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Flexibility And Constraint In Preimplantation Gene Regulation In Mouse, Colin C. Conine, Marina Krykbaeva, Lina Song, Robert C. Brewster, Nir Friedman, Oliver J. Rando 2020 University of Massachusetts Medical School

Flexibility And Constraint In Preimplantation Gene Regulation In Mouse, Colin C. Conine, Marina Krykbaeva, Lina Song, Robert C. Brewster, Nir Friedman, Oliver J. Rando

University of Massachusetts Medical School Faculty Publications

Although many features of embryonic development exhibit remarkable stability in the face of environmental perturbations, it is also clear that some aspects of early embryogenesis can be modulated by non-genetic influences during and after fertilization. Among potential perturbations experienced during reproduction, understanding the consequences of differing ex vivo fertilization methods at a molecular level is imperative for comprehending both the basic biology of early development and the potential consequences of assisted reproduction. Here, we set out to explore stable and flexible aspects of preimplantation gene expression using single-embryo RNA-sequencing of mouse embryos fertilized by natural mating, in vitro fertilization, or ...


Ncapg Dynamically Coordinates The Myogenesis Of Fetal Bovine Tissue By Adjusting Chromatin Accessibility, Xin Hu, Yishen Xing, Xing Fu, Qiyuan Yang, Ling Ren, Yahui Wang, Qian Li, Junya Li, Lupei Zhang 2020 University of Liège

Ncapg Dynamically Coordinates The Myogenesis Of Fetal Bovine Tissue By Adjusting Chromatin Accessibility, Xin Hu, Yishen Xing, Xing Fu, Qiyuan Yang, Ling Ren, Yahui Wang, Qian Li, Junya Li, Lupei Zhang

Open Access Articles

NCAPG is a subunit of condensin I that plays a crucial role in chromatin condensation during mitosis. NCAPG has been demonstrated to be associated with farm animal growth traits. However, its role in regulating myoblast differentiation is still unclear. We used myoblasts derived from fetal bovine tissue as an in vitro model and found that NCAPG was expressed during myogenic differentiation in the cytoplasm and nucleus. Silencing NCAPG prolonged the mitosis and impaired the differentiation due to increased myoblast apoptosis. After 1.5 days of differentiation, silencing NCAPG enhanced muscle-specific gene expression. An assay for transposase-accessible chromatin- high throughput sequencing ...


Cysteine Dioxygenase Enzyme Activity And Gene Expression In The Dimorphic Pathogenic Fungus Histoplasma Capsulatum Is In Both The Mold And Yeast Morphotypes And Exhibits Substantial Strain Variation, Melissa Adams, Glen Shearer 2020 Southwest MS Community College

Cysteine Dioxygenase Enzyme Activity And Gene Expression In The Dimorphic Pathogenic Fungus Histoplasma Capsulatum Is In Both The Mold And Yeast Morphotypes And Exhibits Substantial Strain Variation, Melissa Adams, Glen Shearer

Faculty Publications

In the dimorphism (mold/yeast) Histoplasma capsulatum (Hc) literature are reports that yeast (the so-called pathogenic form) uniquely expresses a cysteine dioxygenase (CDO, approx. 10,500 dal) activity which the mold morphotype (the so-called saprophytic soil form) does not express (C.F., Kumar et al., Biochem 22, 762, 1983). This yeast-specific CDO activity is postulated to play a critical role in the mold-to-yeast shift. A number of years ago, our lab isolated the gene encoding the Hc cysteine dioxygenase (CDO1, Genbank accession AY804144) and noted significant expression in the mold morphotype of several Histoplasma strains and also determined that the ...


Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin CJ Nixon 2020 The University of Western Ontario

Mushroom Body-Specific Gene Regulation By The Swi/Snf Chromatin Remodeling Complex, Kevin Cj Nixon

Electronic Thesis and Dissertation Repository

Over the lifetime of an organism, neurons must establish, remodel, and maintain precise connections in order to form neural circuits that are required for proper nervous system functioning. Disruptions in these processes can lead to neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder. Mutations in genes encoding subunits of the SWI/SNF chromatin remodeling complex have been implicated in ID, yet the role of this complex in neurons is poorly understood. In this project, I established cell-type specific methods to examine the effect of SWI/SNF subunit knockdowns on gene transcription and chromatin structure in the memory-forming ...


Mtorc2-Akt Signaling To Atp-Citrate Lyase Drives Brown Adipogenesis And De Novo Lipogenesis, Camila Martinez Calejman, S. Trefely, S. W. Entwisle, Amelia K. Luciano, Su Myung. Jung, Wen-Yu Hsiao, A. Torres, C. M. Hung, H. Li, N. W. Snyder, J. Villen, K. E. Wellen, David A. Guertin 2020 University of Massachusetts Medical School

Mtorc2-Akt Signaling To Atp-Citrate Lyase Drives Brown Adipogenesis And De Novo Lipogenesis, Camila Martinez Calejman, S. Trefely, S. W. Entwisle, Amelia K. Luciano, Su Myung. Jung, Wen-Yu Hsiao, A. Torres, C. M. Hung, H. Li, N. W. Snyder, J. Villen, K. E. Wellen, David A. Guertin

Open Access Articles

mTORC2 phosphorylates AKT in a hydrophobic motif site that is a biomarker of insulin sensitivity. In brown adipocytes, mTORC2 regulates glucose and lipid metabolism, however the mechanism has been unclear because downstream AKT signaling appears unaffected by mTORC2 loss. Here, by applying immunoblotting, targeted phosphoproteomics and metabolite profiling, we identify ATP-citrate lyase (ACLY) as a distinctly mTORC2-sensitive AKT substrate in brown preadipocytes. mTORC2 appears dispensable for most other AKT actions examined, indicating a previously unappreciated selectivity in mTORC2-AKT signaling. Rescue experiments suggest brown preadipocytes require the mTORC2/AKT/ACLY pathway to induce PPAR-gamma and establish the epigenetic landscape during differentiation ...


An Atlas Of Cell Types In The Mammalian Epididymis And Vas Deferens, Vera D. Rinaldi, Elisa Donnard, Kyle Gellatly, Morten Rasmussen, Alper Kucukural, Onur Yukselen, Manuel Garber, Upasna Sharma, Oliver J. Rando 2020 University of Massachusetts Medical School

An Atlas Of Cell Types In The Mammalian Epididymis And Vas Deferens, Vera D. Rinaldi, Elisa Donnard, Kyle Gellatly, Morten Rasmussen, Alper Kucukural, Onur Yukselen, Manuel Garber, Upasna Sharma, Oliver J. Rando

University of Massachusetts Medical School Faculty Publications

Following spermatogenesis in the testis, mammalian sperm continue to mature over the course of approximately 10 days as they transit a long epithelial tube known as the epididymis. The epididymis is comprised of multiple segments/compartments that, in addition to concentrating sperm and preventing their premature activation, play key roles in remodeling the protein, lipid, and RNA composition of maturing sperm. In order to understand the complex roles for the epididymis in reproductive biology, we generated a single cell atlas of gene expression from the murine epididymis and vas deferens. We recovered all the key cell types of the epididymal ...


Gene Expression Pattern Analysis Of Anterior Hox Genes During Zebrafish (Danio Rerio) Embryonic Development Reveals Divergent Expression Patterns From Other Teleosts, Jeremy M. Brown, Sydney K. Travers, Charsey D. Dodgen, Amanda L. J. Duffus, Adam Davis 2020 University of North Georgia

Gene Expression Pattern Analysis Of Anterior Hox Genes During Zebrafish (Danio Rerio) Embryonic Development Reveals Divergent Expression Patterns From Other Teleosts, Jeremy M. Brown, Sydney K. Travers, Charsey D. Dodgen, Amanda L. J. Duffus, Adam Davis

Georgia Journal of Science

The regional identity of organs and organ systems along the anterior-posterior axis during embryonic development is patterned, in part, by Hox genes, which encode transcription factor proteins that activate or repress the expression of downstream target genes. Divergent nested Hox gene expression patterns may have had a role in facilitating morphological divergence of structures, such as the pharyngeal jaw apparatus, among evolutionarily divergent teleost fishes. Recent studies from several evolutionarily divergent teleosts, such as the Japanese Medaka (Oryzias latipes) and the Nile Tilapia (Oreochromis niloticus), have shown the presence of divergent expression patterns of several Hox genes within paralog groups ...


The Bioethical Significance Of “The Origin Of Man’S Ethical Behavior” (October 1941, Unpublished) By Ernest Everett Just And Hedwig Anna Schnetzler Just, Theodore Walker Jr. 2020 Southern Methodist University

The Bioethical Significance Of “The Origin Of Man’S Ethical Behavior” (October 1941, Unpublished) By Ernest Everett Just And Hedwig Anna Schnetzler Just, Theodore Walker Jr.

Journal of the South Carolina Academy of Science

Abstract –

E. E. Just (1883-1941) is an acknowledged “pioneer” in cell biology, and he is perhaps the pioneer in study of egg cell fertilization. Here we discover that Just also made pioneering contributions to general biology and evolutionary bioethics.

Within Just’s published contributions to observational cell biology, there are substantial fragments of his theory of ethical behavior, a theory with roots in cell biology. In addition to such previously available fragments, Just’s fully developed theory is now available. This recently discovered unpublished book-length manuscript argues for the biological origins of ethical behavior (evolving from cells to humans, within ...


Regulation Of Zebrafish Melanocyte Development By Ligand-Dependent Bmp Signaling, Alec Gramann, Arvind M. Venkatesan, Melissa Guerin, Craig J. Ceol 2019 University of Massachusetts Medical School

Regulation Of Zebrafish Melanocyte Development By Ligand-Dependent Bmp Signaling, Alec Gramann, Arvind M. Venkatesan, Melissa Guerin, Craig J. Ceol

Open Access Articles

Preventing terminal differentiation is important in the development and progression of many cancers including melanoma. Recent identification of the BMP ligand GDF6 as a novel melanoma oncogene showed GDF6-activated BMP signaling suppresses differentiation of melanoma cells. Previous studies have identified roles for GDF6 orthologs during early embryonic and neural crest development, but have not identified direct regulation of melanocyte development by GDF6. Here, we investigate the BMP ligand gdf6a, a zebrafish ortholog of human GDF6, during the development of melanocytes from the neural crest. We establish that the loss of gdf6a or inhibition of BMP signaling during neural crest development ...


Genetic Analysis Of A Novel Ftsk Homolog, Hfka, In Streptomyces Coelicolor Development-Associated Chromosome Segregation, Sumedha Sethi 2019 Duquesne University

Genetic Analysis Of A Novel Ftsk Homolog, Hfka, In Streptomyces Coelicolor Development-Associated Chromosome Segregation, Sumedha Sethi

Electronic Theses and Dissertations

A quintessential phenomenon occurring during prokaryotic development is accurate segregation of the replicated genomes into the daughter cells. Key energy-dependent processes like chromosome condensation and subcellular partitioning of the genomes are driven by conserved proteins like SMC, ParB, FtsK. During its complex developmental cycle, Streptomyces coelicolor segregates its genomes into chains of unicellular spores when its multigenomic syncytial aerial hyphae undergo division.

A novel ftsK-like gene, hfkA (Homolog of FtsK protein A), was examined for function and localization during development-associated chromosome segregation. Individual deletions did not affect segregation, but a ΔhfkA ΔftsK mutant exhibited 8% anucleate spores ...


Intestinal Neurod1 Expression Impairs Paneth Cell Differentiation And Promotes Enteroendocrine Lineage Specification, Joyce H. Li, Subir Ray, Ning Pan, Jody Haigh, Bernd Fritzsch, Andrew B. Leiter 2019 University of Massachusetts Medical School

Intestinal Neurod1 Expression Impairs Paneth Cell Differentiation And Promotes Enteroendocrine Lineage Specification, Joyce H. Li, Subir Ray, Ning Pan, Jody Haigh, Bernd Fritzsch, Andrew B. Leiter

Open Access Articles

Transcription factor Neurod1 is required for enteroendocrine progenitor differentiation and maturation. Several earlier studies indicated that ectopic expression of Neurod1 converted non- neuronal cells into neurons. However, the functional consequence of ectopic Neurod1 expression has not been examined in the GI tract, and it is not known whether Neurod1 can similarly switch cell fates in the intestine. We generated a mouse line that would enable us to conditionally express Neurod1 in intestinal epithelial cells at different stages of differentiation. Forced expression of Neurod1 throughout intestinal epithelium increased the number of EECs as well as the expression of EE specific transcription ...


The Ethics Of Ivf, Breanna Beers 2019 Cedarville University

The Ethics Of Ivf, Breanna Beers

Bioethics in Faith and Practice

In vitro fertilization (IVF) has promised hope to many couples struggling with the pain of infertility. However, as with any new medical technology, the ethical implications of this procedure must be examined, particularly in light of recent events such as the birth of the first genetically modified human beings, made possible by IVF. It is crucial to examine oppositions to IVF based on principle, as well as address concerns related to adjacent issues such as the discard of unused embryos; the selection, payment, privacy, and parental rights of donors and surrogates; the importance of genetic parenthood; new combinations of gametes ...


Robustness Mechanisms Of Temporal Cell-Fate Progression In C. Elegans, Orkan Ilbay 2019 University of Massachusetts Medical School

Robustness Mechanisms Of Temporal Cell-Fate Progression In C. Elegans, Orkan Ilbay

GSBS Dissertations and Theses

Robustness is a ubiquitous property of biological systems, however, underlying mechanisms that help reinforce the optimal phenotypes despite environmental or physiological perturbations are poorly understood.

C. elegans development consists of four larval stages (L1-L4) and well-characterized invariant cell lineages, within which the heterochronic pathway controls the order and timing of cell-fates. Environmental or physiological stress signals can slow or temporarily halt larval stage progression; remarkably, however, temporal cell-fate progression remains unaffected.

We show that two widely conserved signaling pathways, insulin and TGF- β, that regulate C. elegans larval stage progression in response to starvation and crowding, respectively, also regulate a ...


Hox Paralogs Selectively Convert Binding Of Ubiquitous Transcription Factors Into Tissue-Specific Patterns Of Enhancer Activation, Laure Bridoux, Peyman Zarrineh, Joshua Mallen, Mike Phuycharoen, Victor Latorre, Frank Ladam, Marta Losa, Charles G. Sagerstrom, Kimberley A. Mace, Magnus Rattray, Nicoletta Bobola 2019 University of Manchester

Hox Paralogs Selectively Convert Binding Of Ubiquitous Transcription Factors Into Tissue-Specific Patterns Of Enhancer Activation, Laure Bridoux, Peyman Zarrineh, Joshua Mallen, Mike Phuycharoen, Victor Latorre, Frank Ladam, Marta Losa, Charles G. Sagerstrom, Kimberley A. Mace, Magnus Rattray, Nicoletta Bobola

University of Massachusetts Medical School Faculty Publications

Gene expression programs determine cell fate in embryonic development and their dysregulation results in disease. Transcription factors (TFs) control gene expression by binding to enhancers, but how TFs select and activate their target enhancers is still unclear. HOX TFs share conserved homeodomains with highly similar sequence recognition properties, yet they impart the identity of different animal body parts. To understand how HOX TFs control their specific transcriptional programs in vivo, we compared HOXA2 and HOXA3 binding profiles in the mouse embryo. HOXA2 and HOXA3 directly cooperate with TALE TFs and selectively target different subsets of a broad TALE chromatin platform ...


Functional Importance Of Lipin Phosphorylation, Stephanie Elizabeth Hood 2019 University of Arkansas, Fayetteville

Functional Importance Of Lipin Phosphorylation, Stephanie Elizabeth Hood

Theses and Dissertations

Highly conserved throughout evolution, lipins are dual functioning proteins found from yeast to humans. Functioning in the cytoplasm as phosphatidate phosphatase enzymes (PAP), lipins produce diacylglycerol that serves as a precursor for neutral fats and membrane phospholipids. Alternatively, nuclear lipins are responsible for the regulation of metabolic genes. Interestingly, both the mammalian lipin 1 paralog and the single Drosophila Lipin ortholog are highly phosphorylated proteins. Target of rapamycin (TOR) has previously been identified as one of the kinases that controls the subcellular localization of both lipin 1 and Drosophila Lipin. However, other serine and threonine kinases are predicted to be ...


Regulation Of Nuclear-Cytoplasmic Partitioning By The Lin-28-Lin-46 Pathway Reinforces Microrna Repression Of Hbl-1 To Confer Robust Cell-Fate Progression In C. Elegans, Orkan Ilbay, Victor R. Ambros 2019 University of Massachusetts Medical School

Regulation Of Nuclear-Cytoplasmic Partitioning By The Lin-28-Lin-46 Pathway Reinforces Microrna Repression Of Hbl-1 To Confer Robust Cell-Fate Progression In C. Elegans, Orkan Ilbay, Victor R. Ambros

Program in Molecular Medicine Publications

MicroRNAs target complementary mRNAs for degradation or translational repression, reducing or preventing protein synthesis. In Caenorhabditis elegans, the transcription factor HBL-1 (Hunchback-like 1) promotes early larval (L2)-stage cell fates, and the let-7 family microRNAs temporally downregulate HBL-1 to enable the L2-to-L3 cell-fate progression. In parallel to let-7-family microRNAs, the conserved RNA-binding protein LIN-28 and its downstream gene lin-46 also act upstream of HBL-1 in regulating the L2-to-L3 cell-fate progression. The molecular function of LIN-46, and how the lin-28-lin-46 pathway regulates HBL-1, are not understood. Here, we report that the regulation of HBL-1 by the lin-28-lin-46 pathway is independent of ...


Aniseed 2019: 4d Exploration Of Genetic Data For An Extended Range Of Tunicates, J. Dardaillon, D. Dauga, P. Simion, E. Faure, T. A. Onuma, M. B. DeBiasse, A. Louis, K. R. Nitta, M. Naville, L. Besnardeau, W. Reeves, K. Wang, M. Fagotto, M. Guéroult-Bellone, S. Fujiwara, R. Dumollard, M. Veeman, J.-N. Volff, H. Roest Crollius, E. Douzery, J. F. Ryan, Bradley Justin Davidson , '91, H. Nishida, C. Dantec, P. Lemaire 2019 Swarthmore College

Aniseed 2019: 4d Exploration Of Genetic Data For An Extended Range Of Tunicates, J. Dardaillon, D. Dauga, P. Simion, E. Faure, T. A. Onuma, M. B. Debiasse, A. Louis, K. R. Nitta, M. Naville, L. Besnardeau, W. Reeves, K. Wang, M. Fagotto, M. Guéroult-Bellone, S. Fujiwara, R. Dumollard, M. Veeman, J.-N. Volff, H. Roest Crollius, E. Douzery, J. F. Ryan, Bradley Justin Davidson , '91, H. Nishida, C. Dantec, P. Lemaire

Biology Faculty Works

ANISEED (https://www.aniseed.cnrs.fr) is the main model organism database for the worldwide community of scientists working on tunicates, the vertebrate sister-group. Information provided for each species includes functionally-annotated gene and transcript models with orthology relationships within tunicates, and with echinoderms, cephalochordates and vertebrates. Beyond genes the system describes other genetic elements, including repeated elements and cis-regulatory modules. Gene expression profiles for several thousand genes are formalized in both wild-type and experimentally-manipulated conditions, using formal anatomical ontologies. These data can be explored through three complementary types of browsers, each offering a different view-point. A developmental browser summarizes the ...


The Role Of Xenopus Laevis Reck In Ecm Remodeling And Tissue Patterning, Jessica Willson 2019 The University of Western Ontario

The Role Of Xenopus Laevis Reck In Ecm Remodeling And Tissue Patterning, Jessica Willson

Electronic Thesis and Dissertation Repository

Proper cell-cell and cell-extracellular matrix (ECM) interactions are vital for cell migration and patterning of the vertebrate embryo. Matrix metalloproteinases (MMPs) and their inhibitors, reversion-inducing cysteine-rich proteins with Kazal motifs (RECK) and tissue inhibitors of metalloproteinases (TIMPs), are all differentially expressed during embryogenesis to regulate such ECM remodeling events and cell interactions. While TIMPs are a family of 4 secreted proteins that share overlapping substrate specificities of MMPs, RECK is unique in that it is a membrane-anchored MMP inhibitor that is embryonic lethal in mice. I used Xenopus laevis as a model organism to investigate the role of RECK as ...


Investigating The Role Of Lbh During Early Embryonic Development In Xenopus Laevis, Emma Weir 2019 University of Massachusetts Amherst

Investigating The Role Of Lbh During Early Embryonic Development In Xenopus Laevis, Emma Weir

Masters Theses

LBH is a highly conserved protein whose role during vertebrate development is relatively under-studied. In collaboration with the Albertson lab, our lab has previously shown that it is necessary for cranial neural crest cell migration in the zebrafish and in Xenopus laevis. The molecular mechanisms through which it acts are not well understood.

In Xenopus, LBH is a maternally deposited protein. As such, studying its role in early development has not been feasible through the morpholino-mediated knockdown techniques that prevent translation of target genes. Recently, a technique for degrading endogenous proteins was developed, called Trim-Away. This was developed in mammalian ...


Patterns Of Morphological Plasticity In Metriaclima Zebra And Danio Rerio Suggest Differently Canalized Phenotypes Due To Form-Function Relationships, Dylan Jockel 2019 University of Massachusetts Amherst

Patterns Of Morphological Plasticity In Metriaclima Zebra And Danio Rerio Suggest Differently Canalized Phenotypes Due To Form-Function Relationships, Dylan Jockel

Masters Theses

In order to ascertain the degree of compatibility in developmental restructuring and behavioral plasticity between two fish species frequently made subject of laboratory research (Metriaclima zebra & Danio rerio), alternative trophic niche exposure experiments utilizing novel three-prong feeding treatments were conducted to obtain morphometric data, which demonstrated both species do bear some degree of plasticity. The results are somewhat complicated by differences in locality of detectable restructuring, which may be due to disparity in the form-function relationship for each species’ lineage. Each is notable in the manner of respective species’ jaw protrusion, as it is driven by anterior kinethmoid rotation in ...


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