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Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee 2018 The University of Western Ontario

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR ...


Nitro-Fatty Acids Are Formed In Response To Virus Infection And Are Potent Inhibitors Of Sting Palmitoylation And Signaling, Anne Louise Hansen, Mona Motwani, Katherine A. Fitzgerald, Christian K. Holm 2018 Aarhus University

Nitro-Fatty Acids Are Formed In Response To Virus Infection And Are Potent Inhibitors Of Sting Palmitoylation And Signaling, Anne Louise Hansen, Mona Motwani, Katherine A. Fitzgerald, Christian K. Holm

Open Access Articles

The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi-Goutieres syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently ...


Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle 2018 University of Louisville

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences ...


Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt 2018 University of Louisville

Alpha-Amino Methylation And Acetylation Are Novel Regulators Of Myl9 Function., Christopher David Nevitt

Electronic Theses and Dissertations

Dysregulation of alpha-amino post-translational modifications (Nα-PTMs) is found in multiple cancers and developmental disorders. However, the exact roles Nα-PTMs play in regulating protein function remain poorly understood. I sought to clarify the role of Nα-methylation and Nα-acetylation in the regulation of Myosin Regulatory Light Chain 9 (MYL9). MYL9 is a key cytoskeletal regulator and transcription factor and is the first protein confirmed to undergo both Nα-methylation and Nα-acetylation. Through this work I revealed novel regulatory features of MYL9, while also presenting a framework by which to understand the coordinated regulation of proteins by Nα-methylation and Nα-acetylation. Nα-PTM selective mutants of ...


Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor 2018 University of Louisville

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics ...


Anril: A Lncrna At The Cdkn2a/B Locus With Roles In Cancer And Metabolic Disease, Yahui Kong, Chih-Heng Hsieh, Laura C. Alonso 2018 University of Massachusetts Medical School

Anril: A Lncrna At The Cdkn2a/B Locus With Roles In Cancer And Metabolic Disease, Yahui Kong, Chih-Heng Hsieh, Laura C. Alonso

Open Access Articles

The CDKN2A/B genomic locus is associated with risk of human cancers and metabolic disease. Although the locus contains several important protein-coding genes, studies suggest disease roles for a lesser-known antisense lncRNA encoded at this locus, called ANRIL. ANRIL is a complex gene containing at least 21 exons in simians, with many reported linear and circular isoforms. Like other genes, abundance of ANRIL is regulated by epigenetics, classic transcription regulation, splicing, and post-transcriptional influences such as RNA stability and microRNAs. Known molecular functions of ANRIL include in cis and in trans gene regulation through chromatin modification complexes, and influence over ...


Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, Adilson L. Guilherme, David J. Pedersen, Felipe Henriques, Alexander H. Bedard, Elizabeth Henchey, Mark Kelly, Donald A. Morgan, Kamal Rahmouni, Michael P. Czech 2018 University of Massachusetts Medical School

Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, Adilson L. Guilherme, David J. Pedersen, Felipe Henriques, Alexander H. Bedard, Elizabeth Henchey, Mark Kelly, Donald A. Morgan, Kamal Rahmouni, Michael P. Czech

Open Access Articles

OBJECTIVE: Crosstalk between adipocytes and local neurons may be an important regulatory mechanism to control energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) expands sympathetic neurons within white adipose tissue (WAT) and stimulates the appearance of "beige" adipocytes. Here we tested whether WAT DNL activity can also influence neuronal regulation and thermogenesis in brown adipose tissue (BAT).

METHODS AND RESULTS: Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. This ...


The Comparative Genomics Of Bifidobacterium Callitrichos Reflects Dietary Carbohydrate Utilization Within The Common Marmoset Gut, Korin Albert, Asha Rani, David A. Sela 2018 University of Massachusetts Amherst

The Comparative Genomics Of Bifidobacterium Callitrichos Reflects Dietary Carbohydrate Utilization Within The Common Marmoset Gut, Korin Albert, Asha Rani, David A. Sela

Open Access Articles

Bifidobacterium is a diverse genus of anaerobic, saccharolytic bacteria that colonize many animals, notably humans and other mammals. The presence of these bacteria in the gastrointestinal tract represents a potential coevolution between the gut microbiome and its mammalian host mediated by diet. To study the relationship between bifidobacterial gut symbionts and host nutrition, we analyzed the genome of two bifidobacteria strains isolated from the feces of a common marmoset (Callithrix jacchus), a primate species studied for its ability to subsist on host-indigestible carbohydrates. Whole genome sequencing identified these isolates as unique strains of Bifidobacterium callitrichos. All three strains, including these ...


Aerobic Glycolysis Is Essential For Normal Rod Function And Controls Secondary Cone Death In Retinitis Pigmentosa, Lolita Petit, Shan Ma, Joris Cipi, Shun-Yun Cheng, Marina Zieger, Nissim Hay, Claudio Punzo 2018 University of Massachusetts Medical School

Aerobic Glycolysis Is Essential For Normal Rod Function And Controls Secondary Cone Death In Retinitis Pigmentosa, Lolita Petit, Shan Ma, Joris Cipi, Shun-Yun Cheng, Marina Zieger, Nissim Hay, Claudio Punzo

University of Massachusetts Medical School Faculty Publications

Aerobic glycolysis accounts for approximately 80%-90% of glucose used by adult photoreceptors (PRs); yet, the importance of aerobic glycolysis for PR function or survival remains unclear. Here, we further established the role of aerobic glycolysis in murine rod and cone PRs. We show that loss of hexokinase-2 (HK2), a key aerobic glycolysis enzyme, does not affect PR survival or structure but is required for normal rod function. Rods with HK2 loss increase their mitochondrial number, suggesting an adaptation to the inhibition of aerobic glycolysis. In contrast, cones adapt without increased mitochondrial number but require HK2 to adapt to metabolic ...


Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, Adilson L. Guilherme, David J. Pedersen, Felipe Henriques, Alexander H. Bedard, Elizabeth Henchey, Mark Kelly, Kamal Rahmouni, Donald A. Morgan, Michael P. Czech 2018 University of Massachusetts Medical School

Neuronal Modulation Of Brown Adipose Activity Through Perturbation Of White Adipocyte Lipogenesis, Adilson L. Guilherme, David J. Pedersen, Felipe Henriques, Alexander H. Bedard, Elizabeth Henchey, Mark Kelly, Kamal Rahmouni, Donald A. Morgan, Michael P. Czech

University of Massachusetts Medical School Faculty Publications

White adipose tissue (WAT) secretes factors to communicate with other metabolic organs to maintain energy homeostasis. We previously reported that perturbation of adipocyte de novo lipogenesis (DNL) by deletion of fatty acid synthase (FASN) causes expansion of sympathetic neurons within white adipose tissue (WAT) and the appearance of beige adipocytes. Here we report evidence that white adipocyte DNL activity is also coupled to neuronal regulation and thermogenesis in brown adipose tissue (BAT). Induced deletion of FASN in all adipocytes in mature mice (iAdFASNKO) enhanced sympathetic innervation and neuronal activity as well as UCP1 expression in both WAT and BAT. In ...


Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, Michael Price 2018 University of Nebraska Medical Center

Alcohol Drives Oxidation-Dependent Desensitization Of Airway Cilia Motility Responsiveness, Michael Price

Theses & Dissertations

Alcohol abuse, which can impair clearance of pathogens and debris from the airway, is associated with an increase in complications and a higher mortality rate during the progression of pneumonia. With prolonged alcohol exposure, mucociliary clearance (MCC), which depends on the coordinated beating of cilia, is dysfunctional. Effective MCC relies on cAMP-dependent protein kinase (PKA) activation of ciliary beat frequency (CBF). PKA activation and stimulation of CBF are blunted with chronic exposure to alcohol. This phenomenon is known as alcohol-induced ciliary dysfunction (AICD). Previous studies have shown that concomitant feeding of mice with alcohol and antioxidants prevents AICD, suggesting a ...


Pkm2 Influences The Metabolic Fate Of Butyrate In Colorectal Cancer Cells, Megan Louise Pence 2018 University of Tennessee, Knoxville

Pkm2 Influences The Metabolic Fate Of Butyrate In Colorectal Cancer Cells, Megan Louise Pence

University of Tennessee Honors Thesis Projects

No abstract provided.


Efficient Blue To Red Afterglow Tuning In A Binary Nanocomposite Plastic Film, Yan Xia, Huase Ou, Wanbin Li, Gang Han, Zhanjun Li 2018 Jinan University - China

Efficient Blue To Red Afterglow Tuning In A Binary Nanocomposite Plastic Film, Yan Xia, Huase Ou, Wanbin Li, Gang Han, Zhanjun Li

Open Access Articles

Colorful spectra are important for the diverse applications of persistent phosphors. A color conversion concept is developed to obtain abundant persistent luminescence color by mining capacities of known persistent phosphors with the most efficient persistent properties. Here, SiO(2)/Sr(2)MgSi(2)O(7):Eu,Dy nanoparticles are chosen as a blue persistent luminescence donor nanophosphor, while ultrafine CaAlSiN(3):Eu is utilized as a red conversion phosphor to tune the persistent luminescence spectra from blue to red. The red afterglow emission can persist for more than 5 h. The decay of the red afterglow follows nearly the same ...


Effects Of Larval Density On Gene Regulation In Caenorhabditis Elegans During Routine L1 Synchronization, Io Long Chan, Oliver J. Rando, Colin C. Conine 2018 University of Massachusetts Medical School

Effects Of Larval Density On Gene Regulation In Caenorhabditis Elegans During Routine L1 Synchronization, Io Long Chan, Oliver J. Rando, Colin C. Conine

University of Massachusetts Medical School Faculty Publications

Bleaching gravid C. elegans followed by a short period of starvation of the L1 larvae is a routine method performed by worm researchers for generating synchronous populations for experiments. During the process of investigating dietary effects on gene regulation in L1 stage worms by single-worm RNA-Seq, we found that the density of resuspended L1 larvae affects expression of many mRNAs. Specifically, a number of genes related to metabolism and signalling are highly expressed in worms arrested at low density, but are repressed at higher arrest densities. We generated a GFP reporter strain based on one of the most density-dependent genes ...


N-Terminal Sumoylation Of Centromeric Histone H3 Variant Cse4 Regulates Its Proteolysis To Prevent Mislocalization To Non-Centromeric Chromatin, Kentaro Ohkuni, Reuben Levy-Myers, Jack Warren, Wei-Chun Au, Yoshimitsu Takahashi, Richard E. Baker, Munira A. Basrai 2018 National Cancer Institute

N-Terminal Sumoylation Of Centromeric Histone H3 Variant Cse4 Regulates Its Proteolysis To Prevent Mislocalization To Non-Centromeric Chromatin, Kentaro Ohkuni, Reuben Levy-Myers, Jack Warren, Wei-Chun Au, Yoshimitsu Takahashi, Richard E. Baker, Munira A. Basrai

Open Access Articles

Stringent regulation of cellular levels of evolutionarily conserved centromeric histone H3 variant (CENP-A in humans, CID in flies, Cse4 in yeast) prevents its mislocalization to non-centromeric chromatin. Overexpression and mislocalization of CENP-A has been observed in cancers and leads to aneuploidy in yeast, flies, and human cells. Ubiquitin-mediated proteolysis of Cse4 by E3 ligases such as Psh1 and Sumo-Targeted Ubiquitin Ligase (STUbL) Slx5 prevent mislocalization of Cse4. Previously, we identified Siz1 and Siz2 as the major E3 ligases for sumoylation of Cse4. In this study, we have identified lysine 65 (K65) in Cse4 as a site that regulates sumoylation and ...


A Parental Requirement For Dual-Specificity Phosphatase 6 In Zebrafish, Jennifer M. Maurer, Charles G. Sagerstrom 2018 University of Massachusetts Medical School

A Parental Requirement For Dual-Specificity Phosphatase 6 In Zebrafish, Jennifer M. Maurer, Charles G. Sagerstrom

Open Access Articles

BACKGROUND: Signaling cascades, such as the extracellular signal-regulated kinase (ERK) pathway, play vital roles in early vertebrate development. Signals through these pathways are initiated by a growth factor or hormone, are transduced through a kinase cascade, and result in the expression of specific downstream genes that promote cellular proliferation, growth, or differentiation. Tight regulation of these signals is provided by positive or negative modulators at varying levels in the pathway, and is required for proper development and function. Two members of the dual-specificity phosphatase (Dusp) family, dusp6 and dusp2, are believed to be negative regulators of the ERK pathway and ...


Cbx4 Sumoylates Prdm16 To Regulate Adipose Tissue Thermogenesis, Qingbo Chen, Lei Huang, Dongning Pan, Lihua (Julie) Zhu, Yong-Xu Wang 2018 University of Massachusetts Medical School

Cbx4 Sumoylates Prdm16 To Regulate Adipose Tissue Thermogenesis, Qingbo Chen, Lei Huang, Dongning Pan, Lihua (Julie) Zhu, Yong-Xu Wang

Open Access Articles

Transcriptional co-activator Prdm16 controls brown fat development and white fat browning, but how this thermogenic function is modulated post-translationally is poorly understood. Here, we report that Cbx4, a Polycomb group protein, is a SUMO E3 ligase for Prdm16 and that Cbx4-mediated sumoylation of Prdm16 is required for thermogenic gene expression. Cbx4 expression is enriched in brown fat and is induced in adipose tissue by acute cold exposure. Sumoylation of Prdm16 at lysine 917 by Cbx4 blocks its ubiquitination-mediated degradation, thereby augmenting its stability and thermogenic function. Moreover, this sumoylation event primes Prdm16 to be further stabilized by methyltransferase Ehmt1. Heterozygous ...


C9orf72 Ggggcc Repeat-Associated Non-Aug Translation Is Upregulated By Stress Through Eif2alpha Phosphorylation, Weiwei Cheng, Shaopeng Wang, Alexander A. Mestre, Chenglai Fu, Andres Makarem, Fengfan Xian, Lindsey R. Hayes, Rodrigo Lopez-Gonzalez, Kevin Drenner, Jie Jiang, Don W. Cleveland, Shuying Sun 2018 Johns Hopkins University

C9orf72 Ggggcc Repeat-Associated Non-Aug Translation Is Upregulated By Stress Through Eif2alpha Phosphorylation, Weiwei Cheng, Shaopeng Wang, Alexander A. Mestre, Chenglai Fu, Andres Makarem, Fengfan Xian, Lindsey R. Hayes, Rodrigo Lopez-Gonzalez, Kevin Drenner, Jie Jiang, Don W. Cleveland, Shuying Sun

Open Access Articles

Hexanucleotide repeat expansion in C9ORF72 is the most frequent cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we demonstrate that the repeat-associated non-AUG (RAN) translation of (GGGGCC) n -containing RNAs into poly-dipeptides can initiate in vivo without a 5'-cap. The primary RNA substrate for RAN translation of C9ORF72 sense repeats is shown to be the spliced first intron, following its excision from the initial pre-mRNA and transport to the cytoplasm. Cap-independent RAN translation is shown to be upregulated by various stress stimuli through phosphorylation of the alpha subunit of eukaryotic initiation factor-2 (eIF2alpha), the core ...


Marijuana And The Teenage Brain: Public Health Impact, Katie C. Warther 2018 University of Vermont

Marijuana And The Teenage Brain: Public Health Impact, Katie C. Warther

Family Medicine Clerkship Student Projects

This project explores the neurobiological impact of teenage marijuana use, and the ways that public health interventions can help educate adolescents and delay the onset of use.


Impact Of Bodyweight On Tissue-Specific Folate Status, Genome Wide And Gene-Specific Dna Methylation In Normal Breast Tissues From Premenopausal Women, Armina-Lyn Frederick 2018 University of Massachusetts Amherst

Impact Of Bodyweight On Tissue-Specific Folate Status, Genome Wide And Gene-Specific Dna Methylation In Normal Breast Tissues From Premenopausal Women, Armina-Lyn Frederick

Masters Theses

Obesity has reached an epidemic level in the United States. A number of epidemiological studies have established obesity as a critical risk factor for postmenopausal breast cancer (post-BC), whereas a reverse association holds prior to menopause. A significant scientific gap exists in understanding the mechanism(s) underpinning this epidemiological phenomenon, particularly the reverse association between obesity and premenopausal breast cancer (pre-BC). This study aimed to understand how folate metabolism and DNA methylation informs the association between obesity and pre-BC. Fifty normal breast tissue samples were collected from premenopausal women who underwent reduction mammoplasty. We developed and measured the breast tissue ...


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