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The Role Of The Striatal Neuropeptide Neurotensin In The Methamphetamine-Induced Neural Injury In Mice, Qingkun Liu

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) is a widely abused psychostimulant that induces neurotoxicity to several brain regions, including the striatum. Similar to dopamine (DA) in chemical structure, METH can be transported into DA pre-synaptic terminals, evoking the neurodegeneration in DA terminals and post-synaptic striatal neurons. Despite the critical role of DA in METH-induced neurodegeneration, no pharmaceutical therapeutics has been approved for these conditions. It is therefore essential to investigate the endogenous factors regulating the dopaminergic system. The neuropeptide neurotensin has emerged as a potential modulator of METH-induced striatal neurodegeneration mainly due to its intimate interactions with dopamine in the striatum.

In this study, …

Science Identity Transformations Through Place-Based Teaching And Learning In The Natural World, Amy Defelice

Dissertations, Theses, and Capstone Projects

This dissertation includes three main components related through a sociocultural lens of identity transformation. The first component describes the Field Studies program for ninth grade students at Brooklyn Academy of Science and the Environment (BASE High School), and explores how outdoor settings and place-based pedagogies can be used to enhance urban students' science identities. Student researchers took digital photographs of their Field Studies experiences and met in cogenerative dialogues with me, their teacher, where we shared our reflections. The second component explains students' experiences and reactions to a week-long place-based geoscience program held over spring break at Prospect Park. This …

Biological Motion Processing In Typical Development And In The Autism Spectrum, Aaron Krakowski

Dissertations, Theses, and Capstone Projects

Biological motion (BM) analysis and interpretation is a fundamental process of human neurocognition that has been only minimally explored neurophysiologically. In addition to its importance in understanding the underlying roots and development of social cognition, BM processing is a prime candidate domain for exploring the underlying etiology of social cognitive disorders such as the autism spectrum.

In an initial experiment, typical adults observed BM point-light displays of a human actor (UM) as well as their spatially scrambled counterparts (SM), in both an unattended distractor task as well as an explicit attention task. Results showed a neurophysiological response manifested as three …

High Local Diversity Of Trypanosoma In A Common Bat Species, And Implications For The Biogeography And Taxonomy Of The T. Cruzi Clade, Veronika M. Cottontail, Elisabeth K. V. Kalko, Iain Cottontail, Nele Wellinghausen, Marco Tschapka, Susan L. Perkins, C. Miguel Pinto

Publications and Research

The Trypanosoma cruzi clade is a group of parasites that comprises T. cruzi sensu lato and its closest relatives. Although several species have been confirmed phylogenetically to belong to this clade, it is uncertain how many more species can be expected to belong into this group. Here, we present the results of a survey of trypanosome parasites of the bat Artibeus jamaicensis from the Panama´ Canal Zone, an important seed disperser. Using a genealogical species delimitation approach, the Poisson tree processes (PTP), we tentatively identified five species of trypanosomes – all belonging to the T. cruzi clade. A small monophyletic …

Carboxymethylcellulose Hydrogels Support Central Nervous System-Derived Tumor-Cell Chemotactic Migration: Comparison With Conventional Extracellular Matrix Macromolecules, Tanya Singh, Chandrasekhar Kothapalli, Devika Varma, Steven B. Nicoll, Maribel Vazquez

Publications and Research

The local microenvironment plays an important role in maintaining the dynamics of the extracellular matrix and the cell-extracellular matrix relationship. The extracellular matrix is a complex network of macromolecules with distinct mechanical and biochemical characteristics. Disruptions in extracellular matrix homeostasis are associated with the onset of cancer. The extracellular matrix becomes highly disorganized, and the cell-matrix relationship changes, resulting in altered cell-signaling processes and metastasis. Medulloblastoma is one of the most common malignant pediatric brain tumors in the United States. In order to gain a better understanding of the interplay between cell-extracellular matrix interactions and cell-migratory responses in tumors, eight …

Trans‐Spinal Direct Current Stimulation Modifies Spinal Cord Excitability Through Synaptic And Axonal Mechanisms, Zaghloul Ahmed

Publications and Research

Abstract The spinal cord is extremely complex. Therefore, trans‐spinal direct current stimulation (tsDCS) is expected to produce a multitude of neurophysiological changes. Here, we asked how tsDCS differentially affects synaptic and nonsynaptic transmission. We investigated the effects of tsDCS on synaptically mediated responses by stimulating the medullary longitudinal fascicle and recording responses in the sciatic nerve and triceps and tibialis anterior muscles. Response amplitude was increased during cathodal‐tsDCS (c‐tsDCS), but reduced during anodal‐tsDCS (a‐tsDCS). After‐effects were dependent on the frequency of the test stimulation. c‐tsDCS‐reduced responses evoked by low‐frequency (0.5 Hz) test stimulation and increased responses evoked by high‐frequency (400 …

Improving Mycobacterium Bovis Bacillus Calmette-Guèrin As A Vaccine Delivery Vector For Viral Antigens By Incorporation Of Glycolipid Activators Of Nkt Cells, Manjunatha M. Venkataswamy, Tony W. Ng, Shalu S. Kharkwal, Leandro J. Carreño, Alison J. Johnson, Shajo Kunnath-Velayudhan, Zheng Liu, Robert Bittman, Peter J. Jervis, Liam R. Cox, Gurdyal S. Besra, Xiangshu Wen, Weiming Yuan, Moriya Tsuji, Xiangming Li, David D. Ho, John Chan, Sunhee Lee, Richard Frothingham, Barton F. Haynes

Publications and Research

Recombinant Mycobacterium bovis bacillus Calmette-Guèrin (rBCG) has been explored as a vector for vaccines against HIV because of its ability to induce long lasting humoral and cell mediated immune responses. To maximize the potential for rBCG vaccines to induce effective immunity against HIV, various strategies are being employed to improve its ability to prime CD8+ T cells, which play an important role in the control of HIV infections. In this study we adopted a previously described approach of incorporating glycolipids that activate CD1d-restricted natural killer T (NKT) cells to enhance priming of CD8+ T cells by rBCG strains expressing an …

Inhibition Of Phosphodiesterase10a Attenuates Morphine-Induced Conditioned Place Preference, Ying Mu, Zhaoxiang Ren, Jia Jia, Bo Gao, Longtai Zheng, Guanghui Wang, Eitan Friedman, Xuechu Zhen

Publications and Research

Background Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of PDE10A, on acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP). Results The results show that 2.5 mg/kg MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP. The same dose of MP-10 alone did not result in the CPP. Moreover, MP-10 did not alter the expression of …

Sticking Your Neck Out And Burying The Hatchet: What Idioms Reveal About Embodied Simulation, Natalie A. Kacinik

Publications and Research

Idioms are used in conventional language twice as frequently as metaphors, but most research, particularly recent work on embodiment has focused on the latter. However, idioms have the potential to significantly deepen our understanding of embodiment because their meanings cannot be derived from their component words. To determine whether sensorimotor states could activate idiomatic meaning, participants were instructed to engage in postures/actions reflecting various idioms (e.g.,sticking your neck out) relative to non-idiomatic control postures/actions while reading and responding to statements designed to assess idiomatic meaning. The results showed that statements were generally more strongly endorsed after idiom embodiment than control …

Hemispheric Asymmetry In New Neurons In Adulthood Is Associated With Vocal Learning And Auditory Memory, Shuk C. Tsoi, Utsav V. Aiya, Kobi D. Wasner, Mimi L. Phan, Carolyn L. Pytte, David S. Vicario

Publications and Research

Many brain regions exhibit lateral differences in structure and function, and also incorporate new neurons in adulthood, thought to function in learning and in the formation of new memories. However, the contribution of new neurons to hemispheric differences in processing is unknown. The present study combines cellular, behavioral, and physiological methods to address whether 1) new neuron incorporation differs between the brain hemispheres, and 2) the degree to which hemispheric lateralization of new neurons correlates with behavioral and physiological measures of learning and memory. The songbird provides a model system for assessing the contribution of new neurons to hemispheric specialization …

Dynamically-Expressed Prion-Like Proteins Form A Cuticle In The Pharynx Of Caenorhabditis Elegans, Julia B. George-Raizen, Keith R. Shockley, Nicholas F. Trojanowski, Annesia L. Lamb, David M. Raizen

Publications and Research

In molting animals, a cuticular extracellular matrix forms the first barrier to infection and other environmental insults. In the nematode Caenorhabditis elegans there are two types of cuticle: a wellstudied collagenous cuticle lines the body, and a poorly-understood chitinous cuticle lines the pharynx. In the posterior end of the pharynx is the grinder, a tooth-like cuticular specialization that crushes food prior to transport to the intestine for digestion. We here show that the grinder increases in size only during the molt. To gain molecular insight into the structure of the grinder and pharyngeal cuticle, we performed a microarray analysis to …

Atypical Multisensory Integration In Niemann-Pick Type C Disease – Towards Potential Biomarkers, Gizely N. Andrade, Sophie Molholm, John S. Butler, Alice Brown Brandwein, Steven U. Walkley, John J. Foxe

Publications and Research

Background: Niemann-Pick type C (NPC) is an autosomal recessive disease in which cholesterol and glycosphingolipids accumulate in lysosomes due to aberrant cell-transport mechanisms. It is characterized by progressive and ultimately terminal neurological disease, but both pre-clinical studies and direct human trials are underway to test the safety and efficacy of cholesterol clearing compounds, with good success already observed in animal models. Key to assessing the effectiveness of interventions in patients, however, is the development of objective neurobiological outcome measures. Multisensory integration mechanisms present as an excellent candidate since they necessarily rely on the fidelity of long-range neural connections between the …

Pediatric Stroke And Transcranial Direct Current Stimulation: Methods For Rational Individualized Dose Optimization, Bernadette T. Gillick, Adam Kirton, Jason B. Carmel, Preet Minhas, Marom Bikson

Publications and Research

Background: Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective: Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial. Methods: 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 magnetic resonance imaging (MRI) scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials …

Quantification Of Transient Increase Of The Blood–Brain Barrier Permeability To Macromolecules By Optimized Focused Ultrasound Combined With Microbubbles, Lingyan Shi, Paolo Palacio-Mancheno, Joseph Badami, Da Wi Shin, Min Zeng, Luis Cardoso, Raymond Tu, Bingmei M. Fu

Publications and Research

Radioimmunotherapy using a radiolabeled monoclonal antibody that targets tumor cells has been shown to be efficient for the treatment of many malignant cancers, with reduced side effects. However, the blood–brain barrier (BBB) inhibits the transport of intravenous antibodies to tumors in the brain. Recent studies have demonstrated that focused ultrasound (FUS) combined with microbubbles (MBs) is a promising method to transiently disrupt the BBB for the drug delivery to the central nervous system. To find the optimal FUS and MBs that can induce reversible increase in the BBB permeability, we employed minimally invasive multiphoton microscopy to quantify the BBB permeability …

Nesting Behaviour Influences Species-Specific Gas Exchange Across Avian Eggshells, Steven J. Portugal, Golo Maurer, Gavin H. Thomas, Mark E. Hauber, Tomáš Grim, Phillip Cassey

Publications and Research

Carefully controlled gas exchange across the eggshell is essential for the development of the avian embryo. Water vapour conductance (GH2O) across the shell, typically measured as mass loss during incubation, has been demonstrated to optimally ensure the healthy development of the embryo while avoiding desiccation. Accordingly, eggs exposed to sub-optimal gas exchange have reduced hatching success. We tested the association between eggshell GH2O and putative life-history correlates of adult birds, ecological nest parameters and physical characteristics of the egg itself to investigate how variation in GH2O has evolved to maintain optimal water loss across a diverse set of nest environments. …

Detecting Concerted Demographic Response Across Community Assemblages Using Hierarchical Approximate Bayesian Computation, Yvonne L. Chan, David Schanzenbach, Michael J. Hickerson

Publications and Research

Methods that integrate population-level sampling from multiple taxa into a single community-level analysis are an essential addition to the comparative phylogeographic toolkit. Detecting how species within communities have demographically tracked each other in space and time is important for understanding the effects of future climate and landscape changes and the resulting acceleration of extinctions, biological invasions, and potential surges in adaptive evolution. Here, we present a statistical framework for such an analysis based on hierarchical approximate Bayesian computation (hABC) with the goal of detecting concerted demographic histories across an ecological assemblage. Our method combines population genetic data sets from multiple …

Translational Regulation Of The Doubletime/Ckiδ/Ε Kinase By Lark Contributes To Circadian Period Modulation, Yanmei Huang, Gerard P. Mcneil, F. Rob Jackson

Publications and Research

The Drosophila homolog of Casein Kinase I δ/ε, DOUBLETIME (DBT), is required for Wnt, Hedgehog, Fat and Hippo signaling as well as circadian clock function. Extensive studies have established a critical role of DBT in circadian period determination. However, how DBT expression is regulated remains largely unexplored. In this study, we show that translation of dbt transcripts are directly regulated by a rhythmic RNA-binding protein (RBP) called LARK (known as RBM4 in mammals). LARK promotes translation of specific alternative dbt transcripts in clock cells, in particular the dbt-RC transcript. Translation of dbt-RC exhibits circadian changes under free-running conditions, indicative of …

Dog Movie Stars And Dog Breed Popularity: A Case Study In Media Influence On Choice, Stefano Ghirlanda, Alberto Acerbi, Harold Herzog

Publications and Research

Fashions and fads are important phenomena that influence many individual choices. They are ubiquitous in human societies, and have recently been used as a source of data to test models of cultural dynamics. Although a few statistical regularities have been observed in fashion cycles, their empirical characterization is still incomplete. Here we consider the impact of mass media on popular culture, showing that the release of movies featuring dogs is often associated with an increase in the popularity of featured breeds, for up to 10 years after movie release. We also find that a movie's impact on breed popularity correlates …

Transcranial Direct Current Stimulation Facilitates Cognitive Multi-Task Performance Differentially Depending On Anode Location And Subtask, Melissa Scheldrup, Pamela M. Greenwood, Ryan Mckendrick, Jon Strohl, Marom Bikson, Mahtab Alam, R. Andy Mckinley, Raja Parasuraman

Publications and Research

There is a need to facilitate acquisition of real world cognitive multi-tasks that require long periods of training (e.g., air traffic control, intelligence analysis, medicine). Non-invasive brain stimulation—specifically transcranial Direct Current Stimulation (tDCS)—has promise as a method to speed multi-task training. We hypothesized that during acquisition of the complex multi-task Space Fortress, subtasks that require focused attention on ship control would benefit from tDCS aimed at the dorsal attention network while subtasks that require redirection of attention would benefit from tDCS aimed at the right hemisphere ventral attention network. We compared effects of 30 min prefrontal and parietal stimulation to …

Use Of Caenorhabditis Elegans As A Model To Study Alzheimer’S Disease And Other Neurodegenerative Diseases, Adanna G. Alexander, Vanessa Marfil, Chris Li

Publications and Research

Advances in research and technology has increased our quality of life, allowed us to combat diseases, and achieve increased longevity. Unfortunately, increased longevity is accompanied by a rise in the incidences of age-related diseases such as Alzheimer’s disease (AD). AD is the sixth leading cause of death, and one of the leading causes of dementia amongst the aged population in the USA. It is a progressive neurodegenerative disorder, characterized by the prevalence of extracellular Aβ plaques and intracellular neurofibrillary tangles, derived from the proteolysis of the amyloid precursor protein (APP) and the hyperphosphorylation of microtubule-associated protein tau, respectively. Despite years …

Histone Methyltransferase Mmset/Nsd2 Alters Ezh2 Binding And Reprograms The Myeloma Epigenome Through Global And Focal Changes In H3k36 And H3k27 Methylation, Relja Popovic, Eva Martinez-Garcia, Eugenia G. Giannopoulou, Quanwei Zhang, Qingyang Zhang, Teresa Ezponda, Mrinal Y. Shah, Yupeng Zheng, Christine M. Will, Eliza C. Small, Youjia Hua, Marinka Bulic, Yanwen Jiang, Matteo Carrara, Raffaele A. Calogero, William L. Kath, Neil L. Kelleher, Ji-Ping Wang, Olivier Elemento, Jonathan D. Licht

Publications and Research

Overexpression of the histone methyltransferase MMSET in t(4;14)+ multiple myeloma patients is believed to be the driving factor in the pathogenesis of this subtype of myeloma. MMSET catalyzes dimethylation of lysine 36 on histone H3 (H3K36me2), and its overexpression causes a global increase in H3K36me2, redistributing this mark in a broad, elevated level across the genome. Here, we demonstrate that an increased level of MMSET also induces a global reduction of lysine 27 trimethylation on histone H3 (H3K27me3). Despite the net decrease in H3K27 methylation, specific genomic loci exhibit enhanced recruitment of the EZH2 histone methyltransferase and become hypermethylated on …

An Information Theory Account Of Cognitive Control, Jin Fan

Publications and Research

Our ability to efficiently process information and generate appropriate responses depends on the processes collectively called cognitive control. Despite a considerable focus in the literature on the cognitive control of information processing, neural mechanisms underlying control are still unclear, and have not been characterized by considering the quantity of information to be processed. A novel and comprehensive account of cognitive control is proposed using concepts from information theory, which is concerned with communication system analysis and the quantification of information. This account treats the brain as an information-processing entity where cognitive control and its underlying brain networks play a pivotal …

Long-Term Cre-Mediated Retrograde Tagging Of Neurons Using A Novel Recombinant Pseudorabies Virus, Hysell V. Oviedo, Hassasna K. Oyibo, Petr Znamenskiy, Lynn W. Enquist, Anthony M. Zador

Publications and Research

Brain regions contain diverse populations of neurons that project to different long-range targets. The study of these subpopulations in circuit function and behavior requires a toolkit to characterize and manipulate their activity in vivo. We have developed a novel set of reagents based on Pseudorabies Virus (PRV) for efficient and long-term genetic tagging of neurons based on their projection targets. By deleting IE180, the master transcriptional regulator in the PRV genome, we have produced a mutant virus capable of infection and transgene expression in neurons but unable to replicate in or spread from those neurons. IE180-null mutants showed no cytotoxicity, …

Statistical Signs Of Social Influence On Suicides, Hygor Piaget M. Melo, André A. Moreira, Élcio Batista, Hernán A. Makse, José S. Andrade

Publications and Research

By treating the suicide as a social fact, Durkheim envisaged that suicide rates should be determined by the connections between people and society. Under the same framework, he considered that crime is bound up with the fundamental conditions of all social life. The social effect on the occurrence of homicides has been previously substantiated, and confirmed here, in terms of a superlinear scaling relation: by doubling the population of a Brazilian city results in an average increment of 135% in the number of homicides, rather than the expected isometric increase of 100%, as found, for example, for the mortality due …

Rejection Positivity Predicts Trial-To-Trial Reaction Times In An Auditory Selective Attention Task: A Computational Analysis Of Inhibitory Control, Sufen Chen, Robert D. Melara

Publications and Research

A series of computer simulations using variants of a formal model of attention (Melara and Algom, 2003) probed the role of rejection positivity (RP), a slow-wave electroencephalographic (EEG) component, in the inhibitory control of distraction. Behavioral and EEG data were recorded as participants performed auditory selective attention tasks. Simulations that modulated processes of distractor inhibition accounted well for reaction-time (RT) performance, whereas those that modulated target excitation did not. A model that incorporated RP from actual EEG recordings in estimating distractor inhibition was superior in predicting changes in RT as a function of distractor salience across conditions. A …

Rejection Positivity Predicts Trial-To-Trial Reaction Times In An Auditory Selective Attention Task: A Computational Analysis Of Inhibitory Control, Sufen Chen, Robert D. Melara

Publications and Research

A series of computer simulations using variants of a formal model of attention (Melara and Algom, 2003) probed the role of rejection positivity (RP), a slow-wave electroencephalographic (EEG) component, in the inhibitory control of distraction. Behavioral and EEG data were recorded as participants performed auditory selective attention tasks. Simulations that modulated processes of distractor inhibition accounted well for reaction-time (RT) performance, whereas those that modulated target excitation did not. A model that incorporated RP from actual EEG recordings in estimating distractor inhibition was superior in predicting changes in RT as a function of distractor salience across conditions. A model that …

Inferring The Provenance Of An Alien Species With Dna Barcodes: The Neotropical Butterfly Dryas Iulia In Thailand, Noah A. Burg, Ashman Pradhan, Rebecca M. Gonzalez, Emely Z. Morban, Erica W. Zhen, Watana Sakchoowong, David J. Lohman

Publications and Research

The Neotropical butterfly Dryas iulia has been collected from several locations in Thailand and Malaysia since 2007, and has been observed breeding in the wild, using introduced Passiflora foetida as a larval host plant. The butterfly is bred by a butterfly house in Phuket, Thailand, for release at weddings and Buddhist ceremonies, and we hypothesized that this butterfly house was the source of wild, Thai individuals. We compared wing patterns and COI barcodes from two, wild Thai populations with individuals obtained from this butterfly house. All Thai individuals resemble the subspecies D. iulia modesta, and barcodes from wild and captive …

Nucleolar Integrity Is Required For The Maintenance Of Long-Term Synaptic Plasticity, Kim D. Allen, Andrei V. Gourov, Christopher Harte, Peng Gao, Clarice, Darlene Sylvain, Joshua M. Splett, William C. Oxberry, Paula S. Van De Nes, Matthew J. Troy-Regier, Jason Wolk, Juan M. Alarcon, A. Iván Hernández

Publications and Research

Long-term memory (LTM) formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose) polymerase-1 (PARP-1), are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP) in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs. The activity-dependent upregulation of rRNA, as well as L-LTP expression, are poly(ADP-ribosyl)ation (PAR) dependent and …

Carbon Partitioning In Green Algae (Chlorophyta) And The Enolase Enzyme, Jürgen E. W. Polle, Peter Neofotis, Andy Huang, William Chang, Kiran Sury, Eliza M. Wiech

Publications and Research

The exact mechanisms underlying the distribution of fixed carbon within photoautotrophic cells, also referred to as carbon partitioning, and the subcellular localization of many enzymes involved in carbon metabolism are still unknown. In contrast to the majority of investigated green algae, higher plants have multiple isoforms of the glycolytic enolase enzyme, which are differentially regulated in higher plants. Here we report on the number of gene copies coding for the enolase in several genomes of species spanning the major classes of green algae. Our genomic analysis of several green algae revealed the presence of only one gene coding for a …

Modflow: An Insight Into Thirty Years Development Of A Standard Numerical Code For Groundwater Simulations, Dalila Loudyi, Roger Falconer, Binliang Lin

International Conference on Hydroinformatics

Of all of the groundwater flow models widely available, the U.S. Geological Survey three-dimensional modular finite-difference, groundwater flow model, MODFLOW, is regarded by many as the most widely used by government agencies and consultancy firms. The Model was first developed in 1984 and since then many changes, updates and corrections have been introduced to the programme, simultaneously with its growing use. Since its establishment as a world-wide standard for groundwater flow modelling, many programmes have been developed to link MODFLOW to other codes that use groundwater flow information in porous saturated media. Processes such as solute transport, variable density flow, …