Role of ethylene in effective establishment of the peanut-bradyrhizobia symbiotic interaction.

Ethylene has been implicated in nitrogen fixing symbioses in legumes, where rhizobial invasion occurs via infection threads (IT). In the symbiosis between peanut (Arachis hypogaea L.) and bradyrhizobia, the bacteria penetrate the root cortex intercellularly and IT are not formed. Little attention has been paid to the function of ethylene in the establishment of this symbiosis. The aim of this article is to evaluate whether ethylene plays a role in the development of this symbiotic interaction and the participation of Nod Factors (NF) in the regulation of ethylene signalling. Manipulation of ethylene in peanut was accomplished by application of 1-aminocyclopropane-1-carboxylic acid (ACC), which mimics applied ethylene, or AgNO3, which blocks ethylene responses. To elucidate the participation of NF in the regulation of ethylene signalling, we inoculated plants with a mutant isogenic rhizobial strain unable to produce NF and evaluated the effect of AgNO3 on gene expression of NF and ethylene responsive signalling pathways. Data revealed that ethylene perception is required for the formation of nitrogen-fixing nodules, while addition of ACC does not affect peanut symbiotic performance. This phenotypic evidence is in agreement with transcriptomic data from genes involved in symbiotic and ethylene signalling pathways. NF seem to modulate the expression of ethylene signalling genes. Unlike legumes infected through IT formation, ACC addition to peanut does not adversely affect nodulation, but ethylene perception is required for establishment of this symbiosis. Evidence for the contribution of NF to the modulation of ethylene-inducible defence gene expression is provided.

Graphene oxide/titania photocatalytic ozonation of primidone in a visible LED photoreactor.

A graphene oxide-titania (GO/TiO2) composite was synthesized via sol-gel method, and studied in aqueous Primidone mineralization with ozone and LED visible light. The photocatalyst was characterized by different techniques (XRD, TEM, SBET, TGA, UV-vis diffuse reflectance spectroscopy). The band gap value decrease from 3.14 eV for bare TiO2 samples to 2.5 eV in GO/TiO2 composites clearly shows the interaction of GO with TiO2 structure. Approximately 20 mg L-1 of Primidone was removed in less than 20 min if ozone was applied, regardless of the presence or absence of light and catalyst. However, reactivity tests show a synergism effect between photocatalysis and ozonation for mineralization purposes. The combination of ozone and GO improved the activation of TiO2 under visible light. Process optimization led us to select a catalyst dosage of 0.25 g L-1, a light radiance of 359 W m-2 and a GO loading in the catalyst around 0.75%. At these conditions, with photocatalytic ozonation, the presence of GO in the catalyst improved mineralization up to 82% in 2 h compared to 70% reached with bare TiO2. Catalyst reusability shows no decrease of photocatalytic activity. Scavenger tests point to hydroxyl radicals as the main species responsible for Primidone removal.

Validation and comparison of instruments to identify frail patientes in primary care settings: Study protocol.

BACKGROUND: In the last few years several indices and tools, aimed at identifying frail subjects in various care settings have been developed. However, to date none of them has been incorporated into usual practice in the primary care setting. The purposes of this study are: 1) to evaluate the predictive capacity of the Tilburg Frailty Indicator (TFI), the Gérontopôle Frailty Screening Tool (GFST) and the KoS model together with two biomarker levels (SOX2 and p16INK4a) for adverse events related to frailty; 2) to determine differences in the use of healthcare services according to frailty. METHODS/DESIGN: Prospective multicentre cohort study with a 2-year follow-up. The study will be performed in primary care centres of Gipuzkoa and Costa del Sol, both located in Spain. Autonomous, non-institutionalized individuals aged 70 and over that agree to participate in this study will constitute the study population. A total of 900 individuals will be randomly selected from the healthcare administrative data bases of the participating health services. Data will be collected at baseline and at 1 and 2 years. The main independent variables assessed at baseline will be TFI outcomes, GFST and the KoS model, together with the expression of SOX2 and p16INK4a levels. During follow-up, loss of autonomy, the occurrence of death and consumption of healthcare resources will be assessed. DISCUSSION: The main focus of this work is the identification and evaluation of several instruments constructed under different rationales to identify frail subjects in primary care settings. The resulting outcomes have potential for direct application to the primary care practice. Early identification of the onset of functional impairment of elderly is an essential, still unresolved aspect in the prevention of dependence in the scope of primary care.

An oxidative burst and its attenuation by bacterial peroxidase activity is required for optimal establishment of the Arachis hypogaea-Bradyrhizobium sp. symbiosis.

AIMS: The main purpose of this study was to determine whether the Arachis hypogaea L. root oxidative burst, produced at early stages of its symbiotic interaction with Bradyrhizobium sp. SEMIA 6144, and the bacterial antioxidant system are required for the successful development of this interaction. METHODS AND RESULTS: Pharmacological approaches were used to reduce both plant oxidative burst and bacterial peroxidase enzyme activity. In plants whose H2 O2 levels were decreased, a low nodule number, a reduction in the proportion of red nodules (%) and an increase in the bacteroid density were found. The symbiotic phenotype of plants inoculated with a Bradyrhizobium sp. SEMIA 6144 culture showing decreased peroxidase activity was also affected, since the biomass production, nodule number and percentage of red nodules in these plants were lower than in plants inoculated with Bradyrhizobium sp. control cultures. CONCLUSIONS: We demonstrated for the first time that the oxidative burst triggered at the early events of the symbiotic interaction in peanut, is a prerequisite for the efficient development of root nodules, and that the antioxidant system of bradyrhizobial peanut symbionts, particularly the activity of peroxidases, is counteracting this oxidative burst for the successful establishment of the symbiosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results provide new insights into the mechanisms involved in the development of the symbiotic interaction established in A. hypogaea L. a legume infected in an intercellular way.

[Pleuro-pericarditis developed under a leflunomide therapy]. / Pleuro-péricardite développée au décours d'un traitement par léflunomide.

Leflunomide is an immunosuppressant drug used in rheumatoid arthritis and psoriatic arthritis. This product may cause rare but serious interstitial lung disease that appear at the beginning of treatment. This is why leflunomide should be prescribed and monitored in hospital. We present the case of a 71 years old woman who presented a pleuro-pericarditis with an increase of CA 125 during a treatment with leflunomide. This is the second case reported in the literature. The outcome was favorable after discontinuation of leflunomide.

[Ten-year evolution in non-small-cell lung cancer according to sex. Results of the KBP-2010-CPHG study by the College of General Hospital Respiratory Physicians]. / Évolution en 10ans du cancer bronchique non à petites cellules en fonction du sexe. Résultats de l'étude KBP-2010-CPHG du Collège des pneumologues des hôpitaux généraux.

INTRODUCTION: Comparison by sex and presenting features between 2000 and 2010 of the characteristics of new cases of non-small-cell lung cancer (NSCLC). METHODS: Observational KBP-2010-CPHG study similar to KBP-2000-CPHG. Both studies were promoted by the French College of General Hospital Respiratory Physicians (CPHG). KBP-2010-CPHG collected data for 6083 NSCLC diagnosed between January 1st and December 31st, 2010, and followed in the respiratory departments of 119 French general hospitals. RESULTS: In 2010, 24.4 % of the patients were women (16 % in 2000, p<0.0001). Compared to men, women were more commonly non-smokers (34.2 vs 4.7 %) or lighter consumers (37.2 vs 43.7 pack per years) (p<0.0001). Their tumours (mostly adenocarcinoma: 64.6 vs 48.7 %, p<0.0001) were more frequently diagnosed at stage IV (62.4 vs 56.9 %, p=0.0008). EGFR mutation research was more frequently performed (48.5 vs 31.0 %, p<0.0001) and positive (20.6 vs 5.2 %, p<0.0001) in women than men. Their treatment more frequently included targeted therapy (13.4 vs 5.7 %, p<0.0001). Compared to 2000, the percentage of non-smokers increased in men (4.7 vs 2.5 %, p<0.0001) while remaining stable in women (36.1 vs 34.2 %, p=0.32). The percentage of adenocarcinomas increased, particularly in men (48.7 vs 31.5 %, p<0.0001). CONCLUSIONS: The percentage of women with NSCLC has increased in 10years in France. In 2010, the main gender differences persist, but have decreased with the increasing proportion of non-smokers and adenocarcinomas in men. Various hypotheses to explain these changes are discussed.

Osteonecrosis avascular de los maxilares asociada a bifosfonatos: revisión de la literatura / Bisphophonates induced avascular osteonecrosis of the maxilla: literature review

La Osteonecrosis de los maxilares relacionada a los bifosfonatos puede ser definida como una condición patológica caracterizada por la presencia de un área de hueso necrótico expuesto por más de 8 semanas, en pacientes que se encuentran bajo tratamiento con Bifosfonatos y que no han sido sometidos a radioterapia. Los Bifosfonatos son fármacos utilizados ampliamente en la prevención y tratamiento de una variedad de enfermedades metabólicas, como la osteoporosis, cáncer óseo, hipocalcemia asociada a cáncer y para prevenir el desarrollo de metástasis ósea. Los pacientes bajo tratamiento con este fármaco se caracterizan por presentar un remodelado óseo deficiente con una pobre actividad de las células claves para el desarrollo de tal proceso, que son: los osteoblastos, los osteoclastos y osteocitos. La incidencia de esta patología depende de dos factores, que son la potencia y la duración del tratamiento bajo BFF. Por lo cual, aquellos casos donde se administran estos fármacos de manera intravenosa, tienen una incidencia más elevada debido al mayor efecto que se obtiene por esta vía. Es de suma importancia que el especialista y el odontólogo estén conscientes de los riesgos que conllevan la administración de estos fármacos y la prevención y el manejo de la Osteonecrosis. Igualmente informar a los pacientes que van a iniciar una terapia con BFF sobre los beneficios y riesgos que conllevan la administración de estos fármacos, haciendo énfasis en el alto riesgo de Osteonecrosis...

Bisphosphonates induced osteonecrosis of the maxilla can be defined as a pathologic condition characterized by the presence of necrotic exposed bone for more than eight weeks, in patients under BFF treatment without radiotherapy. Bisphosphonates are drugs used widely to prevent and treat a variety of metabolic disorders such as osteoporosis, bone cancer, cancer associated hypocalcaemia and to prevent bony metastasis. Patients treated with this kind of drugs, are characterized for deficient bone remodeling with low activity of key cells involved in the development of such process, they are: o and osteoblast, osteoclast and osteocyst. Incidence of this pathology depends on two factors, they are: the potency and the duration of the treatment. There for, those cases where BFF are administered intravenously, has higher incidence due to the higher effect. It is very important that the specialist and the dentist are aware of the risk related to administration of BFF and the prevention and management of Osteonecrosis. Inform the patients about to initiate BFF therapy regarding the benefits and risk related to the use of BFF and associated osteonecrosis...

[Malignant pleural mesothelioma after radiation treatment for Hodgkin lymphoma]. / Mésothéliome pleural malin après irradiation pour maladie de Hodgkin.

Malignant mesothelioma is a relatively uncommon malignancy. Although the pathogenesis is primarily related to asbestos, the role of ionizing radiation is more controversial. We report the case of a 41-year-old male who developed pleural mesothelioma. He had both, a prior short asbestos exposure and a thoracic radiotherapy for Hodgkin's disease 26years before. The evidence for radiotherapy as cause for mesothelioma is expanding and the diagnosis of mesothelioma in patients who had previous irradiation should be kept in mind.

HLA and celiac disease susceptibility: new genetic factors bring open questions about the HLA influence and gene-dosage effects.

Celiac disease (CD) is a chronic inflammatory disorder triggered after gluten ingestion in genetically susceptible individuals. The major genetic determinants are HLA-DQA1*05 and HLA-DQB1*02, which encode the DQ2 heterodimer. These alleles are commonly inherited in cis with DRB1*03∶01, which is associated with numerous immune-related disorders, in some cases contributing with a different amount of risk depending on the haplotype context. We aimed at investigating those possible differences involving DRB1*03∶01-carrying haplotypes in CD susceptibility. A family (274 trios) and a case-control sample (369 CD cases/461 controls) were analyzed. DRB1*03∶01-carrying individuals were classified according to the haplotype present (ancestral haplotype (AH) 8.1, AH 18.2 or non-conserved haplotype) after genotyping of HLA-DRB1, -DQA1, -DQB1, -B8, TNF -308, TNF -376 and the TNFa and TNFb microsatellites. We observe that the AH 8.1 confers higher risk than the remaining DRB1*03∶01-carrying haplotypes, and this effect only involves individuals possessing a single copy of DQB1*02. CD risk for these individuals is similar to the one conferred by inherit DQA1*05 and DQB1*02 in trans. It seems that an additional CD susceptibility factor is present in the AH 8.1 but not in other DRB1*03∶01-carrying haplotypes. This factor could be shared with individuals possessing DQ2.5 trans, according to the similar risk observed in those two groups of individuals.

Th17-related genes and celiac disease susceptibility.

Th17 cells are known to be involved in several autoimmune or inflammatory diseases. In celiac disease (CD), recent studies suggest an implication of those cells in disease pathogenesis. We aimed at studying the role of genes relevant for the Th17 immune response in CD susceptibility. A total of 101 single nucleotide polymorphisms (SNPs), mainly selected to cover most of the variability present in 16 Th17-related genes (IL23R, RORC, IL6R, IL17A, IL17F, CCR6, IL6, JAK2, TNFSF15, IL23A, IL22, STAT3, TBX21, SOCS3, IL12RB1 and IL17RA), were genotyped in 735 CD patients and 549 ethnically matched healthy controls. Case-control comparisons for each SNP and for the haplotypes resulting from the SNPs studied in each gene were performed using chi-square tests. Gene-gene interactions were also evaluated following different methodological approaches. No significant results emerged after performing the appropriate statistical corrections. Our results seem to discard a relevant role of Th17 cells on CD risk.

Association between shared epitope and anti-citrullinated peptide antibodies in rheumatoid arthritis: A systematic review and meta-analysis

The group of major histocompatibility complex (MHC) alleles known as shared epitope (SE)is to date the strongest rheumatoid arthritis (RA) genetic risk factor. Many studies have shown that the measurement of anti-citrullinated peptides antibodies would be useful in the diagnosis and follow-up of RA. Our aim is to determine the magnitude of the association between the possession of SE alleles and serum positive titres of antibodies against citrullinated peptides. Our selection criteria included case–control or cohort studies, where data involving antibodies against citrullinated peptides and SE in RA patients were available. No date or language restrictions were imposed. Bibliographical databases MEDLINE, Cochrane Database of Systematic Reviews and EMBASE were searched for pertinent literature. Two reviewers independently identified relevant citations and extracted data. Data extraction was then checked by two different reviewers. Five published and one unpublished (own data) studies were included in the final metaanalysis. Overall, 2700 European descent RA patients were included in this meta-analysis. A significant association between SE and positive titres of serum antibodies against citrullinated peptides [OR(95% CI) = 3.19 (2.21–4.60)] was found. Positive titres for antibodies against citrullinated peptides are threefold more frequent in RA patients who carry SE alleles than in those patients lacking them (AU)

El grupo de alelos del complejo mayor de histocompatibilidad (MHC) conocidos como epí-topo compartido (EC) es a día de hoy el más fuerte los factores de riesgo genético a artritisreumatoide (AR). Diferentes estudios han puesto de manifiesto que la presencia de autoanticuerpos contra péptidos citrulinados sería útil en el diagnóstico y seguimiento de la artritisreumatoide. Nuestro objetivo es determinar la magnitud de la asociación entre la posesión de alelos del SE y la presencia de títulos positivos de anticuerpos contra péptidos citrulinados. Nuestros criterios de selección incluyeron estudios de cohortes y caso-control en los que hubiera datos disponibles acerca de los anticuerpos contra péptidos citrulinados y el epítopo compartido en artritis reumatoide. No se hicieron restricciones de fecha ni de idioma. Se realizaron búsquedas en las bases de datos bibliográficas MEDLINE, Cochrane Database of Systematic Reviews y EMBASE. Dos revisores identificaron de manera independiente lascitas relevantes y extrajeron los datos. La extracción de datos fue comprobada posteriormente por dos revisores diferentes de los anteriores. En el meta-análisis definitivo se incluyeron cinco estudios publicados y uno no publicado(datos propios). En total se incluyeron 2700 casos de RA de ascendencia europea en el metaanálisis. Se encontró una asociación significativa entre los títulos de anticuerpos positivos y el hecho de ser portador de alelos del epítopo compartido [OR(95% CI) = 3.19 (2.21–4.60)]. Los títulos positivos de anticuerpos contra péptidos citrulinados son tres veces más frecuentes en pacientes de AR portadores de alelos del EC que en los no portadores (AU)

Study of polymorphisms in 4q27, 10p15, and 22q13 regions in autoantibodies stratified type 1 diabetes patients.

Type 1 diabetes (T1D) is a multifactorial disease mainly associated with the human leukocyte antigen region. Previous studies suggested the association of interleukin-2 (IL2) gene polymorphisms and its alpha- and beta-chain receptor (IL2RA and IL2RB) variants with different autoimmune diseases such as T1D, celiac disease, multiple sclerosis, and rheumatoid arthritis. All T1D studies were conducted in diabetic patients younger than 17 years at diagnosis. The aim of our study was to replicate these associations not only in pediatric patients, but also in individuals with late onset. We performed a genetic association study of chromosomal regions 4q27, 10p15, and 22q13 containing the IL2, IL2RA, and IL2RB genes in 445 T1D subjects and 828 healthy controls. Seven single nucleotide polymorphisms (SNPs) were selected, previously described as genetic factors related to several autoimmune diseases, and were analyzed by TaqMan assays. The reported association with T1D patients of the IL2RA-rs41295061 located in the 10p15 region was replicated and our data suggest a trend of association of the polymorphisms IL2-rs17388568 and IL2-rs6822844 in 4q27. The effect of these markers was independent of the age at disease onset. Furthermore, the polymorphisms studied in 4q27 were not dependent on the presence of autoantibodies; however, the effect of the associated SNP in 10p15 (IL2RA-rs41295061) was specific of patients sera positive for diabetes antibodies. In conclusion, our results seem to indicate that late-onset and young T1D patients share most genetic factors located in the studied regions, but some markers could correlate with the presence of T1D specific autoantibodies.

[Clonal eosinophilia revealed by recurrent Staphylococcus aureus infection]. / Hyperéosinophilie clonale révélée par une infection récurrente à Staphylococcus aureus.

Acquired eosinophilia is currently classified into secondary (reactional to underlying diseases), clonal (presence of a bone marrow histological, cytogenetic or molecular marker of a myeloid malignancy) and idiopathic (neither secondary nor clonal) categories. We report the case of a 47-year-old male who was admitted to the hospital for Staphylococcus aureus recurring infections. An hypereosinophilia was discovered and led to molecular analysis. The identification of FIP1L1-PDGFRA fusion gene permitted the diagnostic of clonal eosinophilia. Treatment by imatinib mesylate induced an haematological remission, the control of the infection and thoracotomy cicatrization. This case is original because of its infectious presentation and the efficacy of imatinib mesylate to control the infectious process.

Utility of oligoclonal IgG band detection for MS diagnosis in daily clinical practice.

An early and accurate diagnosis of multiple sclerosis (MS) is very important, since it allows early treatment initiation, which reduces the activity of the disease. Oligoclonal IgG band (OCGB) detection is a good ancillary tool for MS diagnosis. However, it was argued that its usefulness was limited by the high interlaboratory variability. In the last years, different techniques for OCGB detection have appeared. We performed a blinded aleatorized multicenter study in 19 Spanish hospitals to assess the accuracy and reproducibility of OCGB detection in this new scenario. We studied cerebrospinal fluid (CSF) and serum samples from 114 neurological patients. Every hospital contributed to the study with triplicated pairs of CSF and serum samples of six patients and analyzed 18 different samples. Global analysis rendered a sensitivity of 92.1%, a specificity of 95.1% and a Kappa value of 0.81. This shows that current techniques for OCGB detection have good accuracy and a high interlaboratory reproducibility and thus, represent a good tool for MS diagnosis. When we analyzed separately the different techniques used for OCGB detection, the highest concordance was observed in western blot with alkaline phosphatase detection (kappa=0.91). This indicates that high sensitivity techniques improve the reproducibility of this assay.

Polymorphisms in chromosome region 12q13 and their influence on age at onset of type 1 diabetes.

AIMS/HYPOTHESIS: A complex region covering numerous genes in 12q13 was first associated with type 1 diabetes in the Wellcome Trust Case-Control Consortium (WTCCC) study. Two studies performed in a white population have tested the association of polymorphisms within this region with age at onset of the disease, with seemingly contradictory results. We aimed at replicating three of the strongest signals in a group of patients with early and late disease onset. METHODS: Polymorphisms rs773107, rs2292239 and rs10876864 were genotyped in 444 type 1 diabetic Spanish participants (age at onset 0-65 years) and 861 controls. The influence of single nucleotide polymorphisms (SNPs) on age at onset was tested through stratified and continuous analyses. RESULTS: rs773107 and rs2292239 were significantly associated with the disease, while rs10876864 showed a trend towards statistical significance in the whole population analyses. Comparison of early-onset patients to controls was significant for the three polymorphisms (allelic p < 0.006). Late-onset patients and controls did not reveal statistical differences. Analysis of age at onset in both rs773107 and rs2292239 showed differences between genotypes (p ≤ 0.002), alleles (p ≤ 0.013) and homozygotes for the risk genotype (p ≤ 4 × 10(-4)). Polymorphism rs10876864 showed trends towards statistical significance in the allelic frequencies (p = 0.051) and homozygotes for the risk genotype (p = 0.056). Subjects with risk genotypes had a disease onset between 2 and 5 years earlier than carriers of protective alleles. CONCLUSIONS/INTERPRETATION: We replicate two of the previously studied associations in a Spanish population and find new evidence of the influence of the 12q13 region on age at onset of type 1 diabetes.

The R30Q DLG5 variant is not associated with celiac disease or inflammatory bowel disease in the Spanish population.

Alterations in intestinal epithelial permeability could underlie inflammatory bowel disease (IBD) and celiac disease (CeD) etiology, as supported by previous association studies. One related gene, DLG5 [discs, large homologue 5 (Drosophila)], has been associated with IBD in several populations and with CeD in the Dutch population. We tried to confirm the involvement of DLG5 in CeD performing a case-control study (725 CeD patients and 803 controls) by analysing the R30Q variant (rs1248696). Genetic frequencies did not significantly differ between groups (P > 0.80) and the meta-analysis with the Dutch data did not show any association. Additionally, we evaluated the effect of R30Q in IBD risk (858 patients), as discordant results were previously obtained. No association was detected. Our study does not support the effect of the R30Q DLG5 variant in CeD or IBD predisposition in the Spanish population.

[First intention management of obstructive sleep apnea syndrome (OSAS) by custom-made mandibular advancement device: the medium-term results. Prospective study by the General Hospital Pneumologists College (CPHG)]. / Traitement du syndrome d'apnées obstructives du sommeil (SAOS) par orthèse d'avancée mandibulaire sur mesure, en première intention: quels résultats à moyen terme? Etude prospective du Collège des pneumologues des hôpitaux généraux (CPHG).

OBJECTIVES: To demonstrate the efficacy and tolerance of present generation mandibular advancement devices in the first intention treatment for obstructive sleep apnea syndrome (OSAS), even when severe, after one year. METHODS: Between June 2006 and December 2007, 152 patients (male: 77%; age: 50.9±10.9 years; BMI: 26.3±3.6 kg/m(2); AHI: 25.5±13.9), without previous treatment, requesting management other than continuous positive pressure and dentally apt for a mandibular advancement device, were pre-included in a prospective one-year multicenter study (13 general hospitals). RESULTS: One hundred and twenty-nine patients were assessed at least once after fitting. The efficacy was noted as of day 90: the overall AHI fell from 24.8 to 10.8 (from 40.6 to 17.7 in the 40 patients with AHI>30) and the Epworth index decreased from 11.2 to 6.9 (12.8 to 8.1 for AHI>30). The AHI reduction was independent of gender, age, BMI and baseline AHI. The efficacy was maintained throughout the study period. Only eight patients withdrew for adverse events and seven for reasons of therapeutic failure. CONCLUSION: Mandibular advancement devices proved effective in first intention, including severe OSAS. No predictive individual efficacy factors emerged.

[2 + 2] Photocycloaddition of 2(5H)-furanone to unsaturated compounds. insights from first principles calculations and transient-absorption measurements.

The [2 + 2] photocycloaddition reaction of 2(5H)-furanone to ethylene and acetylene has been investigated by means of DFT and CASSCF methods. In both cases, the reaction involves the formation of a triplet 1,4-biradical intermediate that evolves to the cyclobutane product after spin inversion. For acetylene, the lowest energy path in the triplet surface occurs through the (3)(pi-pi*) state of the 2(5H)-furanone. However, in the reaction with ethylene the lowest energy path in the triplet surface involves the (3)(pi-pi*) state of the alkene. Although reaction through the triplet state of olefins is usually disregarded due to the short lifetime of these species, we have experimentally measured that sensitization of ethylene triplet state can occur at typical synthetic conditions and, thus, lead to photochemical addition to the lactone.

Lack of association of NKX2-3, IRGM, and ATG16L1 inflammatory bowel disease susceptibility variants with celiac disease.

Evidence about the presence of susceptibility factors shared among different autoimmune diseases is increasing. Based on this idea, NKX2-3, ATG16L1, and IRGM which are well-established inflammatory bowel disease risk factors, could be new celiac disease (CD) candidate genes. NKX2-3 encodes a transcription factor that in mice seems to be involved in gut development. The ATG16L1 and IRGM genes act in autophagy, a process related to innate and adaptive immunity. We aimed to study the implication of five polymorphisms in these genes in CD susceptibility: rs10883365 and rs888208 in the NKX2-3 gene, rs2241880 in ATG16L1, and rs10065172 and rs4958847 in IRGM. Association studies were performed using 725 Spanish CD patients and 956 ethnically matched healthy controls, as well as 309 parent-child trios. Genetic frequencies were compared with the chi(2) test and the familial study used the transmission disequilibrium test. Differences between CD patients and controls did not reach significance when genotypic and allelic frequencies were compared. No differential transmission of alleles or haplotypes from heterozygous parents to affected children was observed in the familial study. In conclusion, no evidence of association with CD has been reported for the Crohn's disease susceptibility polymorphisms studied in the NKX2-3, ATG16L1, and IRGM genes.