Sensitization of human melanoma cells for TRAIL-induced apoptosis by a selective aurora kinase A inhibitor

Different therapeutic strategies in metastatic melanoma focused on signalling pathways controlling cell proliferation, cell cycle and apoptosis. While TRAIL (TNF-related apoptosis inducing ligand) has been shown to be an interesting candidate for inducing apoptosis in cancer cells without affecting normal cells, the ability of cancer cells to develop resistance, limits its therapeutic potential. Using a recently established experimental A-375 melanoma cell model for investigating TRAIL resistance, we could demonstrate that the aurora kinase A inhibitor Alisertib (MLN 8237) enhances the proapoptotic effects of TRAIL and sensitizes TRAIL-selected melanoma cells with acquired resistance, associated with an activation of intrinsic mitochondrial apoptotic pathways. In course of this activation an upregulation of p53 in the nuclear fraction was shown. Thus, the aurora kinase A inhibitor Alisertib is able to overcome TRAIL-induced resistance in melanoma cells suggesting the combination of TRAIL and Alisertib as a promising therapeutic strategy for metastatic melanoma.

Exploring the Role of Cities in Electrifying Passenger Transportation

Key Takeaways1. The electrification of passenger vehicles should be one part of a city’s transportation plan. Shifting from internal combustion engine vehicles to plug-in electric vehicles (PEVs) can improve urban air quality, reduce greenhouse gas emissions, and reduce energy consumption.2. Recent studies show that electric vehicle awareness is low even in mature markets; cities should promote electric vehicles to residents by leveraging existing promotional campaigns.3. Various financial and non-financial incentives can effectively encourage electric vehicle uptake, including: free, discounted, or preferential-location parking; free or reduced road and bridge tolls; and allowing electric vehicles to drive in bus or carpool lanes.4. Several cities are restricting or planning to restrict the access that internal combustion engine vehicles (ICEVs) have to certain areas. If these restrictions apply to most (or all) passenger ICEVs, they can promote PEV purchase and use in cities.5. Infrastructure development in cities should follow the same fundamental approach as that used outside of cities. The priority should be ensuring that PEV owners and prospective PEV buyers have access to charging at or near home. Workplace and public charging should be developed for those who cannot access charging at or near home.6. Cities should be strategic in their approach, first identifying the goals they want to achieve, and then exploring what steps they can take to meet these goals. The steps available will likely differ between cities due to the different ways in which roads, parking, and any other vehicle infrastructure is governed

Reduced awareness for osteoporosis in hip fracture patients compared to elderly patients undergoing elective hip replacement

Background: Osteoporotic fractures are associated with a loss of quality of life, but only few patients receive an appropriate therapy. Therefore, the present study aims to investigate the awareness of musculoskeletal patients to participate in osteoporosis assessment and to evaluate whether there are significant differences between acute care patients treated for major fractures of the hip compared to elective patients treated for hip joint replacement.; Methods: From May 2015 to December 2016 patients who were undergoing surgical treatment for proximal femur fracture or total hip replacement due to osteoarthritis and were at risk for an underlying osteoporosis (female > 60 and male > 70 years) were included in the study and asked to complete a questionnaire assessing the awareness for an underlying osteoporosis. ASA Score, FRAX Score, and demographic information have also been examined. Results: In total 268 patients (female = 194 (72.0%)/male = 74 (28%)), mean age 77.7 years (±7.7) undergoing hip surgery were included. Of these, 118 were treated for fracture-related etiology and 150 underwent total hip arthroplasty in an elective care setting. Patients were interviewed about their need for osteoporosis examination during hospitalization. Overall, 76 of 150 patients receiving elective care (50.7%) considered that an examination was necessary, whereas in proximal femur fracture patients the awareness was lower, and the disease osteoporosis was assessed as threatening by significantly fewer newly fractured patients. By comparison, patients undergoing trauma surgery had a considerably greater risk of developing another osteoporotic fracture than patients undergoing elective surgery determined by the FRAX(®) Score (p ≤ 0.001).; Conclusions: The patients’ motivation to endure additional osteoporosis diagnostic testing is notoriously low and needs to be increased. Patients who underwent acute care surgery for a fragility proximal femur fracture, although acutely affected by the potential consequences of underlying osteoporosis, showed lower awareness than the elective comparison population that was also on average 6.1 years younger. Although elective patients were younger and at a lower risk, they seemed to be much more willing to undergo further osteoporosis assessment. In order to better identify and care for patients at risk, interventions such as effective screening, early initiation of osteoporosis therapy in the inpatient setting and a fracture liaison service are important measures

Shelf ice-associated cryo-benthos and environmental features

Incidences of cryo-benthic communities beneath ice shelves are rare and recent discoveries. Combined seal- and ROV-borne imagery and novel sampling technologies allowed for a re-assessment and augmentation of earlier findings on a cryo-benthic isopod community (Antarcturus cf. spinacoronatus), being attached head-down to the underside of floating shelf ice at depths of around 80-150m. The shelf ice-associated cryo-benthos was discovered at Drescher Inlet (-72.83667 -19.15300), Riiser-Larsen Ice Shelf (eastern Weddell Sea). The inlet constitutes a 25km long and between 2 and 4km wide crack in the surrounding shelf ice, which is associated with certain environmental features. Here we compile all available local physical, biological, and biogeochemical data and discuss their relevance in the wider regional context for this faunal hotspot. These include data on shelf, sea and platelet ice, seafloor topography, hydrography and water chemistry, as well as associated pelagic and benthic marine life, in particular affinities of the cryo-benthic isopod community to related fauna occurring in nearby seabed communities using molecular barcoding

Cardiorespiratory fitness is associated with hard and light intensity physical activity but not time spent sedentary in 10–14 year old schoolchildren: the HAPPY study

Sedentary behaviour is a major risk factor for developing chronic diseases and is associated with low cardiorespiratory fitness in adults. It remains unclear how sedentary behaviour and different physical activity subcomponents are related to cardiorespiratory fitness in children. The purpose of this study was to assess how sedentary behaviour and different physical activity subcomponents are associated with 10–14 year-old schoolchildren's cardiorespiratory fitness

Konzepte der Elektromobilität. Ihre Bedeutung für Wirtschaft, Gesellschaft und Umwelt

Gesellschaft und Politik knüpfen große Hoffnung an die Elektromobilität. Allerdings wird sehr kontrovers diskutiert, ob und wie eine umfassende und nachhaltige Verbreitung von Elektrofahrzeugen erreichbar ist. Für die Fortsetzung dieser Debatte ist es wichtig, die Ergebnisse aus der Vielzahl von Förderprogrammen und Studien, die in den letzten Jahren mit unterschiedlichen Fragestellungen und Perspektiven angestoßen wurden, in einem umfassenden Überblick zusammenzuführen – dieser Aufgabe unterziehen sich die Autor/inn/en dieses Bandes. Sie präsentieren hier eine mit zahlreichen Fakten und Daten untermauerte Gesamtschau über den technischen Entwicklungsstand, aussichtsreiche Erstmärkte, Markthochlaufszenarien sowie politische Aktivitäten und veranschaulichen im Rahmen einer ganzheitlichen Bewertung die ökologische, ökonomische und soziale Dimension der Integration von Elektrofahrzeugen in die heutigen Verkehrs- und Energiesysteme. Auf dieser Basis diskutieren sie Handlungsoptionen und liefern die Grundlage für politische Entscheidungen über Ziele und Maßnahmen. Als Baustein einer nachhaltigen Entwicklung hat die Elektromobilität großes Potenzial, dessen Entfaltung freilich Zeit und geeignete Rahmenbedingungen erfordert. Das Buch basiert auf dem TAB-Arbeitsbericht Nr. 153 »Konzepte der Elektromobilität und deren Bedeutung für Wirtschaft, Gesellschaft und Umwelt

Distribution, density and abundance of Antarctic ice seals off Queen Maud Land and the eastern Weddell Sea

The Antarctic Pack Ice Seal (APIS) Program was initiated in 1994 to estimate the abundance of four species of Antarctic phocids: the crabeater seal Lobodon carcinophaga , Weddell seal Leptonychotes weddellii , Ross seal Ommatophoca rossii and leopard seal Hydrurga leptonyx and to identify ecological relationships and habitat use patterns. The Atlantic sector of the Southern Ocean (the eastern sector of the Weddell Sea) was surveyed by research teams from Germany, Norway and South Africa using a range of aerial methods over five austral summers between 1996–1997 and 2000–2001. We used these observations to model densities of seals in the area, taking into account haul-out probabilities, survey-specific sighting probabilities and covariates derived from satellite-based ice concentrations and bathymetry. These models predicted the total abundance over the area bounded by the surveys (30° W and 10° E). In this sector of the coast, we estimated seal abundances of: 514 (95 % CI 337–886) 10^3 crabeater seals, 60.0 (43.2–94.4) 10^3 Weddell seals and 13.2 (5.50–39.7) 10^3 leopard seals. The crabeater seal densities, approximately 14,000 seals per degree longitude, are similar to estimates obtained by surveys in the Pacific and Indian sectors by other APIS researchers. Very few Ross seals were observed (24 total), leading to a conservative estimate of 830 (119–2894) individuals over the study area. These results provide an important baseline against which to compare future changes in seal distribution and abundance

Habitual Physical Activity in Mitochondrial Disease

Mitochondrial disease is the most common neuromuscular disease and has a profound impact upon daily life, disease and longevity. Exercise therapy has been shown to improve mitochondrial function in patients with mitochondrial disease. However, no information exists about the level of habitual physical activity of people with mitochondrial disease and its relationship with clinical phenotype.Habitual physical activity, genotype and clinical presentations were assessed in 100 patients with mitochondrial disease. Comparisons were made with a control group individually matched by age, gender and BMI. = −0.49; 95% CI −0.33, −0.63, P<0.01). There were no systematic differences in physical activity between different genotypes mitochondrial disease.These results demonstrate for the first time that low levels of physical activity are prominent in mitochondrial disease. Combined with a high prevalence of obesity, physical activity may constitute a significant and potentially modifiable risk factor in mitochondrial disease

Mutual Regulation of Bcl-2 Proteins Independent of the BH3 Domain as Shown by the BH3-Lacking Protein Bcl-xAK

The BH3 domain of Bcl-2 proteins was regarded as indispensable for apoptosis induction and for mutual regulation of family members. We recently described Bcl-xAK, a proapoptotic splice product of the bcl-x gene, which lacks BH3 but encloses BH2, BH4 and a transmembrane domain. It remained however unclear, how Bcl-xAK may trigger apoptosis

ANTARES constrains a blazar origin of two IceCube PeV neutrino events

Context. The source(s) of the neutrino excess reported by the IceCube Collaboration is unknown. The TANAMI Collaboration recently reported on the multiwavelength emission of six bright, variable blazars which are positionally coincident with two of the most energetic IceCube events. Objects like these are prime candidates to be the source of the highest-energy cosmic rays, and thus of associated neutrino emission. Aims. We present an analysis of neutrino emission from the six blazars using observations with the ANTARES neutrino telescope. Methods. The standard methods of the ANTARES candidate list search are applied to six years of data to search for an excess of muons ¿ and hence their neutrino progenitors ¿ from the directions of the six blazars described by the TANAMI Collaboration, and which are possibly associated with two IceCube events. Monte Carlo simulations of the detector response to both signal and background particle fluxes are used to estimate the sensitivity of this analysis for different possible source neutrino spectra. A maximum-likelihood approach, using the reconstructed energies and arrival directions of through-going muons, is used to identify events with properties consistent with a blazar origin. Results. Both blazars predicted to be the most neutrino-bright in the TANAMI sample (1653−329 and 1714−336) have a signal flux fitted by the likelihood analysis corresponding to approximately one event. This observation is consistent with the blazar-origin hypothesis of the IceCube event IC 14 for a broad range of blazar spectra, although an atmospheric origin cannot be excluded. No ANTARES events are observed from any of the other four blazars, including the three associated with IceCube event IC20. This excludes at a 90% confidence level the possibility that this event was produced by these blazars unless the neutrino spectrum is flatter than −2.4