A Role for the Measles Virus in Oncology

An association between the measles virus (MV) and classic Hodgkin lymphoma (CHL) was reported by our center in Beer-Sheva, starting in 2003. Our basic evidence on the relationship had been established by immunohistochemistry, using several commercial and specific experimental anti-measles antibodies in about 50% of our patients. It relied also on the reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH) of MV RNA, and overall, was essentially descriptive. The first and only response to our thesis was advanced in 2007 in doublet articles, in a single issue of a Cancer Journal. Our conclusions were hereby dismissed. Since reservations relating the above refutation seemed self-evident, the subsequent publication of several of our articles was launched. They disclosed evidence of an association of the MV with further categories of cancers, as well as its absence in some distinct tumors. A mechanism by which the MV may regulate apoptosis in the tumor cells of CHL was also proposed. A suspected role for the MV in oncomodulation is advocated. We deplore, however, the absence of further interest in our hypothesis among world experts

French Roadmap for complex Systems 2008-2009

This second issue of the French Complex Systems Roadmap is the outcome of the Entretiens de Cargese 2008, an interdisciplinary brainstorming session organized over one week in 2008, jointly by RNSC, ISC-PIF and IXXI. It capitalizes on the first roadmap and gathers contributions of more than 70 scientists from major French institutions. The aim of this roadmap is to foster the coordination of the complex systems community on focused topics and questions, as well as to present contributions and challenges in the complex systems sciences and complexity science to the public, political and industrial spheres

Australia: A Continent Without Native Powdery Mildews? The First Comprehensive Catalog Indicates Recent Introductions and Multiple Host Range Expansion Events, and Leads to the Re-discovery of Salmonomyces as a New Lineage of the Erysiphales

In contrast to Eurasia and North America, powdery mildews (Ascomycota, Erysiphales) are understudied in Australia. There are over 900 species known globally, with fewer than currently 60 recorded from Australia. Some of the Australian records are doubtful as the identifications were presumptive, being based on host plant-pathogen lists from overseas. The goal of this study was to provide the first comprehensive catalog of all powdery mildew species present in Australia. The project resulted in (i) an up-to-date list of all the taxa that have been identified in Australia based on published DNA barcode sequences prior to this study; (ii) the precise identification of 117 specimens freshly collected from across the country; and (iii) the precise identification of 30 herbarium specimens collected between 1975 and 2013. This study confirmed 42 species representing 10 genera, including two genera and 13 species recorded for the first time in Australia. In Eurasia and North America, the number of powdery mildew species is much higher. Phylogenetic analyses of powdery mildews collected from Acalypha spp. resulted in the transfer of Erysiphe acalyphae to Salmonomyces, a resurrected genus. Salmonomyces acalyphae comb. nov. represents a newly discovered lineage of the Erysiphales. Another taxonomic change is the transfer of Oidium ixodiae to Golovinomyces. Powdery mildew infections have been confirmed on 13 native Australian plant species in the genera Acacia, Acalypha, Cephalotus, Convolvulus, Eucalyptus, Hardenbergia, Ixodia, Jagera, Senecio, and Trema. Most of the causal agents were polyphagous species that infect many other host plants both overseas and in Australia. All powdery mildews infecting native plants in Australia were phylogenetically closely related to species known overseas. The data indicate that Australia is a continent without native powdery mildews, and most, if not all, species have been introduced since the European colonization of the continent

Bayesian Modelling of Induced Responses and Neuronal Rhythms

Neural rhythms or oscillations are ubiquitous in neuroimaging data. These spectral responses have been linked to several cognitive processes; including working memory, attention, perceptual binding and neuronal coordination. In this paper, we show how Bayesian methods can be used to finesse the ill-posed problem of reconstructing-and explaining-oscillatory responses. We offer an overview of recent developments in this field, focusing on (i) the use of MEG data and Empirical Bayes to build hierarchical models for group analyses-and the identification of important sources of inter-subject variability and (ii) the construction of novel dynamic causal models of intralaminar recordings to explain layer-specific activity. We hope to show that electrophysiological measurements contain much more spatial information than is often thought: on the one hand, the dynamic causal modelling of non-invasive (low spatial resolution) electrophysiology can afford sub-millimetre (hyper-acute) resolution that is limited only by the (spatial) complexity of the underlying (dynamic causal) forward model. On the other hand, invasive microelectrode recordings (that penetrate different cortical layers) can reveal laminar-specific responses and elucidate hierarchical message passing and information processing within and between cortical regions at a macroscopic scale. In short, the careful and biophysically grounded modelling of sparse data enables one to characterise the neuronal architectures generating oscillations in a remarkable detail

Keep it complex! Prodi’s curse and the EU fiscal governance regime complex

The EU fiscal framework has gradually morphed into a regional regime complex through various reforms of the preventive and corrective arms of the Stability and Growth Pact. A regime complex encourages actors to arbitrage between partially overlapping, parallel and nested rules. By drawing on this central insight, this article demonstrates that regime complexity enables member states to respect the letter but not the spirit of the fiscal rules to lower the cost of compliance. It further shows empirically how regime complexity weakens technocratic enforcement capacity when authority is dispersed across multiple levels of governance by focusing on the example of the general escape clauses during the coronavirus pandemic

Dynamic Influence Networks for Rule-based Models

We introduce the Dynamic Influence Network (DIN), a novel visual analytics technique for representing and analyzing rule-based models of protein-protein interaction networks. Rule-based modeling has proved instrumental in developing biological models that are concise, comprehensible, easily extensible, and that mitigate the combinatorial complexity of multi-state and multi-component biological molecules. Our technique visualizes the dynamics of these rules as they evolve over time. Using the data produced by KaSim, an open source stochastic simulator of rule-based models written in the Kappa language, DINs provide a node-link diagram that represents the influence that each rule has on the other rules. That is, rather than representing individual biological components or types, we instead represent the rules about them (as nodes) and the current influence of these rules (as links). Using our interactive DIN-Viz software tool, researchers are able to query this dynamic network to find meaningful patterns about biological processes, and to identify salient aspects of complex rule-based models. To evaluate the effectiveness of our approach, we investigate a simulation of a circadian clock model that illustrates the oscillatory behavior of the KaiC protein phosphorylation cycle.Comment: Accepted to TVCG, in pres

NK cells in patients undergoing allogeneic stem cell transplantation are influenced by the CMV UL40 gene polymorphism

Natural Killer cells are large granular lymphocytes which take an important role in the immune control of cells with viral infection, mutations or cells coated with antibodies. Traditionally NK cells were believed to be part of the innate immune system. Over the last years, however, it has been shown that NK cells possess adaptive features as well. In humans NK cells with those adaptive features have been described in persons with a positive CMV-serostatus. Furthermore NK cells play an important role in patients undergoing allogeneic stem cell transplantation, most importantly for the control of infections and protection from relapse. With CMV and NK cells both playing an important in allogenic stem cell transplantation, this model seems to be perfect to study the impact of CMV on the generation of adaptive NK cells as well as the clinical impact of adaptive NK cells. We studied the NK cell-CMV interaction with the use of adaptive NK cells derived from CMV-seropositive blood donors and in patients with CMV reactivation after allogeneic stem cell transplantation. Adaptive NK cells derived from CMV-seropositive donors showed a specific tuning of ex vivo effector functions by virus-derived peptides. By sequencing of the CMV UL40 gene in patients with CMV reactivation we could derive the respective peptide encoded for during CMV reactivation. In those patients with CMV-reactivation we were able to show that the generation of certain NK cell populations expressing the NKG2C-receptor is influenced by the CMV-peptide polymorphism. For example the change of one amino acid (VMAPRTLIL to VMAPRTLFL) was able to trigger a difference in the generation of NK cell populations with FACS-defined cell profiles. Adaptive NK cells have strong effector functions and are thereby be thought to have anti-leukemia functions as well. The link of adaptive NK cells to a better clinical outcome after allogeneic stem cell has been suggested by some investigators. Even though our data, because of the small sample size, just give a hint into this direction, the therapeutic use of adaptive NK cells in patients with hematologic malignancy could certainly play an important role in the future.Natürliche Killerzellen sind große granuläre Lymphozyten welche eine wichtige Rolle in der Immunantwort auf Zellen mit Virusinfektion, Mutationen oder antikörper-bedeckte Zellen besitzen. Typischerweise werden NK-Zellen dem angeborenen Immunsystem zugeschrieben. In den letzten Jahren hat sich allerdings herausgestellt, dass NK-Zellen auch adaptive Eigenschaften besitzen. In Menschen sind adaptive NK-Zellen vor allen Dingen in Personen mit positivem CMV-Serostatus beschrieben worden. NK-Zellen spielen außerdem eine wichtige Rolle in Patienten welche eine allogene Stammzelltransplantation erhalten, vor allem zum Schutz vor Infektionen und einem Rezidiv der Grunderkrankung. Da sowohl CMV als auch NK-Zellen eine wichtige Rolle in der allogenen Stammzelltransplantation spielen, eignet sich diese als gutes Modell zur Untersuchung des Einflussen von CMV auf die Generation von adaptiven NK-Zellen, als auch zur Untersuchung der klinischen Relevanz adaptiver NK-Zellen. Wir haben die NK-Zell-CMV-Interaktion mithilfe von adaptiven NK-Zellen von gesunden CMV-seropostivien Blutspendern und innerhalb von Patienten mit CMV-Reaktivierung nach Stammzelltransplantation untersucht. Adaptive NK-Zellen von CMV-seropositiven Spendern zeigten dabei eine präzise Regulierung ihrer Effektor-Aktivitäten durch spezifische Virus-Peptide. Durch die Sequenzierung des CMV UL40-Gens in Patienten mit CMV-Reaktivierung konnten wir auf das jeweilig enkodierte Peptid während CMV-Reaktivierung rückschließen. In dieser Patientenkohorte mit CMV-Reaktivierung konnten wir zeigen, dass die Generation spezifischer NKG2C-positiver NK-Zell-Populationen durch den CMV-Polymorphismus beeinflusst wird. Zum Beispiel konnte der Austausch von nur einer Aminosäure (VMAPRTLIL zu VMAPRTLFL) eine unterschiedliche Generation von NK-Zell-Populationen, definiert durch das durchflusszytometrische Zell-Profil, verursachen. Adaptive NK-Zellen haben starke Effektor-Funktionen, weswegen ihnen auch anti-Leukämie-Effekte zugeschrieben werden. Die Korrelation von adaptiven NK-Zellen mit klinischen Variablen nach allogener Stammzelltransplantation ist von verschiedenen Autoren beschrieben worden. Auch wenn unsere Daten, vor allem aufgrund der kleinen Probenzahl, nur einen kleinen Hinweis in diese Richtung geben, könnte die therapeutische Nutzung von adaptiven NK-Zellen in Patienten mit hämatologischer Grunderkrankung in Zukunft sicherlich eine wichtige Rolle spielen

Field-control, phase-transitions, and life's emergence

Instances of critical-like characteristics in living systems at each organizational level as well as the spontaneous emergence of computation (Langton), indicate the relevance of self-organized criticality (SOC). But extrapolating complex bio-systems to life's origins, brings up a paradox: how could simple organics--lacking the 'soft matter' response properties of today's bio-molecules--have dissipated energy from primordial reactions in a controlled manner for their 'ordering'? Nevertheless, a causal link of life's macroscopic irreversible dynamics to the microscopic reversible laws of statistical mechanics is indicated via the 'functional-takeover' of a soft magnetic scaffold by organics (c.f. Cairns-Smith's 'crystal-scaffold'). A field-controlled structure offers a mechanism for bootstrapping--bottom-up assembly with top-down control: its super-paramagnetic components obey reversible dynamics, but its dissipation of H-field energy for aggregation breaks time-reversal symmetry. The responsive adjustments of the controlled (host) mineral system to environmental changes would bring about mutual coupling between random organic sets supported by it; here the generation of long-range correlations within organic (guest) networks could include SOC-like mechanisms. And, such cooperative adjustments enable the selection of the functional configuration by altering the inorganic network's capacity to assist a spontaneous process. A non-equilibrium dynamics could now drive the kinetically-oriented system towards a series of phase-transitions with appropriate organic replacements 'taking-over' its functions.Comment: 54 pages, pdf fil