Immune modulation and prevention of autoimmune disease by repeated sequences from parasites linked to self antigens

Parasite proteins containing repeats are essential invasion ligands, important for their ability to evade the host immune system and to induce immunosuppression. Here, the intrinsic suppressive potential of repetitive structures within parasite proteins was exploited to induce immunomodulation in order to establish self-tolerance in an animal model of autoimmune neurological disease. We tested the tolerogenic potential of fusion proteins containing repeat sequences of parasites linked to self-antigens. The fusion constructs consist of a recombinant protein containing repeat sequences derived from the S-antigen protein (SAg) of Plasmodium falciparum linked to a CD4 T cell epitope of myelin. They were tested for their efficacy to control the development of experimental autoimmune encephalomyelitis (EAE), In addition, we used the DO11.10 transgenic mouse model to study the immune mechanisms involved in tolerance induced by SAg fusion proteins. We found that repeated sequences of P. falciparum SAg protein linked to self-epitopes markedly protected mice from EAE. These fusion constructs were powerful tolerizing agents not only in a preventive setting but also in the treatment of ongoing disease. The tolerogenic effect was shown to be antigen-specific and strongly dependent on the physical linkage of the T cell epitope to the parasite structure and on the action of anti-inflammatory cytokines like IL-10 and TGF-{beta}. Other mechanisms include down-regulation of TNF-{alpha} accompanied by increased numbers of FoxP3(+) cells. This study describes the use of repetitive structures from parasites linked to defined T cell epitopes as an effective method to induce antigen-specific tolerance with potential applicability for the treatment and prevention of autoimmune diseases

The CHARME "Advanced Big Data Training School for Life Sciences": an example of good practices for training on current bioinformatics challenges

The CHARME “Advanced Big Data Training School for Life Sciences” took place during 3-7 September 2018, at the Campus Nord of the Technical University of Catalonia (UPC) in Barcelona (ES). The school was organised by the Data Management Group (DAMA) of the UPC in collaboration with EMBnet as a follow-up of the first CHARME-EMBnet “Big Data Training School for Life Sciences”, held in Uppsala, Sweden, in September 2017. The learning objectives of the school were defined and agreed during the CHARME “Think Tank Hackathon” that was held in Ljubljana, Slovenia, in February 2018. This article explains in detail the step forward organisation of the training school, the covered contents and the interaction/relationships that thanks to this school have been established between the trainees, the trainers and the organisers.Peer ReviewedPostprint (published version

Proceedings of the “Think Tank Hackathon’’, Big Data Training School for Life Sciences Follow-up, Ljubljana 6th – 7th February 2018

On 6th and 7th February 2018, a Think Tank took place in Ljubljana, Slovenia. It was a follow-up of the “Big Data Training School for Life Sciences” held in Uppsala, Sweden, in September 2017. The focus was on identifying topics of interest and optimising the programme for a forthcoming “Advanced” Big Data Training School for Life Science, that we hope is again supported by the COST Action CHARME (Harmonising standardisation strategies to increase efficiency and competitiveness of European life-science research - CA15110). The Think Tank aimed to go into details of several topics that were - to a degree - covered by the former training school. Likewise, discussions embraced the recent experience of the attendees in light of the new knowledge obtained by the first edition of the training school and how it comes from the perspective of their current and upcoming work. The 2018 training school should strive for and further facilitate optimised applications of Big Data technologies in life sciences. The attendees of this hackathon entirely organised this workshop.Peer ReviewedPostprint (published version

β-Hydroxy-β-Methylbutyrate Supplementation Promotes Antitumor Immunity in an Obesity Responsive Mouse Model of Pancreatic Ductal Adenocarcinoma

Pancreatic cancer (PDAC) is a deadly disease, exacerbated by obesity, which lacks effective therapeutic interventions. Most PDAC has a limited response to immune- and chemotherapy. Treating PDAC is made additionally challenging by the rapid emergence of muscle wasting and cachexia, which predict poor response to several therapies. We have found that dietary supplementation with β-hydroxy-β-methylbutyrate promotes immunosurveillance in PDAC tumors and protects muscle. This dietary supplement has the potential to be an important adjuvant in PDAC therapy, opening the doors to immunotherapy response

Research Notes : United States : Superoxide dismutase (SOD) in soybean

We are using vertical polyacrylamide gel electrophoresis (Davis, 1964) and a staining system modified after Beauchamp and Fridovich (1971) to study superoxide dismutase polymorphisms in the subgenus soja. This staining system generates superoxide radical; hence, it is specific for SOD activity. We re-solve up to 9 SOD bands in dry or germinating soybean cotyledons, and in leaves

Overview of the Nordic Seas CARINA data and salinity measurements

Water column data of carbon and carbon relevant hydrographic and hydrochemical parameters from 188 previously non-publicly available cruises in the Arctic, Atlantic, and Southern Ocean have been retrieved and merged into a new database: CARINA (CARbon IN the Atlantic). The data have been subject to rigorous quality control (QC) in order to ensure highest possible quality and consistency. The data for most of the parameters included were examined in order to quantify systematic biases in the reported values, i.e. secondary quality control. Significant biases have been corrected for in the data products, i.e. the three merged files with measured, calculated and interpolated values for each of the three CARINA regions; the Arctic Mediterranean Seas (AMS), the Atlantic (ATL) and the Southern Ocean (SO). With the adjustments the CARINA database is consistent both internally as well as with GLODAP (Key et al., 2004) and is suitable for accurate assessments of, for example, oceanic carbon inventories and uptake rates and for model validation. The Arctic Mediterranean Seas include the Arctic Ocean and the Nordic Seas, and the quality control was carried out separately in these two areas. This contribution provides an overview of the CARINA data from the Nordic Seas and summarises the findings of the QC of the salinity data. One cruise had salinity data that were of questionable quality, and these have been removed from the data product. An evaluation of the consistency of the quality controlled salinity data suggests that they are consistent to at least ±0.005

A cross-sectional survey to evaluate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination among European travellers to resource-limited destinations

BACKGROUND: Influenza is one of the most common vaccine-preventable diseases in travellers. By performing two cross-sectional questionnaire surveys during winter 2009 and winter 2010 among European travellers to resource-limited destinations, we aimed to investigate knowledge, attitudes and practices (KAP) regarding seasonal influenza vaccination. METHODS: Questionnaires were distributed in the waiting room to the visitors of the University of Zurich Centre for Travel' Health (CTH) in January and February 2009 and January 2010 prior to travel health counselling (CTH09 and CTH10). Questions included demographic data, travel-related characteristics and KAP regarding influenza vaccination. Data were analysed by using SPSS version 14.0 for Windows. Differences in proportions were compared using the Chi-square test and the significance level was set at p 64 yrs (25, 21%) and recommendations of the family physician (27, 22.7%) were the most often reported reasons for being vaccinated. In the multiple logistic regression analyses of the pooled data increasing age (OR = 1.03, 95% CI 1.01 - 1.04), a business trip (OR = 0.39, 95% CI 0.17 - 0.92) and seasonal influenza vaccination in the previous winter seasons (OR = 12.91, 95% CI 8.09 - 20.58) were independent predictors for seasonal influenza vaccination in 2009 or 2010.Influenza vaccination recommended by the family doctor (327, 37.7%), travel to regions with known high risk of influenza (305, 35.1%), and influenza vaccination required for job purposes (233, 26.8%) were most frequently mentioned to consider influenza vaccination. CONCLUSIONS: Risk perception and vaccination coverage concerning seasonal and pandemic influenza was very poor among travellers to resource-limited destinations when compared to traditional at-risk groups. Previous access to influenza vaccination substantially facilitated vaccinations in the subsequent year. Information strategies about influenza should be intensified and include health professionals, e.g. family physicians, travel medicine practitioners and business enterprises

The Self-Administered Witness Interview Tool (SAW-IT): Enhancing witness recall of workplace incidents

Given the often crucial role of witness evidence in Occupational Health and Safety investigation, statements should be obtained as soon as possible after an incident using best practice methods. The present research systematically tested the efficacy of a novel Self-Administered Witness Interview Tool (SAW-IT); an adapted version of the Self-Administered Interview (SAI©) designed to elicit comprehensive information from witnesses to industrial events. The present study also examined whether completing the SAW-IT mitigated the effect of schematic processing on witness recall. Results indicate that the SAW-IT elicited significantly more correct details, as well as more precise information than a traditional incident report form. Neither the traditional report from, nor the SAW-IT mitigated against biasing effects of contextual information about a worker’s safety history, confirming that witnesses should be shielded from extraneous post-event information prior to reporting. Importantly, these results demonstrate that the SAW-IT can enhance the quality of witness reports

The P_33(1232) resonance contribution into the amplitudes M_{1+}^{3/2},E_{1+}^{3/2},S_{1+}^{3/2} from an analysis of the p(e,e'p)\pi^0 data at Q^2 = 2.8, 3.2, and 4 (GeV/c)^2 within dispersion relation approach

Within the fixed-t dispersion relation approach we have analysed the TJNAF and DESY data on the exclusive p(e,e'p)\pi^0 reaction in order to find the P_{33}(1232) resonance contribution into the multipole amplitudes M_{1+}^{3/2},E_{1+}^{3/2},S_{1+}^{3/2}. As an input for the resonance and nonresonance contributions into these amplitudes the earlier obtained solutions of the integral equations which follow from dispersion relations are used. The obtained values of the ratio E2/M1 for the \gamma^* N \to P_{33}(1232) transition are: 0.039\pm 0.029, 0.121\pm 0.032, 0.04\pm 0.031 for Q^2= 2.8, 3.2, and 4 (GeV/c)^2, respectively. The comparison with the data at low Q^2 shows that there is no evidence for the presence of the visible pQCD contribution into the transition \gamma N \to P_{33}(1232) at Q^2=3-4 GeV^2. The ratio S_{1+}^{3/2}/M_{1+}^{3/2} for the resonance parts of multipoles is: -0.049\pm 0.029, -0.099\pm 0.041, -0.085\pm 0.021 for Q^2= 2.8, 3.2, and 4 (GeV/c)^2, respectively. Our results for the transverse form factor G_T(Q^2) of the \gamma^* N \to P_{33}(1232) transition are lower than the values obtained from the inclusive data. With increasing Q^2, Q^4G_T(Q^2) decreases, so there is no evidence for the presence of the pQCD contribution here too

Low-Energy Compton Scattering of Polarized Photons on Polarized Nucleons

The general structure of the cross section of $\gamma N$ scattering with polarized photon and/or nucleon in initial and/or final state is systematically described and exposed through invariant amplitudes. A low-energy expansion of the cross section up to and including terms of order $\omega^4$ is given which involves ten structure parameters of the nucleon (dipole, quadrupole, dispersion, and spin polarizabilities). Their physical meaning is discussed in detail. Using fixed-t dispersion relations, predictions for these parameters are obtained and compared with results of chiral perturbation theory. It is emphasized that Compton scattering experiments at large angles can fix the most uncertain of these structure parameters. Predictions for the cross section and double-polarization asymmetries are given and the convergence of the expansion is investigated. The feasibility of the experimental determination of some of the struture parameters is discussed.Comment: 41 pages of text, 9 figures; minor revisions prior to publication in Phys. Rev.