1,720,963 research outputs found
H3K27 acetylation and gene expression analysis reveals differences in placental chromatin activity in fetal growth restriction
No full textBackground: Posttranslational modification of histone tails such as histone 3 lysine 27 acetylation (H3K27ac) is tightly coupled to epigenetic regulation of gene expression. To explore whether this is involved in placenta pathology, we probed genome-wide H3K27ac occupancy by chromatin immunoprecipitation sequencing (ChIP-seq) in healthy placentas and placentas from pathological pregnancies with fetal growth restriction (FGR). Furthermore, we related specific acetylation profiles of FGR placentas to gene expression changes. Results: Analysis of H3K27ac occupancy in FGR compared to healthy placentas showed 970 differentially acetylated regions distributed throughout the genome. Principal component analysis and hierarchical clustering revealed complete segregation of the FGR and control group. Next, we identified 569 upregulated genes and 521 downregulated genes in FGR placentas by RNA sequencing. Differential gene transcription largely corresponded to expected direction based on H3K27ac status. Pathway analysis on upregulated transcripts originating from hyperacetylated sites revealed genes related to the HIF-1-alpha transcription factor network and several other genes with known involvement in placental pathology (LEP, FLT1, HK2, ENG, FOS). Downregulated transcripts in the vicinity of hypoacetylated sites were related to the immune system and growth hormone receptor signaling. Additionally, we found enrichment of 141 transcription factor binding motifs within differentially acetylated regions. Of the corresponding transcription factors, four were upregulated, SP1, ARNT2, HEY2, and VDR, and two downregulated, FOSL and NR4A1. Conclusion: We demonstrate a key role for genome-wide alterations in H3K27ac in FGR placentas corresponding with changes in transcription profiles of regions relevant to placental function. Future studies on the role of H3K27ac in FGR and placental-fetal development may help to identify novel targets for therapy of this currently incurable disease.</p
Biopsy techniques to study the human placental bed
No full textBackgroundThe physiologic transformation of uterine spiral arteries in the human placental bed is essential for a healthy pregnancy. Failure of this transformation due to deficient trophoblast invasion is widely believed to underlie pregnancy complications such as preeclampsia, foetal growth restriction, miscarriage and preterm labour. Understanding of invasive behaviour and remodelling properties of trophoblasts in the uterine wall is essential in elucidating the aetiology of these pregnancy complications. However, there is a lack of satisfactory specimens of the placental bed to enhance our knowledge on the mechanisms that control trophoblast invasion. Several techniques can be used to obtain biopsies from the placental bed and sample handling can be executed differently depending on the research question.MethodsThis systematic review provides an overview of all studies investigating the placental bed and sampling techniques used. Papers that described surgical techniques, specimen handling, complications and/or success rate of the placental bed biopsy procedures were included. Placental bed biopsies are an essential and feasible technique to study abnormalities in the placental bed associated with pregnancy complications.ResultsDepending on the technique used the likelihood of sampling a spiral artery and trophoblast from the placental bed is 51%–78% per case, without significant complications.ConclusionsCaution is needed when interpreting data if the placental bed is subjected to labour. We propose a uniform sampling technique and conservation protocol for the study of the placental bed and provide tools for selection of the appropriate technique for future placental bed collections
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
Early-onset preeclampsia : Constitutional factors and consequences for future pregnancy outcome and cardiovascular health
No full textIn this thesis, maternal constitutional factors related to long-term cardiovascular health and subsequent pregnancy outcome in women with early-onset preeclampsia is addressed. Aims of the thesis: To evaluate subsequent pregnancy outcome in women with a first pregnancy complicated by early-onset preeclampsia and to study risk factors for recurrence of preeclampsia and preterm delivery; To evaluate subsequent pregnancy outcome in women with a first pregnancy complicated by intrauterine growth restriction without maternal hypertensive disease; To characterize classic cardiovascular risk factors predictive of first cardiovascular events in primiparous women with a history of early-onset preeclampsia; To estimate global risk of major cardiovascular events in primiparous women with previous early-onset preeclampsia; To evaluate a novel circulating marker for ischemia, ischemia modified albumin (IMA), in normal pregnancy and preeclampsia; To provide a comprehensive review of previous studies on inflammatory; changes in preeclampsia, with emphasis on current understanding of the maternal innate and adaptive immune response; To study the role of allelic variants of the innate immunity receptors; Toll-like receptor 4 (TLR4) and nucleotide-binding oligomerization domain 2 (NOD2) and plasma inflammatory biomarkers in women with previous early onset preeclampsia; To evaluate the maternal acute-phase inflammatory response to influenza vaccination, as a model for mild in vivo stimulation of the immune system, in women with a history of early-onset preeclampsia
Variations 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
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
GESTATIONAL DIABETES MELLITUS: Challenges in diagnostics, management and impact
No full textGestational diabetes mellitus (GDM) is one of the most common metabolic disorders of pregnancy and is characterized by hyperglycemia. GDM is associated with adverse short- and long term outcomes of both mothers and their offspring. The research presented in this thesis covers the areas of diagnostics, management and impact of GDM. The main study in this thesis, the SUGAR-DIP trial, is a large, nationwide, multicenter trial, in which a new medication strategy for GDM is evaluated. In the study, a stepwise use of multiple oral glucose lowering drugs is compared to conventional insulin therapy. Oral medication has the advantage of being less invasive and thus more patient-friendly and it is expected that a combination of different oral agents is as effective as insulin. Outcomes of this trial may offer an additional, less burdensome treatment option for women with GDM. In addition to this treatment trial, we evaluate various other aspects of GDM, including the potential effect of newly proposed diagnostic criteria, novel ways to detect fetal overgrowth in diabetic pregnancies and several adverse outcomes related to GDM, such as hypertensive disorders of pregnancy, neonatal hypoglycemia and the effects of maternal diabetes on fetal cardiac development. In all these aspects of GDM, we face a continuous challenge of maintaining the balance between improving health for mothers and their offspring, and the extent of medicalization of pregnancy
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