Analysis of genetic variation among accessions of critically endangered Rhaponticoides iconiensis and Rhaponticoides mykalea based on RAPD and SDSPAGE markers

Rhaponticoides iconiensis (Hub.-Mor.) M.V.Agab and Greuter is a rare and endangered endemic species of the Konya region of Turkey. One related taxon, Rhaponticoides mykalea (Hub.-Mor.) M.V.Agab andGreuter, is morphologically similar but occurs in different geographical locations. This study has been conducted on the biology of this threatened plant in order to understand better the factors that shouldbe included in the development of conservation practices. The genetic variations were studied using RAPD markers and SDS-PAGE profiles of total seed proteins for three R. iconiensis populations and two R. mykalea populations. The analyzed R. iconiensis populations belonged to different soil types (calcareous and volcanic). The analyzed R. iconiensis and R. mykalea populations belonged to different bioclimatic zones. A genetic diversity within populations was detected both by SDS-PAGE and RAPD for R. iconiensis populations. The level of variation did not differ with respect to soil type for the species studied. Populations collected from the same soil types carried more polymorphisms than those grown in different zones. The genetic diversity was revealed more clearly for all populations byRAPD than through analyzing proteins. Differentiation between ecological groups was higher than that revealed within groups. Conservation programs should take into account the level of genetic diversity within population revealed by these markers according to soil types

A generic testing framework for agent-based simulation models

International audienceAgent-based modelling and simulation (ABMS) had an increasing attention during the last decade. However, the weak validation and verification of agent-based simulation models makes ABMS hard to trust. There is no comprehensive tool set for verification and validation of agent-based simulation models, which demonstrates that inaccuracies exist and/or reveals the existing errors in the model. Moreover, on the practical side, many ABMS frameworks are in use. In this sense, we designed and developed a generic testing framework for agent-based simulation models to conduct validation and verification of models. This paper presents our testing framework in detail and demonstrates its effectiveness by showing its applicability on a realistic agent-based simulation case study

Verification of an agent-based disease model of human mycobacterium tuberculosis infection

Agent-Based Models are a powerful class of computational models widely used to simulate complex phenomena in many different application areas. However, one of the most critical aspects, poorly investigated in the literature, regards an important step of the model credibility assessment: solution verification. This study overcomes this limitation by proposing a general verification framework for Agent-Based Models that aims at evaluating the numerical errors associated with the model. A step-by-step procedure, which consists of two main verification studies (deterministic and stochastic model verification), is described in detail and applied to a specific mission critical scenario: the quantification of the numerical approximation error for UISS-TB, an ABM of the human immune system developed to predict the progression of pulmonary tuberculosis. Results provide indications on the possibility to use the proposed model verification workflow to systematically identify and quantify numerical approximation errors associated with UISS-TB and, in general, with any other ABMs

Prominent Plasmacytosis Following Intravenous Immunoglobulin Correlates with Clinical Improvement in Guillain-Barré Syndrome

BACKGROUND: High doses of pooled polyclonal IgG are commonly used to treat numerous autoimmune diseases. Their mode of action nevertheless remains only partially explained. At the same time, until now, no early biological marker has been able to predict their efficacy. METHODOLOGY/PRINCIPAL FINDINGS: In a first pilot retrospective analysis, we reviewed white blood cell counts and blood smears in consecutive patients with autoimmune disease (n = 202) and non-autoimmune disease (n = 104). Autoimmune patients received either intravenous immunoglobulin (IVIg, n = 103), plasma exchange (n = 78) or no specific treatment (n = 21). We then prospectively monitored consecutive autoimmune patients with IVIg injection (n = 67), or without any specific treatment (n = 10) using the same routine laboratory tests, as well as flow cytometry. Both retrospective and prospective analyses identified large plasma-cell mobilization exclusively in IVIg-treated autoimmune patients 7 days after initiation of treatment. The majority of IVIg-mobilized plasma cells were immature HLA-DR(high)/CD138(low)/CXCR4(low) plasma cells expressing intracellular immunoglobulin G which were neither IVIg- nor human IgG-specific. Importantly, we found a strong negative correlation between the absolute number of IVIg-mobilized plasma cells and time to improve neurological function in both retrospective and prospective studies of Guillain-Barré syndrome (GBS), (r = -0.52, p = 0.0031, n = 30, r = -0.47, p = 0.0028, n = 40, respectively). CONCLUSIONS/SIGNIFICANCE: IVIg promotes immature plasma-cell mobilization in patients with GBS, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis and inflammatory myopathy. Prominent day 7 plasma-cell mobilization is a favourable prognostic marker in patients with GBS receiving IVIg treatment

Cross-reactive CD4+ T cells enhance SARS-CoV-2 immune responses upon infection and vaccination

The functional relevance of pre-existing cross-immunity to SARS-CoV-2 is a subject of intense debate. Here, we show that human endemic coronavirus (HCoV)-reactive and SARS-CoV-2-cross-reactive CD4+ T cells are ubiquitous but decrease with age. We identified a universal immunodominant coronavirus-specific spike peptide (S816-830) and demonstrate that pre-existing spike- and S816-830-reactive T cells were recruited into immune responses to SARS-CoV-2 infection and their frequency correlated with anti-SARS-CoV-2-S1-IgG antibodies. Spike-cross-reactive T cells were also activated after primary BNT162b2 COVID-19 mRNA vaccination displaying kinetics similar to secondary immune responses. Our results highlight the functional contribution of pre-existing spike-cross-reactive T cells in SARS-CoV-2 infection and vaccination. Cross-reactive immunity may account for the unexpectedly rapid induction of immunity following primary SARS-CoV-2 immunization and the high rate of asymptomatic/mild COVID-19 disease courses