Cytokines as mediators of chemotherapy-associated cognitive changes: Current evidence, limitations and directions for future research

10.1371/journal.pone.0081234PLoS ONE812-POLN

Antiretroviral therapy partially improves the abnormalities of dendritic cells and lymphoid and myeloid regulatory populations in recently infected HIV patients

This study aimed to evaluate the effects of antiretroviral therapy on plasmacytoid (pDC) and myeloid (mDC) dendritic cells as well as regulatory T (Treg) and myeloid-derived suppressor (MDSC) cells in HIVinfected patients. Forty-five HIV-infected patients (20 of them with detectable HIV load −10 recently infected and 10 chronically infected patients-, at baseline and after antiretroviral therapy, and 25 with undetectable viral loads) and 20 healthy controls were studied. The influence of HIV load, bacterial translocation (measured by 16S rDNA and lipopolysaccharide-binding protein) and immune activation markers (interleukin –IL- 6, soluble CD14, activated T cells) was analyzed. The absolute numbers and percentages of pDC and mDC were significantly increased in patients. Patients with detectable viral load exhibited increased intracellular expression of IL-12 by mDCs and interferon -IFN- α by pDCs. Activated population markers were elevated, and the proportion of Tregs was significantly higher in HIV-infected patients. The MDSC percentage was similar in patients and controls, but the intracellular expression of IL-10 was significantly higher in patients. The achievement of undetectable HIV load after therapy did not modify bacterial translocation parameters, but induce an increase in pDCs, mDCs and MDSCs only in recently infected patients. Our data support the importance of early antiretroviral therapy to preserve dendritic and regulatory cell function in HIV-infected individuals

Construction of Transgenic Plasmodium berghei as a Model for Evaluation of Blood-Stage Vaccine Candidate of Plasmodium falciparum Chimeric Protein 2.9

BACKGROUND:The function of the 19 kDa C-terminal region of the merozoite surface protein 1 (MSP1-19) expressed by Plasmodium has been demonstrated to be conserved across distantly related Plasmodium species. The green fluorescent protein (GFP) is a reporter protein that has been widely used because it can be easily detected in living organisms by fluorescence microscopy and flow cytometry. METHODOLOGY AND RESULTS:In this study, we used gene targeting to generate transgenic P. berghei (Pb) parasites (designated as PfMSP1-19Pb) that express the MSP1-19 of P. falciparum (Pf) and the GFP reporter protein simultaneously. The replacement of the PbMSP1-19 locus by PfMSP1-19 was verified by PCR and Southern analysis. The expression of the chimeric PbfMSP-1 and the GFP was verified by Western blot and fluorescence microscopy, respectively. Moreover, GFP-expressing transgenic parasites in blood stages can be readily differentiated from other blood cells using flow cytometry. A comparison of growth rates between wild-type and the PfMSP1-19Pb transgenic parasite indicated that the replacement of the MSP1-19 region and the expression of the GFP protein were not deleterious to the transgenic parasites. We used this transgenic mouse parasite as a murine model to evaluate the protective efficacy in vivo of specific IgG elicited by a PfCP-2.9 malaria vaccine that contains the PfMSP1-19. The BALB/c mice passively transferred with purified rabbit IgG to the PfCP-2.9 survived a lethal challenge of the PfMSP1-19Pb transgenic murine parasites, but not the wild-type P. berghei whereas the control mice passively transferred with purified IgG obtained from adjuvant only-immunized rabbits were vulnerable to both transgenic and wild-type infections. CONCLUSIONS:We generated a transgenic P. berghei line that expresses PfMSP1-19 and the GFP reporter gene simultaneously. The availability of this parasite line provides a murine model to evaluate the protective efficacy in vivo of anti-MSP1-19 antibodies, including, potentially, those elicited by the PfCP-2.9 malaria vaccine in human volunteers

The emerging role of MIR-146A in the control of hematopoiesis, immune function and cancer

MicroRNA (miRs) represent a class of small non-coding regulatory RNAs playing a major role in the control of gene expression by repressing protein synthesis at the post-transcriptional level. Studies carried out during the last years have shown that some miRNAs plays a key role in the control of normal and malignant hgematopoiesis. In this review we focus on recent progress in analyzing the functional role of miR-146a in the control of normal and malignant hematopoiesis. On the other hand, this miRNA has shown to impact in the control of innate immune responses. Finally, many recent studies indicate a deregulation of miR-146 in many solid tumors and gene knockout studies indicate a role for this miRNA as a tumor suppressor

Epigenetic regulation of mucin genes in human cancers

Mucins are high molecular weight glycoproteins that play important roles in diagnostic and prognostic prediction and in carcinogenesis and tumor invasion. Regulation of expression of mucin genes has been studied extensively, and signaling pathways, transcriptional regulators, and epigenetic modification in promoter regions have been described. Detection of the epigenetic status of cancer-related mucin genes is important for early diagnosis of cancer and for monitoring of tumor behavior and response to targeted therapy. Effects of micro-RNAs on mucin gene expression have also started to emerge. In this review, we discuss the current views on epigenetic mechanisms of regulation of mucin genes (MUC1, MUC2, MUC3A, MUC4, MUC5AC, MUC5B, MUC6, MUC16, and MUC17) and the possible clinical applications of this epigenetic information

Understanding similarities and differences in land use visions for Scotland

The successful transition towards a global society that can live within planetary boundaries is one of the greatest challenges for the twenty-first century. Sustainable land use and land management will be essential to ensure the continued delivery of the ecosystem goods and services needed to support a rapidly growing global population. To support the transition towards sustainable development, decision-makers need to better understand how land use change affects people and the environment. However, these insights are of limited use without societal agreement on future land uses. Understanding synergies and differences between land use visions forms a first step in assessing and comparing alternative pathways towards a sustainable future. This thesis uses a range of methods to understand visions of future land use amongst professional land use stakeholders, society at large, and young people in Scotland. Twenty semi-structured interviews were held with policy experts from the Scottish land use sectors. A nationwide statistically representative web-based survey provided insight into the visions of the Scottish population. And finally, a novel visual interview methodology was used to interview 26 pupils from two high schools in Perthshire. Inductive content analysis and descriptive statistics were used to analyse the results and understand and compare the land use visions of these different groups. As expected, different groups had different visions of future land use. There was, however, general agreement on certain themes, in particular the desire for a more sustainable lifestyle and the importance of a healthy environment. The sectoral stakeholders would like to see more partnerships, dialogue and collaboration; a society that is more engaged and aware about land use; resilient local economies; and short-, medium-, and long-term policies that help to achieve these goals. One of the key challenges for these groups will be how to translate abstract concepts such as ‘healthy ecosystem’ and ‘dialogue and partnerships’ into practice. This clearly requires a shared understanding of what a ‘healthy ecosystem’ means to different stakeholders, as well as appreciation of what true dialogue means and how this can be used to co-create solutions – potentially a radical change from the traditional top-down approaches. The research also identified divisions in Scottish society between those who want to continue a ‘status quo’ lifestyle, and those – in particular younger people (who spent time in the natural environment, through either school or home life) and those from a higher socio-economic background – who want a more sustainable lifestyle and to be more connected with the natural environment. These results are important, as policy makers need to be able to identify the factors that have successfully engaged certain groups and to promote these factors. Programmes that provide access to the natural environment (such as the Duke of Edinburgh’s Award) need to ensure equal opportunities by targeting disadvantaged groups. Simultaneously, it needs to be explored how to encourage those who would like to continue a ‘status quo’ lifestyle into a more sustainable one. Past research has shown how preferences can be influenced and how changes can be initiated by incentives and restrictions in order to promote desired behaviours. The power of the media should be leveraged: programmes such as BBC’s ‘Blue Planet’ highlight how our lifestyle choices impact on the natural environment and can provide the motivation for change. The current issues surrounding Brexit and Climate Change require a national conversation; using methods such as those presented in the thesis to elicit land use visions can help identify the commonalties and differences between stakeholders’ views. This can provide a starting point for dialogue and critical reflection on current instruments and objectives, and how they might be adapted to better reflect Scottish preferences and conditions