Biology Commons^™

The Role Of Biotin And Oxamate In The Carboxyltransferase Reaction Of Pyruvate Carboxylase, Adam D. Lietzan, Yi Lin, Martin St. Maurice

Biological Sciences Faculty Research and Publications

Pyruvate carboxylase (PC) is a biotin-dependent enzyme that catalyzes the MgATP-dependent carboxylation of pyruvate to oxaloacetate, an important anaplerotic reaction in central metabolism. During catalysis, carboxybiotin is translocated to the carboxyltransferase domain where the carboxyl group is transferred to the acceptor substrate, pyruvate. Many studies on the carboxyltransferase domain of PC have demonstrated an enhanced oxaloacetate decarboxylation activity in the presence of oxamate and it has been shown that oxamate accepts a carboxyl group from carboxybiotin during oxaloacetate decarboxylation. The X-ray crystal structure of the carboxyltransferase domain from Rhizobium etli PC reveals that oxamate is positioned in the active site …

Lianas In Gaps Reduce Carbon Accumulation In A Tropical Forest, Stefan A. Schnitzer, Geertje M. F. Van Der Heijden, Joseph Mascaro, Walter P. Carson

Biological Sciences Faculty Research and Publications

Treefall gaps are the “engines of regeneration” in tropical forests and are loci of high tree recruitment, growth, and carbon accumulation. Gaps, however, are also sites of intense competition between lianas and trees, whereby lianas can dramatically reduce tree carbon uptake and accumulation. Because lianas have relatively low biomass, they may displace far more biomass than they contribute, a hypothesis that has never been tested with the appropriate experiments. We tested this hypothesis with an 8‐yr liana removal experiment in central Panama. After 8 years, mean tree biomass accumulation was 180% greater in liana‐free treefall gaps compared to control gaps. …

Structural And Biochemical Studies Of The Carboxyltransferase Domain From Pyruvate Carboxylase, Adam David Lietzan

Dissertations (1934 -)

Pyruvate carboxylase (PC; E.C. 6.4.1.1), a multifunctional biotin-dependent enzyme, catalyzes the bicarbonate- and MgATP-dependent carboxylation of pyruvate to oxaloacetate. To complete the overall reaction, the tethered biotin prosthetic group must first gain access to the biotin carboxylase domain and become carboxylated, and then translocate to the carboxyltransferase (CT) domain where the carboxyl group is transferred from biotin to pyruvate. Kinetic analyses of PC have suggested that the spatially distinct reactions, which occur in the active sites of the BC and CT domains, are well coordinated. To gain insights into the molecular events necessary for coordinating catalysis in the CT domain, …

Impact Of Mtr4 Structural Domains On Its Enzymatic Activities, In The Regulation Of Nuclear Rna Turnover, Li Yan

Dissertations (1934 -)

RNA processing and turnover plays an important role in RNA maturation, metabolism and quality control, which contribute to gene regulation and cell health. The TRAMP complex, composed of an RNA binding protein Air2p, a poly-A polymerase Trf4p, and a RNA helicase Mtr4p, assist nuclear exosome-dependent RNA processing and degradation in Saccharomyces cerevisiae, like tRNAiMet turnover, 5'ETS degradation and rRNA processing. Mtr4p structure reveals a novel protruding arch domain, which contains the recognizable KOW domain and a stalk domain. Except for the two conserved RecA-like helicase domains, the helicase core contains two other structural domains, a winged helix that connects arch …

Water‐Use Advantage For Lianas Over Trees In Tropical Seasonal Forests, Ya-Jun Chen, Kun-Fang Cao, Stefan A. Schnitzer, Za-Xin Fan, Jiao-Lin Zhang, Frans Bongers

Biological Sciences Faculty Research and Publications

• Lianas exhibit peak abundance in tropical forests with strong seasonal droughts, the eco‐physiological mechanisms associated with lianas coping with water deficits are poorly understood.
• We examined soil water partitioning, sap flow, and canopy eco‐physiological properties for 99 individuals of 15 liana and 34 co‐occurring tree species in three tropical forests that differed in soil water availability.
• In the dry season, lianas used a higher proportion of deep soil water in the karst forest (KF ; an area with severe seasonal soil water deficit (SSWD )) and in the tropical seasonal forest (TSF , moderate SSWD ), permitting them to maintain …

Identification Of Sex‐Specific Molecular Markers Using Restriction Site‐Associated Dna Sequencing, Tony Gamble, David Zarkower

Biological Sciences Faculty Research and Publications

A major barrier to evolutionary studies of sex determination and sex chromosomes has been a lack of information on the types of sex‐determining mechanisms that occur among different species. This is particularly problematic in groups where most species lack visually heteromorphic sex chromosomes, such as fish, amphibians and reptiles, because cytogenetic analyses will fail to identify the sex chromosomes in these species. We describe the use of restriction site‐associated DNA (RAD) sequencing, or RAD‐seq, to identify sex‐specific molecular markers and subsequently determine whether a species has male or female heterogamety. To test the accuracy of this technique, we examined the …

Chloride Channels In Stellate Cells Are Essential For Uniquely High Secretion Rates In Neuropeptide-Stimulated Drosophila Diuresis, Pablo Cabrero, Selim Terhzaz, Michael F. Romero, Shireen A. Davies, Edward M. Blumenthal

Biological Sciences Faculty Research and Publications

Epithelia frequently segregate transport processes to specific cell types, presumably for improved efficiency and control. The molecular players underlying this functional specialization are of particular interest. In Drosophila, the renal (Malpighian) tubule displays the highest per-cell transport rates known and has two main secretory cell types, principal and stellate. Electrogenic cation transport is known to reside in the principal cells, whereas stellate cells control the anion conductance, but by an as-yet-undefined route. Here, we resolve this issue by showing that a plasma membrane chloride channel, encoded by ClC-a, is exclusively expressed in the stellate cell and is required …

Living Close To Your Neighbors: The Importance Of Both Competition And Facilitation In Plant Communities, Alexandra Wright, Stefan A. Schnitzer, Peter B. Reich

Biological Sciences Faculty Research and Publications

Recent work has demonstrated that competition and facilitation likely operate jointly in plant communities, but teasing out the relative role of each has proven difficult. Here we address how competition and facilitation vary with seasonal fluctuations in environmental conditions, and how the effects of these fluctuations change with plant ontogeny. We planted three sizes of pine seedlings (Pinus strobus) into an herbaceous diversity experiment and measured pine growth every two weeks for two growing seasons. Both competition and facilitation occurred at different times of year between pines and their neighbors. Facilitation was important for the smallest pines when …

Disturbance And Clonal Reproduction Determine Liana Distribution And Maintain Liana Diversity In A Tropical Forest, Alicia Ledo, Stefan A. Schnitzer

Biological Sciences Faculty Research and Publications

Negative density dependence (NDD) and habitat specialization have received strong empirical support as mechanisms that explain tree species diversity maintenance and distribution in tropical forests. In contrast, disturbance appears to play only a minor role. Previous studies have rarely examined the relative strengths of these diversity maintenance mechanisms concurrently, and few studies have included plant groups other than trees. Here we used a large, spatially explicit data set from Barro Colorado Island, Panama (BCI) to test whether liana and tree species distribution patterns are most consistent with NDD, habitat specialization, or disturbance. We found compelling evidence that trees responded to …

Writing Assignments With A Metacognitive Component Enhance Learning In A Large Introductory Biology Course, Michelle Mynlieff, Anita Manogaran, Martin St. Maurice, Thomas Eddinger

Biological Sciences Faculty Research and Publications

Writing assignments, including note taking and written recall, should enhance retention of knowledge, whereas analytical writing tasks with metacognitive aspects should enhance higher-order thinking. In this study, we assessed how certain writing-intensive “interventions,” such as written exam corrections and peer-reviewed writing assignments using Calibrated Peer Review and including a metacognitive component, improve student learning. We designed and tested the possible benefits of these approaches using control and experimental variables across and between our three-section introductory biology course. Based on assessment, students who corrected exam questions showed significant improvement on postexam assessment compared with their nonparticipating peers. Differences were also observed …

Coordination Of Primer Sugar Synthesis With O-Antigen Initiation In Rhizobium Etli Ce3, Tiezheng Li

Dissertations (1934 -)

All organisms synthesize amidosugars, such as N-acetylglucosamine (GlcNAc), and deoxysugars, such as fucose. They are found in important polysaccharides and glycoconjugates such as glycoproteins. N-acetylquinovosamine (QuiNAc) is both an amido- and a deoxy-sugar. It is found in many examples of an important prokaryotic glycoconjugate, the lipopolysaccharide (LPS) that coats the surface of Gram-negative bacteria. Like N-glycosylation of glycoproteins, LPS has a portion that is synthesized first on a polyprenyl lipid carrier and then transferred to the rest of the molecule. QuiNAc is believed to initiate the O-antigen portion of LPS of Rhizobium etli CE3. Genetic studies identified three genes, wreV, …

Targeted Ngs Gene Panel Identifies Mutations In Rsph1 Causing Primary Ciliary Dyskinesia And A Common Mechanism For Ciliary Central Pair Agenesis Due To Radial Spoke Defects, Alexandros Onoufriadis, Amelia Shoemark, Miriam Schmidts, Mitali Patel, Gina Jimenez, Hui Liu, Biju Thomas, Mellisa Dixon, Robert A. Hirst, Andrew Rutman, Thomas Burgoyne, Christopher Williams, Juliet Scully, Florence Bolard, Jean-Jacques Lafitte, Philip L. Beales, Claire Hogg, Pinfen Yang, Eddie M.K. Chung, Richard D. Emes, Christopher O’Callaghan, Uk 10k, Patrice Bouvagnet, Hannah M. Mitchison

Biological Sciences Faculty Research and Publications

Primary ciliary dyskinesia (PCD) is an inherited chronic respiratory obstructive disease with randomized body laterality and infertility, resulting from cilia and sperm dysmotility. PCD is characterized by clinical variability and extensive genetic heterogeneity, associated with different cilia ultrastructural defects and mutations identified in >20 genes. Next generation sequencing (NGS) technologies therefore present a promising approach for genetic diagnosis which is not yet in routine use. We developed a targeted panel-based NGS pipeline to identify mutations by sequencing of selected candidate genes in 70 genetically undefined PCD patients. This detected loss-of-function RSPH1 mutations in four individuals with isolated central pair (CP) …

The Role Of Prka-Mediated Stimulation Of Fatty Acid Oxidation In The Regulation Of Meiotic Maturation In Mouse Oocytes, Deepa Valsangkar

Dissertations (1934 -)

Meiosis is a defining aspect of sexual reproduction and its outcome often determines reproductive success. In mammalian females, oocytes initiate meiosis in early embryonic stages but arrest in the late prophase of meiosis-I around the time of birth. They remain arrested until hormonal induction during reproductive cycles after puberty, and then resume meiosis until a second arrest at metaphase-II. The process of oocyte meiosis from the release of prophase arrest till the metaphase-II arrest is known as oocyte maturation. Meiotic arrest is a result of maintenance of elevated cAMP levels within the oocyte by its continuous production as well as …

Structural And Functional Studies Of Urea Amidolyase, Yi Lin

Dissertations (1934 -)

Urea amidolyase (UAL) is a key virulence factor that regulates the yeast to hyphae switch in the opportunistic pathogen, Candida albicans. UAL is a multi-domain enzyme with two enzyme activities: urea carboxylase (UC) and allophanate hydrolase (AH). UC is a biotin-dependent carboxylase that adds a carboxyl group to urea to make allophanate by the coordinated action of three domains. Allophanate is subsequently hydrolyzed into NH3 and CO2 in the AH domain. Studies on the structure and function of UAL may lead to treatments for systemic candidiasis and can serve to clarify the molecular basis for multi-functional swinging arm enzymes. In …

Cross-Bridge Mechanisms Of Skeletal Muscle Fatigue: Effects Of Hydrogen Ion, Inorganic Phosphate, And Age, Cassandra Rae Nelson

Dissertations (1934 -)

Intense muscle contraction induces high rates of glycolysis and ATP hydrolysis with resulting increases in inorganic phosphate (Pi) and H+, factors thought to induce fatigue by interfering with steps in the cross-bridge cycle. Force inhibition is less at physiological temperatures; thus the role of low pH in fatigue has been questioned. Effects of pH 6.2 and collective effects with 30 mM Pi on the pCa-force relationship were assessed in skinned fast and slow rat skeletal muscle fibers at low (15°C) and near-physiological temperatures (30°C). At Ca2+ levels characteristic of fatigue, low pH significantly depressed force at both temperatures and in …

Expression Patterns Of Aba And Ga Metabolism Genes And Hormone Levels During Rice Seed Development And Imbibition: A Comparison Of Dormant And Non-Dormant Rice Cultivars, Yang Liu, Jun Fang, Fan Xu, Jinfang Chu, Cunyu Yan, Michael Schläppi, Youping Wang, Chengcai Chu

Biological Sciences Faculty Research and Publications

Seed dormancy is an important agronomic trait in cereals. Using deep dormant (N22), medium dormant (ZH11), and non-dormant (G46B) rice cultivars, we correlated seed dormancy phenotypes with abscisic acid (ABA) and gibberellin (GA) metabolism gene expression profiles and phytohormone levels during seed development and imbibition. A time course analysis of ABA and GA content during seed development showed that N22 had a high ABA level at early and middle seed developmental stages, while at late developmental stage it declined to the level of ZH11; however, its ABA/GA ratio maintained at a high level …

Certain Adenylated Non-Coding Rnas, Including 5′ Leader Sequences Of Primary Microrna Transcripts, Accumulate In Mouse Cells Following Depletion Of The Rna Helicase Mtr4, Jane E. Dorweiler, Ting Ni, Jun Zhu, Stephen Munroe, James T. Anderson

Biological Sciences Faculty Research and Publications

RNA surveillance plays an important role in posttranscriptional regulation. Seminal work in this field has largely focused on yeast as a model system, whereas exploration of RNA surveillance in mammals is only recently begun. The increased transcriptional complexity of mammalian systems provides a wider array of targets for RNA surveillance, and, while many questions remain unanswered, emerging data suggest the nuclear RNA surveillance machinery exhibits increased complexity as well. We have used a small interfering RNA in mouse N2A cells to target the homolog of a yeast protein that functions in RNA surveillance (Mtr4p). We used high-throughput sequencing of polyadenylated …

Context-Dependent Remodeling Of Rad51–Dna Complexes By Srs2 Is Mediated By A Specific Protein–Protein Interaction, Anna K. Lytle, Sofia S. Origanti, Yupeng Qiu, Jeffrey Vongermeten, Sua Myong, Edwin Antony

Biological Sciences Faculty Research and Publications

The yeast Srs2 helicase removes Rad51 nucleoprotein filaments from single-stranded DNA (ssDNA), preventing DNA strand invasion and exchange by homologous recombination. This activity requires a physical interaction between Srs2 and Rad51, which stimulates ATP turnover in the Rad51 nucleoprotein filament and causes dissociation of Rad51 from ssDNA. Srs2 also possesses a DNA unwinding activity and here we show that assembly of more than one Srs2 molecule on the 3′ ssDNA overhang is required to initiate DNA unwinding. When Rad51 is bound on the double-stranded DNA, its interaction with Srs2 blocks the helicase (DNA unwinding) activity of Srs2. Thus, in different …

The Polycyclic Aromatic Hydrocarbon Degradation Potential Of Gulf Of Mexico Native Coastal Microbial Communities After The Deepwater Horizon Oil Spill, Anthony D. Kappell, Yin Wei, Ryan J. Newton, Joy D. Van Nostrand, Jizhong Zhou, Sandra L. Mclellan, Krassimira R. Hristova

Biological Sciences Faculty Research and Publications

The Deepwater Horizon (DWH) blowout resulted in oil transport, including polycyclic aromatic hydrocarbons (PAHs) to the Gulf of Mexico shoreline. The microbial communities of these shorelines are thought to be responsible for the intrinsic degradation of PAHs. To investigate the Gulf Coast beach microbial community response to hydrocarbon exposure, we examined the functional gene diversity, bacterial community composition, and PAH degradation capacity of a heavily oiled and non-oiled beach following the oil exposure. With a non-expression functional gene microarray targeting 539 gene families, we detected 28,748 coding sequences. Of these sequences, 10% were uniquely associated with the severely oil-contaminated beach …

Positions In The Glun2c-Containing Nmdar Regulate Alcohol Sensitivity And Ion Channel Gating, Man Wu

Master's Theses (2009 -)

The N-methyl-D-aspartate (NMDA) receptor, a subtype of glutamate-gated ion channel, has been shown to be a major target of ethanol in the central nervous system (CNS). Previous studies have identified positions in the third and fourth membrane-associated (M) domains of the NMDAR GluN1 and GluN2A subunits that influence ethanol sensitivity. Among the alcohol sensitive sites, a methionine residue is highly conserved in all GluN1 and GluN2 subunits. We proposed the methionine position (Met-821) in the M4 domain of the GluN2C subunit can regulate ethanol sensitivity and ion channel gating. 14 mutations were made at the methionine position, 7 substitutions yielded …

Effects Of Low Cell Ph And Elevated Inorganic Phosphate On The Pca-Force Relationship In Single Muscle Fibers At Near-Physiological Temperatures, Cassandra R. Nelson, Robert H. Fitts

Biological Sciences Faculty Research and Publications

Intense muscle contraction induces high rates of ATP hydrolysis with resulting increases in P_i, H⁺, and ADP, factors thought to induce fatigue by interfering with steps in the cross-bridge cycle. Force inhibition is less at physiological temperatures; thus the role of low pH in fatigue has been questioned. Effects of pH 6.2 and collective effects with 30 mM P_i on the pCa-force relationship were assessed in skinned fast and slow rat skeletal muscle fibers at 15 and 30°C. At 30°C, pH 6.2 + 30 mM P_i significantly depressed peak force in all fiber types, …

Anolis Sex Chromosomes Are Derived From A Single Ancestral Pair, Tony Gamble, Anthony J. Geneva, Richard E. Glor, David Zarkower

Biological Sciences Faculty Research and Publications

To explain the frequency and distribution of heteromorphic sex chromosomes in the lizard genus Anolis, we compared the relative roles of sex chromosome conservation versus turnover of sex‐determining mechanisms. We used model‐based comparative methods to reconstruct karyotype evolution and the presence of heteromorphic sex chromosomes onto a newly generated Anolis phylogeny. We found that heteromorphic sex chromosomes evolved multiple times in the genus. Fluorescent in situ hybridization (FISH) of repetitive DNA showed variable rates of Y chromosome degeneration among Anolis species and identified previously undetected, homomorphic sex chromosomes in two species. We confirmed homology of sex chromosomes in the genus …

Formation Of A Salsolinol-Like Compound, The Neurotoxin, 1-Acetyl-6,7-Dihydroxy-1,2,3,4-Tetrahydroisoquinoline, In A Cellular Model Of Hyperglycemia And A Rat Model Of Diabetes, De-Wei Song, Nian Xin, Bing-Jie Xie, Yu-Juan Li, Ling-Yan Meng, Hong-Mei Li, Michael Schläppi, Yu-Lin Deng

Biological Sciences Faculty Research and Publications

There are statistical data indicating that diabetes is a risk factor for Parkinson's disease (PD). Methylglyoxal (MG), a biologically reactive byproduct of glucose metabolism, the levels of which have been shown to be increase in diabetes, reacts with dopamine to form 1-acetyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (ADTIQ); this formation may provide further insight into the connection between PD and diabetes. In this study, we investigated the role of ADTIQ in these two diseases to determine in an aim to enhance our understanding of the link between PD and diabetes. To this end, a cell model of hyperglycemia and a rat model of diabetes were …

Potent Inhibition Of Mandelate Racemase By A Fluorinated Substrate-Product Analogue With A Novel Binding Mode, Mitesh Nagar, Adam D. Lietzan, Martin St. Maurice, Stephen L. Bearne

Biological Sciences Faculty Research and Publications

Mandelate racemase (MR) from Pseudomonas putida catalyzes the Mg2+-dependent 1,1-proton transfer that interconverts the enantiomers of mandelate. Because trifluorolactate is also a substrate of MR, we anticipated that replacing the phenyl rings of the competitive, substrate-product analogue inhibitor benzilate (Ki = 0.7 mM) with trifluoromethyl groups might furnish an inhibitor. Surprisingly, the substrate-product analogue 3,3,3-trifluoro-2-hydroxy-2-(trifluoromethyl)propanoate (TFHTP) was a potent competitive inhibitor [Ki = 27 ± 4 μM; cf. Km = 1.2 mM for both (R)-mandelate and (R)-trifluorolactate]. To understand the origins of this high binding affinity, we determined the X-ray crystal structure of the MR–TFHTP complex to 1.68 Å resolution. …

Functionally Diverse Biotin-Dependent Enzymes With Oxaloacetate Decarboxylase Activity, Adam D. Lietzan, Martin St. Maurice

Biological Sciences Faculty Research and Publications

Biotin-dependent enzymes catalyze carboxylation, decarboxylation and transcarboxylation reactions that participate in the primary metabolism of a wide range of organisms. In all cases, the overall reaction proceeds via two half reactions that take place in physically distinct active sites. In the first half-reaction, a carboxyl group is transferred to the 1-N′ of a covalently tethered biotin cofactor. The tethered carboxybiotin intermediate subsequently translocates to a second active site where the carboxyl group is either transferred to an acceptor substrate or, in some bacteria and archaea, is decarboxylated to biotin and CO₂ in order to power the export of sodium …

Successful Treatment Of An Mtbe-Impacted Aquifer Using A Bioreactor Self-Colonized By Native Aquifer Bacteria, Kristin A. Hicks, Radomir Schmidt, Michael G. Nickelsen, Susan L. Boyle, Jeffrey M. Baker, Paul M. Tornatore, Krassimira R. Hristova, Kate M. Scow

Biological Sciences Faculty Research and Publications

A field-scale fixed bed bioreactor was used to successfully treat an MTBE-contaminated aquifer in North Hollywood, CA without requiring inoculation with introduced bacteria. Native bacteria from the MTBE-impacted aquifer rapidly colonized the bioreactor, entering the bioreactor in the contaminated groundwater pumped from the site, and biodegraded MTBE with greater than 99 % removal efficiency. DNA sequencing of the 16S rRNA gene identified MTBE-degrading bacteria Methylibium petroleiphilum in the bioreactor. Quantitative PCR showed M. petroleiphilum enriched by three orders of magnitude in the bioreactor above densities pre-existing in the groundwater. Because treatment was carried out by indigenous rather than introduced organisms, …

Sorting Out The Trash: The Spatial Nature Of Eukaryotic Protein Quality Control, Emily M. Sontag, Willianne Im Vonk, Judith Frydman

Biological Sciences Faculty Research and Publications

Failure to maintain protein homeostasis is associated with aggregation and cell death, and underlies a growing list of pathologies including neurodegenerative diseases, aging, and cancer. Misfolded proteins can be toxic and interfere with normal cellular functions, particularly during proteotoxic stress. Accordingly, molecular chaperones, the ubiquitin-proteasome system (UPS) and autophagy together promote refolding or clearance of misfolded proteins. Here we discuss emerging evidence that the pathways of protein quality control (PQC) are intimately linked to cell architecture, and sequester proteins into spatially and functionally distinct PQC compartments. This sequestration serves a number of functions, including enhancing the efficiency of quality control; …

Mechanism Of GabaB Receptor-Activated Increases In L-Type Calcium Current In The Neonatal Mammalian Hippocampus, Andrew S. Karls

Dissertations (1934 -)

Activation of the metabotropic GABA_B receptor has most commonly been demonstrated to produce inhibitory effects on neurons, including the attenuation of voltage-dependent calcium current. However, during the early neonatal period in mammalian development, activation of GABA_B receptors leads to an enhancement of calcium current through a specific class of calcium channels, termed L-type channels, (because they conduct Long-lasting current) . This response peaks at 7 days postnatal, and is only demonstrated in a subset of cells. In the work presented here, the signal transduction pathway of GABA_B receptor-mediated increase of L-type current is described.

GABA_B receptors …

Is Logarithmic Transformation Necessary In Allometry? Ten, One-Hundred, One-Thousand-Times Yes, Joseph Mascaro, Creighton M. Litton, R. Flint Hughes, Amanda Uowolo, Stefan A. Schnitzer

Biological Sciences Faculty Research and Publications

No abstract provided.

Ventral Tegmental Area Regulation Of Stress-Induced Reinstatement Of Cocaine-Seeking Behavior, Jordan Michael Blacktop

Dissertations (1934 -)

No FDA approved medications currently exist for the prevention of drug craving, drug seeking, and relapse to cocaine use. Stress is a major factor in causing relapse in cocaine dependent individuals. Cocaine use is positively correlated with stress-induced craving and relapse outcomes. Corticotropin-releasing factor (CRF) is a 41-amino acid neuropeptide that plays an important role in the stress response and in the reinstatement rodent model of stress-induced relapse. CRF is released during stress in brain regions associated with the effects of drugs of abuse, notably the ventral tegmental area (VTA). This dissertation addresses key unknown mechanisms behind drug-induced neuroplasticity and …