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Articles 571 - 600 of 902
Full-Text Articles in Entire DC Network
Immunological And Hematological Outcomes Following Protracted Low Dose/Low Dose Rate Ionizing Radiation And Simulated Microgravity, Amber M. Paul, Eliah G. Overbey, Willian A. Da Silveira, Nathaniel Szewczyk, Nina C. Nishiyama, Michael J. Pecaut, Sulekha Anand, Jonathan M. Galazka, Xiao Wen Mao
Immunological And Hematological Outcomes Following Protracted Low Dose/Low Dose Rate Ionizing Radiation And Simulated Microgravity, Amber M. Paul, Eliah G. Overbey, Willian A. Da Silveira, Nathaniel Szewczyk, Nina C. Nishiyama, Michael J. Pecaut, Sulekha Anand, Jonathan M. Galazka, Xiao Wen Mao
Publications
Using a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) …
A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction In Murine Polymicrobial Sepsis, Timothy W Phares, Vinayaka Kotraiah, Chun-Shiang Chung, Jacqueline Unsinger, Monty Mazer, Kenneth E. Remy, Cecille D. Browne, Peter Buontempo, Marc Mansour, James Pannucci, Alfred Ayala, Richard S. Hotchkiss, Gabriel M. Gutierrez
A Peptide-Based Checkpoint Immunomodulator Alleviates Immune Dysfunction In Murine Polymicrobial Sepsis, Timothy W Phares, Vinayaka Kotraiah, Chun-Shiang Chung, Jacqueline Unsinger, Monty Mazer, Kenneth E. Remy, Cecille D. Browne, Peter Buontempo, Marc Mansour, James Pannucci, Alfred Ayala, Richard S. Hotchkiss, Gabriel M. Gutierrez
2020-Current year OA Pubs
Sepsis-induced immunosuppression involves both innate and adaptive immunity and is associated with the increased expression of checkpoint inhibitors, such as programmed cell-death protein 1 (PD-1). The expression of PD-1 is associated with poor outcomes in septic patients, and in models of sepsis, blocking PD-1 or its ligands with antibodies increased survival and alleviated immune suppression. While inhibitory antibodies are effective, they can lead to immune-related adverse events (irAEs), in part due to continual blockade of the PD-1 pathway, resulting in hyperactivation of the immune response. Peptide-based therapeutics are an alternative drug modality that provide a rapid pharmacokinetic profile, reducing the …
Optimized Polyepitope Neoantigen Dna Vaccines Elicit Neoantigen-Specific Immune Responses In Preclinical Models And In Clinical Translation, Lijin Li, Xiuli Zhang, Xiaoli Wang, Samuel W Kim, John M Herndon, Michelle K Becker-Hapak, Beatriz M Carreno, Nancy B Myers, Mark A Sturmoski, Michael D Mclellan, Christopher A Miller, Tanner M Johanns, Benjamin R Tan, Gavin P Dunn, Timothy P Fleming, Ted H Hansen, S Peter Goedegebuure, William E Gillanders
Optimized Polyepitope Neoantigen Dna Vaccines Elicit Neoantigen-Specific Immune Responses In Preclinical Models And In Clinical Translation, Lijin Li, Xiuli Zhang, Xiaoli Wang, Samuel W Kim, John M Herndon, Michelle K Becker-Hapak, Beatriz M Carreno, Nancy B Myers, Mark A Sturmoski, Michael D Mclellan, Christopher A Miller, Tanner M Johanns, Benjamin R Tan, Gavin P Dunn, Timothy P Fleming, Ted H Hansen, S Peter Goedegebuure, William E Gillanders
2020-Current year OA Pubs
BACKGROUND: Preclinical studies and early clinical trials have shown that targeting cancer neoantigens is a promising approach towards the development of personalized cancer immunotherapies. DNA vaccines can be rapidly and efficiently manufactured and can integrate multiple neoantigens simultaneously. We therefore sought to optimize the design of polyepitope DNA vaccines and test optimized polyepitope neoantigen DNA vaccines in preclinical models and in clinical translation.
METHODS: We developed and optimized a DNA vaccine platform to target multiple neoantigens. The polyepitope DNA vaccine platform was first optimized using model antigens in vitro and in vivo. We then identified neoantigens in preclinical breast cancer …
Development Of A Highly Selective Plasmodium Falciparum Proteasome Inhibitor With Anti-Malaria Activity In Humanized Mice., Wenhu Zhan, Hao Zhang, John Ginn, Annie Leung, Yi J. Liu, Mayako Michino, Akinori Toita, Rei Okamoto, Tzu-Tshin Wong, Toshihiro Imaeda, Ryoma Hara, Takafumi Yukawa, Sevil Chelebieva, Patrick K. Tumwebaze, Maria Jose Lafuente-Monasterio, Maria Santos Martinez-Martinez, Jeremie Vendome, Thijs Beuming, Kenjiro Sato, Kazuyoshi Aso, Philip J. Rosenthal, Roland A. Cooper, Peter T Meinke, Carl F. Nathan, Laura A. Kirkman, Gang Lin
Development Of A Highly Selective Plasmodium Falciparum Proteasome Inhibitor With Anti-Malaria Activity In Humanized Mice., Wenhu Zhan, Hao Zhang, John Ginn, Annie Leung, Yi J. Liu, Mayako Michino, Akinori Toita, Rei Okamoto, Tzu-Tshin Wong, Toshihiro Imaeda, Ryoma Hara, Takafumi Yukawa, Sevil Chelebieva, Patrick K. Tumwebaze, Maria Jose Lafuente-Monasterio, Maria Santos Martinez-Martinez, Jeremie Vendome, Thijs Beuming, Kenjiro Sato, Kazuyoshi Aso, Philip J. Rosenthal, Roland A. Cooper, Peter T Meinke, Carl F. Nathan, Laura A. Kirkman, Gang Lin
Natural Sciences and Mathematics | Faculty Scholarship
Plasmodium falciparum proteasome (Pf20S) inhibitors are active against Plasmodium at multiple stages-erythrocytic, gametocyte, liver, and gamete activation stages-indicating that selective Pf20S inhibitors possess the potential to be therapeutic, prophylactic, and transmission-blocking antimalarials. Starting from a reported compound, we developed a noncovalent, macrocyclic peptide inhibitor of the malarial proteasome with high species selectivity and improved pharmacokinetic properties. The compound demonstrates specific, time-dependent inhibition of the β5 subunit of the Pf20S, kills artemisinin-sensitive and artemisinin-resistant P. falciparum isolates in vitro and reduces parasitemia in humanized, P. falciparum-infected mice.
Mitochondrial Transfer From Mesenchymal Stem Cells Improves Neuronal Metabolism After Oxidant Injury In Vitro: The Role Of Miro1, Nancy Tseng, Scott C Lambie, Christopher Q Huynh, Bridget Sanford, Manisha Patel, Paco S Herson, D Ryan Ormond
Mitochondrial Transfer From Mesenchymal Stem Cells Improves Neuronal Metabolism After Oxidant Injury In Vitro: The Role Of Miro1, Nancy Tseng, Scott C Lambie, Christopher Q Huynh, Bridget Sanford, Manisha Patel, Paco S Herson, D Ryan Ormond
Faculty, Staff and Students Publications
Stroke-induced cerebral ischemia is a major cause of death and disability. The disruption of blood flow results in neuronal and glial cell death leading to brain injury. Reperfusion restores oxygen to the affected tissue, but can also cause damage through an enhanced oxidative stress and inflammatory response. This study examines mitochondrial transfer from MSC to neurons and the role it plays in neuronal preservation after oxidant injury. We observed the transfer of mitochondria from MSC to mouse neurons in vitro following hydrogen peroxide exposure. The observed transfer was dependent on cell-to-cell contact and led to increased neuronal survival and improved …
An Inactivated Bacterium (Paraprobiotic) Expressing Bacillus Thuringiensis Cry5b As A Therapeutic For Ascaris And Parascaris Spp. Infections In Large Animals, Joseph F. Urban, Martin K. Nielsen, David Gazzola, Yue Xie, Ethiopia Beshah, Yan Hu, Hanchen Li, Florentina Rus, Kelly Flanagan, Austin Draper, Sridhar Vakalapudi, Robert W. Li, Gary R. Ostroff, Raffi V. Aroian
An Inactivated Bacterium (Paraprobiotic) Expressing Bacillus Thuringiensis Cry5b As A Therapeutic For Ascaris And Parascaris Spp. Infections In Large Animals, Joseph F. Urban, Martin K. Nielsen, David Gazzola, Yue Xie, Ethiopia Beshah, Yan Hu, Hanchen Li, Florentina Rus, Kelly Flanagan, Austin Draper, Sridhar Vakalapudi, Robert W. Li, Gary R. Ostroff, Raffi V. Aroian
Maxwell H. Gluck Equine Research Center Faculty Publications
Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus …
Inactivated Rabies Virus Vectored Sars-Cov-2 Vaccine Prevents Disease In A Syrian Hamster Model., Drishya Kurup, Delphine C Malherbe, Christoph Wirblich, Rachael Lambert, Adam J Ronk, Leila Zabihi Diba, Alexander Bukreyev, Matthias J. Schnell
Inactivated Rabies Virus Vectored Sars-Cov-2 Vaccine Prevents Disease In A Syrian Hamster Model., Drishya Kurup, Delphine C Malherbe, Christoph Wirblich, Rachael Lambert, Adam J Ronk, Leila Zabihi Diba, Alexander Bukreyev, Matthias J. Schnell
Department of Microbiology and Immunology Faculty Papers
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent coronavirus that has caused a worldwide pandemic. Although human disease is often asymptomatic, some develop severe illnesses such as pneumonia, respiratory failure, and death. There is an urgent need for a vaccine to prevent its rapid spread as asymptomatic infections accounting for up to 40% of transmission events. Here we further evaluated an inactivated rabies vectored SARS-CoV-2 S1 vaccine CORAVAX in a Syrian hamster model. CORAVAX adjuvanted with MPLA-AddaVax, a TRL4 agonist, induced high levels of neutralizing antibodies and generated a strong Th1-biased immune response. Vaccinated hamsters were protected from …
Pharmacokinetic And Pharmacodynamic Profiling Of Minocycline For Injection Following A Single Infusion In Critically Ill Adults In A Phase Iv Open-Label Multicenter Study (Acumin), Thomas P Lodise, Yasir Hamad, Et Al
Pharmacokinetic And Pharmacodynamic Profiling Of Minocycline For Injection Following A Single Infusion In Critically Ill Adults In A Phase Iv Open-Label Multicenter Study (Acumin), Thomas P Lodise, Yasir Hamad, Et Al
Open Access Publications
Intravenous (i.v.) minocycline is increasingly used to treat infections caused by multidrug-resistant (MDR)
Areas Of Metabolomic Exploration For Helminth Infections, Jeffrey D Whitman, Judy A Sakanari, Makedonka Mitreva
Areas Of Metabolomic Exploration For Helminth Infections, Jeffrey D Whitman, Judy A Sakanari, Makedonka Mitreva
2020-Current year OA Pubs
Helminths represent a diverse category of parasitic organisms that can thrive within a host for years, if not decades, in the absence of treatment. As such, they must establish mechanisms to subsist off their hosts, evade the immune system, and develop a niche among the other cohabiting microbial communities. The complex interplay of biologically small molecules (collectively known as the metabolome) derived from, utilized by, or in response to the presence of helminths within a host is an emerging field of study. In this Perspective, we briefly summarize the current existing literature, categorize key host-pathogen-microbiome interfaces that could be studied …
Characterization And Localization Of Antigens For Serodiagnosis Of Human Paragonimiasis, Kurt C Curtis, Kerstin Fischer, Young-Jun Choi, Makedonka Mitreva, Gary J Weil, Peter U Fischer
Characterization And Localization Of Antigens For Serodiagnosis Of Human Paragonimiasis, Kurt C Curtis, Kerstin Fischer, Young-Jun Choi, Makedonka Mitreva, Gary J Weil, Peter U Fischer
2020-Current year OA Pubs
Paragonimiasis is a foodborne trematode infection that affects 23 million people, mainly in Asia. Lung fluke infections lead frequently to chronic cough with fever and hemoptysis, and are often confused with lung cancer or tuberculosis. Paragonimiasis can be efficiently treated with praziquantel, but diagnosis is often delayed, and patients are frequently treated for other conditions. To improve diagnosis, we selected five Paragonimus kellicotti proteins based on transcriptional abundance, recognition by patient sera, and conservation among trematodes and expressed them as His-fusion proteins in Escherichia coli. Sequences for these proteins have 76-99% identity with amino acid sequences for orthologs in the …
The Gene Ontology Resource: Enriching A Gold Mine., Gene Ontology Consortium, Judith A. Blake, Mary E. Dolan, Harold J. Drabkin, David P. Hill
The Gene Ontology Resource: Enriching A Gold Mine., Gene Ontology Consortium, Judith A. Blake, Mary E. Dolan, Harold J. Drabkin, David P. Hill
Faculty Research 2021
The Gene Ontology Consortium (GOC) provides the most comprehensive resource currently available for computable knowledge regarding the functions of genes and gene products. Here, we report the advances of the consortium over the past two years. The new GO-CAM annotation framework was notably improved, and we formalized the model with a computational schema to check and validate the rapidly increasing repository of 2838 GO-CAMs. In addition, we describe the impacts of several collaborations to refine GO and report a 10% increase in the number of GO annotations, a 25% increase in annotated gene products, and over 9,400 new scientific articles …
Molecular Characterization Of Cryptosporidium Spp. From Humans In Ethiopia, Ambachew W. Hailu, Abraham Degarege, Haileeyesus Adamu, Damien Costa, Venceslas Villier, Abdelmounaim Mouhajir, Loic Favennec, Romy Razakandrainibe, Beyene Petros
Molecular Characterization Of Cryptosporidium Spp. From Humans In Ethiopia, Ambachew W. Hailu, Abraham Degarege, Haileeyesus Adamu, Damien Costa, Venceslas Villier, Abdelmounaim Mouhajir, Loic Favennec, Romy Razakandrainibe, Beyene Petros
Journal Articles: Epidemiology
Data on the distribution and genotype of Cryptosporidium species is limited in Ethiopia. This study examined the presence and genetic diversity of Cryptosporidium species circulating in Ethiopian human population. Stool samples collected from patients who visited rural (n = 94) and urban (n = 93) health centers in Wurgissa and Hawassa district, respectively, were examined for the presence of Cryptosporidium spp. using microscopy, nested PCR and real-time PCR. To detect infection with PCR, analysis of 18S ribosomal RNA was performed. Subtyping was performed by sequencing a fragment of GP60 gene. The overall prevalence of infection was 46% (n = 86) …
Type Iii Interferons: Emerging Roles In Autoimmunity, Sindhu Manivasagam, Robyn S Klein
Type Iii Interferons: Emerging Roles In Autoimmunity, Sindhu Manivasagam, Robyn S Klein
Open Access Publications
Type III interferons (IFNs) or the lambda IFNs (IFNLs or IFN-λs) are antimicrobial cytokines that play key roles in immune host defense at endothelial and epithelial barriers. IFNLs signal
Isolation And Characterization Of A Novel Bacteriophage Wo From Allonemobius Socius Crickets In Missouri, Jonah Kupritz, John Martin, Kerstin Fischer, Kurt C. Curtis, Joseph R. Fauver, Yuefang Huang, Young-Jun Choi, Wandy L. Beatty, Makedonka Mitreva, Peter U. Fischer
Isolation And Characterization Of A Novel Bacteriophage Wo From Allonemobius Socius Crickets In Missouri, Jonah Kupritz, John Martin, Kerstin Fischer, Kurt C. Curtis, Joseph R. Fauver, Yuefang Huang, Young-Jun Choi, Wandy L. Beatty, Makedonka Mitreva, Peter U. Fischer
Journal Articles: Epidemiology
Wolbachia are endosymbionts of numerous arthropod and some nematode species, are important for their development and if present can cause distinct phenotypes of their hosts. Prophage DNA has been frequently detected in Wolbachia, but particles of Wolbachia bacteriophages (phage WO) have been only occasionally isolated. Here, we report the characterization and isolation of a phage WO of the southern ground cricket, Allonemobius socius, and provided the first whole-genome sequence of phage WO from this arthropod family outside of Asia. We screened A. socius abdomen DNA extracts from a cricket population in eastern Missouri by quantitative PCR for Wolbachia surface protein …
Antibodies Against Egf-Like Domains In Ixodes Scapularis Bm86 Orthologs Impact Tick Feeding And Survival Of Borrelia Burgdorferi, Juraj Koči, Sandhya Bista, Payal Chirania, Xiuli Yang, Chrysoula Kitsou, Vipin Singh Rana, Ozlem Buyuktanir Yas, Daniel E. Sonenshine, Utpal Pal
Antibodies Against Egf-Like Domains In Ixodes Scapularis Bm86 Orthologs Impact Tick Feeding And Survival Of Borrelia Burgdorferi, Juraj Koči, Sandhya Bista, Payal Chirania, Xiuli Yang, Chrysoula Kitsou, Vipin Singh Rana, Ozlem Buyuktanir Yas, Daniel E. Sonenshine, Utpal Pal
Biological Sciences Faculty Publications
Ixodes scapularis ticks transmit multiple pathogens, including Borrelia burgdorferi sensu stricto, and encode many proteins harboring epidermal growth factor (EGF)-like domains. We show that I. scapularis produces multiple orthologs for Bm86, a widely studied tick gut protein considered as a target of an anti-tick vaccine, herein termed as Is86. We show that Is86 antigens feature at least three identifiable regions harboring EGF-like domains (termed as EGF-1, EGF-2, and EGF-3) and are differentially upregulated during B. burgdorferi infection. Although the RNA interference-mediated knockdown of Is86 genes did not show any influences on tick engorgement or B. burgdorferi sensu stricto persistence, the …
Targeting Host Glycolysis As A Strategy For Antimalarial Development, Andrew J Jezewski, Yu-Hsi Lin, Julie A Reisz, Rachel Culp-Hill, Yasaman Barekatain, Victoria C Yan, Angelo D'Alessandro, Florian L Muller, Audrey R Odom John
Targeting Host Glycolysis As A Strategy For Antimalarial Development, Andrew J Jezewski, Yu-Hsi Lin, Julie A Reisz, Rachel Culp-Hill, Yasaman Barekatain, Victoria C Yan, Angelo D'Alessandro, Florian L Muller, Audrey R Odom John
Open Access Publications
Glycolysis controls cellular energy, redox balance, and biosynthesis. Antiglycolytic therapies are under investigation for treatment of obesity, cancer, aging, autoimmunity, and microbial diseases. Interrupting glycolysis is highly valued as a therapeutic strategy, because glycolytic disruption is generally tolerated in mammals. Unfortunately, anemia is a known dose-limiting side effect of these inhibitors and presents a major caveat to development of antiglycolytic therapies. We developed specific inhibitors of enolase - a critical enzyme in glycolysis - and validated their metabolic and cellular effects on human erythrocytes. Enolase inhibition increases erythrocyte susceptibility to oxidative damage and induces rapid and premature erythrocyte senescence, rather …
Phylum-Spanning Neuropeptide Gpcr Identification And Prioritization: Shaping Drug Target Discovery Pipelines For Nematode Parasite Control, Louise E Atkinson, Ciaran J Mccoy, Bethany A Crooks, Fiona M Mckay, Paul Mcveigh, Darrin Mckenzie, Allister Irvine, John Harrington, Bruce A Rosa, Makedonka Mitreva, Nikki J Marks, Aaron G Maule, Angela Mousley
Phylum-Spanning Neuropeptide Gpcr Identification And Prioritization: Shaping Drug Target Discovery Pipelines For Nematode Parasite Control, Louise E Atkinson, Ciaran J Mccoy, Bethany A Crooks, Fiona M Mckay, Paul Mcveigh, Darrin Mckenzie, Allister Irvine, John Harrington, Bruce A Rosa, Makedonka Mitreva, Nikki J Marks, Aaron G Maule, Angela Mousley
Open Access Publications
Nematode parasites undermine human health and global food security. The frontline anthelmintic portfolio used to treat parasitic nematodes is threatened by the escalation of anthelmintic resistance, resulting in a demand for new drug targets for parasite control. Nematode neuropeptide signalling pathways represent an attractive source of novel drug targets which currently remain unexploited. The complexity of the nematode neuropeptidergic system challenges the discovery of new targets for parasite control, however recent advances in parasite 'omics' offers an opportunity for the
Noninvasive Immuno-Pet Imaging Of Cd8 + T Cell Behavior In Influenza A Virus-Infected Mice, Paul W Rothlauf, Zeyang Li, Novalia Pishesha, Yushu Joy Xie, Andrew W Woodham, Djenet Bousbaine, Stephen C Kolifrath, Vincent L Verschoor, Hidde L Ploegh
Noninvasive Immuno-Pet Imaging Of Cd8 + T Cell Behavior In Influenza A Virus-Infected Mice, Paul W Rothlauf, Zeyang Li, Novalia Pishesha, Yushu Joy Xie, Andrew W Woodham, Djenet Bousbaine, Stephen C Kolifrath, Vincent L Verschoor, Hidde L Ploegh
Open Access Publications
Immuno-positron emission tomography (immuno-PET) is a noninvasive imaging method that enables tracking of immune cells in living animals. We used a nanobody that recognizes mouse CD8α and labeled it with
Bladder Exposure To Gardnerella Activates Host Pathways Necessary For Escherichia Coli Recurrent Uti, Valerie P O'Brien, Amanda L Lewis, Nicole M Gilbert
Bladder Exposure To Gardnerella Activates Host Pathways Necessary For Escherichia Coli Recurrent Uti, Valerie P O'Brien, Amanda L Lewis, Nicole M Gilbert
Open Access Publications
Recurrent urinary tract infections (rUTI) are a costly clinical problem affecting millions of women worldwide each year. The majority of rUTI cases are caused by uropathogenic
Helminth-Virus Interactions: Determinants Of Coinfection Outcomes, Pritesh Desai, Michael S Diamond, Larissa B Thackray
Helminth-Virus Interactions: Determinants Of Coinfection Outcomes, Pritesh Desai, Michael S Diamond, Larissa B Thackray
Open Access Publications
Viral infections are often studied in model mammalian organisms under specific pathogen-free conditions. However, in nature, coinfections are common, and infection with one organism can alter host susceptibility to infection with another. Helminth parasites share a long coevolutionary history with mammalian hosts and have shaped host physiology, metabolism, immunity, and the composition of the microbiome. Published studies suggest that helminth infection can either be beneficial or detrimental during viral infection. Here, we discuss coinfection studies in mouse models and use them to define key determinants that impact outcomes, including the type of antiviral immunity, the tissue tropism of both the …
Alpha-Single Chains Of Collagen Type Vi Inhibit The Fibrogenic Effects Of Triple Helical Collagen Vi In Hepatic Stellate Cells, Christian Freise, Hyunho Lee, Christopher Chronowski, Doug Chan, Jessica Cziomer, Martin Rühl, Tarkan Dagdelen, Maik Lösekann, Ulrike Erben, Andre Catic, Werner Tegge, Detlef Schuppan, Rajan Somasundaram, Ergun Sahin
Alpha-Single Chains Of Collagen Type Vi Inhibit The Fibrogenic Effects Of Triple Helical Collagen Vi In Hepatic Stellate Cells, Christian Freise, Hyunho Lee, Christopher Chronowski, Doug Chan, Jessica Cziomer, Martin Rühl, Tarkan Dagdelen, Maik Lösekann, Ulrike Erben, Andre Catic, Werner Tegge, Detlef Schuppan, Rajan Somasundaram, Ergun Sahin
Faculty, Staff and Students Publications
The interaction of extracellular matrix (ECM) components with hepatic stellate cells (HSCs) is thought to perpetuate fibrosis by stimulating signaling pathways that drive HSC activation, survival and proliferation. Consequently, disrupting the interaction between ECM and HSCs is considered a therapeutical avenue although respective targets and underlying mechanisms remain to be established. Here we have interrogated the interaction between type VI collagen (CVI) and HSCs based on the observation that CVI is 10-fold upregulated during fibrosis, closely associates with HSCs in vivo and promotes cell proliferation and cell survival in cancer cell lines. We exposed primary rat HSCs and a rat …
The Cardiac Neural Crest Cells In Heart Development And Congenital Heart Defects, Eileen M Burd, Ahmed Babiker, Jessica K Fairley, Divya Bhamidipati, Laila E Woc-Colburn, Blaine A Mathison
The Cardiac Neural Crest Cells In Heart Development And Congenital Heart Defects, Eileen M Burd, Ahmed Babiker, Jessica K Fairley, Divya Bhamidipati, Laila E Woc-Colburn, Blaine A Mathison
Faculty, Staff and Student Publications
No abstract provided.
Aging, But Not Sex And Genetic Diversity, Impacts The Pathobiology Of Bacterial Endophthalmitis, Pawan Kumar Singh, Sukhvinder Singh, Robert Emery Wright, Ramandeep Rattan, Ashok Kumar
Aging, But Not Sex And Genetic Diversity, Impacts The Pathobiology Of Bacterial Endophthalmitis, Pawan Kumar Singh, Sukhvinder Singh, Robert Emery Wright, Ramandeep Rattan, Ashok Kumar
Obstetrics, Gynecology and Women's Health Services Articles
Purpose: Age, sex, and genetics are important biological variables in determining an individual's susceptibility or response to infectious agents; however, their role has not been evaluated in intraocular infections. In this study, we comprehensively examined the impact of these host biological factors in the pathogenesis of experimental bacterial endophthalmitis.
Methods: Endophthalmitis was induced by intravitreal injection of bacteria (Staphylococcus aureus) in the eyes of male and female C57BL/6 mice of different ages: group I (young, 6-8 weeks), group II (mid-age, 18-20 weeks), and group III (old, 1 year). Highly heterogeneous outbred J:DO mice were used for genetic diversity analysis. Eyes …
A Praziquantel Treatment Study Of Immune And Transcriptome Profiles In Schistosoma Haematobium-Infected Gabonese Schoolchildren, Lucja A Labuda, Ayola A Adegnika, Bruce A Rosa, John Martin, Ulysse Ateba-Ngoa, Abena Serwaa Amoah, Honorine Mbenkep Lima, Lynn Meurs, Moustapha Mbow, Mikhael D Manurung, Jeannot F Zinsou, Hermelijn H Smits, Peter G Kremsner, Makedonka Mitreva, Maria Yazdanbakhsh
A Praziquantel Treatment Study Of Immune And Transcriptome Profiles In Schistosoma Haematobium-Infected Gabonese Schoolchildren, Lucja A Labuda, Ayola A Adegnika, Bruce A Rosa, John Martin, Ulysse Ateba-Ngoa, Abena Serwaa Amoah, Honorine Mbenkep Lima, Lynn Meurs, Moustapha Mbow, Mikhael D Manurung, Jeannot F Zinsou, Hermelijn H Smits, Peter G Kremsner, Makedonka Mitreva, Maria Yazdanbakhsh
2020-Current year OA Pubs
BACKGROUND: Although Schistosoma haematobium infection has been reported to be associated with alterations in immune function, in particular immune hyporesponsiveness, there have been only few studies that have used the approach of removing infection by drug treatment to establish this and to understand the underlying molecular mechanisms.
METHODS: Schistosoma haematobium-infected schoolchildren were studied before and after praziquantel treatment and compared with uninfected controls. Cellular responses were characterized by cytokine production and flow cytometry, and in a subset of children RNA sequencing (RNA-Seq) transcriptome profiling was performed.
RESULTS: Removal of S haematobium infection resulted in increased schistosome-specific cytokine responses that were …
Characterization Of Glycan Determinants That Mediate Recognition Of The Major Wuchereria Bancrofti Circulating Antigen By Diagnostic Antibodies, Marla I Hertz, Amy Rush, Thomas B Nutman, Gary J Weil, Sasisekhar Bennuru, Philip J Budge
Characterization Of Glycan Determinants That Mediate Recognition Of The Major Wuchereria Bancrofti Circulating Antigen By Diagnostic Antibodies, Marla I Hertz, Amy Rush, Thomas B Nutman, Gary J Weil, Sasisekhar Bennuru, Philip J Budge
2020-Current year OA Pubs
The Global Program to Eliminate Lymphatic Filariasis (GPELF) relies heavily on a rapid diagnostic test (RDT) to a Wuchereria bancrofti circulating filarial antigen (Wb-CFA) to identify endemic areas and for determining when mass drug administration can stop. The antigen contains a carbohydrate epitope that is recognized by monoclonal antibody AD12. Og4C3, a monoclonal antibody that is used in a commercial ELISA for Wb-CFA recognizes the same moiety. Despite its diagnostic importance, little is known about the structure and function of this "AD12 epitope". It is also present on other W. bancrofti glycoproteins and on glycoproteins of other filarial worms, but …
Efficacy And Safety Of A Single Dose Of Ivermectin, Diethylcarbamazine, And Albendazole For Treatment Of Lymphatic Filariasis In Côte D'Ivoire: An Open-Label Randomized Controlled Trial, Catherine M Bjerum, Allassane F Ouattara, Méité Aboulaye, Olivier Kouadio, Vanga K Marius, Britt J Andersen, Gary J Weil, Benjamin G Koudou, Christopher L King
Efficacy And Safety Of A Single Dose Of Ivermectin, Diethylcarbamazine, And Albendazole For Treatment Of Lymphatic Filariasis In Côte D'Ivoire: An Open-Label Randomized Controlled Trial, Catherine M Bjerum, Allassane F Ouattara, Méité Aboulaye, Olivier Kouadio, Vanga K Marius, Britt J Andersen, Gary J Weil, Benjamin G Koudou, Christopher L King
2020-Current year OA Pubs
BACKGROUND: Improved drug regimens are needed to accelerate elimination of lymphatic filariasis in Africa. This study determined whether a single co-administered dose of ivermectin plus diethylcarbamazine plus albendazole [IDA] is noninferior to standard 3 annual doses of ivermectin plus albendazole (IA) used in many LF-endemic areas of Africa.
METHODS: Treatment-naive adults with Wuchereria bancrofti microfilaremia in Côte d'Ivoire were randomized to receive a single dose of IDA (n = 43) or 3 annual doses of IA (n = 52) in an open-label, single-blinded trial. The primary endpoint was the proportion of participants who were microfilaria (Mf) negative at 36 months. …
Macrophage-Associated Lipin-1 Promotes Β-Oxidation In Response To Proresolving Stimuli, Robert M Schilke, Cassidy M R Blackburn, Shashanka Rao, David M Krzywanski, Brian N Finck, Matthew D Woolard
Macrophage-Associated Lipin-1 Promotes Β-Oxidation In Response To Proresolving Stimuli, Robert M Schilke, Cassidy M R Blackburn, Shashanka Rao, David M Krzywanski, Brian N Finck, Matthew D Woolard
2020-Current year OA Pubs
Macrophages reprogram their metabolism to promote appropriate responses. Proresolving macrophages primarily use fatty acid oxidation as an energy source. Metabolites generated during the catabolism of fatty acids aid in the resolution of inflammation and tissue repair, but the regulatory mechanisms that control lipid metabolism in macrophages are not fully elucidated. Lipin-1, a phosphatidic acid phosphatase that has transcriptional coregulator activity, regulates lipid metabolism in a variety of cells. In this current study, we show that lipin-1 is required for increased oxidative phosphorylation in IL-4 stimulated mouse (
Yebc Regulates Variable Surface Antigen Vlse Expression And Is Required For Host Immune Evasion In Borrelia Burgdorferi, Yan Zhang, Tong Chen, Sajith Raghunandanan, Xuwu Xiang, Jing Yang, Qiang Liu, Diane G Edmondson, Steven J Norris, X Frank Yang, Yongliang Lou
Yebc Regulates Variable Surface Antigen Vlse Expression And Is Required For Host Immune Evasion In Borrelia Burgdorferi, Yan Zhang, Tong Chen, Sajith Raghunandanan, Xuwu Xiang, Jing Yang, Qiang Liu, Diane G Edmondson, Steven J Norris, X Frank Yang, Yongliang Lou
Faculty, Staff and Student Publications
Borrelia burgdorferi, the Lyme disease pathogen causes persistent infection by evading the host immune response. Differential expression of the surface-exposed lipoprotein VlsE that undergoes antigenic variation is a key immune evasion strategy employed by B. burgdorferi. Most studies focused on the mechanism of VlsE antigen variation, but little is known about VlsE regulation and factor(s) that regulates differential vlsE expression. In this study, we investigated BB0025, a putative YebC family transcriptional regulator (and hence designated BB0025 as YebC of B. burgdorferi herein). We constructed yebC mutant and complemented strain in an infectious strain of B. burgdorferi. The yebC mutant could …
In Vitro Susceptibility Of Treponema Pallidum Subsp Pallidum To Doxycycline, Diane G Edmondson, Gary P Wormser, Steven J Norris
In Vitro Susceptibility Of Treponema Pallidum Subsp Pallidum To Doxycycline, Diane G Edmondson, Gary P Wormser, Steven J Norris
Faculty, Staff and Student Publications
Doxycycline is regarded as an effective therapy for early syphilis, and there is increasing interest in using doxycycline for prophylaxis of this infection. However, the MIC of doxycycline for Treponema pallidum subsp. pallidum has not been reported previously. In this study, an in vitro culture system was utilized to determine that the MIC of doxycycline is 0.06 to 0.10 μg/ml for four strains of T. pallidum subsp. pallidum (Nichols, SS14, UW231B, and UW249B). The Nichols strain cultured in vitro with doxycycline was also tested for infectivity in rabbits, and the minimum bactericidal concentration (MBC) was found to be ≤0.1 μg/ml …
Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer
Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer
Open Access Publications
Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual …