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Targeted BCL2 inhibition effectively inhibits neuroblastoma tumour growth

Genomic aberrations of key regulators of the apoptotic pathway have hardly been identified in neuroblastoma. We detected high BCL2 mRNA and protein levels in the majority of neuroblastoma tumours by Affymetrix expression profiling and Tissue Micro Array analysis. This BCL2 mRNA expression is strongly elevated compared to normal tissues and other malignancies. Most neuroblastoma cell lines lack thi

BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition

Although targeting oncogenic mutations in the BRAF serine/threonine kinase with small molecule inhibitors can lead to significant clinical responses in melanoma, it fails to eradicate tumors in nearly all patients. Successful therapy will be aided by identification of intrinsic mechanisms that protect tumor cells from death. Here, we used a bioinformatics approach to identify drug-able, "driver" o

Grb10 is a dual regulator of receptor tyrosine kinase signaling

The adaptor protein Grb10 is a close homolog of Grb7 and Grb14. These proteins are characterized by an N-terminal proline-rich region, a Ras–GTPase binding domain, a PH domain, an SH2 domain and a BPS domain in between the PH and SH2 domains. Human Grb10 gene encodes three splice variants. These variants show differences in functionality. Grb10 associates with multiple proteins including tyrosine

IFNγ in combination with IL-7 enhances immunotherapy in two rat glioma models.

Peripheral immunization, using a combination of interferon-gamma (IFNγ)- and interleukin-7 (IL-7)-producing tumor cells, eradicated 75% of pre-established intracerebral N32 rat glioma tumors, and prolonged survival in the more aggressive RG2 model. Rats immunized with IFNγ- and IL7-transduced N32 cells displayed increases in IFNγ plasma levels and proliferating circulating T cells when compared wi

The string-pulling paradigm in comparative psychology.

String pulling is one of the most widely used paradigms in comparative psychology. First documented 2 millennia ago, it has been a well-established scientific paradigm for a century. More than 160 bird and mammal species have been tested in over 200 studies with countless methodological variations. The paradigm can be used to address a wide variety of issues on animal cognition; for example, what

Enriched housing down-regulates the Toll-like receptor 2 response in the mouse brain after experimental stroke.

Post-ischemic inflammation plays an important role in the evolution of brain injury, recovery and repair after stroke. Housing rodents in an enriched environment provides multisensory stimulation to the brain and enhances functional recovery after experimental stroke, also depressing the release of cytokines and chemokines in the peri-infarct. In order to identify targets for late stroke treatment

Holocene land-cover reconstructions for studies on land cover-climate feedbacks

The major objectives of this paper are: (1) to review the pros and cons of the scenarios of past anthropogenic land cover change (ALCC) developed during the last ten years, (2) to discuss issues related to pollen-based reconstruction of the past land-cover and introduce a new method, REVEALS (Regional Estimates of VEgetation Abundance from Large Sites), to infer long-term records of past land-cove

Considerations in the laboratory assessment of haemostasis

This review outlines a number of key issues when performing laboratory testing of homeostasis. The effect pre-analytical variables have on the reliability and consistency of screening tests is often forgotten due to a lack of understanding and awareness. This can be improved through educating healthcare professionals who are involved in taking blood for assessment. Recent advances in coagulation t

Searching for a Mobilizing Narrative on Climate Change

Global environmental change is real and everywhere, and so is inequality. Such a warmer, stormier, and divided world will create highly differentiated socioecological impacts and responses to climate change with stronger effects on people, places, and livelihoods that contributed the least. This necessitates mitigation, adaptation, and a solid understanding of their interactions with persistent pr

Core-shell structure disclosed in self-assembled Cu-Ag nanoalloy particles.

Core-shell segregation of copper and silver in self-assembled, free nanoparticles is established by means of photoelectron spectroscopy in a wide range of relative Cu-Ag concentrations. These conclusions are based on the analysis of the photon-energy-dependent changes of the Cu 3d and Ag 4d photoelectron spectra. The nanoparticles are formed from mixed Cu-Ag atomic vapor created by magnetron sputt

Biohydrogen production from wheat straw hydrolysate using Caldicellulosiruptor saccharolyticus followed by biogas production in a two-step uncoupled process

A two-step, un-coupled process producing hydrogen (H2) from wheat straw using Caldicellulosiruptor saccharolyticus in a ‘Continuously stirred tank reactor’ (CSTR) followed by anaerobic digestion of its effluent to produce methane (CH4) was investigated. C. saccharolyticus was able to convert wheat straw hydrolysate to hydrogen at maximum production rate of approximately 5.2 L H2/L/Day. The organic

Effect of metal oxide morphology on electron injection from CdSe quantum dots to ZnO

Performance of quantum dot sensitized solar cells relies on a rapid electron injection from quantum dot to metal oxide. We studied the injection process in CdSe-ZnO system by ultrafast time-resolved absorption spectroscopy for two types of acceptor morphologies-nanowires and nanoparticles' films. Based on comparison between experimental data and Marcus theory, we demonstrate that the acceptor morp

Target temperature management after out-of-hospital cardiac arrest-a randomized, parallel-group, assessor-blinded clinical trial-rationale and design

Background Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32 degrees C to 34 degrees C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the

Vigorous physical activity impairs myocardial function in patients with arrhythmogenic right ventricular cardiomyopathy and in mutation positive family members

AimsExercise increases risk of ventricular arrhythmia in subjects with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to investigate the impact of exercise on myocardial function in ARVC subjects. Methods and ResultsWe included 110 subjects (age 4217years), 65 ARVC patients and 45 mutation-positive family members. Athletes were defined as subjects with 4h vigorous exercise/week [

Defining goals in participatory water management: merging local visions and expert judgements

Management by objectives is intrinsic to the EU Water Framework Directive (WFD) and Swedish environmental policy. We describe three approaches to formulating objectives via model-assisted dialogue with local stakeholders concerning eutrophication in a coastal drainage area in south-eastern Sweden: a WFD eco-centred approach based on 'natural state'; Swedish environmental policy reformulated into q

Decrease in the incidence of total hip arthroplasties in patients with rheumatoid arthritis - results from a well defined population in south Sweden

Introduction: One aim of modern pharmacologic treatment in rheumatoid arthritis (RA) is to prevent joint destruction and reduce the need for surgery. Our purpose was to investigate secular trends in the incidence of primary total hip and knee arthroplasties in a well defined sample of patients with RA. Methods: Prevalent cases with RA in 1997 and incident cases from 1997 to 2007 in a community bas