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Candida albicans est un pathogene opportuniste pouvant provoquer des infections systemiques chez des patients immunodeprimes. L’origine de ces infections est principalement d’origine endogene, notamment a partir du tractus gastro-intestinal, ou le champignon peut penetrer a travers la barriere epitheliale intestinale pour gagner ensuite la circulation sanguine. Au niveau de la muqueuse intestinale, les enterocytes forment une monocouche de cellules assurant l’integrite et l’impermeabilite du tissu digestif. Au niveau des plaques de Peyer notamment, les cellules Microfold (ou cellules M) sont associees aux enterocytes et jouent un role important dans l’homeostasie digestive. En effet, ces cellules epitheliales sont specialisees dans l’endocytose d’antigenes, de molecules ou encore de microorganismes presents dans la lumiere intestinale. Elles jouent le role de cellules presentatrices d’antigene puisqu’elles presentent au systeme immunitaire sous-jacent les antigenes endocytes. Ces cellules peuvent egalement etre utilisees par des pathogenes comme Yersinia enterocolitica ou Salmonella typhi comme porte d’entree pour traverser la barriere epitheliale intestinale. L’interaction de certaines bacteries pathogenes avec les cellules M constitue donc une etape importante dans la physiopathologie des infections causees par ces bacteries. Cependant, aucune etude n’a a ce jour etudie l’interaction de C. albicans avec les cellules M. Afin de mieux comprendre les premieres etapes des candidoses invasives a C. albicans , nous avons developpe un modele in vitro decrit par des Rieux et al., 2007, permettant d’obtenir des cellules M a partir de la differenciation d’enterocytes de la lignee Caco-2 mis en contact avec des lymphocytes B Raji. Nous avons ensuite etudie l’interaction specifique de C. albicans avec des cultures mixtes enterocytes/cellules M. A l’aide de techniques de microscopie electronique a balayage et a fluorescence, et de protocoles permettant d’evaluer l’adherence et l’invasion de souches sauvages et de mutants de C. albicans , nous avons pu montrer que C. albicans adherait preferentiellement aux cellules M dans des monocouches mixtes enterocytes/cellules M. De meme, nous avons observe que C. albicans pouvait utiliser les cellules M comme porte d’entree au franchissement de la barriere intestinale. Par ailleurs, alors que C. albicans est capable d’envahir la muqueuse intestinale par penetration active des hyphes dans les cellules epitheliales intestinales, nous avons montre que l’internalisation des levures etait egalement possible au niveau des cellules M par penetration active des hyphes mais egalement par endocytose F-actine dependante : alors que la penetration active dans les monocouches mixtes enterocytes/cellules M est facilitee en partie par certaines invasines associees aux hyphes de C. albicans (dont Als3 et Ssa1), la nature des invasines de C. albicans capables d’induire son endocytose par les cellules M reste a determiner.

Bicarbonate is often a major ionic constituent associated with produced waters from methane gas extraction and coal mining, yet few studies have determined its specific toxicity. Currently, the environmental risk of bicarbonate anion in water discharges is assessed based on the toxicity of sodium chloride or artificial seawater and is regulated via electrical conductivity. Increased NaHCO(3) added to Ceriodaphnia dubia in synthetic or natural water gave similar 48-h 10% effective concentration (EC10) values of 1750 ± 125 mg NaHCO(3)/L (mean ± standard error) and 1670 ± 180 mg NaHCO(3)/L, respectively. Bicarbonate was toxic to C. dubia in both waters with conductivities above 1900 µS/cm. In contrast, when conductivity was elevated with NaCl, toxicity to C. dubia was observed only above 2800 µS/cm. Bicarbonate also impaired C. dubia reproduction with an EC10 of 340 mg NaHCO(3)/L. Major ion composition also influenced Zn bioavailability, a common co-occurring metal contaminant in coal mine waters, with sublethal concentrations of NaHCO(3) and elevated pH increasing Zn toxicity. Higher pH was the dominant parameter determining a 10-fold increase in the 48-h 50% effective concentration (EC50) for Zn toxicity to C. dubia at pH 8.6 of 34 µg Zn/L (95% confidence limit = 32-37 µg Zn/L) compared with the Zn toxicity at approximately circumneutral pH. Exposure of the freshwater shrimp Paratya australiensis (Atyidae) in natural water to increasing bicarbonate gave a mean 10-d 10% lethal concentration (LC10) of 850 ± 115 mg NaHCO(3)/L, associated with a mean conductivity EC10 of 1145 µS/cm, which is considerably lower than toxicity of NaCl and artificial seawater to this species reported elsewhere. Because toxicity was influenced by salt composition, specific ions should be regulated rather than conductivity alone in mine wastewater discharges.

Reaction of squaric acid derivatives with vinyl magnesium bromide followed by treatment with trifluoroethanol allows a new and stereoselective access to functionalized cyclopentenones of type (III)/ (V).

Double addition (1,2-1,4) of vinyl magnesium bromide to squaric acid derivatives allows the preparation of polyoxygenated cyclopentenones (8) in a "one-pot" procedure. The reaction occurs through the intermediate formation of octatetraenes (6). Protonation of this latter intermediate at -78 °C with TFE occurs selectively at the vinyl CH(2) closer to the metallic centers. DFT studies of the cyclization step justify the observed diastereoselectivity.

Este artigo trata da análise de um manuscrito do padre jesuíta Sebastião Beretario que descreve a vida de José de Anchieta. Nosso objetivo não é discutir sobre a figura desse jesuíta, mas sim apreender no texto de Beretario uma série de informações acerca da apreciação que os europeus faziam sobre as Américas e seus habitantes nativos. Nessa descrição podemos apreender os indícios de modernidade que já começava a surgir na Europa do século XVI, além de retratar de certa forma algumas questões ocorridas durante a União Ibérica. This article is a review on a text by the Jesuit priest Sebastian Beretario on the biography of José de Anchieta. But the objective of this article is not to tell about Anchieta, rather to understand in Beretario’s text a great amount of information on the impression of America and the native American inhabitants by the European. This description also show the signs of Modernity in its beginning in Europa at the 16th century and besides display certain issues that happened during the Iberic Union period.

Background It has been hypothesised that people with anorexia nervosa have a higher intelligence quotient (IQ) level than the general population. The purpose of this review was to systematically appraise the research into reported IQ levels in people with anorexia nervosa. Methods A search using the terms intelligence quotient, IQ, intelligence, cognition, eating disorders and anorexia was conducted in electronic databases only. Results In all, 30 peer-reviewed studies written in English that used well established measures of intelligence quotient (the National Adult Reading Test and Wechsler Intelligence Scales) were identified. This review established that people with anorexia nervosa score 10.8 units and 5.9 units above the average intelligence quotient of the normative population on the National Adult Reading Test and Wechsler Intelligence Scales, respectively. An association was found between Body Mass Index and intelligence quotient, as measured by the National Adult Reading Test. Conclusions More studies including other eating disorder categories and recovered people are needed to explore important questions regarding the role of the intelligence quotient in treatment response.

Whilst neuropsychological testing provides the most accurate profile of cognitive functioning, the time consuming nature of individual assessment deems it impossible for many research and clinical settings. This paper presents the development and validation of the Detail and Flexibility Questionnaire (DFlex), a 24-item self-report scale measuring two aspects of neurocognitive functioning; cognitive rigidity (difficulty with set-shifting/flexibility) and attention to detail (weak coherence). Exploratory factor analysis extracted two subscales, further confirmed and refined by item response analysis. Both subscales showed high internal reliability, construct validity (as compared to relevant subscales of the Autistic-Spectrum Quotient) and strong discriminant validity with large effect sizes found between both lifetime eating disorder and healthy control groups, and between current and recovered anorexia nervosa. We suggest using the cognitive rigidity and attention to detail subscales independently to give a rough approximation of these two aspects of cognitive style as they manifest in the context of everyday life.

Observa-se o aumento do número de óbitos tipo suicídio no país, em indivíduos envelhescentes. O trabalho consiste em levantar e comparar dados referentes a estes óbitos, em indivíduos entre 40 e 60 anos, no Estado do Rio de Janeiro. A metodologia baseia-se na investigação quantitativa com análise dos dados obtidos no Sistema de Informação sobre Mortalidade, no período de 2000 a 2005. Esses dados permitem identificar que os suicídios nestes indivíduos aparecem de forma expressiva. Se ha observado entre los adultos mayores el aumento del número de suicidios en el país. El presente trabajo se propone investigar y comparar los datos referentes a estos óbitos en los individuos entre 40 y 60 años, en el Estado de Río de Janeiro, Brasil. La metodología está basada en la investigación cuantitativa con análisis de los datos obtenidos en el Sistema de Información sobre Mortalidad de 2000 a 2005. Los datos permiten identificar que se produjeron de manera expresiva suicidios entre los adultos mayores de esa franja de edad. On constate une augmentation du nombre des suicides parmi les personnes vieillissantes au Brésil. Nous avons relevé et comparé les données sur ce type de décès dans des individus entre 40 et 60 ans, dans l'état de Rio de Janeiro (Brésil). Notre méthodologie est basée sur la recherche quantitative, soit une analyse des données obtenues par le Système d'Information sur la Mortalité de 2000 à 2005. Ces données nous ont permit d'identifier que le suicide chez ces individus se manifeste de façon expressive. The increase in the number of deaths due to suicide in aging individuals has been observed in Brazil. The present work surveyed and compared data referring to these deaths in individuals between 40 and 60 years of age, in the state of Rio de Janeiro. The methodology is based on quantitative investigation with the analysis of data provided by the Mortality Information System, from 2000 to 2005. These data revealed that suicides appear in a significant way in those individuals.

to analyze the audiological profile of elderly patients seen in a clinic from an audiology school clinic in the city of Belo Horizonte.we studied all the charts from the patients who underwent audiologic assessment from April of 2004 and August of 2007 in an audiology clinic in the city of Belo Horizonte.We studied the 313 audiological tests from patients 60 years of age or over. The results from the audiological evaluations as to the type of hearing loss were: auditory thresholds within normal standards - 22.28%; sensorineural hearing loss - 60.62%; mixed hearing loss - 14.70%, conductive hearing loss - 2.40%. The level varied between normal and profound. As to the tympanometry, 83.22% had the type A curve, and the other types of curves obtained made up a total of 16.3%. The percentage of individuals who did not undergo the test was 0.48%. 1.76% of the patients who had unilateral hearing loss and 98.24% had bilateral hearing loss.we found a greater prevalence of sensorineural hearing loss, and the degree of the loss varied from mild to profound, with a prevalence of the moderate degree.

The aim of this chapter is to discuss the concept of endophenotypes within the eating disorder (ED) population. As is common in most forms of psychiatric illness, people with ED have additional psychological problems, as do their family members. Affective disorders, addictions, and autistic spectrum disorders commonly occur in association with the individual and/or in the families of those with ED. This chapter will explore the literature related to underlying biological markers that potentially underpin all of these disorders. Some of the biomarkers fulfi l the criteria for an endophenotype, although this is an area that is poorly developed so far in the eating disorder fi eld. It is possible that core inherited vulnerability traits such as anxiety, rigidity, weak coherence, poor social cognition, compulsivity and impulsivity are some of the features held in common with other disorders.

Previous work has found that women with anorexia nervosa and bulimia nervosa have weak coherence. The aim of this study was to examine whether women who had recovered from an eating disorder (ED) also had weak coherence. A total of 42 recovered ED women and 42 healthy women were assessed with a battery of five neuropsychological tests that measure aspects of global or local functioning. The recovered ED group showed superior local processing and poorer global processing than the healthy group. These results are indicative of weak coherence. The finding that weak coherence is a stable characteristic rather than a state effect suggests that it may be an endophenotype for ED.

BackgroundThis review systematically appraised the research evidence for localversusglobal information processing to test the hypothesis that people with eating disorders (ED) had weak central coherence.MethodSearches on Medline, EMBASE, PsycINFO and ISI Web of Science databases were conducted in November 2006 and subsequently updated in September 2007. Each search was conducted in two steps: (1) neuropsychological tasks measuring central coherence and (2) words related to cognitive functioning in eating disorders. Data were summarized in a meta-analysis if the number of studies for a given test was >5.ResultsData were extracted from 16 studies. Meta-analyses were conducted for four tasks obtaining moderate effect sizes. The majority of studies found global processing difficulties across the ED spectrum. The results are less clear regarding local processing.ConclusionsPeople with ED have difficulties in global processing. It is less certain as to whether they have superior local processing. Currently, there is insufficient evidence to refute the weak central coherence hypothesis.

A vila do Rio Grande de São Pedro foi palco de intensas disputas entre Portugal e Espanha desde sua fundação pelos portugueses em 1737. Essas disputas tiveram seu momento culminante na invasão espanhola a Rio Grande em 1763 e que se prolongou numa ocupação que durou até 1777. Esse conflito mostra-nos uma idéia de fronteira de litígio constante entre portugueses e espanhóis. Ora, a historiografia regional brasileira, ao estudar a formação do Rio Grande do Sul, excluiu por muito tempo a presença espanhola na formação da Capitania. Neste trabalho pretendemos mostrar a importância da presença espanhola na formação da capitania, mas principalmente a sua presença na vila do Rio Grande de São Pedro, inclusive antes mesmo da ocupação. Para isso nos utilizamos de levantamento demográfico da região e de bibliografia especializada no assunto.

Objective: To examine the concept of central coherence in women with bulimia nervosa (BN) and address similarities and difference with those with anorexia nervosa (AN) Method: Forty two women with BN and 42 matched healthy women, completed neuropsychological testing measuring aspects of central coherence: Rey-Osterrieth Complex Figure (RCFT), Embedded Figures Test (EFT), Block Design Test (BD), Homograph Reading Test (HRT), and Sentence Completion Task (SCT). Results: The BN group showed superiority in local processing as measured by EFT and lesser relative advantage from segmentation in BD, and difficulties in global processing in both visual and verbal domains as examined by RCFT, HRT, and SCT. Anxiety levels were associated with low central coherence indices in RCFT. Conclusion: People with BN displayed a profile consistent with the weak central coherence hypothesis. Their pattern of cognitive performance resembles that seen in AN although some differences are apparent. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008.

The aim of this review was to collate and summarise the self-report data regarding anomalies in sensitivity to reward and punishment in eating disorders (ED) with use of a meta-analysis where possible. Electronic databases were searched to December 2008. Studies were required to have a non-eating disorder healthy control group and include at least one self-report measure of sensitivity to reward or punishment in an eating disorder population. Findings were very heterogeneous and inconsistencies between studies and measures were highlighted. In general, patients with anorexia nervosa (restricting type) were less sensitive to reward than healthy controls, whereas patients with bulimia nervosa and anorexia nervosa (binge/purge) type were more sensitive. All ED groups report higher sensitivity to punishment than healthy controls. Individuals with eating disorders differ from healthy controls in measures of reward and punishment sensitivity as measured using the Temperament and Character Inventory, Tridimensional Personality Questionnaire and BIS/BAS scales, but further work is required as there is some heterogeneity in the data. Generating more research using behavioural measures may increase understanding of the findings.

O objetivo do trabalho foi relatar um caso clínico sobre a síndrome de Goldenhar e realizar um levantamento das alterações fonoaudiológicas encontradas no mesmo. O presente estudo foi realizado com uma criança de seis anos e oito meses, do gênero masculino, com diagnóstico da síndrome de Goldenhar. Para o estudo foi realizada anamnese e o paciente foi submetido às avaliações de motricidade orofacial, audiologia clínica completa, educacional e vectoeletronistagmografia computadorizada, voz e linguagem oral e escrita. Foram observadas as seguintes alterações: dificuldade de vedamento labial, bochechas e olhos assimétricos, mordida aberta anterior, amígdalas palatinas hipertróficas e micrognatia, respiração do tipo oro-nasal, dificuldade de coordenação pneumofônica, hábito bucal de apertamento; qualidade vocal ruim com presença de tensão laríngea durante a fonação, habilidades auditivas alteradas, perda auditiva neurossensorial de grau profundo bilateral, curva timpanométrica do tipo A, com ausência de reflexos acústicos, ausência de dados patognomônicos de alteração central no teste vestibular. O paciente não possui fala fluente, faz uso da Língua Brasileira de Sinais, leitura orofacial e gestos para se comunicar, apresenta dificuldades de leitura e escrita e o desenvolvimento de linguagem está adequado à sua faixa etária. Pode-se concluir que é importante que o paciente com a síndrome de Goldenhar receba um acompanhamento multidisciplinar, o que lhe proporcionará um diagnóstico precoce, uma intervenção adequada e um desenvolvimento global satisfatório. The aim of this study was to report a case and analyze the speech, language and hearing deficits observed in the Goldenhar syndrome. The study reports the case of a male six years, eight months old child diagnosed with Goldenhar syndrome. The history of the patient was carried out, and he was submitted to oral motricity, voice, educational, verbal and written language evaluations, full audiological exam, and computerized vectoeletronistagmography. The following alterations were observed: difficulty in closing the lips, asymmetrical cheeks and eyes, anterior open bite, hypertrophic palatine tonsils, micrognathia, oro-nasal breathing, difficulty with pneumophonic coordination, dental tightness, poor vocal quality with presence of laryngeal tension during phonation, poor auditory abilities, profound bilateral sensory loss, type A tympanometric curve with absence of acoustic reflexes, absence of pathognomonic signs of central alteration on the vestibular test. The patient does not have fluent speech, uses the Brazilian Sign Language, orofacial reading and gestures to communicate, presents reading and writing difficulties and chronologically adequate language development. It can be concluded that it is important to the patient with the Goldenhar syndrome to receive multidisciplinary follow-up, which will provide early diagnosis, adequate intervention and satisfactory global development.

Objective: To examine central coherence (local and global processing) in women with anorexia nervosa (AN). Method: 42 women with AN and 42 healthy women (HC) completed neuropsychological testing measuring visuospatial and verbal aspects of central coherence: Rey-Osterrieth Complex Figure (RCFT), Embedded Figures Test (EFT), Homograph Reading Test (HRT), and Sentence Completion Task (SCT). Results: People with AN displayed superior performance on the EFT and poorer performance in RCFT with the exception of accuracy in the copy trial. Long hesitations in the SCT were observed. Verbal coherence tasks were not sensitive enough to detect coherence anomalies in AN. Conclusion: Women with AN have strengths in tasks requiring local processing (EFT) and weaknesses on tasks benefited by global processing (RCFT and SCT). These results are consistent with the weak central coherence account. This trait might play a role in the maintenance of AN and can be addressed in specific clinical interventions.

A Neuropatia Auditiva é um distúrbio na condução do estímulo sonoro, provavelmente relacionado à alteração da mielinização das fibras do nervo auditivo. Os avanços tecnológicos têm levado ao aumento nos recursos de diagnóstico e intervenção nos casos de deficiência auditiva por etiologia de Neuropatia Auditiva. O objetivo do presente estudo foi pesquisar na literatura os resultados obtidos em crianças com Neuropatia Auditiva após implante coclear. Foi realizado um trabalho de revisão bibliográfica em livros, periódicos e internet dos últimos dez anos sobre crianças com Neuropatia Auditiva usuárias de implante coclear. As pesquisas sugerem que a estimulação elétrica é capaz de compensar a dessincronia do nervo e que o implante coclear é um recurso para a (re)habilitação da audição em crianças portadoras de Neuropatia Auditiva. O uso do implante coclear permite melhoria significativa nas habilidades da audição e da comunicação. No entanto, as habilidades adquiridas parecem sofrer influência de diversos fatores como: tempo de uso do dispositivo, existência de um processo terapêutico sistemático, época do diagnóstico e a idade da criança. Auditory Neuropathy is a disorder in the transmission of the sound stimulus, probably related to mielinization alterations of auditory nerve fibers. Technology advances have been increasing diagnostic and intervention resources in cases of hearing loss caused by auditory neuropathy. The aim of the present study was to research the available literature about the results obtained with children with Auditory Neuropathy after cochlear implants. An ample review was conducted on books, articles and the internet, over the last 10 years, regarding children with Auditory Neuropathy, users of cochlear implants. The available data suggest that electric stimulation can compensate neural asynchrony and that cochlear implants aid in the rehabilitation process of children with Auditory Neuropathy. The use of cochlear implant allows significant improvement in communication and hearing abilities. However, the acquired abilities seem to suffer influence from many factors, such as: length of time using the device, the existence of a systematic therapeutic process, when the diagnosis was carried out, and the child's age.

The aim of this paper is to describe the content and processes involved in a series of workshops for carers of people with an eating disorder. These workshops were designed to equip carers with the skills and knowledge needed to be a ‘coach’ and help the person with an eating disorder break free from the traps that block recovery. The first hurdle is to overcome the unhelpful patterns of interpersonal processes between the person with an eating disorder and their carers. In both naturalistic studies and randomised controlled trials (RCT), family factors have been implicated either as moderators or mediators of outcome. High levels of expressed emotion (EE), misattributions about the illness or unhelpful methods of engaging with the eating disorder symptoms contribute to this effect. These workshops aim to reduce EE such as over protection. Carers are introduced to the transtheoretical model of change and the principles of motivational interviewing so that they can help rather than hinder change. They learn how to use reflective listening to reduce confrontation and how to sidestep resistance. Carers learn what is needed to help their daughter change by reflecting on the processes involved in changing their own behaviours in relationship with the person with eating disorders. Once they recognise that they may need to change then they can use their skills, information and insight to help change eating disorder symptoms. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association.

Defective viral genomes (DVGs) generated during Sendai virus infection are the primary triggers of the host antiviral response. DVGs induce the expression type-I interferons (IFN) and other cytokines upon binding through the intracellular viral sensors RIG-I and MDA5. The molecular mechanism behind the superior immunostimulatory activity of DVGs is unknown. To identify RNA motifs that provide potent immunostimulatory activity to DVGs, we generated a series of deletion mutants of a prototype DVG derived from Sendai virus. In vitro transcribed RNA from these mutants were tested for their ability to induce type I IFNs upon transfection. In silico single strand RNA modeling of the mutants folding identified an AU-enriched stem loop domain formed by nucleotides 70-114 of the DVG that is essential for type I IFN induction. Consistent with this prediction, we demonstrate that mutants lacking this region lose their stimulatory activity, while mutants that kept intact this region preserved it Thus, a minimal RNA motif at the 5’ but not the 3’ complimentary sequence is critical for maximal DVG activity and oligonucleotides including such region may represent novel alternatives to be harnessed as potent adjuvants for vaccination.

Ninety-two adolescents, predominantly ethnic minority high school students, participated in a structured Summer Business Institute (SBI). Participating youth were randomly assigned to receive either job social skills or financial management skills training components. Students who additionally received the job social skills training component were more likely to recommend their employment agency to others than were youth who received the financial management component, rated their overall on-the-job work experience more favorably, and demonstrated higher scores in areas that were relevant to the skills that were taught in the job social skills workshops. The financial management component also appeared to be relatively effective, as youth who received this intervention improved their knowledge of financial management issues more than youth who received job social skills, and rated their workshops as more helpful in financial management, as well as insurance management. Future directions are discussed in light of these results.

In infections with viruses well adapted to the host, virus-encoded proteins that delay the cellular response allow the virus to replicate to high titers prior to host intervention. The mechanisms overcoming viral evasion and leading to the production of the primary antiviral cytokine IFNbeta are not well established. We show that the appearance of defective forms of the viral genome may provide the answer. Defective viral genomes, which were until recently considered an epiphenomenon of in vitro virus replication, accumulate in infected cells at a faster rate than standard viral genomes and potently trigger the sustained activation of the transcription factors IRF3 and NF-kB and the production type I IFNs through a mechanism independent of IFN signaling. Remarkably, our work demonstrates that defective viral genomes are generated naturally during respiratory infections in vivo even in mice lacking the type I IFN receptor, and their appearance coincides with the production of cytokines during infections with Sendai virus or influenza virus. Notably, the hallmark antiviral cytokine IFNβ is only expressed in lung epithelial cells containing defective viral genomes, while cells within the lung that contain standard viral genomes alone do not express this cytokine. Together, our data indicate that defective viral genomes generated naturally during viral replication are a primary source of danger signals for the initiation of the host immune response to infection in vivo.

Defective interfering viral genomes (DIVGs) are generated during RNA viral replication. They are strong inducers of dendritic cell maturation and cellular immune responses. Virus stocks rich in DIVGs induce the expression of high levels of IFN-β, IL-12, IL-6 and other cytokines in cell cultures. Previous studies suggest that DIVGs induce cytokine expression through the action of cell pattern recognition receptors, specifically the members of the RIG-I like receptors. Whether DIVG recognition by these viral sensors and the resulting high cytokine expression depends on the DIVG sequence, structure, or length has not been addressed. In vitro transcribed RNA of Sendai virus DIVGs of different lengths and compositions were generated and tested for their stimulatory ability. Our results suggest that DIVGs specific structures and sequences are essential for their ability to trigger high cytokine expression thought RIG-I like receptor recognition. Moreover, we have generated a shorter DIVG with the identified minimal stimulatory motif that induce higher levels of IFN-β expression in vitro. In order to determine its immunostimulatory potential in vivo, we injected mice with DIVG RNA. Higher expression of pro-inflammatory cytokines was detected in the footpad tissue as early as 6 hours post-injection. This SeV-derived oligonucleotide with strong immunostimulatory activity may be then harnessed as a potent adjuvant for vaccination.

Viral recognition by specialized cellular sensors is critical for the innate immune response to virus infection. Detection of viral components by these sensors triggers the production of type I interferon (IFN), the earliest hallmark of viral infection, which plays an essential role in inducing an antiviral state in both infected and non-infected cells. Highly pathogenic respiratory viruses replicate in the lungs to high titers before a detectable anti-viral response begins, indicating that the viruses have devised effective mechanisms to avoid the innate anti-viral response. We have shown that dendritic cells can be potently activated in response to Sendai virus that contains a high dose of defective viral genomes (SeV HD) even in the absence of type I IFN signaling. The induction of anti-viral cytokines is driven by a quick and potent activation of IRF3 and NF-κB independently of IRF7. This response depends on the presence of MAVS that is essential for the signaling of the viral RNA sensors RIG-I and MDA5. Interestingly, our study indicates that infection with SeV HD triggers MDA5, but not RIG-I, in a type I IFN independent manner. This supports the hypothesis that the type I IFN-independent up-regulation of MDA5 is involved in the recognition of viral RNA and the subsequent induction of antiviral genes. In conclusion, this study suggests a previously unappreciated type I IFN independent function of MDA5 in the innate immune response to respiratory viruses.