Elm tree bark extract inhibits HepG2 hepatic cancer cell growth via pro-apoptotic activity

Control of inflammation is widely accepted as an important strategy for cancer chemoprevention. Anti-inflammatory effects of bark extracts of elm tree (BEE) have been amply reported. Therefore, BEE may be a good candidate cancer chemopreventive agent. Considering the high incidence of hepatic cancer and limited therapeutic approaches for treating this disease, it is important to develop liver cancer-specific chemopreventive agents. To evaluate the chemopreventive potential of BEE, we investigated the growth inhibition effect of BEE on the HepG2 human hepatocellular carcinoma cell line. We performed a cell counting kit-8 assay to determine cell viability, and 4,6-diamino-2-phenylindole staining and flow cytometry to measure apoptotic cell death. Finally, the expression levels of pro- and anti-apoptotic proteins were measured. BEE inhibited the growth of HepG2 cells and induced apoptosis in a dose-dependent manner. Pro-apoptotic activity was promoted via the mitochondrial pathway of apoptosis, as demonstrated by the activation of pro-apoptotic proteins Bax, caspase-9, caspase-3, and poly (ADP-ribose) polymerase as well as the down-regulation of the anti-apoptotic protein Bcl-2. These results suggest that BEE may have potential use in hepatic cancer chemoprevention by suppressing cancer cell growth via pro-apoptotic activity

Identification of a novel BCL2-specific inhibitor that binds predominantly to the BH1 domain

The antiapoptotic protein BCL 2 is overexpressed in several cancers and contributes to prolonged cell survival and chemoresistance, lending itself as an excellent target for cancer therapy. Here, we report the design, synthesis, and characterization of Disarib, a novel BCL 2 inhibitor. Disarib showed selective cytotoxicity in BCL 2 high cancer cell lines, and CLL patient primary cells, as compared to BCL 2 low cell lines. BCL 2 knockdown in cells rendered remarkable resistance to Disarib, while sensitivity was regained upon its ectopic expression, establishing target specificity. In silico , biochemical and biophysical studies demonstrated strong affinity of Disarib to BCL 2, but not to other antiapoptotic BCL 2 family members viz., BCL ‐xL , BCL 2A1 etc. Interestingly, biophysical studies showed that BH 1 domain deletion mutant demonstrated ~ 67‐fold reduction in BCL 2‐Disarib interaction, while it was only ~ 20‐fold in the case of BH 3 deletion mutant, suggesting predominant involvement of the BH 1 domain for Disarib binding. Thus, we report identification of a novel BCL 2 inhibitor with a unique mechanism of BCL 2 inhibition, as opposed to the well‐studied BH 3 domain targeting

Status and Recent Results of the Acoustic Neutrino Detection Test System AMADEUS

The AMADEUS system is an integral part of the ANTARES neutrino telescope in the Mediterranean Sea. The project aims at the investigation of techniques for acoustic neutrino detection in the deep sea. Installed at a depth of more than 2000m, the acoustic sensors of AMADEUS are based on piezo-ceramics elements for the broad-band recording of signals with frequencies ranging up to 125kHz. AMADEUS was completed in May 2008 and comprises six "acoustic clusters", each one holding six acoustic sensors that are arranged at distances of roughly 1m from each other. The clusters are installed with inter-spacings ranging from 15m to 340m. Acoustic data are continuously acquired and processed at a computer cluster where online filter algorithms are applied to select a high-purity sample of neutrino-like signals. 1.6 TB of data were recorded in 2008 and 3.2 TB in 2009. In order to assess the background of neutrino-like signals in the deep sea, the characteristics of ambient noise and transient signals have been investigated. In this article, the AMADEUS system will be described and recent results will be presented.Comment: 7 pages, 8 figures. Proceedings of ARENA 2010, the 4th International Workshop on Acoustic and Radio EeV Neutrino Detection Activitie

Control of Mitochondrial Membrane Permeabilization by Adenine Nucleotide Translocator Interacting with HIV-1 Viral Protein R and Bcl-2

Viral protein R (Vpr), an apoptogenic accessory protein encoded by HIV-1, induces mitochondrial membrane permeabilization (MMP) via a specific interaction with the permeability transition pore complex, which comprises the voltage-dependent anion channel (VDAC) in the outer membrane (OM) and the adenine nucleotide translocator (ANT) in the inner membrane. Here, we demonstrate that a synthetic Vpr-derived peptide (Vpr52-96) specifically binds to the intermembrane face of the ANT with an affinity in the nanomolar range. Taking advantage of this specific interaction, we determined the role of ANT in the control of MMP. In planar lipid bilayers, Vpr52-96 and purified ANT cooperatively form large conductance channels. This cooperative channel formation relies on a direct protein–protein interaction since it is abolished by the addition of a peptide corresponding to the Vpr binding site of ANT. When added to isolated mitochondria, Vpr52-96 uncouples the respiratory chain and induces a rapid inner MMP to protons and NADH. This inner MMP precedes outer MMP to cytochrome c. Vpr52-96–induced matrix swelling and inner MMP both are prevented by preincubation of purified mitochondria with recombinant Bcl-2 protein. In contrast to König's polyanion (PA10), a specific inhibitor of the VDAC, Bcl-2 fails to prevent Vpr52-96 from crossing the mitochondrial OM. Rather, Bcl-2 reduces the ANT–Vpr interaction, as determined by affinity purification and plasmon resonance studies. Concomitantly, Bcl-2 suppresses channel formation by the ANT–Vpr complex in synthetic membranes. In conclusion, both Vpr and Bcl-2 modulate MMP through a direct interaction with ANT

Changing practice in dementia care in the community: developing and testing evidence-based interventions, from timely diagnosis to end of life (EVIDEM)

Background Dementia has an enormous impact on the lives of individuals and families, and on health and social services, and this will increase as the population ages. The needs of people with dementia and their carers for information and support are inadequately addressed at all key points in the illness trajectory. Methods The Unit is working specifically on an evaluation of the impact of the Mental Capacity Act 2005, and will develop practice guidance to enhance concordance with the Act. Phase One of the study has involved baseline interviews with practitioners across a wide range of services to establish knowledge and expectations of the Act, and to consider change processes when new policy and legislation are implemented. Findings Phase 1, involving baseline interviews with 115 practitioners, identified variable knowledge and understanding about the principles of the Act. Phase 2 is exploring everyday decision-making by people with memory problems and their carers

Measurement of Atmospheric Neutrino Oscillations with the ANTARES Neutrino Telescope

The data taken with the ANTARES neutrino telescope from 2007 to 2010, a total live time of 863 days, are used to measure the oscillation parameters of atmospheric neutrinos. Muon tracks are reconstructed with energies as low as 20 GeV. Neutrino oscillations will cause a suppression of vertical upgoing muon neutrinos of such energies crossing the Earth. The parameters determining the oscillation of atmospheric neutrinos are extracted by fitting the event rate as a function of the ratio of the estimated neutrino energy and reconstructed flight path through the Earth. Measurement contours of the oscillation parameters in a two-flavour approximation are derived. Assuming maximum mixing, a mass difference of $\Delta m_{32}^2=(3.1\pm 0.9)\cdot 10^{-3}$ eV$^2$ is obtained, in good agreement with the world average value.Comment: 9 pages, 5 figure

A multi-disciplinary education process related to the discharging of children from hospital when the child has been diagnosed with type 1 diabetes - a qualitative study

<p>Abstract</p> <p>Background</p> <p>Worldwide, insulin-dependent type 1 diabetes is one of the most frequently diagnosed long-term endocrine disorders found in children and the incidences of this diseased is still increasing. In Sweden the routines are, according to national guidelines, when the child is diagnosed with type 1 diabetes, the child and its family remains at the hospital for about two weeks. There is limited knowledge about how a diabetes team handles a child and its family from admission to discharge, therefore the purpose of this study was to seek a deeper understanding of how the diabetes team's parent/child education process works, from admission to discharge, among families with a child newly diagnosed with type 1 diabetes.</p> <p>Methods</p> <p>Qualitative data collection was used. Four focus-group interviews, with a sample of three diabetes teams from different paediatric hospitals in the south western part of Sweden, were conducted and the data recorded on tape and then analysed using qualitative content analysis.</p> <p>Results</p> <p>The results indicate that achieving a status of self-care on the part of the patient is the goal of the diabetes education programme. Part of the programme is aimed at guiding the child and its parents towards self-help through the means of providing them with knowledge of the disease and its treatment to enable the whole family to understand the need for cooperation in the process. To do this requires an understanding, by the diabetes team, of the individualities of the family in order to gain an overall picture.</p> <p>Conclusion</p> <p>The results of this study show that the diabetes education programme is specifically designed for each family using the internationally recommended clinical practice guidelines with its specific aims and objectives. Achieving the families' willingness to assist in the self-care of the child care is the goal of the parent education process. To achieve this, the paediatric diabetes specialist nurse and the diabetes specialist paediatrician immediately and deliberately start the process of educating the family using a programme designed to give them the necessary knowledge and skills they will need to manage their child's type 1 diabetes at home.</p

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000