Immunology and Infectious Disease Commons^™

Characterizing The Effect Of Dasatinib On Anti-Tumor Immune Response And Exploring The Potential Of Combining Targeted Therapy And Immunotherapy In A C-Kit Mutant Mastocytoma Model, Yan Yang

Dissertations and Theses (Open Access)

Targeted therapy and immunotherapy eradicate malignant cells through different mechanisms, and the strengths and weaknesses of these two approaches are potentially complementary. Therefore, the combination of molecular targeted drugs with immune- based therapies is considered an attractive approach for improving the therapeutic efficacy of cancer treatment. The mutation and amplification of the c-KIT proto- oncogene are associated with multiple different cancer types, and multiple c-KIT inhibitors have been tested clinically. In spite of some encouraging results using these agents, most patients with c-KIT mutant cancers still relapse due to drug resistance. This also demonstrates the inherent limitation of molecular targeted …

C-Jun N-Terminal Kinases Regulate Adenovirus-Mediated Autophagy And Antigen Presentation, Sarah R. Klein

Dissertations and Theses (Open Access)

Targeted immunotherapy with recombinant, oncolytic adenoviruses is under investigation for the treatment of cancer. Evidence indicates adenoviruses induce autophagy that is required for oncolysis, but the molecular regulation of autophagy in infected cells remains under investigation. Our data suggested the canonical pathway regulating starvation-induced autophagy was not implemented in adenovirus-induced autophagy; however, adenovirus infection triggered phosphorylation of c-Jun N-terminal kinases (JNK) that was essential for autophagy. Adenoviral replication within the host cell elicited JNK pathway activation leading to B cell lymphoma-2 (Bcl-2) phosphorylation. JNK-dependent Bcl-2 phosphorylation stimulated the dissociation of Bcl-2/beclin 1 heterodimers, enabling beclin 1 to initiate autophagy. Moreover, …

Development Of Novel Antifungal Peptides Based On A Natural Model Of Histatin-5 Peptide, Duy Tu Nguyen

Graduate Theses and Dissertations

Our research group is working toward the development of novel antifungal peptides based on a natural model of peptide histatin-5. Histatin-5 is found in human saliva and known to protect our body against oral infections by Candida species. Candidiasis, or an infection caused by Candida species, is considered one of the most medically important fungal infections worldwide. Blood stream infections caused by Candida species are the fourth leading cause of hospital-acquired fungal infections that is associated with high mortality rates and high costs of treatment. This study investigated the modes of action of histatin-5 with the use of one 16-mer …

On Head Lice And Social Interaction In Archaic Andean Coastal Populations, Bernardo Arriaza, Vivien Standen, Karl Reinhard, Aduto Araújo, Jörg Heukelbach, Katharina Dittmar

Karl Reinhard Publications

Archaic mummies from northern Chile were examined for the presence of Pediculus humanus capitis. The excellent preservation of mummies and louse nits/eggs permitted a study of the degree of head lice infestation. We studied 63 Chinchorro mummies (ca. 5000–3000 years B.P.) from the Arica-Camarones coast. An area of 2 cm × 2 cm on each mummy’s head was systematically inspected for louse nits/eggs. Hairs with nits/eggs and lice were collected and analyzed using optic and scanning electronic microscopy. About 79% (50/63) of the mummies resulted positive for pediculosis, with an average of 2.1 nits/ eggs/cm2 per positive individual. Microscopic …

Mechanisms Of The Anti-Pneumococcal Function Of C-Reactive Protein, Toh B. Gang

Electronic Theses and Dissertations

Human C-reactive protein (CRP) increases survival of and decreases bacteremia in mice infected with Streptococcus pneumoniae. Such protection of mice against pneumococcal infection is seen only when CRP is administered into mice 6 hours before to 2 hours after the injection of pneumococci, but not when CRP is given to mice at a later time. Our first aim was to define the mechanism of CRP-mediated initial protection of mice against infection. It was proposed that CRP binds to phosphocholine (PCh) moieties present in the cell wall and activates the complement system on the pneumococcal surface that kills the pathogen. …

From (Un)Willingness To Involvement: Development Of A Successful Study Brand For Recruitment Of Diverse Msm To A Longitudinal Hiv Research, Paula M. Frew, Victoria A. Williams, Eve T. Shapiro, Travis Sanchez, Eli S. Rosenberg, Vincent L. Fenimore, Patrick S. Sullivan

Environmental & Global Health Faculty Research

Background. HIV continues to be a major concern among MSM, yet Black MSM have not been enrolled in HIV research studies in proportionate numbers to White MSM. We developed an HIV prevention research brand strategy for MSM. Methods. Questionnaires and focus groups were conducted with 54 participants. Descriptive statistics and chi-square analyses were performed and qualitative data were transcribed and content analyzed to identify common themes. Results. Formative research results indicated that younger Black MSM (18–29 years) were less likely to think about joining prevention studies compared to older (≥30 years) Black MSM (, ). Qualitative and quantitative results indicate …

Immunoproteomic Analysis Of Proteins Expressed By Two Related Pathogens, Burkholderia Multivorans And Burkholderia Cenocepacia, During Human Infection., Minu Shinoy, Ruth Dennehy, Lorraine Coleman, Stephen Carberru, Kirsten Schaffer, Máire Callaghan, Sean Doyle, Siobhan Mcclean

Articles

Burkholderia cepacia complex (Bcc) is an opportunistic bacterial pathogen that causes chronic infections in people with cystic fibrosis (CF). It is a highly antibiotic resistant organism and Bcc infections are rarely cleared from patients, once they are colonized. The two most clinically relevant species within Bcc are Burkholderia cenocepacia and Burkholderia multivorans. The virulence of these pathogens has not been fully elucidated and the virulence proteins expressed during human infection have not been identified to date. Furthermore, given its antibiotic resistance, prevention of infection with a prophylactic vaccine may represent a better alternative than eradication of an existing infection. We …

The Biology And Taxonomy Of Head And Body Lice: Implications For Louse-Borne Disease Prevention, Denise L. Bonilla, Lance A. Durden, Marina E. Eremeeva, Gregory A. Dasch

Harold W. Manter Laboratory of Parasitology: Library Materials

Sucking lice (Phthiraptera: Anoplura) are obligate blood-feeding ectoparasites of placental mammals including humans. Worldwide, more than 550 species have been described and many are specific to a particular host species of mammal. Three taxa uniquely parasitize humans: the head louse, body louse, and crab (pubic) louse. The body louse, in particular, has epidemiological importance because it is a vector of the causative agents of three important human diseases: epidemic typhus, trench fever, and louse-borne relapsing fever. Since the advent of antibiotics and more effective body louse control measures in the 1940s, these diseases have markedly diminished in incidence. However, due …

A Genome-To-Genome Analysis Of Associations Between Human Genetic Variation, Hiv-1 Sequence Diversity, And Viral Control, Istvan Bartha, Jonathan M. Carlson, Chanson J. Brumme, Paul J. Mclaren, Zabrina L. Brumme, Mina John, David W. Haas, Javier Martinez-Picado, Judith Dalmau, Cecilio Lopez-Galindez, Concepcion Casado, Andri Rauch, Huldrych F. Gunthard, Enos Bernasconi, Pietro Vernazza, Thomas Klimkait, Sabine Yerly, Stephen J. O'Brien, Jennifer Listgarten, Nico Pfeifer, Christoph Lippert, Nicolo Fusi, Zoltan Kutalik, Todd M. Allen, Viktor Muller, P. Richard Harrigan, David Heckerman, Amalio Telenti, Jacques Fellay

Biology Faculty Articles

HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p<2.4 × 10⁻¹²). All associated SNPs mapped to the HLA class I region. Clinical relevance of host and pathogen variation was assessed using VL results. We identified two critical advantages to the use of viral variation …

Membrane Vesicles Nucleate Mineralo-Organic Nanoparticles And Induce Carbonate Apatite Precipitation In Human Body Fluids, Cheng-Yeu Wu, Jan Martel, Wei-Yun Cheng, Chao-Chih He, David M. Ojcius, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Recent studies indicate that membrane vesicles (MVs) secreted by various cells are associated with human diseases, including arthritis, atherosclerosis, cancer, and chronic kidney disease. The possibility that MVs may induce the formation of mineralo-organic nanoparticles (NPs) and ectopic calcification has not been investigated so far. Here, we isolated MVs ranging in size between 20 and 400 nm from human serum and FBS using ultracentrifugation and sucrose gradient centrifugation. The MV preparations consisted of phospholipid-bound vesicles containing the serum proteins albumin, fetuin-A, and apolipoprotein A1; the mineralization-associated enzyme alkaline phosphatase; and the exosome proteins TNFR1 and CD63. Notably, we observed that …

Helminth Parasites Of The Raccoon (Procyon Lotor), Virginia Opossum (Didelphis Virginiana), And Striped Skunk (Mephitis Mephitis) From Keith County, Nebraska, Dennis J. Richardson

Transactions of the Nebraska Academy of Sciences and Affiliated Societies

Nine raccoons (Procyon lotor), 6 Virginia opossums (Didelphis virginiana), and 1 striped skunk (Mephitis mephitis) collected from Keith County, Nebraska were examined for helminth parasites. Raccoons were infected with the nematodes Arthrocephalus lotoris, Baylisascaris procyonis, and Capillaria plica, the trematode Fibricola cratera, and the tapeworm Atriotaenia procyonis. Opossums were infected with 1 nematode, 1 trematode, and 1 cestode species: Physaloptera turgida, Plagiorhchis elegans, and Oochoristica sp., respectively. The single striped skunk was infected with the nematode Physaloptera maxillaris and the cestodes Mesocestoides sp. and Oochoristica sp.

Pritchardia Boliviensis N. Gen., N. Sp. (Anoplocephalidae: Linstowinae), A Tapeworm From Opossums (Didelphidae) In The Yungas And Lowlands Of Bolivia And Atlantic Forest Of Paraguay, Scott Lyell Gardner, F. Agustín Jiménez Ruiz, Mariel L. Campbell

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Pritchardia boliviensis n. gen. n. sp. (Anoplocephalidae: Linstowiinae) is described from marsupials (Marmosops noctivagus, Metachirus nudicaudatus, Gracilinanus sp.) collected in Bolivia and Paraguay. These cestodes have a very small strobila with only three segments, regularly alternating genital pores, genital ducts crossing excretory canals ventrally, ovoid to pyriform cirrus sac, three to five testes, external seminal vesicle present and separated from cirrus sac by long seminal duct surrounded by glandular material, uterus ephemeral, eggs forming rapidly in gravid segments, and seminal receptacle present. Pritchardia boliviensis n. sp. includes a single species that occurs in small marsupials in the family …

Sylvatic Species Of Echinococcus From Rodent Intermediate Hosts In Asia And South America, Scott Lyell Gardner, Altangerel T. Dursahinhan, Gábor R. Rácz, Nyamsuren Batsaikhan, Sumiya Ganzorig, David S. Tinnin, Darmaa Damdinbazar, Charles Wood, A. Townsend Peterson, Erika Alandia, José Luís Mollericona, Jorge Salazar-Bravo

Harold W. Manter Laboratory of Parasitology: Faculty Publications

During a global survey of the diversity of vertebrates and their parasites including the Gobi and desert/steppe biomes ranging from south central to western Mongolia, we found metacestodes (larvae) of Echinococcus multilocularis (Leuckart 1863) in the liver of an individual vole (Microtus limnophilus Büchner 1889) collected in grassland habitat at Har Us Lake, southeast of Hovd, Mongolia. Positive identification of E. multilocularis from near Hovd was made via comparative cyst morphology, study of hooks from the rostellum derived from protoscolexes, and DNA sequencing of the COX1 mitochondrial gene extracted from tissue of the cysts frozen in the field. This …

Identification Of Leptospira Interrogans Phospholipase C As A Novel Virulence Factor Responsible For Intracellular Free Calcium Ion Elevation During Macrophage Death, Jing-Fang Zhao, Hong-Hu Chen, David M. Ojcius, Xin Zhao, Dexter Sun, Yu-Mei Ge, Lin-Li Zheng, Xu'ai Lin, Lan-Juan Li, Jie Yan

All Dugoni School of Dentistry Faculty Articles

Background: Leptospira-induced macrophage death has been confirmed to play a crucial role in pathogenesis of leptospirosis, a worldwide zoonotic infectious disease. Intracellular free Ca²⁺ concentration ([Ca²⁺]i) elevation induced by infection can cause cell death, but [Ca²⁺]i changes and high [Ca²⁺]i-induced death of macrophages due to infection of Leptospira have not been previously reported.

Methodology/Principal Findings: We first used a Ca²⁺-specific fluorescence probe to confirm that the infection of L. interrogans strain Lai triggered a significant increase of [Ca²⁺]i in mouse J774A.1 or human THP-1 macrophages. Laser confocal microscopic examination …

American Society Of Parasitologists Newsletter, V. 35, No. 2, Fall 2013, Scott Lyell Gardner

American Society of Parasitologists: Newsletter

An issue of the American Society of Parasitologists Newsletter, also known as the Newsletter of the Journal of Parasitology.

Distribution Extension Of Escherbothrium Molinae Berman And Brooks, 1994 (Cestoda: Tetraphyllidea: Triloculariidae) In Urotrygon Sp. From The Pacific Coast Of Mexico, Francisco Zaragoza-Tapia, Scott Monks, Griselda Pulido-Flores, Juan Violante-González

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Cestodes collected from the spiral valves of the stingray Urotrygon sp. from the Pacific coast of Mexico were identified as Escherbothrium molinae Berman and Brooks, 1994. The first report of the species was from the Gulf of Nicoya and the Guanacaste coast, Costa Rica; this work represents the second report of the species since the original description and extends its distribution north to Acapulco, Guerrero, Mexico.

Small Molecule Antagonists Of Melanopsin-Mediated Phototransduction, Kenneth A. Jones, Megumi Hatori, Ludovic S. Mure, Jayne R. Bramley, Roman Artymyshyn, Sang-Phyo Hong, Mohammad Marzabadi, Huailing Zhong, Jeffrey Sprouse, Quansheng Zhu, Andrew T. E. Hartwick, Patricia J. Sollars, Gary E. Pickard, Satchidananda Panda

School of Veterinary and Biomedical Sciences: Faculty Publications

Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several CNS responses including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity. Novel sulfonamide compounds inhibiting melanopsin (opsinamides) compete with retinal binding to melanopsin and inhibit its function without affecting rod/cone mediated responses. In vivo administration of opsinamides to mice specifically and reversibly modified melanopsin-dependent light responses including the pupillary light reflex and …

Reported Incidences Of Parasitic Infections In Marine Mammals From 1892 To 1978, John R. Felix

Zea E-Books Collection

The role of parasites in the lives and deaths of marine mammals has been scrutinized by biologists for decades, but the scientific literature prior to 1978 has been difficult to acquire and time-consuming to search. Now this new and extensive bibliography gives researchers a convenient resource for reviewing the classical literature on parasites of marine mammals so that historical infection prevalence and geographical distribution can be easily and properly assessed. This book contains detailed information about accepted (or suspected) taxonomic synonyms and geographical information about the host and/or parasite, covering the parasite groups Acanthocephala, Acarina, Anoplura, Cestoda, Nematoda, and Trematoda, …

Method For Enhancing Specific Immunotherapies In Cancer Treatment, Peter G. Traber, William L. Redmond, Eliezer Zomer, Anatole Klyosov, Stefanie N. Linch

Technology Transfer - Patents

Methods and compositions of the invention relate to the enhancement of specific immunotherapies in cancer treatment. In particular, aspects of the invention relate to novel approaches to boost immune function using a complex carbohydrate pharmaceutical compound alone or in combination with other targeted immunotherapy to increase the efficacy of immunotherapy of cancer.

Resistance Of Human Cytomegalovirus To Cyclopropavir Maps To A Base Pair Deletion In The Open Reading Frame Of Ul97, Brian G. Gentry, Laura E. Vollmer, Ellie D. Hall, Katherine Z. Borysko, Jiri Zemlicka, Jeremy P. Kamil, John C. Drach

Oncology Faculty Publications

Human cytomegalovirus (HCMV) is a widespread pathogen in the human population, affecting many immunologically immature and immunocompromised patients, and can result in severe complications, such as interstitial pneumonia and mental retardation. Current chemotherapies for the treatment of HCMV infections include ganciclovir (GCV), foscarnet, and cidofovir. However, the high incidences of adverse effects (neutropenia and nephrotoxicity) limit the use of these drugs. Cyclopropavir (CPV), a guanosine nucleoside analog, is 10-fold more active against HCMV than GCV (50% effective concentrations [EC₅₀s] = 0.46 and 4.1 μM, respectively). We hypothesize that the mechanism of action of CPV is similar to that …