Digital Commons Network^™

Clustering Neural Spike Trains With Transient Responses, John D. Hunter, Jianhong Wu, John Milton

WM Keck Science Faculty Papers

The detection of transient responses, i.e. nonstationarities, that arise in a varying and small fraction of the total number of neural spike trains recorded from chronically implanted multielectrode grids becomes increasingly difficult as the number of electrodes grows. This paper presents a novel application of an unsupervised neural network for clustering neural spike trains with transient responses. This network is constructed by incorporating projective clustering into an adaptive resonance type neural network (ART) architecture resulting in a PART neural network. Since comparisons are made between inputs and learned patterns using only a subset of the total number of available dimensions, …

Is There A Visitor Effect On Abyssinian Ground Hornbills (Bucorvus Abyssinicus), Papuan Wreathed Hornbills (Aceros Plicatus), Wrinkled Hornbills (Aceros Corrugatus) And Toco Toucans (Ramphastos Toco) In A Captive Zoo Environment?, Susanna Frances Thicks

The Plymouth Student Scientist

Research into the possible effects that zoo visitors have on the captive animals they come to visit is still relatively poorly understood. Most of the studies all ready completed have used non-human primate subjects, but there is a distinct lack of studies using non-primate species. One of the groups that are in particular need of this kind of research is birds. This study examines a potential visitor effect in captive Abyssinian Ground Hornbills (Bucorvus abyssinicus), Papuan Wreathed Hornbills (Aceros plicatus), Wrinkled Hornbills (Aceros corrugatus) and Toco Toucans (Ramphastos toco) at Paignton Zoo Environmental Park®. This study also investigates the evenness …

Differential Gene Expression Associated With Postnatal Equine Articular Cartilage Maturation, Michael J. Mienaltowski, Liping Huang, Arnold J. Stromberg, James N. Macleod

Veterinary Science Faculty Publications

BACKGROUND: Articular cartilage undergoes an important maturation process from neonate to adult that is reflected by alterations in matrix protein organization and increased heterogeneity of chondrocyte morphology. In the horse, these changes are influenced by exercise during the first five months of postnatal life. Transcriptional profiling was used to evaluate changes in articular chondrocyte gene expression during postnatal growth and development.

METHODS: Total RNA was isolated from the articular cartilage of neonatal (0-10 days) and adult (4-5 years) horses, subjected to one round of linear RNA amplification, and then applied to a 9,367-element equine-specific cDNA microarray. Comparisons were made with …

Focus On Rna Isolation: Obtaining Rna For Microrna (Mirna) Expression Profiling Analyses Of Neural Tissue, Wang-Xia Wang, Bernard R. Wilfred, Donald A. Baldwin, R. Benjamin Isett, Na Ren, Arnold J. Stromberg, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are present in all known plant and animal tissues and appear to be somewhat concentrated in the mammalian nervous system. Many different miRNA expression profiling platforms have been described. However, relatively little research has been published to establish the importance of 'upstream' variables in RNA isolation for neural miRNA expression profiling. We tested whether apparent changes in miRNA expression profiles may be associated with tissue processing, RNA isolation techniques, or different cell types in the sample. RNA isolation was performed on a single brain sample using eight different RNA isolation methods, and results were correlated using a conventional …

Rationale For Reading Fluconazole Mics At 24 Hours Rather Than 48 Hours When Testing Candida Spp By The Clsi M27-A2 Standard Method, Luis Ostrosky-Zeichner, John H Rex, Michael A Pfaller, Daniel J Diekema, Barbara D Alexander, David Andes, Steven D Brown, Vishnu Chaturvedi, Mahmoud A Ghannoum, Cindy C Knapp, Daniel J Sheehan, Thomas J Walsh

Faculty, Staff and Student Publications

We investigated if CLSI M27-A2 Candida species breakpoints for fluconazole MIC are valid when read at 24 h. Analysis of a data set showed good correlation between 48- and 24-h MICs, as well as similar outcomes and pharmacodynamic efficacy parameters, except for isolates in the susceptible dose-dependent category, such as Candida glabrata.

Transport Of Ldl-Derived Cholesterol From The Npc1 Compartment To The Er Involves The Trans-Golgi Network And The Snare Protein Complex, Yasuomi Urano, Hiroshi Watanabe, Stephanie R. Murphy, Yohei Shibuya, Yong Geng, Andrew Peden, Catherine Chang, Ta Yuan Chang

Dartmouth Scholarship

Mammalian cells acquire cholesterol mainly from LDL. LDL enter the endosomes, allowing cholesteryl esters to be hydrolyzed by acid lipase. The hydrolyzed cholesterol (LDL-CHOL) enters the Niemann-Pick type C1 (NPC1)-containing endosomal compartment en route to various destinations. Whether the Golgi is involved in LDL-CHOL transport downstream of the NPC1 compartment has not been demonstrated. Using subcellular fractionation and immunoadsorption to enrich for specific membrane fractions, here we show that, when parental Chinese hamster ovary (CHO) cells are briefly exposed to (3)H-cholesteryl linoleate (CL) labeled-LDL, newly liberated (3)H-LDL-CHOL appears in membranes rich in trans-Golgi network (TGN) long before it becomes available …

Focal Cerebral Ischemia In The Tnfalpha-Transgenic Rat, L. Creed Pettigrew, Mark S. Kindy, Stephen W. Scheff, Joe E. Springer, Richard J. Kryscio, Yizhao Li, David S. Grass

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: To determine if chronic elevation of the inflammatory cytokine, tumor necrosis factor-alpha (TNFalpha), will affect infarct volume or cortical perfusion after focal cerebral ischemia.

METHODS: Transgenic (TNFalpha-Tg) rats overexpressing the murine TNFalpha gene in brain were prepared by injection of mouse DNA into rat oocytes. Brain levels of TNFalpha mRNA and protein were measured and compared between TNFalpha-Tg and non-transgenic (non-Tg) littermates. Mean infarct volume was calculated 24 hours or 7 days after one hour of reversible middle cerebral artery occlusion (MCAO). Cortical perfusion was monitored by laser-Doppler flowmetry (LDF) during MCAO. Cortical vascular density was quantified by stereology. …

Transcriptional Response Of Mexican Axolotls To Ambystoma Tigrinum Virus (Atv) Infection, Jennifer D. Cotter, Andrew Storfer, Robert B. Page, Christopher K. Beachy, S. Randal Voss

Biology Faculty Publications

BACKGROUND: Very little is known about the immunological responses of amphibians to pathogens that are causing global population declines. We used a custom microarray gene chip to characterize gene expression responses of axolotls (Ambystoma mexicanum) to an emerging viral pathogen, Ambystoma tigrinum virus (ATV).

RESULT: At 0, 24, 72, and 144 hours post-infection, spleen and lung samples were removed for estimation of host mRNA abundance and viral load. A total of 158 up-regulated and 105 down-regulated genes were identified across all time points using statistical and fold level criteria. The presumptive functions of these genes suggest a robust innate immune …

The Eagleville Times,Volume 6, Issue 20, Debbie Ryan

Eagleville Times

No abstract provided.

Ovarian Development In Mice Requires The Gata4-Fog2 Transcription Complex, Nikolay L. Manuylov, Fatima O. Smagulova, Lyndsay Leach, Sergei G. Tevosian

Dartmouth Scholarship

We have demonstrated previously that mammalian sexual differentiation requires both the GATA4 and FOG2 transcriptional regulators to assemble the functioning testis. Here we have determined that the sexual development of female mice is profoundly affected by the loss of GATA4-FOG2 interaction. We have also identified the Dkk1 gene, which encodes a secreted inhibitor of canonical beta-catenin signaling, as a target of GATA4-FOG2 repression in the developing ovary. The tissue-specific ablation of the beta-catenin gene in the gonads disrupts female development. In Gata4(ki/ki); Dkk1(-/-) or Fog2(-/-); Dkk1(-/-) embryos, the normal ovarian gene expression pattern is partially restored. Control of ovarian development …

Syntaxin 3b Is Essential For The Exocytosis Of Synaptic Vesicles In Ribbon Synapses Of The Retina, Leigh B Curtis, Blair Doneske, Xiaoqin Liu, Christina Thaller, James A Mcnew, Roger Janz

Faculty, Staff and Student Publications

Previous studies have demonstrated that ribbon synapses in the retina do not contain the t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor) syntaxin 1A that is found in conventional synapses of the nervous system. In contrast, ribbon synapses of the retina contain the related isoform syntaxin 3. In addition to its localization in ribbon synapses, syntaxin 3 is also found in nonneuronal cells, where it has been implicated in the trafficking of transport vesicles to the apical plasma membrane of polarized cells. The syntaxin 3 gene codes for four different splice forms, syntaxins 3A, 3B, 3C, and 3D. We demonstrate here …

The Eagleville Times,Volume 6, Issue 19, Debbie Ryan

Eagleville Times

No abstract provided.

Substance Use Among Persons With Syphilis During Pregnancy — Arizona And Georgia, 2018–2021, Lingpeng Cheng, Qin Fang, Sanket Shah, Ivo C Atanasov, Z Hong Zhou

Faculty, Staff and Student Publications

Grass carp reovirus (GCRV) is a member of the Aquareovirus genus of the family Reoviridae, a large family of double-stranded RNA (dsRNA) viruses infecting plants, insects, fishes and mammals. We report the first subnanometer-resolution three-dimensional structures of both GCRV core and virion by cryoelectron microscopy. These structures have allowed the delineation of interactions among the over 1000 molecules in this enormous macromolecular machine and a detailed comparison with other dsRNA viruses at the secondary-structure level. The GCRV core structure shows that the inner proteins have strong structural similarities with those of orthoreoviruses even at the level of secondary-structure elements, indicating …

Missense Mutation In Exon 2 Of Slc36a1 Responsible For Champagne Dilution In Horses, Deborah Cook, Samantha Brooks, Rebecca Bellone, Ernest Bailey

Veterinary Science Faculty Publications

Champagne coat color in horses is controlled by a single, autosomal-dominant gene (CH). The phenotype produced by this gene is valued by many horse breeders, but can be difficult to distinguish from the effect produced by the Cream coat color dilution gene (CR). Three sires and their families segregating for CH were tested by genome scanning with microsatellite markers. The CH gene was mapped within a 6 cM region on horse chromosome 14 (LOD = 11.74 for theta = 0.00). Four candidate genes were identified within the region, namely SPARC [Secreted protein, acidic, cysteine-rich (osteonectin)], SLC36A1 (Solute Carrier 36 family …

Deregulation Of Muc4 In Gastric Adenocarcinoma: Potential Pathobiological Implication In Poorly Differentiated Non-Signet Ring Cell Type Gastric Cancer., S. Senapati, P. Chaturvedi, P. Sharma, G Venkatraman, Jane L. Meza, W. El-Rifai, H. K. Roy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

MUC4 is a large, heavily glycosylated transmembrane mucin, that is implicated in the pathogenesis of various types of cancers. To date, no extensive study has been done to check the expression and functional significance of MUC4 in different types of gastric adenocarcinomas. Here, we report the expression profile of MUC4 in gastric adenocarcinomas and its function in poorly differentiated gastric non-signet ring cell carcinoma (non-SRCC) type cells. Immunohistochemical analysis using tissue microarray (TMA) showed a significant difference in MUC4 expression between normal adjacent (n = 45) and gastric adenocarcinoma (n = 83; P < 0.001). MUC4 expression was not associated with tumour type, stage or with the degree of differentiation. To gain further insight into the significance of MUC4 expression in gastric non-SRCC cells, MUC4 was ectopically expressed in AGS, a poorly differentiated gastric non-signet ring cell line. The MUC4 overexpressing cells (AGS-MUC4) showed a significant increase (P < 0.005) in cell motility and a decrease in cellular aggregation as compared with the vector-transfected cells. Furthermore, in vivo tumorigenicity analysis revealed that animals transplanted with the MUC4 overexpressing cells (AGS-MUC4) had a greater incidence of tumours (83%) in comparison to empty vector control (17%). In addition, the expression of MUC4 resulted in enhanced expression of total cellular ErbB2 and phosphorylated ErbB2. In conclusion, our results showed that MUC4 is overexpressed in gastric adenocarcinoma tissues, and that it has a role in promoting aggressive properties in poorly differentiated gastric non-SRCC cells through the activation of the ErbB2 oncoprotein.

The Fgf System Has A Key Role In Regulating Vascular Integrity, Masahiro Murakami, Loc T. Nguyen, Zhen W. Zhang, Karen L. Moodie, Pater Carmellet, Radu V. Stan, Michael Simons

Dartmouth Scholarship

The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors. The inhibition of FGF …

Spatiotemporally Distributed Frontotemporal Networks For Sentence Reading, Sidney R. Lehky, Xinmiao Peng, Carrie J. Mcadams, Anne B. Sereno

Faculty, Staff and Student Publications

BACKGROUND: A key aspect of representations for object recognition and scene analysis in the ventral visual stream is the spatial frame of reference, be it a viewer-centered, object-centered, or scene-based coordinate system. Coordinate transforms from retinocentric space to other reference frames involve combining neural visual responses with extraretinal postural information.

METHODOLOGY/PRINCIPAL FINDINGS: We examined whether such spatial information is available to anterior inferotemporal (AIT) neurons in the macaque monkey by measuring the effect of eye position on responses to a set of simple 2D shapes. We report, for the first time, a significant eye position effect in over 40% of …

Decreased Expression Of Caveolin 1 In Patients With Systemic Sclerosis: Crucial Role In The Pathogenesis Of Tissue Fibrosis., Francesco Del Galdo, Federica Sotgia, Cecilia J. De Almeida, Jean-Francois Jasmin, Megan Musick, Michael P. Lisanti, Sergio A. Jimenez

Department of Medicine Faculty Papers

OBJECTIVE: Recent studies have implicated caveolin 1 in the regulation of transforming growth factor beta (TGFbeta) downstream signaling. Given the crucial role of TGFbeta in the pathogenesis of systemic sclerosis (SSc), we sought to determine whether caveolin 1 is also involved in the pathogenesis of tissue fibrosis in SSc. We analyzed the expression of CAV1 in affected SSc tissues, studied the effects of lack of expression of CAV1 in vitro and in vivo, and analyzed the effects of restoration of caveolin 1 function on the fibrotic phenotype of SSc fibroblasts in vitro.

METHODS: CAV1 expression in tissues was analyzed by …

An Sp1/Sp3 Binding Polymorphism Confers Methylation Protection, Yanis A. Boumber, Yutaka Kondo, Xuqi Chen, Lanlan Shen, Yi Guo, Carmen Tellez, Marcos R H Estécio, Saira Ahmed, Jean-Pierre J. Issa

Faculty, Staff and Student Publications

Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start site that creates a long allele. Pyrosequencing of homozygous tumors revealed a 2.1-fold higher methylation for the short alleles (P<0.001). Bisulfite sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1-fold more methylated than the long (P<0.001). The comparison of expression levels between unmethylated long and short EBV-transformed cell lines showed no difference in expression in vivo. Electrophorectic mobility shift assay showed that the inserted region of the long allele binds Sp1 and Sp3 transcription factors, a binding that is absent in the short allele. Transient transfection of RIL allele-specific transgenes showed no effects of the additional Sp1 site on transcription early on. However, stable transfection of methylation-seeded constructs showed gradually decreasing transcription levels from the short allele with eventual spreading of de novo methylation. In contrast, the long allele showed stable levels of expression over time as measured by luciferase and approximately 2-3-fold lower levels of methylation by bisulfite sequencing (P<0.001), suggesting that the polymorphic Sp1 site protects against time-dependent silencing. Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state.

The Eagleville Times,Volume 6, Issue 16, Debbie Ryan

Eagleville Times

No abstract provided.

A Protein Methylation Pathway In Chlamydomonas Flagella Is Active During Flagellar Resorption, Mark J. Schneider, Megan Ulland, Roger D. Sloboda

Dartmouth Scholarship

During intraflagellar transport (IFT), the regulation of motor proteins, the loading and unloading of cargo and the turnover of flagellar proteins all occur at the flagellar tip. To begin an analysis of the protein composition of the flagellar tip, we used difference gel electrophoresis to compare long versus short (i.e., regenerating) flagella. The concentration of tip proteins should be higher relative to that of tubulin (which is constant per unit length of the flagellum) in short compared with long flagella. One protein we have identified is the cobalamin-independent form of methionine synthase (MetE). Antibodies to MetE label flagella in a …

Structures And Functions Of The Normal And Injured Human Olfactory Epithelium, Jonathan P Schuermann, Jianwen Jiang, Jorge Cuellar, Oscar Llorca, Liping Wang, Luis E Gimenez, Suping Jin, Alexander B Taylor, Borries Demeler, Kevin A Morano, P John Hart, Jose M Valpuesta, Eileen M Lafer, Rui Sousa

Faculty, Staff and Student Publications

Hsp70s mediate protein folding, translocation, and macromolecular complex remodeling reactions. Their activities are regulated by proteins that exchange ADP for ATP from the nucleotide-binding domain (NBD) of the Hsp70. These nucleotide exchange factors (NEFs) include the Hsp110s, which are themselves members of the Hsp70 family. We report the structure of an Hsp110:Hsc70 nucleotide exchange complex. The complex is characterized by extensive protein:protein interactions and symmetric bridging interactions between the nucleotides bound in each partner protein's NBD. An electropositive pore allows nucleotides to enter and exit the complex. The role of nucleotides in complex formation and dissociation, and the effects of …

Sumoylation Regulates Lamin A Function And Is Lost In Lamin A Mutants Associated With Familial Cardiomyopathies, Yu-Qian Zhang, Kevin D. Sarge

Molecular and Cellular Biochemistry Faculty Publications

Lamin A mutations cause many diseases, including cardiomyopathies and Progeria Syndrome. The covalent attachment of small ubiquitin-like modifier (SUMO) polypeptides regulates the function of many proteins. Until now, no examples of human disease-causing mutations that occur within a sumoylation consensus sequence and alter sumoylation were known. We show that lamin A is sumoylated at lysine 201 and that two lamin A mutants associated with familial dilated cardiomyopathy, E203G and E203K, exhibit decreased sumoylation. E203 occupies the conserved +2 position in the sumoylation consensus Psi KXE. Lamin A mutants E203G, E203K, and K201R all exhibit a similar aberrant subcellular localization and …

A Novel Application Of Quantile Regression For Identification Of Biomarkers Exemplified By Equine Cartilage Microarray Data, Liping Huang, Wenying Zhu, Christopher P. Saunders, James N. Macleod, Mai Zhou, Arnold J. Stromberg, Arne C. Bathke

Veterinary Science Faculty Publications

BACKGROUND: Identification of biomarkers among thousands of genes arrayed for disease classification has been the subject of considerable research in recent years. These studies have focused on disease classification, comparing experimental groups of effected to normal patients. Related experiments can be done to identify tissue-restricted biomarkers, genes with a high level of expression in one tissue compared to other tissue types in the body.

RESULTS: In this study, cartilage was compared with ten other body tissues using a two color array experimental design. Thirty-seven probe sets were identified as cartilage biomarkers. Of these, 13 (35%) have existing annotation associated with …

The Eagleville Times,Volume 6, Issue 13, Debbie Ryan

Eagleville Times

No abstract provided.

Brain Fiber Tract Plasticity In Experimental Spinal Cord Injury: Diffusion Tensor Imaging, Jaivijay Ramu, Juan Herrera, Raymond Grill, Tobias Bockhorst, Ponnada Narayana

Faculty, Staff and Student Publications

Diffusion tensor imaging (DTI) and immunohistochemistry were performed in spinal cord injured rats to understand the basis for activation of multiple regions in the brain observed in functional magnetic resonance imaging (fMRI) studies. The measured fractional anisotropy (FA), a scalar measure of diffusion anisotropy, along the region encompassing corticospinal tracts (CST) indicates significant differences between control and injured groups in the 3 to 4 mm area posterior to bregma that correspond to internal capsule and cerebral peduncle. Additionally, DTI-based tractography in injured animals showed increased number of fibers that extend towards the cortex terminating in the regions that were activated …

Synaptotagmin-2 Controls Regulated Exocytosis But Not Other Secretory Responses Of Mast Cells*, Qun-Fang Wan, Alejandro Vila, Zhen-Yu Zhou, Ruth Heidelberger

Faculty, Staff and Student Publications

To better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of 7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time …

Aluminum Bioavailability From Basic Sodium Aluminum Phosphate, An Approved Food Additive Emulsifying Agent, Incorporated In Cheese, Robert A. Yokel, Clair L. Hicks, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability …

The Eagleville Times,Volume 6, 11, Debbie Ryan

Eagleville Times

No abstract provided.

A New Model For Hemoglobin Ingestion And Transport By The Human Malaria Parasite Plasmodium Falciparum., Michelle D Lazarus, Timothy G Schneider, Theodore F Taraschi

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The current model for hemoglobin ingestion and transport by intraerythrocytic Plasmodium falciparum malaria parasites shares similarities with endocytosis. However, the model is largely hypothetical, and the mechanisms responsible for the ingestion and transport of host cell hemoglobin to the lysosome-like food vacuole (FV) of the parasite are poorly understood. Because actin dynamics play key roles in vesicle formation and transport in endocytosis, we used the actin-perturbing agents jasplakinolide and cytochalasin D to investigate the role of parasite actin in hemoglobin ingestion and transport to the FV. In addition, we tested the current hemoglobin trafficking model through extensive analysis of serial …