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Cornell University
1.
Dowicki, Michael.
The Wing Helix Domain Of Orc4 Is The Primary Determinant Of Dna Binding Specificity Of The Origin Recognition Complex.
Degree: PhD, Genetics, 2015, Cornell University
URL: http://hdl.handle.net/1813/40691
► The process of DNA replication is regulated to ensure that the entire genome is replicated only once during every cell division cycle. Eukaryotic DNA replication…
(more)
▼ The process of DNA replication is regulated to ensure that the entire genome is replicated only once during every cell division cycle. Eukaryotic DNA replication begins with the binding of the Origin Replication Complex (ORC) to multiple replication origins or Autonomously Replicating Sequences (ARSs) on every chromosome. The ORC machinery is conserved from fungal to mammalian systems, however the ARSs to which the ORC binds have diverged significantly. In the budding yeast S. cerevisiae the ORC binds a well-defined 17bp ACS, conversely in the fission yeast S. pombe ORC binds to AT rich sequences in a stochastic manner. Previously the replication origins of the yeast K .lactis have been identified as a 50bp sequence necessary and largely sufficient for replication. Through testing of plasmids constructed to contain either S. cerevisiae or K. lactis ARSs, it was found that each species is largely unable to replicate ARSs from the other species, indicating that the replication machinery has significantly diverged to specifically recognize its own origin sequence. In this thesis, I am examining the role subunits of the ORC complex play in determining the binding specificity of the ORC complex. The ORC proteins contain a DNA binding Winged Helix Domain in their C-termini. I have constructed S. cerevisiae strains containing chimeric ORC proteins which interact with the S. cerevisiae machinery while containing the K. lactis WHD. The chimeric ORC4 and ORC5 proteins fail to substitute for their respective endogenous proteins but the ORC4 chimera results in a dominant loss of silencing at the HMR locus, which is mediated by ORC. ChIP-Seq analysis showed that the chimeric strain binds to a K. lactis ACS at this locus and at several other distinct sites in the S. cerevisiae genome including the centromeres. Additionally the chimeric ORC4 demonstrates the ability to replicate plasmids containing a K. lactis ARS, unlike the wild type S. cerevisiae strain and S. cerevisiae containing a chimeric ORC5. This study suggests that the DNA binding specificity for the S. cerevisiae ORC, K. lactis ORC and most likely ORCs in other fungi is primarily determined by the WHD of Orc4.
Advisors/Committee Members: Tye,Bik-Kwoon (chair), Gu,Zhenglong (committee member), Weiss,Robert S. (committee member).
Subjects/Keywords: DNA Replication; Origin Recognition Complex
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APA (6th Edition):
Dowicki, M. (2015). The Wing Helix Domain Of Orc4 Is The Primary Determinant Of Dna Binding Specificity Of The Origin Recognition Complex. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/40691
Chicago Manual of Style (16th Edition):
Dowicki, Michael. “The Wing Helix Domain Of Orc4 Is The Primary Determinant Of Dna Binding Specificity Of The Origin Recognition Complex.” 2015. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/40691.
MLA Handbook (7th Edition):
Dowicki, Michael. “The Wing Helix Domain Of Orc4 Is The Primary Determinant Of Dna Binding Specificity Of The Origin Recognition Complex.” 2015. Web. 18 Apr 2021.
Vancouver:
Dowicki M. The Wing Helix Domain Of Orc4 Is The Primary Determinant Of Dna Binding Specificity Of The Origin Recognition Complex. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/40691.
Council of Science Editors:
Dowicki M. The Wing Helix Domain Of Orc4 Is The Primary Determinant Of Dna Binding Specificity Of The Origin Recognition Complex. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/40691

Cornell University
2.
Lozano Gonzalez del Valle, Roberto Jesus.
FUNCTIONAL GENOMICS TO AID GENOMIC PREDICTION MODELS IN CASSAVA.
Degree: PhD, Plant Breeding, 2018, Cornell University
URL: http://hdl.handle.net/1813/59500
► Genomic Prediction (GP) is commonly performed using tens of thousands, even millions of single-nucleotide polymorphism (SNP) markers. Associations among the phenotypes and genotypes of a…
(more)
▼ Genomic Prediction (GP) is commonly performed using tens of thousands, even millions of single-nucleotide polymorphism (SNP) markers. Associations among the phenotypes and genotypes of a training population are used to predict the performance of un-phenotyped target populations. Traditionally, the markers used in these studies are treated similarly, irrespective of their position in the genome, their proximity to regulatory elements, or whether they reside within biologically-relevant genes. The content of this dissertation aims to both identify “functional” regions in the cassava (Manihot esculenta) genome and test whether the incorporation of prior biological knowledge enhances the accuracy of GP models in this crop. In 2013, at the onset of this research, very few genomic resources were available within the cassava research community; a draft of the genome sequence had recently been released and a solid platform for low-coverage genotyping using genotyping-bysequencing (GBS) was online. As a means of generating more genomic resources, we first began by identifying nucleotide-binding site leucine-rich repeat (NBS-LRR) genes associated with biotic resistance across the cassava genome. We then leveraged the NBS-LRR information, together with genomic annotations and a transcriptomics experiment, in a second study to identify genes involved in the interaction of cassava with Cassava Brown Streak Virus (CBSV). We later used biologically-informed GP methods to compare models with and without biologically-relevant information. Until the final phase of our research, our efforts had focused on identifying functional elements within the coding fraction of the genome. In an effort to build upon several genome-wide association (GWA) studies illustrating the importance of regulatory regions outside genes, the third study explored cassava’s nascent transcriptome. In doing so, we were able to identify key components of plant transcriptional regulation and candidate enhancer regions that not been previously described. Moreover, we showed that these candidate enhancer regions contributed disproportionately to the SNP heritability of several complex traits. The research presented herein provides holistic insight into cassava’s genomic resources, and it is our hope that it is useful to future research and breeding endeavors within this staple crop species.
Advisors/Committee Members: Jannink, Jean-Luc (chair), Gray, Stewart (committee member), Gu, Zhenglong (committee member).
Subjects/Keywords: Genetics; Functional Genomics; Genomic selection; Agriculture
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APA (6th Edition):
Lozano Gonzalez del Valle, R. J. (2018). FUNCTIONAL GENOMICS TO AID GENOMIC PREDICTION MODELS IN CASSAVA. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/59500
Chicago Manual of Style (16th Edition):
Lozano Gonzalez del Valle, Roberto Jesus. “FUNCTIONAL GENOMICS TO AID GENOMIC PREDICTION MODELS IN CASSAVA.” 2018. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/59500.
MLA Handbook (7th Edition):
Lozano Gonzalez del Valle, Roberto Jesus. “FUNCTIONAL GENOMICS TO AID GENOMIC PREDICTION MODELS IN CASSAVA.” 2018. Web. 18 Apr 2021.
Vancouver:
Lozano Gonzalez del Valle RJ. FUNCTIONAL GENOMICS TO AID GENOMIC PREDICTION MODELS IN CASSAVA. [Internet] [Doctoral dissertation]. Cornell University; 2018. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/59500.
Council of Science Editors:
Lozano Gonzalez del Valle RJ. FUNCTIONAL GENOMICS TO AID GENOMIC PREDICTION MODELS IN CASSAVA. [Doctoral Dissertation]. Cornell University; 2018. Available from: http://hdl.handle.net/1813/59500

Cornell University
3.
Wang, Yiping.
Expression-Based Modeling of Metabolic Flux in Metabolic Diseases.
Degree: PhD, Computational Biology, 2019, Cornell University
URL: http://hdl.handle.net/1813/70080
► Metabolism is one of the most central aspects of the biology of all organisms. All cells possess a bipartite metabolic network, composed of small molecule…
(more)
▼ Metabolism is one of the most central aspects of the biology of all organisms. All cells possess a bipartite metabolic network, composed of small molecule metabolites and enzymes which carry out biochemical reactions on them. This metabolic network is responsible for carrying out numerous cellular functions, including energy generation in the form of ATP, production of antioxidants to control reactive oxygen species levels, and production of biosynthetic molecules necessary for cellular growth, such as amino acids and nucleic acids. However, in Chapter 1, I will describe how one of the most important facets of metabolism, the rate at which each biochemical reaction occurs, or metabolic flux, cannot be easily experimentally measured on a genome-wide scale. This leads us to the need for a computational method that can efficiently infer such metabolic flux. I will describe the approach taken by a group of methods that go by the general name of constraints-based modeling, and how we have previously developed a new method under this framework, called FALCON, which uses metabolic gene expression to predict flux. I will then describe how I applied FALCON to infer differences in metabolic flux in two major groups of metabolic diseases. First, metagenomic sequencing has revealed that the composition of the gut microbiome is linked to several major metabolic diseases, including obesity, type 2 diabetes (T2D), and inflammatory bowel disease (IBD). I used the computational tool PICRUST to infer species-specific metagenomes for each of these diseases, and FALCON to infer fluxes from these results. I discovered that several major pathways, previously shown to be important in human host metabolism, have significantly different flux between the two groups. I also modeled metabolic cooperation and competition between pairs of species in the microbiome, used this to determine the compositional stability of the microbiome, and found that that the microbiome is generally unstable across controls as well as metabolic microbiomes. Second, I also used RNA-Seq data from The Cancer Genome Atlas (TCGA) as input to FALCON. I found a systematic difference in that cancer tissues have a considerably stronger correlation between RNA-seq expression and inferred metabolic flux, which may indicate a more streamlined and efficient metabolism. I also found several pathways that frequently have divergent flux. Among these are sphingolipid metabolism, methionine and cysteine synthesis, and bile acid transformations.
Advisors/Committee Members: Gu, Zhenglong (chair), Yu, Haiyuan (committee member), Myers, Christopher (committee member), Elemento, Olivier (committee member).
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
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APA (6th Edition):
Wang, Y. (2019). Expression-Based Modeling of Metabolic Flux in Metabolic Diseases. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/70080
Chicago Manual of Style (16th Edition):
Wang, Yiping. “Expression-Based Modeling of Metabolic Flux in Metabolic Diseases.” 2019. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/70080.
MLA Handbook (7th Edition):
Wang, Yiping. “Expression-Based Modeling of Metabolic Flux in Metabolic Diseases.” 2019. Web. 18 Apr 2021.
Vancouver:
Wang Y. Expression-Based Modeling of Metabolic Flux in Metabolic Diseases. [Internet] [Doctoral dissertation]. Cornell University; 2019. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/70080.
Council of Science Editors:
Wang Y. Expression-Based Modeling of Metabolic Flux in Metabolic Diseases. [Doctoral Dissertation]. Cornell University; 2019. Available from: http://hdl.handle.net/1813/70080

Cornell University
4.
Nguyen, Xuanmai.
Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway.
Degree: PhD, Nutrition, 2014, Cornell University
URL: http://hdl.handle.net/1813/36193
► The overall objective of this research is to examine the joint effect of multiple variants in folate metabolism on CVD outcome. The intermediary outcome, homocysteine,…
(more)
▼ The overall objective of this research is to examine the joint effect of multiple variants in folate metabolism on CVD outcome. The intermediary outcome, homocysteine, will be investigated as the primary endpoint because the metabolic disruption characterized by elevated homocysteine levels is proposed to mediate the risk of CVD. Because epidemiologic studies are limited by small sample size, and thus reduced statistical power to examine genetic interactions and their combined effects on disease outcome, we utilize computer simulations to study five SNPs in four candidate genes that code for enzymes that are all linked through sequential metabolic steps in homocysteine remethylation. These enzymes are either directly involved in homocysteine remethylation or indirectly linked because they provide essential substrates required for the conversion of homocysteine to methionine by MTR. Using MTR as our focal point, we also considered gene-nutrient interactions among the five variants and varying levels of folate and vitamin B12 to account for the possible effects of nutritional status on disease risk. This approach led to the key finding that having double variants for all possible polymorphisms in a pathway does not necessarily equate to the most deleterious effects, and that only vitamin B12 had an effect on the homocysteine levels as a nutrient cofactor. Our simulations also illustrate how pathways have built-in regulatory mechanisms that researchers might not be able to account for when taking a single candidate gene approach to studying disease outcome. We anticipate that our model will serve as an example of how simulations can help advance the growing idea that disease treatment can be personalized by examining an individual's unique genetic and nutritional profile.
Advisors/Committee Members: Utermohlen, Virginia (chair), Doerschuk, Peter (committee member), Lin, David M. (committee member), Gu, Zhenglong (committee member).
Subjects/Keywords: complex systems; personalized medicine; folate metabolism
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Nguyen, X. (2014). Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/36193
Chicago Manual of Style (16th Edition):
Nguyen, Xuanmai. “Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway.” 2014. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/36193.
MLA Handbook (7th Edition):
Nguyen, Xuanmai. “Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway.” 2014. Web. 18 Apr 2021.
Vancouver:
Nguyen X. Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/36193.
Council of Science Editors:
Nguyen X. Complex Systems Approach To Modeling Folate Metabolism: Examining The Homocysteine Remethylation Pathway. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36193

Cornell University
5.
Xu, Lin.
Dynamics Of Epistasis From Duplicate Genes To Genome-Wide Networks.
Degree: PhD, Genetics, 2012, Cornell University
URL: http://hdl.handle.net/1813/29401
► Epistasis refers to the phenomenon that phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is…
(more)
▼ Epistasis refers to the phenomenon that phenotypic consequences caused by mutation of one gene depend on one or more mutations at another gene. Epistasis is critical for understanding many genetic and evolutionary processes, including pathway organization, evolution of sexual reproduction, mutational load, ploidy, genomic complexity, speciation and the origin of life. However, the epistatic dynamics in biological systems under various internal and external perturbations are largely unknown. In this study, I firstly focused on exploring dynamics of epistasis between duplicate genes. I then investigated the properties of global epistatic networks under different traits. Finally I examined the dynamic changes of epistatic relations among genes under genetic and environmental perturbations. I started my research by investigating the transcriptional dynamics of duplicate genes with negative epistasis under external perturbations. We found an interesting design principle that two epistatically interacting duplicate genes can acquire a fitness advantage under fluctuating environmental perturbations by achieving maximum expression levels asynchronously. Soon after finishing this project, instead of focusing on epistatic relations between duplicate genes, we analyzed a high-throughput experimental dataset investigating epistatic interactions among ~4,000 genes in baker's yeast, Saccharomyces cerevisiae. We showed that epistasis is prevalent (~13% increase from the random expectations) and displays modular architecture among genes that underlie the same growth traits. More interestingly, our results indicate that hub genes responsible for the same growth traits tend to link epistatically with each other more frequently than random expectation. When conducting these projects, we realized that few studies have examined the genome-wide dynamics of epistatic relations under different genetic and environmental perturbations, which might be due to limitations in screening epistatic relations for multiple mutants of the same genes or multiple environmental conditions under the current high-throughput experimental platforms. We addressed this issue theoretically by using Flux Balance Analysis (FBA), which involves the optimization of cellular objective functions and allows prediction of in silico flux values and/or growth. A series of unique properties of epistatic dynamics under various genetic and environmental perturbations have been revealed in our FBA simulations, and some of them are highly consistent with previous experimental studies.
Advisors/Committee Members: Gu, Zhenglong (chair), Yu, Haiyuan (committee member), Myers, Christopher R (committee member), Clark, Andrew (committee member).
Subjects/Keywords: Dynamics; Epistasis; Network
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Xu, L. (2012). Dynamics Of Epistasis From Duplicate Genes To Genome-Wide Networks. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/29401
Chicago Manual of Style (16th Edition):
Xu, Lin. “Dynamics Of Epistasis From Duplicate Genes To Genome-Wide Networks.” 2012. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/29401.
MLA Handbook (7th Edition):
Xu, Lin. “Dynamics Of Epistasis From Duplicate Genes To Genome-Wide Networks.” 2012. Web. 18 Apr 2021.
Vancouver:
Xu L. Dynamics Of Epistasis From Duplicate Genes To Genome-Wide Networks. [Internet] [Doctoral dissertation]. Cornell University; 2012. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/29401.
Council of Science Editors:
Xu L. Dynamics Of Epistasis From Duplicate Genes To Genome-Wide Networks. [Doctoral Dissertation]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/29401

Cornell University
6.
West, Allyson.
Status And Functional Indicators Of Folate And Choline Metabolism Among Third-Trimester Pregnant, Lactating, And Nonpregnant Women: A Set Of Dose Response Studies.
Degree: PhD, Nutrition, 2012, Cornell University
URL: http://hdl.handle.net/1813/30963
► Background: Folate and choline are essential nutrients of particular importance during pregnancy and lactation and among nonpregnant women of reproductive age. However, in the era…
(more)
▼ Background: Folate and choline are essential nutrients of particular importance during pregnancy and lactation and among nonpregnant women of reproductive age. However, in the era of folic acid (FA) fortification, high folate status and supplement use during pregnancy have been linked to adverse outcomes including asthma and eczema in children. No dose response studies conducted with women informed the choline Adequate Intakes (AIs), meanwhile evidence suggests that intakes greater than the current AI could optimize pregnancy endpoints. Research informing intake recommendations and strategies that promote optimal outcomes while avoiding inadequate and excessive intakes of folate and choline are needed. Objective: This research sought to quantify status and functional indicators of folate and choline metabolism in response to controlled intakes among pregnant, lactating, and nonpregnant women. Design: Pregnant (n=26), lactating (n=28), and nonpregnant (n=21) women consumed: a prenatal supplement containing 750 [MICRO SIGN]g FA; 480 or 930 mg choline/d ; and 200 mg docosahexaenoic acid (DHA)/d for 10-12 wks. Biological samples were collected throughout the study. Folate status indicators were measured in all groups. Phosphatidylcholine(PC)-DHA, a functional indicator of choline metabolism, was assessed in pregnant and nonpregnant women. Results: (1) At study-end, serum folate concentrations did not differ (P=0.876) by physiologic group and urinary folate excretion represented ~9-43% of intake. Breastmilk FA concentrations increased (P=0.003), while total folate remained constant (P= 0.244) over time. (2) PC-DHA was greater (P=0.01-0.001) among pregnant women at baseline. PCDHA increased (P<0.001) in both groups regardless of choline intake; however, among nonpregnant women, consumption of 930 mg choline/d led to greater (P=0.011) PC-DHA. Conclusions: (1) The study folate dose yielded supranutritional folate status in all physiologic groups. Given unresolved concerns about exposure to excess FA and the widespread folate adequacy of our FA-fortified population, it may be prudent to reduce the amount of FA in prenatal supplements. (2) Via its capacity to donate methyl groups, a higher choline intake may facilitate synthesis and delivery of DHA to peripheral tissues among nonpregnant women and increase availability of methyl groups during pregnancy. These beneficial endpoints of choline intakes greater than the current AIs warrant further exploration.
Advisors/Committee Members: Caudill, Marie A. (chair), Liu, Rui Hai (committee member), Olson, Christine Marie (committee member), Gu, Zhenglong (committee member).
Subjects/Keywords: folate status; choline metabolism; women of reproductive age
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
West, A. (2012). Status And Functional Indicators Of Folate And Choline Metabolism Among Third-Trimester Pregnant, Lactating, And Nonpregnant Women: A Set Of Dose Response Studies. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/30963
Chicago Manual of Style (16th Edition):
West, Allyson. “Status And Functional Indicators Of Folate And Choline Metabolism Among Third-Trimester Pregnant, Lactating, And Nonpregnant Women: A Set Of Dose Response Studies.” 2012. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/30963.
MLA Handbook (7th Edition):
West, Allyson. “Status And Functional Indicators Of Folate And Choline Metabolism Among Third-Trimester Pregnant, Lactating, And Nonpregnant Women: A Set Of Dose Response Studies.” 2012. Web. 18 Apr 2021.
Vancouver:
West A. Status And Functional Indicators Of Folate And Choline Metabolism Among Third-Trimester Pregnant, Lactating, And Nonpregnant Women: A Set Of Dose Response Studies. [Internet] [Doctoral dissertation]. Cornell University; 2012. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/30963.
Council of Science Editors:
West A. Status And Functional Indicators Of Folate And Choline Metabolism Among Third-Trimester Pregnant, Lactating, And Nonpregnant Women: A Set Of Dose Response Studies. [Doctoral Dissertation]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/30963

Cornell University
7.
Ye, Kaixiong.
The Evolutionary And Clinical Significance Of Regulatory And Mitochondrial Genetic Variants.
Degree: PhD, Nutrition, 2015, Cornell University
URL: http://hdl.handle.net/1813/39371
► Genetic adaptations to local environment during evolution shaped the human genome. Identifying evolutionarily important genetic variants is clinically significant because the mismatch between our slow-evolving…
(more)
▼ Genetic adaptations to local environment during evolution shaped the human genome. Identifying evolutionarily important genetic variants is clinically significant because the mismatch between our slow-evolving genome and the cultural upheaval underlies many diseases of civilization. Recent sequencing technology advances start a Genomic era and promise to elucidate the genetic basis of human health and disease. While most attention had been drawn to protein-coding genes in the nuclear genome, regulatory regions and mitochondrial genome were much less studied. My research aims to investigate the evolutionary and clinical significance of these two categories. Starting my research, I summarized the latest advances in understanding the role of nutrition in human genome evolution and introduced to the Nutrition field population genomics approaches to identify dietary adaptions. My first research project examined the adaptation of regulatory variants to 42 environmental factors. With a newly developed environmental correlation method, I found that expression QTLs are enriched in signals of environmental adaptation and regulatory adaptation are especially important for some environmental factors, like climate, and for some biological pathways, including immune and metabolic pathways. My second project was a case study to test a hypothesis that an Asian-common haplotype was adaptive to the plant-based diet in Asia by enhancing non-heme iron absorption. With an iron absorption study involving 57 Asian women volunteers, I found that consistent to our hypothesis homozygous carriers of the adaptive haplotype absorbed 22% more non-heme iron than non-carriers. Intriguingly, I also observed that compared to Caucasian women, Asian women absorbed more non-heme iron even in face of higher iron store. My third project utilized the next-generation sequencing data from the 1000 Genomes Project and investigated the prevalence and clinical relevance of mitochondrial DNA (mtDNA) heteroplasmy, the presence of multiple versions of mtDNA in a cell. I found that about 90% healthy individuals carry at least one heteroplasmies and at least 20% individuals harbor disease-associated heteroplasmies. I demonstrated that heteroplasmic mutations are highly pathogenic and subject to weak negative selection. My research suggests that heteroplasmic mutations may drift to high frequency across life-span and contribute to age-related diseases.
Advisors/Committee Members: Gu, Zhenglong (chair), Booth, James (committee member), Mezey, Jason G. (committee member), O'Brien, Kimberly O (committee member), Brenna, James Thomas (committee member).
Subjects/Keywords: Adaptation; Regulatory Variants; Mitochondrial Heteroplasmy
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Ye, K. (2015). The Evolutionary And Clinical Significance Of Regulatory And Mitochondrial Genetic Variants. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/39371
Chicago Manual of Style (16th Edition):
Ye, Kaixiong. “The Evolutionary And Clinical Significance Of Regulatory And Mitochondrial Genetic Variants.” 2015. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/39371.
MLA Handbook (7th Edition):
Ye, Kaixiong. “The Evolutionary And Clinical Significance Of Regulatory And Mitochondrial Genetic Variants.” 2015. Web. 18 Apr 2021.
Vancouver:
Ye K. The Evolutionary And Clinical Significance Of Regulatory And Mitochondrial Genetic Variants. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/39371.
Council of Science Editors:
Ye K. The Evolutionary And Clinical Significance Of Regulatory And Mitochondrial Genetic Variants. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/39371

Cornell University
8.
Zhao, Zeping.
Inflammation requires an anti-inflammatory/regenerating protein REG3[beta] to induce insulin resistance.
Degree: PhD, Animal Science, 2018, Cornell University
URL: http://hdl.handle.net/1813/59543
► Inflammation is a well-accepted cause of insulin resistance (IR), and anti-inflammatory treatments (AITs) are supposed to improve insulin sensitivity. Herein, we revealed that knockout of…
(more)
▼ Inflammation is a well-accepted cause of insulin resistance (IR), and anti-inflammatory treatments (AITs) are supposed to improve insulin sensitivity. Herein, we revealed that knockout of a potent anti-inflammatory protein: murine regenerating islet-derived protein 3β (REG3β), paradoxically enhanced insulin sensitivity, and completely blocked development of IR induced by lipopolysaccharide (LPS) or dextran sulfate sodium (DSS)-mediated inflammation in mice. These knockout effects were reversed by exogenous REG3β administration, and conferred by ablating two previously-unknown bindings of REG3β to transmembrane proteins exostosin-like glycosyltransferase 3 (EXTL3) that suppressed expression of insulin receptor (INSR) and protein kinase B (AKT) and cytokine receptor C-X-C motif chemokine receptor 4 (CXCR4) that inhibited phosphorylation of INSR and AKT. Prior conflicting effects of anti-inflammatory drugs on insulin sensitivity could now be explained by their different ability to alter tissue REG3β protein. Suggested human homologue regenerating islet-derived protein 3α (hREG3α) exhibited similar functions to those of REG3β. Our work unveiled REG3β as a potent negative determinant of insulin sensitivity and an essential mediator for inflammation to induce IR. These findings drastically revise current theory on the relationship of inflammation and IR, and offer an exciting new therapy target of IR and a safer, alternative prospect to treat inflammation in diabetes.
Advisors/Committee Members: Lei, Xingen (chair), Brown, William J. (committee member), Gu, Zhenglong (committee member), Sevier, Carolyn S. (committee member).
Subjects/Keywords: anti-inflammation; Insulin resistance; REG3β; Inflammation; Genetics; Molecular biology; Nutrition
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhao, Z. (2018). Inflammation requires an anti-inflammatory/regenerating protein REG3[beta] to induce insulin resistance. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/59543
Chicago Manual of Style (16th Edition):
Zhao, Zeping. “Inflammation requires an anti-inflammatory/regenerating protein REG3[beta] to induce insulin resistance.” 2018. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/59543.
MLA Handbook (7th Edition):
Zhao, Zeping. “Inflammation requires an anti-inflammatory/regenerating protein REG3[beta] to induce insulin resistance.” 2018. Web. 18 Apr 2021.
Vancouver:
Zhao Z. Inflammation requires an anti-inflammatory/regenerating protein REG3[beta] to induce insulin resistance. [Internet] [Doctoral dissertation]. Cornell University; 2018. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/59543.
Council of Science Editors:
Zhao Z. Inflammation requires an anti-inflammatory/regenerating protein REG3[beta] to induce insulin resistance. [Doctoral Dissertation]. Cornell University; 2018. Available from: http://hdl.handle.net/1813/59543

Cornell University
9.
Bardowell, Sabrina.
The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status.
Degree: PhD, Nutrition, 2012, Cornell University
URL: http://hdl.handle.net/1813/31140
► Vitamin E is a group of compounds that are considered to be the most important lipophilic antioxidants, however there is still much unknown about the…
(more)
▼ Vitamin E is a group of compounds that are considered to be the most important lipophilic antioxidants, however there is still much unknown about the biological actions of the various forms of vitamin E as well as the mechanisms that influence the concentration of vitamin E forms in tissues. Despite the common predominance of mainly [gamma]-tocopherol ([gamma]-TOH) in the diet, [alpha]-TOH is present in serum and tissues at levels 5-6 times that of [gamma]-TOH. The biological rational for this selectivity remains an enigma. The focus of this work was on the selective postabsorptive catabolism of non-[alpha]-TOH forms via the vitamin E-[omega]-oxidation pathway. Cytochrome P450 4F2 (CYP4F2) is the only known human enzyme shown to display TOH-[omega]-hydroxylase activity. In an effort to investigate the role of TOH-[omega]-hydroxylase activity in vitamin E metabolism and status, the functional murine ortholog of CYP4F2 was identified and the consequences of its deletion on vitamin E metabolism and status were determined. In vivo and in vitro studies revealed Cyp4f14 to be the major, but not the only, vitamin E-[omega]-hydroxylase in mice, and to have critical function in regulating body-wide vitamin E status. Disruption of Cyp4f14 expression resulted in hyper-accumulation of [gamma]-TOH in mice fed a soybean oil diet in which the major tocopherol was [gamma]-TOH. Supplementation of Cyp4f14-/- mice with high levels of [delta]- and [gamma]-TOH exacerbated the tissue enrichment of these forms of vitamin E. Through the use of metabolic cage studies, previously unappreciated mechanisms of vitamin E elimination were discovered, which served to counterbalance the metabolic deficit observed in Cyp4f14-/- mice. Fecal elimination of unmetabolized TOHs was determined to be a high capacity mechanism to be minimize diet induced accumulation of TOHs, especially at high dietary levels. Additionally, novel [omega]-1 and [omega]-2 vitamin E hydroxylase activities were discovered and were found to quantitatively important vitamin E elimination mechanisms. Cyp4f14-/- mice also revealed the existence of other hepatic TOH-[omega]-hydroxylase enzyme(s). Therefore genetically modified mice, in which no CYP activity was present in the liver, were utilized in order to eliminate all hepatic vitamin E metabolism. Metabolic cage studies revealed the presence of vitamin E hydroxylase activity in non-hepatic tissues. Mouse and human small intestine mucosa were found to have TOH-[omega]-hydoxylase activity, representing at least one site of extra-hepatic vitamin E metabolism. Lastly, the use of cell culture studies demonstrated that two polymorphisms in CYP4F2 functionally alter TOH-[omega]-hydroxylase activity, which may play a role in vitamin E status in humans. Overall, the current works lends new insights into the physiological role of the TOH-[omega]oxidation pathway as well as reveals novel mechanisms of vitamin E metabolism in both mice and humans, which play an important role in the regulation of vitamin E status.
Advisors/Committee Members: Parker, Robert Stanley (chair), Cassano, Patricia Ann (committee member), Gu, Zhenglong (committee member), O'Brien, Kimberly O (committee member).
Subjects/Keywords: vitamin E; cytochrome P450; metabolism
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APA ·
Chicago ·
MLA ·
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CSE |
Export
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APA (6th Edition):
Bardowell, S. (2012). The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/31140
Chicago Manual of Style (16th Edition):
Bardowell, Sabrina. “The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status.” 2012. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/31140.
MLA Handbook (7th Edition):
Bardowell, Sabrina. “The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status.” 2012. Web. 18 Apr 2021.
Vancouver:
Bardowell S. The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status. [Internet] [Doctoral dissertation]. Cornell University; 2012. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/31140.
Council of Science Editors:
Bardowell S. The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status. [Doctoral Dissertation]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/31140

Cornell University
10.
Barker, Brandon.
Advances In Genome-Scale Modeling Applied To Expression-Based Flux Estimation And Epistasis Prediction.
Degree: PhD, Computational Biology, 2014, Cornell University
URL: http://hdl.handle.net/1813/38758
► Quantitative models are increasingly being used to interrogate the metabolic pathways that are contained within complex biological processes, and at a higher level, these models…
(more)
▼ Quantitative models are increasingly being used to interrogate the metabolic pathways that are contained within complex biological processes, and at a higher level, these models are used to explore questions in evolution with complex physiological processes absent in typical, idealized population genetic models. In this work, we focus both on the application of quantitative models in evolution and the development of new quantitative methods for metabolism. An overview of constraint-based modeling and its purview in the field of metabolic modeling is given in Chapter 1. By using a simple version of constraint-based modeling known as flux balance analysis (FBA), we elucidate patterns that occur in gene-gene interactions of deleterious mutations (Chapters 2 and 3). Because many biological problems relate to systems that are not well-suited to FBA, especially when establishing a physiologically accurate flux is desirable, we address the problem of estimating metabolic fluxes using constraint-based models and readily available gene expression data by developing a new methodology and software (called FALCON; Chapter 4). We then take advantage of the FALCON method by using it in the development of approaches that enable the simulation of beneficial mutations and reveal some of the influences that metabolic networks bring to bear on the study of adaptation (Chapter 5).
Advisors/Committee Members: Gu, Zhenglong (chair), Christini, David (committee member), Myers, Christopher R (committee member), Stillman, Michael Eugene (committee member).
Subjects/Keywords: metabolic modeling; systems biology; flux balance analysis
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
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APA (6th Edition):
Barker, B. (2014). Advances In Genome-Scale Modeling Applied To Expression-Based Flux Estimation And Epistasis Prediction. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/38758
Chicago Manual of Style (16th Edition):
Barker, Brandon. “Advances In Genome-Scale Modeling Applied To Expression-Based Flux Estimation And Epistasis Prediction.” 2014. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/38758.
MLA Handbook (7th Edition):
Barker, Brandon. “Advances In Genome-Scale Modeling Applied To Expression-Based Flux Estimation And Epistasis Prediction.” 2014. Web. 18 Apr 2021.
Vancouver:
Barker B. Advances In Genome-Scale Modeling Applied To Expression-Based Flux Estimation And Epistasis Prediction. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/38758.
Council of Science Editors:
Barker B. Advances In Genome-Scale Modeling Applied To Expression-Based Flux Estimation And Epistasis Prediction. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/38758

Cornell University
11.
Chen, Hong.
The Role Of Gene Duplication During The Evolution Of Aerobic Fermentation In Yeast.
Degree: PhD, Nutrition, 2012, Cornell University
URL: http://hdl.handle.net/1813/31040
► The genetic basis underlying how organisms adapt to different environments and evolve new life style is a central issue of molecular evolution. The evolution of…
(more)
▼ The genetic basis underlying how organisms adapt to different environments and evolve new life style is a central issue of molecular evolution. The evolution of aerobic fermentation in yeasts is one of those good examples. So far the underlying genetic basis of this phenotypic evolution remains unclear. Gene duplication, as a primary source of materials for evolutionary novelties, has long been thought to play an important role in the adaptation of organisms to their environments. It was hypothesized that whole genome duplication (WGD) led to the development of this efficient fermentative life style. However, it remains unclear how the WGD genes are regulated during the switch of energy metabolism, an issue which should be the essence of the "WGD-Fermentation hypothesis". In this study, I first used a genome-wide expression dataset during robust metabolic oscillation in response to oxygen in budding yeast (Tu et al. 2005) to investigate the distribution of WGD genes in metabolic cycle. An enrichment of WGD genes was found underlying the physiological response of S. cerevisiae to oxygen change. Our results provided new evidence for the WGD-Fermentation hypothesis. In the next, I explored in more detail about what were the important WGD genes that contributed greatly to the evolution of aerobic fermentation. Two WGD genes are brought to the front to study this issue due to their importance on regulating energy metabolism. One of the two genes is pyruvate kinase (PYK), and the other is the target of rapamycin (TOR). In both cases, I revealed positive correlations between the copy number of these genes and the strength of aerobic fermentation on a yeast phylogenetic tree, which implies that gene duplication events of PYK and TOR are possible to facilitate the evolution of aerobic fermentation. In the PYK experiment, I found that yeasts with higher capabilities on the allosteric regulation of PYK tend to have higher fermentation abilities. I then assumed that the strengthened allosteric regulation of PYK after gene duplication might be important in the development of fermentation lifestyle in yeast. Further study on T403E mutant which is defect in allosteric regulation on PYK supported this assumption, as T403E mutant showed raised oxidative phosphorylation and decreased fermentation rate compared with the control. In the TOR experiment, I mimicked the TOR gene duplication during yeast history and doubled the TOR gene in a Crabtree-negative yeast K.lactis. I observed that the fermentation ratio in the doubled TOR mutant was significantly increased compared with the control, which supported that TOR gene duplication contributed greatly to the evolution of fermentative life style. In the view of the similar features shared by fermenting yeast and cancer cells on aerobic fermentation, our studies on PYK and TOR may shed lights on the mechanism how the Warburg effect is regulated in tumor cells.
Advisors/Committee Members: Gu, Zhenglong (chair), Henry, Susan A. (committee member), Mezey, Jason G. (committee member), Qian, Shu-Bing (committee member).
Subjects/Keywords: aerobic fermentation; gene duplication; pyruvate kinase
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chen, H. (2012). The Role Of Gene Duplication During The Evolution Of Aerobic Fermentation In Yeast. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/31040
Chicago Manual of Style (16th Edition):
Chen, Hong. “The Role Of Gene Duplication During The Evolution Of Aerobic Fermentation In Yeast.” 2012. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/31040.
MLA Handbook (7th Edition):
Chen, Hong. “The Role Of Gene Duplication During The Evolution Of Aerobic Fermentation In Yeast.” 2012. Web. 18 Apr 2021.
Vancouver:
Chen H. The Role Of Gene Duplication During The Evolution Of Aerobic Fermentation In Yeast. [Internet] [Doctoral dissertation]. Cornell University; 2012. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/31040.
Council of Science Editors:
Chen H. The Role Of Gene Duplication During The Evolution Of Aerobic Fermentation In Yeast. [Doctoral Dissertation]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/31040

Cornell University
12.
Zhang, Ruoyu.
CELLULAR AND CELL-FREE MITOCHONDRIAL DNA HETEROPLASMY AND ITS MEDICAL SIGNIFICANCE.
Degree: PhD, Nutrition, 2018, Cornell University
URL: http://hdl.handle.net/1813/59293
► Since the discovery of pathogenic mitochondrial DNA (mtDNA) mutations in the 1980's, these mutations have been shown to be involved in a number of human…
(more)
▼ Since the discovery of pathogenic mitochondrial DNA (mtDNA) mutations in the 1980's, these mutations have been shown to be involved in a number of human diseases and have caught increasing attention. The emergence of next generation sequencing technology has allowed us to do more comprehensive studies of these mutations in the mitochondrial genome, especially for low frequency heteroplasmic mutations. In my research projects, I combined experimental and computational approaches to investigate mtDNA heteroplasmies in different medical disciplines. I first conducted a literature review to summarize recent findings on the implications of mtDNA mutations in human diseases, with a focus on complex diseases such as cancer, neurodegenerative diseases and aging. My first project was to investigate mtDNA heteroplasmy and copy number variations in a general healthy population. This population-based study indicated that both mtDNA quality and quantity decreased with age. I further found that mtDNA copy number was associated with serum bicarbonate level and white blood cell counts, while aggregate heteroplasmy load was associated with blood apolipoprotein B level. These results suggested that maintaining optimal mtDNA copy number and preventing the expansion of heteroplasmy could promote healthy aging. In my second project, I first identified heteroplasmies in 466 pairs of DNA and RNA sequencing data. I verified that most of the heteroplasmies were transcribed to RNA regardless of their pathogenic potentials. I then experimentally tested whether the heteroplasmy frequencies could change over time. My test showed that a heteroplasmy with ~50% frequency could decrease to ~1% in only 28 days. Moreover, these observed heteroplasmy dynamics could significantly affect certain gene expression levels. My third project focused on mtDNA fragments circulating in blood stream in a cell-free format. I developed an experiment protocol tailored for sequencing short DNA fragments from plasma samples. After analyzing the sequencing data, I found that the fragment length of mtDNA in plasma is much shorter than that of nuclear DNA. We also demonstrated that mtDNA heteroplasmy was detectable in the plasma sample, suggesting its potential to serve as a biomarker in different clinical applications.
Advisors/Committee Members: Gu, Zhenglong (chair), Brenna, James Thomas (committee member), Sullivan, Patrick J. (committee member), De Vlaminck, Iwijn (committee member).
Subjects/Keywords: Genetics; Nutrition; Aging; Dynamics; heteroplasmy; mtDNA; cell-free DNA; Bioinformatics
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Zhang, R. (2018). CELLULAR AND CELL-FREE MITOCHONDRIAL DNA HETEROPLASMY AND ITS MEDICAL SIGNIFICANCE. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/59293
Chicago Manual of Style (16th Edition):
Zhang, Ruoyu. “CELLULAR AND CELL-FREE MITOCHONDRIAL DNA HETEROPLASMY AND ITS MEDICAL SIGNIFICANCE.” 2018. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/59293.
MLA Handbook (7th Edition):
Zhang, Ruoyu. “CELLULAR AND CELL-FREE MITOCHONDRIAL DNA HETEROPLASMY AND ITS MEDICAL SIGNIFICANCE.” 2018. Web. 18 Apr 2021.
Vancouver:
Zhang R. CELLULAR AND CELL-FREE MITOCHONDRIAL DNA HETEROPLASMY AND ITS MEDICAL SIGNIFICANCE. [Internet] [Doctoral dissertation]. Cornell University; 2018. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/59293.
Council of Science Editors:
Zhang R. CELLULAR AND CELL-FREE MITOCHONDRIAL DNA HETEROPLASMY AND ITS MEDICAL SIGNIFICANCE. [Doctoral Dissertation]. Cornell University; 2018. Available from: http://hdl.handle.net/1813/59293

Cornell University
13.
Gupta, Diwakar.
Arginine and proline metabolism is associated with older adult skeletal muscle mass and altered by inflammation in primary human muscle cells.
Degree: M.S., Nutrition, Nutrition, 2017, Cornell University
URL: http://hdl.handle.net/1813/56804
► Age-related loss of skeletal muscle mass (sarcopenia) adversely affects muscle tissue-specific and whole-body homeostasis, suggesting an undefined relationship between muscle mass and whole-body circulation that…
(more)
▼ Age-related loss of skeletal muscle mass (sarcopenia) adversely affects muscle tissue-specific and whole-body homeostasis, suggesting an undefined relationship between muscle mass and whole-body circulation that underlies the etiology of sarcopenia.
To investigate, 344 metabolites and analytes were measured in serum from 19 older adults. Arginine and proline metabolism was the pathway most closely associated with skeletal muscle index (SMI), a measure of skeletal muscle mass. Subsequently, gene expression of related transport and regulatory enzymes was measured.
Younger and older adult muscle tissue had similar inflammatory signaling and gene expression of CAT-1 and CAT-2, the cationic amino acid transporters that allow arginine into muscle. However, the proinflammatory cytokine TNF-α increased CAT-2 gene expression in differentiated human primary skeletal muscle cells. TNF-α also altered the expression of arginine metabolic genes regulating polyamine synthesis and proline production.
Changes in arginine availability and metabolism may underlie the relationship between inflammation and skeletal muscle mass.
Advisors/Committee Members: Thalacker-Mercer, Anna E. (chair), Libert, Sergiy (committee member), Brenna, James Thomas (committee member), Gu, Zhenglong (committee member).
Subjects/Keywords: Nutrition; metabolomics; arginine metabolism; inflammation susceptibility; myoblasts; sarcopenia
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Gupta, D. (2017). Arginine and proline metabolism is associated with older adult skeletal muscle mass and altered by inflammation in primary human muscle cells. (Masters Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/56804
Chicago Manual of Style (16th Edition):
Gupta, Diwakar. “Arginine and proline metabolism is associated with older adult skeletal muscle mass and altered by inflammation in primary human muscle cells.” 2017. Masters Thesis, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/56804.
MLA Handbook (7th Edition):
Gupta, Diwakar. “Arginine and proline metabolism is associated with older adult skeletal muscle mass and altered by inflammation in primary human muscle cells.” 2017. Web. 18 Apr 2021.
Vancouver:
Gupta D. Arginine and proline metabolism is associated with older adult skeletal muscle mass and altered by inflammation in primary human muscle cells. [Internet] [Masters thesis]. Cornell University; 2017. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/56804.
Council of Science Editors:
Gupta D. Arginine and proline metabolism is associated with older adult skeletal muscle mass and altered by inflammation in primary human muscle cells. [Masters Thesis]. Cornell University; 2017. Available from: http://hdl.handle.net/1813/56804

Cornell University
14.
Si, Yuan.
Metabolic determinants of longevity: dietary supplementation and mitochondria.
Degree: PhD, Nutrition, 2018, Cornell University
URL: http://hdl.handle.net/1813/59452
► Aging is a natural and inevitable process that leads to the irreversible impairment of biological functions and increased vulnerability to death. Great efforts have been…
(more)
▼ Aging is a natural and inevitable process that leads to the irreversible impairment of biological functions and increased vulnerability to death. Great efforts have been spent to study the mechanisms underlying the aging process, with the ultimate goal of developing effective interventions to delay the onset of aging and to extend lifespan. Mitochondria, more than just being the powerhouses of the cell, are involved in a wide range of cellular and metabolic processes. Multiple lines of evidence have suggested that mitochondria play a vital role in the process of aging. Therefore, my research aims to investigate the effect of both dietary supplements and mitochondrial DNA content on lifespan. Chapter one reviews the contemporary knowledge of mitochondrial DNA genetics and the implication of mitochondrial dysfunction in human diseases. It also summarizes the interaction between mitochondria and different dietary components or dietary patterns. I want to emphasize the importance of investigating the role of mitochondria in the development of complex diseases and to suggest future directions in identifying nutritional interventions to restore mitochondrial functions. Chapter two and Chapter three describe the discoveries of two compounds that extend the lifespan of Drosophila melanogaster. The first one is konjac glucomannan hydrolysate, which can promote longevity in both genders across different genetic backgrounds, and regardless of mating status. By investigating the potential underlying mechanisms, we found it extends the lifespan through promoting the growth of gut microbiome and preserving the intestinal proliferative homeostasis. The second compound is oligofructose, the hydrolyzed form of inulin. It can also prolong the lifespan but is restricted to specific genetic backgrounds and mating status. Revealed by the transcriptome analysis, it is very likely that it extends lifespan through the inhibition of mitochondrial respiration and suppression of stress signaling pathways. Chapter four describes an exploratory project on the relationship between mitochondrial DNA content and lifespan in both normal and stress conditions. By implementing both survival test and transcriptome analysis, we found a possible connection between mtDNA copy number and the lifespan in male flies through regulation of fertility.
Advisors/Committee Members: Gu, Zhenglong (chair), Lee, Siu Sylvia (committee member), McCormick, Charles Chipley W (committee member), Buchon, Nicolas S. (committee member), Han, Chun (committee member).
Subjects/Keywords: Nutrition; Molecular biology; Drosophila melanogaster; konjac; longevity; mitochondrial DNA copy number; oligofructose
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Si, Y. (2018). Metabolic determinants of longevity: dietary supplementation and mitochondria. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/59452
Chicago Manual of Style (16th Edition):
Si, Yuan. “Metabolic determinants of longevity: dietary supplementation and mitochondria.” 2018. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/59452.
MLA Handbook (7th Edition):
Si, Yuan. “Metabolic determinants of longevity: dietary supplementation and mitochondria.” 2018. Web. 18 Apr 2021.
Vancouver:
Si Y. Metabolic determinants of longevity: dietary supplementation and mitochondria. [Internet] [Doctoral dissertation]. Cornell University; 2018. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/59452.
Council of Science Editors:
Si Y. Metabolic determinants of longevity: dietary supplementation and mitochondria. [Doctoral Dissertation]. Cornell University; 2018. Available from: http://hdl.handle.net/1813/59452

Cornell University
15.
Cao, Chang.
Utilization Of Heme And Non-Heme Iron Sources During Pregnancy.
Degree: PhD, Nutrition, 2014, Cornell University
URL: http://hdl.handle.net/1813/38768
► Intestinal iron absorption increases during pregnancy to support maternal and fetal iron demands. Although knowledge on non-heme iron absorption has advanced substantially since identification of…
(more)
▼ Intestinal iron absorption increases during pregnancy to support maternal and fetal iron demands. Although knowledge on non-heme iron absorption has advanced substantially since identification of the hormone hepcidin in 2000, the mechanisms of heme iron absorption remain elusive. Catabolism of senescent red blood cells releases 10-times more iron into the circulation daily than does iron absorption from the diet, yet the contribution of this endogenous maternal heme iron source to fetal iron transfer is unknown. The human placenta abundantly expresses an array of heme transporters but it is unclear whether these proteins play a role in placental heme utilization. The objective of this research was to explore the mechanism and regulation of heme and non-heme iron utilization in the duodenum and the placenta, the two major sites of iron flux during pregnancy. To address these questions, stable iron isotopes (57Fe and 58Fe) were used to measure duodenal heme and non-heme iron absorption in rats and placental transfer of iron derived from maternal red blood cell catabolism and from maternal diet in pregnant women. In Sprague Dawley rats, hepcidin up-regulation suppressed the absorption of both heme and nonheme iron but the effect was more pronounced for non-heme. Hepcidin was inversely associated with iron transporters on the apical but not basolateral side of the duodenum, suggesting apical iron transport is the primary target of hepcidin action. The stable iron isotope study in pregnant women (n=16, ages 17-35 years) indicated that iron derived from maternal red blood cells was transferred to the fetus, revealing the importance of maternal red cell iron stores in supporting fetal iron demands. In a cohort of pregnant adolescents (13-18 years), placental protein expression of two putative heme transporters were associated with neonatal iron status, consistent with a role of these proteins in placental iron transport. Future research is needed to elucidate the roles of these transporters in the uptake and intracellular trafficking of heme in the placenta and to characterize the sources of heme iron in the circulation and inter-tissue heme trafficking pathways.
Advisors/Committee Members: O'Brien, Kimberly O (chair), Cassano, Patricia Ann (committee member), Davisson, Robin L (committee member), Gu, Zhenglong (committee member).
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APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Cao, C. (2014). Utilization Of Heme And Non-Heme Iron Sources During Pregnancy. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/38768
Chicago Manual of Style (16th Edition):
Cao, Chang. “Utilization Of Heme And Non-Heme Iron Sources During Pregnancy.” 2014. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/38768.
MLA Handbook (7th Edition):
Cao, Chang. “Utilization Of Heme And Non-Heme Iron Sources During Pregnancy.” 2014. Web. 18 Apr 2021.
Vancouver:
Cao C. Utilization Of Heme And Non-Heme Iron Sources During Pregnancy. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/38768.
Council of Science Editors:
Cao C. Utilization Of Heme And Non-Heme Iron Sources During Pregnancy. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/38768

Cornell University
16.
Sung, Guanjen.
Perceptions Of Medicinal And Medicated Food Use Of Taiwanese Immigrant Families In The Us: A Multi-Method Exploratory Study.
Degree: PhD, Nutrition, 2013, Cornell University
URL: http://hdl.handle.net/1813/34244
► This study investigates the perceptions of medicinal and medicated food (MMF) use of Taiwanese immigrant families in the US. The background of use of food…
(more)
▼ This study investigates the perceptions of medicinal and medicated food (MMF) use of Taiwanese immigrant families in the US. The background of use of food as medicine and for health promotion in Chinese history and in Taiwan and the situation of immigrants with transnational ties suggested that the Family Food Decision Making (FFDM) framework could be fruitfully applied along with the life course perspective (LCP) and expanded by the study. Informed by initial informant engagement, a preliminary framework informed design of the survey, including a questionnaire answered by 113 participants. The results were analyzed using descriptive statistics. Together with informant engagement of survey participants, it revealed a need to build trust relationships and social connections in interviewing. A constructivist grounded theory (CGT) approach to in-depth interviews was applied, with modifications for CGT analysis incorporating language translation. Twelve interviews were conducted. The building of trust and a pattern of interviewee behavior resulted in a distinctively egalitarian interview style. The study's findings show that Taiwanese immigrants perceive the meaning of MMF in terms of taste and medicinal effectiveness and can practice amateur or connoisseur MMF usages. Parents are a major influence on transmission of MMF use; personality, religious food practices, and degrees of connection with Taiwanese Chinese medicine use also affect FFDM. Childhood training to accept MMF taste can further continuance of MMF use in later life. Recently increased transnational contacts contribute to bi-directional Taiwan/US influences on MMF sourcing and knowledge transmission. This has affected synergistically changing MMF environments in both places. These and other insights contribute to theorization about interactions of MMF meaning, family FDM dynamics, and human environmental influences, e.g., food traditions and systems and social relations. An MMF-expanded framework is developed from the FFDM Ecological System Framework. Methodological insights on building trust relationships and egalitarian influences on the interviewing mode inspired development of a dyadic dialogue method (DDM) that could aid FFDM Collaborative Engaged Research. The study also suggests three directions for future FFDM and MMF research: incorporating concern with FFDM efficacy, familycommunity MMF use collaborative engaged research, and exploration of Taiwan and US MMF systems.
Advisors/Committee Members: Gillespie, Ardyth Harris (chair), Wethington, Elaine (committee member), Gillespie Jr, Gilbert W. (committee member), Gu, Zhenglong (committee member).
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Sung, G. (2013). Perceptions Of Medicinal And Medicated Food Use Of Taiwanese Immigrant Families In The Us: A Multi-Method Exploratory Study. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/34244
Chicago Manual of Style (16th Edition):
Sung, Guanjen. “Perceptions Of Medicinal And Medicated Food Use Of Taiwanese Immigrant Families In The Us: A Multi-Method Exploratory Study.” 2013. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/34244.
MLA Handbook (7th Edition):
Sung, Guanjen. “Perceptions Of Medicinal And Medicated Food Use Of Taiwanese Immigrant Families In The Us: A Multi-Method Exploratory Study.” 2013. Web. 18 Apr 2021.
Vancouver:
Sung G. Perceptions Of Medicinal And Medicated Food Use Of Taiwanese Immigrant Families In The Us: A Multi-Method Exploratory Study. [Internet] [Doctoral dissertation]. Cornell University; 2013. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/34244.
Council of Science Editors:
Sung G. Perceptions Of Medicinal And Medicated Food Use Of Taiwanese Immigrant Families In The Us: A Multi-Method Exploratory Study. [Doctoral Dissertation]. Cornell University; 2013. Available from: http://hdl.handle.net/1813/34244
17.
Kaufman, Andrew.
INFLAMMATION ARISING FROM OBESITY REDUCES TASTE BUD ABUNDANCE AND RENEWAL.
Degree: PhD, Food Science and Technology, 2017, Cornell University
URL: http://hdl.handle.net/1813/47774
► Despite evidence that the ability to taste is weakened by obesity and rescued with weight loss intervention, few studies have investigated the molecular effects of…
(more)
▼ Despite evidence that the ability to taste is weakened by obesity and rescued with weight loss intervention, few studies have investigated the molecular effects of obesity on the physiology of taste. Taste bud cells undergo continual turnover, even in adulthood, exhibiting an average life span of about 10 days, tightly controlled by a balance of proliferation and cell death. Recent data reveal that an acute inflammation event can upset this balance. I demonstrate that chronic low-grade inflammation brought on by an obesogenic diet reduces the number of taste buds in gustatory tissues of mice, by attenuating the renewal of taste cells, and is likely the cause of taste dysfunction seen in obese populations.
Advisors/Committee Members: Dando, Robin (chair), Kawate, Toshimitsu (committee member), Gu, Zhenglong (committee member).
Subjects/Keywords: Food science; Obesity; Development; Inflammation; Developmental biology; Taste bud; Molecular biology
…Cornell University College of Veterinary Medicine. 8 week old
male mice were fed on either… …approved by the Cornell University Institutional Animal Care and Use Committee.
Quantitative…
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APA (6th Edition):
Kaufman, A. (2017). INFLAMMATION ARISING FROM OBESITY REDUCES TASTE BUD ABUNDANCE AND RENEWAL. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/47774
Chicago Manual of Style (16th Edition):
Kaufman, Andrew. “INFLAMMATION ARISING FROM OBESITY REDUCES TASTE BUD ABUNDANCE AND RENEWAL.” 2017. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/47774.
MLA Handbook (7th Edition):
Kaufman, Andrew. “INFLAMMATION ARISING FROM OBESITY REDUCES TASTE BUD ABUNDANCE AND RENEWAL.” 2017. Web. 18 Apr 2021.
Vancouver:
Kaufman A. INFLAMMATION ARISING FROM OBESITY REDUCES TASTE BUD ABUNDANCE AND RENEWAL. [Internet] [Doctoral dissertation]. Cornell University; 2017. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/47774.
Council of Science Editors:
Kaufman A. INFLAMMATION ARISING FROM OBESITY REDUCES TASTE BUD ABUNDANCE AND RENEWAL. [Doctoral Dissertation]. Cornell University; 2017. Available from: http://hdl.handle.net/1813/47774
18.
Minchella, Peter.
Iron Homeostasis And Anemia In Hiv And Tuberculosis.
Degree: PhD, Nutrition, 2015, Cornell University
URL: http://hdl.handle.net/1813/40696
► Background: Evidence supports a role for iron homeostasis in the pathogenesis of HIV and tuberculosis. The iron regulatory peptide, hepcidin, inhibits both dietary iron absorption…
(more)
▼ Background: Evidence supports a role for iron homeostasis in the pathogenesis of HIV and tuberculosis. The iron regulatory peptide, hepcidin, inhibits both dietary iron absorption and iron efflux leading to macrophage iron retention. Conditions associated with elevated hepcidin, which include altered concentrations of ferritin, transferrin and hemoglobin, may favor Mycobacterium tuberculosis iron acquisition, HIV progression and anemia. In light of this, we investigated iron homeostasis biomarkers as risk factors for incident TB and mortality in an HIVseropositive cohort and also for progression to TB in an HIV-seromixed cohort. In addition, we characterized iron homeostasis during TB therapy in order to identify causes of anemia and inform selection of safe, effective and well-timed treatments for anemia. Methods: Clinical and demographic data and archived plasma and serum samples from two research platforms were utilized in this work: the Medical Research Council (MRC) HIV clinical cohort and the MRC TB case contact study. Analysis of iron homeostasis biomarker concentrations was conducted at MRC laboratories in The Gambia. Results: During HIV Clinical Cohort follow up, 32 incident tuberculosis cases were identified and 64% of the 196 participants died. Greater hepcidin was associated with significantly increased likelihood of tuberculosis and greater all-cause mortality. This was consistent with observed higher ferritin and hepcidin concentrations in HIV-seromixed contacts of infectious TB cases that progressed to TB earlier. Analysis of biomarkers and anemia during TB therapy revealed that anemia of inflammation was predominant TB diagnosis, declining significantly after six months of treatment; however, a corresponding reduction was not evident for anemia with iron-responsive components. Hepcidin concentrations significantly declined after 2 months of TB treatment. Conclusions: Changes in iron homeostasis biomarkers are associated with incident TB and mortality in HIV and progression to TB disease among contacts of infectious TB cases. Further studies are needed to elucidate mechanisms and determine the clinical utility of monitoring iron homeostasis biomarkers. TB therapy is associated with significant reductions in anemia of inflammation, but iron-based interventions are needed for anemia with iron responsive components. Monitoring hepcidin reveals a window for intervention opening as early as two months into TB treatment.
Advisors/Committee Members: McDermid,Joann M. (chair), Gu,Zhenglong (committee member), Rudd,Brian D (committee member), McCormick,Charles Chipley W (committee member).
Subjects/Keywords: Hepcidin, Ferritin, Transferrin,; Inflammation, Africa
Record Details
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Record Details
Similar Records
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❌
APA ·
Chicago ·
MLA ·
Vancouver ·
CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Minchella, P. (2015). Iron Homeostasis And Anemia In Hiv And Tuberculosis. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/40696
Chicago Manual of Style (16th Edition):
Minchella, Peter. “Iron Homeostasis And Anemia In Hiv And Tuberculosis.” 2015. Doctoral Dissertation, Cornell University. Accessed April 18, 2021.
http://hdl.handle.net/1813/40696.
MLA Handbook (7th Edition):
Minchella, Peter. “Iron Homeostasis And Anemia In Hiv And Tuberculosis.” 2015. Web. 18 Apr 2021.
Vancouver:
Minchella P. Iron Homeostasis And Anemia In Hiv And Tuberculosis. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Apr 18].
Available from: http://hdl.handle.net/1813/40696.
Council of Science Editors:
Minchella P. Iron Homeostasis And Anemia In Hiv And Tuberculosis. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/40696
.