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Articles 1 - 27 of 27

Full-Text Articles in Cell Biology

A Critical Role Of Vmp1 In Lipoprotein Secretion, Hideaki Morishita, Yan G. Zhao, Norito Tamura, Taki Nishimura, Yuki Kanda, Yuriko Sakamaki, Mitsuyo Okazaki, Dongfang Li, Noboru Mizushima Sep 2019

A Critical Role Of Vmp1 In Lipoprotein Secretion, Hideaki Morishita, Yan G. Zhao, Norito Tamura, Taki Nishimura, Yuki Kanda, Yuriko Sakamaki, Mitsuyo Okazaki, Dongfang Li, Noboru Mizushima

Open Access Articles

Lipoproteins are lipid-protein complexes that are primarily generated and secreted from the intestine, liver, and visceral endoderm and delivered to peripheral tissues. Lipoproteins, which are assembled in the endoplasmic reticulum (ER) membrane, are released into the ER lumen for secretion, but its mechanism remains largely unknown. Here, we show that the release of lipoproteins from the ER membrane requires VMP1, an ER transmembrane protein essential for autophagy and certain types of secretion. Loss of vmp1, but not other autophagy-related genes, in zebrafish causes lipoprotein accumulation in the intestine and liver. Vmp1 deficiency in mice also leads to lipid accumulation in ...


Distinct Features Of Nucleolus-Associated Domains In Mouse Embryonic Stem Cells, Aizhan Bizhanova, Aimin Yan, Jun Yu, Lihua Julie Zhu, Paul D. Kaufman Aug 2019

Distinct Features Of Nucleolus-Associated Domains In Mouse Embryonic Stem Cells, Aizhan Bizhanova, Aimin Yan, Jun Yu, Lihua Julie Zhu, Paul D. Kaufman

University of Massachusetts Medical School Faculty Publications

Background Heterochromatin in eukaryotic interphase cells frequently localizes to the nucleolar periphery (nucleolus-associated domains, NADs) and the nuclear lamina (lamina-associated domains, LADs). Gene expression in somatic cell NADs is generally low, but NADs have not been characterized in mammalian stem cells.

Results Here, we generated the first genome-wide map of NADs in mouse embryonic stem cells (mESCs) via deep sequencing of chromatin associated with biochemically-purified nucleoli. As we had observed in mouse embryonic fibroblasts (MEFs), the large Type I subset of NADs overlaps with constitutive LADs and is enriched for features of constitutive heterochromatin, including late replication timing and low ...


Yap Drives Cutaneous Squamous Cell Carcinoma Formation And Progression, Zoe Vincent-Mistiaen, Ahmed Elbediwy, Hannah Vanyai, Jennifer L. Cotton, Gordon Stamp, Emma Nye, Bradley Spencer-Dene, Gareth J. Thomas, Junhao Mao, Barry Thompson Sep 2018

Yap Drives Cutaneous Squamous Cell Carcinoma Formation And Progression, Zoe Vincent-Mistiaen, Ahmed Elbediwy, Hannah Vanyai, Jennifer L. Cotton, Gordon Stamp, Emma Nye, Bradley Spencer-Dene, Gareth J. Thomas, Junhao Mao, Barry Thompson

Open Access Articles

Squamous cell carcinoma (SCC) can progress to malignant metastatic cancer, including an aggressive subtype known as spindle cell carcinoma (spSCC). spSCC formation involves epithelial-to-mesenchymal transition (EMT), yet the molecular basis of this event remains unknown. The transcriptional co-activator YAP undergoes recurrent amplification in human SCC and overexpression of YAP drives SCC formation in mice. Here, we show that human spSCC tumours also feature strong nuclear localisation of YAP and overexpression of activated YAP (NLS-YAP-5SA) with Keratin-5 (K5-CreERt) is sufficient to induce rapid formation of both SCC and spSCC in mice. spSCC tumours arise at sites of epithelial scratch wounding, where ...


Transgneic Endothelin 3 Regulates Murine Pigment Production And Coat Color, Javier Pino Oct 2017

Transgneic Endothelin 3 Regulates Murine Pigment Production And Coat Color, Javier Pino

FIU Electronic Theses and Dissertations

Pigmentation plays a protective role against damage caused by ultraviolet (UV) irradiation. Humans with fair skin and light hair have a higher susceptibility to UV-induced DNA damage that can lead to the development of skin cancers. The melanocytes found in the skin and hair follicles depend on different signaling molecules for their proper development and pigment production. α-Melanocyte Stimulating Hormone (α-msh) binds to the Melanocortin 1 receptor (Mc1r) to regulate pigment production and the switch between eumelanin and pheomelanin. Lethal yellow mice (Ay) overexpress the agouti signaling protein, which inhibits the binding of α-msh, resulting in a yellow coat ...


Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, Markus Parzival Vallaster Aug 2017

Intergenerational Effects Of Nicotine In An Animal Model Of Paternal Nicotine Exposure, Markus Parzival Vallaster

GSBS Dissertations and Theses

Environmental conditions imposed onto organisms during certain phases of their life cycles such as embryogenesis or puberty can not only impact the organisms’ own health, but also affect subsequent generations. The underlying mechanisms causing intergenerational phenotypes are not encoded in the genome, but the result of reversible epigenetic modifications. This work investigates in a mouse model the impact of paternal nicotine exposure on the next generation regarding addictive behavior modulation, metabolic changes, and molecular mechanisms. It provides evidence that male offspring from nicotine-exposed fathers (NIC offspring) is more resistant to lethal doses of nicotine. This phenotype is gender-specific and depends ...


Glycolytic Reliance Promotes Anabolism In Photoreceptors, Yashodhan Chinchore, Tedi Begaj, David Wu, Eugene Drokhlyansky, Constance L. Cepko Jun 2017

Glycolytic Reliance Promotes Anabolism In Photoreceptors, Yashodhan Chinchore, Tedi Begaj, David Wu, Eugene Drokhlyansky, Constance L. Cepko

Senior Scholars Program

Vertebrate photoreceptors are among the most metabolically active cells, exhibiting a high rate of ATP consumption. This is coupled with a high anabolic demand, necessitated by the diurnal turnover of a specialized membrane-rich organelle, the outer segment, which is the primary site of phototransduction. How photoreceptors balance their catabolic and anabolic demands is poorly understood. Here, we show that rod photoreceptors in mice rely on glycolysis for their outer segment biogenesis. Genetic perturbations targeting allostery or key regulatory nodes in the glycolytic pathway impacted the size of the outer segments. Fibroblast growth factor signaling was found to regulate glycolysis, with ...


Macrophages Are Necessary For Epimorphic Regeneration In African Spiny Mice, Jennifer Simkin, Thomas R. Gawriluk, John C. Gensel, Ashley W. Seifert May 2017

Macrophages Are Necessary For Epimorphic Regeneration In African Spiny Mice, Jennifer Simkin, Thomas R. Gawriluk, John C. Gensel, Ashley W. Seifert

Biology Faculty Publications

How the immune system affects tissue regeneration is not well understood. In this study, we used an emerging mammalian model of epimorphic regeneration, the African spiny mouse, to examine cell-based inflammation and tested the hypothesis that macrophages are necessary for regeneration. By directly comparing inflammatory cell activation in a 4 mm ear injury during regeneration (Acomys cahirinus) and scarring (Mus musculus), we found that both species exhibited an acute inflammatory response, with scarring characterized by stronger myeloperoxidase activity. In contrast, ROS production was stronger and more persistent during regeneration. By depleting macrophages during injury, we demonstrate a functional requirement for ...


Dna Methylation Directs Genomic Localization Of Mbd2 And Mbd3 In Embryonic Stem Cells, Sarah J. Hainer, Kurtis N. Mccannell, Jun Yu, Ly-Sha Ee, Lihua (Julie) Zhu, Oliver J. Rando, Thomas G. Fazzio Nov 2016

Dna Methylation Directs Genomic Localization Of Mbd2 And Mbd3 In Embryonic Stem Cells, Sarah J. Hainer, Kurtis N. Mccannell, Jun Yu, Ly-Sha Ee, Lihua (Julie) Zhu, Oliver J. Rando, Thomas G. Fazzio

Open Access Articles

Cytosine methylation is an epigenetic and regulatory mark that functions in part through recruitment of chromatin remodeling complexes containing methyl-CpG binding domain (MBD) proteins. Two MBD proteins, Mbd2 and Mbd3, were previously shown to bind methylated or hydroxymethylated DNA, respectively; however, both of these findings have been disputed. Here, we investigated this controversy using experimental approaches and re-analysis of published data and find no evidence for methylation-independent functions of Mbd2 or Mbd3. We show that chromatin localization of Mbd2 and Mbd3 is highly overlapping and, unexpectedly, we find Mbd2 and Mbd3 are interdependent for chromatin association. Further investigation reveals that ...


A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. Van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page Oct 2016

A Widely Employed Germ Cell Marker Is An Ancient Disordered Protein With Reproductive Functions In Diverse Eukaryotes, Michelle A. Carmell, Gregoriy A. Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C. Van Wolfswinkel, Kyomi J. Igarashi, Daniel W. Bellott, Michael Nefedov, Peter W. Reddien, George C. Enders, Vladimir N. Uversky, Craig C. Mello, David C. Page

Open Access Articles

The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells ...


Regulation Of X-Linked Gene Expression During Early Mouse Development By Rlim, Feng Wang, Jongdae Shin, Jeremy Shea, Jun Yu, Ana Boskovic, Meg Byron, Xiaochun Zhu, Alex K. Shalek, Aviv Regev, Jeanne B. Lawrence, Eduardo M. Torres, Lihua J. Zhu, Oliver J. Rando, Ingolf Bach Sep 2016

Regulation Of X-Linked Gene Expression During Early Mouse Development By Rlim, Feng Wang, Jongdae Shin, Jeremy Shea, Jun Yu, Ana Boskovic, Meg Byron, Xiaochun Zhu, Alex K. Shalek, Aviv Regev, Jeanne B. Lawrence, Eduardo M. Torres, Lihua J. Zhu, Oliver J. Rando, Ingolf Bach

Open Access Articles

Mammalian X-linked gene expression is highly regulated as female cells contain two and male one X chromosome (X). To adjust the X gene dosage between genders, female mouse preimplantation embryos undergo an imprinted form of X chromosome inactivation (iXCI) that requires both Rlim (also known as Rnf12) and the long non-coding RNA Xist. Moreover, it is thought that gene expression from the single active X is upregulated to correct for bi-allelic autosomal (A) gene expression. We have combined mouse genetics with RNA-seq on single mouse embryos to investigate functions of Rlim on the temporal regulation of iXCI and Xist. Our ...


An Alternative Splicing Program Promotes Adipose Tissue Thermogenesis, Santiago Vernia, Yvonne J. K. Edwards, Myoung Souk Han, Julie Cavanagh-Kyros, Tamera Barrett, Jason K. Kim, Roger J. Davis Sep 2016

An Alternative Splicing Program Promotes Adipose Tissue Thermogenesis, Santiago Vernia, Yvonne J. K. Edwards, Myoung Souk Han, Julie Cavanagh-Kyros, Tamera Barrett, Jason K. Kim, Roger J. Davis

University of Massachusetts Medical School Faculty Publications

Alternative pre-mRNA splicing expands the complexity of the transcriptome and controls isoform-specific gene expression. Whether alternative splicing contributes to metabolic regulation is largely unknown. Here we investigated the contribution of alternative splicing to the development of diet-induced obesity. We found that obesity-induced changes in adipocyte gene expression include alternative pre-mRNA splicing. Bioinformatics analysis associated part of this alternative splicing program with sequence specific NOVA splicing factors. This conclusion was confirmed by studies of mice with NOVA deficiency in adipocytes. Phenotypic analysis of the NOVA-deficient mice demonstrated increased adipose tissue thermogenesis and improved glycemia. We show that NOVA proteins mediate a ...


Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis Aug 2016

Suppression Of Ischemia In Arterial Occlusive Disease By Jnk-Promoted Native Collateral Artery Development, Kasmir Ramo, Koichi Sugamura, Siobhan M. Craige, John F. Keaney Jr., Roger J. Davis

Davis Lab Publications

Arterial occlusive diseases are major causes of morbidity and mortality. Blood flow to the affected tissue must be restored quickly if viability and function are to be preserved. We report that disruption of the mixed-lineage protein kinase (MLK) - cJun NH2-terminal kinase (JNK) signaling pathway in endothelial cells causes severe blockade of blood flow and failure to recover in the murine femoral artery ligation model of hindlimb ischemia. We show that the MLK-JNK pathway is required for the formation of native collateral arteries that can restore circulation following arterial occlusion. Disruption of the MLK-JNK pathway causes decreased Dll4/Notch signaling, excessive ...


Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots Aug 2016

Optimization Of A Genomic Editing System Using Crispr/Cas9-Induced Site-Specific Gene Integration, Jillian L. Mccool Ms., Nick Hum, Gabriela G. Loots

STAR (STEM Teacher and Researcher) Presentations

The CRISPR-Cas system is an adaptive immune system found in bacteria which helps protect against the invasion of other microorganisms. This system induces double stranded breaks at precise genomic loci (1) in which repairs are initiated and insertions of a target are completed in the process. This mechanism can be used in eukaryotic cells in combination with sgRNAs (1) as a tool for genome editing. By using this CRISPR-Cas system, in addition to the “safe harbor locus,” ROSAβ26, the incorporation of a target gene into a site that is not susceptible to gene silencing effects can be achieved through few ...


The Histone H3k9 Demethylase Kdm3a Promotes Anoikis By Transcriptionally Activating Pro-Apoptotic Genes Bnip3 And Bnip3l, Victoria E. Pedanou, Stephane Gobeil, Sebastien Tabaries, Tessa M. Simone, Lihua Julie Zhu, Peter M. Siegel, Michael R. Green Jul 2016

The Histone H3k9 Demethylase Kdm3a Promotes Anoikis By Transcriptionally Activating Pro-Apoptotic Genes Bnip3 And Bnip3l, Victoria E. Pedanou, Stephane Gobeil, Sebastien Tabaries, Tessa M. Simone, Lihua Julie Zhu, Peter M. Siegel, Michael R. Green

Open Access Articles

Epithelial cells that lose attachment to the extracellular matrix undergo a specialized form of apoptosis called anoikis. Here, using large-scale RNA interference (RNAi) screening, we find that KDM3A, a histone H3 lysine 9 (H3K9) mono- and di-demethylase, plays a pivotal role in anoikis induction. In attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression. RNAi-mediated knockdown of KDM3A substantially reduces apoptosis following detachment and, conversely, ectopic expression of KDM3A induces cell death in attached cells. We find that KDM3A promotes anoikis through transcriptional activation ...


Excitatory Transmission Onto Agrp Neurons Is Regulated By Cjun Nh2-Terminal Kinase 3 In Response To Metabolic Stress, Santiago Vernia, Caroline Morel, Joseph C. Madara, Julie Cavanagh-Kyros, Tamera Barrett, Kathryn O. Chase, Norman J. Kennedy, Dae Young Jung, Jason K. Kim, Neil Aronin, Richard A. Flavell, Bradford B. Lowell, Roger J. Davis Feb 2016

Excitatory Transmission Onto Agrp Neurons Is Regulated By Cjun Nh2-Terminal Kinase 3 In Response To Metabolic Stress, Santiago Vernia, Caroline Morel, Joseph C. Madara, Julie Cavanagh-Kyros, Tamera Barrett, Kathryn O. Chase, Norman J. Kennedy, Dae Young Jung, Jason K. Kim, Neil Aronin, Richard A. Flavell, Bradford B. Lowell, Roger J. Davis

Davis Lab Publications

The cJun NH2-terminal kinase (JNK) signaling pathway is implicated in the response to metabolic stress. Indeed, it is established that the ubiquitously expressed JNK1 and JNK2 isoforms regulate energy expenditure and insulin resistance. However, the role of the neuron-specific isoform JNK3 is unclear. Here we demonstrate that JNK3 deficiency causes hyperphagia selectively in high fat diet (HFD)-fed mice. JNK3 deficiency in neurons that express the leptin receptor LEPRb was sufficient to cause HFD-dependent hyperphagia. Studies of sub-groups of leptin-responsive neurons demonstrated that JNK3 deficiency in AgRP neurons, but not POMC neurons, was sufficient to cause the hyperphagic response. These ...


Near-Infrared Photoactivatable Control Of Ca Signaling And Optogenetic Immunomodulation, Lian He, Yuanwei Zhang, Guolin Ma, Peng Tan, Zhan Jun Li, Shengbing Zhang, Xiang Wu, Ji Jing, Shaohai Fang, Lijuan Zhou, Youjun Wang, Yun Huang, Patrick Hogan, Gang Han, Yubin Zhou Dec 2015

Near-Infrared Photoactivatable Control Of Ca Signaling And Optogenetic Immunomodulation, Lian He, Yuanwei Zhang, Guolin Ma, Peng Tan, Zhan Jun Li, Shengbing Zhang, Xiang Wu, Ji Jing, Shaohai Fang, Lijuan Zhou, Youjun Wang, Yun Huang, Patrick Hogan, Gang Han, Yubin Zhou

Open Access Articles

The application of current channelrhodopsin-based optogenetic tools is limited by the lack of strict ion selectivity and the inability to extend the spectra sensitivity into the near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable optogenetic platform (termed "Opto-CRAC") that selectively and remotely controls Ca2+ oscillations and Ca2+-responsive gene expression to regulate the function of non-excitable cells, including T lymphocytes, macrophages and dendritic cells. When coupled to upconversion nanoparticles, the optogenetic operation window is shifted from the visible range to NIR wavelengths to enable wireless photoactivation of Ca2+-dependent signaling and optogenetic modulation of immunoinflammatory responses. In a ...


A Mitochondria-Anchored Isoform Of The Actin-Nucleating Spire Protein Regulates Mitochondrial Division, Uri Manor, Sadie Bartholomew, Gonen Golani, Eric Christenson, Michael Kozlov, Henry Higgs, James Spudich, Jennifer Lippincott-Schwartz Aug 2015

A Mitochondria-Anchored Isoform Of The Actin-Nucleating Spire Protein Regulates Mitochondrial Division, Uri Manor, Sadie Bartholomew, Gonen Golani, Eric Christenson, Michael Kozlov, Henry Higgs, James Spudich, Jennifer Lippincott-Schwartz

Open Dartmouth: Faculty Open Access Scholarship

Mitochondrial division, essential for survival in mammals, is enhanced by an inter-organellar process involving ER tubules encircling and constricting mitochondria. The force for constriction is thought to involve actin polymerization by the ER-anchored isoform of the formin protein inverted formin 2 (INF2). Unknown is the mechanism triggering INF2-mediated actin polymerization at ER-mitochondria intersections. We show that a novel isoform of the formin-binding, actin-nucleating protein Spire, Spire1C, localizes to mitochondria and directly links mitochondria to the actin cytoskeleton and the ER. Spire1C binds INF2 and promotes actin assembly on mitochondrial surfaces. Disrupting either Spire1C actin- or formin-binding activities reduces mitochondrial constriction ...


Intraflagellar Transport 27 Is Essential For Hedgehog Signaling But Dispensable For Ciliogenesis During Hair Follicle Morphogenesis, Ning Yang, Li Li, Thibaut Eguether, John P. Sundberg, Gregory J. Pazour, Jiang Chen Jun 2015

Intraflagellar Transport 27 Is Essential For Hedgehog Signaling But Dispensable For Ciliogenesis During Hair Follicle Morphogenesis, Ning Yang, Li Li, Thibaut Eguether, John P. Sundberg, Gregory J. Pazour, Jiang Chen

Program in Molecular Medicine Publications and Presentations

Hair follicle morphogenesis requires precisely controlled reciprocal communications, including hedgehog (Hh) signaling. Activation of the Hh signaling pathway relies on the primary cilium. Disrupting ciliogenesis results in hair follicle morphogenesis defects due to attenuated Hh signaling; however, the loss of cilia makes it impossible to determine whether hair follicle phenotypes in these cilia mutants are caused by the loss of cilia, disruption of Hh signaling, or a combination of these events. In this study, we characterized the function of Ift27, which encodes a subunit of intraflagellar transport (IFT) complex B. Hair follicle morphogenesis of Ift27-null mice was severely impaired, reminiscent ...


Intraflagellar Transport 27 Is Essential For Hedgehog Signaling But Dispensable For Ciliogenesis During Hair Follicle Morphogenesis, Ning Yang, Li Li, Thibaut Eguether, John P. Sundberg, Gregory J. Pazour, Jiang Chen Jun 2015

Intraflagellar Transport 27 Is Essential For Hedgehog Signaling But Dispensable For Ciliogenesis During Hair Follicle Morphogenesis, Ning Yang, Li Li, Thibaut Eguether, John P. Sundberg, Gregory J. Pazour, Jiang Chen

Open Access Articles

Hair follicle morphogenesis requires precisely controlled reciprocal communications, including hedgehog (Hh) signaling. Activation of the Hh signaling pathway relies on the primary cilium. Disrupting ciliogenesis results in hair follicle morphogenesis defects due to attenuated Hh signaling; however, the loss of cilia makes it impossible to determine whether hair follicle phenotypes in these cilia mutants are caused by the loss of cilia, disruption of Hh signaling, or a combination of these events. In this study, we characterized the function of Ift27, which encodes a subunit of intraflagellar transport (IFT) complex B. Hair follicle morphogenesis of Ift27-null mice was severely impaired, reminiscent ...


Ciliary Proteins Bbs8 And Ift20 Promote Planar Cell Polarity In The Cochlea, Helen L. May-Simera, Ronald S. Petralia, Mireille Montcouquiol, Ya-Xian Wang, Katherine B. Szarama, Yun Liu, Weichun Lin, Michael R. Deans, Gregory J. Pazour, Matthew W. Kelley Feb 2015

Ciliary Proteins Bbs8 And Ift20 Promote Planar Cell Polarity In The Cochlea, Helen L. May-Simera, Ronald S. Petralia, Mireille Montcouquiol, Ya-Xian Wang, Katherine B. Szarama, Yun Liu, Weichun Lin, Michael R. Deans, Gregory J. Pazour, Matthew W. Kelley

Program in Molecular Medicine Publications and Presentations

Primary cilia have been implicated in the generation of planar cell polarity (PCP). However, variations in the severity of polarity defects in different cilia mutants, coupled with recent demonstrations of non-cilia-related actions of some cilia genes, make it difficult to determine the basis of these polarity defects. To address this issue, we evaluated PCP defects in cochlea from a selection of mice with mutations in cilia-related genes. Results indicated notable PCP defects, including mis-oriented hair cell stereociliary bundles, in Bbs8 and Ift20 single mutants that are more severe than in other cilia gene knockouts. In addition, deletion of either Bbs8 ...


Isolation Of Myogenic Nuclei From Whole Muscle Tissue, Owen Brewer Jan 2015

Isolation Of Myogenic Nuclei From Whole Muscle Tissue, Owen Brewer

Undergraduate Honors Theses

Isolation of myogenic cell populations from whole skeletal muscle is necessary to elucidate the molecular repair mechanisms involved in skeletal muscle maintenance and regeneration that can be damaged when affected by diseases or aging, often severely impacting quality of life and lifespan. Skeletal muscle tissue is composed of hundreds of myofibers that are syncytia comprised of hundreds of nuclei named myonuclei. External to the sarcolemma(plasma membrane) of each myofiber is the basal lamina. Satellite cells, which reside between the basal lamina and the sarcolemma, are self-renewing muscle stem cells that maintain and repair muscle tissue. I have developed a ...


Molecular Mechanisms Regulating Neonatal Oocyte Survival And Primordial Follicle Formation In The Mouse Ovary, Robin L. Jones Dec 2012

Molecular Mechanisms Regulating Neonatal Oocyte Survival And Primordial Follicle Formation In The Mouse Ovary, Robin L. Jones

Biology - Dissertations

In mammals, formation of the primordial follicle is a complex process involving the breakdown of germ cell cysts, where oocytes must separate from each other and subsequently become surrounded by somatic cells. As cysts separate, a large number of germ cells are lost by apoptosis, however the mechanisms by which cyst breakdown and germ cell death occur are not well understood. We first hypothesized that two anti-apoptotic regulators from the BCL2 family of proteins, BCL2 and MCL1, may be responsible for regulating neonatal oocyte survival. To elucidate the effects of BCL2 in the neonatal ovary, we examined ovaries of both ...


Characterization Of Structure And Function Of The Mouse Retina Using Pattern Electroretinography, Pupil Light Reflex, And Optical Coherence Tomography, Kabhilan Mohan, Matthew M. Harper, Helga Kecova, Eun-Ah Ye, Tatjana Lazic, Donald S. Sakaguchi, Randy H. Kardon, Sinisa D. Grozdanic, Cr: Biomed Vision Technologies, Neuroptics Inc. Sep 2012

Characterization Of Structure And Function Of The Mouse Retina Using Pattern Electroretinography, Pupil Light Reflex, And Optical Coherence Tomography, Kabhilan Mohan, Matthew M. Harper, Helga Kecova, Eun-Ah Ye, Tatjana Lazic, Donald S. Sakaguchi, Randy H. Kardon, Sinisa D. Grozdanic, Cr: Biomed Vision Technologies, Neuroptics Inc.

Genetics, Development and Cell Biology Publications

Objective  To perform in vivo analysis of retinal functional and structural parameters in healthy mouse eyes.

Animal Studied  Adult C57BL/6 male mice (n = 37).

Procedures  Retinal function was evaluated using pattern electroretinography (pERG) and the chromatic pupil light reflex (cPLR). Structural properties of the retina and nerve fiber layer (NFL) were evaluated using spectral-domain optical coherence tomography (SD-OCT).

Results  The average pERG amplitudes were found to be 11.2 ± 0.7 μV (P50-N95, mean ± SEM), with an implicit time for P50-N95 interval of 90.4 ± 5.4 ms. Total retinal thickness was 229.5 ± 1.7 μm (mean ± SEM ...


Impact Of Collateral Enlargement On Smooth Muscle Phenotype, Alexander Jerome Bynum Dec 2011

Impact Of Collateral Enlargement On Smooth Muscle Phenotype, Alexander Jerome Bynum

Master's Theses and Project Reports

Peripheral Artery Disease is a very serious disease characterized by an arterial occlusion due to atherosclerotic plaques. In response to an arterial occlusion, arteriogenesis occurs, causing smooth muscle cells to transition from a contractile to synthetic state. Also following an arterial occlusion, functional impairment was seen in the collateral circuit. An immunofluorescence protocol was developed in order to assess the impact of collateral enlargement (arteriogenesis) on smooth muscle phenotype at various time points. Smooth muscle α-actin was used to mark all smooth muscle cells, Ki-67 was used to label proliferating smooth muscle cells, and a fluorescent nuclear stain was used ...


The Development And Analysis Of A Closed System Of Vitrification For Mammalian Embryos, Jennifer Graves-Herring Dec 2008

The Development And Analysis Of A Closed System Of Vitrification For Mammalian Embryos, Jennifer Graves-Herring

All Dissertations

Embryo cryopreservation is an integral part of assisted reproduction because it allows for future use of these embryos. Cryopreservation occurs when there are supernumerary embryos or when an embryo transfer cannot be performed.
There are two main methods to cryopreserve embryos. The most recent is vitrification, which uses high concentrations of cryoprotectants, a short time to cool and avoids ice crystals. The 'gold standard' is the slow-cool method, which uses low concentrations of cryoprotectants, a long time to cool embryos and produces extracellular ice crystals.
Prior to introducing vitrification as part of the human cryopreservation regime, it is important that ...


Jun N-Terminal Kinase 1 Regulates Epithelial-To-Mesenchymal Transition Induced By Tgf-Beta1, John F. Alcorn, Amy S. Guala, Jos Van Der Velden, Brian Mcelhinney, Charles G. Irvin, Roger J. Davis, Yvonne M.W. Janssen-Heininger Apr 2008

Jun N-Terminal Kinase 1 Regulates Epithelial-To-Mesenchymal Transition Induced By Tgf-Beta1, John F. Alcorn, Amy S. Guala, Jos Van Der Velden, Brian Mcelhinney, Charles G. Irvin, Roger J. Davis, Yvonne M.W. Janssen-Heininger

Davis Lab Publications

Transforming growth factor beta1 (TGF-beta1) is a cardinal cytokine in the pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal transition (EMT). As a molecular interaction between TGF-beta1 and Jun N-terminal kinase (JNK) has been demonstrated, the goal of this study was to elucidate whether JNK plays a role in TGF-beta1-induced EMT. Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were comparatively evaluated for their ability to undergo EMT in response to TGF-beta1. Wild-type MTEC exposed to TGF-beta1 demonstrated a prominent induction of mesenchymal mediators and a loss of epithelial markers, in conjunction with a loss ...


Bcma Is Essential For The Survival Of Long-Lived Bone Marrow Plasma Cells, Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling-Li Lin, George Mantchev, Richard J. Bram, Randolph J. Noelle Jan 2004

Bcma Is Essential For The Survival Of Long-Lived Bone Marrow Plasma Cells, Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling-Li Lin, George Mantchev, Richard J. Bram, Randolph J. Noelle

Open Dartmouth: Faculty Open Access Scholarship

Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by inter- leukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this 􏰀-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival ...