+publisher:"Cornell University" +contributor:("Cohen, Paula")

Cornell University

1. Bozza, Christopher. Mapping And Cytological Characterization Of Maize Meiotic Mutants Segii And Dsycs.

Degree: M.S., Plant Biology, Plant Biology, 2012, Cornell University

► Homologous pairing during meiosis is an important process for the fidelity of recombination and chromosome segregation. The activity of homologous pairing has been linked to… (more)

▼ Homologous pairing during meiosis is an important process for the fidelity of recombination and chromosome segregation. The activity of homologous pairing has been linked to events that occur during the early stages of recombination, namely double strand break formation and single end invasion. The exact activities that regulate the genetic network of homologous pairing are not completely understood. The first chapter of this dissertation provides a review of research regarding homologous pairing. To understand more about the activity, a forward genetics approach was used to identify two mutants of maize, segII and dsyCS. Cytological characterization of these mutants and mapping the genetic lesion underlying each of their phenotypes comprise the second and third chapters. Combining FISH and immunolocalization studies, the segII mutant displays abnormalities beginning at the leptotene stage of meiosis, which result in reduced installation of DSB repair proteins, non-homologous pairing, reduced chiasmata, and crossovers between non-homologous chromosomes. Application of cisplatin to segII mutants to induce double strand breaks at leptotene partially rescues repair protein installation, suggesting that a lack of DSBs underlies the abnormal meiotic phenotype of segII. Analysis of the segII mutant also indicates that maize displays crossover homeostasis through its reduced single end invasion events. The number of chiasmata is disproportionally reduced when compared to the number of SEI: 26% versus 2% respectively. The dsyCS mutant was also analyzed using FISH and immunolocazliation studies. It displays a similar repair protein abnormality to segII, a more severe pairing phenotype than segII and, most notably, a high rate of anaphase bridges. A FISH probe to the telomeres reveals interchromosomal connections at diakinesis, which suggests that improper telomere repair is at least partially responsible for the bridges. dsyCS displays non-homologous crossovers, and together with segII and the previously characterized zmRad51 mutant, suggests that maize has at least three genetic paths to create nonhomologous chiasmata. Advisors/Committee Members: Pawlowski, Wojciech (chair), Cohen, Paula (committee member), Rose, Jocelyn (committee member), Scanlon, Michael J. (committee member).

Subjects/Keywords: Meiosis; Homologous Pairing; chiasmata; recombination; segII; dsyCS; sei; Crossover homeostasis

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APA (6^th Edition):

Bozza, C. (2012). Mapping And Cytological Characterization Of Maize Meiotic Mutants Segii And Dsycs. (Masters Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/31407

Chicago Manual of Style (16^th Edition):

Bozza, Christopher. “Mapping And Cytological Characterization Of Maize Meiotic Mutants Segii And Dsycs.” 2012. Masters Thesis, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/31407.

MLA Handbook (7^th Edition):

Bozza, Christopher. “Mapping And Cytological Characterization Of Maize Meiotic Mutants Segii And Dsycs.” 2012. Web. 17 Jan 2021.

Vancouver:

Bozza C. Mapping And Cytological Characterization Of Maize Meiotic Mutants Segii And Dsycs. [Internet] [Masters thesis]. Cornell University; 2012. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/31407.

Council of Science Editors:

Bozza C. Mapping And Cytological Characterization Of Maize Meiotic Mutants Segii And Dsycs. [Masters Thesis]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/31407

Cornell University

2. Mainiero, Samantha. Understanding How Chromosome Structure Influences Recombination.

Degree: M.S., Plant Biology, Plant Biology, 2015, Cornell University

URL: http://hdl.handle.net/1813/40718

► Meiotic recombination results in the exchange of DNA between homologous chromosomes, creating allelic diversity while at the same time ensuring correct segregation of chromosomes during… (more)

Subjects/Keywords: meiosis; chromosome; maize

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APA (6^th Edition):

Mainiero, S. (2015). Understanding How Chromosome Structure Influences Recombination. (Masters Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/40718

Chicago Manual of Style (16^th Edition):

Mainiero, Samantha. “Understanding How Chromosome Structure Influences Recombination.” 2015. Masters Thesis, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/40718.

MLA Handbook (7^th Edition):

Mainiero, Samantha. “Understanding How Chromosome Structure Influences Recombination.” 2015. Web. 17 Jan 2021.

Vancouver:

Mainiero S. Understanding How Chromosome Structure Influences Recombination. [Internet] [Masters thesis]. Cornell University; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/40718.

Council of Science Editors:

Mainiero S. Understanding How Chromosome Structure Influences Recombination. [Masters Thesis]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/40718

Cornell University

3. Brosnahan, Margaret. Invasion And Survival: Immunological Studies Of The Equine Chorionic Girdle.

Degree: PhD, Immunology, 2015, Cornell University

URL: http://hdl.handle.net/1813/39386

► Successful mammalian pregnancy requires precise modulation of normal biological processes to ensure the survival of the feto-placental tissues while preserving the good health of the… (more)

▼ Successful mammalian pregnancy requires precise modulation of normal biological processes to ensure the survival of the feto-placental tissues while preserving the good health of the mother. The original research presented in this dissertation encompasses studies in both of these areas. The first part of this work addresses the long-standing question as to how feto-placental tissues, specifically invasive trophoblast, survive in the hostile environment of the maternal immune system. The Antczak laboratory previously developed an ectopic trophoblast transplant system to facilitate studies of the maternal immune response to invasive trophoblast in the horse. Single transplants of horse chorionic girdle into the vulvar mucosa of non-pregnant horse recipients were found to have lifespans and physiologic effects upon recipients similar to endometrial cups in a normal horse pregnancy. The current studies first expanded the trophoblast transplant system to include multiple rather than single transplants in individual recipients. The objective of this was to examine ectopic trophoblast survival in an immunologically primed as compared to naïve recipient. These serial transplants had lifespans similar to the single transplants, suggesting that the mechanisms protecting the trophoblast from immune destruction are initiated by the trophoblast itself. A series of transplants then was performed using Jenny donkeys as recipients. In each donkey recipient, primary transplants had lifespans of similar length to the horse-to-horse transplants, with second and subsequent transplants having progressively shorter lifespans. This pattern suggests that the horse-to-donkey transplants were subjected to a classic destructive memory response. The second body of work addresses the question as to how normal placentation disrupts maternal anatomy and physiology without causing adverse effects. This work was initiated with the discovery of interleukin 22 (IL22) mRNA in day 34 chorionic girdle using gene expression array analysis. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) then revealed that IL22 mRNA was rapidly upregulated in the chorionic girdle between days 32 and 35 of pregnancy. This represented the first identification of IL22 expression by a non-immune cell type. Interleukin 22 receptor RA1 (IL22RA1) mRNA was identified in pregnant endometrium, and in situ hybridization localized the mRNA to both the luminal and glandular epithelia. A monoclonal antibody was then generated against horse IL22. Mice were immunized with a fusion protein containing recombinant horse IL4 and IL22. Murine splenic cells were fused with SP 2/O myeloma cells to generate hybridoma cell lines. A monoclonal antibody to equine IL22 was identified. IL22 protein was then successfully detected in day 35 chorionic girdle. Knowing that IL22 in other biological systems has a role in preserving the integrity of mucosal surfaces and in epithelial cell proliferation, it was hypothesized that IL22 produced from the chorionic girdle binds receptor in… Advisors/Committee Members: Antczak, Douglas Francis (chair), Cohen, Paula (committee member), Wagner, Bettina (committee member).

Subjects/Keywords: equine; trophoblast; immunology

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APA (6^th Edition):

Brosnahan, M. (2015). Invasion And Survival: Immunological Studies Of The Equine Chorionic Girdle. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/39386

Chicago Manual of Style (16^th Edition):

Brosnahan, Margaret. “Invasion And Survival: Immunological Studies Of The Equine Chorionic Girdle.” 2015. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/39386.

MLA Handbook (7^th Edition):

Brosnahan, Margaret. “Invasion And Survival: Immunological Studies Of The Equine Chorionic Girdle.” 2015. Web. 17 Jan 2021.

Vancouver:

Brosnahan M. Invasion And Survival: Immunological Studies Of The Equine Chorionic Girdle. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/39386.

Council of Science Editors:

Brosnahan M. Invasion And Survival: Immunological Studies Of The Equine Chorionic Girdle. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/39386

Cornell University

4. Zhou, Adele. Understanding regulation of meiosis in Arabidopsis and maize.

Degree: PhD, Biochemistry, Molecular and Cell Biology, 2018, Cornell University

URL: http://hdl.handle.net/1813/59496

► Meiosis is a specialized cell division that is required for sexual reproduction. Homologous chromosome pairing and meiotic recombination are two defining processes of prophase I… (more)

▼ Meiosis is a specialized cell division that is required for sexual reproduction. Homologous chromosome pairing and meiotic recombination are two defining processes of prophase I of meiosis and are required for the generation of genetic variation. Core proteins involved in these processes are well studied, but it is not well understood how meiosis is regulated. In this dissertation, I shed light on how meiosis is regulated by long non-coding RNAs (lncRNAs) in Arabidopsis thaliana, as well as how meiotic recombination is regulated by chromatin in maize. Many long non-coding RNAs (lncRNAs) have been identified in various species but few have been functionally analyzed. Of the few lncRNAs that have been analyzed, they have been found to play roles in regulating gene expression and modifying chromatin. However, the functions of the vast majority of them are unknown and no lncRNAs have been identified in Arabidopsis meiosis. On the other hand, significantly more genes are expressed during meiosis than the number of genes actually required for meiosis completion, suggesting that there is a mechanism controlling gene expression post-transcriptionally, possibly involving lncRNAs. This situation prompted us to conduct a systematic analysis of lncRNAs in Arabidopsis meiosis. We generated a bioinformatics pipeline that utilizes RNA-seq data from Arabidopsis meiocytes and somatic tissues to identify novel lncRNAs that are specific to meiosis. We then established a multistep mutant screen to identify lncRNAs that are functional in meiosis and found that lncRNAs play a role in overall fertility in Arabidopsis thaliana. Chapter 3 of this dissertation focuses on understanding the role of chromatin in the regulation of meiotic recombination events that result in crossovers (COs) in maize. In this species, double strand breaks (DSBs) are evenly distributed along chromosomes, including pericentromeric and centromeric regions. However, CO distribution does not follow the DSB distribution. Instead, COs are enriched in distal chromosome regions and suppressed in pericentromeric and centromeric regions. We investigated the dynamics of recombination events in relationship to chromatin states in order to understand how this distribution is formed. We further studied the CO/non-crossover (NCO) decision through its relationship with chromatin. We found that DNA methylation is a major contributor to the decision of which DSBs become COs and this decision is progressively enforced when meiotic DSBs are repaired. Interestingly, this process proceeds differently in B73 and CML228, two maize inbreds with dramatically differing numbers of recombination events. Advisors/Committee Members: Pawlowski, Wojciech (chair), Cohen, Paula (committee member), Richards, Eric Jean (committee member).

Subjects/Keywords: Genetics; meiosis; Molecular biology; crossovers; double strand breaks; epigenetic marks; non-coding RNAs; recombination; Plant sciences

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APA (6^th Edition):

Zhou, A. (2018). Understanding regulation of meiosis in Arabidopsis and maize. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/59496

Chicago Manual of Style (16^th Edition):

Zhou, Adele. “Understanding regulation of meiosis in Arabidopsis and maize.” 2018. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/59496.

MLA Handbook (7^th Edition):

Zhou, Adele. “Understanding regulation of meiosis in Arabidopsis and maize.” 2018. Web. 17 Jan 2021.

Vancouver:

Zhou A. Understanding regulation of meiosis in Arabidopsis and maize. [Internet] [Doctoral dissertation]. Cornell University; 2018. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/59496.

Council of Science Editors:

Zhou A. Understanding regulation of meiosis in Arabidopsis and maize. [Doctoral Dissertation]. Cornell University; 2018. Available from: http://hdl.handle.net/1813/59496

Cornell University

5. Chu, Erin Tsi-Jia. MECHANISMS AND CONSEQUENCES OF DNA METHYLATION IN TWO MODEL SPECIES.

Degree: PhD, Comparative Biomedical Sciences, 2017, Cornell University

URL: http://hdl.handle.net/1813/59013

► Epigenetic modifications are known to regulate gene expression in a heritable manner, and can broadly be divided into three interacting classes: DNA methylation, histone modifications,… (more)

▼ Epigenetic modifications are known to regulate gene expression in a heritable manner, and can broadly be divided into three interacting classes: DNA methylation, histone modifications, and chromatin interactions. While the trans acting factors that establish, maintain, and remove DNA methylation are well-known, the cis acting mechanisms that direct DNA methylation to specific genomic locations remain elusive. Two gene classes offer insights into cis-acting mechanisms for DNA methylation: imprinted loci, and transposable elements. A locus spanning both is the murine Rasgrf1 locus. Rasgrf1 has a cis element, a series of tandem repeats, required for DNA methylation, but also harbors a long noncoding RNA, the pitRNA. The pitRNA is driven by the repeats and is targeted by piRNAs, small RNAs that mediate transposable element methylation in the mammalian male germline. However, the effects of the pitRNA versus the repeats have not yet been separated. My work, where I used CRISPR/Cas9 genome editing to generate a targeted mutant system permitting inducible control of the pitRNA, is the first to query the sufficiency of the pitRNA independently. Using quantitative qPCR and targeted bisulfite sequencing, I demonstrated that expression of the lncRNA at physiological levels in the male germline is insufficient to impart DNA methylation at Rasgrf1. These findings were complimented by additional in vitro studies, where I identified Sp1 as a transcription factor that binds the repeats and is required for pitRNA expression. Sp1 binds secondary DNA structure and has recently been identified as a regulating factor at another imprinted gene. Together, these findings support an alternative, critical role for the repeats beyond their known role in regulating pitRNA expression. Beyond mechanism, DNA methylation in the context of disease are an area of active study, though its utility in non-traditional model organisms is nascent. The second focus of my thesis speaks to this. I performed reduced representation bisulfite analysis on two dog breeds with highly diverse morphology and disease risks. While this work is largely preliminary, two differentially methylated regions have direct association with differential disease risk between these two breeds, suggesting that the canine methylome could be used as method of disease surveillance. Advisors/Committee Members: Soloway, Paul (chair), Schimenti, John C. (committee member), Cohen, Paula (committee member), Kurpios, Natasza (committee member).

Subjects/Keywords: Genetics; Molecular biology

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APA (6^th Edition):

Chu, E. T. (2017). MECHANISMS AND CONSEQUENCES OF DNA METHYLATION IN TWO MODEL SPECIES. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/59013

Chicago Manual of Style (16^th Edition):

Chu, Erin Tsi-Jia. “MECHANISMS AND CONSEQUENCES OF DNA METHYLATION IN TWO MODEL SPECIES.” 2017. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/59013.

MLA Handbook (7^th Edition):

Chu, Erin Tsi-Jia. “MECHANISMS AND CONSEQUENCES OF DNA METHYLATION IN TWO MODEL SPECIES.” 2017. Web. 17 Jan 2021.

Vancouver:

Chu ET. MECHANISMS AND CONSEQUENCES OF DNA METHYLATION IN TWO MODEL SPECIES. [Internet] [Doctoral dissertation]. Cornell University; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/59013.

Council of Science Editors:

Chu ET. MECHANISMS AND CONSEQUENCES OF DNA METHYLATION IN TWO MODEL SPECIES. [Doctoral Dissertation]. Cornell University; 2017. Available from: http://hdl.handle.net/1813/59013

Cornell University

6. Strong, Edward. Towards The Understanding Of Ccnb1Ip1 As A Co-Regulator Of Meiotic Crossing-Over In The Mouse.

Degree: PhD, Genetics, 2014, Cornell University

URL: http://hdl.handle.net/1813/36075

► It is clear that there are many genes required for meiosis in mammals that are not present in the more tractable model organisms. To identify… (more)

Subjects/Keywords: Meiosis; Sumoylation; CCNB1IP1

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APA (6^th Edition):

Strong, E. (2014). Towards The Understanding Of Ccnb1Ip1 As A Co-Regulator Of Meiotic Crossing-Over In The Mouse. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/36075

Chicago Manual of Style (16^th Edition):

Strong, Edward. “Towards The Understanding Of Ccnb1Ip1 As A Co-Regulator Of Meiotic Crossing-Over In The Mouse.” 2014. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/36075.

MLA Handbook (7^th Edition):

Strong, Edward. “Towards The Understanding Of Ccnb1Ip1 As A Co-Regulator Of Meiotic Crossing-Over In The Mouse.” 2014. Web. 17 Jan 2021.

Vancouver:

Strong E. Towards The Understanding Of Ccnb1Ip1 As A Co-Regulator Of Meiotic Crossing-Over In The Mouse. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/36075.

Council of Science Editors:

Strong E. Towards The Understanding Of Ccnb1Ip1 As A Co-Regulator Of Meiotic Crossing-Over In The Mouse. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36075

Cornell University

7. Cheong, Soon Hon. Factors Associated With The Clearance Of Uterine Inflammation And Resumption Of Ovarian Cyclicity In Postpartum Dairy Cows.

Degree: PhD, Veterinary Medicine, 2012, Cornell University

URL: http://hdl.handle.net/1813/31001

► Reproductive performance is paramount to efficient milk production in dairy cows. Many postpartum cows do not clear uterine inflammation and resume normal ovarian cyclicity by… (more)

▼ Reproductive performance is paramount to efficient milk production in dairy cows. Many postpartum cows do not clear uterine inflammation and resume normal ovarian cyclicity by the time they are presented for reinsemination. This dissertation aimed to study of factors associated with the delay in clearance of uterine inflammation and resumption of ovarian cyclicity in the postpartum cow. Subclinical endometritis (SCE) is the presence of inflammation in the uterus beyond the normal involution without any other signs of disease. A large epidemiological study was performed obtaining uterine samples, risk factors and reproductive outcome data from 38 commercial dairy herds. Cow-level risk factors for SCE identified were: ketosis, milk production and metritis. Reagent strip test was evaluated as a potential cow-side test for SCE. Reagent strip tests were found to be strongly associated with SCE, however low sensitivity and specificity limits its potential use. The effects uterine sample collections on economically important outcomes on sampled cows were tested and no detrimental effects were found. The main difference between early postpartum follicles that will ovulate and those that do is the ability to produce a rise in circulating estradiol concentrations. A novel follicle fate prediction method was used to identify cows that will likely go on to ovulate or not using follicle growth parameters and circulating estradiol concentrations. This allowed for follicular fluid collection and steroid hormone analyses. In non-ovulatory cows; the theca cell function was impaired, there were fewer luteinizing hormone pulses, and had more severe negative energy balance primarily due to decreased feed intake compared with ovulatory cows. Uterine health association with follicular function was evaluated. Certain bacterial isolates were associated with reduced follicle growth. Follicular fluid endotoxin levels were found to be higher in non-ovulatory cow and they also had higher circulating haptoglobin levels which are an indicator for acute phase response. Negative energy balance and uterine health disorders were associated with both SCE and non-ovulation. Advisors/Committee Members: Gilbert, Robert Owen (chair), Roberson, Mark Stephen (committee member), Nydam, Daryl Van (committee member), Cohen, Paula (committee member).

Subjects/Keywords: Dairy Cow; Ovarian cyclicity; Uterine health

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APA (6^th Edition):

Cheong, S. H. (2012). Factors Associated With The Clearance Of Uterine Inflammation And Resumption Of Ovarian Cyclicity In Postpartum Dairy Cows. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/31001

Chicago Manual of Style (16^th Edition):

Cheong, Soon Hon. “Factors Associated With The Clearance Of Uterine Inflammation And Resumption Of Ovarian Cyclicity In Postpartum Dairy Cows.” 2012. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/31001.

MLA Handbook (7^th Edition):

Cheong, Soon Hon. “Factors Associated With The Clearance Of Uterine Inflammation And Resumption Of Ovarian Cyclicity In Postpartum Dairy Cows.” 2012. Web. 17 Jan 2021.

Vancouver:

Cheong SH. Factors Associated With The Clearance Of Uterine Inflammation And Resumption Of Ovarian Cyclicity In Postpartum Dairy Cows. [Internet] [Doctoral dissertation]. Cornell University; 2012. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/31001.

Council of Science Editors:

Cheong SH. Factors Associated With The Clearance Of Uterine Inflammation And Resumption Of Ovarian Cyclicity In Postpartum Dairy Cows. [Doctoral Dissertation]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/31001

Cornell University

8. Mohan, Swapna. Investigating The Role Of The Mapk Proteins Erk1 And Erk2 On Mammalian Gametogenesis.

Degree: PhD, Physiology, 2014, Cornell University

URL: http://hdl.handle.net/1813/36175

► Gametogenesis is one of the most important biological processes in the life of an organism because it results in the production of gametes, haploid cells… (more)

▼ Gametogenesis is one of the most important biological processes in the life of an organism because it results in the production of gametes, haploid cells that pass on the organism's genetic material to its offspring. However, it a very complicated, intricate process that demands a very high level of regulation. This regulation is to ensure error free meiotic and post-meiotic divisions resulting in a haploid gamete. Errors during the meiotic process can result in defective embryos or fetal demise. Among mammals, humans exhibit a very high rate of gamete defects (~25%) leading to high rates of early embryo loss. Stage-specific cell signaling cascades such as the MAPK pathway regulate meiosis and germ-cell development. In addition to this, MAPKs specifically ERKs, are thought to be involved in cellular division, cytoskeletal reorganization and segregation of genetic material. So far pharmacological approaches have been used to study the action of ERKs in oocytes in vitro using inhibitors of the ERK pathway. However, these are not truly reflective of the physiological environment of the ovary. Hence, in order to better understand the mechanism of action of ERKs on oocyte division, I have generated an Erk2 conditional deletion system driven by an oocyte specific Cre on an Erk1 null background. I hypothesized that deregulation of the MAPK pathway in oocytes will produce drastic changes in the cytokinesis and in chromosome segregation. Mutant females were found to be infertile, with gross chromosome misalignment on metaphase spindles in oocytes, and severe early embryonic loss. This phenotype was accompanied by loss of phosphorylation of several downstream targets such as MSK1 and histone H3. Several possible new targets have also been identified in this study by comparing phosphrylation profiles of oocytes from various genotypes. Our results demonstrate that ERK activity specifically within the oocyte is essential for meiotic resumption and for normal pre-implantation development. Advisors/Committee Members: Cohen, Paula (chair), Johnson, Patricia A (committee member), Coonrod, Scott A. (committee member), Southard, Teresa L (committee member), Roberson, Mark Stephen (committee member).

Subjects/Keywords: ERK; Oocyte; Meiosis

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APA (6^th Edition):

Mohan, S. (2014). Investigating The Role Of The Mapk Proteins Erk1 And Erk2 On Mammalian Gametogenesis. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/36175

Chicago Manual of Style (16^th Edition):

Mohan, Swapna. “Investigating The Role Of The Mapk Proteins Erk1 And Erk2 On Mammalian Gametogenesis.” 2014. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/36175.

MLA Handbook (7^th Edition):

Mohan, Swapna. “Investigating The Role Of The Mapk Proteins Erk1 And Erk2 On Mammalian Gametogenesis.” 2014. Web. 17 Jan 2021.

Vancouver:

Mohan S. Investigating The Role Of The Mapk Proteins Erk1 And Erk2 On Mammalian Gametogenesis. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/36175.

Council of Science Editors:

Mohan S. Investigating The Role Of The Mapk Proteins Erk1 And Erk2 On Mammalian Gametogenesis. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36175

Cornell University

9. Chuang, Chen-hua. Unique Regulatory Mechanisms For Dna Replication And Genome Maintenance In Mammals.

Degree: PhD, Physiology, 2012, Cornell University

URL: http://hdl.handle.net/1813/29249

► DNA replication is a fundamental process in all organisms. Using single stranded DNA (ssDNA) as a template, DNA polymerase synthesizes new DNA to produce an… (more)

▼ DNA replication is a fundamental process in all organisms. Using single stranded DNA (ssDNA) as a template, DNA polymerase synthesizes new DNA to produce an exact copy of the genome. However, most DNA polymerases lack the ability to unwind the double stranded DNA (dsDNA) necessary to expose ssDNA [1]. Therefore, an additional DNA helicase is required to initiate DNA replication by unwinding dsDNA and exposure of ssDNA as a template. In eukaryotes, genetic and biochemical assays have shown the MCM (minichromosome maintenance) family of proteins functions in a hexameric complex as the genomic DNA replication helicase [2]. MCMs have been well studied through in vitro biochemistry, cells in culture, and simple model organisms including S. cerevisiea and Xenopus laevis. These experimentally tractable systems have shown that misrelated or dysfunctional MCMs have deleterious consequences, especially genomic instability (GIN). However, there are still several major unresolved issues that need to be addressed. (1) The "MCM paradox" described that the MCMs are in excess of the number of origins. What is the function of these excess MCMs, and how does it relate to cells and animals? (2) The "MCM puzzle" indicates that mini-MCM complexes exist, but their functions are still unclear (3) Very little is known about the function of the MCM helicase with respect to the health of whole animals. To accomplish these issues and explore the relationship between MCMs and disease, I generated mice deficient in MCMs as a model of in vivo disease in this thesis. The mice which carry 50% reduction of Mcm2, 3, 4, 6, and 7 is phenotypically identical to wild-type at least through 1 year of age. Further reduction of Mcms to 70% causes several detrimental phenotypes, including embryonic lethality, growth retardation, genomic instability, and cancer susceptibility. Most importantly, the reduction of MCM3 rescues most of the detrimental phenotypes in other MCM deficient mice, suggesting a unique function of MCM3. Highly similar to in vitro results, I showed that the MCM3/5 dimer inhibits the MCM2-7 complex from binding chromatin and hinders cell cycle. I also discovered that the Mcm4Chaos3 mutation induces a pan-downregulation of Mcm2-7 post-transcriptionally. The pan-down regulation of Mcm2-7 is a self-preservation mechanism because it reduces MCM3 levels that block the recruitment of chromatin bound MCM2-7. Finally, I identified that Mcm hypomorphic mice possess a unique gender bias phenotype. The male animals are more resistant to MCM insufficiency due to a testosterone protective effect. In summary, this dissertation explores the function of the excess MCMs in aspects of cell cycle and in whole animals. It builds understanding about the regulation of MCMs with emphasis upon cancer formation as a result of MCM deficiency. The MCM hypomorphic mice also reveal a post-transcriptional regulation of Mcms that responded to helicase complex instability or insufficiency. The unique negative function of the MCM3/5 dimer overturns the current theory that… Advisors/Committee Members: Schimenti, John C. (chair), Weiss, Robert S. (committee member), Tye, Bik-Kwoon (committee member), Cohen, Paula (committee member).

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APA (6^th Edition):

Chuang, C. (2012). Unique Regulatory Mechanisms For Dna Replication And Genome Maintenance In Mammals. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/29249

Chicago Manual of Style (16^th Edition):

Chuang, Chen-hua. “Unique Regulatory Mechanisms For Dna Replication And Genome Maintenance In Mammals.” 2012. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/29249.

MLA Handbook (7^th Edition):

Chuang, Chen-hua. “Unique Regulatory Mechanisms For Dna Replication And Genome Maintenance In Mammals.” 2012. Web. 17 Jan 2021.

Vancouver:

Chuang C. Unique Regulatory Mechanisms For Dna Replication And Genome Maintenance In Mammals. [Internet] [Doctoral dissertation]. Cornell University; 2012. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/29249.

Council of Science Editors:

Chuang C. Unique Regulatory Mechanisms For Dna Replication And Genome Maintenance In Mammals. [Doctoral Dissertation]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/29249

Cornell University

10. Sones, Jenny. Defects In Periimplantation Signaling Contribute To Adverse Pregnancy Outcomes In The Bph/5 Mouse Model Of Preeclampsia.

Degree: PhD, Physiology, 2015, Cornell University

URL: http://hdl.handle.net/1813/39356

► Preeclampsia (PE) is a devastating disorder of pregnancy that affects 10% of pregnancies worldwide. While it is a leading cause of perinatal morbidity and mortality,… (more)

▼ Preeclampsia (PE) is a devastating disorder of pregnancy that affects 10% of pregnancies worldwide. While it is a leading cause of perinatal morbidity and mortality, the cause of PE is unknown. To date the only definitive treatment is delivery of the placenta and the baby, which is often preterm and/or growth restricted. The origins of PE are generally regarded to be early in pregnancy at the time of placenta formation as placental developmental abnormalities often characterize PE pregnancies. In these thesis studies, early pregnancy events required for proper placentation, implantation and decidualization, were investigated in the BPH/5 spontaneous mouse model of PE. We discovered profound developmental defects in implantation, decidualization, and placentation in BPH/5 mice. Along with evidence of decidual hypoxia, these defects were associated with a distinct molecular signature of aberrant embryo-uterine interactions. We identified significant dysregulation in the periimplantation period, particularly in the overexpression of cyclooxygenase 2 (Cox2) in the maternal uterine environment. Using pharmacological intervention at early pregnancy with a selective Cox2 inhibitor, we confirmed that defects in Cox2 signaling during the periimplantation period have "ripple effects" impacting downstream adverse pregnancy outcomes at mid and late gestation in BPH/5 mice, including fetal growth restriction and demise. Finally, investigations in the periimplantation period lead us to discover deficiencies in immunoregulatory pathways crucial for placental development at the maternal-fetal interface in BPH/5 mice. We showed dramatic loss of decidual Natural Killer (dNK) cells and this was associated with overexpression of IL-15 in BPH/5 implantation sites. Furthermore, we linked Cox2 inhibition with a reduction in IL-15. Altogether, this points towards inflammation in the maternal uterine environment during early pregnancy having a central role in the poor fetoplacental and pregnancy outcomes associated with this model and highlights Cox2 inhibitors as potential therapeutics to prevent fetal morbidity/mortality associated with PE. Importantly, our data supports the "ripple effect" hypothesis that defects in early pregnancy events are the source of downstream adverse pregnancy outcomes using the BPH/5 mouse model of PE. Advisors/Committee Members: Davisson, Robin L (chair), Cohen, Paula (committee member), Roberson, Mark Stephen (committee member), Quirk, Susan Mary (committee member).

Subjects/Keywords: preeclampsia; pregnancy; placenta

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APA (6^th Edition):

Sones, J. (2015). Defects In Periimplantation Signaling Contribute To Adverse Pregnancy Outcomes In The Bph/5 Mouse Model Of Preeclampsia. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/39356

Chicago Manual of Style (16^th Edition):

Sones, Jenny. “Defects In Periimplantation Signaling Contribute To Adverse Pregnancy Outcomes In The Bph/5 Mouse Model Of Preeclampsia.” 2015. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/39356.

MLA Handbook (7^th Edition):

Sones, Jenny. “Defects In Periimplantation Signaling Contribute To Adverse Pregnancy Outcomes In The Bph/5 Mouse Model Of Preeclampsia.” 2015. Web. 17 Jan 2021.

Vancouver:

Sones J. Defects In Periimplantation Signaling Contribute To Adverse Pregnancy Outcomes In The Bph/5 Mouse Model Of Preeclampsia. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/39356.

Council of Science Editors:

Sones J. Defects In Periimplantation Signaling Contribute To Adverse Pregnancy Outcomes In The Bph/5 Mouse Model Of Preeclampsia. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/39356

11. Rinaldi, Vera Da Silva Garcia. Genetically dissecting the meiotic checkpoint active during prophase I in female mice.

Degree: PhD, Comparative Biomedical Sciences, 2017, Cornell University

URL: http://hdl.handle.net/1813/56716

► Females have a non-renewable number of gametes at birth. These oocytes are extremely sensitive to environmental factors that generate DNA damage. Oocyte death due to… (more)

▼ Females have a non-renewable number of gametes at birth. These oocytes are extremely sensitive to environmental factors that generate DNA damage. Oocyte death due to DNA damage can result in infertility and ovarian failure. In contrast to postnatal oocytes, at earlier stages of gametogenesis these cells withstand hundreds of developmentally programmed DNA breaks (DSBs). During the first meiotic division these DSBs promote synapsis (homologous chromosomes pairing), and recombination, which are both essential for sexual reproduction and environmental fitness. However, DSB repair and synapsis need to occur in a timely manner, or the quality of the gametes becomes compromised. The mechanisms that guarantee oocyte quality were hypothesized to operate through two independent pathways: one that surveys DNA integrity, and the other synapsis. However, I present experimental evidence that oocytes defective for either DNA repair or synapsis are eliminated by the same DNA damage response. Furthermore, through the detailed analysis of DNA repair dynamics, I provide evidence that the protein HORMAD2, which localizes to unsynapsed chromosomes, regulates DSB-repair. I hypothesize that HORMAD2 interferes with repair by preventing broken DNA from using the sister chromatid as a repair template. This “block to sister-chromatid repair” (BSCR) assures that the homologous chromosome is the substrate of choice. Whereas BSCR guarantees homologous recombination, it also prevents unsynapsed chromosomes from fixing DSBs. Thus, failure to synapse will result in persistent DSBs. Since DNA damage causes oocyte death postnatally, unsynapsed chromosome will trigger the DNA damage checkpoint. Through the understanding of this checkpoint, I was able to test if the transient inhibition of the DNA damage checkpoint protein (CHK2) prevents oocyte death. My finding that oocyte death was prevented, and fertility was preserved, provides evidence that chemically protecting oocyte from DNA damaging agents is a viable clinical approach. This result will hopefully translate into a treatment to delay ovarian failure. Taken together these results have implications on our current understanding of the prophase I checkpoint. TEACHING AS RESEARCH My interest in improving teaching strategies led me to research the qualitative outcome of using a novel teaching tool during the laboratory section of a histology course. I tested an interactive response system (IRS) as formative assessment tool. I found that IRS results in a positive experience, however my study was not able to detect quantitative difference on students’ grades was detected. Advisors/Committee Members: Schimenti, John C. (chair), Coonrod, Scott A. (committee member), Alani, Eric E. (committee member), Cohen, Paula (committee member).

Subjects/Keywords: teaching; Developmental biology; meiosis; Biology; Genetics; reproduction; DNA-damage checkpoint; fertility; gametogenesis

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APA (6^th Edition):

Rinaldi, V. D. S. G. (2017). Genetically dissecting the meiotic checkpoint active during prophase I in female mice. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/56716

Chicago Manual of Style (16^th Edition):

Rinaldi, Vera Da Silva Garcia. “Genetically dissecting the meiotic checkpoint active during prophase I in female mice.” 2017. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/56716.

MLA Handbook (7^th Edition):

Rinaldi, Vera Da Silva Garcia. “Genetically dissecting the meiotic checkpoint active during prophase I in female mice.” 2017. Web. 17 Jan 2021.

Vancouver:

Rinaldi VDSG. Genetically dissecting the meiotic checkpoint active during prophase I in female mice. [Internet] [Doctoral dissertation]. Cornell University; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/56716.

Council of Science Editors:

Rinaldi VDSG. Genetically dissecting the meiotic checkpoint active during prophase I in female mice. [Doctoral Dissertation]. Cornell University; 2017. Available from: http://hdl.handle.net/1813/56716

Cornell University

12. Sun, Xianfei. Investigating Mammalian Meiosis: The Role Of Mismatch Repair Proteins And Their Interactors.

Degree: PhD, Physiology, 2012, Cornell University

URL: http://hdl.handle.net/1813/31179

► Prophase I is the defining stage of meiosis when chromosomes must first pair with their homologous partner, then synapse, and undergo precisely controlled reciprocal recombination.… (more)

▼ Prophase I is the defining stage of meiosis when chromosomes must first pair with their homologous partner, then synapse, and undergo precisely controlled reciprocal recombination. Due to the complexity of the process, meiotic recombination requires highly ordered cooperation from various proteins, including the mismatch repair (MMR) protein family. Mouse MLH3 belongs to the MutL homolog family that functions as effector molecules for MMR. Research has suggested that MLH3 has critical roles in both DNA mismatch repair and meiosis. In the research for this thesis, I investigated two unique structural features of mouse MLH3: the potential endonuclease domain DQHA(X)2E(X)4E, and the large mammalian-specific region within exon 2. To investigate the function of the conserved endonuclease domain of MLH3, a transgenic mouse line containing a point mutation in this potential endonuclease domain was made. I hypothesized that, due to the conservation of this domain, disruption of this domain would lead to the abolishment of normal meiotic progression in vivo. To explore the function of the exon 2 region of mouse MLH3, I performed yeast two-hybrid assay and identified nine possible interacting partners of this region. To further screen for key sub-motifs within this region, a microsatellite instability reporter assay was tested. It is hypothesized that the unique region in exon 2 is important for the function of mouse MLH3 in maintaining genome integrity, and confers mammalian-specific functions to MLH3 in higher eukaryotes. Mouse CNTD1 is a newly identified cyclin-related protein. Its worm ortholog, COSA-1, functions in conjunction with the MMR pathway to process crossovers during meiosis. To explore the role of mouse CNTD1 in mammalian gametogenesis, I generated Cntd1 gene targeted mice. Consistent with the findings in C. elegans, deletion of Cntd1 in mice caused severe defects in meiotic CO formation, which leads to sterility in both males and females. No epididymal sperm were found in Cntd1 mutant males, and mutant females underwent severe oocyte-depletion after puberty. These data indicate a pivotal role for CNTD1 in regulating meiotic COs, possibly by helping select the sites of late recombination nodules through promoting or stabilizing other Class I CO-promoting proteins on meiotic chromosomes. Advisors/Committee Members: Cohen, Paula (chair), Weiss, Robert S. (committee member), Wolfner, Mariana Federica (committee member), Fortune, Joanne Elizabeth (committee member).

Subjects/Keywords: Mouse meiosis; mismatch repair protein; meiotic recombination; mlh3; cntd1

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APA (6^th Edition):

Sun, X. (2012). Investigating Mammalian Meiosis: The Role Of Mismatch Repair Proteins And Their Interactors. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/31179

Chicago Manual of Style (16^th Edition):

Sun, Xianfei. “Investigating Mammalian Meiosis: The Role Of Mismatch Repair Proteins And Their Interactors.” 2012. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/31179.

MLA Handbook (7^th Edition):

Sun, Xianfei. “Investigating Mammalian Meiosis: The Role Of Mismatch Repair Proteins And Their Interactors.” 2012. Web. 17 Jan 2021.

Vancouver:

Sun X. Investigating Mammalian Meiosis: The Role Of Mismatch Repair Proteins And Their Interactors. [Internet] [Doctoral dissertation]. Cornell University; 2012. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/31179.

Council of Science Editors:

Sun X. Investigating Mammalian Meiosis: The Role Of Mismatch Repair Proteins And Their Interactors. [Doctoral Dissertation]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/31179

Cornell University

13. Trevino, Lindsey. Development And Progression Of Ovarian Cancer: Insights From The Hen Model Of The Disease.

Degree: PhD, Physiology, 2011, Cornell University

URL: http://hdl.handle.net/1813/33567

► Ovarian cancer is the leading cause of reproductive cancer death in U.S. women. This high mortality rate is due, in part, to the lack of… (more)

▼ Ovarian cancer is the leading cause of reproductive cancer death in U.S. women. This high mortality rate is due, in part, to the lack of early detection methods and incomplete understanding of the origin of the disease. Animal models of ovarian cancer can shed light on the genetic and biological factors that influence tumor development and/or progression, as well as identify strategies for prevention, early detection and treatment. One animal model, the domestic hen, has a high spontaneous incidence of the disease that is age-dependent, similar to women. Although previous studies utilizing the hen as a model for ovarian cancer have characterized chicken ovarian tumors and tested putative prevention and treatment strategies of the disease, our understanding of the development and progression of ovarian cancer in the hen is still limited. Our objectives were 1) to further characterize chicken ovarian tumors through global gene expression analysis; 2) to test the effect of progestin and estrogen together, as commonly delivered in "the pill", as well as progestin and estrogen alone on ovarian cancer prevalence in the hen; and 3) to determine estrogen receptor subtype expression in chicken ovarian tumors. The second and third objectives were based on evidence in women that steroid hormones play a role in ovarian cancer, with estrogen associated with an increased risk and progesterone associated with a decreased risk of the disease. We have shown that administration of "the pill" is associated with a significant decrease in ovarian cancer prevalence, as well as egg production, suggesting that ovulation is important for the initiation of ovarian cancer. Furthermore, we observed that chicken ovarian tumors over-express oviduct-related genes, even at early stages, providing evidence that tumors possibly arise from the epithelial cells of the oviduct. Finally, our results also support a role for steroid hormones, particularly estrogen, in mediating ovarian tumor progression. Collectively, our studies have provided information regarding the development and progression of ovarian cancer in the hen that may help unlock the mysteries of the disease in women. Advisors/Committee Members: Johnson, Patricia A (chair), Roberson, Mark Stephen (committee member), Cohen, Paula (committee member), Travis, Alexander J. (committee member).

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APA (6^th Edition):

Trevino, L. (2011). Development And Progression Of Ovarian Cancer: Insights From The Hen Model Of The Disease. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/33567

Chicago Manual of Style (16^th Edition):

Trevino, Lindsey. “Development And Progression Of Ovarian Cancer: Insights From The Hen Model Of The Disease.” 2011. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/33567.

MLA Handbook (7^th Edition):

Trevino, Lindsey. “Development And Progression Of Ovarian Cancer: Insights From The Hen Model Of The Disease.” 2011. Web. 17 Jan 2021.

Vancouver:

Trevino L. Development And Progression Of Ovarian Cancer: Insights From The Hen Model Of The Disease. [Internet] [Doctoral dissertation]. Cornell University; 2011. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/33567.

Council of Science Editors:

Trevino L. Development And Progression Of Ovarian Cancer: Insights From The Hen Model Of The Disease. [Doctoral Dissertation]. Cornell University; 2011. Available from: http://hdl.handle.net/1813/33567

Cornell University

14. Brown, Jessica. ANALYSIS OF GnRH AS A CENTRAL REGULATOR OF FERTILITY: EXPLORING THE MULTIPLE ROLES OF ERK SIGNALING.

Degree: PhD, Comparative Biomedical Sciences, 2017, Cornell University

URL: http://hdl.handle.net/1813/51653

► Extracellular signal-regulated kinase (ERK) signaling is required for function of the hypothalamic-pituitary-gonadal axis. This axis is regulated by interconnected hormonal feedback loops, permitting reproduction. Gonadotropin… (more)

▼ Extracellular signal-regulated kinase (ERK) signaling is required for function of the hypothalamic-pituitary-gonadal axis. This axis is regulated by interconnected hormonal feedback loops, permitting reproduction. Gonadotropin releasing hormone (GnRH) is secreted by the hypothalamus to act on the pituitary, resulting in gonadotropin secretion. The gonadotropins, luteinizing hormone (LH) and follicle stimulating hormone (FSH) are produced and secreted by pituitary gonadotropes, and act on the gonads, promoting steroidogenesis and gametogenesis. This dissertation focuses on two isoforms of ERK, ERK 1 and ERK 2. Although they do appear to have some redundant functions, ERK 1 is not able to compensate for loss of ERK 2. ERK1 null mice are viable and fertile, whereas loss of ERK2 is embryonic lethal. Therefore, ERK 2 has to be knocked out in a tissue or time dependent manner. For the studies included here, we utilize a mouse model of GnRHR associated ERK loss. This model allows us to investigate the role of ERK in pituitary gonadotropin production and secretion. ERK loss significantly reduced gonadotropin production, and this model allowed us to characterize the effects of hypogonadotropism as animals aged. We followed those studies with an investigation into GnRHR localization and function in the murine placenta, and the effects of ERK loss on placentation, gestation, and parturition. These experiments revealed abnormal histology and vascularization, prolonged gestation and dystocia, and absolute fetal mortality. Finally, we utilized unbiased screening techniques (RNA sequencing) to identify novel targets of GnRH signaling downstream of the ERK cascade. This revealed a bile acid receptor, TGR5, which has a functional role in gonadotropin production in the pituitary. Female TGR5 knockout are subfertile, with a marked delay in the onset of puberty. The studies in this dissertation describe the role of ERK in multiple aspects of the HPG axis. All of the studies have clinical implications, either in the understanding and treatment of idiopathic hypogonadotropic hypogonadism (IHH) or in understanding links between puberty, nutrition, metabolism and fertility. Advisors/Committee Members: Roberson, Mark S (chair), Cohen, Paula E. (chair), Cheong, Soon Hon (committee member), Kurpios, Natasza (committee member), Navratil, Amy M (committee member).

Subjects/Keywords: Placenta; Developmental biology; Biology; Metabolism; ERK; GnRH; pituitary; reproduction

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APA (6^th Edition):

Brown, J. (2017). ANALYSIS OF GnRH AS A CENTRAL REGULATOR OF FERTILITY: EXPLORING THE MULTIPLE ROLES OF ERK SIGNALING. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/51653

Chicago Manual of Style (16^th Edition):

Brown, Jessica. “ANALYSIS OF GnRH AS A CENTRAL REGULATOR OF FERTILITY: EXPLORING THE MULTIPLE ROLES OF ERK SIGNALING.” 2017. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/51653.

MLA Handbook (7^th Edition):

Brown, Jessica. “ANALYSIS OF GnRH AS A CENTRAL REGULATOR OF FERTILITY: EXPLORING THE MULTIPLE ROLES OF ERK SIGNALING.” 2017. Web. 17 Jan 2021.

Vancouver:

Brown J. ANALYSIS OF GnRH AS A CENTRAL REGULATOR OF FERTILITY: EXPLORING THE MULTIPLE ROLES OF ERK SIGNALING. [Internet] [Doctoral dissertation]. Cornell University; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/51653.

Council of Science Editors:

Brown J. ANALYSIS OF GnRH AS A CENTRAL REGULATOR OF FERTILITY: EXPLORING THE MULTIPLE ROLES OF ERK SIGNALING. [Doctoral Dissertation]. Cornell University; 2017. Available from: http://hdl.handle.net/1813/51653

Cornell University

15. Stephens, Claire. Follicle Selection And Growth In The Domestic Hen Ovary.

Degree: PhD, Animal Science, 2015, Cornell University

URL: http://hdl.handle.net/1813/40897

► Ovarian follicle selection and development in domestic hens is highly regulated. A single small follicle (approximately 6-8 mm in diameter) is selected daily and enters… (more)

▼ Ovarian follicle selection and development in domestic hens is highly regulated. A single small follicle (approximately 6-8 mm in diameter) is selected daily and enters the pre-ovulatory hierarchy, continuing to grow until ovulation occurs. We investigated the mechanism(s) involved in follicle selection and subsequent growth before ovulation. In the first study, we found bone morphogenetic protein 15 (BMP15) mRNA primarily in the oocyte, and BMP15 protein was detected in 6 and 8 mm follicles around the time of follicle selection. In addition, BMP15 altered mRNA expression of genes associated with follicle selection. Granulosa cell culture with BMP15 increased mRNA levels of follicle stimulating hormone receptor (FSHR) and decreased both anti-Müllerian hormone (AMH) and occludin (OCLN). OCLN protein, a tight junction protein, also decreased, suggesting that this oocyte factor may play a pivotal role in follicle selection into the pre-ovulatory hierarchy. Liver-derived yolk material enters follicles via capillaries in the theca layer, ultimately reaching oocytes via paracellular spaces between granulosa cells. Yolk is incorporated into the oocyte by receptor-mediated endocytosis. OCLN may regulate access of yolk material to the oocyte surface. We determined expression and regulation of OCLN in small follicles. OCLN mRNA expression decreased with increasing follicle size. The regulation of OCLN transcripts in laying hens was investigated by granulosa cell culture. BMP15, epidermal growth factor (EGF) and activin B decreased OCLN expression, whereas activin A increased OCLN mRNA, suggesting local factors may regulate yolk access to the oocyte. Broiler breeder hens have aberrant follicle development that is modulated by limiting feed intake. Restricted diets produce more ordered follicle development and yolk uptake, but the causative factors are unknown. We examined metabolic-related factors in the liver and global gene expression to identify altered transcripts that contribute to abnormal follicular growth. The GH/IGF1-axis may be overstimulated in hens on an ad libitum diet and feed intake alters genes involved in lipid metabolism. These studies offer new insights into specific intra-ovarian and extra-ovarian factors mediating follicle selection and growth in the hen. Advisors/Committee Members: Johnson,Patricia A (chair), Roberson,Mark Stephen (committee member), Cohen,Paula (committee member), Fortune,Joanne Elizabeth (committee member).

Subjects/Keywords: ovary; follicle development; hen

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APA (6^th Edition):

Stephens, C. (2015). Follicle Selection And Growth In The Domestic Hen Ovary. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/40897

Chicago Manual of Style (16^th Edition):

Stephens, Claire. “Follicle Selection And Growth In The Domestic Hen Ovary.” 2015. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/40897.

MLA Handbook (7^th Edition):

Stephens, Claire. “Follicle Selection And Growth In The Domestic Hen Ovary.” 2015. Web. 17 Jan 2021.

Vancouver:

Stephens C. Follicle Selection And Growth In The Domestic Hen Ovary. [Internet] [Doctoral dissertation]. Cornell University; 2015. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/40897.

Council of Science Editors:

Stephens C. Follicle Selection And Growth In The Domestic Hen Ovary. [Doctoral Dissertation]. Cornell University; 2015. Available from: http://hdl.handle.net/1813/40897

16. Raghavan, Vandana. INCOMPATIBILITIES IN MISMATCH REPAIR GENES MLH1-PMS1 CONTRIBUTE TO A WIDE RANGE OF MUTATION RATES IN HUMAN ISOLATES OF BAKER'S YEAST.

Degree: PhD, Biochemistry, Molecular and Cell Biology, 2019, Cornell University

URL: http://hdl.handle.net/1813/67771

► The mismatch repair (MMR) pathway maintains genome stability by repairing mutations incorporated in the genome during replication and recombination. While most microorganisms tend to have… (more)

▼ The mismatch repair (MMR) pathway maintains genome stability by repairing mutations incorporated in the genome during replication and recombination. While most microorganisms tend to have low mutation rates, a higher mutation rate can provide transient adaptive advantage to stress conditions by promoting adaptive mutations. Variants of the MMR genes, MLH1 and PMS1 from different yeast strains can display an incompatibility that results in a high mutation rate. MLH1 and PMS1 function as a heterodimer and the incompatibility is a result of single amino acid polymorphism in each protein. The incompatibility provides an adaptive advantage under stress but does so at the cost of long-term fitness. I identified 18 baker’s yeast isolates from 1011 yeast isolates surveyed that contain the incompatible MLH1-PMS1 genotype in a heterozygous state. I tested the mutation rates of two clinical heterozygous diploid isolates, YJS5885 and YJS5845, and their spore clones. While both of these isolates were non-mutators, their meiotic spore progeny displayed mutation rates that varied over a 340-fold range, and MLH1-PMS1 incompatibility was the major driver of high mutation rate. The range in mutation rates might be in part because these isolates are heterozygous for several genes that may be modifying the mutation rate. My data are consistent with the variance in mutation rate contributing to adaptation to stress conditions through the acquisition of beneficial mutations, with high mutation rates leading to long-term fitness costs that are buffered by mating, or eliminated through natural selection. Furthermore, I observed that one of the isolates was aneuploid and generated aneuploid spore clones at a high frequency. Aneuploidy also provides a transient adaptive advantage under stress conditions. Thus, I obtained evidence for mechanisms in clinical yeast isolates that may provide an adaptive advantage in the human body. Advisors/Committee Members: Alani, Eric E. (chair), Peters, Joseph E. (committee member), Cohen, Paula (committee member).

Subjects/Keywords: Molecular biology; Genetics; Biochemistry; Adaptation; mismatch repair; baker's yeast; clinical isolates; genetic incompatibility; Saccharomyces cerevisiae

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APA (6^th Edition):

Raghavan, V. (2019). INCOMPATIBILITIES IN MISMATCH REPAIR GENES MLH1-PMS1 CONTRIBUTE TO A WIDE RANGE OF MUTATION RATES IN HUMAN ISOLATES OF BAKER'S YEAST. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/67771

Chicago Manual of Style (16^th Edition):

Raghavan, Vandana. “INCOMPATIBILITIES IN MISMATCH REPAIR GENES MLH1-PMS1 CONTRIBUTE TO A WIDE RANGE OF MUTATION RATES IN HUMAN ISOLATES OF BAKER'S YEAST.” 2019. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/67771.

MLA Handbook (7^th Edition):

Raghavan, Vandana. “INCOMPATIBILITIES IN MISMATCH REPAIR GENES MLH1-PMS1 CONTRIBUTE TO A WIDE RANGE OF MUTATION RATES IN HUMAN ISOLATES OF BAKER'S YEAST.” 2019. Web. 17 Jan 2021.

Vancouver:

Raghavan V. INCOMPATIBILITIES IN MISMATCH REPAIR GENES MLH1-PMS1 CONTRIBUTE TO A WIDE RANGE OF MUTATION RATES IN HUMAN ISOLATES OF BAKER'S YEAST. [Internet] [Doctoral dissertation]. Cornell University; 2019. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/67771.

Council of Science Editors:

Raghavan V. INCOMPATIBILITIES IN MISMATCH REPAIR GENES MLH1-PMS1 CONTRIBUTE TO A WIDE RANGE OF MUTATION RATES IN HUMAN ISOLATES OF BAKER'S YEAST. [Doctoral Dissertation]. Cornell University; 2019. Available from: http://hdl.handle.net/1813/67771

17. Toledo, Melissa. MOLECULAR MECHANISMS ORCHESTRATING CROSSOVER FORMATION AND DISTRIBUTION DURING MAMMALIAN MEIOSIS.

Degree: PhD, Molecular and Integrative Physiology, 2017, Cornell University

URL: http://hdl.handle.net/1813/51577

► In mammalian meiosis, homologous chromosomes pair, synapse, and undergo genetic recombination, or the exchange of genetic material through crossing over. The appropriate frequency and distribution… (more)

▼ In mammalian meiosis, homologous chromosomes pair, synapse, and undergo genetic recombination, or the exchange of genetic material through crossing over. The appropriate frequency and distribution of crossovers is essential for ensuring equal segregation of homologs at the first meiotic division. Crossover formation is initiated by 250-300 DSBs of which 90% are resolved as non-crossovers, while 10% are resolved as crossovers. MLH1/MLH3 (MutLγ) contains a putative endonuclease domain in MLH3 thought to be essential for crossover formation. One focus of this thesis was to elucidate the role of MutLγ in crossover resolution in vivo, while investigating how MutLγ is recruited to chromosomes at the appropriate time and frequency. We generated an Mlh3D1185N mouse (Mlh3DN/DN) harboring a point mutation within the endonuclease domain. Mlh3DN/DN males are infertile, yet exhibit normal mating behavior. Mlh3DN/DN spermatocytes exhibit normal DSB formation, synapsis, and localization of MutLγ to chromosomes. However, Mlh3DN/DN pachytene spermatocytes exhibit persistence of RAD51 and BLM. Diakinesis-staged cells show reduced crossovers, but somewhat elevated above that of Mlh3-/- males. Thus, the MLH3 endonuclease domain is essential for processing of the majority of DSB events ultimately destined to become crossovers. CNTD1 is implicated in designating DSB repair intermediates to become crossovers in male meiosis; however, the meiotic phenotype of Cntd1GT/GT females is unknown. Thus, the second focus of this thesis was to elucidate CNTD1 function during prophase I in females. Cntd1GT/GT females are infertile, yet exhibit normal mating behavior. Initial DSB processing events are normal in Cntd1GT/GT oocytes, yet pachytene oocytes have a high rate of synapsis defects and fail to recruit MutLγ to chromosomes, leading to significantly fewer chiasmata compared to Cntd1+/+ oocytes. Cntd1GT/GT oocytes also show severe spindle defects and abnormal chromosome arrangement. Histologically, pre-pubertal Cntd1GT/GT ovaries have fewer follicles when compared to Cntd1+/+ ovaries, and are depleted of oocytes by adulthood. Thus, CNTD1 is not essential for early DSB processing events, but is required for MutLγ recruitment and Class I crossover designation. Crossover formation (MLH3) and designation (CNTD1) must be controlled temporally, spatially, and quantitatively. It is this fascinating and exquisitely complex regulation that forms the basis for the studies outlined in this thesis. Advisors/Committee Members: Cohen, Paula E (chair), Johnson, Patricia A (committee member), Pawlowski, Wojtek (committee member), Schimenti, John C (committee member).

Subjects/Keywords: CNTD1; crossover designation; crossover formation; meiosis; MLH3; Genetics; Molecular biology

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APA (6^th Edition):

Toledo, M. (2017). MOLECULAR MECHANISMS ORCHESTRATING CROSSOVER FORMATION AND DISTRIBUTION DURING MAMMALIAN MEIOSIS. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/51577

Chicago Manual of Style (16^th Edition):

Toledo, Melissa. “MOLECULAR MECHANISMS ORCHESTRATING CROSSOVER FORMATION AND DISTRIBUTION DURING MAMMALIAN MEIOSIS.” 2017. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/51577.

MLA Handbook (7^th Edition):

Toledo, Melissa. “MOLECULAR MECHANISMS ORCHESTRATING CROSSOVER FORMATION AND DISTRIBUTION DURING MAMMALIAN MEIOSIS.” 2017. Web. 17 Jan 2021.

Vancouver:

Toledo M. MOLECULAR MECHANISMS ORCHESTRATING CROSSOVER FORMATION AND DISTRIBUTION DURING MAMMALIAN MEIOSIS. [Internet] [Doctoral dissertation]. Cornell University; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/51577.

Council of Science Editors:

Toledo M. MOLECULAR MECHANISMS ORCHESTRATING CROSSOVER FORMATION AND DISTRIBUTION DURING MAMMALIAN MEIOSIS. [Doctoral Dissertation]. Cornell University; 2017. Available from: http://hdl.handle.net/1813/51577

18. Milano, Carolyn Rose. MutS[gamma] FUNCTION DURING MOUSE MEIOSIS.

Degree: PhD, Genetics, Genomics and Development, 2019, Cornell University

URL: http://hdl.handle.net/1813/67364

► MutSγ is a highly conserved heterodimer comprised of MSH4 (MutS homolog 4) and MSH5 (MutS homolog 5). MutSγ complex is widely conserved across many lineages… (more)

▼ MutSγ is a highly conserved heterodimer comprised of MSH4 (MutS homolog 4) and MSH5 (MutS homolog 5). MutSγ complex is widely conserved across many lineages of eukaryotes with few exceptions. Unlike other MutS complexes, MSH4-MSH5 function is specific to, and essential for meiosis. Prophase I of meiosis harbors two events critical for proper segregation of homologs at the end of meiosis I: pairing/synapsis and homologous recombination. Loss of MutSγ function results in severe defects in one or both of these events in budding yeast (S. cerevisiae), in the nematode (C. elegans), among some plants including A. thaliana, and in mammals such as M. musculus. Specifically, in M. musculus loss of either MSH4 or MSH5 results in loss of meiocytes prior to pachynema. This suggests a function for MutSγ preceding pachynema has a critical role for cell vitality in mammals. The loss of meiocytes prior to pachynema in Msh5-/- or Msh4-/- makes it impossible to understand the function of MutSγ in crossover regulation. To further establish a function for mammalian MSH5, this work looks at two mouse lines, each with a different mutation in the Msh5 coding sequence. The first mouse (Msh5GA/GA) harbors a point mutation in the ATP binding domain of MSH5, predicted to disrupt binding. The second line (Msh5ΔC/ΔC) contains a deletion of the MSH5 c-terminus. Both of these mouse lines show a less severe phenotype in spermatogenesis than does Msh5-/-, allowing for phenotypic analysis of homologous recombination events throughout prophase I. A proportion of Msh5GA/GA spermatocytes can progress to diakinesis of MI, thus alleviating the early loss of spermatocytes in Msh5-/- animals. Chromosome spread analysis of Msh5GA/GA spermatocytes reveals abnormal pairing/synapsis between non-homologous chromosomes. Across eukaryotes MutSγ is associated with class I CO repair events. Surprisingly in Msh5GA/GA spermatocytes, all chiasmata are lost or fail to form in these mutant spermatocytes. These findings identify MutSγ as essential to all CO regulation in mouse. The Msh5ΔC/ΔC mice confer infertility phenotypes, a result which identifies this domain as essential for proper MutSγ function. A proportion of Msh5ΔC/ΔC spermatocytes achieve full autosomal synapsis during pachynema, suggesting the c-terminal domain is less important for homolog synapsis. In the Msh5ΔC/ΔC pachynema spermatocytes there is a reduction of class I CO establishment in, identifying this domain as necessary for normal CO establishment. These findings provide the first direct evidence that MutSγ is necessary for the normal recruitment of class I CO machinery during prophase I. Taken together the results suggest that MutSγ function is integral to not only homolog pairing and synapsis, but also to the establishment of all crossovers in mouse. Advisors/Committee Members: Cohen, Paula (chair), Alani, Eric E. (committee member), Wolfner, Mariana Federica (committee member), Chappie, Joshua S. (committee member).

Subjects/Keywords: Genetics; crossover; Molecular biology; meiosis; fertility

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APA (6^th Edition):

Milano, C. R. (2019). MutS[gamma] FUNCTION DURING MOUSE MEIOSIS. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/67364

Chicago Manual of Style (16^th Edition):

Milano, Carolyn Rose. “MutS[gamma] FUNCTION DURING MOUSE MEIOSIS.” 2019. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/67364.

MLA Handbook (7^th Edition):

Milano, Carolyn Rose. “MutS[gamma] FUNCTION DURING MOUSE MEIOSIS.” 2019. Web. 17 Jan 2021.

Vancouver:

Milano CR. MutS[gamma] FUNCTION DURING MOUSE MEIOSIS. [Internet] [Doctoral dissertation]. Cornell University; 2019. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/67364.

Council of Science Editors:

Milano CR. MutS[gamma] FUNCTION DURING MOUSE MEIOSIS. [Doctoral Dissertation]. Cornell University; 2019. Available from: http://hdl.handle.net/1813/67364

19. White, Simone Lenora. Investigating the Female's Role in Sperm Competition in Drosophila Melanogaster.

Degree: M.S., Genetics and Development, Genetics and Development, 2017, Cornell University

URL: http://hdl.handle.net/1813/51676

► The process of fertilization involves many interactions between males, females, and their gametes. This is even more complex in cases of multiple mating, such as… (more)

Subjects/Keywords: Genetics

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

White, S. L. (2017). Investigating the Female's Role in Sperm Competition in Drosophila Melanogaster. (Masters Thesis). Cornell University. Retrieved from http://hdl.handle.net/1813/51676

Chicago Manual of Style (16^th Edition):

White, Simone Lenora. “Investigating the Female's Role in Sperm Competition in Drosophila Melanogaster.” 2017. Masters Thesis, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/51676.

MLA Handbook (7^th Edition):

White, Simone Lenora. “Investigating the Female's Role in Sperm Competition in Drosophila Melanogaster.” 2017. Web. 17 Jan 2021.

Vancouver:

White SL. Investigating the Female's Role in Sperm Competition in Drosophila Melanogaster. [Internet] [Masters thesis]. Cornell University; 2017. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/51676.

Council of Science Editors:

White SL. Investigating the Female's Role in Sperm Competition in Drosophila Melanogaster. [Masters Thesis]. Cornell University; 2017. Available from: http://hdl.handle.net/1813/51676

Cornell University

20. Modzelewski, Andrew. Systematic Analysis Of Rnai Components In Mouse Spermatogenesis.

Degree: PhD, Genetics, 2014, Cornell University

URL: http://hdl.handle.net/1813/36047

Subjects/Keywords: Argonaute 4; RITS; Meiotic Silencing

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Modzelewski, A. (2014). Systematic Analysis Of Rnai Components In Mouse Spermatogenesis. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/36047

Chicago Manual of Style (16^th Edition):

Modzelewski, Andrew. “Systematic Analysis Of Rnai Components In Mouse Spermatogenesis.” 2014. Doctoral Dissertation, Cornell University. Accessed January 17, 2021. http://hdl.handle.net/1813/36047.

MLA Handbook (7^th Edition):

Modzelewski, Andrew. “Systematic Analysis Of Rnai Components In Mouse Spermatogenesis.” 2014. Web. 17 Jan 2021.

Vancouver:

Modzelewski A. Systematic Analysis Of Rnai Components In Mouse Spermatogenesis. [Internet] [Doctoral dissertation]. Cornell University; 2014. [cited 2021 Jan 17]. Available from: http://hdl.handle.net/1813/36047.

Council of Science Editors:

Modzelewski A. Systematic Analysis Of Rnai Components In Mouse Spermatogenesis. [Doctoral Dissertation]. Cornell University; 2014. Available from: http://hdl.handle.net/1813/36047

Open Access Theses and Dissertations