Life Sciences Commons^™

Autophagy And Lipid Homeostasis In C. Elegans, Melissa J. Silvestrini

Dissertations, Theses, and Capstone Projects

The worldwide prevalence of obesity, particularly in developed nations, has become an epidemic in recent decades and the trend is continuing to rise. Moreover, the prevalence of obesity in children and adolescents is rising at an alarming rate. Obesity is associated with an increased risk of metabolic disorders including heart disease, insulin resistance, type 2 diabetes and nonalcoholic fatty liver disease. Therefore it is no surprise that lipid-related metabolic disorders have become a significant burden to our healthcare system. In recent years, the conserved cellular recycling process of autophagy has been linked to several lipid-related metabolic disorders, including insulin resistance, …

Adult Neurogenesis In Avian Auditory Cortex, Caudomedial Nidopallium (Ncm): Lateralization And Effects Of Statins, Shuk C. Tsoi

Dissertations, Theses, and Capstone Projects

In the first part of this paper, we investigated the basic relationship between learning, memory and adult neurogenesis using zebra finches. We found that in the auditory cortex, the left hemisphere had more new neurons than the right hemisphere. This lateralization was correlated with song learning and memory. In the second part, we used juvenile zebra finches as a model organism to study the effects of Lipitor on learning, memory and neurogenesis. We found that Lipitor impaired song learning and memory storage. Lipitor treatments also changed the morphology of new neurons and size of old neurons, suggesting statins may affect …

Implementing An Mhealth System For Substance Use Disorders In Primary Care: A Mixed Methods Study Of Clinicians’ Initial Expectations And First Year Experiences, Marie-Louise Mares, David H. Gustafson, Joseph E. Glass, Andrew Quanbeck, Helene Mcdowell, Fiona Mctavish, Amy K. Atwood, Lisa A. Marsch, Chanetelle Thomas, Dhavan Shah, Randall Brown, Andrew Isham, Mary Jane Nealon, Victoria Ward

Publications and Research

Background: Millions of Americans need but don’t receive treatment for substance use, and evidence suggests that addiction-focused interventions on smart phones could support their recovery. There is little research on implementation of addiction-related interventions in primary care, particularly in Federally Qualified Health Centers (FQHCs) that provide primary care to underserved populations. We used mixed methods to examine three FQHCs’ implementation of Seva, a smart-phone app that offers patients online support/discussion, health-tracking, and tools for coping with cravings, and offers clinicians information about patients’ health tracking and relapses. We examined (a) clinicians’ initial perspectives about implementing Seva, and (b) the first …

A Pretargeted Approach For The Multimodal Pet/Nirf Imaging Of Colorectal Cancer, Pierre Adumeau, Kathryn E. Carnazza, Christian Brand, Sean D. Carlin, Thomas Reiner, Brian J. Agnew, Jason S. Lewis, Brian M. Zeglis

Publications and Research

The complementary nature of positron emission tomography (PET) and near-infrared fluorescence (NIRF) imaging makes the development of strategies for the multimodal PET/NIRF imaging of cancer a very enticing prospect. Indeed, in the context of colorectal cancer, a single multimodal PET/NIRF imaging agent could be used to stage the disease, identify candidates for surgical intervention, and facilitate the image-guided resection of the disease. While antibodies have proven to be highly effective vectors for the delivery of radioisotopes and fluorophores to malignant tissues, the use of radioimmunoconjugates labeled with long-lived nuclides such as 89Zr poses two important clinical complications: high radiation doses …

Motor Experience Reprograms Development Of A Genetically-Altered Bilateral Corticospinal Motor Circuit, Najet Serradj, John H. Martin

Publications and Research

Evidence suggests that motor experience plays a role in shaping development of the corticospinal system and voluntary motor control, which is a key motor function of the system. Here we used a mouse model with conditional forebrain deletion of the gene for EphA4 (Emx1-Cre:EphA4tm2Kldr), which regulates development of the laterality of corticospinal tract (CST). We combined study of Emx1-Cre:EphA4tm2Kldr with unilateral forelimb constraint during development to expand our understanding of experience-dependent CST development from both basic and translational perspectives. This mouse develops dense ipsilateral CST projections, a bilateral motor cortex motor representation, and bilateral motor phenotypes. Together these phenotypes can …

Fhf-Independent Conduction Of Action Potentials Along The Leak-Resistant Cerebellar Granule Cell Axon, Katarzyna Dover, Christopher Marra, Sergio Solinas, Marko Popovic, Sathyaa Subramaniyam, Dejan Zecevic, Egidio D'Angelo, Mitchell Goldfarb

Publications and Research

Neurons in vertebrate central nervous systems initiate and conduct sodium action potentials in distinct subcellular compartments that differ architecturally and electrically. Here, we report several unanticipated passive and active properties of the cerebellar granule cell’s unmyelinated axon. Whereas spike initiation at the axon initial segment relies on sodium channel (Nav)-associated fibroblast growth factor homologous factor (FHF) proteins to delay Nav inactivation, distal axonal Navs show little FHF association or FHF requirement for high-frequency transmission, velocity and waveforms of conducting action potentials. In addition, leak conductance density along the distal axon is estimated as o1% that of somatodendritic membrane. The faster …

Myelinating Glia Differentiation Is Regulated By Extracellular Matrix Elasticity, Mateusz M. Urbanski, Lyle Kingsbury, Daniel Moussouros, Imran Kassim, Saraf Mehjabeen, Navid Paknejad, Alicia Meléndez

Publications and Research

The mechanical properties of living tissues have a significant impact on cell differentiation, but remain unexplored in the context of myelin formation and repair. In the PNS, the extracellular matrix (ECM) incorporates a basal lamina significantly denser than the loosely organized CNS matrix. Inhibition of non-muscle myosin II (NMII) enhances central but impairs peripheral myelination and NMII has been implicated in cellular responses to changes in the elasticity of the ECM. To directly evaluate whether mechanotransduction plays a role in glial cell differentiation, we cultured Schwann cells (SC) and oligodendrocytes (OL) on matrices of variable elastic modulus, mimicking either their …

Ifn-G Induces Histone 3 Lysine 27 Trimethylation In A Small Subset Of Promoters To Stably Silence Gene Expression In Human Macrophages, Yu Qiao, Kyuho Kang, Eugenia Giannopoulou, Celeste Fang, Lionel B. Ivashkiv

Publications and Research

The mechanisms by which IFN-g activates expression of interferon-stimulated genes that have inflammatory and host defense functions are well understood. In contrast, little is known about how IFN-g represses gene expression. By using transcriptomic and epigenomic analysis, we found that stable repression of a small group of genes by IFN-g is associated with recruitment of the histone methyltransferase EZH2 and deposition of the negative mark histone 3 lysine 27 trimethylation (H3K27me3) at their promoters. Repressed genes included MERTK, PPARG, and RANK, which have anti-inflammatory functions and promote osteoclast differentiation. Gene repression and H3K27me3 persisted after IFN-g signaling was terminated, and …

Receptor-Type Guanylyl Cyclase At 76c (Gyc76c) Regulates De Novo Lumen Formation During Drosophila Tracheal Development, Monn Monn Myat, Unisha Patel

Publications and Research

Lumen formation and maintenance are important for the development and function of essential organs such as the lung, kidney and vasculature. In the Drosophila embryonic trachea, lumena formde novo to connect the different tracheal branches into an interconnected network of tubes. Here, we identify a novel role for the receptor type guanylyl cyclase at 76C (Gyc76C) in de novo lumen formation in the Drosophila trachea.We show that in embryosmutant for gyc76C or its downsteam effector protein kinase G (PKG) 1, tracheal lumena are disconnected. Dorsal trunk (DT) cells of gyc76C mutant embryos migrate to contact each other and complete the …

Temporal Regularity Increases With Repertoire Complexity In The Australian Pied Butcherbird’S Song, Eathan Janney, Hollis Taylor, Constance Scharff, David Rothenberg, Lucas C. Parra, Ofer Tchernichovski

Publications and Research

Music maintains a characteristic balance between repetition and novelty. Here, we report a similar balance in singing performances of free-living Australian pied butcherbirds. Their songs include many phrase types. The more phrase types in a bird’s repertoire, the more diverse the singing performance can be. However, without sufficient temporal organization, avian listeners may find diverse singing performances difficult to perceive and memorize. We tested for a correlation between the complexity of song repertoire and the temporal regularity of singing performance. We found that different phrase types often share motifs (notes or stereotyped groups of notes). These shared motifs reappeared in …

Nmr And Structural Data For Connexin 32 And Connexin 26 N-Terminal Peptides, Yuskel Batir, Thaddeus A. Bargiello, Terry L. Dowd

Publications and Research

In this article we present 1H and 13C chemical shift assignments, secondary structural propensity data and normalized temperature coefficient data for N-terminal peptides of Connexin 26(Cx26), Cx26G12R and Cx32G12R mutants seen in syndromic deafness and Charcot Marie Tooth Disease respectively, published in “Structural Studies of N-Terminal Mutants of Connexin 26 and Connexin 32 Using 1HNMR Spectroscopy” (Y.Batir,T.A.Bargiello,T.L.Dowd, 2016)[1]. The mutation G12R affects thestructure of both Cx26 and Cx32 peptides differently. We present data from secondary structure propensity chemical shift analysis which calculates a secondary structurepropensity (SSP) score for both disordered or folded peptides and proteins using the difference between the …

The Off-Label Use, Utility And Potential Value Of Tdcs In The Clinical Care Of Particular Neuropsychiatric Conditions, Marom Bikson, Bhaskar Paneri, James Giordano

Publications and Research

No abstract provided.

A Global Edna Comparison Of Freshwater Bacterioplankton Assemblages Focusing On Large-River Floodplain Lakes Of Brazil, Michael Tessler, Mercer R. Brugler, Rob Desalle, Rebecca Hersch, Luiz Felipe M. Velho, Bianca T. Segovia, Fabio A. Lansac-Toha, Michael J. Lemke

Publications and Research

With its network of lotic and lentic habitats that shift during changes in seasonal connection, the tropical and subtropical large-river systems represent possibly the most dynamic of all aquatic environments. Pelagic water samples were collected from Brazilian floodplain lakes (total n = 58) in four floodpulsed systems (Amazon [n = 21], Araguaia [n = 14], Paraná [n = 15], and Pantanal [n = 8]) in 2011–2012 and sequenced via 454 for bacterial environmental DNA using 16S amplicons; additional abiotic field and laboratory measurements were collected for the assayed lakes.We report here a global comparison of the bacterioplankton makeup of freshwater …

A Species-Level Phylogeny Of Extant Snakes With Description Of A New Colubrid Subfamily And Genus, Alex Figueroa, Alexander D. Mckelvy, L. Lee Grismer, Charles D. Bell, Simon P. Lailvaux

Publications and Research

Background With over 3,500 species encompassing a diverse range of morphologies and ecologies, snakes make up 36% of squamate diversity. Despite several attempts at estimating higherlevel snake relationships and numerous assessments of generic- or species-level phylogenies, a large-scale species-level phylogeny solely focusing on snakes has not been completed. Here, we provide the largest-yet estimate of the snake tree of life using maximum likelihood on a supermatrix of 1745 taxa (1652 snake species + 7 outgroup taxa) and 9,523 base pairs from 10 loci (5 nuclear, 5 mitochondrial), including previously unsequenced genera (2) and species (61).

Results Increased taxon sampling resulted …

Insights Into The Molecular Roles Of Heparan Sulfate Proteoglycans (Hspgs-Syndecans) In Autocrine And Paracrine Growth Factor Signaling In The Pathogenesis Of Hodgkin's Lymphoma, Rajendra Ghardbaran

Publications and Research

Syndecans (SDC, SYND) comprise a group of four structurally related type 1 transmembrane heparan sulfate proteoglycans (HSPGs) that play important roles in tumorigenic processes. SDCs exert signaling via their protein cores and their conserved transmembrane and cytoplasmic domains or by forming complexes with growth factors (GFs). In classical Hodgkin's lymphoma (cHL), a lymphoid neoplasm of predominantly B cell origin, SDC1 and SDC4 are the active SDCs, and a number of GF (vascular endothelial growth factor, fibroblast growth factor, etc.) signaling pathways have been studied. However, despite extensive pre-clinical and clinical research on SDC-mediated GF signaling in many cancer types, there …

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.

From Sensory Perception To Lexical-Semantic Processing: An Erp Study In Non-Verbal Children With Autism, Chiara Cantiani, Naseem A. Choudhury, Yan H. Yu, Valerie L. Shafer, Richard G. Schwartz, April A. Benasich

Publications and Research

This study examines electrocortical activity associated with visual and auditory sensory perception and lexical-semantic processing in nonverbal (NV) or minimally-verbal (MV) children with Autism Spectrum Disorder (ASD). Currently, there is no agreement on whether these children comprehend incoming linguistic information and whether their perception is comparable to that of typically developing children. Event-related potentials (ERPs) of 10 NV/MV children with ASD and 10 neurotypical children were recorded during a picture-word matching paradigm. Atypical ERP responses were evident at all levels of processing in children with ASD. Basic perceptual processing was delayed in both visual and auditory domains but overall was …

Social Defeat Stress Induces Depression-Like Behavior And Alters Spine Morphology In The Hippocampus Of Adolescent Male C57bl/6 Mice, Sergio D. Iñiguez, Antonio Aubry, Lace M. Riggs, Jason B. Alipio, Roseanna M. Zanca, Francisco J. Flores-Ramirez, Mirella A. Hernandez, Steven J. Nieto, David Musheyev, Peter Serrano

Publications and Research

Social stress, including bullying during adolescence, is a risk factor for common psychopathologies such as depression. To investigate the neural mechanisms associated with juvenile social stress-induced mood-related endophenotypes, we examined the behavioral, morphological, and biochemical effects of the social defeat stress model of depression on hippocampal dendritic spines within the CA1 stratum radiatum. Adolescent (postnatal day 35) male C57BL/6 mice were subjected to defeat episodes for 10 consecutive days. Twenty-four h later, separate groups of mice were tested on the social interaction and tail suspension tests. Hippocampi were then dissected and Western blots were conducted to quantify protein levels for …

Anomaly Detection In Host Signaling Pathways For The Early Prognosis Of Acute Infection, Kun Wang, Stanley Langevin, Corey S. O'Hern, Mark D. Shattuck, Serenity Ogle, Adriana Forero, Juliet Morrison, Richard Slayden, Michael G. Katze, Michael Kirby

Publications and Research

Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic …

Molecular Basis For Strain Variation In The Saccharomyces Cerevisiae Adhesin Flo11p, Subit Barua, Li Li, Peter N. Lipke, Anne M. Dranginis

Publications and Research

FLO11 encodes a yeast cell wall flocculin that mediates a variety of adhesive phenotypes in Saccharomyces cerevisiae. Flo11p is implicated in many developmental processes, including flocculation, formation of pseudohyphae, agar invasion, and formation of microbial mats and biofilms. However, Flo11p mediates different processes in different yeast strains. To investigate the mechanisms by which FLO11 determines these differences in colony morphology, flocculation, and invasion, we studied gene structure, function, and expression levels. Nonflocculent Saccharomyces cerevisiae 1278b cells exhibited significantly higher FLO11 mRNA expression, especially in the stationary phase, than highly flocculent S. cerevisiae var. diastaticus. The two strains varied in cell …

Force Sensitivity In Saccharomyces Cerevisiae Flocculins, Cho X. Chan, Sofiane El-Kirat-Chatel, Ivor G. Joseph, Desmond N. Jackson, Caleen B. Ramsook, Yves F. Dufrêne, Peter N. Lipke

Publications and Research

Many fungal adhesins have short, -aggregation-prone sequences that play important functional roles, and in the Candida albicans adhesin Als5p, these sequences cluster the adhesins after exposure to shear force. Here, we report that Saccharomyces cerevisiae flocculins Flo11p and Flo1p have similar -aggregation-prone sequences and are similarly stimulated by shear force, despite being nonhomologous. Shear from vortex mixing induced the formation of small flocs in cells expressing either adhesin. After the addition of Ca2, yeast cells from vortex-sheared populations showed greatly enhanced flocculation and displayed more pronounced thioflavin-bright surface nanodomains. At high concentrations, amyloidophilic dyes inhibited Flo1p- and Flo11p-mediated agar invasion …

Physical Separation From The Mate Diminishes Male’S Attentiveness Towards Other Females: A Study In Monogamous Prairie Voles Microtus Ochrogaster, Christine J. Delevan, Natalia A. Rodriguez, Karine M. Legzim, Fayeza Aliou, Jamie T. Parker, Maryam Bashad

Publications and Research

We tested whether continuous cohabitation in monogamous voles affects the mated male’s attentiveness to his breeding partner versus another female. Each male was housed in a 3-chamber apparatus with a Focal female (FF) and a Control female (CF) for 13 days then placed in a T-maze to assess his attentiveness to and memory of those females. The Distal male remained physically separated from both females, but received their distal cues. The Separate male cohabited with the FF for 3 days then remained physically separated from both females. The Disrupt male’s continuous cohabitation with the FF was disrupted by having him …

Does Cognitive Impairment Affect Rehabilitation Outcome In Parkinson’S Disease?, Davide Ferrazzoli, Paola Ortelli, Roberto Maestri, Rossana Bera, Nir Giladi, Maria Felice Ghilardi, Gianni Pezzoli, Giusseppe Frazzitta

Publications and Research

Background: The cognitive status is generally considered as a major determinant of rehabilitation outcome in Parkinson’s disease (PD). No studies about the effect of cognitive impairment on motor rehabilitation outcomes in PD have been performed before.

Objective: This study is aimed to evaluate the impact of cognitive decline on rehabilitation outcomes in patients with PD.

Methods: We retrospectively identified 485 patients with PD hospitalized for a 4-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT) between January 2014 and September 2015. According to Mini Mental State Examination (MMSE), patients were divided into: group 1—normal cognition (score 27–30), group 2—mild cognitive …

Inducing Application Of Interdisciplinary Frameworks: Experiences From The Domains Of Information Literacy And Responsible Conduct Of Research, Anne E. Leonard, Jean E. Hillstrom

Publications and Research

Constructivist frameworks for information literacy and research ethics can be developed and nurtured in the context of an interdisciplinary course. Using the frameworks of two disciplines, students went on an experiential journey in support of ethics foundations through guest lectures and active learning exercises. This study describes the development and content of the responsible conduct of research and information literacy modules and discusses the role of each in an interdisciplinary course. Learning goals for both modules were evaluated by examining student responses in a free-writing exercise at the end of the semester, concluding with a discussion of the structural and …

Prophylactic Bacteriophage Administration More Effective Than Post-Infection Administration In Reducing Salmonella Enterica Serovar Enteritidis Shedding In Quail, Mosab Ahmadi, M. Amir Karimi Torshizi, Shaban Rahimi, John J. Dennehy

Publications and Research

Infections caused by Salmonella bacteria, often through poultry products, are a serious public health issue. Because of drawbacks associated with antibiotic prophylaxis, alternative treatments are sought. Bacterial viruses (bacteriophages) may provide an effective alternative, but concerns remain with respect to bacteriophage stability and effectiveness. To this end, we assessed the stability of a novel bacteriophage isolated from poultry excreta, siphovirus PSE, and its effectiveness in reducing Salmonella enterica serovar Enteritidis colonization in vitro and in vivo. Moreover, we sought to determine how the timing (prophylactic or therapeutic) and route (oral gavage or vent lip) of PSE administration impacted its effectiveness. …

Prenatal Cocaine Exposure Upregulates Bdnf-Trkb Signaling, Andreas Stucky, Kalindi P. Bakshi, Eitan Friedman, Hoau-Yan Wang

Publications and Research

Prenatal cocaine exposure causes profound changes in neurobehavior as well as synaptic function and structure with compromised glutamatergic transmission. Since synaptic health and glutamatergic activity are tightly regulated by brain-derived neurotrophic factor (BDNF) signaling through its cognate tyrosine receptor kinase B (TrkB), we hypothesized that prenatal cocaine exposure alters BDNF-TrkB signaling during brain development. Here we show prenatal cocaine exposure enhances BDNF-TrkB signaling in hippocampus and prefrontal cortex (PFCX) of 21-day-old rats without affecting the expression levels of TrkB, P75NTR, signaling molecules, NMDA receptor—NR1 subunit as well as proBDNF and BDNF. Prenatal cocaine exposure reduces activity-dependent proBDNF and BDNF release …

Odorant Receptors Can Mediate Axonal Identity And Gene Choice Via Campindependent Mechanisms, Kiavash Movahedi, Xavier Grosmaitre, Paul Feinstein

Publications and Research

Odorant receptors (ORs) control several aspects of cell fate in olfactory sensory neurons (OSNs), including singular gene choice and axonal identity. The mechanisms of OR-induced axon guidance have been suggested to principally rely on G-protein signalling. Here, we report that for a subset of OSNs, deleting G proteins or altering their levels of signalling does not affect axonal identity. Signalling-deficient ORs or surrogate receptors that are unable to couple to Gs/Golf still provide axons with distinct identities and the anterior–posterior targeting of axons does not correlate with the levels of cAMP produced by genetic modifications. In addition, we refine the …

Leaf Protein And Mineral Concentrations Across The “Miracle Tree” Genus Moringa, Mark E. Olson, Renuka P. Sankaran, Jed W. Fahey, Michael A. Grusak, David Odee, Wasif Nouman

Publications and Research

The moringa tree Moringa oleifera is a fast-growing, drought-resistant tree cultivated across the lowland dry tropics worldwide for its nutritious leaves. Despite its nutritious reputation, there has been no systematic survey of the variation in leaf nutritional quality across M. oleifera grown worldwide, or of the other species of the genus. To guide informed use of moringa, we surveyed protein, macro-, and micro- nutrients across 67 common garden samples of 12 Moringa taxa, including 23 samples of M. oleifera. Moringa oleifera, M. concanensis, M. stenopetala, an M. concanensis X oleifera hybrid, and M. longituba were highest in protein, with M. …

Mousensor: A Versatile Genetic Platform To Create Super Sniffer Mice For Studying Human Odor Coding, Charlotte D'Hulst, Raena B. Mina, Zachary Gershon, Sophie Jamet, Antonio Cerullo, Delia Tomoiaga, Li Bai, Leonardo Belluscio, Matthew E. Rogers, Yevgeniy Sirotin, Paul Feinstein

Publications and Research

Typically, 0.1% of the total number of olfactory sensory neurons (OSNs) in the main olfactory epithelium express the same odorant receptor (OR) in a singular fashion and their axons coalesce into homotypic glomeruli in the olfactory bulb. Here, we have dramatically increased the total number of OSNs expressing specific cloned OR coding sequences by multimerizing a 21-bp sequence encompassing the predicted homeodomain binding site sequence, TAATGA, known to be essential in OR gene choice. Singular gene choice is maintained in these ‘‘MouSensors.’’ In vivo synaptopHluorin imaging of odor-induced responses by known M71 ligands shows functional glomerular activation in an M71 …

Nmrfx Processor: A Cross-Platform Nmr Data Processing Program, Michael Norris, Bayard Fetler, Jan Marchant, Bruce A. Johnson

Advanced Science Research Center

NMRFx Processor is a new program for the processing of NMR data. Written in the Java programming language, NMRFx Processor is a cross-platform application and runs on Linux, Mac OS X and Windows operating systems. The application can be run in both a graphical user interface (GUI) mode and from the command line. Processing scripts are written in the Python programming language and executed so that the low-level Java commands are automatically run in parallel on computers with multiple cores or CPUs. Processing scripts can be generated automatically from the parameters of NMR experiments or interactively constructed in the GUI. …