Inhibition of c-Myc Oncoprotein Limits the Growth of Human Melanoma Cells by Inducing Cellular Crisis

Abstract Here, we show that inhibition of c-Myc causes a proliferative arrest of M14 melanoma cells through cellular crisis, evident by the increase in size, multiple nuclei, vacuolated cytoplasm, induction of senescence-associated β-galactosidase activity and massive apoptosis. The c-Myc-induced crisis is associated with decreased human telomerase reverse transcriptase expression, telomerase activity, progressive telomere shortening, glutathione (GSH), depletion and, increased production of reactive oxygen species. Treatment of control cells with l-buthionine sulfoximine decreases GSH to levels of c-Myc low expressing cells, but it does not modify the growth kinetic of the cells. Surprisingly, when GSH is increased in the c-Myc low expressing cells by treatment with N-acetyl-l-cysteine, cells escape crisis. To test the hypothesis that both oxidative stress and telomerase dysfunction are involved in the c-Myc-dependent crisis, we directly inhibited telomerase function and glutathione levels. Inactivation of telomerase, by expression of a catalytically inactive, dominant negative form of reverse transcriptase, reduces cellular lifespan by inducing telomere shortening. Treatment of cells with l-buthionine sulfoximine decreases GSH content and accelerates cell crisis. Analysis of telomere status demonstrated that oxidative stress affects c-Myc-induced crisis by increasing telomere dysfunction. Our results demonstrate that inhibition of c-Myc oncoprotein induces cellular crisis through cooperation between telomerase dysfunction and oxidative stress

Saturated areas through the lens: 2. Spatio-temporal variability of streamflow generation and its relationship with surface saturation

Investigating the spatio-temporal variability of streamflow generation is fundamental to interpret the hydrological and biochemical functioning of catchments. In humid temperate environments, streamflow generation is often linked to the occurrence of near stream surface saturated areas, which mediate hydrological connectivity between hillslopes and streams. In this second contribution of a series of two papers, we used salt dilution gauging to investigate the spatio-temporal variability of streamflow in different subcatchments and for different reaches in the Weierbach catchment (0.42 km2) and explored the topographical controls on streamflow variability. Moreover, we mapped stream network expansion and contraction dynamics. Finally, we combined the information on the spatio-temporal variability of streamflow with the characterization of riparian surface saturation dynamics of seven different areas within the catchment (mapped with thermal infrared imagery, as presented in our first manuscript). We found heterogeneities in the streamflow contribution from different portions of the catchment. Although the size of the contributing area could explain differences in subcatchments' and reaches' net discharge, no clear topographic controls could be found when considering the area-normalized discharge. This suggests that some local conditions exert control on the variability of specific discharge (e.g., local bedrock characteristics and occurrence of perennial springs). Stream network dynamics were found not to be very responsive to changes in catchment's discharge (i.e., total active stream length vs. stream outlet discharge relationship could be described through a power law function with exponent = 0.0195). On the contrary, surface saturation dynamics were found to be in agreement with the level of streamflow contribution from the correspondent reach in some of the investigated riparian areas. This study represents an example of how the combination of different techniques can be used to characterize the internal heterogeneity of the catchment and thus improve our understanding of how hydrological connectivity is established and streamflow is generated.</p

Saturated areas through the lens: 1. Spatio-temporal variability of surface saturation documented through thermal infrared imagery

Surface saturated areas are key features in generating run-off. A detailed characterization of the expansion and contraction of surface saturation in riparian zones and its connectivity to the stream is fundamental to improve our understanding of the spatial and temporal variability of streamflow generation processes. In this first contribution of a series of two papers, we used ground-based thermal infrared imagery for characterizing riparian surface saturation seasonal dynamics of seven different riparian areas in the Weierbach catchment (0.42 km2), a small forested catchment in Luxembourg. We collected biweekly panoramic images of the seven areas over a period of 2 years. We identified the extension of saturation in each collected panoramic image (i.e., percentage of pixels corresponding to saturated surfaces in each riparian area) to generate time series of surface saturation. Riparian surface saturation in all areas was seasonally variable, and its dynamics were in accordance with lower hillslope groundwater level fluctuations. Surface saturation in the different areas related to catchment outlet discharge through power law relationships. Differences in these relationships for different areas could be associated with the location of the areas along the stream network and to a possible influence of local riparian morphology on the development of surface saturation, suggesting a certain degree of intracatchment heterogeneity. This study paves the way for a subsequent investigation of the spatio-temporal variability of streamflow generation in the catchment, presented in our second contribution.</p

Simulations of distributed systems in a computing centre

Modern computing centres addressed to High Energy Physics user communities have to deal with rapidly hard- ware and software systems evolution. These centres normally face a variety of problems associated with the dimensioning and configuration of several services which must satisfy per- formance targets under different usage patterns. Therefore, the identification of key variables and the estimation of their impact on services performances is challenging. For example, given an hardware-software configuration for a considered service, how will service performance vary in relation to user dependent settings? Will it be able to support a certain number of requests per minute over the common parameter ranges? In addition, it is difficult to generalize the impact of same settings over different usage scenarios. Therefore, the design of a mathematical model able to relate services performance to key variables in the user computing patterns under common hardware-software settings can help to optimize the exploitation of computing resources. In the present work, starting from the analysis of a typical job of ATLAS as representative HEP user communities, we focus on how local data movement operations use hardware- software resources of INFN-CNAF computing centre and which variables affect data movement performances. As a result of this framework analysis we identify GridFTP protocol and GPFS data storage as core services whose performance to study in depen- dancy of typical user defined variables. We therefore decompose data movement commands in operations of increasing complexity i.e., cp, globus-url-copy with and without network, and after defining the mean throughput per file per unit size as target metric, we conduct a quantitative analysis of the contribution and relevance of considered variables across explored usage scenarios. Finally, we conduct a qualitative fit analysis of the behaviour of chosen throughput metric as a function of relevant user dependent variables. For each scenario and for each variables a best fit model function is selected according to R-square goodness of fit index

Habilidad competitiva del cultivo de girasol frente a las malezas.

Las malezas son perjudiciales para la producción de granos por la competencia que ejercen por recursos como agua, luz y nutrientes, así como también por las interferencias que causan en la cosecha.Fil: Carpaneto, Bárbara Bettina. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.Fil: Carpaneto, Bárbara Bettina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Panaggio, Néstor Hernán. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.Fil: Panaggio, Néstor Hernán. Universidad Nacional de Mar del Plata. Facultad de Ciencias Agrarias; Argentina.Fil: Giuliano, Silvio Fabián. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina.Fil: Antonelli, Carlos Alberto. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentina

Defence strategies and antibiotic resistance gene abundance in enterococci under stress by exposure to low doses of peracetic acid

partially_open12noPeracetic acid (PAA) is an organic compound used efficiently as disinfectant in wastewater treatments. Yet, at low doses it may cause selection; thus, the effect of low doses of PAA on Enterococcus faecium as a proxy of human-related microbial waste was evaluated. Bacteria were treated with increasing doses of PAA (from 0 to 25 mg L1 min) and incubated in regrowth experiments under non-growing, limiting conditions and under growing, favorable conditions. The changes in bacterial abundance, in bacterial phenotype (number and composition of small cell clusters), and in the abundance of an antibiotic resistance gene (ARG) was evaluated. The experiment demonstrated that the selected doses of PAA efficiently removed enterococci, and induced a long-lasting effect after PAA inactivation. The relative abundance of small clusters increased during the experiment when compared with that of the inoculum. Moreover, under growing favorable conditions the relative abundance of small clusters decreased and the number of cells per cluster increased with increasing PAA doses. A strong stability of the measured ARG was found, not showing any effect during the whole experiment. The results demonstrated the feasibility of low doses of PAA to inactivate bacteria. However, the stress induced by PAA disinfection promoted a bacterial adaptation, even if potentially without affecting the abundance of the ARG.openTurolla, Andrea; Sabatino, Raffaella; Fontaneto, Diego; Eckert, Ester M.; Colinas, Noemi; Corno, Gianluca; Citterio, Barbara; Biavasco, Francesca; Antonelli, Manuela; Mauro, Alessandro; Mangiaterra, Gianmarco; Di Cesare, AndreaTurolla, Andrea; Sabatino, Raffaella; Fontaneto, Diego; Eckert, Ester M.; Colinas, Noemi; Corno, Gianluca; Citterio, Barbara; Biavasco, Francesca; Antonelli, Manuela; Mauro, Alessandro; Mangiaterra, Gianmarco; Di Cesare, Andre

Final results of the second prospective AIEOP protocol for pediatric intracranial ependymoma

BACKGROUND: This prospective study stratified patients by surgical resection (complete = NED vs incomplete = ED) and centrally reviewed histology (World Health Organization [WHO] grade II vs III). METHODS: WHO grade II/NED patients received focal radiotherapy (RT) up to 59.4 Gy with 1.8 Gy/day. Grade III/NED received 4 courses of VEC (vincristine, etoposide, cyclophosphamide) after RT. ED patients received 1-4 VEC courses, second-look surgery, and 59.4 Gy followed by an 8-Gy boost in 2 fractions on still measurable residue. NED children aged 1-3 years with grade II tumors could receive 6 VEC courses alone. RESULTS: From January 2002 to December 2014, one hundred sixty consecutive children entered the protocol (median age, 4.9 y; males, 100). Follow-up was a median of 67 months. An infratentorial origin was identified in 110 cases. After surgery, 110 patients were NED, and 84 had grade III disease. Multiple resections were performed in 46/160 children (28.8%). A boost was given to 24/40 ED patients achieving progression-free survival (PFS) and overall survival (OS) rates of 58.1% and 68.7%, respectively, in this poor prognosis subgroup. For the whole series, 5-year PFS and OS rates were 65.4% and 81.1%, with no toxic deaths. On multivariable analysis, NED status and grade II were favorable for OS, and for PFS grade II remained favorable. CONCLUSIONS: In a multicenter collaboration, this trial accrued the highest number of patients published so far, and results are comparable to the best single-institution series. The RT boost, when feasible, seemed effective in improving prognosis. Even after multiple procedures, complete resection confirmed its prognostic strength, along with tumor grade. Biological parameters emerging in this series will be the object of future correlatives and reports

Case report: lenvatinib in neoadjuvant setting in a patient affected by invasive poorly differentiated thyroid carcinoma

We report a case of an elderly woman presenting with a huge cervical mass invading the tracheal lumen. Diagnosed as invasive poorly differentiated thyroid cancer, after an endotracheal biopsy, stenting and radiotherapy, it was judged eligible for total thyroidectomy, but surgery was delayed due to pulmonary thromboembolism. The patient was therefore treated with lenvatinib with a neoadjuvant intent until hemodynamic stability was obtained. Thyroidectomy and radioiodine therapy were then performed and the postdose scan revealed an area of modest uptake in the anterior part of the neck. The patient is now in a good clinical status and she continues her follow-up program without any adjuvant therapy

Evidence of historical seismicity and volcanism in the Armenian Highland (from Armenian and other sources)

This work presents a summary on the development of studies of historical earthquakes in Armenia and adjacent parts of Turkey and Iran. Since ancient times, this region has been an arena where active geodynamic and seismic history intermingled with no less active and dynamic evolution of human cultures and societies. A long-term historical record in this region beginning as early as the 8th century B.C. provides abundant evidence that can make an inestimable contribution to studies of historical seismicity and volcanism in the area. We discuss the main research methodology and sources used, and dwell on the principal catalogues of historical earthquakes compiled to date