1,720,960 research outputs found
Prenatal stress-mediated fetal programming of obesity in diet-induced obese and dietary resistant rats
Get PDFGenotype, diet and environment or life style factors are known to be associated with the development of obesity and metabolic syndrome in adults. However, recent evidence suggests that prenatal factors could contribute to obesity as well. One of the prenatal factors implicated in the development of metabolic syndrome in the offspring is stress, which is known to increase circulating glucocorticoids during pregnancy. Prolonged exposure of the developing fetus to excess glucocorticoid levels results in long lasting neuroendocrine changes which predispose the offspring to obesity and other cardiovascular disorders. Considering the fact that 30% of today's maternal population is obese, it is also important to address the impact of prenatal stress in the background of maternal obesity. Hence, we used diet-induced obese (DIO) and dietary resistant (DR) rat model to explore the mechanisms underlying prenatal stress mediated fetal programming of obesity in DIO and DR rats. Prenatal stress was associated with catch up growth and hyperinsulinemia in the DIO offspring. Although, prenatal stress reduced birth weight in the DR offspring, it did not result in any other adverse metabolic outcomes. Next, we investigated the role of stress axis hyperactivation in prenatal stress-induced metabolic programming in the DIO offspring. In the DIO rats, prenatal stress resulted in hyperactivation of stress axis marked by increased norepinephrine (NE) levels in the paraventricular nucleus in the  hypothalamus and increased corticotrophin releasing hormone levels in the median eminence. However, the serum corticosterone (CORT) levels were not altered in the prenatally stressed DIO and DR offspring. Despite, no change in circulating CORT levels, glucocorticoids might play a role in metabolic syndrome through increasing 11β-hydroxysteroid dehydrogenase enzyme (11βHSD1) in the target tissues. 11βHSD1 is highly expressed in metabolically active tissues like liver and adipose tissue and is involved in the intracellular generation of CORT by converting inactive 11-dehydroCORT to active CORT. Hence, we investigated the role of 11βHSD1 in the liver and adipose tissue in prenatal stress mediated metabolic programming. Prenatal stress significantly increased 11βHSD1 mRNA and protein expression in the visceral adipose tissue accompanied with hypertrophied adipocytes in the DIO offspring. There were no differences in 11βHSD1 expression in the liver suggesting prenatal stress results in tissue-specific programming of 11βHSD1 expression. Taken together, the results suggest that prenatal stress produces differential metabolic effects in DIO and DR rats. Further, 11βHSD1 could mediate the metabolic effects observed in the prenatally stressed offspring and thus may be a potential mechanism for fetal origins of obesity.Thesis (Ph. D.)--Michigan State University. Pharmacology and Toxicology-Environmental Toxicology, 2012Includes bibliographical references (pages 159-178
Low dose chronic estradiol-17beta exposure induces ovarian pathology and inhibits tuberoinfundibular dopaminergic neuronal function by inducing a proinflammatory state within the arcuate nucleus
No full textEstrogen exposure is known to cause hyperprolactinemia which can lead to the development of mammary and pituitary tumors. This hyperprolactinemia is associated with a decrease in the activity of tuberoinfundibular dopaminergic (TIDA) neurons of the hypothalamus. Perikarya of TIDA neurons are located in the arcuate nucleus (AN) of the hypothalamus and their axon terminals extend to the median eminence (ME). Here, dopamine is secreted into the hypophyseoportal circulation and acts on lactotrophs in the anterior pituitary gland to provide tonic inhibition of prolactin release. Therefore, if the activity of TIDA neuronal function is inhibited by estrogen, there is a decrease in dopamine (DA) levels, prolactin is no longer inhibited and a state of hyperprolactinemia ensues. Though it has been established that estrogens inhibit TIDA function, the mechanism by which estrogen exerts this effect has not been clearly elucidated. We hypothesized that a low dose of estradiol17-\ue2 (E2) would cause an increase in IL-1\ue2 and nitrate levels within the arcuate nucleus (AN), and that this local proinflammatory environment would damage TIDA neurons through nitration of tyrosine hydroxylase, which is the rate-limiting enzyme in DA synthesis. To test this hypothesis, we exposed reproductivelyintact and ovariectomized female Sprague-Dawley rats to E2 by subcutaneously implanting them with slow-release E2 pellets which release E2 at 20ng per day for 90 days. After 90 days of exposure, the animals were sacrificed and serum was collected for hormonal analysis, brain sections were microdissected to analyze IL-1\ue2 and nitrate levels in the AN via ELISA and modified Griess assay, respectively, the ME was microdissected and analyzed for the neurotransmitter DA using high performance liquid chromatography (HPLC), and western blot was performed to measure tyrosine hydroxylase (TH) and nitration of TH (nT) in the ME. Our results demonstrate that indeed, chronic exposure to a low dose of E2 increased serum prolactin, decreased DA levels in the ME, increased IL-1\ue2 and nitrate concentrations in the AN and increased the ratio of nT to TH in the ME. These findings provide strong evidence that chronic exposure to a low level of E2 induces a proinflammatory state within the AN and this may be a possible mechanism by which E2 exposure causes inhibition of TIDA activity and hyperprolactinemia.Additionally, estrogen exposure is known to affect the reproductive axis and to induce ovarian follicular cysts. Exposure to estrogen has been implicated as a model for polycystic ovary syndrome (PCOS) in women. However, most studies claiming this association, have primarily focused on the ovarian morphologic phenotype and have not thoroughly assessed the other clinical parameters that would correlate with those seen in women with PCOS. We explored whether our paradigm of chronic exposure to low levels E2 could cause changes in ovarian morphology and hormonal profiles similar to that of PCOS. Adult female rats were sham-implanted (control) or implanted with slow-release E2 (20 ng/day) pellets for 30 (E-30), 60 (E-60), or 90 (E-90) days. Old constant estrous (OCE) rats were used for comparison. At the end oftreatment, ovaries were collected and subjected to histological examination and Mullerian inhibiting substance (MIS) immunohistochemistry. We found that follicular size increased with E2 exposure and the number of corpora lutea (CL) decreased in a exposure-dependent manner indicating failure of ovulation. Estradiol treatment was associated with a decrease of MIS immunolabeling in follicles. Serum testosterone (T) levels decreased in a duration dependent manner with E2 treatment. Also, the ratio of serum LH to FSH remained unaffected in different groups. While ovarian changes observed in this model are similar to that seen in PCOS, the hormonal profiles are very different from that observed in PCOS and we therefore determined that this may not be a true model for this condition.Thesis (Ph. D.)--Michigan State University. Pathology, 2011Includes bibliographical references (pages 142-158
BT2 as a novel therapeutic compound for Alzheimer’s disease
No full textAlzheimer’s disease (AD) is estimated to be the sixth leading cause of death in the U.S. without any effective treatment strategies. Our lab has shown that elevated branched-chain amino acids (BCAAs) may play a causal role in the progression of AD-related pathology. Our pilot data revealed that 8 weeks of dietary BCAA restriction in AD mice alleviated AD-related brain pathology and improved cognitive function. Although we observed beneficial effects from dietary intervention, this approach is practically challenging because BCAAs are found in a wide variety of foods. This prompted us to test the effects of pharmacologically lowering BCAAs in AD mice using BT2, a small molecule that increases BCAA breakdown. First, we used cognitively impaired APP/PS1 and wildtype (WT) mice to test the effects of BT2 on cognitive function, AD-related pathology and associated metabolic dysfunction. We found that BT2 did not alleviate cognitive impairment or AD-related pathology in late-stage APP/PS1 mice. We then used cognitively intact 6-week-old 5xFAD mice and wildtype (WT) mice to test the effects of BT2 on early AD-related brain pathology. BT2 lowered plasma BCAAs as expected, normalized 5xFAD FBG levels to WTs, restored key neurotransmitters (NTs) associated with memory and learning functions, and reduced GSK3β which may help minimize the formation of neurofibrillary tangles (NFTs). Next, we wanted to test if BT2 prevents and/or delays the progression of cognitive decline or AD-related pathology if administered in the early stages of AD development before the onset of cognitive impairment in 5xFAD mice. At 17 weeks of age, the 5xFAD BT2 group displayed higher cognition compared to 5xFAD controls based on spontaneous alternation during Y Maze and restored key NTs. Our findings suggest that early intervention with BT2 has therapeutic effects on AD-related pathology and cognitive impairment in 5xFAD mice. Further research is needed to test different dosing, durations, sex, and route of administration
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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