On the contrary, in the Truzzo granitic complex and Roffna rhyolites, the main metals are Zn and Pb. Moreover, the comparison between the abundance sequences of the above mentioned elements clearly highlights that : 1) the various rock types have different amounts of trace elements; 2) the sequence of abundance is different as regards rock chemistry; 3) the absolute value of all trace element sums is very different in the various rock types (e.i.>2000 ppm in ophiolites and < 200 ppm in granites). During the development of "Progetto Valchiavenna" performed by Dipartimento di Scienze della Terra "A.Desio", some new samplings of the outcropping rock types were made and the geochemical analyses of major and trace elements have increased the chemical knowledge of all the main rock types in the Valchiavenna area. Some maps of trace element distribution are presented, which are useful in making provision for the elemental amounts in soils. A brief illustration of a case study regarding a restrict zone of the neighbourhood of Chiavenna was reported as an example of the integration of chemical knowledge on rocks, soils and vegetation. The high Mg content of ophiolite outcrops (average 16 wt% MgO, with some values reaching up to 38 wt%) correspond to as many Cr and Ni concentrations ( up to 2000 ppm). Chromium and nickel determined in some soil sections sampled near Chiavenna, Prosto di Piuro and Uschione have shown contents between 450 e 1600 ppm and 400 and 1800 ppm, respectively. These values exceed the mean contents for soils assigned for different uses. The presence of high levels of metals in soils exerts a pressure on plant species leading to the selection of a specific flora; in particular, the ultramafic sites have an unusual flora related to the effects of Mg and Ni toxicities. On the soils of the Chiavenna area, endemic plant species and Ni-hyperaccumulators (e.i. Alyssum) have not been found. Nevertheless, some species like Hypericum perforatum , Brachypodium pinnatum , Vincetoxicum hirundinaria and Silene vulgaris typical of ofiolithic outcrops are present. Moreover, the metal content determined in some species shows higher values in roots than in aboveground part. This is a strategy that the plant displays to defend itself from the effects of element toxicities

La geologia e il paesaggio sulla e nell'etichetta. il progetto di Lucilia Gregori.

The wines, as well as other cultural expressions, they can become a tool to promote sustainable development in Italy, as well as a culture of responsible consumption. Socio-economic development of a country is closely linked to the geomorphological assect of the itself: even if at different scales, the endogenous and exogenous processes, and rocks, such as landscape elements, influence the development of the environment and form the basis spatio-temporal development of a region. By integrating a variety of information on the geology and land use, it is possible to study the link between landscapes and wine areas

Path-based methods for the determination of nondispersive drainage directions in grid-based digital elevation models

Path-based methods for the determination of nondispersive drainage directions ingrid-based digital elevation models are presented. These methods extend the descriptivecapabilities of the classical D8 method by cumulating the deviations between selected andtheoretical drainage directions along the drainage paths. It is shown that either angular ortransversal deviations can be employed. Accordingly, two classes of methods designatedD8-LAD (eight drainage directions, least angular deviation) and D8-LTD (eight drainagedirections, least transversal deviation) are developed. Detailed tests on four syntheticdrainage systems of known geometry and on the Liro catchment (central Italian Alps)indicate that the proposed methods provide significant improvement over the D8 methodfor the determination of drainage directions and drainage areas