ON THE ROLE OF VIRUSES IN THE EVOLUTION OF IMMUNE RESPONSES

Mutual influences of viruses on the immune system and vice versa which lead to a biological balance are considered, with clinical and/or experimental findings. Numbers and turnover of immune cells can be correlated with numbers and growth rate of viruses; certain viruses apparently have adapted to systemic or local immune effector mechanisms. The biological balance of viruses and immune system guarentees overall protection of both host and parasite. It alos may lead to conditions where immune protective mechanisms causes cell and tissue damage leading to disease. Immunologically mediated disease may be influenced by immune regulation via HLA antigen and may therefore explain HLA-disease associations. Finally, the different specificities of antibodies vs. T Cells and the differing kinetics of their immunological memory are outlined and correlated with immune escape, immune protection and the resulting possible evolutionary pressures on viruse

Instantaneous Power Spectrum

The estimation of time varying spectra is a complicated one. The use of classical techniques coupled with the local stationarity assumption is met with only moderate success. Of the many time frequency distribution functions used in the signal analysis, none present fully satisfactory spectra. The performance of the spectrogram, Instantaneous Power Spectra (IPS) the Wigner-Ville Distribution (WD) and various aspects of the Rihaczek distribution (RD) for a variety of signal nonstationarities are compared. WD has the most narrow main-lobes but suffers from spectral cross-terms. IPS, the real part of the RD consistently shows a broadened main-lobe without cross-terms. The squared magnitude of the RD places sharp peaks along the crest of the main-lobe and is otherwise very similar to IPS. The imaginary part of the RD shows a sensitivity to discontinuous frequency changes i.e., frequency shift keying.http://archive.org/details/instantaneouspow1094537553Lieutenant, Unuted States NavyApproved for public release; distribution is unlimited

GiViP: A Visual Profiler for Distributed Graph Processing Systems

Analyzing large-scale graphs provides valuable insights in different application scenarios. While many graph processing systems working on top of distributed infrastructures have been proposed to deal with big graphs, the tasks of profiling and debugging their massive computations remain time consuming and error-prone. This paper presents GiViP, a visual profiler for distributed graph processing systems based on a Pregel-like computation model. GiViP captures the huge amount of messages exchanged throughout a computation and provides an interactive user interface for the visual analysis of the collected data. We show how to take advantage of GiViP to detect anomalies related to the computation and to the infrastructure, such as slow computing units and anomalous message patterns.Comment: Appears in the Proceedings of the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

Neurons are MHC Class I-Dependent Targets for CD8 T Cells upon Neurotropic Viral Infection

Following infection of the central nervous system (CNS), the immune system is faced with the challenge of eliminating the pathogen without causing significant damage to neurons, which have limited capacities of renewal. In particular, it was thought that neurons were protected from direct attack by cytotoxic T lymphocytes (CTL) because they do not express major histocompatibility class I (MHC I) molecules, at least at steady state. To date, most of our current knowledge on the specifics of neuron-CTL interaction is based on studies artificially inducing MHC I expression on neurons, loading them with exogenous peptide and applying CTL clones or lines often differentiated in culture. Thus, much remains to be uncovered regarding the modalities of the interaction between infected neurons and antiviral CD8 T cells in the course of a natural disease. Here, we used the model of neuroinflammation caused by neurotropic Borna disease virus (BDV), in which virus-specific CTL have been demonstrated as the main immune effectors triggering disease. We tested the pathogenic properties of brain-isolated CD8 T cells against pure neuronal cultures infected with BDV. We observed that BDV infection of cortical neurons triggered a significant up regulation of MHC I molecules, rendering them susceptible to recognition by antiviral CTL, freshly isolated from the brains of acutely infected rats. Using real-time imaging, we analyzed the spatio-temporal relationships between neurons and CTL. Brain-isolated CTL exhibited a reduced mobility and established stable contacts with BDV-infected neurons, in an antigen- and MHC-dependent manner. This interaction induced rapid morphological changes of the neurons, without immediate killing or impairment of electrical activity. Early signs of neuronal apoptosis were detected only hours after this initial contact. Thus, our results show that infected neurons can be recognized efficiently by brain-isolated antiviral CD8 T cells and uncover the unusual modalities of CTL-induced neuronal damage

Borna disease virus (BDV) circulating immunocomplex positivity in addicted patients in the Czech Republic: a prospective cohort analysis

<p>Abstract</p> <p>Background</p> <p>Borna disease virus (BDV) is an RNA virus belonging to the family Bornaviridae. Borna disease virus is a neurotropic virus that causes changes in mood, behaviour and cognition. BDV causes persistent infection of the central nervous system. Immune changes lead to activation of infection. Alcohol and drug dependence are associated with immune impairment.</p> <p>Methods</p> <p>We examined the seropositivity of BDV circulating immunocomplexes (CIC) in patients with alcohol and drug dependence and healthy individuals (blood donors). We examined 41 addicted patients for the presence of BDV CIC in the serum by ELISA at the beginning of detoxification, and after eight weeks of abstinence. This is the first such study performed in patients with alcohol and drug dependence.</p> <p>Results</p> <p>BDV CIC positivity was detected in 36.59% of addicted patients on day 0 and in 42.86% on day 56. The control group was 37.3% positive. However, we did not detect higher BDV CIC positivity in addicted patients in comparison with blood donors (p = 0.179). The significantly higher level of BDV CIC was associated with lower levels of GGT (gamma glutamyl transferase) (p = 0.027) and approached statistical significance with the lower age of addicted patients (p = 0.064). We did not find any association between BDV CIC positivity and other anamnestic and demographic characteristics.</p> <p>Conclusions</p> <p>In our study addicted patients did not have significantly higher levels of BDV CIC than the control group. The highest levels of BDV CIC were detected in patients with lower levels of GGT and a lower age.</p> <p>Trial registration</p> <p>This study was approved by the ethical committee of the University Hospital Medical Faculty of Charles University in Pilsen, Czech Republic (registration number 303/2001).</p

Aerosols Transmit Prions to Immunocompetent and Immunodeficient Mice

Prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. However, prions are not generally considered to be airborne. Here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing PrPC, efficiently develop scrapie upon exposure to aerosolized prions. NSE-PrP transgenic mice, which express PrPC selectively in neurons, were also susceptible to airborne prions. Aerogenic infection occurred also in mice lacking B- and T-lymphocytes, NK-cells, follicular dendritic cells or complement components. Brains of diseased mice contained PrPSc and transmitted scrapie when inoculated into further mice. We conclude that aerogenic exposure to prions is very efficacious and can lead to direct invasion of neural pathways without an obligatory replicative phase in lymphoid organs. This previously unappreciated risk for airborne prion transmission may warrant re-thinking on prion biosafety guidelines in research and diagnostic laboratories

Modulation of NKp30- and NKp46-Mediated Natural Killer Cell Responses by Poxviral Hemagglutinin

Natural killer (NK) cells are an important element in the immune defense against the orthopox family members vaccinia virus (VV) and ectromelia virus (ECTV). NK cells are regulated through inhibitory and activating signaling receptors, the latter involving NKG2D and the natural cytotoxicity receptors (NCR), NKp46, NKp44 and NKp30. Here we report that VV infection results in an upregulation of ligand structures for NKp30 and NKp46 on infected cells, whereas the binding of NKp44 and NKG2D was not significantly affected. Likewise, infection with ectromelia virus (ECTV), the mousepox agent, enhanced binding of NKp30 and, to a lesser extent, NKp46. The hemagglutinin (HA) molecules from VV and ECTV, which are known virulence factors, were identified as novel ligands for NKp30 and NKp46. Using NK cells with selectively silenced NCR expression and NCR-CD3ζ reporter cells, we observed that HA present on the surface of VV-infected cells, or in the form of recombinant soluble protein, was able to block NKp30-triggered activation, whereas it stimulated the activation through NKp46. The net effect of this complex influence on NK cell activity resulted in a decreased NK lysis susceptibility of infected cells at late time points of VV infection when HA was expression was pronounced. We conclude that poxviral HA represents a conserved ligand of NCR, exerting a novel immune escape mechanism through its blocking effect on NKp30-mediated activation at a late stage of infection

The Open Anchoring Quest Dataset: Anchored Estimates from 96 Studies on Anchoring Effects

People’s estimates are biased toward previously considered numbers (anchoring). We have aggregated all available data from anchoring studies that included at least two anchors into one large dataset. Data were standardized to comprise one estimate per row, coded according to a wide range of variables, and are available for download and analyses online (https://metaanalyses.shinyapps.io/OpAQ/). Because the dataset includes both original and meta-data it allows for fine-grained analyses (e.g., correlations of estimates for different tasks) but also for meta-analyses (e.g., effect sizes for anchoring effects)