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

Checkpoints in TNF-Induced Cell Death: Implications in Inflammation and Cancer.

Tumor necrosis factor (TNF) is a proinflammatory cytokine that coordinates tissue homeostasis by regulating cytokine production, cell survival, and cell death. However, how life and death decisions are made in response to TNF is poorly understood. Many inflammatory pathologies are now recognized to be driven by aberrant TNF-induced cell death, which, in most circumstances, depends on the kinase Receptor-interacting serine/threonine-protein kinase 1 (RIPK1). Recent advances have identified ubiquitin (Ub)-mediated phosphorylation of RIPK1 as belonging to crucial checkpoints for cell fate in inflammation and infection. A better understanding of these checkpoints might lead to new approaches for the treatment of chronic inflammatory diseases fueled by aberrant RIPK1-induced cell death, and/or reveal novel strategies for anticancer immunotherapies, harnessing the ability of RIPK1 to trigger immunogenic cell death

Acute primary repair of the anterior cruciate ligament with anterolateral ligament augmentation

Acute injuries of the anterior cruciate ligament are often associated with concurrent injuries to the structures of the anterolateral complex, specifically the anterolateral ligament. Some injury patterns of the anterior cruciate ligament involve tearing of the majority of the ligament from the femoral origin, leaving a large, viable ligament remnant. In these patients, a repair of the anterior cruciate ligament back to the femoral origin can be undertaken. Subsequently, percutaneous repair of the anterolateral ligament can be performed through anatomical, percutaneous suture tape augmentation. The combined technique of anterior cruciate ligament repair with anterolateral ligament reinforcement is presented

In-office needle arthroscopic assessment after primary ACL repair. Short-term results in 15 patients

Purpose: In-office needle arthroscopy has been reported as a diagnostic tool for different knee pathologies. In addi- tion, ACL repair has seen a resurgence with the advent of innovative orthopedic devices. The aim of this study was to assess clinical, radiological, and in-office needle arthroscopic findings in 15 adult patients who underwent acute (within 14 days from injury) anterior cruciate ligament (ACL) repair. Methods: Fifteen patients voluntarily participated in the study. A second-look arthroscopy was performed with an in-office needle arthroscopy at an average of 7.2 months after the primary repair. The parameters included in the investigation were the continuity of the anatomical footprint of the repaired ACL, subjective assessment of the ACL tension with the probe, and synovial coverage of the ACL. All patients had a Magnetic Resonance Imaging (MRI) at 6 months after repair and an arthrometric evaluation with the KT-1000. Clinical evaluation with the scores, Tegner Lysholm Knee Scoring Scale (TLKSS), the Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) was performed at the final follow-up of 2 years. Moreover, a correlation between the characteristics of ACL appearance at the time of the second look in-office needle arthroscopy, MRI and KT-1000 was performed. Results: The mean TLKSS was 97.86, the mean KOOS was 98.08 and the mean subjective IKDC was 96.71. The objec- tive IKDC was A in 10 patients and B in 5 patients. ACL healing was graded as A in 11 patients and B in 4 patients. Synovial coverage was graded as good in 10 patients and fair in 5 while MRI assessment showed a type I ACL in 10 patients, type II in 4 patients and type III in 1 patient. Conclusion: In-office needle arthroscopy is a reliable tool to assess the condition of a repaired ACL. In addition, ACL repair performed in acute proximal tears demonstrated excellent clinical results

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 [...

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