Medical Microbiology Commons^™

A Microrna Profile Associated With Opisthorchis Viverrini-Induced Cholangiocarcinoma In Tissue And Plasma., Jordan Plieskatt, Gabriel Rinaldi, Yanjun Feng, Jin Peng, Samantha Easley, Xinying Jia, Jeremy Potriquet, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi, Banchob Sripa, Paul J Brindley, Jeffrey Bethony, Jason Mulvenna

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive tumor of the bile duct, and a significant public health problem in East Asia, where it is associated with infection by the parasiteOpisthorchis viverrini. ICC is often detected at an advanced stage and with a poor prognosis, making a biomarker for early detection a priority.

Methods

We have comprehensively profiled miRNA expression levels in ICC tumor tissue using small RNA-Seq and validated these profiles using quantitative PCR on matched plasma samples.

Results

Distinct miRNA profiles were associated with increasing histological differentiation of ICC tumor tissue. We also observed that histologically …

Opisthorchiasis: An Overlooked Danger, Ludmila M. Ogorodova, Olga S. Fedorova, Banchob Sripa, Viatcheslav A. Mordvinov, Aleksei V. Katokhin, Paul J. Brindley, The Topic Consortium

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Opisthorchiasis: An Overlooked Danger., Ludmila M Ogorodova, Olga S Fedorova, Banchob Sripa, Viatcheslav A Mordvinov, Aleksei V Katokhin, Jennifer Keiser, Peter Odermatt, Paul J. Brindley, Oleg A Mayboroda, Thirumalaisamy P Velavan, Maxim B Freidin, Alexey E Sazonov, Irina V Saltykova, Mariya Y Pakharukova, Yulia V Kovshirina, Kostas Kaloulis, Olga Y Krylova, Maria Yazdanbakhsh

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Apparent Role For Borrelia Burgdorferi Luxs During Mammalian Infection, William K. Arnold, Christina R. Savage, Alyssa D. Antonicello, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Lyme disease spirochete, Borrelia burgdorferi, controls protein expression patterns during its tick-mammal infection cycle. Earlier studies demonstrated that B. burgdorferi synthesizes 4,5-dihydroxy-2,3-pentanedione (autoinducer-2 [AI-2]) and responds to AI-2 by measurably changing production of several infection-associated proteins. luxS mutants, which are unable to produce AI-2, exhibit altered production of several proteins. B. burgdorferi cannot utilize the other product of LuxS, homocysteine, indicating that phenotypes of luxS mutants are not due to the absence of that molecule. Although a previous study found that a luxS mutant was capable of infecting mice, a critical caveat to those results is that bacterial …

Antimicrobial Peptides In 2014., Guangshun Wang, Biswajit Mishra, Kyle Lau, Tamara Lushnikova, Radha Golla, Xiuqing Wang

Journal Articles: Pathology and Microbiology

This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release …

Lipid And Protein Co-Regulation Of Pi3k Effectors Akt And Itk In Lymphocytes, Xinxin Wang, Leonard B. Hills, Yina H. Huang

Dartmouth Scholarship

The phosphoinositide 3-kinase (PI 3-kinase, PI3K) pathway transduces signals critical for lymphocyte function. PI3K generates the phospholipid PIP3 at the plasma membrane to recruit proteins that contain pleckstrin homology (PH) domains - a conserved domain found in hundreds of mammalian proteins. PH domain-PIP3 interactions allow for rapid signal propagation and confer a spatial component to these signals. The kinases Akt and Itk are key PI3K effectors that bind PIP3 via their PH domains and mediate vital processes - such as survival, activation, and differentiation - in lymphocytes. Here, we review the roles and regulation of PI3K signaling in lymphocytes with …

Prolonged-Acting, Multi-Targeting Gallium Nanoparticles Potently Inhibit Growth Of Both Hiv And Mycobacteria In Co-Infected Human Macrophages., Prabagaran Narayanasamy, Barbara L. Switzer, Bradley E. Britigan

Journal Articles: Pathology and Microbiology

Human immunodeficiency virus (HIV) infection and Mycobacterium tuberculosis (TB) are responsible for two of the major global human infectious diseases that result in significant morbidity, mortality and socioeconomic impact. Furthermore, severity and disease prevention of both infections is enhanced by co-infection. Parallel limitations also exist in access to effective drug therapy and the emergence of resistance. Furthermore, drug-drug interactions have proven problematic during treatment of co-incident HIV and TB infections. Thus, improvements in drug access and simplified treatment regimens are needed immediately. One of the key host cells infected by both HIV and TB is the mononuclear phagocyte (MP; monocyte, …

Lymph Node But Not Intradermal Injection Site Macrophages Are Critical For Germinal Center Formation And Antibody Responses To Rabies Vaccination., Andrew G Lytle, Shixue Shen, James Mcgettigan

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: Replication-deficient rabies virus (RABV)-based vaccines induce rapid and potent antibody responses via T cell-independent and T cell-dependent mechanisms. To further investigate early events in vaccine-induced antibody responses against RABV infections, we studied the role of macrophages as mediators of RABV-based vaccine immunogenicity. In this report, we show that a recombinant matrix gene-deleted RABV-based vaccine (rRABV-ΔM) infects and activates primary murine macrophages in vitro. Immunization of mice with live RABV-based vaccines results in accumulation of macrophages at the site of immunization, which suggests that macrophages in tissues support the development of effective anti-RABV B cell responses. However, we show that …

Zhx2 Enhances The Cytotoxicity Of Chemotherapeutic Drugs In Liver Tumor Cells By Repressing Mdr1 Via Interfering With Nf-Ya, Hongxin Ma, Xuetian Yue, Lifen Gao, Xiaohong Liang, Wenjiang Yan, Zhenyu Zhang, Haixia Shan, Hualin Zhang, Brett T. Spear, Chunhong Ma

Microbiology, Immunology, and Molecular Genetics Faculty Publications

We previously reported the tumor suppressor function of Zinc-fingers and homeoboxes 2 (ZHX2) in hepatocellular carcinoma (HCC). Other studies indicate the association of increased ZHX2 expression with improved response to high dose chemotherapy in multiple myeloma. Here, we aim to test whether increased ZHX2 levels in HCC cells repress multidrug resistance 1(MDR1) expression resulting in increased sensitivity to chemotherapeutic drugs. We showed evidence that increased ZHX2 levels correlated with reduced MDR1 expression and enhanced the cytotoxicity of CDDP and ADM in different HCC cell lines. Consistently, elevated ZHX2 significantly reduced ADM efflux in HepG2 cells and greatly increased the CDDP-mediated …

Memory T Cells Specific For Murine Cytomegalovirus Re-Emerge After Multiple Challenges And Recapitulate Immunity In Various Adoptive Transfer Scenarios., Michael Quinn, Holly Turula, Mayank Tandon, Berthony Deslouches, Toktam Moghbeli, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Reconstitution of CMV-specific immunity after transplant remains a primary clinical objective to prevent CMV disease, and adoptive immunotherapy of CMV-specific T cells can be an effective therapeutic approach. Because of viral persistence, most CMV-specific CD8(+) T cells become terminally differentiated effector phenotype CD8(+) T cells (TEFF). A minor subset retains a memory-like phenotype (memory phenotype CD8(+) T cells [TM]), but it is unknown whether these cells retain memory function or persist over time. Interestingly, recent studies suggest that CMV-specific CD8(+) T cells with different phenotypes have different abilities to reconstitute sustained immunity after transfer. The immunology of human CMV infections …

In Vivo Cigarette Smoke Exposure Decreases Ccl20, Slpi, And Bd-1 Secretion By Human Primary Nasal Epithelial Cells, James Jukosky, Benoit J. Gosselin, Leah Foley, Tenzin Dechen, Steven Fiering, Mardi A. Crane-Godreau

Dartmouth Scholarship

Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of …

Two Potential Hookworm Daf-16 Target Genes, Snr-3 And Lpp-1: Gene Structure, Expression Profile, And Implications Of A Cis-Regulatory Element In The Regulation Of Gene Expression, Xin Gao, Kevin Goggin, Camille Dowling, Jason Qian, John Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Hookworms infect nearly 700 million people, causing anemia and developmental stunting in heavy infections. Little is known about the genomic structure or gene regulation in hookworms, although recent publication of draft genome assemblies has allowed the first investigations of these topics to be undertaken. The transcription factor DAF-16 mediates multiple developmental pathways in the free living nematode Caenorhabditis elegans, and is involved in the recovery from the developmentally arrested L3 in hookworms. Identification of downstream targets of DAF-16 will provide a better understanding of the molecular mechanism of hookworm infection.

Methods

Genomic Fragment 2.23 containing a DAF-16 binding …

Intake Of Erythrocytes Required For Reproductive Development Of Female Schistosoma Japonicum., Jipeng Wang, Shuqi Wang, Xiufeng Liu, Bin Xu, Riyi Chai, Pan Zhou, Chuan Ju, Jun Sun, Paul J. Brindley, Wei Hu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

The reproductive development and maturation of female schistosomes are crucial since their released eggs are responsible for the host immunopathology and transmission of schistosomiasis. However, little is known about the nutrients required by female Schistosoma japonicum during its sexual maturation. We evaluated the promoting effect of several nutrients (calf serum, red blood cells (RBCs), ATP and hypoxanthine) on the reproductive development of pre-adult females at 18 days post infection (dpi) from mixed infections and at 50 dpi from unisexual infections of laboratory mice in basic medium RPMI-1640. We found RBCs, rather than other nutrients, promoted the female sexual maturation and …

An Improved Method For Generating Axenic Entomopathogenic Nematodes., Shruti Yadav, Upasana Shokal, Steven Forst, Ioannis Eleftherianos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Steinernema carpocapsae are parasitic nematodes that invade and kill insects. The nematodes are mutualistically associated with the bacteria Xenorhabdus nematophila and together form an excellent model to study pathogen infection processes and host anti-nematode/antibacterial immune responses. To determine the contribution of S. carpocapsae and their associated X. nematophila to the successful infection of insects as well as to investigate the interaction of each mutualistic partner with the insect immune system, it is important to develop and establish robust methods for generating nematodes devoid of their bacteria.

FINDINGS: To produce S. carpocapsae nematodes without their associated X. nematophila bacteria, we …

Of Monkeys And Men: Immunomic Profiling Of Sera From Humans And Non-Human Primates Resistant To Schistosomiasis Reveals Novel Potential Vaccine Candidates., Mark S Pearson, Luke Becker, Patrick Driguez, Neil D Young, Soraya Gaze, Jeffrey M. Bethony, +12 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Schistosoma haematobium affects more than 100 million people throughout Africa and is the causative agent of urogenital schistosomiasis. The parasite is strongly associated with urothelial cancer in infected individuals and as such is designated a group I carcinogen by the International Agency for Research on Cancer. Using a protein microarray containing schistosome proteins, we sought to identify antigens that were the targets of protective IgG1 immune responses in S. haematobium-exposed individuals that acquire drug-induced resistance (DIR) to schistosomiasis after praziquantel treatment. Numerous antigens with known vaccine potential were identified, including calpain (Smp80), tetraspanins, glutathione-S-transferases, and glucose transporters (SGTP1), as well …

The Carcinogenic Liver Fluke Opisthorchis Viverrini Is A Reservoir For Species Of Helicobacter., Raksawan Deenonpoe, Chariya Chomvarin, Chawalit Pairojkul, Yaowalux Chamgramol, Alex Loukas, Paul J. Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

There has been a strong, positive correlation between opisthorchiasis-associated cholangiocarcinoma and infection with Helicobacter. Here a rodent model of human infection with Opisthorchis viverrini was utilized to further investigate relationships of apparent co-infections with O. viverrini and H. pylori. A total of 150 hamsters were assigned to five groups: i) Control hamsters not infected with O. viverrini; ii) O. viverrini-infected hamsters; iii) non-O. viverrini infected hamsters treated with antibiotics (ABx); iv) O. viverrini-infected hamsters treated with ABx; and v) O. viverrini-infected hamsters treated both with ABx and praziquantel (PZQ). Stomach, gallbladder, liver, colonic tissue, colorectal feces and O. viverrini worms …

Comparison Of Findings Using Ultrasonography And Cystoscopy In Urogenital Schistosomiasis In A Public Health Centre In Rural Angola, Julio Santos, Jacinta Chaves, Heriberto Araujo, Nuno Vale, Jose Manuel Costa, Paul J. Brindley, Carlos Lopes, Jean Naples, Clive Shiff, Jorge Dupret, Lucio Lara Santos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Schistosomiasis is a chronic disease caused by infection with parasitic worms of the genus Schistosoma. In sub-Saharan Africa, infections with S. haematobium are most common. Cystoscopic examination (CE) has been accepted as the gold-standard test for detecting the late manifestations of schistosomiasis, including urothelial cancer of the bladder. However, this procedure is invasive and 10 - 40% of tumours may remain undetected. A non-invasive examination and a new generation of biomarkers are needed for better monitoring of the disease.

Objective. To assess the usefulness of ultrasound (US) scans for monitoring of structural urinary tract disease by local public health …

Isolated Candida Infection Of The Lung, Yousef Shweihat Md, James Perry, Darshana T. Shah Phd

Biochemistry and Microbiology

Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.

Gene Function In Schistosomes: Recent Advances Toward A Cure, Arnon D. Jurburg, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Expression Of Interferon Gamma By A Recombinant Rabies Virus Strongly Attenuates The Pathogenicity Of The Virus Via Induction Of Type I Interferon., Darryll A Barkhouse, Samantha A Garcia, Emily K Bongiorno, Aurore Lebrun, Milosz Faber, D Craig Hooper, Phd

Department of Cancer Biology Faculty Papers

UNLABELLED: Previous animal model experiments have shown a correlation between interferon gamma (IFN-γ) expression and both survival from infection with attenuated rabies virus (RABV) and reduction of neurological sequelae. Therefore, we hypothesized that rapid production of murine IFN-γ by the rabies virus itself would induce a more robust antiviral response than would occur naturally in mice. To test this hypothesis, we used reverse engineering to clone the mouse IFN-γ gene into a pathogenic rabies virus backbone, SPBN, to produce the recombinant rabies virus designated SPBNγ. Morbidity and mortality were monitored in mice infected intranasally with SPBNγ or SPBN(-) control virus …

Microbiological Contamination Of Mobile Phones Of Clinicians In Intensive Care Units And Neonatal Care Units In Public Hospitals In Kuwait, Mohammed Heyba, Mohammad Ismaiel, Abdulrahman Alotaibi, Mohamed Mahmoud, Hussain Baqer, Ali Safar, Noura Al-Sweih, Abdullah Al-Taiar

Community & Environmental Health Faculty Publications

Background: The objective of this study was to explore the prevalence of microbiological contamination of mobile phones that belong to clinicians in intensive care units (ICUs), pediatric intensive care units (PICUs), and neonatal care units (NCUs) in all public secondary care hospitals in Kuwait. The study also aimed to describe mobile phones disinfection practices as well as factors associated with mobile phone contamination.

Methods: This is a cross-sectional study that included all clinicians with mobile phones in ICUs, PICUs, and NCUs in all secondary care hospitals in Kuwait. Samples for culture were collected from mobile phones and transported for microbiological …

Anti-Cancer Activity Of Withaferin A In B-Cell Lymphoma., M K Mckenna, B W Gachuki, S S Alhakeem, K N Oben, V M Rangnekar, R C Gupta, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Withaferin A (WA), a withanolide from the plant, Ashwagandha (Withania somnifera) used in Ayurvedic medicine, has been found to be valuable in the treatment of several medical ailments. WA has been found to have anticancer activity against various solid tumors, but its effects on hematological malignancies have not been studied in detail. WA strongly inhibited the survival of several human and murine B cell lymphoma cell lines. Additionally, in vivo studies with syngeneic-graft lymphoma cells suggest that WA inhibits the growth of tumor but does not affect other proliferative tissues. We demonstrate that WA inhibits the efficiency of NF-κB nuclear …

Expression Of Enteropathogenic Escherichia Coli Map Is Significantly Different Than That Of Other Type Iii Secreted Effectors In Vivo., Mai Nguyen, Jason Rizvi, Gail Hecht

Department of Medicine Faculty Papers

The enteropathogenic Escherichia coli (EPEC) locus of enterocyte effacement (LEE)-encoded effectors EspF and Map are multifunctional and have an impact on the tight junction barrier while the non-LEE-encoded proteins NleH1 and NleH2 possess significant anti-inflammatory activity. In order to address the temporal expression of these important genes in vivo, their promoters were cloned upstream of the luxCDABE operon, and luciferase expression was measured in EPEC-infected mice by bioluminescence using an in vivo imaging system (IVIS). Bioluminescent images of living mice, of excised whole intestines, and of whole intestines longitudinally opened and washed were assessed. The majority of bioluminescent bacteria localized …

Rhabdovirus-Based Vaccine Platforms Against Henipaviruses., Drishya Kurup, Christoph Wirblich, Heinz Feldmann, Andrea Marzi, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

UNLABELLED: The emerging zoonotic pathogens Hendra virus (HeV) and Nipah virus (NiV) are in the genus Henipavirus in the family Paramyxoviridae. HeV and NiV infections can be highly fatal to humans and livestock. The goal of this study was to develop candidate vaccines against henipaviruses utilizing two well-established rhabdoviral vaccine vector platforms, recombinant rabies virus (RABV) and recombinant vesicular stomatitis virus (VSV), expressing either the codon-optimized or the wild-type (wt) HeV glycoprotein (G) gene. The RABV vector expressing the codon-optimized HeV G showed a 2- to 3-fold increase in incorporation compared to the RABV vector expressing wt HeV G. There …

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 …