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Articles 1 - 30 of 32
Full-Text Articles in Medicine and Health Sciences
Bacterial Rna:Dna Hybrids Are Activators Of The Nlrp3 Inflammasome, Sivapriya Kailasan Vanaja, Vijay A. K. Rathinam, Maninjay K. Atianand, Parisa Kalantari, Brian M. Skehan, Katherine A. Fitzgerald, John M. Leong
Bacterial Rna:Dna Hybrids Are Activators Of The Nlrp3 Inflammasome, Sivapriya Kailasan Vanaja, Vijay A. K. Rathinam, Maninjay K. Atianand, Parisa Kalantari, Brian M. Skehan, Katherine A. Fitzgerald, John M. Leong
Katherine A. Fitzgerald
Enterohemorrhagic Escherichia coli (EHEC) is an extracellular pathogen that causes hemorrhagic colitis and hemolytic uremic syndrome. The proinflammatory cytokine, interleukin-1beta, has been linked to hemolytic uremic syndrome. Here we identify the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome as an essential mediator of EHEC-induced IL-1beta. Whereas EHEC-specific virulence factors were dispensable for NLRP3 activation, bacterial nucleic acids such as RNA:DNA hybrids and RNA gained cytosolic access and mediated inflammasome-dependent responses. Consistent with a direct role for RNA:DNA hybrids in inflammasome activation, delivery of synthetic EHEC RNA:DNA hybrids into the cytosol triggered NLRP3-dependent responses, …
Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald
Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald
Katherine A. Fitzgerald
Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …
Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo
Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo
Katherine A. Fitzgerald
Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis. Deficiency of …
Binge Ethanol And Liver: New Molecular Developments, Shivendra Shukla, Stephen Pruett, Gyongyi Szabo, Gavin Arteel
Binge Ethanol And Liver: New Molecular Developments, Shivendra Shukla, Stephen Pruett, Gyongyi Szabo, Gavin Arteel
Gyongyi Szabo
Binge consumption of alcohol is an alarming global health problem. Binge (acute) ethanol (EtOH) is implicated in the pathophysiology of alcoholic liver disease (ALD). New studies from experimental animals and from humans indicate that binge EtOH has profound effects on immunological, signaling, and epigenetic parameters of the liver. This is in addition to the known metabolic effects of acute EtOH. Binge EtOH alters the levels of several cellular components and dramatically amplifies liver injury in chronically EtOH exposed liver. These studies highlight the importance of molecular investigations into binge effects of EtOH for a better understanding of ALD and also …
Chronic Alcohol-Induced Microrna-155 Contributes To Neuroinflammation In A Tlr4-Dependent Manner In Mice, Dora Lippai, Shashi Bala, Timea Csak, Evelyn A. Kurt-Jones, Gyongyi Szabo
Chronic Alcohol-Induced Microrna-155 Contributes To Neuroinflammation In A Tlr4-Dependent Manner In Mice, Dora Lippai, Shashi Bala, Timea Csak, Evelyn A. Kurt-Jones, Gyongyi Szabo
Gyongyi Szabo
INTRODUCTION: Alcohol-induced neuroinflammation is mediated by pro-inflammatory cytokines and chemokines including tumor necrosis factor-alpha (TNFalpha), monocyte chemotactic protein-1 (MCP1) and interleukin-1-beta (IL-1beta). Toll-like receptor-4 (TLR4) pathway induced nuclear factor-kappaB (NF-kappaB) activation is involved in the pathogenesis of alcohol-induced neuroinflammation. Inflammation is a highly regulated process. Recent studies suggest that microRNAs (miRNAs) play crucial role in fine tuning gene expression and miR-155 is a major regulator of inflammation in immune cells after TLR stimulation. AIM: To evaluate the role of miR-155 in the pathogenesis of alcohol-induced neuroinflammation. METHODS: Wild type (WT), miR-155- and TLR4-knockout (KO) mice received 5% ethanol-containing or isocaloric …
Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo
Toll-Like Receptors In Liver Disease, Jan Petrasek, Timea Csak, Gyongyi Szabo
Gyongyi Szabo
Activation of inflammatory signaling pathways is of central importance in the pathogenesis of alcoholic liver disease (ALD) and nonalcoholic steatohepatitis (NASH). Recent studies demonstrated that Toll-like receptors, the sensors of microbial and endogenous danger signals, are expressed and activated in innate immune cells as well as in parenchymal cells in the liver and thereby contribute to ALD and NASH. In this review, we emphasize the importance of gut-derived endotoxin and its recognition by TLR4 in the liver. The significance of TLR-induced intracellular signaling pathways and cytokine production as well as the contribution of individual cell types to the inflammation is …
Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo
Sting-Irf3 Pathway Links Endoplasmic Reticulum Stress With Hepatocyte Apoptosis In Early Alcoholic Liver Disease, Jan Petrasek, Arvin Iracheta-Vellve, Timea Csak, Abhishek Satishchandran, Karen Kodys, Evelyn A. Kurt-Jones, Katherine A. Fitzgerald, Gyongyi Szabo
Gyongyi Szabo
Emerging evidence suggests that innate immunity drives alcoholic liver disease (ALD) and that the interferon regulatory factor 3 (IRF3),a transcription factor regulating innate immune responses, is indispensable for the development of ALD. Here we report that IRF3 mediates ALD via linking endoplasmic reticulum (ER) stress with apoptotic signaling in hepatocytes. We found that ethanol induced ER stress and triggered the association of IRF3 with the ER adaptor, stimulator of interferon genes (STING), as well as subsequent phosphorylation of IRF3. Activated IRF3 associated with the proapoptotic molecule Bax [B-cell lymphoma 2 (Bcl2)-associated X protein] and contributed to hepatocyte apoptosis. Deficiency of …
Annotated Bibliography: Interaction With Animals (1998-2013), Erich Yahner
Annotated Bibliography: Interaction With Animals (1998-2013), Erich Yahner
Erich Yahner, MSLIS
No abstract provided.
Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee
Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee
Mary M. Lee
Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both …
A Single Base Pair Mutation Encoding A Premature Stop Codon In The Mis Type Ii Receptor Is Responsible For Canine Persistent Mullerian Duct Syndrome, Wenfang Wu, Shengqin Wan, Pujar Shashikant, Mark Haskins, Donald Schlafer, Mary Lee, Vicki Meyers-Wallen
A Single Base Pair Mutation Encoding A Premature Stop Codon In The Mis Type Ii Receptor Is Responsible For Canine Persistent Mullerian Duct Syndrome, Wenfang Wu, Shengqin Wan, Pujar Shashikant, Mark Haskins, Donald Schlafer, Mary Lee, Vicki Meyers-Wallen
Mary M. Lee
Mullerian inhibiting substance (MIS), a secreted glycoprotein in the transforming growth factor-beta family of growth factors, mediates regression of the Mullerian ducts during embryonic sex differentiation in males. In persistent Mullerian duct syndrome (PMDS), rather than undergoing involution, the Mullerian ducts persist in males, giving rise to the uterus, fallopian tubes, and upper vagina. Genetic defects in MIS or its receptor (MISRII) have been identified in patients with PMDS. The phenotype in the canine model of PMDS derived from the miniature schnauzer breed is strikingly similar to that of human patients. In this model, PMDS is inherited as a sex-limited …
Hsisp Annotated Bibliography: Interaction With Animals (1998-2013), Erich Yahner
Hsisp Annotated Bibliography: Interaction With Animals (1998-2013), Erich Yahner
Erich Yahner
No abstract provided.
Hsisp Annotated Bibliography: Attitudes Toward Animals (1998-2013), Erich Yahner
Hsisp Annotated Bibliography: Attitudes Toward Animals (1998-2013), Erich Yahner
Erich Yahner, MSLIS
No abstract provided.
Multiple Specificities In The Murine Cd4+ And Cd8+ T-Cell Response To Dengue Virus, Alan Rothman, Ichiro Kurane, Francis Ennis
Multiple Specificities In The Murine Cd4+ And Cd8+ T-Cell Response To Dengue Virus, Alan Rothman, Ichiro Kurane, Francis Ennis
Alan Rothman
The target epitopes, serotype specificity, and cytolytic function of dengue virus-specific T cells may influence their theoretical roles in protection against secondary infection as well as the immunopathogenesis of dengue hemorrhagic fever. To study these factors in an experimental system, we isolated dengue virus-specific CD4+ and CD8+ T-cell clones from dengue-2 virus-immunized BALB/c mice. The T-cell response to dengue virus in this mouse strain was heterogeneous; we identified at least five different CD4+ phenotypes and six different CD8+ phenotypes. Individual T-cell clones recognized epitopes on the dengue virus pre-M, E, NSl/NS2A, and NS3 proteins and were restricted by the I-Ad, …
Dengue Virus Protein Recognition By Virus-Specific Murine Cd8+ Cytotoxic T Lymphocytes, Alan L. Rothman, Ichiro Kurane, Ching-Juh Lai, Michael Bray, Barry Falgout, Ruhe Men, Francis A. Ennis
Dengue Virus Protein Recognition By Virus-Specific Murine Cd8+ Cytotoxic T Lymphocytes, Alan L. Rothman, Ichiro Kurane, Ching-Juh Lai, Michael Bray, Barry Falgout, Ruhe Men, Francis A. Ennis
Alan Rothman
The identification of the protein targets for dengue virus-specific T lymphocytes may be useful for planning the development of subunit vaccines against dengue. We studied the recognition by murine dengue virus-specific major histocompatibility complex class I-restricted, CD8+ cytotoxic T lymphocytes (CTL) of dengue virus proteins using recombinant vaccinia viruses containing segments of the dengue virus genome. CTL from H-2k mice recognized a single serotype-cross-reactive epitope on the nonstructural (NS) protein NS3. CTL from H-2b mice recognized a serotype-cross-reactive epitope that was localized to NS4a or NS4b. CTL from H-2d mice recognized at least three epitopes: a serotype-specific epitope on one …
Cross-Reactive Memory Cd8(+) T Cells Alter The Immune Response To Heterologous Secondary Dengue Virus Infections In Mice In A Sequence-Specific Manner, Coreen Beaumier, Anuja Mathew, Hema Bashyam, Alan Rothman
Cross-Reactive Memory Cd8(+) T Cells Alter The Immune Response To Heterologous Secondary Dengue Virus Infections In Mice In A Sequence-Specific Manner, Coreen Beaumier, Anuja Mathew, Hema Bashyam, Alan Rothman
Alan Rothman
Dengue virus is the causative agent of dengue fever and the more-severe dengue hemorrhagic fever (DHF). Human studies suggest that the increased risk of DHF during secondary infection is due to immunopathology partially mediated by cross-reactive memory T cells from the primary infection. To model T cell responses to sequential infections, we immunized mice with different sequences of dengue virus serotypes and measured the frequency of peptide-specific T cells after infection. The acute response after heterologous secondary infections was enhanced compared with the acute or memory response after primary infection. Also, the hierarchy of epitope-specific responses was influenced by the …
Analysis Of Murine Cd8(+) T-Cell Clones Specific For The Dengue Virus Ns3 Protein: Flavivirus Cross-Reactivity And Influence Of Infecting Serotype, Anne C. Spaulding, Ichiro Kurane, Francis A. Ennis, Alan L. Rothman
Analysis Of Murine Cd8(+) T-Cell Clones Specific For The Dengue Virus Ns3 Protein: Flavivirus Cross-Reactivity And Influence Of Infecting Serotype, Anne C. Spaulding, Ichiro Kurane, Francis A. Ennis, Alan L. Rothman
Alan Rothman
Serotype-cross-reactive dengue virus-specific cytotoxic T lymphocytes (CTL) induced during a primary dengue virus infection are thought to play a role in the immunopathogenesis of dengue hemorrhagic fever (DHF) during a secondary dengue virus infection. Although there is no animal model of DHF, we previously reported that murine dengue virus-specific CTL responses are qualitatively similar to human dengue virus-specific CTL responses. We used BALB/c mice to study the specificity of the CTL response to an immunodominant epitope on the dengue virus NS3 protein. We mapped the minimal H-2Kd-restricted CTL epitope to residues 298 to 306 of the dengue type 2 virus …
Immune Mediated And Inherited Defences Against Flaviviruses, Margo Brinton, Ichiro Kurane, Anuja Mathew, Lingling Zeng, Pei Shi, Alan Rothman, Francis Ennis
Immune Mediated And Inherited Defences Against Flaviviruses, Margo Brinton, Ichiro Kurane, Anuja Mathew, Lingling Zeng, Pei Shi, Alan Rothman, Francis Ennis
Alan Rothman
BACKGROUND: Flavivirus infection elicits an abundant immune response in the host which is directed against a number of the viral proteins. Resistance to flavivirus-induced disease can also be controlled via a non-immune mechanism involving the product of a naturally occurring murine gene, Flv. OBJECTIVES: To review studies that have reported the mapping of epitopes on flavivirus proteins that elicit T- or B-cell immune responses in mice or humans and to discuss a possible mechanism for flavivirus-specific genetic resistance. STUDY DESIGN: Purified viral proteins and synthetic peptides were used to map B-cell epitopes. Purified proteins, vaccinia-expressed viral protein fragments and synthetic …
Increased Production Of Interleukin-8 In Primary Human Monocytes And In Human Epithelial And Endothelial Cell Lines After Dengue Virus Challenge, Irene Bosch, Kris Xhaja, Luis Estevez, Gregory Raines, Heather Melichar, Rajas Warke, Marcia Fournier, Francis Ennis, Alan Rothman
Increased Production Of Interleukin-8 In Primary Human Monocytes And In Human Epithelial And Endothelial Cell Lines After Dengue Virus Challenge, Irene Bosch, Kris Xhaja, Luis Estevez, Gregory Raines, Heather Melichar, Rajas Warke, Marcia Fournier, Francis Ennis, Alan Rothman
Alan Rothman
The more severe form of dengue virus infection, dengue hemorrhagic fever, is characterized by plasma leakage and derangements in hemostasis. As elevated interleukin-8 (IL-8) levels have been observed in sera from patients with more severe disease manifestations, a study was initiated to look at the effect of dengue virus infection in vitro on proinflammatory cytokine secretion and expression. A significant increase in IL-8 levels in the culture supernatant of primary human monocytes infected with dengue 2 virus (D2V) New Guinea C (NGC) was found by enzyme-linked immunosorbent assay. Additionally, by reverse transcriptase PCR, the mRNA was also augmented. Among the …
Robust Intrapulmonary Cd8 T Cell Responses And Protection With An Attenuated N1l Deleted Vaccinia Virus, Anuja Mathew, Joel O'Bryan, William L. Marshall, Girish J. Kotwal, Masanori Terajima, Sharone Green, Alan L. Rothman, Francis A. Ennis
Robust Intrapulmonary Cd8 T Cell Responses And Protection With An Attenuated N1l Deleted Vaccinia Virus, Anuja Mathew, Joel O'Bryan, William L. Marshall, Girish J. Kotwal, Masanori Terajima, Sharone Green, Alan L. Rothman, Francis A. Ennis
Alan Rothman
BACKGROUND: Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the immunogenicity of an attenuated strain of vaccinia virus engineered to inactivate the N1L gene (vGK5). Using the intranasal route, this recombinant virus was 2 logs less virulent compared to the wildtype VACV-WR. Infection by the intranasal, intraperitoneal, and tail scarification routes resulted in the robust induction of cytolytic virus-specific CD8 T cells in the spleens and the lungs. VACV-specific antibodies were also detected in the sera of mice infected 3-5 months prior with the attenuated …
Identification And Analysis For Cross-Reactivity Among Hantaviruses Of H-2b-Restricted Cytotoxic T-Lymphocyte Epitopes In Sin Nombre Virus Nucleocapsid Protein, Ken Maeda, Kim West, Tomoko Toyosaki-Maeda, Alan Rothman, Francis Ennis, Masanori Terajima
Identification And Analysis For Cross-Reactivity Among Hantaviruses Of H-2b-Restricted Cytotoxic T-Lymphocyte Epitopes In Sin Nombre Virus Nucleocapsid Protein, Ken Maeda, Kim West, Tomoko Toyosaki-Maeda, Alan Rothman, Francis Ennis, Masanori Terajima
Alan Rothman
Sin Nombre virus (SNV) causes hantavirus pulmonary syndrome (HPS), with a high rate of mortality in humans who are infected by the transmission of virus from the natural rodent host. In humans, cytotoxic T lymphocytes (CTL) specific for SNV appear to play an important role in the pathogenicity of HPS. There is a correlation between the frequencies of SNV-specific CTLs and the severity of HPS disease. In order to create a mouse model to study the role of SNV-specific T cells in vivo, T cell responses to SNV nucleocapsid (N) protein in B6.PL Thy1(a)/Cy mice (H-2(b)) immunized with plasmid DNA …
Dengue Virus-Specific Murine T-Lymphocyte Proliferation: Serotype Specificity And Response To Recombinant Viral Proteins, Alan L. Rothman, Ichiro Kurane, Yi-Ming Zhang, Ching-Juh Lai, Francis A. Ennis
Dengue Virus-Specific Murine T-Lymphocyte Proliferation: Serotype Specificity And Response To Recombinant Viral Proteins, Alan L. Rothman, Ichiro Kurane, Yi-Ming Zhang, Ching-Juh Lai, Francis A. Ennis
Alan Rothman
Definition of the T-lymphocyte responses to dengue viruses should aid in the development of safe and effective vaccines and help to explain the pathophysiology of dengue hemorrhagic fever and dengue shock syndrome. In this study, we demonstrated that dengue virus-specific T lymphocytes were detected in spleen cells from dengue virus-immune mice using an in vitro proliferation assay. Following immunization with a single dose of infectious dengue virus, murine lymphocytes showed increased proliferation when incubated in the presence of viral antigens of the same serotype but not in the presence of control antigens. Depletion experiments with antibody and complement showed that …
Identification Of Murine Poxvirus-Specific Cd8+ Ctl Epitopes With Distinct Functional Profiles, Anuja Mathew, Masanori Terajima, Kim West, Sharone Green, Alan Rothman, Francis Ennis, Jeffrey Kennedy
Identification Of Murine Poxvirus-Specific Cd8+ Ctl Epitopes With Distinct Functional Profiles, Anuja Mathew, Masanori Terajima, Kim West, Sharone Green, Alan Rothman, Francis Ennis, Jeffrey Kennedy
Alan Rothman
Murine T cell epitopes against vaccinia virus (VV) have not been characterized to date in part due to the large and complex genome of VV. We have identified and characterized two CD8+ T cell epitopes on the A47L (modified VV Ankara strain (MVA)-029) and J6R (MVA-043) proteins of VV that are Db and Kb restricted, respectively. Following i.p. immunization with VV New York City Board of Health (NYCBH) strain, MVA-029 peptide-stimulated splenocytes secreted IFN-gamma from 7 days to 7 mo postimmunization, and virus-stimulated effectors were also able to lyse MVA-029-pulsed target cells at the same time points. In contrast, MVA-043 …
The Public Health Impacts Of Concentrated Animal Feeding Operations On Local Communities, Michael Greger, Gowri Koneswaran
The Public Health Impacts Of Concentrated Animal Feeding Operations On Local Communities, Michael Greger, Gowri Koneswaran
Michael Greger, MD, FACLM
Large-scale farm animal production facilities, also known as concentrated animal feeding operations (CAFOs), release a significant amount of contaminants into the air and water. Adverse health effects related to exposure to these contaminants among CAFO workers have been welldocumented; however, less is known about their impact on the health of residents in nearby communities. Epidemiological research in this area suggests that neighboring residents are at increased risk of developing neurobehavioral symptoms and respiratory illnesses, including asthma. Additional research is needed to better understand community-scale exposures and health outcomes related to the management practices and emissions of CAFOs.
Medical Training Using Simulation: Toward Fewer Animals And Safer Patients, Jonathan Balcombe
Medical Training Using Simulation: Toward Fewer Animals And Safer Patients, Jonathan Balcombe
Jonathan Balcombe, PhD
This paper presents the current status of computer-based simulation in medicine. Recent technological advances have enabled this field to emerge from esoteric explorations in academic laboratories to commercially available simulators designed to train users to perform medical procedures from start to finish. Today, more than a dozen companies are producing virtual reality simulators and interactive manikins for training in endoscopy, laparoscopy, anaesthesia, trauma management, angiography, and needle insertion. For many of these procedures, thousands of animals are still being used in training. Yet simulation has many advantages that can transcend scientific, ethical, economic and logistical problems that arise when using …
The Genome Of Anopheles Darlingi, The Main Neotropical Malaria Vector, Osvaldo Marinotti, Adam R. Wespiser, Daniel R. Caffrey, Douglas T. Golenbock, Neal S. Silverman
The Genome Of Anopheles Darlingi, The Main Neotropical Malaria Vector, Osvaldo Marinotti, Adam R. Wespiser, Daniel R. Caffrey, Douglas T. Golenbock, Neal S. Silverman
Neal Silverman
Anopheles darlingi is the principal neotropical malaria vector, responsible for more than a million cases of malaria per year on the American continent. Anopheles darlingi diverged from the African and Asian malaria vectors approximately 100 million years ago (mya) and successfully adapted to the New World environment. Here we present an annotated reference A. darlingi genome, sequenced from a wild population of males and females collected in the Brazilian Amazon. A total of 10 481 predicted protein-coding genes were annotated, 72% of which have their closest counterpart in Anopheles gambiae and 21% have highest similarity with other mosquito species. In …
Acute Modulation Of Sugar Transport In Brain Capillary Endothelial Cell Cultures During Activation Of The Metabolic Stress Pathway, Anthony Cura, Anthony Carruthers
Acute Modulation Of Sugar Transport In Brain Capillary Endothelial Cell Cultures During Activation Of The Metabolic Stress Pathway, Anthony Cura, Anthony Carruthers
Anthony J. Cura
GLUT1-catalyzed equilibrative sugar transport across the mammalian blood-brain barrier is stimulated during acute and chronic metabolic stress; however, the mechanism of acute transport regulation is unknown. We have examined acute sugar transport regulation in the murine brain microvasculature endothelial cell line bEnd.3. Acute cellular metabolic stress was induced by glucose depletion, by potassium cyanide, or by carbonyl cyanide p-trifluoromethoxyphenylhydrazone, which reduce or deplete intracellular ATP within 15 min. This results in a 1.7-7-fold increase in V(max) for zero-trans 3-O-methylglucose uptake (sugar uptake into sugar-free cells) and a 3-10-fold increase in V(max) for equilibrium exchange transport (intracellular [sugar] = extracellular [sugar]). …
Dolichol-Linked Oligosaccharide Selection By The Oligosaccharyltransferase In Protist And Fungal Organisms, Daniel Kelleher, Sulagna Banerjee, Anthony Cura, John Samuelson, Reid Gilmore
Dolichol-Linked Oligosaccharide Selection By The Oligosaccharyltransferase In Protist And Fungal Organisms, Daniel Kelleher, Sulagna Banerjee, Anthony Cura, John Samuelson, Reid Gilmore
Anthony J. Cura
The dolichol-linked oligosaccharide Glc3Man9GlcNAc2-PP-Dol is the in vivo donor substrate synthesized by most eukaryotes for asparagine-linked glycosylation. However, many protist organisms assemble dolichol-linked oligosaccharides that lack glucose residues. We have compared donor substrate utilization by the oligosaccharyltransferase (OST) from Trypanosoma cruzi, Entamoeba histolytica, Trichomonas vaginalis, Cryptococcus neoformans, and Saccharomyces cerevisiae using structurally homogeneous dolichol-linked oligosaccharides as well as a heterogeneous dolichol-linked oligosaccharide library. Our results demonstrate that the OST from diverse organisms utilizes the in vivo oligo saccharide donor in preference to certain larger and/or smaller oligosaccharide donors. Steady-state enzyme kinetic experiments reveal that the binding affinity of the tripeptide …
Long Term Recall Of Memory Cd8 T Cells In Mice To First And Third Generation Smallpox Vaccines, Sharone Green, Francis Ennis, Anuja Mathew
Long Term Recall Of Memory Cd8 T Cells In Mice To First And Third Generation Smallpox Vaccines, Sharone Green, Francis Ennis, Anuja Mathew
Sharone Green
Since long-term immunity is a critical component of any effective vaccine, we compared over a 15-month period, the strength, durability and specificity of immunity of an attenuated smallpox vaccine Modified Vaccinia Ankara (MVA) to the New York City Board of Health (NYCBH) vaccine. The frequencies of CD8(+) T cells to an immunodominant CD8 T cell epitope B8R(20-27) remained remarkably stable in mice given either MVA or NYCBH. Both groups were also protected from a lethal intranasal challenge with Western Reserve strain of vaccinia virus (VACV-WR). Cytokine responses to virus-specific peptides were detectable with significant boosting upon challenge. Expression of most …
Robust Intrapulmonary Cd8 T Cell Responses And Protection With An Attenuated N1l Deleted Vaccinia Virus, Anuja Mathew, Joel O'Bryan, William L. Marshall, Girish J. Kotwal, Masanori Terajima, Sharone Green, Alan L. Rothman, Francis A. Ennis
Robust Intrapulmonary Cd8 T Cell Responses And Protection With An Attenuated N1l Deleted Vaccinia Virus, Anuja Mathew, Joel O'Bryan, William L. Marshall, Girish J. Kotwal, Masanori Terajima, Sharone Green, Alan L. Rothman, Francis A. Ennis
Sharone Green
BACKGROUND: Vaccinia viruses have been used as a model for viral disease and as a protective live vaccine. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the immunogenicity of an attenuated strain of vaccinia virus engineered to inactivate the N1L gene (vGK5). Using the intranasal route, this recombinant virus was 2 logs less virulent compared to the wildtype VACV-WR. Infection by the intranasal, intraperitoneal, and tail scarification routes resulted in the robust induction of cytolytic virus-specific CD8 T cells in the spleens and the lungs. VACV-specific antibodies were also detected in the sera of mice infected 3-5 months prior with the attenuated …
Identification Of Murine Poxvirus-Specific Cd8+ Ctl Epitopes With Distinct Functional Profiles, Anuja Mathew, Masanori Terajima, Kim West, Sharone Green, Alan Rothman, Francis Ennis, Jeffrey Kennedy
Identification Of Murine Poxvirus-Specific Cd8+ Ctl Epitopes With Distinct Functional Profiles, Anuja Mathew, Masanori Terajima, Kim West, Sharone Green, Alan Rothman, Francis Ennis, Jeffrey Kennedy
Sharone Green
Murine T cell epitopes against vaccinia virus (VV) have not been characterized to date in part due to the large and complex genome of VV. We have identified and characterized two CD8+ T cell epitopes on the A47L (modified VV Ankara strain (MVA)-029) and J6R (MVA-043) proteins of VV that are Db and Kb restricted, respectively. Following i.p. immunization with VV New York City Board of Health (NYCBH) strain, MVA-029 peptide-stimulated splenocytes secreted IFN-gamma from 7 days to 7 mo postimmunization, and virus-stimulated effectors were also able to lyse MVA-029-pulsed target cells at the same time points. In contrast, MVA-043 …