1,720,959 research outputs found
Novel Targets of FASD Pathogenesis in the Developing Hippocampus
Get PDFPrenatal alcohol exposure can contribute to fetal alcohol spectrum disorders (FASD), characterized by a myriad of developmental impairments affecting behavior and cognition. Studies show many of these functional impairments are associated with the hippocampus, a structure exhibiting exquisite vulnerability to developmental alcohol exposure and critically implicated in learning and memory, however mechanisms underlying alcohol-induced hippocampal deficits remain poorly understood. Utilizing a high-throughput RNA-Seq approach to address the neurobiological and molecular basis of prenatal alcohol-induced hippocampal functional deficits, we hypothesized that chronic binge prenatal alcohol exposure alters gene expression and global molecular pathways in the fetal hippocampus. Timed-pregnant Sprague Dawley rats were randomly assigned to a pair-fed control (PF) or binge-alcohol treatment (ALC) group on gestational day (GD) 4. ALC dams acclimatized from GD 5-10 with a daily treatment of 4.5 g/kg alcohol and subsequently received 6 g/kg on GDs 11-20. PF dams received a once-daily maltose dextrin gavage on GDs 5-20, isocalorically matching ALC counterparts.
On GD 21, bilateral hippocampi were dissected, flash frozen, and stored at -80��C. Total RNA was then isolated from homogenized tissues. Samples were normalized to ~4nM and pooled equally. Sequencing was performed by Illumina NextSeq 500 on a 75 cycle, single end sequencing run. RNA-Seq identified 13,388 genes, of these, 76 genes showed a significant difference (P 2) in expression between the PF and ALC groups. 49 genes showed sex-dependent dysregulation, of which, 23 were significantly altered in ALC-exposed females, 26 were altered in ALC-exposed males, and 2 were altered in both ALC-exposed males and females compared with PF offspring. We conclude that chronic binge alcohol exposure during pregnancy dysregulates fetal hippocampal gene expression in a sex-specific manner. Identification of subtle, transcriptome-level dysregulation in hippocampal molecular pathways offers potential mechanistic insights underlying FASD pathogenesis
THE ROLE OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 6 IN PLACENTAL DEVELOPMENT UNDER GESTATIONAL DIABETES
Get PDFAbnormal placenta development has been indicated in preeclampsia and gestational diabetes (GDM), which are both common yet serious complications in approximately 10% of pregnancies. Proprotein convertase subtilisin/kexin-6 (PCSK6) is a protease that processes precursor proteins into active forms. Based on previous reports of PCSK6 expression in the placenta, involvement in embryonic development and vascular remodeling, we hypothesized that PCSK6 plays an important role in placenta development. Our WT placentas had a dynamic expression of PCSK6 in glycogen trophoblast cells (GlyT). In mouse hyperglycemic (HG) pregnancies, PCSK6 protein levels were decreased which led us to further pursue the interaction of PCSK6 and HG. The current study applied a PCSK6 transgenic mouse model consisting of four groups: WT and PCSK6 knockout (KO) placentas from normoglycemic (NG) and HG pregnancies. Histological examination of placenta disclosed that HG, but not PCSK6 KO, increased GlyT area within the junctional zone via differentiation. The spiral arteries (SpAs) in PCSK6 KO placentas, under NG and HG conditions, had decreased inner to outer diameter ratios and reduced trophoblast giant cell association compared to the WT placentas. Consistently, PCSK6 KO placentas over-phosphorylate ��-catenin, a key protein to regulate transcription of migratory proteins. In the labyrinth, PCSK6 KO affected fetal capillary area while HG affected maternal lacunae area. PCSK6 KO-HG placentas had increased interhaemal membrane thickness. From these factors, the calculated diffusion capacity was increased in PCSK6 KO under NG but decreased under HG. In summary, our study demonstrated that PCSK6 is involved in SpA remodeling and glucose-dependent angiogenesis. Our study indicated a potential role of PCSK6 in preeclampsia and GDM related placenta dysfunctions. Future study will focus on understanding the molecular mechanisms underlying how PCSK6 deletion disrupted normal placenta development and function
Mechanisms underlying fetal alcohol spectrum disorders: ovine model
Get PDFMaternal alcohol abuse during pregnancy can result in a range of structural and
functional abnormalities that include lifelong physical, mental, behavioral and learning
disabilities, now collectively termed as Fetal Alcohol Spectrum Disorders (FASD). The
incidence of FASD is now estimated be as high as 10 per 1000 live births. Each year,
40,000 babies are born with FASD in the United States at an estimated cost of 6 billion. Because of the magnitude of this
problem and because the incidence has not decreased in spite intensive efforts to educate
women to not abuse alcohol during pregnancy, ways to prevent or mitigate the effects of
prenatal alcohol exposure must be explored in addition to education. Therefore, we
wished to identify the precise mechanisms by which alcohol mediates the
neurodevelopmental damage in order to develop intervention/amelioration strategies.
The present study was conducted using an ovine model system. The large body
mass of the ovine fetus, the longer gestation that is more similar to that of humans, and
that all three trimester equivalents occur in utero, make the sheep an excellent model to
study the effects of alcohol on the developing fetus. Our study establishes that maternal alcohol exposure does not result in fetal cerebral hypoxia. Instead, alcohol results in
hypercapnea and acidemia leading to a cascade of events in the maternal and fetal
compartments that include deficits in the levels of glutamine and glutamine-related
amino acids, alterations in endocrine axes, oxidative stress, alteration in cardiovascular
homeostasis and fetal neuronal loss. Further, we demonstrate that inhibiting the novel
two-pore domain acid sensitive potassium channel (TASK) expressed in the cerebellar
granule cells and the peripheral and central chemoreceptors may prove to a be potential
therapeutic strategy. Preventive strategies that are safe to use in pregnant women and
that involve glutamine-related pathways are also suggested. Finally, the study also
establishes the beneficial effects of moderate alcohol consumption on the fetal skeletal
system
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Variations on the Author
Get PDF“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
Get PDFWe 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
Developmental Outcomes of Prenatal E-cig Aerosol Vaping
Get PDFElectronic cigarettes (e-cigs) are tobacco products that have become popular among youth and young adults due to targeted advertising and misconceptions about their safety. The unfounded perception that e-cigs are less harmful than traditional cigarettes may result in the use of e-cigs during pregnancy. There are limited studies evaluating the effects of e-cig aerosol exposure on pregnancy in animal models and only a single report of gestational e-cig exposure in humans. To examine the impact of prenatal e-cig aerosol exposure on pregnancy and development we utilized a pregnant Sprague-Dawley rat model combined with a chronic, whole-body, environmental exposure to e-cig aerosols generated by commercially available e-cig atomizers. We found that exposure to e-cig aerosols containing nicotine significantly reduced fetal and neonatal growth, but aerosols without nicotine did not. Growth restriction was accompanied by reduced blood flow in the maternal uterine artery and fetal umbilical artery. Analysis of signature amino acid profile revealed altered concentrations in maternal and fetal plasma of animals exposed to e-cig aerosols with nicotine. Amino acid concentrations in the fetal lungs were altered by e-cig aerosols regardless of nicotine. RNA sequencing of fetal lung transcriptome showed altered expression after exposure to e-cig aerosols with and without nicotine. E-cig aerosols containing nicotine altered neonatal lung morphology and produced trends in respiratory mechanics that may increase the workload of breathing. Interestingly, e-cig aerosols with and without nicotine reduced the area of the pressure-volume loop during forced oscillation techniques which may indicate increased atelectasis in neonatal lungs. The effects of prenatal e-cig aerosol exposure were more pronounced in animals exposed to aerosols containing nicotine, however, e-cig aerosols without nicotine were also found to effect the physiology of pregnancy. Further studies will be required to identify molecular mechanisms of e-cig aerosol induced alterations to pregnancy and development. The data presented in these studies lay a foundation for our understanding of prenatal exposure to e-cig aerosols by providing evidence that e-cig vaping during pregnancy can have deleterious outcomes for the developing offspring
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe 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
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