The Myth of Cyberwar: Bringing War in Cyberspace Back Down to Earth

Cyberwar has been described as a revolution in military affairs, a transformation of technology and doctrine capable of overturning the prevailing world order. This characterization of the threat from cyberwar, however, reflects a common tendency to conflate means and ends; studying what could happen in cyberspace (or anywhere else) makes little sense without considering how conflict over the internet is going to realize objectives commonly addressed by terrestrial warfare. To supplant established modes of conflict, cyberwar must be capable of furthering the political ends to which force or threats of force are commonly applied, something that in major respects cyberwar fails to do. As such, conflict over the internet is much more likely to serve as an adjunct to, rather than a substitute for, existing modes of terrestrial force. Indeed, rather than threatening existing political hierarchies, cyberwar is much more likely to simply augment the advantages of status quo powers. </jats:p

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

Accelerated and Improved Quantification of Lymphocytic Choriomeningitis Virus (LCMV) Titers by Flow Cytometry

Lymphocytic choriomeningitis virus (LCMV), a natural murine pathogen, is a member of the Arenavirus family, may cause atypical meningitis in humans, and has been utilized extensively as a model pathogen for the study of virus-induced disease and immune responses. Historically, viral titers have been quantified by a standard plaque assay, but for non-cytopathic viruses including LCMV this requires lengthy incubation, so results cannot be obtained rapidly. Additionally, due to specific technical constraints of the plaque assay including the visual detection format, it has an element of subjectivity along with limited sensitivity. In this study, we describe the development of a FACS-based assay that utilizes detection of LCMV nucleoprotein (NP) expression in infected cells to determine viral titers, and that exhibits several advantages over the standard plaque assay. We show that the LCMV-NP FACS assay is an objective and reproducible detection method that requires smaller sample volumes, exhibits a ∼20-fold increase in sensitivity to and produces results three times faster than the plaque assay. Importantly, when applied to models of acute and chronic LCMV infection, the LCMV-NP FACS assay revealed the presence of infectious virus in samples that were determined to be negative by plaque assay. Therefore, this technique represents an accelerated, enhanced and objective alternative method for detection of infectious LCMV that is amenable to adaptation for other viral infections as well as high throughput diagnostic platforms

Barriers of attendance to dog rabies static point vaccination clinics in Blantyre, Malawi

<div><p>Rabies is a devastating yet preventable disease that causes around 59,000 human deaths annually. Almost all human rabies cases are caused by bites from rabies-infected dogs. A large proportion of these cases occur in Sub Saharan Africa (SSA). Annual vaccination of at least 70% of the dog population is recommended by the World Health Organisation in order to eliminate rabies. However, achieving such high vaccination coverage has proven challenging, especially in low resource settings. Despite being logistically and economically more feasible than door-to-door approaches, static point (SP) vaccination campaigns often suffer from low attendance and therefore result in low vaccination coverage. Here, we investigated the barriers to attendance at SP offering free rabies vaccinations for dogs in Blantyre, Malawi. We analysed data for 22,924 dogs from a city-wide vaccination campaign in combination with GIS and household questionnaire data using multivariable logistic regression and distance estimation techniques. We found that distance plays a crucial role in SP attendance (i.e. for every km closer the odds of attending a SP point are 3.3 times higher) and that very few people are willing to travel more than 1.5 km to bring their dog for vaccination. Additionally, we found that dogs from areas with higher proportions of people living in poverty are more likely to be presented for vaccination (ORs 1.58-2.22). Furthermore, puppies (OR 0.26), pregnant or lactating female dogs (OR 0.60) are less likely to be presented for vaccination. Owners also reported that they did not attend an SP because they were not aware of the campaign (27%) or they could not handle their dog (19%). Our findings will inform the design of future rabies vaccination programmes in SSA which may lead to improved vaccination coverage achieved by SP alone.</p></div

CXCR5⁺ follicular cytotoxic T cells control viral infection in B cell follicles

During unresolved infections, some viruses escape immunological control and establish a persistant reservoir in certain cell types, such as human immunodeficiency virus (HIV), which persists in follicular helper T cells (TFH cells), and Epstein-Barr virus (EBV), which persists in B cells. Here we identified a specialized group of cytotoxic T cells (TC cells) that expressed the chemokine receptor CXCR5, selectively entered B cell follicles and eradicated infected TFH cells and B cells. The differentiation of these cells, which we have called 'follicular cytotoxic T cells' (TFC cells), required the transcription factors Bcl6, E2A and TCF-1 but was inhibited by the transcriptional regulators Blimp1, Id2 and Id3. Blimp1 and E2A directly regulated Cxcr5 expression and, together with Bcl6 and TCF-1, formed a transcriptional circuit that guided TFC cell development. The identification of TFC cells has far-reaching implications for the development of strategies to control infections that target B cells and TFH cells and to treat B cell–derived malignancies

Measuring Apoptotic Cell Engulfment (Efferocytosis) Efficiency

Efferocytosis is the process of recognizing and removing dead and dying cells, performed by a variety of phagocytic cells including macrophages. It has recently been shown that liver X receptor (LXR) signaling in macrophages regulates the expression of important efferocytosis receptors, bridging and signaling molecules. Here we describe a sensitive yet robust efferocytosis assay, optimized to measure bone marrow-derived macrophage (BMDM) apoptotic cell engulfment capability. This assay can be applied to genetically or pharmacologically altered BMDMs