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Articles 5671 - 5700 of 7166

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Population And Demographic Structure Of Ixodes Scapularis Say In The Eastern United States., Joyce M. Sakamoto, Jerome Goddard, Jason L. Rasgon Jul 2014

Population And Demographic Structure Of Ixodes Scapularis Say In The Eastern United States., Joyce M. Sakamoto, Jerome Goddard, Jason L. Rasgon

CALS Publications

INTRODUCTION: The most significant vector of tick-borne pathogens in the United States is Ixodes scapularis Say (the blacklegged tick). Previous studies have identified significant genetic, behavioral and morphological differences between northern vs. southern populations of this tick. Because tick-borne pathogens are dependent on their vectors for transmission, a baseline understanding of the vector population structure is crucial to determining the risks and epidemiology of pathogen transmission. METHODS: We investigated population genetic variation of I. scapularis populations in the eastern United States using a multilocus approach. We sequenced and analyzed the mitochondrial COI and 16S genes and three nuclear genes (serpin2, …

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The Anoikis Effector Bit1 Displays Tumor Suppressive Function In Lung Cancer Cells., Xin Yao, Scott Jennings, Shubha Kale Ireland, Tri Pham Jul 2014

The Anoikis Effector Bit1 Displays Tumor Suppressive Function In Lung Cancer Cells., Xin Yao, Scott Jennings, Shubha Kale Ireland, Tri Pham

Faculty and Staff Publications

The mitochondrial Bit1 (Bcl-2 inhibitor of transcription 1) protein is a part of an apoptotic pathway that is uniquely regulated by integrin-mediated attachment. As an anoikis effector, Bit1 is released into the cytoplasm following loss of cell attachment and induces a caspase-independent form of apoptosis. Considering that anoikis resistance is a critical determinant of transformation, we hypothesized that cancer cells may circumvent the Bit1 apoptotic pathway to attain anchorageindependence and tumorigenic potential. Here, we provide the first evidence of the tumor suppressive effect of Bit1 through a mechanism involving anoikis induction in human lung adenocarcinoma derived A549 cells. Restitution of …

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Redox Proteomic Identification Of Hne-Bound Mitochondrial Proteins In Cardiac Tissues Reveals A Systemic Effect On Energy Metabolism After Doxorubicin Treatment, Y. Zhao, Sumitra Miriyala, L. Miao, Mihail I. Mitov, David M. Schnell, Sanjit Kumar Dhar, J. Cai, J. B. Klein, Rukhsana Sultana, D. Allan Butterfield, Mary Vore, I. Batinic-Haberle, Subbarao Bondada, Daret K. St. Clair Jul 2014

Redox Proteomic Identification Of Hne-Bound Mitochondrial Proteins In Cardiac Tissues Reveals A Systemic Effect On Energy Metabolism After Doxorubicin Treatment, Y. Zhao, Sumitra Miriyala, L. Miao, Mihail I. Mitov, David M. Schnell, Sanjit Kumar Dhar, J. Cai, J. B. Klein, Rukhsana Sultana, D. Allan Butterfield, Mary Vore, I. Batinic-Haberle, Subbarao Bondada, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Doxorubicin (DOX), one of the most effective anticancer drugs, is known to generate progressive cardiac damage, which is due, in part, to DOX-induced reactive oxygen species (ROS). The elevated ROS often induce oxidative protein modifications that result in alteration of protein functions. This study demonstrates that the level of proteins adducted by 4-hydroxy-2-nonenal (HNE), a lipid peroxidation product, is significantly increased in mouse heart mitochondria after DOX treatment. A redox proteomics method involving two-dimensional electrophoresis followed by mass spectrometry and investigation of protein databases identified several HNE-modified mitochondrial proteins, which were verified by HNE-specific immunoprecipitation in cardiac mitochondria from the …

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Tissue Triage And Freezing For Models Of Skeletal Muscle Disease, Hui Meng, Paul M. L. Janssen, Robert W. Grange, Lin Yang, Alan H. Beggs, Lindsay C. Swanson, Stacy A. Cossette, Alison Frase, Martin K. Childers, Henk Granzier, Emanuela Gussoni, Michael W. Lawlor Jul 2014

Tissue Triage And Freezing For Models Of Skeletal Muscle Disease, Hui Meng, Paul M. L. Janssen, Robert W. Grange, Lin Yang, Alan H. Beggs, Lindsay C. Swanson, Stacy A. Cossette, Alison Frase, Martin K. Childers, Henk Granzier, Emanuela Gussoni, Michael W. Lawlor

Biostatistics Faculty Publications

Skeletal muscle is a unique tissue because of its structure and function, which requires specific protocols for tissue collection to obtain optimal results from functional, cellular, molecular, and pathological evaluations. Due to the subtlety of some pathological abnormalities seen in congenital muscle disorders and the potential for fixation to interfere with the recognition of these features, pathological evaluation of frozen muscle is preferable to fixed muscle when evaluating skeletal muscle for congenital muscle disease. Additionally, the potential to produce severe freezing artifacts in muscle requires specific precautions when freezing skeletal muscle for histological examination that are not commonly used when …

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Transcriptome Of The Female Synganglion Of The Black-Legged Tick Ixodes Scapularis (Acari: Ixodidae) With Comparison Between Illumina And 454 Systems, Noble Egekwu, Daniel E. Sonenshine, Brooke W. Bissinger, R. Michael Roe Jul 2014

Transcriptome Of The Female Synganglion Of The Black-Legged Tick Ixodes Scapularis (Acari: Ixodidae) With Comparison Between Illumina And 454 Systems, Noble Egekwu, Daniel E. Sonenshine, Brooke W. Bissinger, R. Michael Roe

Biological Sciences Faculty Publications

Illumina and 454 pyrosequencing were used to characterize genes from the synganglion of female Ixodes scapularis. GO term searching success for biological processes was similar for samples sequenced by both methods. However, for molecular processes, it was more successful for the Illumina samples than for 454 samples. Functional assignments of transcripts predicting neuropeptides, neuropeptide receptors, neurotransmitter receptors and other genes of interest was done, supported by strong e-values (<-6), and high consensus sequence alignments. Transcripts predicting 15 putative neuropeptide prepropeptides ((allatostatin, allatotropin, bursicon α, corticotropin releasing factor (CRF), CRF-binding protein, eclosion hormone, FMRFamide, glycoprotein A, insulin-like peptide, ion transport peptide, myoinhibitory peptide, inotocin ( = neurophysin-oxytocin), Neuropeptide F, sulfakinin and SIFamide)) and transcripts predicting receptors for 14 neuropeptides (allatostatin, calcitonin, cardioacceleratory peptide, corazonin, CRF, eclosion hormone, gonadotropin-releasing hormone/AKH-like, insulin-like peptide, neuropeptide F, proctolin, pyrokinin, SIFamide, sulfakinin and tachykinin) are reported. Similar to Dermacentor variabilis, we found transcripts matching pro-protein convertase, essential for converting neuropeptide hormones to their mature form. Additionally, transcripts predicting 6 neurotransmitter/neuromodulator receptors (acetylcholine, GABA, dopamine, glutamate, octopamine and …

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Noninvasive Assessment Of Cardiac Abnormalities In Experimental Autoimmune Myocarditis By Magnetic Resonance Microscopy Imaging In The Mouse., Chandirasegaran Massilamany, Vahid Khalilzad-Sharghi, Arunakumar Gangaplara, David Steffen, Shadi F. Othman, Jay Reddy Jun 2014

Noninvasive Assessment Of Cardiac Abnormalities In Experimental Autoimmune Myocarditis By Magnetic Resonance Microscopy Imaging In The Mouse., Chandirasegaran Massilamany, Vahid Khalilzad-Sharghi, Arunakumar Gangaplara, David Steffen, Shadi F. Othman, Jay Reddy

All Faculty Articles - School of Engineering and Computer Science

Myocarditis is an inflammation of the myocardium, but only -10% of those affected show clinical manifestations of the disease. To study the immune events of myocardial injuries, various mouse models of myocarditis have been widely used. This study involved experimental autoimmune myocarditis (EAM) induced with cardiac myosin heavy chain (Myhc)-α 334-352 in A/J mice; the affected animals develop lymphocytic myocarditis but with no apparent clinical signs. In this model, the utility of magnetic resonance microscopy (MRM) as a non-invasive modality to determine the cardiac structural and functional changes in animals immunized with Myhc-α 334-352 is shown. EAM and healthy mice …

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Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus And Vesicular Stomatitis Virus Replication In Sensory Neurons And Fibroblasts, Pamela C. Rosato, David A. Leib Jun 2014

Intrinsic Innate Immunity Fails To Control Herpes Simplex Virus And Vesicular Stomatitis Virus Replication In Sensory Neurons And Fibroblasts, Pamela C. Rosato, David A. Leib

Dartmouth Scholarship

Herpes simplex virus 1 (HSV-1) establishes lifelong latent infections in the sensory neurons of the trigeminal ganglia (TG), wherein it retains the capacity to reactivate. The interferon (IFN)-driven antiviral response is critical for the control of HSV-1 acute replication. We therefore sought to further investigate this response in TG neurons cultured from adult mice deficient in a variety of IFN signaling components. Parallel experiments were also performed in fibroblasts isolated concurrently. We showed that HSV-1 replication was comparable in wild-type (WT) and IFN signaling-deficient neurons and fibroblasts. Unexpectedly, a similar pattern was observed for the IFN-sensitive vesicular stomatitis virus (VSV). …

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Skpa Restrains Synaptic Terminal Growth During Development And Promotes Axonal Degeneration Following Injury, E. J. Brace, Chunlai Wu, Vera Valakh, Aaron Diantonio Jun 2014

Skpa Restrains Synaptic Terminal Growth During Development And Promotes Axonal Degeneration Following Injury, E. J. Brace, Chunlai Wu, Vera Valakh, Aaron Diantonio

Open Access Publications

The Wallenda (Wnd)/dual leucine zipper kinase (DLK)-Jnk pathway is an evolutionarily conserved MAPK signaling pathway that functions during neuronal development and following axonal injury. Improper pathway activation causes defects in axonal guidance and synaptic growth, whereas loss-of-function mutations in pathway components impairs axonal regeneration and degeneration after injury. Regulation of this pathway is in part through the E3 ubiquitin ligase Highwire (Hiw), which targets Wnd/DLK for degradation to limit MAPK signaling. To explore mechanisms controlling Wnd/DLK signaling, we performed a large-scale genetic screen in Drosophila to identify negative regulators of the pathway. Here we describe the identification and characterization of …

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Metabolic Suppression In Mammalian Hibernation: The Role Of Mitochondria., James F Staples Jun 2014

Metabolic Suppression In Mammalian Hibernation: The Role Of Mitochondria., James F Staples

Biology Publications

Hibernation evolved in some small mammals that live in cold environments, presumably to conserve energy when food supplies are low. Throughout the winter, hibernators cycle spontaneously between torpor, with low metabolism and near-freezing body temperatures, and euthermia, with high metabolism and body temperatures near 37°C. Understanding the mechanisms underlying this natural model of extreme metabolic plasticity is important for fundamental and applied science. During entrance into torpor, reductions in metabolic rate begin before body temperatures fall, even when thermogenesis is not active, suggesting active mechanisms of metabolic suppression, rather than passive thermal effects. Mitochondrial respiration is suppressed during torpor, especially …

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Pattern Of Mutation Rates In The Germline Of Drosophila Melanogaster Males From A Large-Scale Mutation Screening Experiment, Jian-Jun Gao, Xue-Rong Pan, Jing Hu, Li Ma, Jian-Min Wu, Ye-Lin Shao, Shi-Meng Ai, Shu-Qun Liu, Sara A Barton, Ronny C Woodruff, Ya-Ping Zhang, Yun-Xin Fu Jun 2014

Pattern Of Mutation Rates In The Germline Of Drosophila Melanogaster Males From A Large-Scale Mutation Screening Experiment, Jian-Jun Gao, Xue-Rong Pan, Jing Hu, Li Ma, Jian-Min Wu, Ye-Lin Shao, Shi-Meng Ai, Shu-Qun Liu, Sara A Barton, Ronny C Woodruff, Ya-Ping Zhang, Yun-Xin Fu

Faculty, Staff and Student Publications

The sperm or eggs of sexual organisms go through a series of cell divisions from the fertilized egg; mutations can occur at each division. Mutations in the lineage of cells leading to the sperm or eggs are of particular importance because many such mutations may be shared by somatic tissues and also may be inherited, thus having a lasting consequence. For decades, little has been known about the pattern of the mutation rates along the germline development. Recently it was shown from a small portion of data that resulted from a large-scale mutation screening experiment that the rates of recessive …

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Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan Jun 2014

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …

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An Asian Origin Of Virulent Aeromonas Hydrophila Responsible For Disease Epidemics In United States-Farmed Catfish, Mohammad J. Hossain, Dawei Sun, Donald J. Mcgarey, Shannon Wrenn Jun 2014

An Asian Origin Of Virulent Aeromonas Hydrophila Responsible For Disease Epidemics In United States-Farmed Catfish, Mohammad J. Hossain, Dawei Sun, Donald J. Mcgarey, Shannon Wrenn

Faculty Articles

Unlabelled: Since 2009, catfish farming in the southeastern United States has been severely impacted by a highly virulent and clonal population of Aeromonas hydrophila causing motile Aeromonas septicemia (MAS) in catfish. The possible origin of this newly emerged highly virulent A. hydrophila strain is unknown. In this study, we show using whole-genome sequencing and comparative genomics that A. hydrophila isolates from diseased grass carp in China and catfish in the United States have highly similar genomes. Our phylogenomic analyses suggest that U.S. catfish isolates emerged from A. hydrophila populations of Asian origin. Furthermore, we identified an A. hydrophila strain isolated …

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Divergent Transcriptional Responses To Low Temperature Among Populations Of Alpine And Lowland Species Of New Zealand Stick Insects (Micrarchus)., Luke T Dunning, Alice B Dennis, Brent J Sinclair, Richard D Newcomb, Thomas R Buckley Jun 2014

Divergent Transcriptional Responses To Low Temperature Among Populations Of Alpine And Lowland Species Of New Zealand Stick Insects (Micrarchus)., Luke T Dunning, Alice B Dennis, Brent J Sinclair, Richard D Newcomb, Thomas R Buckley

Biology Publications

In widespread and genetically structured populations, temperature variation may lead to among-population differentiation of thermal biology. The New Zealand stick insect genus Micrarchus contains four species that inhabit different thermal environments, two of which are geographically widespread. RNA-Seq and quantitative PCR were used to investigate the transcriptional responses to cold shock among lowland and alpine species to identify cold-responsive transcripts that differ between the species and to determine whether there is intraspecific geographical variation in gene expression. We also used mitochondrial DNA, nuclear 28S ribosomal DNA and transcriptome-wide SNPs to determine phylogeographic structure and the potential for differences in genetic …

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Extracellular Traps Are Associated With Human And Mouse Neutrophil And Macrophage Mediated Killing Of Larval Strongyloides Stercoralis., Sandra Bonne-Annee, Laura A. Kerepesi, Jessica A. Hess, Jordan Wesolowski, Fabienne Paumet, James B. Lok, Thomas J. Nolan, David Abraham Jun 2014

Extracellular Traps Are Associated With Human And Mouse Neutrophil And Macrophage Mediated Killing Of Larval Strongyloides Stercoralis., Sandra Bonne-Annee, Laura A. Kerepesi, Jessica A. Hess, Jordan Wesolowski, Fabienne Paumet, James B. Lok, Thomas J. Nolan, David Abraham

Department of Microbiology and Immunology Faculty Papers

Neutrophils are multifaceted cells that are often the immune system's first line of defense. Human and murine cells release extracellular DNA traps (ETs) in response to several pathogens and diseases. Neutrophil extracellular trap (NET) formation is crucial to trapping and killing extracellular pathogens. Aside from neutrophils, macrophages and eosinophils also release ETs. We hypothesized that ETs serve as a mechanism of ensnaring the large and highly motile helminth parasite Strongyloides stercoralis thereby providing a static target for the immune response. We demonstrated that S. stercoralis larvae trigger the release of ETs by human neutrophils and macrophages. Analysis of NETs revealed …

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The Human Metapneumovirus Small Hydrophobic Protein Has Properties Consistent With Those Of A Viroporin And Can Modulate Viral Fusogenic Activity, Cyril Masante, Farah El Najjar, Andres Chang, Angela Jones, Carole L. Moncman, Rebecca Ellis Dutch Jun 2014

The Human Metapneumovirus Small Hydrophobic Protein Has Properties Consistent With Those Of A Viroporin And Can Modulate Viral Fusogenic Activity, Cyril Masante, Farah El Najjar, Andres Chang, Angela Jones, Carole L. Moncman, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Human metapneumovirus (HMPV) encodes three glycoproteins: the glycoprotein, which plays a role in glycosaminoglycan binding, the fusion (F) protein, which is necessary and sufficient for both viral binding to the target cell and fusion between the cellular plasma membrane and the viral membrane, and the small hydrophobic (SH) protein, whose function is unclear. The SH protein of the closely related respiratory syncytial virus has been suggested to function as a viroporin, as it forms oligomeric structures consistent with a pore and alters membrane permeability. Our analysis indicates that both the full-length HMPV SH protein and the isolated SH protein transmembrane …

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Overexpression Of The Astrocyte Glutamate Transporter Glt1 Exacerbates Phrenic Motor Neuron Degeneration, Diaphragm Compromise, And Forelimb Motor Dysfunction Following Cervical Contusion Spinal Cord Injury., Ke Li, Charles Nicaise, Daniel Sannie, Tamara J Hala, Elham Javed, Jessica L Parker, Rajarshi Putatunda, Kathleen A Regan, Valérie Suain, Jean-Pierre Brion, Fred Rhoderick, Megan C Wright, David J Poulsen, Angelo C Lepore May 2014

Overexpression Of The Astrocyte Glutamate Transporter Glt1 Exacerbates Phrenic Motor Neuron Degeneration, Diaphragm Compromise, And Forelimb Motor Dysfunction Following Cervical Contusion Spinal Cord Injury., Ke Li, Charles Nicaise, Daniel Sannie, Tamara J Hala, Elham Javed, Jessica L Parker, Rajarshi Putatunda, Kathleen A Regan, Valérie Suain, Jean-Pierre Brion, Fred Rhoderick, Megan C Wright, David J Poulsen, Angelo C Lepore

Farber Institute for Neuroscience Faculty Papers

A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, …

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Identifying The Provenance Of Leach's Storm Petrels In The North Atlantic Using Polychlorinated Biphenyl Signatures Derived From Comprehensive Two-Dimensional Gas Chromatography With Time-Of-Flight Mass Spectrometry., David Megson, Thomas A. Brown, Glenn W. Johnson, Gwen O'Sullivan, Anthony W.J. Bicknell, Stephen C. Votier, Maeve C. Lohan, Sean Comber, Robert Kalin, Paul J. Worsfold May 2014

Identifying The Provenance Of Leach's Storm Petrels In The North Atlantic Using Polychlorinated Biphenyl Signatures Derived From Comprehensive Two-Dimensional Gas Chromatography With Time-Of-Flight Mass Spectrometry., David Megson, Thomas A. Brown, Glenn W. Johnson, Gwen O'Sullivan, Anthony W.J. Bicknell, Stephen C. Votier, Maeve C. Lohan, Sean Comber, Robert Kalin, Paul J. Worsfold

School of Geography, Earth and Environmental Sciences

PCB signatures can be used for source identification, exposure studies, age dating and bio-monitoring. This study uses comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC-ToFMS) to produce a PCB signature comprised of over 80 PCBs for individual Leach's storm petrels (Oceanodroma leucorhoa). The Leach's storm petrel is a relatively small, elusive, understudied pelagic bird, which only returns to remote islands under darkness during the breeding season. Samples were obtained from 25 Leach's storm petrels found dead in Canada and the UK following storm events in 2006 and 2009. Tissue samples were extracted and analysed by GCxGC-ToFMS and results showed …

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Synthetic Triterpenoid Induces 15-Pgdh Expression And Suppresses Inflammation-Driven Colon Carcinogenesis, Sung Hee Choi, Byung-Gyu Kim, Janet Robinson, Steve Fink, Min Yan, Michael B. Sporn, Sanford D. Markowitz, John J. Letterio May 2014

Synthetic Triterpenoid Induces 15-Pgdh Expression And Suppresses Inflammation-Driven Colon Carcinogenesis, Sung Hee Choi, Byung-Gyu Kim, Janet Robinson, Steve Fink, Min Yan, Michael B. Sporn, Sanford D. Markowitz, John J. Letterio

Dartmouth Scholarship

Colitis-associated colon cancer (CAC) develops as a result of inflammation-induced epithelial transformation, which occurs in response to inflammatory cytokine-dependent downregulation of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and subsequent suppression of prostaglandin metabolism. Agents that both enhance 15-PGDH expression and suppress cyclooxygenase-2 (COX-2) production may more effectively prevent CAC. Synthetic triterpenoids are a class of small molecules that suppress COX-2 as well as inflammatory cytokine signaling. Here, we found that administration of the synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-C28-methyl ester (CDDO-Me) suppresses CAC in mice. In a spontaneous, inflammation-driven intestinal neoplasia model, deletion of Smad4 specifically in T cells led to progressive production of inflammatory cytokines, …

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An Early Cambrian Agglutinated Tubular Lophophorate With Brachiopod Characters., Z-F Zhang, G. X. Li, L. E. Holmer, G. A. Brock, U. Balthasar, C. B. Skovsted, D. J. Fu, X-L Zhang, H. Z. Wang, A. Butler, Z-L Zhang, C. Q. Cao, J. Han, J. N. Liu, D. G. Shu May 2014

An Early Cambrian Agglutinated Tubular Lophophorate With Brachiopod Characters., Z-F Zhang, G. X. Li, L. E. Holmer, G. A. Brock, U. Balthasar, C. B. Skovsted, D. J. Fu, X-L Zhang, H. Z. Wang, A. Butler, Z-L Zhang, C. Q. Cao, J. Han, J. N. Liu, D. G. Shu

School of Geography, Earth and Environmental Sciences

The morphological disparity of lophotrochozoan phyla makes it difficult to predict the morphology of the last common ancestor. Only fossils of stem groups can help discover the morphological transitions that occurred along the roots of these phyla. Here, we describe a tubular fossil Yuganotheca elegans gen. et sp. nov. from the Cambrian (Stage 3) Chengjiang Lagerstätte (Yunnan, China) that exhibits an unusual combination of phoronid, brachiopod and tommotiid (Cambrian problematica) characters, notably a pair of agglutinated valves, enclosing a horseshoe-shaped lophophore, supported by a lower bipartite tubular attachment structure with a long pedicle with coelomic space. The terminal bulb of …

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Lack Of Protection Following Passive Transfer Of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies, Anne-Sophie Dugast, Ying Chan, Michelle Hoffner, Anna Licht, Joseph Nkolola, Hualin Li, Hendrik Streeck, Todd J. Suscovich, Musie Ghebremichael, Margaret E. Ackerman, Dan H. Barouch, Galit Alter May 2014

Lack Of Protection Following Passive Transfer Of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies, Anne-Sophie Dugast, Ying Chan, Michelle Hoffner, Anna Licht, Joseph Nkolola, Hualin Li, Hendrik Streeck, Todd J. Suscovich, Musie Ghebremichael, Margaret E. Ackerman, Dan H. Barouch, Galit Alter

Dartmouth Scholarship

Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred …

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Attitudes Of Canadian Citizens Toward Farm Animal Welfare: A Qualitative Study, Jeffrey M. Spooner, Catherine A. Schuppli, David Fraser May 2014

Attitudes Of Canadian Citizens Toward Farm Animal Welfare: A Qualitative Study, Jeffrey M. Spooner, Catherine A. Schuppli, David Fraser

Farm Animal Welfare Collection

As part of a larger project to determine if there are animal-welfare-related values shared by some commercial food–animal producers and non-producers in Canada, open-ended, semi-structured interviews were conducted to elicit opinions about animal welfare among 24 urban and rural residents not involved in commercial animal production. All participants possessed a self-described interest in food animal well-being and were therefore assumed to represent the views of Canadian non-producers most apt to engage in efforts to shape the animal welfare policies of governments and businesses. Participants described animal welfare in moral or ethical terms, expressed virtually unanimous support for animals having access …

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Control Of Cellular Motility By Neuropilin-Mediated Physical Interactions, Xiaobo Li, Matthew W. Parker, Craig W. Vander Kooi May 2014

Control Of Cellular Motility By Neuropilin-Mediated Physical Interactions, Xiaobo Li, Matthew W. Parker, Craig W. Vander Kooi

Molecular and Cellular Biochemistry Faculty Publications

The neuropilin (Nrp) family consists of multifunctional cell surface receptors with critical roles in a number of different cell and tissue types. A core aspect of Nrp function is in ligand-dependent cellular migration, where it controls the multistep process of cellular motility through integration of ligand binding and receptor signaling. At a molecular level, the role of Nrp in migration is intimately connected to the control of adhesive interactions and cytoskeletal reorganization. Here, we review the physiological role of Nrp in cellular adhesion and motility in the cardiovascular and nervous systems. We also discuss the emerging pathological role of Nrp …

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Pharmacologic Suppression Of Jak1/2 By Jak1/2 Inhibitor Azd1480 Potently Inhibits Il-6-Induced Experimental Prostate Cancer Metastases Formation., Lei Gu, Pooja Talati, Paraskevi Vogiatzi, Ana L Romero-Weaver, Junaid Abdulghani, Zhiyong Liao, Benjamin E. Leiby, David T. Hoang, Tuomas Mirtti, Kalle Alanen, Michael Zinda, Dennis Huszar, Marja T. Nevalainen May 2014

Pharmacologic Suppression Of Jak1/2 By Jak1/2 Inhibitor Azd1480 Potently Inhibits Il-6-Induced Experimental Prostate Cancer Metastases Formation., Lei Gu, Pooja Talati, Paraskevi Vogiatzi, Ana L Romero-Weaver, Junaid Abdulghani, Zhiyong Liao, Benjamin E. Leiby, David T. Hoang, Tuomas Mirtti, Kalle Alanen, Michael Zinda, Dennis Huszar, Marja T. Nevalainen

Department of Medical Oncology Faculty Papers

Metastatic prostate cancer is lethal and lacks effective strategies for prevention or treatment, requiring novel therapeutic approaches. Interleukin-6 (IL-6) is a cytokine that has been linked with prostate cancer pathogenesis by multiple studies. However, the direct functional roles of IL-6 in prostate cancer growth and progression have been unclear. In the present study, we show that IL-6 is produced in distant metastases of clinical prostate cancers. IL-6-activated signaling pathways in prostate cancer cells induced a robust 7-fold increase in metastases formation in nude mice. We further show that IL-6 promoted migratory prostate cancer cell phenotype, including increased prostate cancer cell …

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Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap Apr 2014

Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap

Dartmouth Scholarship

Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially …

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A Device For Performing Automated Balloon Catheter Inflation Ischemia Studies, Silas Leavesley, Whitley Ledkins, Petra Rocic Apr 2014

A Device For Performing Automated Balloon Catheter Inflation Ischemia Studies, Silas Leavesley, Whitley Ledkins, Petra Rocic

NYMC Faculty Publications

Coronary collateral growth (arteriogenesis) is a physiological adaptive response to transient and repetitive occlusion of major coronary arteries in which small arterioles (native collaterals) with minimal to no blood flow remodel into larger conduit arteries capable of supplying adequate perfusion to tissue distal to the site of occlusion. The ability to reliably and reproducibly mimic transient, repetitive coronary artery occlusion (ischemia) in animal models is critical to the development of therapies to restore coronary collateral development in type II diabetes and the metabolic syndrome. Current animal models for repetitive coronary artery occlusion implement a pneumatic occluder (balloon) that is secured …

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Utilizing Animal Assisted Interventions In Elementary Schools, Catherine E. France Apr 2014

Utilizing Animal Assisted Interventions In Elementary Schools, Catherine E. France

Counseling

Animal Assisted Interventions in the elementary school counseling setting involves the school counselor choosing to bring in an animal, commonly a dog, to assist in counseling interventions with a student. The counselor uses the dog as a tool to build a secure and trusting rapport with the student. The counselor is the facilitator of the session; the dog is used in a variety of ways to increase and aide in the benefits of the counseling session. This project illustrates the positive impact of the human-animal bond, the steps necessary to bring animal assisted interventions into a school, and the theoretical …

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Evaluation Of A Method For Nitrotyrosine Site Identification And Relative Quantitation Using A Stable Isotope-Labeled Nitrated Spike-In Standard And High Resolution Fourier Transform Ms And Ms/Ms Analysis, Kent W. Seeley, Alison R. Fertig, Craig P. Dufresne, Joao P. C. Pinho, Stanley M. Stevens Jr. Apr 2014

Evaluation Of A Method For Nitrotyrosine Site Identification And Relative Quantitation Using A Stable Isotope-Labeled Nitrated Spike-In Standard And High Resolution Fourier Transform Ms And Ms/Ms Analysis, Kent W. Seeley, Alison R. Fertig, Craig P. Dufresne, Joao P. C. Pinho, Stanley M. Stevens Jr.

Molecular Biosciences Faculty Publications

The overproduction of reactive oxygen and nitrogen species (ROS and RNS) can have deleterious effects in the cell, including structural and possible activity-altering modifications to proteins. Peroxynitrite is one such RNS that can result in a specific protein modification, nitration of tyrosine residues to form nitrotyrosine, and to date, the identification of nitrotyrosine sites in proteins continues to be a major analytical challenge. We have developed a method by which 15N-labeled nitrotyrosine groups are generated on peptide or protein standards using stable isotope-labeled peroxynitrite (O15NOO−), and the resulting standard is mixed with representative samples in …

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Expression Of Murine 5-Aminolevulinate Synthase Variants Causes Protoporphyrin Ix Accumulation And Light-Induced Mammalian Cell Death, Erica J. Fratz, Gregory A. Hunter, Gloria C. Ferreira Apr 2014

Expression Of Murine 5-Aminolevulinate Synthase Variants Causes Protoporphyrin Ix Accumulation And Light-Induced Mammalian Cell Death, Erica J. Fratz, Gregory A. Hunter, Gloria C. Ferreira

Chemistry Faculty Publications

5-Aminolevulinate synthase (ALAS; EC 2.3.1.37) catalyzes the first committed step of heme biosynthesis in animals. The erythroid-specific ALAS isozyme (ALAS2) is negatively regulated by heme at the level of mitochondrial import and, in its mature form, certain mutations of the murine ALAS2 active site loop result in increased production of protoporphyrin IX (PPIX), the precursor for heme. Importantly, generation of PPIX is a crucial component in the widely used photodynamic therapies (PDT) of cancer and other dysplasias. ALAS2 variants that cause high levels of PPIX accumulation provide a new means of targeted, and potentially enhanced, photosensitization. In order to assess …

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The Gut Of Geographically Disparate Ciona Intestinalis Harbors A Core Microbiota, Larry J. Dishaw, Jaime Flores-Torres, Simon Lax, Kristina Gemayel, Brittany Leigh, Daniela Melillo, M. Gail Mueller, Lenina Natale, Ivana Zucchetti, Rosaria De Santis, Maria Rosaria Pinto, Gary W. Litman, Jack W. Gilbert Apr 2014

The Gut Of Geographically Disparate Ciona Intestinalis Harbors A Core Microbiota, Larry J. Dishaw, Jaime Flores-Torres, Simon Lax, Kristina Gemayel, Brittany Leigh, Daniela Melillo, M. Gail Mueller, Lenina Natale, Ivana Zucchetti, Rosaria De Santis, Maria Rosaria Pinto, Gary W. Litman, Jack W. Gilbert

Marine Science Faculty Publications

It is now widely understood that all animals engage in complex interactions with bacteria (or microbes) throughout their various life stages. This ancient exchange can involve cooperation and has resulted in a wide range of evolved host-microbial interdependencies, including those observed in the gut. Ciona intestinalis, a filter-feeding basal chordate and classic developmental model that can be experimentally manipulated, is being employed to help define these relationships. Ciona larvae are first exposed internally to microbes upon the initiation of feeding in metamorphosed individuals; however, whether or not these microbes subsequently colonize the gut and whether or not Ciona forms …

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Multisensory Integration And Behavioral Plasticity In Sharks From Different Ecological Niches, Jayne M. Gardiner, Jelle Atema, Robert E. Hueter, Philip J. Motta Apr 2014

Multisensory Integration And Behavioral Plasticity In Sharks From Different Ecological Niches, Jayne M. Gardiner, Jelle Atema, Robert E. Hueter, Philip J. Motta

Integrative Biology Faculty and Staff Publications

The underwater sensory world and the sensory systems of aquatic animals have become better understood in recent decades, but typically have been studied one sense at a time. A comprehensive analysis of multisensory interactions during complex behavioral tasks has remained a subject of discussion without experimental evidence. We set out to generate a general model of multisensory information extraction by aquatic animals. For our model we chose to analyze the hierarchical, integrative, and sometimes alternate use of various sensory systems during the feeding sequence in three species of sharks that differ in sensory anatomy and behavioral ecology. By blocking senses …

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