+publisher:"Penn State University" +contributor:("Richard W Ordway, Committee Member")

Penn State University

1. Zhao, Na. Investigation of the molecular genetics of Drosophila synapse assembly.

Degree: 2014, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/22720

► The nervous system consists of billions of neurons that interconnect to form functional neural circuits and networks. Synapses, the fundamental units of nervous system, are… (more)

▼ The nervous system consists of billions of neurons that interconnect to form functional neural circuits and networks. Synapses, the fundamental units of nervous system, are the highly-specialized cell junctions that mediate intercellular communication. The coordinated synaptic growth and plasticity ensures synaptic transmission upon intrinsic and environmental stimulus. Insight into the mechanism of synapse assembly is critical to our understanding of the nervous system and neurological diseases. In this study, by using the well-established model organism, Drosophila melanogaster, I aimed to gain further insight into the important regulatory components involved in synapse development. In particular, serine-threonine kinase Akt, heparan sulfate proteoglycans (HSPGs) and genes affecting cytoskeleton organization were investigated for their functions in the assembly of postsynaptic specializations. Akt is an integral element of phosphatidylinositide 3-Kinase (PI3K)-Target of Rapamycin (TOR)-Ras homolog enriched in brain (Rheb) signaling, a pathway that known to affect synapse assembly in both vertebrates and Drosophila. In this work, the role of Akt in synapse assembly has been examined at the Drosophila neuromuscular junction (NMJ), a glutamatergic synapse that displays developmental and activity-dependent plasticity. The single Drosophila Akt family member, Akt1 selectively altered the postsynaptic targeting of one glutamate receptor subunit, GluRIIA, and was required for the expansion of a specialized postsynaptic membrane compartment, the subsynaptic reticulum (SSR). A novel function of heparan sulfate-modified proteoglycans at the postsynaptic muscle cells has been identified as regulating a cellular membrane trafficking event, autophagy. HSPGs are a ubiquitous class of macromolecules that play important roles in molecular signaling and morphogen distribution in the extracellular spaces. Loss of HS-biosynthesis in the muscle cell disrupted the organization of SSR, and produced changes in mitochondrial morphology and numbers. Molecular and genetic findings showed these phenotypes were resulted from inappropriate activation of autophagy. Reducing autophagy in animals with globally compromised HS biosynthesis partially rescued the associated lethality, showing that autophagy is critically affected by HS production. Further evidence showed that HSPGs control autophagy via regulation of PI3K, a downstream mediator of a number of growth factors. A forward genetic screen was performed in our lab, designed to identify potential Akt1 downstream effectors and other novel genes required for synapse assembly. DnaJ2 (CG10565) and Acinus were identified for their specific requirements in the regulation of glutamate receptor composition and postsynaptic membrane organization respectively. Further experiments revealed that Acinus mediates autophagosome maturation. Animals defective for autophagy exhibited disorganization of both SSR membrane structures and α-Spectrin networks, suggesting that autophagy may affect synapse… Advisors/Committee Members: Scott Brian Selleck, Dissertation Advisor/Co-Advisor, Scott Brian Selleck, Committee Chair/Co-Chair, Bernhard Luscher, Committee Member, Richard W Ordway, Committee Member, Zhi Chun Lai, Committee Member.

Subjects/Keywords: synapse development; GluRIIA localization; subsynaptic reticulum; Akt; heparan sulfate proteolycan; autophagy; Acinus; spectrin

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

APA (6^th Edition):

Zhao, N. (2014). Investigation of the molecular genetics of Drosophila synapse assembly. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/22720

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhao, Na. “Investigation of the molecular genetics of Drosophila synapse assembly.” 2014. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/22720.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhao, Na. “Investigation of the molecular genetics of Drosophila synapse assembly.” 2014. Web. 14 Apr 2021.

Vancouver:

Zhao N. Investigation of the molecular genetics of Drosophila synapse assembly. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/22720.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhao N. Investigation of the molecular genetics of Drosophila synapse assembly. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/22720

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

2. Chen, Li. Investigation of the molecular basis underlying a multi-step model of axon injury responses.

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/26347

► Neurons are susceptible to a range of genetic and environmental insults. The ability to survive and recover from these insults is critical to maintaining a… (more)

▼ Neurons are susceptible to a range of genetic and environmental insults. The ability to survive and recover from these insults is critical to maintaining a healthy and functional nervous system. The goal of my study is to identify the molecular and cellular mechanisms behind two axon injury responses, self-protection and axon regeneration, and study the relationship between the two. I have established a conditioning lesion assay in Drosophila larval sensory neurons to identify an endogenous protective response. I have discovered that traumatic axon injury protects dendrites against a secondary injury, and this protection requires DLK-JNK-fos-dependent upregulation of microtubule dynamics. Furthermore, the microtubule nucleation protein γTub23C is important for injury-induced microtubule dynamics and protection. Strikingly, this microtubule-based protection is activated in two types of chronic stresses including expressing poly-Q neurodegenerative disease proteins and compromising kinesin-3-mediated axonal transport. In both scenarios, microtubule dynamics antagonize long-term neurodegeneration. Therefore, neurons may utilize upregulated microtubule dynamics as a general survival strategy to resist a variety of acute and chronic neuronal insults. Nicotinamide mononucleotide adenylyltransferases (Nmnats) are well-established neuroprotective factors. I have found that endogenous Nmnat is required for axon injury-induced protection. Genetic analysis suggests that Nmnat is subject to positive regulation by the DLK-JNK-fos pathway and negative regulation by a caspase cascade downstream of mitochondrial fission. Together, these results reveal a high degree of signaling complexity in Nmnat regulation. Why is Nmnat so tightly regulated? Protection is an early axon injury response and axon regeneration occurs after its inactivation. Hyperactivation of Nmnat caused by JNK and fos overexpression or reduction of the initiator caspase Dronc, however, results in abnormalprotection in conjunction with axon regeneration defects. These defects can be rescued by reducing Nmnat. This suggests that (1) completion of neuroprotection is necessary for axon regeneration; (2) coordination between protection and axon regeneration relies on a tight control of Nmnat activity. In summary, my results suggest that axon injury responses can be divided into multiple steps, such as protection and regeneration, and each step involves distinct regulatory mechanisms. As a beginning effort to untangle the complex regulatory networks of this multi-step model, I have uncovered that the DLK pathway protects neurons through Nmnat and microtubules early after axon injury, and later inactivates Nmnat through mitochondrial fission and caspases to turn protection off and allow axons to regenerate. Advisors/Committee Members: Melissa Rolls, Dissertation Advisor/Co-Advisor, William O Hancock, Committee Member, Richard W Ordway, Committee Member, Douglas Cavener, Committee Member, Zhi Chun Lai, Committee Member.

Subjects/Keywords: axon regeneration; neuroprotection; microtubules; gamma-tubulin; Nmnat; DLK; JNK; fos; caspases; mitochondria

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

APA (6^th Edition):

Chen, L. (2015). Investigation of the molecular basis underlying a multi-step model of axon injury responses. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/26347

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chen, Li. “Investigation of the molecular basis underlying a multi-step model of axon injury responses.” 2015. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/26347.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chen, Li. “Investigation of the molecular basis underlying a multi-step model of axon injury responses.” 2015. Web. 14 Apr 2021.

Vancouver:

Chen L. Investigation of the molecular basis underlying a multi-step model of axon injury responses. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/26347.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen L. Investigation of the molecular basis underlying a multi-step model of axon injury responses. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/26347

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

3. Wu, Xia. Targeting and function of extrasynaptic GABAA receptors.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/16080

► γ-aminobutyric acid type-A receptors (GABAARs) are localized at both synaptic and extrasynaptic sites, mediating phasic and tonic inhibition, respectively. Although the targeting mechanism of synaptic… (more)

▼ γ-aminobutyric acid type-A receptors (GABAARs) are localized at both synaptic and extrasynaptic sites, mediating phasic and tonic inhibition, respectively. Although the targeting mechanism of synaptic GABAA receptors has been extensively studied, the exact mechanism underlying extrasynaptic GABAA-receptor targeting was not known. The primary objective of this thesis was to elucidate the targeting mechanisms for distinct GABAA receptors, with special focus on the extrasynaptic GABAA receptors. Previous studies suggest an important role of γ2 and δ subunits in synaptic versus extrasynaptic targeting of GABAARs. Here, we demonstrate differential function of α2 and α6 subunits in guiding the localization of GABAARs. To study the targeting of specific subtypes of GABAARs, we used a molecularly engineered GABAergic synapse model to precisely control the GABAA-R subunit composition. We found that in neuron-HEK cell heterosynapses, GABAergic events mediated by α2β3γ2 receptors were very fast (rise time ~2 ms), whereas events mediated by α6β3δ receptors were very slow (rise time ~20 ms). Such an order of magnitude difference in rise time could not be attributed to the minute differences in receptor kinetics. Interestingly, synaptic events mediated by α6β3 or α6β3γ2 receptors were significantly slower than those mediated by α2β3 or α2β3γ2 receptors, suggesting a differential role of α subunit in receptor targeting. This was confirmed by differential targeting of the same δ-γ2 chimeric subunits to synaptic or extrasynaptic sites, depending on whether it was co-assembled with the α2 or α6 subunit. In addition, insertion of a gephyrin-binding site into the intracellular domain of α6 and δ subunits brought α6β3δ receptors closer to synaptic sites. Therefore, the α subunits, together with the γ2 and δ subunits, play a critical role in governing synaptic versus extrasynaptic targeting of GABAARs, possibly through differential interactions with gephyrin. For the second part of this thesis, I investigated the functional interaction between synaptic and extrasynaptic GABAA receptors. Our data showed that ectopically expressing extrasynaptic α6β3δ-receptors in mouse pyramidal neurons significantly increased tonic currents, as expected. Surprisingly, the increase of tonic inhibition was accompanied with a substantial reduction of the fast synaptic GABAergic transmission, suggesting a possible homeostatic regulation of the total inhibition. Overexpressing the α6 subunit alone induced an upregulation of the δ subunit expression level, and suppressed phasic inhibition similar to that with α6β3δ subunits. Blocking all GABAA receptors after overexpressing α6β3δ subunits did not restore the level of synaptic GABAergic transmission, suggesting that receptor activation is not required for the interplay between synaptic and extrasynaptic GABAA receptors. Furthermore, insertion of a gephyrin-binding-site (GBS) into the intracellular loop of α6 and δ subunits recruited α6GBSβ3δGBS-receptors to postsynaptic sites, but failed to rescue synaptic… Advisors/Committee Members: Gong Chen, Dissertation Advisor/Co-Advisor, Bernhard Luscher, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Timothy J Jegla, Committee Member, Bruce Gluckman, Special Member.

Subjects/Keywords: extrasynaptic GABAA receptor; targeting; tonic inhibition; gephyrin; alpha subunit; delta subunit; homeostatic regulation

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

APA (6^th Edition):

Wu, X. (2012). Targeting and function of extrasynaptic GABAA receptors. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/16080

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wu, Xia. “Targeting and function of extrasynaptic GABAA receptors.” 2012. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/16080.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wu, Xia. “Targeting and function of extrasynaptic GABAA receptors.” 2012. Web. 14 Apr 2021.

Vancouver:

Wu X. Targeting and function of extrasynaptic GABAA receptors. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/16080.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wu X. Targeting and function of extrasynaptic GABAA receptors. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/16080

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

4. Sun, Chicheng. The function of neuroligin-2 in neuronal development and neuropsychiatric disorders.

Degree: 2013, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/17363

► Synapse is the functional unit for brain functions. Neuroligins are a family of cell adhesion molecules found at the postsynaptic sites of both excitatory glutamatergic… (more)

▼ Synapse is the functional unit for brain functions. Neuroligins are a family of cell adhesion molecules found at the postsynaptic sites of both excitatory glutamatergic and inhibitory GABAergic synapses. The trans-synaptic interactions between neuroligins and their presynaptic receptor neurexins regulate synapse formation and function. First, I investigated the functional defects of novel neuroligin-2 mutations linked to schizophrenia. In a cohort of 584 schizophrenia patients, we identified novel neuroligin-2 missense point mutations. Among them, I identified R215H as a loss-of-function mutation applying a heterologous GABAergic synapse induction assay. The R215H mutant was defective in mediating cell adhesion and in promoting GABAergic synapse formation. Mechanistically, the R215H mutant showed significantly reduced cell surface expression possibly due to incomplete glycosylation. My work suggests that defect in GABAergic synapse formation may be a potential risk factor for schizophrenia. In the second part of my thesis, I reported a novel function of neuroligin-2 in regulating GABA functional switch from excitation to inhibition through KCC2. KCC2 expression was significantly reduced after knockdown of neuroligin-2 by shRNA-mediated RNA interference. Knockdown of neuroligin-2 abolished GABA functional switch in developing neurons and reversed GABA action to excitatory in mature neurons. Overexpression of shRNA proof neuroligin-2 rescued both decreased KCC2 expression and delayed GABA functional switch induced by shRNAs. Using gramicidin-perforated patch clamp recordings, I further demonstrated that neuroligin-2 expression level directly regulates GABA equilibrium potential. In addition, I showed that KCC2 overexpression rescued glutamatergic synapse loss induced by knockdown of neuroligin-2, suggesting that neuroligin-2 regulates glutamatergic synapses through KCC2. In summary, my findings uncovered a new function of neuroligin-2 in regulating GABA functional switch and glutamatergic synapse formation. Therefore, in addition to its conventional role of cell adhesion at GABAergic synapses, neuroligin-2 may serve as a master regulator in balancing excitation and inhibition in the brain. Dysfunctions of neuroligin-2 may cause excitation/inhibition imbalance and contribute to the etiology of neuropsychiatric disorders, as indicated by the case of neuroligin-2 R215H mutant in schizophrenia. Advisors/Committee Members: Gong Chen, Dissertation Advisor/Co-Advisor, Douglas Cavener, Committee Chair/Co-Chair, Zhi Chun Lai, Committee Member, Richard W Ordway, Committee Member, Rick Owen Gilmore, Committee Member.

Subjects/Keywords: Neuroligin; Synapse; GABA; Schizophrenia; KCC2

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

APA (6^th Edition):

Sun, C. (2013). The function of neuroligin-2 in neuronal development and neuropsychiatric disorders. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/17363

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sun, Chicheng. “The function of neuroligin-2 in neuronal development and neuropsychiatric disorders.” 2013. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/17363.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sun, Chicheng. “The function of neuroligin-2 in neuronal development and neuropsychiatric disorders.” 2013. Web. 14 Apr 2021.

Vancouver:

Sun C. The function of neuroligin-2 in neuronal development and neuropsychiatric disorders. [Internet] [Thesis]. Penn State University; 2013. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/17363.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sun C. The function of neuroligin-2 in neuronal development and neuropsychiatric disorders. [Thesis]. Penn State University; 2013. Available from: https://submit-etda.libraries.psu.edu/catalog/17363

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

5. Mattie, Floyd J. Kinesin-2 and +TIP dependent directed growth maintains the uniformly polarized microtubule array in Drosophila dendrites.

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12542

► In many differentiated cells microtubules are organized into polarized noncentrosomal arrays, yet few mechanisms that control the formation or maintenance of these arrays have been… (more)

▼ In many differentiated cells microtubules are organized into polarized noncentrosomal arrays, yet few mechanisms that control the formation or maintenance of these arrays have been identified. To study such arrays, I have utilized Drosophila dendritic arborization (da) neurons. These neurons have a polarized cytoskeleton that consists of two types of noncentrosomal arrays. Both the axonal and dendritic microtubule arrays consist of uniformly oriented microtubules, but the microtubules of the axon are oriented with plus-ends outward, while the microtubules of the dendrite are oriented with plus-ends inward. We have identified a novel mechanism that allows for the maintenance of uniform microtubule polarity in the branched dendrites of these highly polarized cells. All plus-ends in these dendrites grow towards the cell body. Thus, to maintain uniform microtubule polarity in dendrites, I hypothesized that the direction of microtubule growth must be controlled at branch points. Undirected growth through branch points would disrupt the uniform polarity, as growing microtubules could turn either towards or away from the cell body at each branch. To test this hypothesis, I have used whole, live Drosophila larvae for imaging growing microtubule plus-ends tagged with EB1-GFP in dendritic arborization (da) neurons. I have found that growing microtubules navigate dendrite branch points by turning the same direction 98% of the time. Observation of the plus-end behavior led to the hypothesis that growing plus-ends may be guided along pre-existing tracks of some sort. A UAS-EB1-RFP fly line was generated to test this hypothesis, and I found that the paths of growing plus-ends aligned with stable microtubule tracks. We named this phenomenon directed microtubule growth. Next, candidate proteins that may be involved in directed microtubule growth were targeted. A combination of RNAi, mutant, and dominant negative phenotypic analyses indicated that Kinesin-2 (KIF3), and the +TIPS, EB1 and APC (adenomatous polyposis coli), are required for uniform microtubule polarity specifically in dendrites. Additionally, I have investigated the extent to which dendritic geometry can compensate for disrupted directed growth. I found that in the comb dendrite of the ddaE class I da neuron uniform polarity can be more severely disrupted than in other da neurons. An analysis of the dendritic branching patterns revealed that the comb dendrite’s geometry created less of an inward bias, and thus microtubule growth was more easily randomized by disrupting the directed growth machinery. I also have shown that the Kinesin-2 subunit Kap3 can physically interact with Apc, Apc with Apc2, and Apc with EB1. Furthermore, I have found that GFP-Apc2 is highly enriched at dendritic branch points. I hypothesized that Apc would behave in the same manner, and so created UAS-GFP-Apc and UAS-RFP-Apc transgenic fly lines to test this hypothesis. Only when co-expressed with GFP-Apc2 was RFP-Apc localized to the branch points. Thus the over-expression of GFP-Apc2 can… Advisors/Committee Members: Melissa Rolls, Dissertation Advisor/Co-Advisor, Melissa Rolls, Committee Chair/Co-Chair, Wendy Hanna Rose, Committee Member, Graham Hugh Thomas, Committee Member, Lorraine C Santy, Committee Member, Richard W Ordway, Committee Member.

Subjects/Keywords: dendrite; polarity; microtubule; Kinesin-2; +TIP; neuron; APC; adenomatous polyposis coli; EB1; noncentrosomal

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APA (6^th Edition):

Mattie, F. J. (2011). Kinesin-2 and +TIP dependent directed growth maintains the uniformly polarized microtubule array in Drosophila dendrites. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12542

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Mattie, Floyd J. “Kinesin-2 and +TIP dependent directed growth maintains the uniformly polarized microtubule array in Drosophila dendrites.” 2011. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/12542.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Mattie, Floyd J. “Kinesin-2 and +TIP dependent directed growth maintains the uniformly polarized microtubule array in Drosophila dendrites.” 2011. Web. 14 Apr 2021.

Vancouver:

Mattie FJ. Kinesin-2 and +TIP dependent directed growth maintains the uniformly polarized microtubule array in Drosophila dendrites. [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/12542.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Mattie FJ. Kinesin-2 and +TIP dependent directed growth maintains the uniformly polarized microtubule array in Drosophila dendrites. [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12542

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

6. Zhang, Yifan. INVESTIGATION OF FUNCTION AND REGULATORY MECHANISM OF GENES CONTROLLING TISSUE GROWTH IN DROSOPHILA MELANOGASTER.

Degree: 2016, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/h702q637s

► The regulatory mechanism of tissue growth and organ size control in multicellular organisms is a long-standing question in developmental biology. It is known that proper… (more)

▼ The regulatory mechanism of tissue growth and organ size control in multicellular organisms is a long-standing question in developmental biology. It is known that proper organ size is determined by coordination of cell proliferation, cell apoptosis and cell growth, whereas how these processes are integrated and regulated is still under exploration. Previous studies have identified various genes and signaling pathways regulating tissue growth. In this dissertation, by using the well-established model organism, Drosophila melanogaster, I investigated the function and regulatory mechanism of different genes and pathways in controlling tissue growth in three different projects. In the first project, the function of a novel gene, Drosophila defender against apoptotic cell death 1 (dDad1), in regulating tissue growth and cell apoptosis is discussed. Loss of dDad1 decreases organ size due to induction of cell apoptosis and suppression of cell proliferation. Our study reveals that two important signaling pathways, c-Jun kinase (JNK) pathway and UPR pathway, Perk-Atf4 branch in particular, are essential for cell apoptosis induced by dDad1 knockdown. Moreover, as a homologue of human DAD1, which is a subunit of oligosaccharide transferases (OST) complex, Drosophila Dad1 is also found to involve in N-glycosylation, and lack of dDad1 may lead to tissue growth defect through OST complex. In addition, cell compensatory proliferation was observed in our model and Perk-Atf4 signaling appears to play an essential role in promoting proliferation of neighboring cells to maintain the tissue homeostasis. Collectively, this study demonstrates the function and regulatory mechanism of a novel gene, dDad1, in cell apoptosis and compensatory proliferation, providing further insight in tissue growth and homeostasis regulation in Drosophila. The second project aims to improve understanding of the role of microRNA bantam in growth control. In Drosophila, bantam has been identified as an important growth regulator through suppressing cell apoptosis and enhancing cell proliferation. Bioinformatics tools predict mats, which is a core component of growth suppressive pathway Hippo signaling, as a potential target of miRNA bantam. Since miRNAs are negative regulators of gene expression, the level of Mats is supposed to be downregulated by bantam. However, we found that microRNA ban upregulates Mats protein level in both developing tissues and cell lines of Drosophila. Further genetic experiment supports that bantam acts to enhance mats function. Our data suggest a model that miRNA bantam increases Mats protein level through an unidentified factor that may affect its protein stability. In the third project, we found that protein kinase A (Pka), an important growth regulator, regulates Hippo pathway activity. In Drosophila, loss of Pka-C1, a catalytic subunit of Pka, promotes cell proliferation and induces supernumerary wing tissue, while overexpressing Pka-C1 stimulates cell apoptosis and decreases wing size. We found that Hippo pathway… Advisors/Committee Members: Zhi-Chun Lai, Dissertation Advisor/Co-Advisor, Yanming Wang, Committee Chair/Co-Chair, Robert Paulson, Committee Member, Richard W Ordway, Committee Member, Wendy Hanna-Rose, Outside Member.

Subjects/Keywords: growth control; cell apoptosis; ER stress; JNK signaling; Hippo signaling

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

APA (6^th Edition):

Zhang, Y. (2016). INVESTIGATION OF FUNCTION AND REGULATORY MECHANISM OF GENES CONTROLLING TISSUE GROWTH IN DROSOPHILA MELANOGASTER. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/h702q637s

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhang, Yifan. “INVESTIGATION OF FUNCTION AND REGULATORY MECHANISM OF GENES CONTROLLING TISSUE GROWTH IN DROSOPHILA MELANOGASTER.” 2016. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/h702q637s.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhang, Yifan. “INVESTIGATION OF FUNCTION AND REGULATORY MECHANISM OF GENES CONTROLLING TISSUE GROWTH IN DROSOPHILA MELANOGASTER.” 2016. Web. 14 Apr 2021.

Vancouver:

Zhang Y. INVESTIGATION OF FUNCTION AND REGULATORY MECHANISM OF GENES CONTROLLING TISSUE GROWTH IN DROSOPHILA MELANOGASTER. [Internet] [Thesis]. Penn State University; 2016. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/h702q637s.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang Y. INVESTIGATION OF FUNCTION AND REGULATORY MECHANISM OF GENES CONTROLLING TISSUE GROWTH IN DROSOPHILA MELANOGASTER. [Thesis]. Penn State University; 2016. Available from: https://submit-etda.libraries.psu.edu/catalog/h702q637s

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

7. Guo, Ziyuan. In Vivo Reprogramming for �Brain Repair.

Degree: 2015, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/26399

► Neuronal loss accompanying reactive gliosis and scarring is the major cause of dysfunction after brain injury and in neurodegenerative disorders, which are difficult to reverse… (more)

▼ Neuronal loss accompanying reactive gliosis and scarring is the major cause of dysfunction after brain injury and in neurodegenerative disorders, which are difficult to reverse with existing treatment approaches. Besides loss of neurons, gliosis is a common pathological process after brain injury, involving the activation of glial cells to proliferate and become hypertrophic to occupy the injured brain areas. Glial scar inhibits brain functional recovery. The primary objective of this thesis is to demonstrate the proof-of-concept that converting reactive glial cells into functional neurons in injured or diseased brain may provide a potential new approach for brain repair. Glial cells, including astrocytes, NG2 cells, and microglia, undergo reactive response to injury in order to form a defense system against the invasion of micro-organisms and cytotoxins into surrounding tissue. However, once activated, many reactive glial cells will stay in the injury sites and secrete neuroinhibitory factors to prevent neuronal growth, eventually forming glial scar inside the brain. So far, there is little success in the attempt to reverse glial scar after its formation. My recent work demonstrates that reactive glial cells in the cortex of stab-injured or Alzheimer’s disease (AD) model mice can be directly reprogrammed into functional neurons in vivo, through retroviral expression of a single neural transcription factor, NeuroD1 (Guo et al., 2014). Cortical slice recordings revealed both spontaneous and evoked synaptic responses in NeuroD1-converted-neurons, suggesting that they can integrate into local neural circuits. NeuroD1 expression was also able to reprogram cultured human cortical astrocytes into functional neurons. My studies therefore suggest that direct reprogramming of reactive glial cells into functional neurons in vivo could provide a possible approach for repair of injured or diseased brain. The majority of astrocyte-converted neurons are glutamatergic, raising a concern whether in vivo reprogramming might tilt the excitation-inhibition (E/I) balance. Therefore, we further demonstrate that co-expression of NeuroD1 with another neural transcriptional factor Dlx2 efficiently reprograms NG2 glial cells into GABAergic neurons both in vitro and in vivo. Interestingly, the NG2-converted GABAergic neurons in the striatum are different from those converted in the prefrontal cortex, suggesting a regional influence on in vivo reprogramming. Brain slice recordings show that the NG2-converted GABAergic neurons are fully functional, with some firing fast-spiking action potentials, a characteristic feature of parvalbumin interneurons. More importantly, we have regenerated both excitatory and inhibitory neurons in the same cortical region by reprogramming astrocytes into glutamatergic neurons and NG2 cells into GABAergic neurons. Thus, my studies demonstrate that different glial cells can be reprogrammed into distinct subtypes of neurons to keep E/I balance and help functional recovery. Although cellular reconstruction by direct… Advisors/Committee Members: Gong Chen, Dissertation Advisor/Co-Advisor, Richard W Ordway, Committee Member, Timothy J Jegla, Committee Member, Yingwei Mao, Committee Member, Na Xiong, Committee Member.

Subjects/Keywords: In vivo reprogramming; Brain repair; NeuroD1; Dlx2; E/I balance; Long-range projection; Reactive gliosis

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

APA (6^th Edition):

Guo, Z. (2015). In Vivo Reprogramming for �Brain Repair. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/26399

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Guo, Ziyuan. “In Vivo Reprogramming for �Brain Repair.” 2015. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/26399.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Guo, Ziyuan. “In Vivo Reprogramming for �Brain Repair.” 2015. Web. 14 Apr 2021.

Vancouver:

Guo Z. In Vivo Reprogramming for �Brain Repair. [Internet] [Thesis]. Penn State University; 2015. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/26399.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Guo Z. In Vivo Reprogramming for �Brain Repair. [Thesis]. Penn State University; 2015. Available from: https://submit-etda.libraries.psu.edu/catalog/26399

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

8. Wang, Rong. PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells.

Degree: 2014, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/21417

► Insulin synthesis and secretion, as well as cell proliferation are under tight regulation in pancreatic β-cells to maintain glucose homeostasis. Dysfunction in any of these… (more)

▼ Insulin synthesis and secretion, as well as cell proliferation are under tight regulation in pancreatic β-cells to maintain glucose homeostasis. Dysfunction in any of these aspects leads to development of diabetes. PERK (EIF2AK3) is essential for normal development and function of the insulin-secreting β-cell. Genetic ablation of PERK in humans and mice results in permanent neonatal diabetes featuring insufficient β-cell mass, impaired insulin synthesis and ablated insulin secretion. However, previous attempts to identify the primary functions of PERK were confounded by those severe abnormalities within PERK-deficient β-cells. Here, I used a newly developed and highly specific inhibitor of PERK to determine the immediate effects of acute PERK activity inhibition. Stimulated subcellular Ca2+ signaling and insulin secretion in human and rodent β-cells was found to be rapidly reduced as a consequence of acute inhibition of PERK. These PERK-dependent dysfunctions stem from alterations in store-operated Ca2+ entry, sarcoplasmic-endoplasmic reticulum Ca2+ ATPase activity, and possibly some of the transient receptor potential channels. I also found that PERK regulates calcineurin, and pharmacological inhibition of calcineurin results in similar defects on stimulus-secretion coupling. My findings by using PERK inhibitor demonstrate that PERK acutely regulates β-cell Ca2+ signaling and insulin secretion. In addition, I used an alternative strategy to identify the primary functions of PERK by examining mice with one copy of the loss-of function Perk mutation (Perk heterozygous mice). Longitudinal studies were conducted to assess serum glucose and insulin, intracellular insulin synthesis and storage, insulin secretion, and β-cell proliferation in Perk heterozygous mice. I found that Perk heterozygous mice first exhibited elevated proinsulin synthesis, changes in ER chaperone expression, and enhanced insulin secretion during neonatal and juvenile development, followed by enhanced β-cell proliferation and a substantial increase in β-cell mass at the adult stage. These effects of Perk heterozygosity are opposite to what has been learned from previously studies using Perk knockout mice and therefore suggest an inverted U-shaped dose effect on insulin production and secretion with half-dosage (Perk heterozygotes) defining the maximum. Moreover, because commonly used sensitive markers for ER stress were not differentially expressed in Perk heterozygous mice, these PERK-dependent differences are not likely to entail the well-known function of PERK in ER stress response. Taken together my thesis work suggests that PERK has two major functions in the pancreatic β-cells: 1) acutely regulating insulin secretion through modulation of Ca2+ dynamics in a calcineurin-dependent pathway; and 2) impacting proinsulin folding and quality control in a longer-term through modulation of ER chaperone expression. These two major functions of PERK coordinate with each other and influence whole-body insulin production and glucose… Advisors/Committee Members: Douglas Cavener, Dissertation Advisor/Co-Advisor, Zhi Chun Lai, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Gong Chen, Committee Member, Melissa Rolls, Committee Member.

Subjects/Keywords: PERK eIF2alpha kinase; Ca2+ dynamics; insulin secretion; insulin biosynthesis; diabetes; ER stress; beta cell proliferation

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

APA (6^th Edition):

Wang, R. (2014). PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/21417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wang, Rong. “PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells.” 2014. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/21417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wang, Rong. “PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells.” 2014. Web. 14 Apr 2021.

Vancouver:

Wang R. PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/21417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wang R. PERK eIF2alpha kinase regulates cell proliferation, insulin synthesis and secretion in pancreatic beta cells. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/21417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

9. Khanna, Mansi Rajendra. ROLE OF THE SPECTRIN BASED MEMBRANE SKELETON IN PLASMA MEMBRANE PROTEIN PRESENTATION: A PROTEOMIC APPROACH.

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/11976

► The plasma membrane (PM) and its associated proteins play an important role in determining how a cell interacts with its neighbours as well as how… (more)

▼ The plasma membrane (PM) and its associated proteins play an important role in determining how a cell interacts with its neighbours as well as how it responds to the components of, and conditions in the extracellular environment. As a reflection of this, more than 50% of the current drug targets lie at the cell surface. The amount of a protein at the cell surface is determined by its rate of delivery, internalization, recycling and degradation. All these parameters are subject to change under normal physiological adjustments, development, varying environmental influences and pathological conditions. The spectrin based membrane skeleton (SBMS) is a ubiquitous feature of all metazoan cells. This network of spectrin and associated proteins is attached directly or indirectly to plasma membrane proteins. Among the numerous functions of the SBMS, are roles in protein trafficking and turnover that determine levels of plasma membrane proteins. Regulated spectrin proteolysis, mediated by calpain, occurs under normal physiological conditions for various cellular processes, including establishment of synaptic contacts, long-term potentiation and platelet activation. Spectrin cleavage is also observed in age-related pathologies such as stroke and other ischemic events, Alzheimer’s and Parkinson’s diseases. However, little is known about the consequences of spectrin breakdown per se under these conditions. The goal of this work is to establish the fruit fly, Drosophila melanogaster as model system for some aspects of ischemic stroke, of which spectrin breakdown is a hallmark. The hypothesis being tested in this work is that disruption of the SBMS will affect the levels of many proteins at the cell surface under pathological conditions. The significance of this with respect to an ischemic stroke is that changes in levels of cell surface proteins in the event of SBMS breakdown need to be compensated for in post-stroke drug therapies and rehabilitation. In order to observe changes in the cell surface proteome under SBMS breakdown, one would first need to establish what it looks in normal conditions. Towards this, I developed a technique to isolate pure PM that employs a unique combination of density gradient centrifugation and aqueous two-phase affinity partitioning (2PAP). Density gradient centrifugation is an accepted method of fractionation on the basis of the buoyant densities of biomolecules and organelles but results in an overlap in cellular compartments due to similarities in densities. 2PAP is an established method for PM isolation in vertebrate model systems and makes use of the glycosylation pattern of PM proteins to isolate them from those in other compartments. My work demonstrates that a novel combination of both the techniques results in a robust PM preparation, which neither technique can achieve on its own. Using the new technique, 432 proteins were identified from Drosophila heads by MudPIT, of which 22% were found to be known PM residents and 34% are currently unassigned to any compartment and represent candidate… Advisors/Committee Members: Graham Hugh Thomas, Dissertation Advisor/Co-Advisor, Graham Hugh Thomas, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Hong Ma, Committee Member, Melissa Rolls, Committee Member, Bruce A Stanley, Committee Member.

Subjects/Keywords: spectrin; proteomics

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

APA (6^th Edition):

Khanna, M. R. (2011). ROLE OF THE SPECTRIN BASED MEMBRANE SKELETON IN PLASMA MEMBRANE PROTEIN PRESENTATION: A PROTEOMIC APPROACH. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/11976

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Khanna, Mansi Rajendra. “ROLE OF THE SPECTRIN BASED MEMBRANE SKELETON IN PLASMA MEMBRANE PROTEIN PRESENTATION: A PROTEOMIC APPROACH.” 2011. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/11976.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Khanna, Mansi Rajendra. “ROLE OF THE SPECTRIN BASED MEMBRANE SKELETON IN PLASMA MEMBRANE PROTEIN PRESENTATION: A PROTEOMIC APPROACH.” 2011. Web. 14 Apr 2021.

Vancouver:

Khanna MR. ROLE OF THE SPECTRIN BASED MEMBRANE SKELETON IN PLASMA MEMBRANE PROTEIN PRESENTATION: A PROTEOMIC APPROACH. [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/11976.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Khanna MR. ROLE OF THE SPECTRIN BASED MEMBRANE SKELETON IN PLASMA MEMBRANE PROTEIN PRESENTATION: A PROTEOMIC APPROACH. [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/11976

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

10. Singh, Yogesh. Investigation of Serotonin Transmission using Electroanalytical Methods .

Degree: 2011, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/12021

► Serotonin (5-hydroxytryptamine; 5-HT) functions as a signaling molecule throughout the brain and in many peripheral tissues. The serotonin system regulates a diverse array of biological… (more)

▼ Serotonin (5-hydroxytryptamine; 5-HT) functions as a signaling molecule throughout the brain and in many peripheral tissues. The serotonin system regulates a diverse array of biological functions, including mood, anxiety states, cognition, reward-related behavior, motor function, gut motility, and appetitive behavior, among many others. Treatment of neuropsychiatric disorders using drugs that directly affect serotonin transmission has provided evidence for the involvement of the serotonin system in generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, and major depressive disorder. The focus of this thesis is on investigating serotonin neurotransmission as it relates to the etiology and treatment of these disorders. Currently, the most widely studied variant in psychiatric genetics is the 5 hydroxytryptamine transporter-linked polymorphic region (5-HTTLPR). This commonly occurring polymorphism has been linked to differences in trait anxiety, heightened stress responsiveness, susceptibility to depression, and variable treatment responsiveness. The human 5-HTTLPR is hypothesized to alter serotonin transmission whereby the short variant, a 43-base pair deletion in the promoter region, leads to reduced transcriptional efficiency resulting in lower SERT mRNA levels, decreased SERT expression, reduced serotonin reuptake, and increases in extracellular serotonin. Moreover, it has been suggested that higher levels of extracellular serotonin, particularly during key developmental periods, alter activation of postsynaptic receptors and downstream targets, ultimately leading to changes in the neural circuitry that modulate anxiety and mood. However, studies on the effects of the 5-HTTLPR in have produced conflicting results, possibly because of the influence of additional polymorphisms in the human serotonin transporter (SERT) gene, factors affecting in study design, and measurement issues. Rhesus macaques express an evolutionarily related SERT gene polymorphism termed the rh5-HTTLPR. At present, no other polymorphisms in the promoter region of the rhesus SERT gene have been identified suggesting that this animal model provides a means to study directly the influence of the 5-HTTLPR on serotonin neurotransmission. One of the goals of this thesis was to elucidate the effect of the 5-HTTLPR on serotonin transmission in rhesus peripheral blood lymphocytes (PBLs). We investigated rhesus PBLs because they express the same SERT gene as neurons and glia in the central nervous system. Additionally, we wanted to begin to investigate whether peripheral cells, such as lymphocytes, can be used as surrogates of SERT function in the brain. We utilized high-speed chronoamperometry to measure serotonin transport because this technique provides kinetically resolved measurements of uptake with the sensitivity to detect small but biologically relevant changes in transporter function. However, one of the problems associated with serotonin measurements in biological samples using carbon fiber microelectrode (CFM)… Advisors/Committee Members: Dr Anne M Andrews, Dissertation Advisor/Co-Advisor, Anne M Andrews, Committee Chair/Co-Chair, Paul S Weiss, Committee Chair/Co-Chair, Andrew Ewing, Committee Member, Richard W Ordway, Committee Member.

Subjects/Keywords: Boron-doped diamond electrode; 5-HTTLPR; Carbon fiber Voltammetry; Electrochemistry; Serotonin Transporter; Electrode Coating

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

APA (6^th Edition):

Singh, Y. (2011). Investigation of Serotonin Transmission using Electroanalytical Methods . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/12021

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Singh, Yogesh. “Investigation of Serotonin Transmission using Electroanalytical Methods .” 2011. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/12021.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Singh, Yogesh. “Investigation of Serotonin Transmission using Electroanalytical Methods .” 2011. Web. 14 Apr 2021.

Vancouver:

Singh Y. Investigation of Serotonin Transmission using Electroanalytical Methods . [Internet] [Thesis]. Penn State University; 2011. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/12021.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Singh Y. Investigation of Serotonin Transmission using Electroanalytical Methods . [Thesis]. Penn State University; 2011. Available from: https://submit-etda.libraries.psu.edu/catalog/12021

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

11. Deng, Yaoting. Regulation of Hippo Signaling for Growth Control.

Degree: 2014, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/23417

► In multicellular organisms, the coordination of cell proliferation, cell death and cellular growth are crucial for the organ size control and the maintenance of organ… (more)

▼ In multicellular organisms, the coordination of cell proliferation, cell death and cellular growth are crucial for the organ size control and the maintenance of organ function. The mechanisms that regulate these crucial processes provide insight into diseases, such as cancer. The Hippo (Hpo) signaling regulates cell number mainly by inhibiting cell proliferation and promoting cell apoptosis, and this signaling is highly conserved from Drosophila to mammals. Hpo is the key kinase of Hpo signaling; however, the way in which Hpo kinase activity is regulated remains less understood. In this project, I investigated how Hpo kinase is activated and regulated by upstream molecules both in vivo and in vitro. I found that Hpo dimerization could facilitate its activation by auto-phosphorylation. Moreover, membrane association appears to increase Hpo dimerization efficiency, and upstream molecules Expanded/Merlin/Kibra promote Hpo membrane association. Therefore, both dimerization and membrane association are critical for Hpo kinase to be activated. This mechanism provides essential insight to reveal the mystery that how upstream molecules transduce signal to Hpo signaling. In another project, I investigated Yap1 (a major downstream effector of mammalian Hpo signaling) activity regulation in mammalian pancreatic beta β-cells under free fatty acids (FFAs) treatment. Mammalian pancreatic β-cells are responsible for the production of insulin and therefore play a pivotal role in development and glucose homeostasis. Among many factors, high concentrations of saturated free fatty acids (FFAs) such as palmitate are known to have a negative effect on β-cell viability, which might induce type 2 diabetes. In this study, I demonstrated that Hpo signaling effector Yap1 plays a crucial role in regulating β-cell survival under FFA treatment. I found that Yap1 is activated through F-actin accumulation in a time-delayed manner to enhance β-cells viability during palmitate-induced apoptosis. Moreover, Connective Tissue Growth Factor (CTGF), one of the downstream targets of Yap1, was identified to repress palmitate-induced β-cell apoptosis. These discoveries support a model in which Yap1 could positively regulate β-cell survival under FFA treatment, and this model might lead to the development of new strategies for potential treatment of diabetes. Advisors/Committee Members: Zhi Chun Lai, Dissertation Advisor/Co-Advisor, Zhi Chun Lai, Committee Chair/Co-Chair, Melissa Rolls, Committee Member, Pamela Hankey Giblin, Committee Member, Richard W Ordway, Committee Member, Wendy Hanna Rose, Committee Member, Yanming Wang, Committee Member.

Subjects/Keywords: Hippo pathway; Hippo; transphosphorylation; dimerization; Merlin; Expanded; Kibra; FFA; β-cells; Yap; F-actin; apoptosis

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

APA (6^th Edition):

Deng, Y. (2014). Regulation of Hippo Signaling for Growth Control. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/23417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Deng, Yaoting. “Regulation of Hippo Signaling for Growth Control.” 2014. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/23417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Deng, Yaoting. “Regulation of Hippo Signaling for Growth Control.” 2014. Web. 14 Apr 2021.

Vancouver:

Deng Y. Regulation of Hippo Signaling for Growth Control. [Internet] [Thesis]. Penn State University; 2014. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/23417.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Deng Y. Regulation of Hippo Signaling for Growth Control. [Thesis]. Penn State University; 2014. Available from: https://submit-etda.libraries.psu.edu/catalog/23417

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

12. Fetchko, Michael John. MOLECULAR GENETIC ANALYSIS OF DROSOPHILA EYE DEVELOPMENT: INVESTIGATION OF A LEUCINE-RICH REPEAT PROTEIN'S ROLE IN CELL-CELL COMMUNICATION.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/5931

► Abstract Within this thesis I report the identification and isolation of loss-of-function mutations in the Drosophila gp150 gene; a gene required for viability, fertility, and… (more)

▼ Abstract Within this thesis I report the identification and isolation of loss-of-function mutations in the Drosophila gp150 gene; a gene required for viability, fertility, and proper development of the eye, wing, and sensory organs. Gp150 encodes an ~150kd transmembrane protein with an extracellular domain composed of 18 Leucine-rich repeat (LRR) domains and a short cytoplasmic domain containing three conserved tyrosine phosphorylation motifs (Tian and Zinn, 1994; Dhulkotia, 2000). Structural analysis of Gp150 suggests a requirement of both the extracellular and cytoplasmic domain for Gp150 activity. In the eye, removal of gp150 function causes defects in the refinement of R8 cells and the subsequent recruitment of cells into ommatidial clusters leading to the formation of adult eyes with fused ommatidia and ommatidia with too many or too few R-cells. Overexpression of gp150 causes dose dependent defects within second and third instar eye imaginal disks. Due to similarities between phenotypes produced by gp150 loss and gain of function and phenotypes produced through loss of notch signaling, genetic interactions were tested between Notch signaling components and gp150. All genetic assays tested strongly implicate gp150 as a regulator of Notch signaling. Through expression analysis, we show that Gp150 is expressed within tissues where gp150 phenotypes arise. Within the third instar eye disk, Gp150 is expressed at high levels within the morphogenetic furrow (MF) region. This expression is consistent with the proposed role of gp150 modulating Notch signaling during early ommatidial development. Expression analysis also revealed that Gp150 is localized to intracellular vesicles which co-localize with the Notch ligand Delta within cells of the MF. These vesicles are most likely endosomes as Gp150 was shown to co-localize with the late endosomal markers DRab7. Therefore, it is proposed that Gp150 modulates the Notch pathway through endocytic trafficking. Advisors/Committee Members: Zhi Chun Lai, Committee Chair/Co-Chair, Esther Siegfried, Committee Member, Richard W Ordway, Committee Member, Susan Abmayr, Committee Member, Olanrewaju A Sodeinde, Committee Member.

Subjects/Keywords: DROSOPHILA; EYE DEVELOPMENT; DEVELOPMENT; TISSUE PATTERNING; NOTCH PATHWAY; CELL-CELL SIGNALING

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

APA (6^th Edition):

Fetchko, M. J. (2008). MOLECULAR GENETIC ANALYSIS OF DROSOPHILA EYE DEVELOPMENT: INVESTIGATION OF A LEUCINE-RICH REPEAT PROTEIN'S ROLE IN CELL-CELL COMMUNICATION. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/5931

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Fetchko, Michael John. “MOLECULAR GENETIC ANALYSIS OF DROSOPHILA EYE DEVELOPMENT: INVESTIGATION OF A LEUCINE-RICH REPEAT PROTEIN'S ROLE IN CELL-CELL COMMUNICATION.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/5931.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Fetchko, Michael John. “MOLECULAR GENETIC ANALYSIS OF DROSOPHILA EYE DEVELOPMENT: INVESTIGATION OF A LEUCINE-RICH REPEAT PROTEIN'S ROLE IN CELL-CELL COMMUNICATION.” 2008. Web. 14 Apr 2021.

Vancouver:

Fetchko MJ. MOLECULAR GENETIC ANALYSIS OF DROSOPHILA EYE DEVELOPMENT: INVESTIGATION OF A LEUCINE-RICH REPEAT PROTEIN'S ROLE IN CELL-CELL COMMUNICATION. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/5931.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Fetchko MJ. MOLECULAR GENETIC ANALYSIS OF DROSOPHILA EYE DEVELOPMENT: INVESTIGATION OF A LEUCINE-RICH REPEAT PROTEIN'S ROLE IN CELL-CELL COMMUNICATION. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/5931

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

13. Piontkivska, Olena. Evolution of multigene families: histone and major histocompatibility complex genes.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6047

► To understand the mode and mechanism of evolution of multigene families, I studied the evolutionary pattern of the highly conserved histone H3 and H4 and… (more)

▼ To understand the mode and mechanism of evolution of multigene families, I studied the evolutionary pattern of the highly conserved histone H3 and H4 and the highly divergent MHC gene families. (1) The primary purpose of the study of the histone H3 gene family was to investigate whether this family has evolved following the model of concerted evolution as was claimed by some previous authors. The results of the phylogenetic analysis of H3 genes from animals, plants and fungi indicated that while H3 protein sequences are highly conserved even between different kingdoms, the level of nucleotide sequence divergence at silent sites is generally very high and often close to the saturation level. These results suggest that the high degree of conservation of H3 proteins is primarily caused by purifying selection and that H3 nucleotide sequences evolve following the model of birth-and-death evolution. This study also suggested that the replication-dependent H3 genes may have evolved from the replication-independent H3 genes. (2) Histone H4 protein is among the most highly conserved proteins in eukaryotes. Statistical and phylogenetic analyses of the protein and DNA sequences of H4 genes from various organisms showed that the evolutionary pattern of this gene family is essentially the same as that of the H3 gene family. That is, the sequence homogeneity of H4 proteins is primarily caused by purifying selection, whereas nucleotide sequences evolve following the birth-and-death model of evolution. My study also indicated that all five classes of histone genes (H1, H2A, H2B, H3 and H4) were derived from archaebacteria rather than from eubacteria and that they diverged at nearly the same time before the separation of eukaryotic kingdoms, protists, plants, fungi and animals. (3) It has been suggested that MHC genes are subject to birth-and-death evolution with a high rate of gene turnover, but the rate of gene turnover has never been studied. To obtain some insight into this problem, I estimated the time of occurrence of gene duplication events that generated new MHC loci as well as the times of divergence of allelic lineages in polymorphic MHC class I loci of primate species. The results showed that one of these loci, namely locus F, diverged from the other loci about 46-66 million years ago (MYA). Other class I loci such as classical locus C in great apes and the duplicated B locus in macaques have appeared relatively recently about 21-28 MYA. The major diversification of class I loci was estimated to have occurred about 35-49 MYA, which is before the time of separation of Old World -New World monkeys. The most recent common ancestors of different allelic lineages at the A, B and C loci in humans were estimated to have appeared at least 14-19, 10-15 and 13-17 MYA, respectively. These results suggest that the rate of gene turnover in primate MHC class I genes is indeed quite rapid, as was previously conjectured. Advisors/Committee Members: Masatoshi Nei, Committee Chair/Co-Chair, Claude Walker Depamphilis, Committee Member, David Michael Geiser, Committee Member, Zhi Chun Lai, Committee Member, Richard W Ordway, Committee Member.

Subjects/Keywords: histone; H3; H4; multigene family; concerted evolution; birth-and-death evolution; purifying selection; MHC; class I; divergence time; primates

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APA (6^th Edition):

Piontkivska, O. (2008). Evolution of multigene families: histone and major histocompatibility complex genes. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6047

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Piontkivska, Olena. “Evolution of multigene families: histone and major histocompatibility complex genes.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/6047.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Piontkivska, Olena. “Evolution of multigene families: histone and major histocompatibility complex genes.” 2008. Web. 14 Apr 2021.

Vancouver:

Piontkivska O. Evolution of multigene families: histone and major histocompatibility complex genes. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/6047.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Piontkivska O. Evolution of multigene families: histone and major histocompatibility complex genes. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6047

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

14. Lee, Hyun-Gwan. ROLES OF THE OCTOPAMINE RECEPTOR OAMB IN ASSOCIATIVE LEARNING, MEMORY, AND REPRODUCTION IN DROSOPHILA MELANOGASTER .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8440

► Octopamine, a biogenic monoamine, is a major neuromodulator in invertebrates. It plays a crucial role in various adaptive behaviors and in female reproduction. To mediate… (more)

▼ Octopamine, a biogenic monoamine, is a major neuromodulator in invertebrates. It plays a crucial role in various adaptive behaviors and in female reproduction. To mediate these diverse effects, octopamine binds to specific receptors and activates distinct signal transduction pathways. The underlying intracellular mechanism, however, remains unclear. Two octopamine receptors, OAMB-K3 and OAMB-AS, are produced by alternative splicing of oamb transcripts and were distinctly characterized to activate for cAMP and intracellular calcium increases. Remarkably, both receptors are highly enriched in the mushroom bodies and the central complex of the brain, where both locations have been found to be key neural substrates for associative learning and memory. Furthermore, OAMB is expressed in the thoracico-abdominal ganglion, the female reproductive system, and mature eggs in the ovary. To explore OAMB¡¯s role in conditioned courtship as a natural form of associative learning and female reproduction, null and various hypomorphic oamb mutants were generated by P-element mediated dysgenesis. oamb null mutants were found to be viable without gross anatomical defects and oamb females displayed normal courtship and copulation behaviors. oamb null mutant males were also normal in acquisition, but were impaired in short-term memory retention for conditioned courtship behaviors. Transgenic OAMB-AS expression, driven by pan neuronal elav-GAL4, rescues the memory deficit of oamb in short-term memory retention for conditioned courtship, suggesting that neuronal OAMB-AS is crucial for this behavior. oamb null mutant females have been found to be sterile. To investigate the tissue type(s) and intracellular effectors that OAMB mediates ovulation, the GAL4/UAS binary system was employed. Transgenic oamb females, with adults ubiquitously expressing either OAMB-K3 or -AS driven by heat shock-GAL4, were fecund, indicating that OAMB plays a physiological, and not a developmental, role in ovulation. Neural OAMB expression, however, is deficient for inducing ovulation in oamb null mutant females. To identify OAMB¡¯s functional site, the enhancer GAL4 line oamb-RS-GAL4 was generated so that GAL4 could be specifically expressed in the reproductive system. Remarkably, strong oamb-RS-GAL4 expression was detectable in the oviduct epithelial cells, where endogenous OAMB is found. oamb females, with transgenic OAMB-K3 or -AS expression driven by oamb-RS-GAL4, were fully fertile, suggesting that OAMB is crucial in oviduct epithelial cells for regulating ovulation. To identify for downstream OAMB signaling molecules involved with ovulation, transgenes expressing constitutively active Ca2+/calmodulin-dependent protein kinase II (CaMKIICA), CaMKII inhibitor peptide ala, and dNOS-IR were expressed by oamb-RS-GAL4 in adult oviduct epithelial cells. Ovulation defects of oamb females were rescued by transgeneic CaMKIICA expression in adult oviduct epithelium. CaMKII inhibitor peptides ala and dNOS-IR driven by oamb-RS-GAL4, however, reduced female fecundity in a… Advisors/Committee Members: Kyung An Han, Committee Member, Richard W Ordway, Committee Member, Zhi Chun Lai, Committee Chair/Co-Chair, Graham Hugh Thomas, Committee Member, David Scott Gilmour, Committee Member.

Subjects/Keywords: octpamine receptor; OAMB; Conditioned courtship; Ovulation; CaMKII

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

APA (6^th Edition):

Lee, H. (2008). ROLES OF THE OCTOPAMINE RECEPTOR OAMB IN ASSOCIATIVE LEARNING, MEMORY, AND REPRODUCTION IN DROSOPHILA MELANOGASTER . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8440

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lee, Hyun-Gwan. “ROLES OF THE OCTOPAMINE RECEPTOR OAMB IN ASSOCIATIVE LEARNING, MEMORY, AND REPRODUCTION IN DROSOPHILA MELANOGASTER .” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/8440.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lee, Hyun-Gwan. “ROLES OF THE OCTOPAMINE RECEPTOR OAMB IN ASSOCIATIVE LEARNING, MEMORY, AND REPRODUCTION IN DROSOPHILA MELANOGASTER .” 2008. Web. 14 Apr 2021.

Vancouver:

Lee H. ROLES OF THE OCTOPAMINE RECEPTOR OAMB IN ASSOCIATIVE LEARNING, MEMORY, AND REPRODUCTION IN DROSOPHILA MELANOGASTER . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/8440.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lee H. ROLES OF THE OCTOPAMINE RECEPTOR OAMB IN ASSOCIATIVE LEARNING, MEMORY, AND REPRODUCTION IN DROSOPHILA MELANOGASTER . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8440

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

15. Wei, Jianwen. PERK IS ESSENTIAL FOR NEONATAL SKELETAL DEVELOPMENT TO REGULATE OSTEOBLAST BIOLOGY.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8441

► PERK (eukaryotic translation initiation factor 2 alpha kinase 3) is an endoplasmic reticulum (ER) resident transmembrane protein. In response to alterations of ER homeostasis, PERK… (more)

▼ PERK (eukaryotic translation initiation factor 2 alpha kinase 3) is an endoplasmic reticulum (ER) resident transmembrane protein. In response to alterations of ER homeostasis, PERK is activated to modulate specific mRNA translational upregulation as well as transient repression of global protein synthesis through phosphorylating eIF2 at serine 51. Loss-function mutations of PERK in humans and mice cause severe neonatal development defects, including diabetes, growth retardation, exocrine pancreatic atrophy and multiple skeletal dysplasias. To investigate the physiological functions of PERK in regulation of mammalian skeletal development, comprehensive analyses were carried out on tissue, cellular and molecular levels in PERK-deficient mice and Perk-/- osteoblasts. Neonatal Perk-/- mice are severely osteopenic, which is in part caused by multiple defects in osteoblasts (bone forming cells), including a deficiency in the number of mature osteoblasts, impaired osteoblast differentiation, and reduced secretion of type I collagen. Further studies showed that compromised osteoblast differentiation and maturation in the absence of PERK is associated with decreased expression of Runx2 and Osterix, two key regulators of osteoblast development. Besides the differentiation defect, the low osteoblast mass phenotype in Perk-/- mice is also caused by reduced osteoblast proliferation. Perk-/- osteoblasts exhibit slow cell cycle progression along with reduced expression of key cell cycle factors including cyclin D, cyclin E, cyclin A, Cdc2, and CDK2. In addition, abnormal retention of procollagen I within the endoplasmic reticulum and reduced mature collagen production are manifested in Perk-/- osteoblasts. The imperfect collagen biosynthesis in Perk-/- osteoblasts is coincident with compromised ATF6 and IRE1/XBP1 UPR pathways. Normal osteoblast viability, normal global protein synthesis, low procollagen synthesis rate and no upregulation of ER stress markers are observed in Perk-/- osteoblasts, suggesting that the osteoblast defects are not due to persistent activation of the classical unfolded protein response. In addition, normal expression and activity of ATF4 seen in Perk-/- osteoblasts, together with its distinct role in controlling collagen synthesis, suggests that ATF4 is not a major target of PERK in regulation of osteoblast biology. Advisors/Committee Members: Zhi Chun Lai, Committee Chair/Co-Chair, Douglas Cavener, Committee Member, Richard W Ordway, Committee Member, Carol V Gay, Committee Member, Pamela J Mitchell, Committee Member.

Subjects/Keywords: PERK; osteoblast; Runx2; procollagen; proliferation; endoplasmic reticulum

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

APA (6^th Edition):

Wei, J. (2008). PERK IS ESSENTIAL FOR NEONATAL SKELETAL DEVELOPMENT TO REGULATE OSTEOBLAST BIOLOGY. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8441

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Wei, Jianwen. “PERK IS ESSENTIAL FOR NEONATAL SKELETAL DEVELOPMENT TO REGULATE OSTEOBLAST BIOLOGY.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/8441.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Wei, Jianwen. “PERK IS ESSENTIAL FOR NEONATAL SKELETAL DEVELOPMENT TO REGULATE OSTEOBLAST BIOLOGY.” 2008. Web. 14 Apr 2021.

Vancouver:

Wei J. PERK IS ESSENTIAL FOR NEONATAL SKELETAL DEVELOPMENT TO REGULATE OSTEOBLAST BIOLOGY. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/8441.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Wei J. PERK IS ESSENTIAL FOR NEONATAL SKELETAL DEVELOPMENT TO REGULATE OSTEOBLAST BIOLOGY. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8441

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

16. Jiang, Min. FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/8546

► Endocytosis plays a fundamental role in regulating cell signaling, protein and lipid trafficking, and uptake of nutrients and pathogens in all eukaryotic cells. In astrocytes,… (more)

▼ Endocytosis plays a fundamental role in regulating cell signaling, protein and lipid trafficking, and uptake of nutrients and pathogens in all eukaryotic cells. In astrocytes, endocytosis is particularly important for the uptake of nutrients. However, the molecular mechanisms underlying astroglial endocytosis are poorly understood. Using live fluorescence imaging with FM dye, we identify a rapid and constitutive endocytosis mechanism in cultured astrocytes. The endocytic uptake of FM dye is much faster than that of transferrin and the internalized FM dye is not colocalized with clathrin, indicating a clathrin-independent endocytic pathway. Moreover, this rapid endocytosis is caveolae-independent as indicated by intact FM dye uptake after blocking caveolae formation and lack of colocalization of FM puncta and caveolin. In addition, rapid endocytosis is independent of dynamin but potently regulated by the early endosomal protein Rab5. After being internalized, FM dye is quickly sorted through early endosomes and transported to lysosomes. Interestingly, this rapid form of endocytosis is substantially regulated by intracellular Ca2+. The neural and gliotransmitters ATP and glutamate induce an increase of intracellular Ca2+ in astrocytes, which greatly enhances rapid endocytosis. Furthermore, ATP is internalized through the same endocytic pathway as FM dye. This suggests a potential feedback control of the ATP signaling pathway in astrocytes. Moreover, amyloid beta peptide also significantly increases the rapid endocytosis through increasing intracellular Ca2+ in astrocytes. These results suggest that astroglial cells posess a unique endocytic pathway that is independent of clathrin and dynamin but tightly regulated by intracellular Ca2+ in response to physiological and pathological stimuli. Advisors/Committee Members: Gong Chen, Committee Member, Bernhard Luscher, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Andrew Ewing, Committee Member, Matthew Whim, Committee Member.

Subjects/Keywords: astrocytes; endocytosis; clathrin

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

APA (6^th Edition):

Jiang, M. (2008). FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/8546

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Jiang, Min. “FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES .” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/8546.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Jiang, Min. “FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES .” 2008. Web. 14 Apr 2021.

Vancouver:

Jiang M. FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/8546.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Jiang M. FUNCTIONAL CHARACTERIZATION OF A NOVEL CLATHRIN-INDEPENDENT ENDOCYTOSIS IN ASTROCYTES . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/8546

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

17. Rohrbaugh, Margaret C. MOLECULAR AND GENETIC STUDIES OF CELLULAR REGULATORY MECHANISMS USING DROSOPHILA MELANOGASTER AS A MODEL SYSTEM.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6117

► Proper organismal development and cell survival requires integration of a number of signaling pathways and regulatory molecules. Intracellular and extracellular molecules coordinate to regulate a… (more)

▼ Proper organismal development and cell survival requires integration of a number of signaling pathways and regulatory molecules. Intracellular and extracellular molecules coordinate to regulate a number of cell functions including cell differentiation, proliferation and morphogenesis. Many of these molecules and signaling pathways are highly conserved throughout evolution. Due to this, studies in model organisms have been critical in defining the basic concepts that govern all cell functions. This thesis focuses on using Drosophila melanogaster as a model system. Drosophila has been an effective model system for nearly one hundred years helping to define the components necessary for processes such as neural and embryonic development. We demonstrate three effective uses of Drosophila. In the first study, we have identified an eye specific enhancer for the yan gene, a general inhibitor of differentiation. In the developing eye, yan is required to inhibit neuronal differentiation until proper inductive signaling is initiated. Analysis of the yan enhancer identified a regulatory mechanism involving the Notch pathway and Receptor Tyrosine Kinase (RTK) pathway mediated by the Drosophila EGF Receptor (DER). This model provides the first example where these two key pathways integrate in a competitive manner at the DNA sequence level. The second study identifies patterning and degeneration defects within the Drosophila ovary caused by mutations in gp150. In the eye, gp150 has been shown to be involved in regulating ommatidial assembly via interactions with components of the Notch pathway. Analysis of gp150’s expression pattern and mutant phenotype in the ovary indicate that it may be interacting with the Notch pathway in the ovary as well. The final study uses the eye as a model to study cell proliferation. We provide initial phenotypic characterization of a mutation in a novel tumor supressor gene. Combined, these three examples demonstrate the effectiveness of Drosophila as a model system. In particular, studies of the yan enhancer make a significant contribution to our understanding of the amount of integration required between major signaling pathways involved in cell development and differentiation. Advisors/Committee Members: Zhi Chun Lai, Committee Chair/Co-Chair, Ross Cameron Hardison, Committee Member, Richard W Ordway, Committee Member, Benjamin Franklin Pugh, Committee Member, Esther Siegfried, Committee Member.

Subjects/Keywords: Drosophila; Yan; Cell Cycle; Notch Signaling; Development; Gp150

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

APA (6^th Edition):

Rohrbaugh, M. C. (2008). MOLECULAR AND GENETIC STUDIES OF CELLULAR REGULATORY MECHANISMS USING DROSOPHILA MELANOGASTER AS A MODEL SYSTEM. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6117

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rohrbaugh, Margaret C. “MOLECULAR AND GENETIC STUDIES OF CELLULAR REGULATORY MECHANISMS USING DROSOPHILA MELANOGASTER AS A MODEL SYSTEM.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/6117.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rohrbaugh, Margaret C. “MOLECULAR AND GENETIC STUDIES OF CELLULAR REGULATORY MECHANISMS USING DROSOPHILA MELANOGASTER AS A MODEL SYSTEM.” 2008. Web. 14 Apr 2021.

Vancouver:

Rohrbaugh MC. MOLECULAR AND GENETIC STUDIES OF CELLULAR REGULATORY MECHANISMS USING DROSOPHILA MELANOGASTER AS A MODEL SYSTEM. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/6117.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rohrbaugh MC. MOLECULAR AND GENETIC STUDIES OF CELLULAR REGULATORY MECHANISMS USING DROSOPHILA MELANOGASTER AS A MODEL SYSTEM. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6117

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

18. Sombers, Leslie A. THE DETECTION AND ANALYSIS OF ‘PRESYNAPTIC’ MECHANISMS MODULATING EXOCYTOTIC NEUROTRANSMITTER RELEASE EVENTS FROM SINGLE PC12 CELLS USING AMPEROMETRY AND TRANSMISSION ELECTRON MICROSCOPY.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6272

► Understanding vesicular exocytosis is fundamental to developing insight into chemistry, biology and physics of neurotransmission. Through the direct ‘presynaptic’ observation of quantal release using amperometry… (more)

▼ Understanding vesicular exocytosis is fundamental to developing insight into chemistry, biology and physics of neurotransmission. Through the direct ‘presynaptic’ observation of quantal release using amperometry it becomes strikingly evident that the exocytotic release event is plastic and regulated by multiple mechanisms. Electrochemistry is particularly useful for these types of studies as it provides highly sensitive qualitative and quantitative information for electroactive neurochemicals that are easily oxidized or reduced. The overall goal of this thesis is to use amperometry, in conjunction with electron microscopy, for the study of exocytosis events. By combining these approaches it is possible to study exocytotic mechanisms in more detail and thus to better understand specific regulatory aspects of communication between single cells. Exocytosis has been studied by a variety of methods; however, when living cells are used it is difficult to discriminate between the molecular effects of membrane proteins and the mechanics of lipid-membrane driven processes. Thus, this thesis describes the use of a novel liposome-lipid nanotube network as an artificial cell model that undergoes the later stages of exocytosis. This model shows that membrane mechanics, even without protein intervention, are sufficient to drive the expansion of the fusion pore to the final stage of exocytosis and can affect the rate of transmitter release through the fusion pore. The bulk of this thesis describes the analysis of exocytosis at a single PC12 cells. Many spikes in amperometric records of exocytosis events from many different cell types initially exhibit a pre-spike feature, or foot, which represents a steady-state flux of neurotransmitter through a stable fusion pore spanning both the vesicle and plasma membranes and connecting the vesicle lumen to the extracellular fluid. It has been well established that the volume of secretory vesicles can be modulated. Results presented in this thesis are the first evidence indicating that vesicular volume prior to secretion is strongly correlated with the characteristics of amperometric foot events. Amperometry and transmission electron microscopy have been used to determine that as vesicle size is decreased the frequency with which foot events are observed increases, the amount and duration of neurotransmitter released in the foot portion of the event decreases, and vesicles release a greater percentage of their total contents in the foot portion of the event. These previously unidentified correlations provide new insight into how vesicle volume can modulate the activity of the exocytotic fusion pore. Amperometric data have also been collected from PC12 cells in high osmolarity saline solutions, and these data are used to further clarify the biophysical characteristics of the fusion pore. When exocytosis is measured under high osmolarity conditions, dissociation of the dense core vesicle matrix is largely inhibited and thus membrane properties and release dynamics are changed. … Advisors/Committee Members: Andrew Ewing, Committee Chair/Co-Chair, Anne M Andrews, Committee Member, Christine Dolan Keating, Committee Member, Richard W Ordway, Committee Member.

Subjects/Keywords: Fusion pore; exocytosis; amperometry; transmission electron microscopy; PC12 cells; vesicle volume; foot

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

APA (6^th Edition):

Sombers, L. A. (2008). THE DETECTION AND ANALYSIS OF ‘PRESYNAPTIC’ MECHANISMS MODULATING EXOCYTOTIC NEUROTRANSMITTER RELEASE EVENTS FROM SINGLE PC12 CELLS USING AMPEROMETRY AND TRANSMISSION ELECTRON MICROSCOPY. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6272

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sombers, Leslie A. “THE DETECTION AND ANALYSIS OF ‘PRESYNAPTIC’ MECHANISMS MODULATING EXOCYTOTIC NEUROTRANSMITTER RELEASE EVENTS FROM SINGLE PC12 CELLS USING AMPEROMETRY AND TRANSMISSION ELECTRON MICROSCOPY.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/6272.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sombers, Leslie A. “THE DETECTION AND ANALYSIS OF ‘PRESYNAPTIC’ MECHANISMS MODULATING EXOCYTOTIC NEUROTRANSMITTER RELEASE EVENTS FROM SINGLE PC12 CELLS USING AMPEROMETRY AND TRANSMISSION ELECTRON MICROSCOPY.” 2008. Web. 14 Apr 2021.

Vancouver:

Sombers LA. THE DETECTION AND ANALYSIS OF ‘PRESYNAPTIC’ MECHANISMS MODULATING EXOCYTOTIC NEUROTRANSMITTER RELEASE EVENTS FROM SINGLE PC12 CELLS USING AMPEROMETRY AND TRANSMISSION ELECTRON MICROSCOPY. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/6272.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sombers LA. THE DETECTION AND ANALYSIS OF ‘PRESYNAPTIC’ MECHANISMS MODULATING EXOCYTOTIC NEUROTRANSMITTER RELEASE EVENTS FROM SINGLE PC12 CELLS USING AMPEROMETRY AND TRANSMISSION ELECTRON MICROSCOPY. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6272

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

19. Iida, Kaori. Functions of PERK eIF2 Alpha Kinase in the Mouse Exocrine Pancreas .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6825

► The absence of PERK eIF2 alpha kinase causes a number of pathological conditions in both mice and humans. Based on cell culture experiments, it has… (more)

▼ The absence of PERK eIF2 alpha kinase causes a number of pathological conditions in both mice and humans. Based on cell culture experiments, it has been shown that PERK is activated by endoplasmic reticulum (ER) stress and subsequently represses global protein synthesis by phosphorylating its substrate, the alpha subunit of translation initiation factor 2 (eIF2 alpha). Because the general translation repression results in the reduction of newly synthesized protein entering the ER, this function of PERK has been considered as an adaptive response to the accumulation of unfolded protein in the ER (i.e., ER stress). According to the most widely stated hypothesis, the major function of PERK in vivo is also explained by this response against ER stress. This model predicts that highly secretory cells, which are assumed to have fluctuating ER stress as part of normal functions, would be unable to control translation in the absence of PERK. Consequently the Perk-/- cells would be predicted to accumulate ER stress and eventually die through apoptosis (referred as the ER stress-UPR model in this thesis). In this project, however, I have found that the absence of PERK does not result in elevated ER stress or apoptosis in pancreatic acinar cells in vivo. The Perk-/- exocrine pancreas shows pancreatitis-like phenotypes with massive oncotic cell death starting around postnatal day 19. Analyses of acinar cell-specific conditional Perk knockout mice have revealed that this phenotype is cell-autonomous to acinar cells with a very high penetrance. Contrary to what is predicted by the ER stress-UPR model, the mutant acinar cells show normal protein synthesis rates and secretion before the onset of extensive cell death. Surprisingly, ER stress marker genes are not significantly elevated either before or during the period of the cell death. Moreover, analyses on the form of cell death indicate that mutant acinar cells die through oncosis rather than apoptosis. These results suggest that a major in vivo function of PERK in pancreatic acinar cells is different from alleviation of ER stress proposed by the ER stress-UPR model. Advisors/Committee Members: Douglas Cavener, Committee Member, Diana Lynn Cox Foster, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Ross Cameron Hardison, Committee Member, Pamela J Mitchell, Committee Member.

Subjects/Keywords: acinar cells; oncosis; pancreatitis; PERK; ER stress

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

APA (6^th Edition):

Iida, K. (2008). Functions of PERK eIF2 Alpha Kinase in the Mouse Exocrine Pancreas . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6825

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Iida, Kaori. “Functions of PERK eIF2 Alpha Kinase in the Mouse Exocrine Pancreas .” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/6825.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Iida, Kaori. “Functions of PERK eIF2 Alpha Kinase in the Mouse Exocrine Pancreas .” 2008. Web. 14 Apr 2021.

Vancouver:

Iida K. Functions of PERK eIF2 Alpha Kinase in the Mouse Exocrine Pancreas . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/6825.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Iida K. Functions of PERK eIF2 Alpha Kinase in the Mouse Exocrine Pancreas . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6825

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

20. Ahn, Younwook. MOLECULAR AND GENETIC STUDIES OF TRANSCRIPTION FACTOR AP-2 IN DROSOPHILA APPENDAGE DEVELOPMENT .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6397

► Transcription factor AP-2 has essential roles in nervous system, oro-facial and limb development based on studies of Drosophila and vertebrate model organisms. Previous studies have… (more)

▼ Transcription factor AP-2 has essential roles in nervous system, oro-facial and limb development based on studies of Drosophila and vertebrate model organisms. Previous studies have shown that dAP-2, the sole AP-2 family gene in Drosophila, is expressed in leg, antennal, and labial imaginal discs (anlaga of adult legs, antennae and proboscis, respectively) in multiple domains along the proximal-distal (PD) axis of the growing appendage. In leg imaginal discs of late larvae and early pupae, dAP-2 is expressed in nine domains of epithelial cells that presage boundaries (joints) between the ten segments comprising the adult leg. Genetic analysis has established that dAP-2 is required cell-autonomously for leg joint development and non-autonomously for outgrowth of leg segments. This thesis presents contributions I have made to broaden our understanding of molecular mechanisms regulating expression of dAP-2 in developing legs and antennae. I report the identification of multiple cis-regulatory elements each responsible for activation of particular domains of dAP-2 expression along the PD-axis of the leg and antenna. Molecular, genetic and biochemical analyses of one of these enhancers, PrF, which activates expression at the proximal end of the presumptive femur, reveals that it is directly regulated by Hox transcription factors and their homeodomain cofactor Extradenticle (Exd). Hox proteins, Exd, and Homothorax (Hth, a homeodomain protein required for nuclear localization of Exd) and their vertebrate orthologs have ancient roles in development of proximal regions of limbs. However, until this thesis, direct target genes for Hox and Exd proteins in leg development were unknown. Our analysis of dAP-2 transcriptional enhancers reveals that the seemingly simple repetitive pattern of dAP-2 expression in developing limbs is mediated by multiple separable enhancers each responsible for activation of a particular portion of the dAP-2 expression pattern and responding to region- and appendage-specific regulatory factors. Also described in the thesis are experiments using tissue-specific RNA interference (RNAi) to induce spatiotemporally restricted loss of dAP-2 and two other proteins, Nubbin, a POU-domain transcription factor implicated in limb development, and CG10440, a BTB/POZ protein reported to be a protein:protein interaction partner for dAP-2. Advisors/Committee Members: Richard W Ordway, Committee Member, Robert Paulson, Committee Member, Pamela J Mitchell, Committee Chair/Co-Chair, Wendy Hanna Rose, Committee Member, Graham Hugh Thomas, Committee Member.

Subjects/Keywords: Hox proteins; transcriptional regulation; enhancers; gene expression; limb development

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

APA (6^th Edition):

Ahn, Y. (2008). MOLECULAR AND GENETIC STUDIES OF TRANSCRIPTION FACTOR AP-2 IN DROSOPHILA APPENDAGE DEVELOPMENT . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6397

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ahn, Younwook. “MOLECULAR AND GENETIC STUDIES OF TRANSCRIPTION FACTOR AP-2 IN DROSOPHILA APPENDAGE DEVELOPMENT .” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/6397.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ahn, Younwook. “MOLECULAR AND GENETIC STUDIES OF TRANSCRIPTION FACTOR AP-2 IN DROSOPHILA APPENDAGE DEVELOPMENT .” 2008. Web. 14 Apr 2021.

Vancouver:

Ahn Y. MOLECULAR AND GENETIC STUDIES OF TRANSCRIPTION FACTOR AP-2 IN DROSOPHILA APPENDAGE DEVELOPMENT . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/6397.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ahn Y. MOLECULAR AND GENETIC STUDIES OF TRANSCRIPTION FACTOR AP-2 IN DROSOPHILA APPENDAGE DEVELOPMENT . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6397

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

21. Shimizu, Takeshi. The Drosophila Model of Cancer: Characterization of a Conserved Tumour Suppressor and Its Role in the Control of Cell Proliferation and Apoptosis.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7118

► Within this dissertation, I present the discovery and characterization of Drosophila mob as tumour suppressor, mats. It is a gene designated CG13852 by the Berkley… (more)

Subjects/Keywords: cancer biology; tumor suppressor; wts; lats; hpo; mats; Drosophila

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

APA (6^th Edition):

Shimizu, T. (2008). The Drosophila Model of Cancer: Characterization of a Conserved Tumour Suppressor and Its Role in the Control of Cell Proliferation and Apoptosis. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7118

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Shimizu, Takeshi. “The Drosophila Model of Cancer: Characterization of a Conserved Tumour Suppressor and Its Role in the Control of Cell Proliferation and Apoptosis.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/7118.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Shimizu, Takeshi. “The Drosophila Model of Cancer: Characterization of a Conserved Tumour Suppressor and Its Role in the Control of Cell Proliferation and Apoptosis.” 2008. Web. 14 Apr 2021.

Vancouver:

Shimizu T. The Drosophila Model of Cancer: Characterization of a Conserved Tumour Suppressor and Its Role in the Control of Cell Proliferation and Apoptosis. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/7118.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Shimizu T. The Drosophila Model of Cancer: Characterization of a Conserved Tumour Suppressor and Its Role in the Control of Cell Proliferation and Apoptosis. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7118

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

22. Sayeed, Ayaz. SECRETORY PROTEIN FOLDING AND THE QUALITY CONTROL OF MISFOLDED GLYCOPROTEINS.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6663

► The Endoplasmic Reticulum (ER) provides a special environment that caters to the maturation of secretory and membrane proteins. The folding of these proteins into their… (more)

▼ The Endoplasmic Reticulum (ER) provides a special environment that caters to the maturation of secretory and membrane proteins. The folding of these proteins into their native conformations within the ER lumen is a process of paramount importance. How protein folding actually takes place inside the cell however, is still poorly understood. The identification of genes and proteins that constitute the folding machinery in the ER therefore, is an important step towards understanding secretory protein folding. Here we employ a powerful genetic screen that allows the isolation of mutants defective in various secretory pathway functions. A parallel effort was made to optimize existing methods to assay protein folding and also to develop new tools that are greatly needed to better study protein folding in vivo. Using these methods, we have identified several genes that may play a role in protein folding. In addition, we describe the identification and characterization of a novel gene, undiscovered at the time of discovery that appears to play a role in the folding of some secretory proteins. While protein folding is a remarkable process, it is not free from errors which can result in incorrect protein folding. Such aberrantly folded proteins are known to be inherently toxic and their accumulation in cells can be detrimental. In the (ER), a quality control system exists to detect, retain and ultimately degrade terminally misfolded proteins, thereby alleviating the stress they cause. While much is known about the later events of this ER associated protein degradation (ERAD), it is not clear how the quality control machinery differentiates aberrantly folded proteins from actively folding or properly folded ones, and selectively delivers them to the degradation machinery. Past studies have shown that specific N-linked glycan structures function as signals for the targeting of misfolded glycoproteins to ERAD via a lectin targeting machinery. Recently it was discovered by our group that, of the many glycans that may be present on a protein, only certain glycans function as ERAD targeting signals, suggesting that additional components within the substrate may comprise the ERAD targeting signal Here we show that specific regions within the polypeptide chain that are proximal to an ERAD glycan act in conjunction with it to target a model misfolded glycoprotein substrate for degradation. Furthermore, we show that these protein-glycan determinants can be moved out of their context within the protein and still retain their functionality. Further characterization of the properties of such quality control determinants will shed more light on one of the most fundamental questions of protein quality control, i.e., how misfolded proteins are selectively degraded over other “healthy” proteins. The presence of such determinants on glycoproteins is an unanticipated finding and holds promise for the establishment of new paradigms in the field of protein quality control. Advisors/Committee Members: Wesley Tsoekjen Ng, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, David Scott Gilmour, Committee Member, Richard John Frisque, Committee Member.

Subjects/Keywords: Endoplasmic Reticulum; Protein Folding; Protein Degradation; Protein Quality Control

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

APA (6^th Edition):

Sayeed, A. (2008). SECRETORY PROTEIN FOLDING AND THE QUALITY CONTROL OF MISFOLDED GLYCOPROTEINS. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6663

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Sayeed, Ayaz. “SECRETORY PROTEIN FOLDING AND THE QUALITY CONTROL OF MISFOLDED GLYCOPROTEINS.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/6663.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Sayeed, Ayaz. “SECRETORY PROTEIN FOLDING AND THE QUALITY CONTROL OF MISFOLDED GLYCOPROTEINS.” 2008. Web. 14 Apr 2021.

Vancouver:

Sayeed A. SECRETORY PROTEIN FOLDING AND THE QUALITY CONTROL OF MISFOLDED GLYCOPROTEINS. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/6663.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Sayeed A. SECRETORY PROTEIN FOLDING AND THE QUALITY CONTROL OF MISFOLDED GLYCOPROTEINS. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6663

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

23. Nelms, Brian Lewis. SUPPRESSION OF egl-13 SOX DOMAIN MUTANTS REVEALS A NOVEL FUNCTION FOR SOME MEIOTIC GENES.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7181

► The gene egl-13 is needed for the proper development of the C. elegans uterine seam cell, an essential component of the egg-laying apparatus. In order… (more)

Subjects/Keywords: C. elegans; egl-13; him-8; uterine; development

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

APA (6^th Edition):

Nelms, B. L. (2008). SUPPRESSION OF egl-13 SOX DOMAIN MUTANTS REVEALS A NOVEL FUNCTION FOR SOME MEIOTIC GENES. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7181

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Nelms, Brian Lewis. “SUPPRESSION OF egl-13 SOX DOMAIN MUTANTS REVEALS A NOVEL FUNCTION FOR SOME MEIOTIC GENES.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/7181.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Nelms, Brian Lewis. “SUPPRESSION OF egl-13 SOX DOMAIN MUTANTS REVEALS A NOVEL FUNCTION FOR SOME MEIOTIC GENES.” 2008. Web. 14 Apr 2021.

Vancouver:

Nelms BL. SUPPRESSION OF egl-13 SOX DOMAIN MUTANTS REVEALS A NOVEL FUNCTION FOR SOME MEIOTIC GENES. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/7181.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Nelms BL. SUPPRESSION OF egl-13 SOX DOMAIN MUTANTS REVEALS A NOVEL FUNCTION FOR SOME MEIOTIC GENES. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7181

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

24. Rizkalla, Hany Waheeb. The Role of the Wingless Signaling Pathway in Cell Fate Specification .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6367

► Cell-cell communication is essential for the proper development of any multicellular organism. Signal transduction pathways are crucial in the regulation of many cellular interactions during… (more)

▼ Cell-cell communication is essential for the proper development of any multicellular organism. Signal transduction pathways are crucial in the regulation of many cellular interactions during the growth and patterning of such organisms. The Wingless (Wg) signal transduction pathway is essential for many developmental processes during Drosophila embryogenesis. Wg is a member of the Wnt family of conserved signaling glycoproteins, and it is required for the segmentation of the embryonic epidermis, specification of cardiac and somatic muscle precursors, and patterning of the embryonic midgut. In addition, during the larval stages, Wg is involved in wing, leg, and eye imaginal disc growth and patterning. The ultimate objective of the Wg signal transduction pathway is the cytoplasmic stabilization and subsequent nuclear translocation of the Armadillo (Arm) protein. Inside the nucleus, Arm functions as a transcriptional activator to activate Wg target genes. In the absence of Wg, Arm is rapidly phosphorylated and targeted for degradation by a collection of proteins that comprise the “destruction complex”. The serine/threonine kinase Zeste-White 3 (Zw3), a negative regulator of the Wg signaling pathway, is a component of this destruction complex. The work presented in this thesis expands our understanding of the role that Wg signaling plays in the specification of the somatic musculature. An additional aim of this thesis is to add insight into the role of the N-terminus of Glycogen Synthase Kinase (GSK), the vertebrate homologue of Zw3. Wg is required for the specification of the muscle progenitor cells expressing the muscle identity genes S59 and nautilus (nau). To address whether this specification is mediated by the canonical Wg pathway, reciprocal gain-of-function and loss-of-function experiments were performed. In addition, an examination into the relationship between the Wg and Notch (N) signaling pathways in the specification of muscle founder and fusion-competent cells was conducted. The results demonstrate that Wg and N act reciprocally in mediating a binary decision between muscle founder and fusion-competent cell fates in the somatic mesoderm. Zw3 and GSK-3â are very closely related serine/threonine kinases that serve as essential negative regulators of Wg/Wnt signaling. In addition to their structural similarity, they share functional similarity as well since GSK-3â, but not the related GSK-3á, can rescue a zw3 mutant embryo. One hypothesis that is tested is that the difference in regulation between GSK-3â/á is due to differences found in their amino terminal region, which is the region that is required for pseudosubstrate inhibition. Various isoforms of Zw3, which have either the entire unique amino terminus deleted, the N-terminus replaced with that of GSK-3â or replaced with that of GSK-3á, were created and tested, utilizing in vivo assays, to determine differences in activity. The results suggest that unlike GSK regulation, Wg-mediated Zw3 inactivation does not depend on pseudosubstrate binding in vivo.… Advisors/Committee Members: Esther Siegfried, Committee Chair/Co-Chair, David Scott Gilmour, Committee Member, Richard W Ordway, Committee Member, Stephen Wade Schaeffer, Committee Member.

Subjects/Keywords: somatic mesoderm; signal transduction; Wnt; Wingless signaling; Drosophila melanogaster; myogenesis; cell specification; founder cell; Zeste white 3; GSK-3

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

APA (6^th Edition):

Rizkalla, H. W. (2008). The Role of the Wingless Signaling Pathway in Cell Fate Specification . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6367

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rizkalla, Hany Waheeb. “The Role of the Wingless Signaling Pathway in Cell Fate Specification .” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/6367.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rizkalla, Hany Waheeb. “The Role of the Wingless Signaling Pathway in Cell Fate Specification .” 2008. Web. 14 Apr 2021.

Vancouver:

Rizkalla HW. The Role of the Wingless Signaling Pathway in Cell Fate Specification . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/6367.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rizkalla HW. The Role of the Wingless Signaling Pathway in Cell Fate Specification . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6367

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

25. Yao, Jun. FUNCTIONAL ROLE OF CYTOSKELETON PROTEIN ACTIN IN SYNAPSE MATURATION AND PLASTICITY.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7802

► Long-term synaptic plasticity, which is accompanied by both functional and morphological changes of synapses, may involve not only postsynaptic potentiation, but also presynaptic enhancement. Activation… (more)

▼ Long-term synaptic plasticity, which is accompanied by both functional and morphological changes of synapses, may involve not only postsynaptic potentiation, but also presynaptic enhancement. Activation of postsynaptic silent synapses has been found to contribute significantly to long-term synaptic plasticity during early developmental stage of neurons. Postsynaptic silent synapses only show NMDA receptor (NMDAR) activity but not AMPA receptor (AMPAR) activity before the induction of LTP. Postsynaptic silent synapses are activated through NMDAR-dependent insertion of AMPARs to postsynaptic density. On the other hand, presynaptic silent synapses have also been found during recent years. Presynaptic silent synapses are likely due to very low probability of neurotransmitter release. However, not like postsynaptic silent synapses, the mechanism underlying activation of presynaptic silent synapses is not well understood. Actin is an essential type of cytoskeleton protein which plays a vital role in synapse development and synaptic plasticity. Postsynaptically, actin filaments may undergo activity-dependent remodeling and play a critical role in the maintenance of LTP and stabilizing/destabilizing dendritic spines. In presynaptic terminals, actin filaments are surrounding synaptic vesicles and thus may regulate synaptic vesicle cycling. Moreover, activity-dependent presynaptic actin redistribution facilitates new synapse formation. In addition, actin was found to maintain synaptic integrity during neuronal development. The main objective of this doctoral thesis was to address the functional role of the actin during the activation of presynaptic silent synapses and long-term synaptic plasticity. Here, I have shown that repetitive spaced stimulation induced long-term synaptic plasticity in immature but not mature hippocampal neurons. Functional FM imaging and retrospective immunostaining revealed a transition of presynaptic silent boutons into active ones in response to repetitive stimulation. Electrophysiology analysis and FM imaging indicated that the activation of presynaptic silent synapses may be triggered by L-type Ca2+ channel-mediated Ca2+ influx and is dependent on downstream PKA/PKC signaling cascades, but independent of postsynaptic NMDA receptors. Moreover, inhibition of actin polymerization prevented the activation of presynaptic silent synapses, whereas promoting actin polymerization facilitates the conversion of silent to active synapses. In summary, our data suggest that the activation of presynaptic silent synapses significantly contribute to the long-term synaptic plasticity during early developmental stage of rat hippocampal neurons, and actin polymerization plays an important role in regulating such presynaptic plasticity. Advisors/Committee Members: Gong Chen, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Zhi Chun Lai, Committee Member, Si Qiong Liu, Committee Member, Pamela J Mitchell, Committee Member.

Subjects/Keywords: actin; activity; synaptic platicity; presynaptic; silent synapse; hippocampus

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

APA (6^th Edition):

Yao, J. (2008). FUNCTIONAL ROLE OF CYTOSKELETON PROTEIN ACTIN IN SYNAPSE MATURATION AND PLASTICITY. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7802

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yao, Jun. “FUNCTIONAL ROLE OF CYTOSKELETON PROTEIN ACTIN IN SYNAPSE MATURATION AND PLASTICITY.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/7802.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yao, Jun. “FUNCTIONAL ROLE OF CYTOSKELETON PROTEIN ACTIN IN SYNAPSE MATURATION AND PLASTICITY.” 2008. Web. 14 Apr 2021.

Vancouver:

Yao J. FUNCTIONAL ROLE OF CYTOSKELETON PROTEIN ACTIN IN SYNAPSE MATURATION AND PLASTICITY. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/7802.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yao J. FUNCTIONAL ROLE OF CYTOSKELETON PROTEIN ACTIN IN SYNAPSE MATURATION AND PLASTICITY. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7802

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

26. Kim, Youngcho. DISTINCTIVE ROLES OF DOPAMINE AND OCTOPAMINE RECEPTORS IN OLFACTORY LEARNING OF DROSOPHILA MELANOGASTER .

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7783

► Drosophila has robust behavioral plasticity to avoid or prefer the odor that predicts punishment or food reward, respectively. Both types of plasticity are mediated by… (more)

▼ Drosophila has robust behavioral plasticity to avoid or prefer the odor that predicts punishment or food reward, respectively. Both types of plasticity are mediated by the mushroom body (MB) neurons in the brain, in which various signaling molecules play crucial roles. However, important yet unresolved molecules are the receptors that initiate aversive or reward learning cascades in the MB. The dDA1 represents one of the Drosophila dopamine receptors that activate the cAMP cascade. To gain insights into the role of dDA1, we generated a polyclonal antibody against the unique sequence in dDA1 and investigated dDA1 distribution in the central nervous system (CNS) of Drosophila melanogaster. In both larval and adult CNS pronounced dDA1 immunoreactivity was present in the neuropil of the mushroom bodies, a brain structure crucial for learning and memory in insects, and four unpaired neurons in each thoracic segment. The adult CNS also exhibited intense dDA1 immunoreactivity in the central complex, a structure controlling higher-order motor function, moderate expression in several neurosecretory cells, and weak staining in two unpaired neurons in the mesothoracic neuromere. The dDA1 expression in these areas was only detected in the adult, but not in the third instars larval CNS. Given the findings that dDA1 and the octopamine receptor OAMB are highly expressed in the MB and use cAMP as a cellular signaling prompt us to test the roles of these receptors in associative learning using two classical conditioning paradigms: negatively and positively reinforced olfactory conditioning. Negatively reinforced olfactory conditioning has been well-characterized and flies show robust and reliable performance; however, olfactory conditioning utilizing positive reinforcement has shown to be less effective in that flies display low learning performance with highly variable scores. Therefore, we developed a novel assay for positively reinforced (appetitive) olfactory conditioning. In this assay, flies were involuntarily exposed to appetitive unconditioned stimulus sucrose along with conditioned stimulus odor during training and their preference to the odor previously associated with sucrose was measured to assess learning and memory capacities. After one training session, wild-type Canton S flies displayed reliable performance, which was enhanced after two training cycles with 1 or 15 min inter-training intervals. Higher performance scores were also obtained by increasing sucrose concentration. Memory in Canton-S flies decayed slowly when measured at 30 min, 1 h and 3 h after training, whereas memory had declined significantly at 6 h and 12 h post-training. When the octopamine-deficient t¥âh flies was challenged, they exhibited poor performance, validating the utility of this assay. As the Drosophila model offers vast genetic and transgenic resources, the new appetitive conditioning described here provides a useful tool for elucidating the molecular and cellular underpinnings of reward learning and memory. Similar to negatively… Advisors/Committee Members: Kyung An Han, Committee Chair/Co-Chair, Bernhard Luscher, Committee Member, Byron C Jones, Committee Member, Pamela J Mitchell, Committee Member, Richard W Ordway, Committee Member.

Subjects/Keywords: Octopamine receptor; Dopamine receptor; Aversive conditioning; Reward conditioning; Associative learning; Drosophila; Classical Olfactory conditioning

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APA (6^th Edition):

Kim, Y. (2008). DISTINCTIVE ROLES OF DOPAMINE AND OCTOPAMINE RECEPTORS IN OLFACTORY LEARNING OF DROSOPHILA MELANOGASTER . (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7783

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kim, Youngcho. “DISTINCTIVE ROLES OF DOPAMINE AND OCTOPAMINE RECEPTORS IN OLFACTORY LEARNING OF DROSOPHILA MELANOGASTER .” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/7783.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kim, Youngcho. “DISTINCTIVE ROLES OF DOPAMINE AND OCTOPAMINE RECEPTORS IN OLFACTORY LEARNING OF DROSOPHILA MELANOGASTER .” 2008. Web. 14 Apr 2021.

Vancouver:

Kim Y. DISTINCTIVE ROLES OF DOPAMINE AND OCTOPAMINE RECEPTORS IN OLFACTORY LEARNING OF DROSOPHILA MELANOGASTER . [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/7783.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kim Y. DISTINCTIVE ROLES OF DOPAMINE AND OCTOPAMINE RECEPTORS IN OLFACTORY LEARNING OF DROSOPHILA MELANOGASTER . [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7783

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

27. LI, YULIN. The growth retardation and liver dysfunction of PERK knockout mice.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7744

► Mutations of PKR-like Endoplasmic Reticulum Kinase (PERK) eIF2alpha kinase cause multiple phenotypes in both human and mice. Perk mutations in human result in Wolcott- Rallison… (more)

▼ Mutations of PKR-like Endoplasmic Reticulum Kinase (PERK) eIF2alpha kinase cause multiple phenotypes in both human and mice. Perk mutations in human result in Wolcott- Rallison syndrome. The human patients had neonatal diabetes, osteoporosis and growth retardation. However, according to clinical observations, most of the Wolcott-Rallison syndrome patients also had recurrent liver dysfunction/failure and they died from liver dysfunction instead of diabetes and osteoporosis. I used the Perk-/- mice to study the growth retardation of the mice and found out that Insulin-Like Growth Factor I (IGF-I) was closely correlated with the body weight of both wild type and knockout mice. The serum IGF-I reduction in Perk-/- mice was due to reduced IGF-I mRNA level in liver. Injection of recombinant IGF-I in neonatal Perk-/- mice partially rescued their growth retardation, suggesting that the IGF-I was important for their growth retardation. The IGF-I changes were also correlated with the development of liver dysfunction in Perk-/- mice. In the neonatal Perk-/- mouse liver, where the dramatic reduction of IGF-I level was found, I also observed severe fat accumulation, increased glycogen storage and other mild pathological changes. I further tested whether this liver dysfunction was a hepatocyte cell autonomous defect using both liver specific Perk conditional knockout mouse models and liver specific Perk transgenic mouse model. With the liver specific Cre expression, I was able to obtain considerable Perk gene deletion in neonatal mouse liver, but no phenotype was observed. In addition to the liver specific conditional knockout mice models, I also constructed a liver specific Perk transgenic mouse model and was able to confirm the expression of functional Perk in the mice but it failed to rescue the growth retardation and liver dysfunction in the global Perk-/- mice. Taken together, these results suggest that the growth retardation and liver dysfunction in the Perk-/- mice may not be a cell autonomous defect of hepatocytes. Moreover, our data suggest that the Perk-/- liver dysfunction closely resembles the metabolic syndrome seen in protein energy malnutrition. Advisors/Committee Members: Douglas Cavener, Committee Member, Gong Chen, Committee Member, Bernhard Luscher, Committee Chair/Co-Chair, Richard W Ordway, Committee Member, Robert Paulson, Committee Member.

Subjects/Keywords: PERK; Liver dysfunction; Steatosis; Wolcott-Rallison syndrome; growth retardation; EIF2AK3

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

APA (6^th Edition):

LI, Y. (2008). The growth retardation and liver dysfunction of PERK knockout mice. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7744

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

LI, YULIN. “The growth retardation and liver dysfunction of PERK knockout mice.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/7744.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

LI, YULIN. “The growth retardation and liver dysfunction of PERK knockout mice.” 2008. Web. 14 Apr 2021.

Vancouver:

LI Y. The growth retardation and liver dysfunction of PERK knockout mice. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/7744.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

LI Y. The growth retardation and liver dysfunction of PERK knockout mice. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7744

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

28. Zou, Beiyan. A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7850

► Synaptic transmission is a fundamental aspect of neural function. This process typically occurs at chemical synapses, where presynaptic release of chemical neurotransmitters leads to excitation… (more)

▼ Synaptic transmission is a fundamental aspect of neural function. This process typically occurs at chemical synapses, where presynaptic release of chemical neurotransmitters leads to excitation or inhibition of the postsynaptic cell. Neurotransmitter release is triggered by calcium influx through presynaptic voltage-gated calcium channels. In Drosophila, the molecular basis of presynaptic calcium channel function has been defined through our analysis of a temperature-sensitive (TS) paralytic mutant of the calcium channel alpha1 subunit gene, cacophony (cac). This mutant, referred to as cacTS2, has also served as a starting point for further genetic analysis. To broaden our understanding of the functions and interactions of cac-encoded calcium channels, we have conducted a screen for genetic modifiers of cacTS2. Of ten mutations recovered, four were intragenic and six were extragenic. Analysis of intragenic modifiers has broadened our understanding of intramolecular interactions within the calcium channel alpha1 subunit. Here we report characterization of three extragenic enhancers of cacTS2, which map to a single locus designated as e(cac)A. Genetic analysis, sequencing analysis, complementation tests, immunoblotting and immunocytochemistry have shown that e(cac)A is futsch, the homolog of microtubule-associated protein 1 (MAP1) in Drosophila. Electrophysiological analysis of synaptic transmission has revealed that futsch mutations enhance the synaptic phenotype of cacTS2. Furthermore, immunocytochemical analysis indicates that the localization of presynaptic calcium channels, microtubules and actin as well as the distribution of synaptic vesicles is normal in futsch mutants, suggesting a role for dMAP1/FUTSCH in synaptic function. Accordingly, dMAP1/FUTSCH exhibits a punctate distribution along microtubules within presynaptic boutons and extending to active zones. Taken together, our findings have implicated novel molecular mechanisms of synaptic transmission, in which a specialized form of presynaptic microtubule-based cytoskeleton may function in synaptic transmission through interactions with presynaptic calcium channels. A part of this work has revealed posttranslational proteolytic processing of a dMAP1/FUTSCH protein precursor as demonstrated previously for mammalian MAP1s. A ~20kD fragment of dMAP1/FUTSCH was specifically detected using a newly developed anti-LCf antibody and this was shown to be a dMAP1/FUTSCH light chain by colocalization with the heavy chain at the neuromuscular synapses and co-immunoprecipitation of the heavy and light chains. These findings demonstrated a structural conservation among MAP1 proteins. Further molecular and functional characterization is expected to define the in vivo roles of MAP1 in synaptic transmission and the underlying mechanisms. Advisors/Committee Members: Douglas Cavener, Committee Chair/Co-Chair, Gong Chen, Committee Member, Kyung An Han, Committee Member, Zhi Chun Lai, Committee Member, Richard W Ordway, Committee Member.

Subjects/Keywords: synaptic transmission; MAP1; presynaptic calcium channel; cacophony; futsch; Drosophila

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

APA (6^th Edition):

Zou, B. (2008). A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7850

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zou, Beiyan. “A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/7850.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zou, Beiyan. “A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA.” 2008. Web. 14 Apr 2021.

Vancouver:

Zou B. A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/7850.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zou B. A ROLE FOR MAP1 IN SYNAPTIC FUNCTION REVEALED THROUGH INTERACTIONS WITH PRESYNAPTIC CALCIUM CHANNELS IN DROSOPHILA. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7850

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

29. Schilder, Rudolf. Mechanics, Metabolism & Menosporinae: An integrative analysis of dragonfly flight performance.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/7196

► I present an integrative, multi-level study of inter- and intraspecific variability in dragonfly flight performance, and relate this to ecological fitness traits. My studies show… (more)

Subjects/Keywords: mechanics; metabolism; muscle; insect flight muscle; infection; gregarine; parasite

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

APA (6^th Edition):

Schilder, R. (2008). Mechanics, Metabolism & Menosporinae: An integrative analysis of dragonfly flight performance. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/7196

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Schilder, Rudolf. “Mechanics, Metabolism & Menosporinae: An integrative analysis of dragonfly flight performance.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/7196.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Schilder, Rudolf. “Mechanics, Metabolism & Menosporinae: An integrative analysis of dragonfly flight performance.” 2008. Web. 14 Apr 2021.

Vancouver:

Schilder R. Mechanics, Metabolism & Menosporinae: An integrative analysis of dragonfly flight performance. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/7196.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Schilder R. Mechanics, Metabolism & Menosporinae: An integrative analysis of dragonfly flight performance. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/7196

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Penn State University

30. Phillips, Matthew D. A Novel Role for beta(Heavy)-Spectrin in Early Endosome Recycling in the Drosophila melanogaster Larval Midgut.

Degree: 2008, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/6637

► Polarity is essential for the function of epithelial tissues. Epithelial polarity is marked by the division of the plasma membrane into apical and basolateral membrane… (more)

▼ Polarity is essential for the function of epithelial tissues. Epithelial polarity is marked by the division of the plasma membrane into apical and basolateral membrane domains, a division actively maintained by the delivery and retention of proteins in each domain. In parallel, an apicolateral junctional complex passively maintains the distinct biochemical composition of each domain by acting as a molecular fence. Both of these mechanisms for maintaining epithelial polarity depend to some degree on the cytoskeleton, a complex network of microtubules and F-Actin that is essential for polarized protein delivery, and interacts with integral membrane proteins and components of the junctional complex. The Spectrin-based membrane skeleton (SBMS) is a specialization of the actin cytoskeleton that forms a lattice on flat membranes. There it both regulates the transport of vesicles and provides a stable platform for the binding of adaptor proteins such as Ankyrin. The discovery that the Spectrin skeleton is polarized in epithelia, with different isoforms isolated to different domains, provides a mechanism to explain how differences in apical and basolateral domains are maintained. Spectrin tetramers are composed of two alpha and two beta subunits. beta-Spectrin isoforms are thought to be central for activities that contribute to the polarization of Spectrin tetramers, as well as their distinct functions. Drosophila melanogaster is ideal for studying the role of beta subunits in the function of the SBMS, since it only encodes two isoforms: a conventional beta and a beta heavy (betaH). The Drosophila Spectrin skeleton is polarized in epithelia, with basolateral (alpha/beta)2 and apical (alpha/betaH)2 tetramers. Previous results have shown that the Spectrin skeleton acts as a molecular scaffold, stabilizing a subset of membrane proteins at a particular membrane domain. However, my results point to a different effect on polarity. In betaH mutants, the apical Spectrin skeleton is lost, and defects in midgut acidification point to a loss of the apical proton-pumping V-type ATPase. Immunohistochemical work presented herein shows that the lack of midgut acidification is correlated with the loss of this V-ATPase not only from the apical membrane, but from a system of early endosomes involved in protein recycling. The early endosome pathway itself is compromised in these mutants, yet my work also shows that the delivery of apical proteins does not apparently require the SBMS. These results suggest that in betaH mutants an entire class of proteins normally recycled to and from the membrane may be prematurely degraded in the lysosome. For example, the trace mineral copper demonstrates a defective and lesser accumulation in betaH mutant midgut cells, suggesting the apically localized copper transporter Ctr-1 may also be affected. In addition, this work demonstrates functional differences in the polarizing activities of the epithelia derived from the surface ectoderm vs. the midgut. The C-terminal domain of betaH… Advisors/Committee Members: Graham Hugh Thomas, Committee Chair/Co-Chair, Carol V Gay, Committee Member, Simon Gilroy, Committee Member, Richard W Ordway, Committee Member.

Subjects/Keywords: Drosophila; midgut; cuprophilic; cell polarity; endocytosis; spectrin

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

APA (6^th Edition):

Phillips, M. D. (2008). A Novel Role for beta(Heavy)-Spectrin in Early Endosome Recycling in the Drosophila melanogaster Larval Midgut. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/6637

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Phillips, Matthew D. “A Novel Role for beta(Heavy)-Spectrin in Early Endosome Recycling in the Drosophila melanogaster Larval Midgut.” 2008. Thesis, Penn State University. Accessed April 14, 2021. https://submit-etda.libraries.psu.edu/catalog/6637.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Phillips, Matthew D. “A Novel Role for beta(Heavy)-Spectrin in Early Endosome Recycling in the Drosophila melanogaster Larval Midgut.” 2008. Web. 14 Apr 2021.

Vancouver:

Phillips MD. A Novel Role for beta(Heavy)-Spectrin in Early Endosome Recycling in the Drosophila melanogaster Larval Midgut. [Internet] [Thesis]. Penn State University; 2008. [cited 2021 Apr 14]. Available from: https://submit-etda.libraries.psu.edu/catalog/6637.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Phillips MD. A Novel Role for beta(Heavy)-Spectrin in Early Endosome Recycling in the Drosophila melanogaster Larval Midgut. [Thesis]. Penn State University; 2008. Available from: https://submit-etda.libraries.psu.edu/catalog/6637

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations