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Braza F.,Instituto Gulbenkian Of Cincia | Brouard S.,Nantes University Hospital Center | Chadban S.,Royal Prince Alfred Hospital | Chadban S.,University of Sydney | Goldstein D.R.,Yale University
Nature Reviews Nephrology | Year: 2016

Graft inflammation impairs the induction of solid organ transplant tolerance and enhances acute and chronic rejection. Elucidating the mechanisms by which inflammation is induced after organ transplantation could lead to novel therapeutics to improve transplant outcomes. In this Review we describe endogenous substances-damage-associated molecular patterns (DAMPs)-that are released after allograft reperfusion and induce inflammation. We also describe innate immune signalling pathways that are activated after solid organ transplantation, with a focus on Toll-like receptors (TLRs) and their signal adaptor, MYD88. Experimental and clinical studies have yielded a large body of evidence that TLRs and MYD88 are instrumental in initiating allograft inflammation and promoting the development of acute and chronic rejection. Ongoing clinical studies are testing TLR inhibition strategies in solid organ transplantation, although avoiding compromising host defence to pathogens is a key challenge. Further elucidation of the mechanisms by which sterile inflammation is induced, maintained and amplified within the allograft has the potential to lead to novel anti-inflammatory treatments that could improve outcomes for solid organ transplant recipients. © 2016 Macmillan Publishers Limited.


Cantarelli P.,French Institute of Health and Medical Research | Cantarelli P.,Paris-Sorbonne University | Cantarelli P.,University of Milan | Debin M.,French Institute of Health and Medical Research | And 29 more authors.
BMC Public Health | Year: 2014

Background: The Internet is becoming more commonly used as a tool for disease surveillance. Similarly to other surveillance systems and to studies using online data collection, Internet-based surveillance will have biases in participation, affecting the generalizability of the results. Here we quantify the participation biases of Influenzanet, an ongoing European-wide network of Internet-based participatory surveillance systems for influenza-like-illness. Methods. In 2011/2012 Influenzanet launched a standardized common framework for data collection applied to seven European countries. Influenzanet participants were compared to the general population of the participating countries to assess the representativeness of the sample in terms of a set of demographic, geographic, socio-economic and health indicators. Results: More than 30,000 European residents registered to the system in the 2011/2012 season, and a subset of 25,481 participants were selected for this study. All age classes (10 years brackets) were represented in the cohort, including under 10 and over 70 years old. The Influenzanet population was not representative of the general population in terms of age distribution, underrepresenting the youngest and oldest age classes. The gender imbalance differed between countries. A counterbalance between gender-specific information-seeking behavior (more prominent in women) and Internet usage (with higher rates in male populations) may be at the origin of this difference. Once adjusted by demographic indicators, a similar propensity to commute was observed for each country, and the same top three transportation modes were used for six countries out of seven. Smokers were underrepresented in the majority of countries, as were individuals with diabetes; the representativeness of asthma prevalence and vaccination coverage for 65+ individuals in two successive seasons (2010/2011 and 2011/2012) varied between countries. Conclusions: Existing demographic and national datasets allowed the quantification of the participation biases of a large cohort for influenza-like-illness surveillance in the general population. Significant differences were found between Influenzanet participants and the general population. The quantified biases need to be taken into account in the analysis of Influenzanet epidemiological studies and provide indications on populations groups that should be targeted in recruitment efforts. © 2014 Cantarelli et al.; licensee BioMed Central Ltd.


Thornhill J.A.,University of Glasgow | McVeigh P.,Queen's University of Belfast | Jurberg A.D.,Instituto Gulbenkian Of Cincia | Kusel J.R.,University of Glasgow
Parasitology | Year: 2010

It has been observed that fluorescent membrane-impermeant molecules can enter the cercariae as they penetrate mouse skin. The hypothesis to be tested was that such molecules, which included Lucifer Yellow and a variety of fluorescent dextrans, entered the parasite through the nephridiopore and excretory tubules as well as through the surface membrane. FITC-labelled poly-L-lysine (molecular weight 10 kDa), added at 4C during syringe transformation, was found to enter the nephridiopore and labelled the excretory bladder and sometimes the excretory tubules. This finding indicates that macromolecules (10 kDa) can enter the nephridiopore. It was found that linoleic acid (a normal constituent of skin) greatly stimulated uptake of Lucifer Yellow and dextrans into the excretory/subtegumental region of 2-h-old schistosomula. This correlated with an increased uptake of membrane-impermeant propidium iodide at 37C. Since increased uptake of propidium iodide occurs when membranes become permeable, the surface membrane could also be a pathway of transport of the membrane-impermeant molecules into the schistosomulum. © 2010 Cambridge University Press.


Bajardi P.,University of Turin | Bajardi P.,ISI Foundation | Paolotti D.,ISI Foundation | Vespignani A.,ISI Foundation | And 22 more authors.
PLoS ONE | Year: 2014

Internet-based systems for epidemiological studies have advantages over traditional approaches as they can potentially recruit and monitor a wider range of individuals in a relatively inexpensive fashion. We studied the association between communication strategies used for recruitment (offline, online, face-to-face) and follow-up participation in nine Internet-based cohorts: the Influenzanet network of platforms for influenza surveillance which includes seven cohorts in seven different European countries, the Italian birth cohort Ninfea and the New Zealand birth cohort ELF. Follow-up participation varied from 43% to 89% depending on the cohort. Although there were heterogeneities among studies, participants who became aware of the study through an online communication campaign compared with those through traditional offline media seemed to have a lower follow-up participation in 8 out of 9 cohorts. There were no clear differences in participation between participants enrolled face-to-face and those enrolled through other offline strategies. An Internet-based campaign for Internet-based epidemiological studies seems to be less effective than an offline one in enrolling volunteers who keep participating in follow-up questionnaires. This suggests that even for Internet-based epidemiological studies an offline enrollment campaign would be helpful in order to achieve a higher participation proportion and limit the cohort attrition.


Faustino L.,University of Sao Paulo | Mucida D.,Rockefeller University | Keller A.C.,University Federal Of So Paulo | Demengeot J.,Instituto Gulbenkian Of Cincia | And 6 more authors.
Clinical and Developmental Immunology | Year: 2012

Foxp3 +CD25 +CD4 + regulatory T cells are vital for peripheral tolerance and control of tissue inflammation. In this study, we characterized the phenotype and monitored the migration and activity of regulatory T cells present in the airways of allergic or tolerant mice after allergen challenge. To induce lung allergic inflammation, mice were sensitized twice with ovalbumin/aluminum hydroxide gel and challenged twice with intranasal ovalbumin. Tolerance was induced by oral administration of ovalbumin for 5 consecutive days prior to OVA sensitization and challenge. We detected regulatory T cells (Foxp3 +CD25 +CD4 + T cells) in the airways of allergic and tolerant mice; however, the number of regulatory T cells was more than 40-fold higher in allergic mice than in tolerant mice. Lung regulatory T cells expressed an effector/memory phenotype (CCR4(high)CD62L(low) CD44(high)CD54(high)CD69 +) that distinguished them from naive regulatory T cells (CCR4(int)CD62L(high)CD44(int)CD54(int)CD69 -). These regulatory T cells efficiently suppressed pulmonary T-cell proliferation but not Th2 cytokine production. Copyright © 2012 Lucas Faustino et al.


Pacheco P.R.,Hospital of Divino Espirito Santo of Ponta Delgada | Pacheco P.R.,Instituto Gulbenkian Of Cincia | Branco C.C.,Hospital of Divino Espirito Santo of Ponta Delgada | Branco C.C.,Instituto Gulbenkian Of Cincia | And 5 more authors.
BMC Research Notes | Year: 2010

Background: Human leukocyte antigen (HLA) genes are characterized by high levels of polymorphism and linkage disequilibrium (LD), important characteristics to study the genetic background of human populations and their genetic structure. Here, we analyse the allele distribution and LD extent of HLA class I and II in So Miguel Island population (Azores archipelago, Portugal). Findings: The sample set was composed of 106 healthy blood donors living in So Miguel Island obtained from the anonymized Azorean DNA bank. HLA class I (-A,-B and-Cw) and class II (-DRB1,-DQB1,-DPA1 and-DPB1) genotyping was performed by PCR-SSP Olerup SSP™ (GenoVision Inc.), according to the manufacturer's instructions. Genetic diversity values, based on the 7 loci, ranged from 0.821 both for HLA-DPA1 and-DQB1 to 0.934 for HLA-B, with a mean value of 0.846. Analysis of 5 HLA-A-Cw-B-DRB1-DQB1 haplotypes revealed that A*01- Cw*07-B*08-DRB1*03-DQB1*02 is the most frequent in So Miguel (7.9%) followed by A*24-B*08-Cw*07-DRB1*03- DQB1*02 (3.8%). In addition, even though the reports of high LD for HLA markers in worldwide populations, So Miguel islanders do not have extensive LD (average D' = 0.285). Conclusions: In summary, the results demonstrate high variability of HLA in So Miguel Island population as well as absence of genetic structure and extensive LD. The data here presented suggest that in So Miguel islanders autoimmune diseases studies will necessarily encompass a more focused analysis of HLA extended haplotypes as well as the evaluation of other non-HLA candidate genes. © 2010 Mota-Vieira et al; licensee BioMed Central Ltd.


Schneider N.,University of Veterinary Medicine Hannover | Chikhi L.,CNRS Biological Evolution and Diversity Laboratory | Chikhi L.,Toulouse 1 University Capitole | Chikhi L.,Instituto Gulbenkian Of Cincia | And 2 more authors.
BMC Evolutionary Biology | Year: 2010

Background. Pleistocene events have shaped the phylogeography of many taxa worldwide. Their genetic signatures in tropical species have been much less explored than in those living in temperate regions. We analysed the genetic structure of a Malagasy primate species, a mouse lemur with a wide distribution (M. murinus), in order to investigate such phylogeographic processes on a large tropical island. We also evaluated the effects of anthropogenic pressures (fragmentation/deforestation) and natural features (geographic distance, rivers) on genetic structure in order to complement our understanding of past and present processes of genetic differentiation. Results. The analysis of the mitochondrial D-loop sequences of 195 samples from 15 study sites (10 from a continuous forest and five from isolated forest fragments) from two adjacent Inter-River-Systems (IRSs) revealed that forest fragmentation and the river restrict gene flow, thereby leading to an increased genetic differentiation between populations beyond the effect of isolation-by-distance. Demographic simulations detected signals of two successive spatial expansions that could be preliminarily dated to the late Pleistocene and early Holocene. The haplotype network revealed geographic structure and showed deep molecular divergences within and between the IRSs that would be congruent with a two-step colonization scenario. Conclusions. This study supports the hypothesis of a relatively recent spatial expansion of the grey mouse lemur in northwestern Madagascar, which may also explain why this taxon, in contrast to its congeners, has not yet undergone allopatric speciation in the studied area and possibly across its presently wide range. © 2010 Schneider et al; licensee BioMed Central Ltd.


Brito P.H.,Instituto Gulbenkian Of Cincia | Guilherme E.,Instituto Gulbenkian Of Cincia | Soares H.,Instituto Gulbenkian Of Cincia | Soares H.,University of Lisbon | And 2 more authors.
BMC Evolutionary Biology | Year: 2010

Background. The rate and fitness effects of mutations are key in understanding the evolution of every species. Traditionally, these parameters are estimated in mutation accumulation experiments where replicate lines are propagated in conditions that allow mutations to randomly accumulate without the purging effect of natural selection. These experiments have been performed with many model organisms but we still lack empirical estimates of the rate and effects of mutation in the protists. Results. We performed a mutation accumulation (MA) experiment in Tetrahymena thermophila, a species that can reproduce sexually and asexually in nature, and measured both the mean decline and variance increase in fitness of 20 lines. The results obtained with T. thermophila were compared with T. pyriformis that is an obligate asexual species. We show that MA lines of T. thermophila go to extinction at a rate of 1.25 clonal extinctions per bottleneck. In contrast, populations of T. pyriformis show a much higher resistance to extinction. Variation in gene copy number is likely to be a key factor in explaining these results, and indeed we show that T. pyriformis has a higher mean copy number per cell than T. thermophila. From fitness measurements during the MA experiment, we infer a rate of mutation to copy number variation of 0.0333 per haploid MAC genome of T. thermophila and a mean effect against copy number variation of 0.16. A strong effect of population size in the rate of fitness decline was also found, consistent with the increased power of natural selection. Conclusions. The rate of clonal extinction measured for T. thermophila is characteristic of a mutational degradation and suggests that this species must undergo sexual reproduction to avoid the deleterious effects detected in the laboratory experiments. We also suggest that an increase in chromosomal copy number associated with the phenotypic assortment of amitotic divisions can provide an alternative mechanism to escape the deleterious effect of random chromosomal copy number variation in species like T. pyriformis that lack the resetting mechanism of sexual reproduction. Our results are relevant to the understanding of cell line longevity and senescence in ciliates. © 2010 Brito et al; licensee BioMed Central Ltd.


PubMed | Public Health Agency of Sweden, ISI Foundation, Instituto Gulbenkian Of Cincia, University of Turin and 5 more.
Type: Journal Article | Journal: PloS one | Year: 2014

Internet-based systems for epidemiological studies have advantages over traditional approaches as they can potentially recruit and monitor a wider range of individuals in a relatively inexpensive fashion. We studied the association between communication strategies used for recruitment (offline, online, face-to-face) and follow-up participation in nine Internet-based cohorts: the Influenzanet network of platforms for influenza surveillance which includes seven cohorts in seven different European countries, the Italian birth cohort Ninfea and the New Zealand birth cohort ELF. Follow-up participation varied from 43% to 89% depending on the cohort. Although there were heterogeneities among studies, participants who became aware of the study through an online communication campaign compared with those through traditional offline media seemed to have a lower follow-up participation in 8 out of 9 cohorts. There were no clear differences in participation between participants enrolled face-to-face and those enrolled through other offline strategies. An Internet-based campaign for Internet-based epidemiological studies seems to be less effective than an offline one in enrolling volunteers who keep participating in follow-up questionnaires. This suggests that even for Internet-based epidemiological studies an offline enrollment campaign would be helpful in order to achieve a higher participation proportion and limit the cohort attrition.


Tarapore D.,Instituto Gulbenkian Of Cincia | Tarapore D.,University of Lisbon | Tarapore D.,University Pierre and Marie Curie | Lima P.U.,University of Lisbon | And 4 more authors.
Bioinspiration and Biomimetics | Year: 2015

Fault detection and fault tolerance represent two of the most important and largely unsolved issues in the field of multirobot systems (MRS). Efficient, long-term operation requires an accurate, timely detection, and accommodation of abnormally behaving robots. Most existing approaches to fault-tolerance prescribe a characterization of normal robot behaviours, and train a model to recognize these behaviours. Behaviours unrecognized by the model are consequently labelled abnormal or faulty. MRS employing these models do not transition well to scenarios involving temporal variations in behaviour (e.g., online learning of new behaviours, or in response to environment perturbations). The vertebrate immune system is a complex distributed system capable of learning to tolerate the organism's tissues even when they change during puberty or metamorphosis, and to mount specific responses to invading pathogens, all without the need of a genetically hardwired characterization of normality. We present a generic abnormality detection approach based on a model of the adaptive immune system, and evaluate the approach in a swarm of robots. Our results reveal the robust detection of abnormal robots simulating common electro-mechanical and software faults, irrespective of temporal changes in swarm behaviour. Abnormality detection is shown to be scalable in terms of the number of robots in the swarm, and in terms of the size of the behaviour classification space. © 2015 IOP Publishing Ltd.

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