Revisiting G3BP1 as a RasGAP binding protein: sensitization of tumor cells to chemotherapy by the RasGAP 317-326 sequence does not involve G3BP1.

RasGAP is a multifunctional protein that controls Ras activity and that is found in chromosomal passenger complexes. It also negatively or positively regulates apoptosis depending on the extent of its cleavage by caspase-3. RasGAP has been reported to bind to G3BP1 (RasGAP SH3-domain-binding protein 1), a protein regulating mRNA stability and stress granule formation. The region of RasGAP (amino acids 317-326) thought to bind to G3BP1 corresponds exactly to the sequence within fragment N2, a caspase-3-generated fragment of RasGAP, that mediates sensitization of tumor cells to genotoxins. While assessing the contribution of G3BP1 in the anti-cancer function of a cell-permeable peptide containing the 317-326 sequence of RasGAP (TAT-RasGAP₃₁₇₋₃₂₆), we found that, in conditions where G3BP1 and RasGAP bind to known partners, no interaction between G3BP1 and RasGAP could be detected. TAT-RasGAP₃₁₇₋₃₂₆ did not modulate binding of G3BP1 to USP10, stress granule formation or c-myc mRNA levels. Finally, TAT-RasGAP₃₁₇₋₃₂₆ was able to sensitize G3BP1 knock-out cells to cisplatin-induced apoptosis. Collectively these results indicate that G3BP1 and its putative RasGAP binding region have no functional influence on each other. Importantly, our data provide arguments against G3BP1 being a genuine RasGAP-binding partner. Hence, G3BP1-mediated signaling may not involve RasGAP

Combined acl and segond repair in combined acute proximal acl tears and segond fracture

A renewed interest in anterior cruciate ligament preservation has been noted using arthroscopic primary repair in patients with proximal tears, but the main concern remained the control of the rotational instability. Segond fracture occurs in less than 10% of cases of acute anterolateral instability, but it can result in continued rotation instability. The aim of this study is to describe the surgical technique to acutely repair both the anterior cruciate ligament and Segond fracture in the acute setting

The Impact of Treated Urban Wastewaters and Flood Discharge on the Quality of Bathing Water

What do we know about the Adriatic Sea and the state of its health [...

Non-invasive computer navigation can quantify the pivot shift maneuver with good to excellent reliability in healthy volunteers

Purpose: The aim of this study was to determine the inter- and intra-observer reliability of knee laxity assessment using a non-invasive navigation system in a population of healthy young athletes. It was hypothesized that knee laxity parameters recorded using non-invasive computer navigation would demonstrate good inter- and intra- observer reliability. Methods: Healthy volunteers aged between 18 to 30 years were recruited to the study. Static and dynamic knee laxity parameters including anterior tibial translation and tibial rotation during the pivot shift test were recorded on awake patients using non-invasive computer navigation by two independent observers: at the first visit each athlete was evaluated by the consultant and resident surgeons independently; 6 weeks after the first visit all the participants were re-tested only by the resident surgeon. Inter- and intra-observer reliability was calculated and then interpreted according to Cicchetti’s criteria. Results: One hundred healthy volunteers were recruited to the study, of these 38 were women (38%), and the average age was 25.5 ± 2.4 years. According to Cicchetti’s criteria the intra- and inter-observer reliability for static measurements were fair for anterior tibial translation (0.572 and 0.529, respectively) and excellent for total passive tibial rotation (0.859 and 0.883, respectively). For the dynamic measurements of translation and rotation during the pivot shift maneuver both measurements demonstrated good to excellent reliability with intra and inter observer reliability ranging from 0.684 to 0.936. Conclusion: Non-invasive navigation for the assessment of knee laxity is associated with fair to excellent inter- and intra-observer reliability in a population of healthy volunteers

2D continuous spectrum of shear Alfven waves in the presence of a magnetic island

The radial structure of the continuous spectrum of shear Alfven modes is calculated in the presence of a magnetic island in tokamak plasmas. Modes with the same helicity of the magnetic island are considered in a slab model approximation. In this framework, with an appropriate rotation of the coordinates the problem reduces to 2 dimensions. Geometrical effects due to the shape of the flux surface's cross section are retained to all orders. On the other hand, we keep only curvature effects responsible of the beta induced gap in the low-frequency part of the continuous spectrum. New continuum accumulation points are found at the O-point of the magnetic island. The beta-induced Alfven Eigenmodes (BAE) continuum accumulation point is found to be positioned at the separatrix flux surface. The most remarkable result is the nonlinear modification of the BAE continuum accumulation point frequency

The Interreg Project AdSWiM: Managed Use of Treated Wastewater for the Quality of the Adriatic Sea

The Italy-Croatia Cross Border Cooperation (CBC) Programme is the financial instrument supporting the cooperation between the two European Member States overlooking the Adriatic Sea. The first call for proposals was launched in 2017, identifying four priority axes of intervention. Subsequently, in 2019, the kick-off of the AdSWiM project “Managed use of treated urban wastewater for the quality of the Adriatic Sea” took place in Udine (IT). Adriatic marine waters are generally classified as good to excellent based on the Bathing Water Directive (2006/7/EC). Nevertheless, issues of low productivity or the lack of nutrients have been often suggested, especially on the Italian side. The project addresses the question of whether wastewater treatment plants (WWTPs) discharging to the sea, after applying appropriate pollution control and management technologies, can modulate the nutrient content of their effluents to support localized depleted areas. This idea is borrowed from one of the motivations that support the reuse of treated wastewater for irrigation, thus leading to the return of nutrients (nitrogen, phosphorus, potassium, etc.) to natural biogeochemical cycles. However, the hypothesis of modulating the nutrient composition of wastewater opens up to several critical aspects, including legislative and technological ones. Being aware of the delicate environmental implications, we have undertaken the project involving WWTPs, research centers, municipalities, and legal experts with the aim of investigating in detail the problems related to wastewater reuse, especially with regard to the content of nutrients. Our experimental approach aimed to evaluate appropriate and possibly new treatment technologies to reduce the microbial load and to implement chemical and microbiological tests on the treated wastewater. Results have shown that it can be tricky to draw decisive conclusions because (i) the wastewater management systems differ between the two sides of the Adriatic sea due to the different levels of technological development of WWTPs; (ii) the Italian and Croatian coasts deeply differ in geographic characteristics (i.e., topography, orography, current circuits, presence of rivers) and anthropogenic pressure (i.e., exploitation levels, population density); (iii) the new treatment technologies to lower bacterial contamination need further efforts to raise their technological level of readiness (TRL) and make them implementable in the existing WWTPs. However, in terms of chemical control methodologies, the proposed sensors and biosensors gave positive results, managing to decrease the detection limits for the measured parameters, and the tested technologies for microbiological monitoring were also effective. In particular, the latter was carried out by using recent molecular biology techniques, capable of resolving the microbiota in treated wastewater, which emerged to be strictly related to the features of the WWTPs

An integrated study of the chemical composition of Antarctic aerosol to investigate natural and anthropogenic sources

During the 2010-11 austral summer, an aerosol sampling campaign was carried out at a coastal Antarctic site (Terra Nova Bay, Victoria Land). In this work, previously published data about water-soluble organic compounds and major and trace elements were merged with novel measurements of major ions, carboxylic acids and persistent organic pollutants (polychlorobiphenyls, polycyclic aromatic hydrocarbons, polychlorinated naphthalenes, polybrominated diphenylethers and organochlorine pesticides) in order to provide a chemical characterisation of Antarctic aerosol and to investigate its sources. The persistent organic pollutants were determined using a high-volume sampler, able to collect both particulate and gaseous fractions, whereas remaining compounds were determined by performing an aerosol size fractionation with a PM10 cascade impactor. Ionic species represented 58% (350 ng m(-3)) of the sum of concentrations of all detected compounds (596 ng m(-3)) in our Antarctic PM10 aerosol samples due to natural emission. Trace concentrations of persistent organic pollutants highlighted that the occurrence of these species can be due to long-range atmospheric transport or due to the research base. Factor analysis was applied to the dataset obtained from the samples collected with the PM10 sampler in order to make a distinction between anthropogenic, crustal and biogenic sources using specific chemical markers

Dynamical correlations and collective excitations of Yukawa liquids

In dusty (complex) plasmas, containing mesoscopic charged grains, the grain-grain interaction in many cases can be well described through a Yukawa potential. In this Review we summarize the basics of the computational and theoretical approaches capable of describing many-particle Yukawa systems in the liquid and solid phases and discuss the properties of the dynamical density and current correlation spectra of three- and two-dimensional strongly coupled Yukawa systems, generated by molecular dynamics simulations. We show details of the $\omega(k)$ dispersion relations for the collective excitations in these systems, as obtained theoretically following the quasilocalized charge approximation, as well as from the fluctuation spectra created by simulations. The theoretical and simulation results are also compared with those obtained in complex plasma experiments.Comment: 54 pages, 31 figure

In-situ trace metal (Cd, Pb, Cu) speciation along the Po River plume (Northern Adriatic Sea) using submersible systems

Highlights • In-situ trace metal speciation in the Adriatic Sea by submersible voltammetric sensors • Metal species distribution mainly affected by Po River outflow. • Metal dynamic concentrations below legal limits • Cu dynamic concentrations toxic to sensitive phytoplankton Abstract Information on the distribution and speciation of trace metals is of critical importance for our ability to interpret the links between the bioavailability and uptake of an element, and its biogeochemical cycle in coastal environments. Within the framework of the European Project “In-situ automated Monitoring of Trace metal speciation in Estuaries and Coastal zones in relation with the biogeochemical processes (IMTEC)”, the chemical speciation of Cd, Pb and Cu was carried out along the Po River plume in the period 27 October – 2 November 2002. During the cruise, five Voltammetric In-situ Profiling systems and one Multi Physical Chemical Profiler, as well as conventional voltammetric instruments, were successfully applied in order to evaluate the distribution of Cd, Pb and Cu between different fractions (free ion, dynamic, colloidal, dissolved and particulate fractions) and to assess the evolution of these fractions during estuarine mixing and in the water column. Dynamic concentrations were 0.05–0.2 nmol L−1 Cd, 0.02–0.2 nmol L−1 Pb, and 0.15–4.0 nmol L−1Cu. Cd was mainly present as dynamic fraction (40–100% of the dissolved Cd). High proportions of Pb (~70%) and Cu (~80%) were present as colloids probably of biogenic origin. Principal components analysis reveals a strong influence of the Po River discharge on the spatial and vertical distributions of metal species. Almost all the metal fractions globally decreased following the salinity gradient. Metal concentrations are far below (at least one order of magnitude lower) the Environmental Quality Standard established by the Italian law. However, the Cu dynamic fraction showed concentrations likely to be toxic to sensitive phytoplankton community and to have negative effects on larva development of coastal macroinvertebrate species (toxicity data extracted from literature)

Energy Metabolism in H460 Lung Cancer Cells: Effects of Histone Deacetylase Inhibitors

BACKGROUND: Tumor cells are characterized by accelerated growth usually accompanied by up-regulated pathways that ultimately increase the rate of ATP production. These cells can suffer metabolic reprogramming, resulting in distinct bioenergetic phenotypes, generally enhancing glycolysis channeled to lactate production. In the present work we showed metabolic reprogramming by means of inhibitors of histone deacetylase (HDACis), sodium butyrate and trichostatin. This treatment was able to shift energy metabolism by activating mitochondrial systems such as the respiratory chain and oxidative phosphorylation that were largely repressed in the untreated controls. METHODOLOGY/PRINCIPAL FINDINGS: Various cellular and biochemical parameters were evaluated in lung cancer H460 cells treated with the histone deacetylase inhibitors (HDACis), sodium butyrate (NaB) and trichostatin A (TSA). NaB and TSA reduced glycolytic flux, assayed by lactate release by H460 cells in a concentration dependent manner. NaB inhibited the expression of glucose transporter type 1 (GLUT 1), but substantially increased mitochondria bound hexokinase (HK) activity. NaB induced increase in HK activity was associated to isoform HK I and was accompanied by 1.5 fold increase in HK I mRNA expression and cognate protein biosynthesis. Lactate dehydrogenase (LDH) and pyruvate kinase (PYK) activities were unchanged by HDACis suggesting that the increase in the HK activity was not coupled to glycolytic flux. High resolution respirometry of H460 cells revealed NaB-dependent increased rates of oxygen consumption coupled to ATP synthesis. Metabolomic analysis showed that NaB altered the glycolytic metabolite profile of intact H460 cells. Concomitantly we detected an activation of the pentose phosphate pathway (PPP). The high O(2) consumption in NaB-treated cells was shown to be unrelated to mitochondrial biogenesis since citrate synthase (CS) activity and the amount of mitochondrial DNA remained unchanged. CONCLUSION: NaB and TSA induced an increase in mitochondrial function and oxidative metabolism in H460 lung tumor cells concomitant with a less proliferative cellular phenotype