A model of chronic IgE-mediated food allergy in ovalbumin-sensitized mice

Food allergy is most frequently the result of IgE-mediated hypersensitivity reactions. Here, we describe a chronic model in which some of the intestinal and systemic consequences of continuous egg white solution ingestion by ovalbumin-sensitized eight-week-old BALB/c mice, 6 animals per group, of both sexes, were investigated. There was a 20% loss of body weight that began one week after antigen exposure and persisted throughout the experiment (3 weeks). The sensitization procedure induced the production of anti-ovalbumin IgG1 and IgE, which were enhanced by oral antigen exposure (129% for IgG1 and 164% for IgE, compared to sensitization values). Intestinal changes were determined by jejunum edema at 6 h (45% Evans blue extravasation) and by a significant eosinophil infiltration with a peak at 48 h. By day 21 of continuous antigen exposure, histological findings were mild, with mast cell hyperplasia (100%) and increased mucus production (483%). Altogether, our data clearly demonstrate that, although immune stimulation was persistently occurring in response to continuous oral antigen exposure, regulatory mechanisms were occurring in the intestinal mucosa, preventing overt pathology. The experimental model described here reproduces the clinical and pathological changes of mild chronic food allergy and may be useful for mechanistic studies of this common clinical condition.

Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation

Fanconi anemia (FA) is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA) in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30%) FA patients studied. Thirteen of the 80 (16.25%) were homozygotes and 11 of the 80 (13.75%) were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

Effect of lipoarabinomannan from Mycobacterium avium subsp avium in Freund’s incomplete adjuvant on the immune response of cattle

The aim of the present study was to determine whether lipoarabinomannan (LAM), in combination with Freund’s incomplete adjuvant (FIA), was able to improve cell-mediated and antibody-mediated immune responses against ovalbumin (OVA) in cattle. Twenty-three calves were assigned to four treatment groups, which were subcutaneously immunized with either OVA plus FIA, OVA plus FIA and LAM from Mycobacterium avium subsp avium, FIA plus LAM, or FIA alone. Lymphoproliferation, IFN-γ production and cell subpopulations on peripheral blood mononuclear cells before and 15 days after treatment were evaluated. Delayed hypersensitivity was evaluated on day 57. Specific humoral immune response was measured by ELISA. Inoculation with LAM induced higher levels of lymphoproliferation and IFN-γ production in response to ConA and OVA (P < 0.05). Specific antibody titers were similar in both OVA-immunized groups. Interestingly, our results showed that the use of LAM in vaccine preparations improved specific cell immune response evaluated by lymphoproliferation and IFN-γ production by at least 50 and 25%, respectively, in cattle without interfering with tuberculosis and paratuberculosis diagnosis.

High-frequency electroacupuncture versus carprofen in an incisional pain model in rats

The objective of the present study was to compare the effect of electroacupuncture (EA) and carprofen (CP) on postoperative incisional pain using the plantar incision (PI) model in rats. A 1-cm longitudinal incision was made through skin, fascia and muscles of a hind paw of male Wistar rats and the development of mechanical and thermal hypersensitivity was determined over 4 days using the von Frey and Hargreaves methods, respectively. Based on the experimental treatments received on the third postoperative day, the animals were divided into the following groups: PI+CP (CP, 2 mg/kg, po); PI+EAST36 (100-Hz EA applied bilaterally at the Zusanli point (ST36)); PI+EANP (EA applied to a non-acupoint region); PI+IMMO (immobilization only); PI (vehicle). In the von Frey test, the PI+EAST36 group had higher withdrawal force thresholds in response to mechanical stimuli than the PI, PI+IMMO and PI+EANP groups at several times studied. Furthermore, the PI+EAST36 group showed paw withdrawal thresholds in response to mechanical stimuli that were similar to those of the PI+CP group. In the Hargreaves test, all groups had latencies higher than those observed with PI. The PI+EAST36 group was similar to the PI+IMMO, PI+EANP and PI+CP groups. We conclude that 100-Hz EA at the ST36 point, but not at non-acupoints, can reduce mechanical nociception in the rat model of incisional pain, and its effectiveness is comparable to that of carprofen.

In vitro digestibility of globulins from sapucaia (Lecythis pisonis Camb.) nuts by mammalian digestive proteinases

Sapucaia (Lecythis pisonis Camb.) raw nuts collected from Brazil were analyzed to determine the proximate composition, amino acid profile of protein fractions, in vitro protein digestibility and antinutritional factors in order to evaluate their potential as a protein alimentary complement. The nuts contained adequate amounts of essential amino acids, fatty acids and minerals. In the present study, no hemagglutinating or inhibitory activities were observed in any of the samples investigated, indicating low or non-detectable levels of proteinase inhibitors or lectins in the samples. In vitro digestibility of in natura and heated nut globulins by mammalian digestive proteinases was carried out using trypsin + chymotrypsin + peptidase, with resulting mean values of approximately 70.30 and 71.35%, respectively. Taken together, the results suggest that sapucaia nuts may provide a new source of protein to use as a potential nutritional agent.

Comparison of phenol content and antioxidant capacity of nuts

Frequent nut intake is associated with protective effects against cardiovascular diseases. In addition to the generally high contents of unsaturated fatty acids, polyphenol compounds seem to be also implicated in health promoting effects of nuts due to their antioxidant properties. In this way, eleven different kinds of nuts, including pinhao seeds (Araucaria angustifolia) and Brazil nuts (Bertholletia excelsa), typical of Brazil, were analyzed for the content of phenol compounds, including the potent anti-mutagenic and anti-cancer ellagic acid, and antioxidant capacity of methanolic extracts. The antioxidant capacity varied a hundred times among the different nuts, from 1.2 to 120 mg of Trolox equivalents.100 g-1 (FW). Total ellagic acid was determined after acid hydrolysis of ellagitannins and ellagic acid glycosides, and it was detected in only 3 of the 11 samples. The content of free and total ellagic acid in nuts varied from 0.37 to 41 and from 149 (chestnuts) to 823 (walnuts) mg.100 g-1 (FW), respectively. Among nuts, samples with the highest contents of ellagic acid (walnuts and pecans) also presented the highest total phenol contents and DPPH radical scavenging capacities. Pinhao seeds and Brazil nuts did not present significant amounts of phenols nor antioxidant capacity.

Fatty acids profile of pulp and nuts of Brazilian fruits

Fruits and nuts from the North and Northeast regions of Brazil were collected to determine the fatty acid profile of their oils. The species studied were Brazil (Bertholletia excelsa H.B.K.), Mucajá (Couma rigida M.), Inajá (Maximiliana maripa D.), Jenipapo (Genipa Americana L.), and Buriti (Mauritia flexuosa L.) nuts. Fatty acid methyl esters were analyzed by gas chromatography with flame ionization detection (GC-FID). Brazil nut major fatty acid was 18:3n-3 (α-linolenic acid), and Buriti nut had approximately 23 times more 18:3n-3 than the pulp. Mucajá nut presented high content of 12:0 (lauric acid) and 16:0 (palmitic acid), and Mucajá pulp showed significant levels of 18:2n-6 (linoleic acid). Considering the PUFA (polyunsaturated fatty acid) sum values, almost all fruits and nuts analyzed presented very high levels of these compounds. Regarding n-6/n-3 ratio, only Brazil Nut, Buriti Nut, Inajá pulp, and Jenipapo pulp corresponded to the desired profile. These Brazilian fruits and nuts could be of potential interest due to their high nutritive value and lipid content.

Prevalent fatty acids in cashew nuts obtained from conventional and organic cultivation in different stages of processing

Brazil is one of the three largest producers of fruits in the world, and among those fruit trees, the cashew tree stands out due to the high nutritional and commercial value of its products. During its fruit processing, there are losses in some compounds and few studies address this issue. Over the last decade the conventional system of food production has been substituted for the organic cultivation system, which is a promising alternative source of income given the global demand for healthy food. Therefore, this research aimed to characterize and quantify the prevalent fatty acids found in cashew nuts obtained from conventional and organic cultivation during various stages of processing. The prevalent fatty acids found were palmitic, linoleic, oleic, and stearic acid. The average of these fatty acids were 6.93 ± 0.55; 16.99 ± 0.61; 67.62 ± 1.00 and 8.42 ± 0.55 g/100 g, respectively. There was no reduction in the palmitic, oleic and stearic fatty acid contents during processing. Very little difference was observed between the nuts obtained from conventional and organic cultivation, indicating that the method of cultivation used has little or no influence on the content of cashew nut fatty acids.

Characterization of biomasses from the north and northeast regions of Brazil for processes in biorefineries

Abstract In search for renewable energy sources, the Brazilian residual biomasses stand out due to their favorable physical and chemical properties, low cost, and their being less pollutant. Therefore, they are likely to be used in biorefineries in the production of chemical inputs to substitute fossil fuels. This substitution is possible due to the high contents of carbohydrates (>40%), low contents of extractives (<20%), ashes (<8%) and moisture (<8%) found in these residual biomasses. High calorific values of all residues also offer them the chance to be used in combustion. A principal components analysis (PCA) was performed for better understanding of the samples and their hysic-chemical properties. Thus, this study aimed to characterize biomasses from the north (babassu residues, such as mesocarp and endocarp; pequi and Brazil nut) and northeast (agave and coconut) regions of Brazil, in order to contribute to the preservation of the environment and strengthen the economy of the region.

Immunomodulatory effects of supercritical fluid CO2 extracts from freeze-dried powder of Tenebrio molitor larvae (yellow mealworm)

Abstract In order to take full advantage of Tenebrio molitor larvae (yellow mealworm) resources, the supercritical CO2 fluid freeze-dried powder of T. molitor larvae (fdTML) extraction on the immune systems of mice was carried out. The results about the effects of supercritical CO2 fluid fdTML extraction on carbon expurgation and phagocytosis of peritoneal macrophages experiments of mice indicated that the fdTML extraction enhanced observably carbon expurgatory index, phagocytic rate and phagocytic index. The fdTML extraction could stimulate response of delayed hypersensitivity. The proliferation of ConA-induced mitogenic reponse for spleen lymphocyte was also increased. The amount of hemolytic antibody in mice serum increased compared with those of the control group mice. The half of hemolysis values in serum of treated mice increased compared to the control group. Furthermore, serum NO content in all treatment groups was higher than that of the control group whereas acid phosphatase and alkaline phosphatase activity was only significantly higher relative to the control group. Our findings suggest that supercritical CO2 fluid the fdTML extraction has potential as a health food supplement.

Gender-toiminta osana sotilaallista kriisinhallintaa : rekrytointi, koulutus ja operatiivinen toiminta

Kansainväliset sotilaalliset kriisinhallintaoperaatiot ovat muuttuneet yhä vaativammiksi, ja kriisinhallinnan tehtäväkenttä on laajentunut ja monipuolistunut. Operaatioalueella olevilta kriisinhallintahenkilöiltä odotetaan yhä enemmän kykyä yhteistyöhön kaikkien toimijoiden kanssa yhteiskunnan vakauden ja turvallisuuden palauttamiseksi ja säilyttämiseksi. Yhdistyneiden kansakuntien päätöslauselman 1325 ”Naiset, rauha ja turvallisuus” täytäntöönpanolla halutaankin hyödyttää koko yhteiskunnan vakautta ja kehitystä. Suomen kansallisen toimintaohjelman ja Pääesikunnan normin mukaan Suomi tukee naisten kouluttautumista kohti vaativimpia tehtäviä ja esittää naisia kansainvälisiin johtotehtäviin. Suomi varmistaa, että kaikilla kriisinhallintatehtäviin lähtevillä on ihmisoikeus- ja tasa-arvokysymysten asiantuntemus sekä kyky tehdä yhteistyötä sisällyttämällä YK:n päätöslauselma 1325, kansainvälinen oikeus, kansainvälinen humanitaarinen oikeus sekä ihmisoikeusvelvoitteet kaikkeen kriisinhallintakoulutukseen. Suomi sisällyttää gender-näkökulman osak-si kriisinhallintajoukkojen operatiivista toimintaa huomioimalla gender-näkökulman operaatioiden suunnittelussa, toimeenpanossa ja raportoinnissa YK:n päätöslauselman 1325 ja operaatiokohtaisten määräysten mukaisesti. Tutkielman tarkoituksena oli tutkia puolustusvoimien virassa olevien naisupseerien motiiveja hakeutua kriisinhallintatehtäviin, naisten osallistumisen vaikutuksia kriisinhallintaoperaatioihin sekä gender-näkökulman huomioimista koulutuksessa ja kriisinhallintajoukon operatiivisessa toiminnassa. Tutkimusongelmana oli vähäinen aiempi tiedon määrä Suomen kansallisessa toimintaohjelmassa ja Pääesikunnassa määritetyn gender-toiminnan toteutumisesta. Päätutkimuskysymyksen avulla pyrittiinkin selvittämään, miten gender-toiminta on toteutu-nut sotilaallisen kriisinhallinnan rekrytoinnissa, koulutuksessa ja operatiivisessa toiminnassa. Tutkimusstrategiana sovellettiin monimenetelmäistä tiedonkeruutapaa määrällisen ja laadullisen aineiston saamiseksi. Tutkimusmenetelminä käytettiin survey-tutkimusta ja sisällönanalyysiä, joiden avulla pyrittiin kuvaamaan naisupseerien, operaatioista kotiutuneiden rauhanturvaajien sekä Afganistanin kriisinhallintaoperaatiossa (ISAF) palvelleiden SKJA:n komentajien ja naisupseerien käsityksiä, mielipiteitä ja asenteita tutkittavasta aiheesta. Tutkielman empiirinen osuus perustuu naisupseereille suunnattuun kyselyyn sekä SKJA:n komentajien ja naisupseerien sähköpostihaastatteluun. Tutkielmassa hyödynnettiin lisäksi Porin prikaatin kotiutuneille rauhanturvaajille teettämän tasa-arvokyselyn tuloksia. Tutkielman tuloksena ilmeni, että naisrauhanturvaajien kriisinhallintatehtäviin osallistumisen vaikutuksista merkittävimpiä olivat yhteyden saaminen paikalliseen naisväestöön. Myös miesten ja naisten työskentely yhdessä samoissa tehtävissä nähtiin tärkeänä esimerkkinä sukupuolten tasa-arvosta. Sukupuolen liiallinen korostaminen nähtiin haitalliseksi, ja tehtävän vaatimukset tuleekin asettaa tehtävässä tarvittavien ominaisuuksien, tietojen ja taitojen mukaisesti. Positiivisten vaikutusten saavuttamiseksi naisten määrän kriisinhallintatehtävissä tulisi kasvaa nykyisestä, mutta sen ei tule olla itseisarvo. Merkittävimmät naisupseerien kriisinhallintatehtäviin hakeutumattomuuden syyt olivat perheen perustamiseen liittyvät sosiaaliset syyt. Kriisinhallintatehtäviin hakeutumisen motivaatiota kasvattavista tekijöistä tärkeimpiä olivat ammattitaidon ja itsensä kehittäminen. Gender-koulutuksen osalta ilmeni, että Suomessa annetaan gender-peruskoulutus mutta operaatioalueella ei täydennyskoulutusta annettu. Gender-näkökulman huomioon ottaminen kriisinhallintajoukon operatiivisessa suunnittelussa, toimeenpanossa ja raportoinnissa ei myöskään tulosten perusteella toteutunut. Tutkielman johtopäätöksenä todetaan, että naisupseerit ovat pääosin halukkaita palvelemaan kriisinhallintatehtävissä, vaikka osallistuminen onkin henkilömäärältään vähäistä. Naisten mahdollisuuteen hakeutua kriisinhallintatehtäviin voidaan vaikuttaa laatimalla urasuunnitelma varhaisemmassa vaiheessa ja lisäämällä naisupseereille kohdennettua tietoa kriisinhallintatehtävistä. Kriisinhallintatehtäviin halukkaita naisia on enemmän kuin näyttäisi olevan mahdollista irrottaa kotimaan tehtävistä. Gender-koulutuksen todettiin olevan liian yleisellä tasolla eikä sitä kyetty konkreettisesti huomioimaan ja soveltamaan joukon operatiivisessa toiminnassa. Koulutuksen pääpainon tulisikin olla operatiivisessa vaikuttavuudessa osana kaikkea koulutusta. Gender-näkökulma tulisi saada integroitua osaksi kaikkea kriisinhallintajoukon toimintaa operaation vaikuttavuuden ja tavoitteiden täyttymisen näkökulmaa. Operaation tavoitteita asetettaessa tulisi muistaa, että kriisinhallintaoperaatioilla pyritään kokonaisvaltaisesti turvallisuusympäristön parantamiseen ja normaaliyhteiskunnan toimintojen ja palvelujen palauttamiseen. Gender-toiminnan kehittämisessä tärkeää onkin ymmärtää sen vaikutus ja kytkeminen nimenomaan paikallisväestön eri ihmisryhmien huomioimiseen ja tasavertaisuuteen ihmisoikeuksien näkökulmasta. Tutkielman tulosten mukaan kehityskohteita gender-toiminnan parantamiseksi on olemassa, ja mikäli kriisinhallintaoperaatioiden vaikuttavuutta halutaan tehostaa, näyttäisi siihen myös olevan keinoja.

Individual differences in risk-taking and associated characteristics : a test of specificity in executive functions /

Multiple measures have been devised by clinicians and theorists from many different backgrounds for the purpose of assessing the influence of the frontal lobes on behaviour. Some utilize self-report measures to investigate behavioural characteristics such as risktaking, sensation seeking, impulsivity, and sensitivity to reward and punishment in an attempt to understand complex human decision making. Others rely more on neuroimaging and electrophysiological investigation involving experimental tasks thought to demonstrate executive functions in action, while other researchers prefer to study clinical populations with selective damage. Neuropsychological models of frontal lobe functioning have led to a greater appreciation of the dissociations among various aspects of prefrontal cortex function. This thesis involves (1) an examination of various psychometric and experimental indices of executive functions for coherence as one would predict on the basis of highly developed neurophysiological models of prefrontal function, particularly those aspects of executive function that involve predominantly cognitive abilities versus processes characterized by affect regulation; and (2) investigation of the relations between risk-taking, attentional abilties and their associated characteristics using a neurophysiological model of prefrontal functions addressed in (1). Late adolescence is a stage in which the prefrontal cortices undergo intensive structural and functional maturational changes; this period also involves increases in levels of risky and sensation driven behaviours, as well as a hypersensitivity to reward and a reduction in inhibition. Consequently, late adolescence spears to represent an ideal developmental period in which to examine these decision-making behaviours due to the maximum variability of behavioural characteristics of interest. Participants were 45 male undergraduate 18- to 19-year olds, who completed a battery of measures that included self-report, experimental and behavioural measures designed to assess particular aspects of prefrontal and executive functioning. As predicted, factor analysis supported the grouping of executive process by type (either primarily cognitive or affective), conforming to the orbitofrontal versus dorsolateral typology; risk-taking and associated characteristics were associated more with the orbitofrontal than the dorsolateral factor, whereas attentional and planning abilities tended to correlate more strongly with the dorsolateral factor. Results are discussed in light of future assessment, investigation and understanding of complex human decision-making and executive functions. Implications, applications and suggestions for future research are also proposed.

Stelco records, 1951-1989

The Steel Company of Canada (Stelco) was formed in 1910 with the incorporation of the Canada Screw Co. Ltd., the Montreal Rolling Mills Co., the Dominion Wire Manufacturing Co. Ltd., the Hamilton Steel and Iron Co. Ltd., and the Canada Bolt and Nut Co. Ltd. By the 1920s, the company was the largest producer of steel ingots in Canada. The 1930s saw continued success and expansion of the company as Stelco increased its iron and steel capacity by 50 percent. The company continued to prosper throughout the next several decades, with sales revenues exceeding one billion dollars in 1974. In 1980, the company officially changed its name to Stelco, in order to simplify its name in both the French and English language. The company began to experience financial difficulties beginning with the recession in 1982. The troubles persisted for the next 25 years as a result of a decreased demand for steel, labour disputes, and high steel imports. In 2004, Stelco entered bankruptcy protection. By 2007, Stelco had lost $240 million in its first four quarters after emerging from bankruptcy protection. That same year Stelco was purchased by the United States Steel Corp. Despite efforts to restructure the company, bankruptcy was again declared in 2014.

Les mécanismes endogènes de modulation de la douleur et leur dysfonction dans le syndrome de l'intestin irritable

La douleur est une expérience subjective multidimensionnelle accompagnée de réponses physiologiques. Ces dernières sont régulées par des processus cérébraux qui jouent un rôle important dans la modulation spinale et cérébrale de la douleur. Cependant, les mécanismes de cette régulation sont encore mal définis et il est essentiel de bien les comprendre pour mieux traiter la douleur. Les quatre études de cette thèse avaient donc comme objectif de préciser les mécanismes endogènes de modulation de la douleur par la contreirritation (inhibition de la douleur par une autre douleur) et d’investiguer la dysfonction de ces mécanismes chez des femmes souffrant du syndrome de l’intestin irritable (Sii). Dans un premier temps, un modèle expérimental a été développé pour mesurer l’activité cérébrale en imagerie par résonance magnétique fonctionnelle concurremment à l’enregistrement du réflexe nociceptif de flexion (RIII : index de nociception spinale) et des réponses de conductance électrodermale (SCR : index d’activation sympathique) évoqués par des stimulations électriques douloureuses. La première étude indique que les différences individuelles d’activité cérébrale évoquée par les stimulations électriques dans les cortex orbitofrontal (OFC) et cingulaire sont associées aux différences individuelles de sensibilité à la douleur, de réactivité motrice (RIII) et de réactivité autonomique (SCR) chez des sujets sains. La deuxième étude montre que l’analgésie par contreirritation produite chez des sujets sains est accompagnée de l’inhibition de l’amygdale par OFC et d’une modulation du réflexe RIII par la substance grise périaqueducale (PAG) et le cortex somesthésique primaire (SI). Dans les troisième et quatrième études, il est montré que la contreirritation ne produit pas d’inhibition significative de la douleur et du réflexe RIII chez les patientes Sii en comparaison aux contrôles. De plus, les résultats indiquent que la sévérité des symptômes psychologiques est associée au déficit de modulation de la douleur et à une hypersensibilité diffuse chez les patientes Sii. Dans l’ensemble, cette thèse précise le rôle de certaines structures cérébrales dans les multiples composantes de la douleur et dans l’analgésie par contreirritation et montre que les patientes Sii présentent une dysfonction des mécanismes spinaux et cérébraux impliqués dans la perception et la modulation de la douleur.

Regulation of the memory T cell development and islet beta-cell survival by DAPK-related apoptosis-inducing protein kinase 2 (Drak2)

Drak2 est un membre de la famille des protéines associées à la mort et c’est une sérine/thréonine kinase. Chez les souris mutantes nulles Drak2, les cellules T ne présentent aucune défectuosité apparente en apoptose induite par activation, après stimulation avec anti-CD3 et anti-CD28, mais ont un seuil de stimulation réduit, comparées aux cellules T de type sauvage (TS). Dans notre étude, l’analyse d’hybridation in situ a révélé que l’expression de Drak2 est ubiquiste au stade de la mi-gestation chez les embryons, suivie d’une expression plus focale dans les divers organes pendant la période périnatale et l’âge adulte, notamment dans le thymus, la rate, les ganglions lymphatiques, le cervelet, les noyaux suprachiasmatiques, la glande pituitaire, les lobes olfactifs, la médullaire surrénale, l’estomac, la peau et les testicules. Nous avons créé des souris transgéniques (Tg) Drak2 en utilisant le promoteur humain beta-actine. Ces souris Tg montraient des ratios normaux entre cellules T versus B et entre cellules CD4 versus CD8, mais leur cellularité et leur poids spléniques étaient inférieurs comparé aux souris de type sauvage. Après activation TCR, la réponse proliférative des cellules T Tg Drak2 était normale, même si leur production d’interleukine (IL)-2 et IL-4 mais non d’interféron-r était augmentée. Les cellules T Tg Drak2 activées ont démontré une apoptose significativement accrue en présence d’IL-2 exogène. Au niveau moléculaire, les cellules T Tg Drak2 ont manifesté une augmentation moins élevée des facteurs anti-apoptotiques durant l’activation; un tel changement a probablement rendu les cellules vulnérables aux attaques subséquentes d’IL-2. L’apoptose compromise dans les cellulesT Tg Drak2 a été associée à un nombre réduit de cellules T ayant le phénotype des cellules mémoires (CD62Llo) et avec des réactions secondaires réprimées des cellules T dans l’hypersensibilité de type différé. Ces résultats démontrent que Drak2 s’exprime dans le compartiment des cellules T mais n’est pas spécifique aux cellules T; et aussi qu’il joue des rôles déterminants dans l’apoptose des cellules T et dans le développement des cellules mémoires T. En outre, nous avons recherché le rôle de Drak2 dans la survie des cellules beta et le diabète. L’ARNm et la protéine Drak2 ont été rapidement induits dans les cellules beta de l’îlot après stimulation exogène par les cytokines inflammatoires ou les acides gras libres et qui est présente de façon endogène dans le diabète, qu’il soit de type 1 ou de type 2. La régulation positive de Drak2 a été accompagnée d’une apoptose accrue des cellules beta. L’apoptose des cellules beta provoquée par les stimuli en question a été inhibée par la chute de Drak2 en utilisant petit ARNi. Inversement, la surexpression de Drak2 Tg a mené à l’apoptose aggravée des cellules beta déclenchée par les stimuli. La surexpression de Drak2 dans les îlots a compromis l’augmentation des facteurs anti-apoptotiques, tels que Bcl-2, Bcl-xL et Flip, sur stimulation par la cytokine et les acides gras libres. De plus, les expériences in vivo ont démontré que les souris Tg Drak2 étaient sujettes au diabète de type 1 dans un modèle de diabète provoqué par de petites doses multiples de streptozotocine et qu’elles étaient aussi sujettes au diabète de type 2 dans un modèle d’obésité induite par la diète. Nos données montrent que Drak2 est défavorable à la survie des cellules beta. Nous avons aussi étudié la voie de transmission de Drak2. Nous avons trouvé que Drak2 purifiée pouvait phosphoryler p70S6 kinase dans une analyse kinase in vitro. Lasurexpression de Drak2 dans les cellules NIT-1 a entraîné l’augmentation de la phosphorylasation p70S6 kinase tandis que l’abaissement de Drak2 dans ces cellules a réduit la phosphorylation. Ces recherches mécanistes ont prouvé que p70S6 kinase était véritablement un substrat de Drak2 in vitro et in vivo. Cette étude a découvert les fonctions importantes de Drak2 dans l’homéostasie des cellules T et le diabète. Nous avons prouvé que p70S6 kinase était un substrat de Drak2. Nos résultats ont approfondi nos connaissances de Drak2 à l’intérieur des systèmes immunitaire et endocrinien. Certaines de nos conclusions, comme les rôles de Drak2 dans le développement des cellules mémoires T et la survie des cellules beta pourraient être explorées pour des applications cliniques dans les domaines de la transplantation et du diabète.