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dna methylation as a predisposition factor in the pathogenesis of congenital hypothyroidism
Full text linkCongenital hypothyroidism (CH) is the most frequent endocrinopathy in newborn. If not promptly treated lead to a severe impairment of psychomotor development. The etiophatogenesis of CH is still poorly understood; although several causative genes are identified, they can explain only a small portion of the pathological phenotypes. This scenario is further complicated if we focused on the incidence of CH in different context. In fact, epidemiological data indicate that children born prematurely have a 3-5 fold higher risk of CH. In addition premature infants born small for gestational age (SGA) have a risk of 12% higher to develop IC compared to prematures with appropriate development (AGA). The mechanisms that justify the increased risk of IC are still unknown. Some studies report that aberrant methylation patterns are associated with prematurity, intrauterine fetal development and the onset of some diseases. This project is focused on the study of DNA methylation, as predisposing factor to permanent thyroid dysfunction with neonatal onset.
Using the Illumina Infinium-HumanMethylation27 technology we analyzed the global DNA methylation patterns (AVG) and selected the differentially methylated genes (DMGs) between 31 CH-cases born premature, AGA or SGA, and 28 term or preterm controls. To better understand the relationship between the DNA methylation and the premature birth, the intrauterine growth and the thyroid defect, the following groups were selected according to the gestational age at birth: 12 CH-with very preterm birth (CH-VPB37wks). The same subjects were then analyzed according to intrauterine growth (20 CH-SGA, 11 CH-AGA than 6 C-SGA and 20 C-AGA) or the degree of CH: 19 with overt CH (OH, TSH>10 U/L) and 12 with mild CH (MH, TSH<10 U/L) than 16 CPB and 12 CTB.
The global methylation analysis showed that infants born prematurely and SGA have a significant hypomethylation than term-controls. These data were confirmed by the gene-specific methylation analysis, through which we selected a large group of differentially methylated genes (DMGs) in CH-cases than term controls. Interestingly, the 95% of the DMGs are hypomethylated and the 70% of them are represented by CpG sites located in DNA non-coding regions. The gene ontology analysis revealed that genes involved in fetal growth and thyroid hormone metabolism were included among DMGs. The analysis of nine maternal genomic DNA for polymorphisms at the MTHFR revealed the possible association with folate deficiency during pregnancy and the global hypomethylation status of affected newborns.
This is the first work exploring the role of epigenetic influences in the predisposition to congenital hypothyroidism. Our results suggest that genomic instability caused by global hypomethylation of non-coding regions may be related to premature birth and fetal growth delay. Under these conditions, thyroid defects are more frequent than expected and could result from the increased expression of predisposing genes, rather than from the reduced expression of protective genes. The role of maternal conditions during pregnancy seems to be a key factor to determine a proper DNA methylation pattern on fetus. Based on the Developmental Origin of Health and Disease Theory, we can assume that adverse condition during pregnancy, such as folate deficiency, may produce a fetal epigenetic reprogramming and the adaptation of preterm neonate to the extrauterine life includes among other dysfunctions a thyroid functional impairment. If this data will be confirmed by further experiments, this could represent a new predisposing factor to take into account during pregnancy to prevent and improve the prenatal screening of CH
Valutazione degli intangibili
No full textForse qualcuno non si è ancora accorto che la Finanza è radicalmente cambiata. Per sempre. Per un decennio e più la Finanza aziendale (corporate finance) è stata maltrattata, abusata, confusa con altre discipline - essenzialmente quantitative - se non contrabbandata per pura modellistica da "computer-dipendenti". No, la Finanza aziendale è (ed è sempre stata) la disciplina che studia raccolta e impiego di risorse; che mira al conseguimento di un equilibrio di lungo termine attraverso adeguati processi di pianificazione e programmazione; che controlla e gestisce il rischio, nell’operatività ordinaria e straordinaria. La Finanza aziendale mette nel suo mirino gli imprenditori, le imprese, le istituzioni; attraverso i mercati e la dinamica dei flussi, ricerca l’equilibrio di sistema e si ispira alla sostenibilità. A trent’anni dall'uscita del Trattato di Finanza Aziendale curato da un Maestro della materia, Giorgio Pivato, un’opera (in due volumi) che riscopre e conferma il vero senso, i contenuti più radicati della Finanza aziendale
Role of Jagged1-Notch pathway in thyroid development
No full textThe zebrafish thyroid gland shows a unique pattern of growth. Despite the lack of a compact gland, the zebrafish thyroid tissue originates from the pharyngeal endoderm and the main genes involved in its patterning and early development are conserved between zebrafish and mammals. In recent years, the research has been focused to the search of novel candidate genes and environmental factors underlying congenital hypothyroidism. Among these, it has been demonstrated that the Notch signalling plays a central role during zebrafish thyroid development. In this review, we will provide an overview of the current knowledge of the distinct roles of the Notch signalling and of the jag1a and jag1b ligands during the different phases of thyroid organogenesis. Furthermore, we will discuss the role of JAG1 variants in congenital thyroid defects
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Stima dello stato di corrosione di tubazioni interrate in acciaio in presenza di correnti vaganti
No full textVariations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
In vivo Functional Consequences of Human THRA Variants Expressed in the Zebrafish
Full text linkBackground: Heterozygous mutations in the thyroid hormone receptor alpha (THRA) gene cause resistance to thyroid hormone alpha (RTHα), a disease characterized by variable manifestations reminiscent of untreated congenital hypothyroidism but a raised triiodothyronine/thyroxine ratio and normal thyrotropin levels. It was recently described that zebrafish embryos expressing a dominant negative (DN) form of thraa recapitulate the key features of RTHα, and that zebrafish and human receptors are functionally interchangeable. Methods: This study expressed several human thyroid hormone receptor alpha (hTRα) variants in zebrafish embryos and analyzed the resulting phenotypes. Results: All hTRα-injected embryos showed variable defects, including cerebral and cardiac edema likely caused by an aberrant looping during heart development, anemia, and an incomplete formation of the vascular network. Moreover, the hTRα-injected embryos presented severe defects of motorneurons and craniofacial development, thus affecting their autonomous feeding and swimming behaviors. Surprisingly, expression of all hTRα mutants had no detectable effect on thyrotropin beta and thyrotropin-releasing hormone transcripts, indicating that their DN action is limited on the thyroid hormone reception beta 2 targets at the hypothalamic/pituitary level in vivo. As previously described in vitro, treatment with high triiodothyronine doses can efficiently revert the observed defects only in embryos injected with missense hTRα variants. Conclusion: Injection of human THRA variants in zebrafish embryos causes tissue-specific defects recapitulating most of the RTHα clinical and biochemical manifestations. The described manipulation of zebrafish embryos represents a novel in vivo model to screen the functional consequences of THRA variants and the rescue potential of new therapeutic compounds
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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