96 research outputs found

    Eef1a2 Promotes Cell Growth, Inhibits Apoptosis and Activates JAK/STAT and AKT Signaling in Mouse Plasmacytomas

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    The canonical function of EEF1A2, normally expressed only in muscle, brain, and heart, is in translational elongation, but recent studies suggest a non-canonical function as a proto-oncogene that is overexpressed in a variety of solid tumors including breast and ovary. Transcriptional profiling of a spectrum of primary mouse B cell lineage neoplasms showed that transcripts encoding EEF1A2 were uniquely overexpressed in plasmacytomas (PCT), tumors of mature plasma cells. Cases of human multiple myeloma expressed significantly higher levels of EEF1A2 transcripts than normal bone marrow plasma cells. High-level expression was also a feature of a subset of cell lines developed from mouse PCT and from the human MM.Heightened expression of EEF1A2 was not associated with increased copy number or coding sequence mutations. shRNA-mediated knockdown of Eef1a2 transcripts and protein was associated with growth inhibition due to delayed G1-S progression, and effects on apoptosis that were seen only under serum-starved conditions. Transcriptional profiles and western blot analyses of knockdown cells revealed impaired JAK/STAT and PI3K/AKT signaling suggesting their contributions to EEF1A2-mediated effects on PCT induction or progression.EEF1A2 may play contribute to the induction or progression of some PCT and a small percentage of MM. Eef1a2 could also prove to be a useful new marker for a subset of MM and, ultimately, a possible target for therapy

    Crystal Structure of HIV-1 gp41 Including Both Fusion Peptide and Membrane Proximal External Regions

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    The HIV-1 envelope glycoprotein (Env) composed of the receptor binding domain gp120 and the fusion protein subunit gp41 catalyzes virus entry and is a major target for therapeutic intervention and for neutralizing antibodies. Env interactions with cellular receptors trigger refolding of gp41, which induces close apposition of viral and cellular membranes leading to membrane fusion. The energy released during refolding is used to overcome the kinetic barrier and drives the fusion reaction. Here, we report the crystal structure at 2 Å resolution of the complete extracellular domain of gp41 lacking the fusion peptide and the cystein-linked loop. Both the fusion peptide proximal region (FPPR) and the membrane proximal external region (MPER) form helical extensions from the gp41 six-helical bundle core structure. The lack of regular coiled-coil interactions within FPPR and MPER splay this end of the structure apart while positioning the fusion peptide towards the outside of the six-helical bundle and exposing conserved hydrophobic MPER residues. Unexpectedly, the section of the MPER, which is juxtaposed to the transmembrane region (TMR), bends in a 90°-angle sideward positioning three aromatic side chains per monomer for membrane insertion. We calculate that this structural motif might facilitate the generation of membrane curvature on the viral membrane. The presence of FPPR and MPER increases the melting temperature of gp41 significantly in comparison to the core structure of gp41. Thus, our data indicate that the ordered assembly of FPPR and MPER beyond the core contributes energy to the membrane fusion reaction. Furthermore, we provide the first structural evidence that part of MPER will be membrane inserted within trimeric gp41. We propose that this framework has important implications for membrane bending on the viral membrane, which is required for fusion and could provide a platform for epitope and lipid bilayer recognition for broadly neutralizing gp41 antibodies

    Using visual methods to understand physical activity maintenance following cardiac rehabilitation

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    © 2015 Hardcastle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Few studies have explored the factors associated with long-term maintenance of exercise following cardiac rehabilitation. The present study used auto-photography and interviews to explore the factors that influence motivation and continued participation in physical activity among post cardiac rehabilitation patients. Twenty-three semi-structured interviews were conducted alongside participant-selected photographs or drawings with participants that had continued participation in physical activity for at least two years following the cardiac rehabilitation programme. Participants were recruited from circuit training classes in East Sussex in the UK. Thematic content analysis revealed seven main themes: fear of death and ill health avoidance, critical incidents, overcoming aging, social influences, being able to enjoy life, provision of routine and structure, enjoyment and psychological well-being. Fear of death, illness avoidance, overcoming aging, and being able to enjoy life were powerful motives for continued participation in exercise. The social nature of the exercise class was also identified as a key facilitator of continued participation. Group-based exercise suited those that continued exercise participation post cardiac rehabilitation and fostered adherence

    Glycogen metabolism has a key role in the cancer microenvironment and provides new targets for cancer therapy

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    <span style="font-size:15.0pt;line-height:115%;font-family:"Times New Roman"; mso-fareast-font-family:Calibri;mso-bidi-font-family:"Times New Roman"; color:#231F20;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: AR-SA" lang="EN-US">Utilization of seaweeds in enhancing productivity and quality of black gram [<i style="mso-bidi-font-style:normal"><span style="font-size:15.0pt;line-height:115%;font-family:"Times New Roman"; mso-fareast-font-family:Calibri;mso-bidi-font-family:"Times New Roman"; color:#222222;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: AR-SA" lang="EN-US">Vigna </span></i><i style="mso-bidi-font-style:normal"><span style="font-size:15.0pt;line-height:115%;font-family:"Times New Roman"; mso-fareast-font-family:Calibri;mso-bidi-font-family:"Times New Roman"; color:#231F20;mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language: AR-SA" lang="EN-US">mungo </span></i><span style="font-size:15.0pt;line-height: 115%;font-family:"Times New Roman";mso-fareast-font-family:Calibri;mso-bidi-font-family: "Times New Roman";color:#231F20;mso-ansi-language:EN-US;mso-fareast-language: EN-US;mso-bidi-language:AR-SA" lang="EN-US">(L.)<i style="mso-bidi-font-style:normal"> </i>Hepper] for sustainable agriculture</span></span>

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    16-22Seaweed and seaweed-derived products have been widely used as biostimulants for crop production, however, the biostimulatory potential of many seaweed’s extract has not been fully exploited due to the lack of scientific data on field experiments. In present investigation, a field experiment was carried to study the corollary of foliar application of seaweed extract on black gram [Vigna mungo (L.) Hepper] under rainfed condition during rainy (kharif) season of 2010. Seaweed extracts (prepared from Kappaphycus alvarezii and Gracilaria edulis) were applied to the foliage at diverse concentrations (0, 2.5, 5, 10 and 15%) twice during the crop period. It was found that both the extracts were very effective and enhanced the yield, growth and improved the quality of the produce. The yield of seed had increased by 47.52% and 42.52% with the application of K. alvarezii and G. edulis extracts, respectively when applied at 10% conc. Not only this, but other yield attributing characters, viz. number of pods/plant, pod weight, seed weight/plant and test weight of seed also have been augmented. The quality of seeds was also improved under the influence of the seaweed extract treatments. The foliar application of seaweed extracts to black gram crop has significantly increased uptake of almost all the nutrients. Thus, foliar applications of seaweed extracts could be a promising option for yield enhancement and sustainable agriculture
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