Altered Nrf2/Keap1-Bach1 equilibrium in pulmonary emphysema

BACKGROUND: Oxidative stress, resulting from the increased oxidative burden and decreased level of antioxidant proteins, plays a role in the pathophysiology of smoking-related pulmonary emphysema. Expression of several antioxidant proteins, such as heme oxygenase-1 (HO-1), glutathione peroxidase 2 (GPX2) and NAD(P)H:quinone oxidoreductase 1 (NQO1), results from an equilibrium created by positive or negative regulation by the transcription factors Nrf2, Keap1 and Bach1, respectively. However, whether the expression of these transcription factors is altered in emphysema and could account for decreased expression of antioxidant proteins is not known. A study was undertaken to investigate the expression and subcellular localisation of Nrf2, Keap1 and Bach1 as potential regulators of HO-1, GPX2 and NQO1 in alveolar macrophages, a key cell in oxidative stress, in lung surgical specimens from non-smokers without emphysema and smokers with and without emphysema. METHODS AND RESULTS: Western blot, immunohistochemical and laser scanning confocal analysis revealed that the Nrf2 protein level decreased significantly in whole lung tissue and alveolar macrophages (cytosol and nucleus) in patients with emphysema compared with those without emphysema. Conversely, Bach1 and Keap1 levels were increased in patients with emphysema. These modifications were associated with a parallel decrease in the expression of HO-1, GPX2 and NQO1 at the cellular level, which was inversely correlated with airway obstruction and distension indexes, and increased macrophage expression of the lipid peroxidation product 4-hydroxy-2-nonenal. Silencing RNA experiments in vitro in THP-1 cells were performed to confirm the cause-effect relation between the loss of Nrf2 and the decrease in HO-1, NQO1 and GPX2 expression. Nrf2/Keap1-Bach1 equilibrium was altered in alveolar macrophages in pulmonary emphysema, which points to a decreased stress response phenotype. CONCLUSIONS: This finding opens a new view of the pathophysiology of emphysema and could provide the basis for new therapeutic approaches based on preservation and/or restoration of such equilibrium

Convergence calls: multimedia storytelling at British news websites

This article uses qualitative interviews with senior editors and managers from a selection of the UK's national online news providers to describe and analyse their current experimentation with multimedia and video storytelling. The results show that, in a period of declining newspaper readership and TV news viewing, editors are keen to embrace new technologies, which are seen as being part of the future of news. At the same time, text is still reported to be the cornerstone for news websites, leading to changes in the grammar and function of news video when used online. The economic rationale for convergence is examined and the article investigates the partnerships sites have entered into in order to be able to serve their audience with video content. In-house video is complementing syndicated content, and the authors examine the resulting developments in newsroom training and recruitment practices. The article provides journalism and interactive media scholars with case studies on the changes taking place in newsrooms as a result of the shift towards multimedia, multiplatform news consumption

Africa in the click stream: audience metrics and foreign correspondents in africa

Digital technologies have transformed the relationship between news outlets, journalists and their audiences. Notably, editors can now monitor their websites and discern the exact news preferences of their readers. Research suggests that some editors are using this data to help them produce more popular, ‘click friendly’ content. To date, research on this phenomenon has focused on journalists working within newsrooms. This article adds to the literature by exploring the relationship of foreign correspondents in Africa with their audiences, and asks whether readership metrics are influencing the journalists’ selection and development of news stories. Drawing on 67 interviews with foreign correspondents in East and West Africa, the article identifies three different approaches to audience metrics: correspondents who are 1) data-driven; 2) data informed; and 3) data denialists. The article discusses the implications of these approaches for the media image of Africa that is distributed around the globe

Phase Transition of a Non-Linear Opinion Dynamics with Noisy Interactions

International audienceIn several real \emph{Multi-Agent Systems} (MAS), it has been observed that only weaker forms of\emph{metastable consensus} are achieved, in which a large majority of agents agree on some opinion while other opinions continue to be supported by a (small) minority of agents. In this work, we take a step towards the investigation of metastable consensus for complex (non-linear) \emph{opinion dynamics} by considering the famous \undecided dynamics in the binary setting, which is known to reach consensus exponentially faster than the \voter dynamics. We propose a simple form of uniform noise in which each message can change to another one with probability $p$ and we prove that the persistence of a \emph{metastable consensus} undergoes a \emph{phase transition} for $p=\frac 16$. In detail, below this threshold, we prove the system reaches with high probability a metastable regime where a large majority of agents keeps supporting the same opinion for polynomial time. Moreover, this opinion turns out to be the initial majority opinion, whenever the initial bias is slightly larger than its standard deviation.On the contrary, above the threshold, we show that the information about the initial majority opinion is ``lost'' within logarithmic time even when the initial bias is maximum.Interestingly, using a simple coupling argument, we show the equivalence between our noisy model above and the model where a subset of agents behave in a \emph{stubborn} way

Bone Marrow–generated Dendritic Cells Pulsed with Tumor Extracts or Tumor RNA Induce Antitumor Immunity against Central Nervous System Tumors

Recent studies have shown that the brain is not a barrier to successful active immunotherapy that uses gene-modified autologous tumor cell vaccines. In this study, we compared the efficacy of two types of vaccines for the treatment of tumors within the central nervous system (CNS): dendritic cell (DC)-based vaccines pulsed with either tumor extract or tumor RNA, and cytokine gene–modified tumor vaccines. Using the B16/F10 murine melanoma (B16) as a model for CNS tumor, we show that vaccination with bone marrow–generated DCs, pulsed with either B16 cell extract or B16 total RNA, can induce specific cytotoxic T lymphocytes against B16 tumor cells. Both types of DC vaccines were able to protect animals from tumors located in the CNS. DC-based vaccines also led to prolonged survival in mice with tumors placed before the initiation of vaccine therapy. The DC-based vaccines were at least as effective, if not more so, as vaccines containing B16 tumor cells in which the granulocytic macrophage colony-stimulating factor gene had been modified. These data support the use of DC-based vaccines for the treatment of patients with CNS tumors

Management and resistance in the digital newsroom

What happens when there is conflict between the profit motivations of a news outlet and the professional values of its journalists? Questions of managerial influence and journalistic autonomy have interested media scholars from the seminal work of Warren Breed onwards. However, there have only been a handful of studies since the introduction of audience metrics which, this research suggests, allow managers to more efficiently monitor and discipline their journalists. This article presents an ethnographic case study of a Reuters newswire bureau during a time of conflict between the management and journalists. The article outlines the strategies that management used to incentivize their journalists to change their reporting priorities. These included the strategic dissemination of audience metrics and praise, and the hiring and promotion of ‘appropriate’ journalists to positions of influence. These interventions changed who was considered a ‘good journalist’ at the newswire, disrupting existing hierarchies, and eventually changing the culture of the newsroom. The article draws on the insights of Pierre Bourdieu’s field theory to help explain how managerial power operates, and the role that individual journalists play producing and reinforcing newsroom norms

Dendritic cell defects in patients with cancer: mechanisms and significance

Dendritic cells (DCs) are a complex network of antigen-presenting cells that have an essential role in the modulation of primary immunity. There has been increasing evidence that DCs isolated from patients with malignancy demonstrate functional deficiencies that inhibit the capacity to mount an effective anti-tumor response. In this issue of Breast Cancer Research, Pinzon-Charry and colleagues investigate one of the possible mechanisms by which tumors induce DC dysfunction to evade host immune surveillance. They demonstrate that DCs isolated from the circulation of patients with early-stage breast cancer exhibit increased rates of spontaneous apoptosis. In vitro studies suggest that a soluble factor secreted by breast cancer cells is responsible for this phenomenon. In contrast, ex vivo conditioning of DCs with CD-40 ligand and IL-12 was protective against tumor-induced apoptosis

The Ethical Implications of an Elite Press

Newspaper publishers are well into the process of bifurcating what once was a single mass-market product. Particularly for larger papers, website versions are taking over the mass-market role, while remaining print products are moving toward targeting a much smaller and more elite readership. This article explores theoretical and ethical issues raised by such a two-tiered newspaper structure and suggests directions for empirical study. Broadly, concerns center on the widening knowledge gap between print and online newspaper readers and its implications for civic discourse and democratic vitality. More narrowly, issues encompass a potential bifurcation of normative standards, including diverging markers of credibility, accuracy, and privacy