410 research outputs found
A Role of Visceral Adipose and Gastric Tissue in Inflammatory Conditions Associated With Metabolic Syndrome
No full textObesity has reached epidemic proportions globally. Obesity is accompanied by co-morbidities affecting multiple peripheral tissues. Obesity associated non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the US. The molecular mechanisms underlying the development and the progression of NAFLD, however, remain poorly understood. Stomach is an important endocrine organ that produces a number of bioactive peptides with important roles in the metabolism of energy. Stomach is located in the vicinity of the liver, but so far it has been largely neglected as an organ with potentially important role in obesity and associated NAFLD. This study provides the evidence for the contribution of the stomach-specific expression changes in a number of molecules previously implicated in inflammation and energy homeostasis to the pathogenesis of obesity-associated NAFLD. White adipose tissue (WAT) represents the majority of adipose tissue in humans, is the main fat storage organ. In contrast, brown adipose tissue (BAT) has a unique ability to spend energy through producing heat in mitochondrial "uncoupling". The facultative nature of BAT activity and its distribution within WAT depots complicate the detection of BAT in adult humans. In this study, the expression of genes involved in transcriptional regulation of brown adipocyte-specific UCP1 gene and BAT differentiation was assessed as quantitative indicator of BAT activity in adipose of adult humans.This work is embargoed by the author and will not be available until June 2014
TRANSCRIPTOME ANALYSIS OF EPICARDIAL ADIPOSE TISSUE AND MYOCARDIUM IN DIFFERENTIAL BODY MASS STATES
No full textThis work is embargoed by the author and will not be publicly available until May 15, 2025.Cardiomyopathy is characterized by a physiological change in the function and anatomy of the cardiovascular systems, leading to morbidity and mortality. Epicardial Adipose tissue (EAT) is functionally distinct from peripheral adipose, where it serves as a cardiovascular regulator rather than an energy repository. The molecular mechanisms by which epicardial adiposity could contribute to coronary artery disease remain poorly understood. This study examined the relative epicardial coverage by EAT, as well as gene expression and molecular pathways in the EAT and proximal myocardium of individuals belonging to three different weight categories. We showed that in both myocardium and EAT the changes from a normal body mass index to obesity result in adverse metabolic state. We have also determined that the positional coverages of epicardial adipose tissue in varying states of body differ, and can be used as a novel clinical marker for heart disease2025-05-1
A Machine Learning and Networks Approach to Infer Disease Mechanisms
No full textAll biological problems, including cancer, mental disorders, rare diseases, and immunological disorders, are complex multisystem pathophysiological shifts facilitated by functional changes. Multiple points of origin and mechanisms can contribute, including genetic mutations, epigenetic factors, protein misfolding, and differential gene expression, which promote such functional abnormalities. This dissertation describes mega-analysis and machine learning methods to identify and select essential entities that are prime candidates for drivers of such disorganization. Furthermore, heterogeneous networks have been employed to achieve a more thorough pathway analysis that takes protein-protein interactions into account. This dissertation contains four projects, investigating PPARD’s role in major depressive disorder, exploring the link between schizophrenia and myocardial infarctions, identifying the connections between atopic dermatitis and major depressive disorder, and finally, biomarker identification for survival status prediction of patients with brain cancer.This work is embargoed by the author and will not be publicly available until 2024-08-31.2024-08-3
Bioinformatics of Genome Regulation and Systems Biology
No full textThis eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contac
A Study of Systemic Inflammation and Brown Adipose Cells Embedded in Visceral Adipose of Obese Patients
No full textObesity has become a major epidemic, not just in the US, but in many other industrialized nations around the world. Obesity has risen due to the natural conflict between availability of calorie-rich foods and energy efficient metabolisms naturally selected for tens of thousands of years in the past. Unfortunately, obesity is detrimental to health as it is associated with a number of chronic conditions including type II diabetes and liver disease. This study explores the effects of the accumulation of visceral adipose on systemic inflammation as measured within adipose itself, in circulation, and in the liver parenchyma as determined by histopathology. The cross-talk between omental deposits of adipose and liver was analyzed by profiling serum cytokine levels, adipose gene expression, and liver biopsy histopathology for 241 morbidly obese patients undergoing bariatric surgery. We showed that the levels of pro-inflammatory cytokines increase in parallel with an increase in the severity of liver disease, while the levels of anti-inflammatory factors decrease. Additionally, we studied expression levels of genes that define the differentiation and activity of brown adipose cells within visceral adipose collected from the same cohort of morbidly obese subjects. We showed that expression levels for genes specific for brown adipose tissue decrease proportionally to the increase in both serum and histological indicators of systemic inflammation. Importantly, our study is the first to provide evidence that scattered brown adipocytes may be present in visceral adipose of morbidly obese subjects and that their numbers or activity levels may diminish with an increase in systemic inflammation associated with obesity and metabolic syndrome.This thesis was embargoed by the author and will not be available until May 30, 2019
Mitochondrial Haplogroups in Obese Patients Predisposed to Non-Alcoholic Fatty Liver Disease (NAFLD)
No full textLiver diseases are considered a significant health problem worldwide. Non-alcoholic fatty liver disease (NAFLD), which is widely considered the hepatic manifestation of the metabolic syndrome, is a complex multifactorial disease trait where environment and genetic variations interact to determine the wide spectrum of disease progression. One of the key challenges is to predict the progression of NAFLD. Our central hypothesis is that certain mitochondrial genotype or genotypes may serve as an indicator of increased susceptibility to the progressive course of NAFLD. In this study, the association of sequence variations (haplogroups) in the control loop of mitochondria was investigated. A total of 115 cases of morbidly obese patients with liver biopsy results were included (average BMI=48.0±11.1; White=80.2%; African-American=17.4%; Females=75.6%). All these patients also had metabolic syndrome. Among 86 profiled individuals, 64 (74.4%) were diagnosed with NAFLD. After extracting DNA from whole blood cells and amplifying 1122 base pairs of control loops by PCR and Sanger sequencing, all samples have been categorized into one of 11 haplogroups (H, L, K, U, J, T, M, W, N, C, and X). The most common haplogroup in this study (34.9%) was H haplogroup, while other haplogroups including L (15.1%), K (13.95%), U (11.6%), J (11.6%), T (7.0%), M, W, N, C, and X (1.2% each) were less common. The presence of NAFLD was found to be associated significantly with non-L haplogroups (H, K, T, C, U, M, N, J, W, X) (80.84% vs 38.4%) (Fisher’s test, two tailed P= 0.003). Within the major haplogroups, the prevalence of NAFLD varied: H (80.00%), L (38.46%), K (83.33%), J and U (80.00% each) (Fisher’s test two tailed P= 0.068). Moreover, within L haplogroups, L3 shows the least tendency to develop NAFLD. Further investigations are warranted to assess why in individuals with East African L3 haplogroup the susceptibility to NAFLD is reduced.This thesis was embargoed by the author and will not be available until July 23, 2015
A Study of RNA Editing in Human Peripheral Blood Mononuclears and Endotheliocytes by NextGen Sequencing
No full textRNA editing is a process of post-transcriptional modification of the nucleotide sequence in a transcript that leads to a change in the information content of the RNA. The alteration of nucleotides in the mRNA can have several consequences at the molecular level, including modified protein products as well as creation or deletion of splice sites. Two types of RNA editing have been known to take place in mRNA: Adenosine (A) to Inosine (I) and Cytidine (C) to Uridine (U), both of which involve deamination of the nucleotide with the help of deaminase enzymes. The “A to I” RNA editing is facilitated by deaminating enzymes known as ADARs (Adenosine Deaminase that Act on RNA). ADARs specifically recognize double stranded RNA structure or RNA duplex structure as their substrate. Though previous studies have shown some evidence of low level sporadic occurrence of RNA editing in other human tissues, brain remains to be the only tissue where RNA editing has been studied systematically. In this study, we investigated “A to I” RNA editing in human PBMCs (peripheral blood mononuclear cells). We were also interested in looking at RNA editing in the umbilical endotheliocytes that are capable of producing interferons. Specifically, the cDNA derived from PBMCs and endothelial cells, was sequenced by NextGen sequencing. The PBMCs’ genomic DNA was sequenced by Sanger sequencing and the sequences were analyzed. Since inosine is recognized as guanosine (G) by most enzymes, A-to-I substitution leads to A-to-G transition in the edited substrate and therefore, any kind of “A to I” RNA editing event will be detected as A to G changes in the transcripts. The multiple sequence alignment tool SeqmanPro was used to assemble all the transcripts together, which revealed that the A to G change frequency was significantly high over 14% in TLR2 at a specific site, in most of the samples of PBMCs and endotheliocytes. At the same consensus position 26, the PMBCs genomic DNA possessed an Adenosine, which was confirmed by the distinct peak in the chromatogram obtained from Sequencher software. The presence of these A to G mismatches within the transcripts, therefore, suggests that “A to I” RNA editing takes place in PBMCs and in endothelial cells.This thesis has been embargoed and will not be available until September 16, 2018
Jūratė Baranova ir filosofijos kelias į Lietuvos bendrojo ugdymo mokyklą
No full textThe article analyses the contribution of Professor Jūratė Baranova to the introduction of philosophy teaching into the Lithuanian general school. There is a discussion about the need of philosophy teaching, the initiatives of Baranova and her colleagues’ mutual activities preparing textbooks and other teaching tools. The courses initiated, the philosophy education programmes for teachers and teacher re-skilling programmes, as well as students’ Philosophy Olympiads are presented. The educational projects of Baranova and her co-authors are reviewed, focusing on teaching cultural literacy at school whilst using dialogue, argumentation and multimodality. The author concludes that Baranova was one of the key contributors amongst Lithuanian professors and teachers, who made an input to the introduction and development of philosophy education at schools.Straipsnyje tyrinėjamas filosofijos profesorės Jūratės Baranovos indėlis į filosofijos mokymo Lietuvos bendrojo ugdymo mokykloje tradicijos kūrimą. Aptariama filosofijos mokymo poreikis, Baranovos ir jos kolegų keltos iniciatyvos, bendros veiklos pradedant rengti vadovėlius bei kitas mokymo priemones. Pristatomi inicijuoti kursai ir filosofijos rengimo programos mokytojams bei mokytojų perkvalifikavimo kursai, taip pat organizuotos filosofijos olimpiados. Apžvelgiama Baranovos individualiai ar su bendraautoriais vykdyti mokslo projektai, skirti bendrojo ugdymo mokyklos kultūrinio raštingumo tyrimams ir plėtotei, taikant dialogą, argumentavimą ir multimodalų ugdymą. Konstatuojama, kad Baranovos indėlis yra vienas didžiausių tarp tų Lietuvos mokslininkų ar pedagogų, kurie vienaip ar kitaip prisidėjo prie filosofijos mokymo mokykloje kūrimo
Investigating Reproductive Senescence in Captive Asian Elephants (Elephas maximus) Through Long-term Hormone Monitoring
No full textWhether or not elephants experience reproductive senescence, or the decline of reproductive function with age, has been a matter of some debate among researchers. While it has been shown to occur in other non-human species, data on reproductive senescence in both extant species of elephant have produced mixed results. In this study, statistical methods were applied to two previously published data sets on captive Asian elephants (Elephas maximus) to determine if age-related changes in reproductive and metabolic hormones could be detected. Multinomial regression analysis found that younger individuals (15.8-35.8 years old) had significantly higher average progestogen levels than older individuals (45.8-55.8 years old). For a separate subgroup of 11 longitudinally profiled individuals, mean hormone concentrations were profiled on an individual level across approximately 10-20 years. Interestingly, no significant age-associated changes were detected for progesterone, but the levels of several other hormones changed significantly, including that for reproductive hormones FSH and LH, both of which increased with age, and metabolic hormones, namely, cortisol, which has increased, and total T3, which has decreased. These results warrant further attention from researchers seeking to determine how Asian elephants experience reproductive aging, particularly in the North American population that is composed predominantly of post-reproductive females
SARS-CoV-2 ORF3a Interacts and Stabilizes HMOX1 Expression and Function
No full textThis thesis describes the interaction between SARS-CoV-2 Open Reading Frame 3a (ORF3a) and the Heme Oxygenase 1 (HMOX1). SARS-CoV-2 is a novel coronavirus and the causative agent of COVID-19, the highly contagious infection behind the 2019 COVID-19 pandemic. SARS-CoV-2 ORF3a is a viroporin, a small virally encoded membrane protein that acts as an ion channel. Its expression causes cell apoptosis, necrosis, lysosomal damage, and disrupts host cell autophagy. It is also implicated in the egress of SARS-CoV-2 virions from infected cells. HMOX1 is an enzyme encoded by a human gene capable of modulating immune activity with an active role in suppressing viral infections and inflammatory pathways. In this thesis, we use confocal microscopy and a co-immunoprecipitation protocol to shed light on the interaction between SARS-CoV-2 ORF3a and HMOX1. Using this approach, we show that SARS-CoV-2 ORF3a and HMOX1 co-localize in the endoplasmic reticulum (ER). We also found that that ORF3a expression stabilizes HMOX1 protein levels within cells. These results suggest that ORF3a may affect TRC8, an important E3 ligase that help direct protein traffic through the ER and which is known to ubiquitinate HMOX1. These observations lay the foundation for additional studies aimed at studying the HMOX1/ORF3a interaction. They also suggest that SARS-CoV-2 targets TRC8 and potentially other E3 ligases to redirect ER trafficking
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