HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1

An estimated 10–20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), with endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is the causative agent of adult T cell leukemia (ATL) and HTLV-1 associated myopathy/tropic spastic paraparesis (HAM/TSP). HTLV-1 expresses several regulatory and accessory genes that function at different stages of the virus life cycle. The regulatory gene Tax-1 is required for efficient virus replication, as it drives transcription of viral gene products, and has also been demonstrated to play a key role in the pathogenesis of the virus. Several studies have identified a PDZ binding motif (PBM) at the carboxyl terminus of Tax-1 and demonstrated the importance of this domain for HTLV-1 induced cellular transformation. Using a mass spectrometry-based proteomics approach we identified sorting nexin 27 (SNX27) as a novel interacting partner of Tax-1. Further, we demonstrated that their interaction is mediated by the Tax-1 PBM and SNX27 PDZ domains. SNX27 has been shown to promote the plasma membrane localization of glucose transport 1 (GLUT1), one of the receptor molecules of the HTLV-1 virus, and the receptor molecule required for HTLV-1 fusion and entry. We postulated that Tax-1 alters GLUT1 localization via its interaction with SNX27. We demonstrate that over expression of Tax-1 in cells causes a reduction of GLUT1 on the plasma membrane. Furthermore, we show that knockdown of SNX27 results in increased virion release and decreased HTLV-1 infectivity. Collectively, we demonstrate the first known mechanism by which HTLV-1 regulates a receptor molecule post-infection.</div

Study protocol: Delayed intervention randomised controlled trial within the Medical Research Council (MRC) Framework to assess the effectiveness of a new palliative care service

Background: Palliative care has been proposed to help meet the needs of patients who suffer progressive non-cancer conditions but there have been few evaluations of service development initiatives. We report here a novel protocol for the evaluation of a new palliative care service in this context. Methods/Design: Using the MRC Framework for the Evaluation of Complex Interventions we modelled a new palliative care and neurology service for patients severely affected by Multiple Sclerosis (MS). We conducted qualitative interviews with patients, families and staff, plus a literature review to model and pilot the service. Then we designed a delayed intervention randomised controlled trial to test its effectiveness as part of phase II of the MRC framework. Inclusion criteria for the trial were patients identified by referring clinicians as having unresolved symptoms or psychological concerns. Referrers were advised to use a score of greater than 8 on the Expanded Disability Scale was a benchmark. Consenting patients newly referred to the new service were randomised to either receive the palliative care service immediately (fast-track) or after a 12-week wait (standard best practice). Face to face interviews were conducted at baseline (before intervention), and at 4–6, 10–12 (before intervention for the standard-practice group), 16– 18 and 22–24 weeks with patients and their carers using standard questionnaires to assess symptoms, palliative care outcomes, function, service use and open comments. Ethics committee approval was granted separately for the qualitative phase and then for the trial. Discussion: We publish the protocol trial here, to allow methods to be reviewed in advance of publication of the results. The MRC Framework for the Evaluation of Complex Interventions was helpful in both the design of the service, methods for evaluation in convincing staff and the ethics committee to accept the trial. The research will provide valuable information on the effects of palliative care among non-cancer patients and a method to evaluate palliative care in this context

Key considerations for a regional SocMon strategy for the Bay of Bengal Large Marine Ecosystem countries in South Asia

Socio-economic Monitoring (SocMon) is an approach and set of tools for conducting socio-economic monitoring of changes in coastal communities. Key considerations included: importance of local partnerships; government and civil society partnerships; emphasis of adapting SocMon to local needs and priorities; capacity building; engaging with local stakeholders; inter and intra-regional collaboration; importance of language; and importance of language

Report of the SocMon capacity development workshop for the Bay of Bengal Large Marine Ecosystem countries in South Asia, St Martin's Island, Bangladesh, 2-11 January, 2015

Socio-economic Monitoring (SocMon) is an approach and set of tools for conducting socio-economic monitoring of changes in coastal communities. Planned outputs of the workshop included: training of local staff i SocMon methodologies; draft a SocMon report for St. Martin's Island; a workplan for implementing the SocMon; a communication strategy; and key inputs to a regional SocMon strateg

Groundwater quality mapping using geographic information system (GIS): A case study of Gulbarga City, Karnataka, India

Spatial variations in ground water quality in the corporation area of Gulbarga City located in the northern part of Karnataka State, India, have been studied using geographic information system (GIS) technique. GIS, a tool which is used for storing, analyzing and displaying spatial data is also used for investigating ground water quality information. For this study, water samples were collected from 76 of the bore wells and open wells representing the entire corporation area. The water samples were analyzed for physico-chemical parameters like TDS, TH, Cl&lt;sup&gt;-&lt;/sup&gt; and NO&lt;sub&gt;3&lt;/sub&gt;&lt;sup&gt;-&lt;/sup&gt;, using standard techniques in the laboratory and compared with the standards. The ground water quality information maps of the entire study area have been prepared using GIS spatial interpolation technique for all the above&nbsp; parameters. The results obtained in this study and the spatial database established in GIS will be helpful for monitoring and managing ground water pollution in the study area. Mapping was coded for potable zones, in the absence of better alternate source and non-potable zones in the study area, in terms of water quality. Keywords: Groundwater pollution, drinking-water, physico-chemical parameters, spatial interpolation

Why are we failing to implement imaging studies with radiolabelled new molecular entities in early oncology drug development?

In early drug development advanced imaging techniques can help with progressing new molecular entities (NME) to subsequent phases of drug development and thus reduce attrition. However, several organizational, operational, and regulatory hurdles pose a significant barrier, potentially limiting the impact these techniques can have on modern drug development. Positron emission tomography (PET) of radiolabelled NME is arguably the best example of a complex technique with a potential to deliver unique decision-making data in small cohorts of subjects. However, to realise this potential the impediments to timely inclusion of PET into the drug development process must be overcome. In the present paper, we discuss the value of PET imaging with radiolabelled NME during early anticancer drug development, as exemplified with one such NME. We outline the multiple hurdles and propose options on how to streamline the organizational steps for future studies

Report of the SocMon capacity development workshop for the Bay of Bengal Large Marine Ecosystem countries in South Asia, Vidathaltivu, Northern Province, Sri Lanka, 3-11 March, 2015

This Socioeconomic Monitoring (SocMon) training workshop was coordinated by the Small Fisher Federation of Lanka (SFFL). Planned outputs included: participants from Mannar trained in SocMon methodologies; draft SocMon reports fro Vidathaltivu; a workplan for Mannar; a communication strategy for Vidathaltivu/ Mannar; and key inputs to a regional SocMon strateg