Medicine and Health Sciences Commons^™

Classification Of Current Anticancer Immunotherapies., Lorenzo Galluzzi, Erika Vacchelli, José-Manuel Bravo-San Pedro, Aitziber Buqué, Laura Senovilla, Elisa Elena Baracco, Norma Bloy, Francesca Castoldi, Jean-Pierre Abastado, Patrizia Agostinis, Ron N. Apte, Fernando Aranda, Maha Ayyoub, Philipp Beckhove, Jean-Yves Blay, Laura Bracci, Anne Caignard, Chiara Castelli, Federica Cavallo, Estaban Celis, Vincenzo Cerundolo, Aled Clayton, Mario P. Colombo, Lisa Coussens, Madhav V. Dhodapkar, Alexander M. Eggermont, Douglas T. Fearon, Wolf H. Fridman, Jitka Fučíková, Dmitry I. Gabrilovich, Jérôme Galon, Abhishek Garg, François Ghiringhelli, Giuseppe Giaccone, Eli Gilboa, Sacha Gnjatic, Axel Hoos, Anne Hosmalin, Dirk Jäger, Pawel Kalinski, Klas Kärre, Oliver Kepp, Rolf Kiessling, John M. Kirkwood, Eva Klein, Alexander Knuth, Claire E. Lewis, Roland Liblau, Michael T. Lotze, Enrico Lugli, Jean-Pierre Mach, Fabrizio Mattei, Domenico Mavilio, Ignacio Melero, Cornelis J. Melief, Elizabeth A. Mittendorf, Lorenzo Moretta, Adekunke Odunsi, Hideho Okada, Anna Karolina Palucka, Marcus E. Peter, Kenneth J. Pienta, Angel Porgador, George C. Prendergast, Gabriel A. Rabinovich, Nicholas P. Restifo, Naiyer Rizvi, Catherine Sautès-Fridman, Hans Schreiber, Barbara Seliger, Hiroshi Shiku, Bruno Silva-Santos, Mark J. Smyth, Daniel E. Speiser, Radek Spisek, Pramod K. Srivastava, James E. Talmadge, Eric Tartour, Sjoerd H. Van Der Burg, Benoît J. Van Den Eynde, Richard Vile, Hermann Wagner, Jeffrey S. Weber, Theresa L. Whiteside, Jedd D. Wolchok, Laurence Zitvogel, Weiping Zou, Guido Kroemer

Journal Articles: Pathology and Microbiology

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification …

P53 And Cancer-Associated Sialylated Glygans Are Surrogate Markers Of Cancerization Of The Bladder Associated With Schistosoma Haematobium Infection, Julio Santos, Elisabete Fernandes, Jose Alexandre Ferreira, Luis Lima, Ana Tavares, Andreia Peixoto, Beatriz Parreira, Jose Manuel Correia Da Costa, Paul J. Brindley, Carlos Lopes, Lucio L. Santos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers.

Methodology/Principal Findings

Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder …

Expression Of Suppressor Of Cytokine Signaling 1 (Socs1) Impairs Viral Clearance And Exacerbates Lung Injury During Influenza Infection., Keer Sun, Sharon Salmon, Vijaya Kumar Yajjala, Christopher Bauer, Dennis W. Metzger

Journal Articles: Pathology and Microbiology

Suppressor of cytokine signaling (SOCS) proteins are inducible feedback inhibitors of cytokine signaling. SOCS1-/- mice die within three weeks postnatally due to IFN-γ-induced hyperinflammation. Since it is well established that IFN-γ is dispensable for protection against influenza infection, we generated SOCS1-/-IFN-γ-/- mice to determine whether SOCS1 regulates antiviral immunity in vivo. Here we show that SOCS1-/-IFN-γ-/- mice exhibited significantly enhanced resistance to influenza infection, as evidenced by improved viral clearance, attenuated acute lung damage, and consequently increased survival rates compared to either IFN-γ-/- or WT animals. Enhanced viral clearance in SOCS1-/-IFN-γ-/- mice coincided with a rapid onset of adaptive immune …

The Mirnaome Of Opisthorchis Viverrini Induced Intrahepatic Cholangiocarcinoma, Jin Peng, Yanjun Feng, Gabriel Rinaldi, Ponlapat Yonglitthipagon, Samantha Easley, Therawach Laha, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony, Jordan L. Plieskatt

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer, arising in the biliary ducts that extend into the liver. The highest incidence of ICC occurs in Southeast Asia, particularly in the Mekong River Basin countries of Thailand, Laos, Cambodia, and Vietnam, where it is strongly associated with chronic infection by the food-borne liver fluke Opisthorchis viverrini (OV), one of only three eukaryote pathogens considered Group one carcinogens. Intrahepatic cholangiocarcinoma is usually diagnosed at an advanced stage, with a poor prognosis and survival often less than 24 months. Hence, biomarkers that enable the early detection of ICC would be desirable and have a …

Profiling Mirnas In Nasopharyngeal Carcinoma Ffpe Tissue By Microarray And Next Generation Sequencing, Jin Peng, Yanjun Feng, Gabriel Rinaldi, Paul H. Levine, Samantha Easley, Elizabeth Martinez, Salman Hashmi, Nader Sadeghi, Paul J. Brindley, Jason P. Mulvenna, Jeffrey M. Bethony, Jordan L. Plieskatt

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Nasopharyngeal carcinoma (NPC) is a non-lymphomatous, squamous-cell carcinoma that occurs in the epithelial lining of the nasopharynx. Nasopharyngeal carcinoma has a geographically well-defined distribution worldwide, with the highest prevalence in China, Southeast Asia, and Northern Africa. Symptoms of nascent NPC may be unapparent or trivial, with diagnosis based on the histopathology of biopsied tissue following endoscopy of the nasopharynx. The tumor node metastasis (TNM) staging system is the benchmark for the prognosis of NPC and guides treatment strategy. However, there is a consensus that the TNM system is not sufficiently specific for the prognosis of NPC, as it does not …

Strengths And Weaknesses Of Hybrid Tpr Technology For Obtaining Structural And Mechanistic Insights Into Tpr Proteins, Shanshan Yu

Theses and Dissertations (ETD)

Tetratricopeptide (TPR) repeats are a 34-residue helix-turn-helix motif that when repeated pack into a superhelical structure. TPR domains are frequently found mediating protein-protein interactions, often through a central groove. One protein complex bearing numerous TPR repeats is the Anaphase Promoting Complex (APC). The anaphase-promoting complex (APC) is a multi-subunit complex, which orchestrates mitotic cell cycles. APC is an E3 ligase in the ubiquitin cascade, and directs the 26S proteosome degradation of cell-cycle regulators. Throughout mitotic progression, proteins that are key regulators of the cell cycle are assembled with polyubiquitin chains by APC.

One domain of the human APC is comprised …

Surface Attachment Induces Pseudomonas Aeruginosa Virulence, Albert Siryaporn, Sherry L. Kuchma, George A. Ou2019toole, Zemer Gitai

Dartmouth Scholarship

Pseudomonas aeruginosa infects every type of host that has been examined by deploying multiple virulence factors. Previous studies of virulence regulation have largely focused on chemical cues, but P. aeruginosa may also respond to mechanical cues. Using a rapid imaging-based virulence assay, we demonstrate that P. aeruginosa activates virulence in response to attachment to a range of chemically distinct surfaces, suggesting that this bacterial species responds to mechanical properties of its substrates. Surface-activated virulence requires quorum sensing, but activating quorum sensing does not induce virulence without surface attachment. The activation of virulence by surfaces also requires the surface-exposed protein PilY1, …

Role Of Host Micrornas In Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis, Zhiqiang Qin, Francesca Peruzzi, Krzysztof Reiss, Lu Dai

School of Medicine Faculty Publications

MicroRNAs (miRNAs) are small non-coding RNA species that can bind to both untranslated and coding regions of target mRNAs, causing their degradation or post-transcriptional modification. Currently, over 2500 miRNAs have been identified in the human genome. Burgeoning evidence suggests that dysregulation of human miRNAs can play a role in the pathogenesis of a variety of diseases, including cancer. In contrast, only a small subset of human miRNAs has been functionally validated in the pathogenesis of oncogenic viruses, in particular, Kaposi's sarcoma-associated herpesvirus (KSHV). KSHV is the etiologic agent of several human cancers, such as primary effusion lymphoma (PEL) and Kaposi's …

Plasticity In The Contribution Of T Cell Receptor Variable Region Residues To Binding Of Peptide-Hla-A2 Complexes, Sheena N. Smith, Daniel Sommermeyer, Kurt H. Piepenbrink, Sydney J. Blevins, Helga Bernhard, Wolfgang Uckert, Brian M. Baker, David M. Kranz

Food for Health: Publications

One hypothesis to account for MHC-restriction by T cell receptors (TCRs) holds that there are several evolutionary-conserved residues in TCR variable regions that contact MHC. While this ‘germline-codon’ hypothesis is supported by various lines of evidence, it has been difficult to test. The difficulty stems in part from the fact that TCRs exhibit low affinities for pep/MHC, thus limiting the range of binding energies that can be assigned to these key interactions using mutational analyses. To measure the magnitude of binding energies involved, here we used high affinity TCRs engineered by mutagenesis of CDR3. The TCRs included a high-affinity, MART-1/ …

Chip-Seq And In Vivo Transcriptome Analyses Of The Aspergillus Fumigatus Srebp Srba Reveals A New Regulator Of The Fungal Hypoxia Response And Virulence, Dawoon Chung, Bridget M. Barker, Charles C. Carey, Brittney Merriman

Dartmouth Scholarship

The Aspergillus fumigatus sterol regulatory element binding protein (SREBP) SrbA belongs to the basic Helix-Loop-Helix (bHLH) family of transcription factors and is crucial for antifungal drug resistance and virulence. The latter phenotype is especially striking, as loss of SrbA results in complete loss of virulence in murine models of invasive pulmonary aspergillosis (IPA). How fungal SREBPs mediate fungal virulence is unknown, though it has been suggested that lack of growth in hypoxic conditions accounts for the attenuated virulence. To further understand the role of SrbA in fungal infection site pathobiology, chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) was …

Impact Of Gender On The Decision To Participate In A Clinical Trial: A Cross-Sectional Study, Lucas Lobato, Jeffrey M. Bethony, Fernanda Bicalho Pereira, Shannon Lee Grahek, David J. Diemert, Maria Flavia Gazzinelli

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

In order for Informed Consent to be ethical and valid each clinical trial participant must be able to make a voluntary decision to participate, free from pressure or coercion. Nonetheless, many factors may influence the decision reached, and such influences may be different for male and female volunteers. Being aware of these differences may help researches develop better processes for obtaining consent that safeguard the right of autonomy for all participants. The goal of this study was to evaluate potential gender-based differences in the factors influencing clinical trial participation.

Methods

This cross-sectional study was conducted in the Northeast region …

Caspase-3 Mediates The Pathogenic Effect Of Yersinia Pestis Yopm In Liver Of C57bl/6 Mice And Contributes To Yopm's Function In Spleen, Zhan Ye, Amanda A. Gorman, Annette M. Uittenbogaard, Tanya Myers-Morales, Alan M. Kaplan, Donald A. Cohen, Susan C. Straley

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The virulence protein YopM of the plague bacterium Yersinia pestis has different dominant effects in liver and spleen. Previous studies focused on spleen, where YopM inhibits accumulation of inflammatory dendritic cells. In the present study we focused on liver, where PMN function may be directly undermined by YopM without changes in inflammatory cell numbers in the initial days of infection, and foci of inflammation are easily identified. Mice were infected with parent and ΔyopM-1 Y. pestis KIM5, and effects of YopM were assessed by immunohistochemistry and determinations of bacterial viable numbers in organs. The bacteria were found …

Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin

Dartmouth Scholarship

Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …

Strengthening Neglected Tropical Disease Research Through Enhancing Research-Site Capacity: An Evaluation Of A Novel Web Application To Facilitate Research Collections, Tanzin Furtado, Samuel Franzen, Francois Van Loggerenberg, Gwenaelle Carn, Shannon Grahek, Megan Mcbride, Maureen Power, Barbara Savarese, Margaret Ann Snowden, Gwynn Stevens, Almarie Uys, Trudie Lang

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Ido2 In Immunomodulation And Autoimmune Disease., George C Prendergast, Richard Metz, Alexander J Muller, Lauren M F Merlo, Laura Mandik-Nayak

Department of Microbiology and Immunology Faculty Papers

IDO2 is a relative of IDO1 implicated in tryptophan catabolism and immune modulation but its specific contributions to normal physiology and pathophysiology are not known. Evolutionary genetic studies suggest that IDO2 has a unique function ancestral to IDO1. In mice, IDO2 gene deletion does not appreciably affect embryonic development or hematopoiesis, but it leads to defects in allergic or autoimmune responses and in the ability of IDO1 to influence the generation of T regulatory cells. Gene expression studies indicate that IDO2 is a basally and more narrowly expressed gene than IDO1 and that IDO2 is uniquely regulated by AhR, which …

Helicobacter-Pylori Negative Gastritis In Children—A New Clinical Enigma, Yoram Elitsur, Deborah L. Preston

Biochemistry and Microbiology

The decrease in the prevalence of Helicobacter pylori (Hp) infection in children in the world gave rise to a new pathological finding termed as Hp-negative gastritis. Unfortunately, the term “Hp-negative gastritis” has not been identified as a pathological process and has the status of a “second cousin”; in most publications it was never mentioned as a subject to be dealt with, but was “left over” data that was never the topic of the manuscripts’ discussions. Only recently has the topic captured the attention of the pathologists who described this phenomenon in adults, yet the pathological and/or clinical spectrum or significance …

Temporal And Stochastic Control Of Staphylococcus Aureus Biofilm Development., Derek E. Moormeier, Jeffrey L. Bose, Alexander R. Horswill, Kenneth W. Bayles

Journal Articles: Pathology and Microbiology

Biofilm communities contain distinct microniches that result in metabolic heterogeneity and variability in gene expression. Previously, these niches were visualized within Staphylococcus aureus biofilms by observing differential expression of the cid and lrg operons during tower formation. In the present study, we examined early biofilm development and identified two new stages (designated "multiplication" and "exodus") that were associated with changes in matrix composition and a distinct reorganization of the cells as the biofilm matured. The initial attachment and multiplication stages were shown to be protease sensitive but independent of most cell surface-associated proteins. Interestingly, after 6 h of growth, an …

Assessment Of Anthelmintic Efficacy Of Mebendazole In School Children In Six Countries Where Soil-Transmitted Helminths Are Endemic, Bruno Levecke, Antonio Montresor, Marco Albonico, Shaali M. Ame, Jerzy M. Behnke, Jeffrey M. Bethony, +15 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND:

Robust reference values for fecal egg count reduction (FECR) rates of the most widely used anthelmintic drugs in preventive chemotherapy (PC) programs for controlling soil-transmitted helminths (STHs; Ascaris lumbricoides, Trichuris trichiura, and hookworm) are still lacking. However, they are urgently needed to ensure detection of reduced efficacies that are predicted to occur due to growing drug pressure. Here, using a standardized methodology, we assessed the FECR rate of a single oral dose of mebendazole (MEB; 500 mg) against STHs in six trials in school children in different locations around the world. Our results are compared with those previously obtained …

Smarter Vaccine Design Will Circumvent Regulatory T Cell-Mediated Evasion In Chronic Hiv And Hcv Infection, Leonard Moise, Frances Terry, Andres H. Gutierrez, Ryan Tassone, Phyllis Losikoff, Stephen H. Gregory, Chris Bailey-Kellogg

Dartmouth Scholarship

Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic infection is suppression of viral-specific effector CD4(+) and CD8(+) T cells by stimulating regulatory T cells (Tregs) educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a T cell receptor (TCR)-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses …

Analysis Of Candida Albicans Mutants Defective In The Cdk8 Module Of Mediator Reveal Links Between Metabolism And Biofilm Formation, Allia K. Lindsay, Diana K. Morales, Zhongle Liu, Nora Grahl, Anda Zhang, Sven D. Willger, Lawrence C. Myers, Deborah A. Hogan

Dartmouth Scholarship

Candida albicans biofilm formation is a key virulence trait that involves hyphal growth and adhesin expression. Pyocyanin (PYO), a phenazine secreted by Pseudomonas aeruginosa, inhibits both C. albicans biofilm formation and development of wrinkled colonies. Using a genetic screen, we identified two mutants, ssn3Δ/Δ and ssn8Δ/Δ, which continued to wrinkle in the presence of PYO. Ssn8 is a cyclin-like protein and Ssn3 is similar to cyclin-dependent kinases; both proteins are part of the heterotetrameric Cdk8 module that forms a complex with the transcriptional co-regulator, Mediator. Ssn3 kinase activity was also required for PYO sensitivity as a kinase dead mutant maintained …

Hiv-1 Infection Of Macrophages Induces Retention Of Cholesterol Transporter Abca1 In The Endoplasmic Reticulum, Beda Brichacek, Christina Darwish, Anastas Popratiloff, Larisa Dubrovsky, Michael I. Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Transformation Of Human Cathelicidin Ll-37 Into Selective, Stable, And Potent Antimicrobial Compounds., Guangshun Wang, Mark L. Hanke, Biswajit Mishra, Tamara Lushnikova, Cortney E. Heim, Vinai Chittezham Thomas, Kenneth W. Bayles, Tammy Kielian

Journal Articles: Pathology and Microbiology

This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli but not methicillin-resistant Staphylococcus aureus (MRSA). It possesses a unique nonclassic amphipathic structure with hydrophobic defects. By repairing the hydrophobic defects, the peptide (17BIPHE2) gained activity against the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species. In vitro, 17BIPHE2 could disrupt bacterial membranes and bind to DNA. In vivo, the peptide …

Role Of Adaptor Trfa And Clppc In Controlling Levels Of Ssra-Tagged Proteins And Antitoxins In Staphylococcus Aureus, Niles P. Donegan, Jonathan S. Marvin, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus responds to changing extracellular environments in part by adjusting its proteome through alterations of transcriptional priorities and selective degradation of the preexisting pool of proteins. In Bacillus subtilis, the proteolytic adaptor protein MecA has been shown to play a role in assisting with the proteolytic degradation of proteins involved in competence and the oxidative stress response. However, the targets of TrfA, the MecA homolog in S. aureus, have not been well characterized. In this work, we investigated how TrfA assists chaperones and proteases to regulate the proteolysis of several classes of proteins in S. aureus. …

Differential Spatial Repositioning Of Activated Genes In Biomphalaria Glabrata Snails Infected With Schistosoma Mansoni, Halime D. Arican-Goktas, Wannaporn Ittiprasert, Joanna M. Bridger, Matty Knight

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro thatBiomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their …

Enhanced Expression Of Codon Optimized Mycobacterium Avium Subsp. Paratuberculosis Antigens In Lactobacillus Salivarius, Christopher D. Johnston, John P. Bannatine, Rodney Govender, Lorraine Endersen, Daniel Pletzer, Helge Weingart, Aidan Coffey, Jim O'Mahony, Roy D. Sleator

Department of Biological Sciences Publications

It is well documented that open reading frames containing high GC content show poor expression in A+T rich hosts. Specifically, G+C-rich codon usage is a limiting factor in heterologous expression of Mycobacterium avium subsp. paratuberculosis (MAP) proteins using Lactobacillus salivarius. However, re-engineering opening reading frames through synonymous substitutions can offset codon bias and greatly enhance MAP protein production in this host. In this report, we demonstrate that codon-usage manipulation of MAP2121c can enhance the heterologous expression of the major membrane protein (MMP), analogous to the form in which it is produced natively by MAP bacilli. When heterologously over-expressed, antigenic determinants …

Diminished Humoral Responses Against And Reduced Gene Expression Levels Of Human Endogenous Retrovirus-K (Herv-K) In Psoriasis, Rashmi Gupta, Henri-Alexandre Michaud, Xue Zeng, Maya Debbaneh, Sarah T. Arron, R. Brad Jones, Christopher E. Ormsby, Douglas F. Nixon, Wilson Liao

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Vaccination With A Genetically Modified Brugia Malayi Cysteine Protease Inhibitor-2 Reduces Adult Parasite Numbers And Affects The Fertility Of Female Worms Following A Subcutaneous Challenge Of Mongolian Gerbils (Meriones Unguiculatus) With B. Malayi Infective Larvae., Sridhar Arumugam, Junfei Wei, Danielle Ward, David Abraham, Sara Lustigman, Bin Zhan, Thomas R. Klei

Department of Microbiology and Immunology Faculty Papers

Vaccination of Mongolian gerbils with Brugia malayi cysteine protease inhibitor-2 in which the amino acid Asn66 was mutated to Lys66 (Bm-CPI-2M) resulted in reduced parasite numbers of 48.6% and 48.0% at 42 and 90 days p.i. with B. malayi L3s. Fertility of female worms was also affected at 90 days p.i. In vitro killing of L3s observed in the presence of gerbil peritoneal exudate cells and anti-Bm-CPI-2M sera suggests antibody-dependent cell-mediated cytotoxicity as a putative protective mechanism. These observations suggest that Bm-CPI-2M is a promising prophylactic and anti-fecundity vaccine candidate.

Hemichannels In Neurodegenerative Diseases: Is There A Link To Pathology?, Megan Bosch, Tammy Kielian

Journal Articles: Pathology and Microbiology

Although originally considered a structural component of gap junctions, connexin hemichannels (HCs) are now recognized as functional entities capable of influencing metabolic gradients within the CNS, allowing direct communication between the intra- and extracellular milieus. Besides connexins, HCs can also be formed by pannexins, which are not capable of gap junction assembly. Both positive and negative effects have been attributed to HC activity in the context of neurodegenerative diseases. For example, HCs can exert neuroprotective effects by promoting the uptake of neurotoxic molecules, whereas chronic HC opening can disrupt molecular gradients leading to cellular dysfunction and death. The latter scenario …

Efficacy Of Novel Antifouling/Antimicrobial Coatings For The Prevention Of Urinary Device Associated Infection And Encrustation, Thomas O. Tailly

Electronic Thesis and Dissertation Repository

Device associated urinary tract infections are a very important healthcare issue. Despite best efforts in preventing and treating these infections, many patients and physicians are still confronted with this problem. Our research group is involved in testing and evaluating new stent coatings for the prevention of device associated infections and device encrustation. In the current project, we tested two new coating copolymers, both based on a long chain polymer backbone and mussel adhesive protein to this purpose in a rabbit and porcine model. The results demonstrate efficiency of one copolymer in preventing infections in the rabbit model. Interestingly there is …

Epoxide-Mediated Differential Packaging Of Cif And Other Virulence Factors Into Outer Membrane Vesicles, A. E. Ballok, L. M. Filkins, J.. M. Bomberger, B. A. Stanton, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a number of secreted bacterial proteins, including phospholipases, alkaline phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide hydrolase, was shown to be regulated at the transcriptional level by epoxides, which serve as ligands of the repressor, CifR. Here, we tested whether epoxides have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in the presence of specific epoxi