Estudio de los efectos de los gradientes de temperatura en la difusión de neutrones térmicos

Se ha mostrado que la solución de la ecuación de colisión de Boltzmann para una mezcla binaria muy diluida, cuando la función de distribución del componente más concentrado está prefijada, puede hacerse por un método enteramente análogo al de Enskog. Como consecuencia de las condiciones del problema, se puede fijar solamente un parámetro arbitrario: la densidad de neutrones en cada elemento de volumen, y se puede obtener por el método de los invariantes de colisión, solamente una ecuación de conservación: la del número de neutrones. Se han aplicado estos resultados al caso de neutrones térmicos en un moderador, fijando convenientemente la función de distribución de los núcleos y considerando a estos y a los neutrones como esferas rígidas. Se ha obtenido de este modo la ley de difusión de neutrones corregida por los efectos de gradientes de temperatura; este efecto tiene el mismo origen que la difusión térmica. Se han hecho algunas aplicaciones numéricas en casos de interés práctico, o de realización experimental posible, para gradientes térmicos del orden de diez grados por centímetro. Se han calculado en esos casos variaciones del flujo escalar de neutrones de 2 a 3% o de 3 a 10% respectivamente, respecto a los mismos fenómenos con gradientes térmicos nulos. Resulta de todo esto, que la corrección a la ley de difusión por gradientes de temperatura, puede ser de interés para el caso de neutrones térmicos en medios dispersores, con variaciones de temperatura que se presentan habitualmente.Fil: Foglio, Mario Eusebio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

High prevalence of human cytomegalovirus in a population of periodontally healthy subjects

Background: Human cytomegalovirus (HCMV) appears to be more frequent in periodontally affected patients than in healthy control groups. Based on this assumption, it has been suggested that HCMV may play a role in the pathogenesis of periodontal disease. Objective: The objective of this uncontrolled study was to assess the occurrence of HCMV in a large unselected population of periodontally healthy subjects. Study Design: Fifty consecutive periodontally healthy patients satisfied the inclusion criteria. Two samples of gingival crevicular fluids were taken from two non-bleeding on probing sites for each patient. Samples were collected from the anterior and the posterior area. Polymerase chain reaction (PCR) was used to identify the presence of HCMV. Results: HCMV was detected in 17 (33%) out of 50 participants. Ten subjects showed presence of HCMV on both anterior and posterior sites, whereas the remaining 7 only had HCMV present in the anterior sites. No differences were noticed between HCMV positive and HCMV negative in terms of smoking (p = 0.33), drinking habits (p=0,94) or the presence of prosthodontic restorations (p= 0,89). Conclusions: HCMV was detected in a high proportion of periodontally healthy subjects. Its presence was not found to be influenced by smoking or drinking habits

A role for non-coding Tsix transcription in partitioning chromatin domains within the mouse X-inactivation centre

<p>Abstract</p> <p>Background</p> <p>Delimiting distinct chromatin domains is essential for temporal and spatial regulation of gene expression. Within the X-inactivation centre region (<it>Xic</it>), the <it>Xist </it>locus, which triggers X-inactivation, is juxtaposed to a large domain of H3K27 trimethylation (H3K27me3).</p> <p>Results</p> <p>We describe here that developmentally regulated transcription of <it>Tsix</it>, a crucial non-coding antisense to <it>Xist</it>, is required to block the spreading of the H3K27me3 domain to the adjacent H3K4me2-rich <it>Xist </it>region. Analyses of a series of distinct <it>Tsix </it>mutations suggest that the underlying mechanism involves the RNA Polymerase II accumulating at the <it>Tsix </it>3'-end. Furthermore, we report additional unexpected long-range effects of <it>Tsix </it>on the distal sub-region of the <it>Xic</it>, involved in <it>Xic</it>-<it>Xic </it>trans-interactions.</p> <p>Conclusion</p> <p>These data point toward a role for transcription of non-coding RNAs as a developmental strategy for the establishment of functionally distinct domains within the mammalian genome.</p

Genetic analysis of an F2 intercross between two chicken lines divergently selected for body-weight

<p>Abstract</p> <p>Background</p> <p>We have performed Quantitative Trait Loci (QTL) analysis of an F₂intercross between two chicken lines divergently selected for juvenile body-weight. In a previous study 13 identified loci with effects on body-weight, only explained a small proportion of the large variation in the F₂population. Epistatic interaction analysis however, indicated that a network of interacting loci with large effect contributed to the difference in body-weight of the parental lines. This previous analysis was, however, based on a sparse microsatellite linkage map and the limited coverage could have affected the main conclusions. Here we present a revised QTL analysis based on a high-density linkage map that provided a more complete coverage of the chicken genome. Furthermore, we utilized genotype data from ~13,000 SNPs to search the genome for potential selective sweeps that have occurred in the selected lines.</p> <p>Results</p> <p>We constructed a linkage map comprising 434 genetic markers, covering 31 chromosomes but leaving seven microchromosomes uncovered. The analysis showed that seven regions harbor QTL that influence growth. The pair-wise interaction analysis identified 15 unique QTL pairs and notable is that nine of those involved interactions with a locus on chromosome 7, forming a network of interacting loci. The analysis of ~13,000 SNPs showed that a substantial proportion of the genetic variation present in the founder population has been lost in either of the two selected lines since ~60% of the SNPs polymorphic among lines showed fixation in one of the lines. With the current marker coverage and QTL map resolution we did not observe clear signs of selective sweeps within QTL intervals.</p> <p>Conclusion</p> <p>The results from the QTL analysis using the new improved linkage map are to a large extent in concordance with our previous analysis of this pedigree. The difference in body-weight between the parental chicken lines is caused by many QTL each with a small individual effect. Although the increased chromosomal marker coverage did not lead to the identification of additional QTL, we were able to refine the localization of QTL. The importance of epistatic interaction as a mechanism contributing significantly to the remarkable selection response was further strengthened because additional pairs of interacting loci were detected with the improved map.</p

An Autosomal-Recessive Form of Cutis Laxa Is Due to Homozygous Elastin Mutations, and the Phenotype May Be Modified by a Heterozygous Fibulin 5 Polymorphism

Cutis laxa (CL) is a heterogeneous group of connective tissue disorders characterized by loose, sagging skin and variable involvement of other organs. Autosomal-dominant forms are relatively mild, and may be caused by mutations in the elastin gene, whereas the more severe recessive forms have been associated with mutations in the fibulin 4 and fibulin 5 genes, as well as in a vesicular ATPase subunit. We describe here a previously unreported autosomal-recessive form of CL caused by homozygous recessive mutations in exon 12 of the elastin gene (p.P211S) in three patients from two related consanguineous Syrian families. Furthermore, we found that the presence of a polymorphism in the fibulin 5 gene in one of the patients seems to modify the phenotype, producing more severe symptoms. This polymorphism (p.L301M) was associated with mild symptoms in the mother of the patient, who was heterozygous for both the elastin and fibulin 5 mutations. To our knowledge, autosomal-recessive CL owing to homozygous mutations in the elastin gene has not been reported previously

Novel Crohn Disease Locus Identified by Genome-Wide Association Maps to a Gene Desert on 5p13.1 and Modulates Expression of PTGER4

To identify novel susceptibility loci for Crohn disease (CD), we undertook a genome-wide association study with more than 300,000 SNPs characterized in 547 patients and 928 controls. We found three chromosome regions that provided evidence of disease association with p-values between 10(−6) and 10(−9). Two of these (IL23R on Chromosome 1 and CARD15 on Chromosome 16) correspond to genes previously reported to be associated with CD. In addition, a 250-kb region of Chromosome 5p13.1 was found to contain multiple markers with strongly suggestive evidence of disease association (including four markers with p < 10(−7)). We replicated the results for 5p13.1 by studying 1,266 additional CD patients, 559 additional controls, and 428 trios. Significant evidence of association (p < 4 × 10(−4)) was found in case/control comparisons with the replication data, while associated alleles were over-transmitted to affected offspring (p < 0.05), thus confirming that the 5p13.1 locus contributes to CD susceptibility. The CD-associated 250-kb region was saturated with 111 SNP markers. Haplotype analysis supports a complex locus architecture with multiple variants contributing to disease susceptibility. The novel 5p13.1 CD locus is contained within a 1.25-Mb gene desert. We present evidence that disease-associated alleles correlate with quantitative expression levels of the prostaglandin receptor EP4, PTGER4, the gene that resides closest to the associated region. Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4

ADAM33, a New Candidate for Psoriasis Susceptibility

Psoriasis is a chronic skin disorder with multifactorial etiology. In a recent study, we reported results of a genome-wide scan on 46 French extended families presenting with plaque psoriasis. In addition to unambiguous linkage to the major susceptibility locus PSORS1 on Chromosome 6p21, we provided evidence for a susceptibility locus on Chromosome 20p13. To follow up this novel psoriasis susceptibility locus we used a family-based association test (FBAT) for an association scan over the 17 Mb candidate region. A total of 85 uncorrelated SNP markers located in 65 genes of the region were initially investigated in the same set of large families used for the genome wide search, which consisted of 295 nuclear families. When positive association was obtained for a SNP, candidate genes nearby were explored more in detail using a denser set of SNPs. Thus, the gene ADAM33 was found to be significantly associated with psoriasis in this family set (The best association was on a 3-SNP haplotype P = 0.00004, based on 1,000,000 permutations). This association was independent of PSORS1. ADAM33 has been previously associated with asthma, which demonstrates that immune system diseases may be controlled by common susceptibility genes with general effects on dermal inflammation and immunity. The identification of ADAM33 as a psoriasis susceptibility gene identified by positional cloning in an outbred population should provide insights into the pathogenesis and natural history of this common disease

Brain

We report a composite extreme phenotype design using distribution of white matter hyperintensities and brain infarcts in a population-based cohort of older persons for gene-mapping of cerebral small vessel disease. We demonstrate its application in the 3C-Dijon whole exome sequencing (WES) study (n = 1924, nWESextremes = 512), with both single variant and gene-based association tests. We used other population-based cohort studies participating in the CHARGE consortium for replication, using whole exome sequencing (nWES = 2,868, nWESextremes = 956) and genome-wide genotypes (nGW = 9924, nGWextremes = 3308). We restricted our study to candidate genes known to harbour mutations for Mendelian small vessel disease: NOTCH3, HTRA1, COL4A1, COL4A2 and TREX1. We identified significant associations of a common intronic variant in HTRA1, rs2293871 using single variant association testing (Pdiscovery = 8.21 × 10-5, Preplication = 5.25 × 10-3, Pcombined = 4.72 × 10-5) and of NOTCH3 using gene-based tests (Pdiscovery = 1.61 × 10-2, Preplication = 3.99 × 10-2, Pcombined = 5.31 × 10-3). Follow-up analysis identified significant association of rs2293871 with small vessel ischaemic stroke, and two blood expression quantitative trait loci of HTRA1 in linkage disequilibrium. Additionally, we identified two participants in the 3C-Dijon cohort (0.4%) carrying heterozygote genotypes at known pathogenic variants for familial small vessel disease within NOTCH3 and HTRA1. In conclusion, our proof-of-concept study provides strong evidence that using a novel composite MRI-derived phenotype for extremes of small vessel disease can facilitate the identification of genetic variants underlying small vessel disease, both common variants and those with rare and low frequency. The findings demonstrate shared mechanisms and a continuum between genes underlying Mendelian small vessel disease and those contributing to the common, multifactorial form of the disease

Estudio de los efectos de los gradientes de temperatura en la difusión de neutrones térmicos

Se ha mostrado que la solución de la ecuación de colisión de Boltzmann para una mezcla binaria muy diluida, cuando la función de distribución del componente más concentrado está prefijada, puede hacerse por un método enteramente análogo al de Enskog. Como consecuencia de las condiciones del problema, se puede fijar solamente un parámetro arbitrario: la densidad de neutrones en cada elemento de volumen, y se puede obtener por el método de los invariantes de colisión, solamente una ecuación de conservación: la del número de neutrones. Se han aplicado estos resultados al caso de neutrones térmicos en un moderador, fijando convenientemente la función de distribución de los núcleos y considerando a estos y a los neutrones como esferas rígidas. Se ha obtenido de este modo la ley de difusión de neutrones corregida por los efectos de gradientes de temperatura; este efecto tiene el mismo origen que la difusión térmica. Se han hecho algunas aplicaciones numéricas en casos de interés práctico, o de realización experimental posible, para gradientes térmicos del orden de diez grados por centímetro. Se han calculado en esos casos variaciones del flujo escalar de neutrones de 2 a 3% o de 3 a 10% respectivamente, respecto a los mismos fenómenos con gradientes térmicos nulos. Resulta de todo esto, que la corrección a la ley de difusión por gradientes de temperatura, puede ser de interés para el caso de neutrones térmicos en medios dispersores, con variaciones de temperatura que se presentan habitualmente.Fil: Foglio, Mario Eusebio. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Daily and annually variation of unstimulated whole saliva flow rate and ph and their relation with body profile in healthy young adults.

AIM: To analyse pH and flow rate (FR) of unstimulated whole saliva (UWS), detecting their possible correlations both among themselves and with body profile; in addition to identify daily, annually and gender differences. MATERIALS AND METHODS: Eighty-one (47 ?; 34 ?) healthy young adults (mean age 22.7±4.09 years old) were enrolled. Saliva was sampled using spitting method. The data were statistically analysed using Pearson's coefficient, ANOVA or Kruskal-Wallis test, Student's t test or the Wilcoxon-Mann-Whitney test. RESULTS: The mean UWS/FR was 0.643 ml/min (range 0.164-1.656 ml/min; percentile 25 = 0.400 ml/min; percentile 50 = 0.643 ml/min, percentile 75 = 0.832 ml/min; median = 0.590 ml/min) and no significant differences were found in gender. The mean UWS/pH was 6.95 (range 6.06-7.91, S.D. 0.28, RSD % 4.08): pH was higher in males (7.02) than females (6.92; p = 0.009). The UWS/FR increased almost steadily during the day: from 0.593 ml/min at 9:00 to 0.669 ml/min at 17:00 (p = 0.04), the greatest increase was found between 9:00 and 11:00. Through the seasons the UWS/FR decreased from summer to spring with a difference of 0.048 ml/min (p < 0.05). The UWS/pH showed a slight increase between 9:00 and 17:00 (p < 0.05). There were little differences in UWS/pH among the seasons (max. 0.09; p < 0.05). Only a significant correlation between UWS/FR and pH was found (R = 0.20; p = 0.008). CONCLUSIONS: We did not find correlations between body profile vs UWS/FR or pH. UWS/FR varies more widely than UWS/pH: maintaining a proper acid/base balance is an essential factor for the homeostasis of the oral cavity and probably this would explain the reason for the lack of the variables evaluated influencing UWS/pH