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You searched for +publisher:"Temple University" +contributor:("Gallo, Gianluca;"). Showing records 1 – 3 of 3 total matches.

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Temple University

1. Nemani, Neeharika. Molecular Determinant of Mitochondrial Shape Change.

Degree: PhD, 2018, Temple University

Biomedical Sciences

Mitochondria shape cytosolic Ca2+ (cCa2+) transients. Ca2+ entry into the mitochondria is driven by the highly negative mitochondrial membrane potential and through a highly selective channel, the Mitochondrial Calcium Uniporter (MCU). Mitochondrial Ca2+ (mCa2+) is utilized by the matrix dehydrogenases for maintaining cellular bioenergetics. The TCA cycle-derived NADH and FADH2 are mCa2+ dependent thus, feed into the electron transport chain (ETC) to generate ATP. Either loss of mCa2+ or metabolite uptake by the mitochondria results in a bioenergetic crisis and mitochondrial dysfunction. Reciprocally, sudden elevation of cCa2+ under conditions of stroke or ischemia/reperfusion injury (I/R) drives excessive mCa2+ overload that in turn leads to the opening of a large channel, the mitochondrial permeability transition pore (PTP) that triggers necrotic cell death. Thus, Ca2+ and metabolite equilibrium is essential to maintain a healthy mitochondrial pool. Our laboratory has previously showed that loss of mCa2+ uptake leads to decreased ATP generation and cell survival through autophagy. Although metabolite scarcity also results in similar reduction in ATP generation, the molecular mechanisms by which metabolites control mitochondrial ion homeostasis remain elusive. Deprivation of glucose or supplementation of mitochondrial pyruvate carrier (MPC) transport blocker UK5099 and or carnitine-dependent fatty acid blocker etomoxir triggered an increase in the expression of MICU1, a regulator of the mitochondrial calcium uniporter (MCU) but not the MCU core subunit. Consistently, either RNAi-mediated deletion of MPC isoforms or dominant negative human mutant MPC1 R97W showed significant induction of MICU1 protein abundance and inhibition of MCU-mediated mCa2+ uptake. Moreover, TCA cycle substrate-dependent MICU1 expression is under the control of EGR1 transcriptional regulation. Reciprocally, the MICU1 dependent inhibition of mCa2+ uptake exhibited lower NADH production and oxygen consumption and ATP production. The reduction of mitochondrial pyruvate by MPC knockdown is linked to higher production of mitochondrial ROS and elevated autophagy markers. These studies reveal an unexpected regulation of MCU-mediated mCa2+ flux machinery involving major TCA cycle substrate availability and possibly MICU1 to control cellular switch between glycolysis and oxidative phosphorylation. While mCa2+ is required for energy generation, sustained elevation of mCa2+ results in mitochondrial swelling and necrotic death. Hence, it was thought that preventing mCa2+ overload can be protective under conditions of elevated cCa2+. Contrary to this, mice knocked-out for MCU, that demonstrated no mCa2+ uptake and hence no mitochondrial swelling, however failed protect cells from I/R- mediated cell death. MCU-/- animals showed a similar infarct size comparable to that of control animals, suggesting that prevention of MCU-mediated mCa2+ overload alone is not sufficient to protect cells from Ca2+ -induced necrosis. The absence of mCa2+…

Advisors/Committee Members: Goldfinger, Lawrence;, Muniswamy, Madesh, Golemis, Erica A., Tian, Ying, Gallo, Gianluca;.

Subjects/Keywords: Molecular biology; Biochemistry;

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

APA (6th Edition):

Nemani, N. (2018). Molecular Determinant of Mitochondrial Shape Change. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,511170

Chicago Manual of Style (16th Edition):

Nemani, Neeharika. “Molecular Determinant of Mitochondrial Shape Change.” 2018. Doctoral Dissertation, Temple University. Accessed October 17, 2019. http://digital.library.temple.edu/u?/p245801coll10,511170.

MLA Handbook (7th Edition):

Nemani, Neeharika. “Molecular Determinant of Mitochondrial Shape Change.” 2018. Web. 17 Oct 2019.

Vancouver:

Nemani N. Molecular Determinant of Mitochondrial Shape Change. [Internet] [Doctoral dissertation]. Temple University; 2018. [cited 2019 Oct 17]. Available from: http://digital.library.temple.edu/u?/p245801coll10,511170.

Council of Science Editors:

Nemani N. Molecular Determinant of Mitochondrial Shape Change. [Doctoral Dissertation]. Temple University; 2018. Available from: http://digital.library.temple.edu/u?/p245801coll10,511170


Temple University

2. Sheikh, Imran Sana. The Role of C3-C4 Propriospinal Interneurons on Reaching and Grasping Behaviors Pre- and Post-Cervical Spinal Cord Injury.

Degree: PhD, 2018, Temple University

Biomedical Sciences

Greater than 50% of all spinal cord injuries (SCIs) in humans occur at the cervical level and the biggest desire of quadriplegic patients is recovery of hand and digit function. Several weeks after spinal cord injury, re-organization and re-modeling of spared endogenous pathways occurs and plasticity of both supraspinal and interneuronal networks are believed to mediate functional recovery. Propriospinal interneurons (PNs) are neurons found entirely in the spinal cord with axons projecting to different spinal segments. PNs function by modulating locomotion, integrating supraspinal motor pathways and peripheral sensory afferents. Recent studies have postulated that if PNs are spared following SCI, these neurons can contribute to functional recovery by establishing synaptic connections onto motor neurons. However, to what extent cervical PNs are involved in recovery of reaching behavior is not known. In our first study, we generated a lentiviral vector that permits highly efficient retrograde transport (HiRet) upon uptake at synaptic terminals in order to map supraspinal and interneuronal populations terminating near forelimb motoneurons (MNs) innervating the limb. With this vector, we found neurons labeled within the C3-C4 spinal cord and in the red nucleus, two major populations which are known to modulate forelimb reaching behavior. We also proceeded to use a novel two-viral vector method to specifically label ipsilateral C3-C4 PNs with tetracycline-inducible GFP. Histological analysis showed detailed labeling of somas, dendrites along with axon terminals. Based on this data, we proceeded to determine the contribution of C3-C4 PNs and rubrospinal neurons on forelimb reaching and grasping before and after cervical SCI. In our second study, we have examined a double-infection technique for shutdown of PNs and rubrospinal neurons (RSNs) in adult rats. Adult rats were microinjected with a lentiviral vector expressing tetracycline-inducible inhibitory DREADDs into C6-T1 spinal levels. Adeno-associated viral vectors (AAV2) expressing TetON mixed with GIRK2 were injected into the red nucleus and C3-C4 spinal levels respectively. Rats were tested for deficits in reaching behaviors upon application of doxycycline and clozapine-n-oxide (CNO) administration. No behavioral deficits were observed pre-injury. Rats then received a C5 spinal cord lesion to sever cortical input to forelimb motoneurons and were allowed four weeks to spontaneously recover. Upon re-administration of CNO to activate inhibitory DREADDs, deficits were observed in forelimb reaching. Histological analysis of the C3-C4 spinal cord and red nucleus showed DREADD+ neurons co-expressing GIRK2 in somas and dendrites of PNs and RSNs. PN terminals expressing DREADD were observed near C6-T1 motoneurons and in the brainstem. Control animals did not show substantial deficits with CNO administration. These results indicate both rubro- and propriospinal pathways are necessary for recovery of forelimb reaching. In a separate study, we sought to…

Advisors/Committee Members: Smith, George M.;, Selzer, Michael, Gallo, Gianluca, Li, Shuxin, Unterwald, Ellen M., Lemay, Michel A.;.

Subjects/Keywords: Neurosciences;

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

APA (6th Edition):

Sheikh, I. S. (2018). The Role of C3-C4 Propriospinal Interneurons on Reaching and Grasping Behaviors Pre- and Post-Cervical Spinal Cord Injury. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,522459

Chicago Manual of Style (16th Edition):

Sheikh, Imran Sana. “The Role of C3-C4 Propriospinal Interneurons on Reaching and Grasping Behaviors Pre- and Post-Cervical Spinal Cord Injury.” 2018. Doctoral Dissertation, Temple University. Accessed October 17, 2019. http://digital.library.temple.edu/u?/p245801coll10,522459.

MLA Handbook (7th Edition):

Sheikh, Imran Sana. “The Role of C3-C4 Propriospinal Interneurons on Reaching and Grasping Behaviors Pre- and Post-Cervical Spinal Cord Injury.” 2018. Web. 17 Oct 2019.

Vancouver:

Sheikh IS. The Role of C3-C4 Propriospinal Interneurons on Reaching and Grasping Behaviors Pre- and Post-Cervical Spinal Cord Injury. [Internet] [Doctoral dissertation]. Temple University; 2018. [cited 2019 Oct 17]. Available from: http://digital.library.temple.edu/u?/p245801coll10,522459.

Council of Science Editors:

Sheikh IS. The Role of C3-C4 Propriospinal Interneurons on Reaching and Grasping Behaviors Pre- and Post-Cervical Spinal Cord Injury. [Doctoral Dissertation]. Temple University; 2018. Available from: http://digital.library.temple.edu/u?/p245801coll10,522459


Temple University

3. Skuba, Andrew. In vivo imaging analysis of the regeneration failure of dorsal root axons in adult mice.

Degree: PhD, 2014, Temple University

Cell Biology

After injury, dorsal root (DR) axons regenerate in the peripheral nervous system (PNS), but turn around or stop at the dorsal root entry zone (DREZ), the entrance into the central nervous system (CNS). Examination of the dynamic axon regeneration that occurs following injury to the DR provides the opportunity to advance our understanding of what happens to sensory axons as they approach and arrive at the DREZ and expands our knowledge of sensory axon regeneration failure at the entrance to the spinal cord. Additionally, findings from these studies may offer potential avenues to provide insight into regeneration failure elsewhere in the central nervous system. Nevertheless, our understanding of the cellular and molecular processes underlying the failure of DR axons to regenerate through the DREZ is incomplete. The goal of my thesis work was to determine whether application of the time lapse-in vivo imaging technique is feasible and useful in studying dorsal root regeneration. I have also applied recently developed post-mortem analyses to the axons monitored in vivo, which provided additional insights into the mechanisms that prevent axon regeneration at the DREZ. Results in Chapters 2 and 3 demonstrate that wide-field microscopy is indeed feasible and useful for monitoring regenerating sensory axons immediately before, during, and in the days to weeks after lumbar (L5) DR crush. I was surprised to find that most axons were immobilized abruptly and chronically at the CNS portion of the DREZ, with their axon tips and shafts exhibiting features of differentiated nerve terminals. This observation raises the possibility, which has not been appreciated previously, that DR axons stop at the DREZ because their regeneration is terminated prematurely by forming synaptic contacts with unidentified postsynaptic cells. To confirm the immobilization of DR axons at the DREZ, I applied two-photon microscopy to examine the axon behavior at the DREZ at high resolution. Results described in Chapter 4 confirm those obtained with the time-lapse imaging performed with wide-field microscopy: axons arrested soon after their arrival at the DREZ did not exhibit even subtle movements. Light microscopic analyses of the failed axon tips monitored in vivo demonstrated that almost all axons stopped at the CNS territory of the DREZ, and that axon tips and adjacent shafts intensely immunolabeled with synapse markers. Ultrastructural analyses revealed that numerous axonal profiles had the characteristic features of pre- but not postsynaptic endings. Findings from these studies lead us to speculate that most, if not all, dorsal root axons become arrested as they enter the CNS territory of the DREZ by forming presynaptic terminals on non-neuronal cellular elements that differ from the dystrophic-like endings formed by a few axons. In the chapter 5, I discuss what I have found to be the key factors for successful monitoring of regenerating dorsal root axons in living animals; the feasibility, usefulness and limitations of the available…

Advisors/Committee Members: Son, Young-Jin, Barbe, Mary F.;, Son, Young-Jin, Barbe, Mary F., Gallo, Gianluca, Kim, Seonhee, Smith, George M., Ramirez, Servio;.

Subjects/Keywords: Cellular biology; Neurosciences;

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

APA (6th Edition):

Skuba, A. (2014). In vivo imaging analysis of the regeneration failure of dorsal root axons in adult mice. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,292900

Chicago Manual of Style (16th Edition):

Skuba, Andrew. “In vivo imaging analysis of the regeneration failure of dorsal root axons in adult mice.” 2014. Doctoral Dissertation, Temple University. Accessed October 17, 2019. http://digital.library.temple.edu/u?/p245801coll10,292900.

MLA Handbook (7th Edition):

Skuba, Andrew. “In vivo imaging analysis of the regeneration failure of dorsal root axons in adult mice.” 2014. Web. 17 Oct 2019.

Vancouver:

Skuba A. In vivo imaging analysis of the regeneration failure of dorsal root axons in adult mice. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2019 Oct 17]. Available from: http://digital.library.temple.edu/u?/p245801coll10,292900.

Council of Science Editors:

Skuba A. In vivo imaging analysis of the regeneration failure of dorsal root axons in adult mice. [Doctoral Dissertation]. Temple University; 2014. Available from: http://digital.library.temple.edu/u?/p245801coll10,292900

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