Celiac Disease And Neurological Symptoms,
2013
Liberty University
Celiac Disease And Neurological Symptoms, Lauren V. Cook
Senior Honors Theses
New research has revealed that Celiac disease, an autoimmune illness affecting the small intestine, has more ties with neurological side effects than once was thought. The classic and most well known presentation of Celiac disease is gastrointestinal, including symptoms such as abdominal pains, nausea, diarrhea, and flatulence. Researchers have more recently found a correlation between Celiac disease and neurological illnesses such as epilepsy, depression, dementia, and ADHD. Physician awareness of the disease and the neurological side of the illness should be heightened in order for patients to receive earlier diagnosis and a better quality of life. Because of the difficulty …
Secretion Of Tcpf By The Vibrio Cholerae Toxin-Coregulated Pilus Biogenesis Apparatus Requires An N-Terminal Determinant,
2013
Dartmouth College
Secretion Of Tcpf By The Vibrio Cholerae Toxin-Coregulated Pilus Biogenesis Apparatus Requires An N-Terminal Determinant, Christina J. Megli, Ronald K. Taylor
Dartmouth Scholarship
Type IV pili are important for microcolony formation, biofilm formation, twitching motility, and attachment. We and others have shown that type IV pili are important for protein secretion across the outer membrane, similar to type II secretion systems. This study explored the relationship between protein secretion and pilus formation in Vibrio cholerae. The toxin-coregulated pilus (TCP), a type IV pilus required for V. cholerae pathogenesis, is necessary for the secretion of the colonization factor TcpF (T. J. Kirn, N. Bose, and R. K. Taylor, Mol. Microbiol. 49:81–92, 2003). This phenomenon is not unique to V. cholerae; secreted …
Neuroinflammation And Psychiatric Illness,
2013
New York University School of Medicine
Neuroinflammation And Psychiatric Illness, Souhel Najjar, Daniel M. Pearlman, Kenneth Alper, Amanda Najjar, Orrin Devinsky
Dartmouth Scholarship
Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence …
Icad Deficiency In Human Colon Cancer And Predisposition To Colon Tumorigenesis: Linkage To Apoptosis Resistance And Genomic Instability,
2013
LSU Health Sciences Center - New Orleans
Icad Deficiency In Human Colon Cancer And Predisposition To Colon Tumorigenesis: Linkage To Apoptosis Resistance And Genomic Instability, Youssef Errami, Hassan Brim, Karine Oumouna-Benachour, Mustapha Oumouna, Amarjit S. Naura, Hogyoung Kim, Jihang Ju, Christian J. Davis, Jong G. Kim, Hassan Ashktorab, Kenneth Fallon, Ming Xu, Jianhua Zhang, Luis Del Valle, A Hamid Boulares
School of Medicine Faculty Publications
We previously showed that DNA fragmentation factor, which comprises a caspase-3-activated DNase (CAD) and its inhibitor (ICAD), may influence the rate of cell death by generating PARP-1-activating DNA breaks. Here we tested the hypothesis that ICAD-deficient colon epithelial cells exhibiting resistance to death stimuli may accumulate additional genetic modifications, leading to a tumorigenic phenotype. We show that ICAD deficiency may be associated with colon malignancy in humans. Indeed, an examination of ICAD expression using immunohistochemistry in an array of both colon cancer and normal tissues revealed that ICAD expression levels were severely compromised in the cancerous tissues. Upon DNA damage …
Development Of A Diagnostic Test Set To Assess Agreement In Breast Pathology: Practical Application Of The Guidelines For Reporting Reliability And Agreement Studies (Grras),
2013
University of Washington
Development Of A Diagnostic Test Set To Assess Agreement In Breast Pathology: Practical Application Of The Guidelines For Reporting Reliability And Agreement Studies (Grras), Natalia V. Oster, Patricia A. Carney, Kimberly H. Allison, Donald L. Weaver, Lisa Reisch, Gary Longton, Tracy Onega
Dartmouth Scholarship
Diagnostic test sets are a valuable research tool that contributes importantly to the validity and reliability of studies that assess agreement in breast pathology. In order to fully understand the strengths and weaknesses of any agreement and reliability study, however, the methods should be fully reported. In this paper we provide a step-by-step description of the methods used to create four complex test sets for a study of diagnostic agreement among pathologists interpreting breast biopsy specimens. We use the newly developed Guidelines for Reporting Reliability and Agreement Studies (GRRAS) as a basis to report these methods.
Molecular Architecture Of The Uncleaved Hiv-1
Envelope Glycoprotein Trimer,
2013
Dana-Farber Cancer Institute
Molecular Architecture Of The Uncleaved Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Luis Castillo-Menendez, Liping Wang, Christopher Gu, Alon Herschhorn, Anik Désormeaux, Andrés Finzi, Shi-Hua Xiang, Joseph Sodroski
Nebraska Center for Virology: Faculty Publications
The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer, a membrane-fusing machine, mediates virus entry into host cells and is the sole virusspecific target for neutralizing antibodies. Binding the receptors, CD4 and CCR5/CXCR4, triggers Env conformational changes from the metastable unliganded state to the fusion-active state. We used cryo-electron microscopy to obtain a 6-Å structure of the membranebound, heavily glycosylated HIV-1 Env trimer in its uncleaved and unliganded state. The spatial organization of secondary structure elements reveals that the unliganded conformations of both gp120 and gp41 subunits differ from those induced by receptor binding. The gp120 trimer association domains, which …
Variations In The Biological Functions Of Hiv-1 Clade C
Envelope In A Shiv-Infected Rhesus Macaque During
Disease Progression,
2013
University of Nebraska-Lincoln
Variations In The Biological Functions Of Hiv-1 Clade C Envelope In A Shiv-Infected Rhesus Macaque During Disease Progression, For Yue Tso, Levon Abrahamyan, Shiu-Lok Hu, Ruth M. Ruprecht, Charles Wood
Nebraska Center for Virology: Faculty Publications
A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection …
Kaposi’S Sarcoma-Associated Herpesvirus Transactivator Rta Induces Cell Cycle Arrest In G0/G1 Phase By Stabilizing And Promoting Nuclear Localization Of P27Kip,
2013
University of Nebraska-Lincoln
Kaposi’S Sarcoma-Associated Herpesvirus Transactivator Rta Induces Cell Cycle Arrest In G0/G1 Phase By Stabilizing And Promoting Nuclear Localization Of P27Kip, Pankaj Kumar, Charles Wood
Nebraska Center for Virology: Faculty Publications
The Kaposi’s sarcoma-associated herpesvirus (KSHV) immediate-early gene, replication, and transcription activator (KRta) is a key viral protein that serves as the master regulator for viral lytic replication. In this study, we investigated the role of K-Rta in cell cycle regulation and found that the expression of K-Rta in doxycycline (Dox)-inducible BJAB cells induced cell cycle arrest in G0/G1 phase. Western blot analysis of key cell cycle regulators revealed that K-Rta-mediated cell cycle arrest was associated with a decrease in cyclin A and phosphorylated Rb (pS807/pS811) protein levels, both markers of S phase progression, and an increase in …
Low-Abundance Resistant Mutations In Hiv-1 Subtype C
Antiretroviral Therapy-Naïve Individuals As Revealed By
Pyrosequencing,
2013
University of Nebraska-Lincoln
Low-Abundance Resistant Mutations In Hiv-1 Subtype C Antiretroviral Therapy-Naïve Individuals As Revealed By Pyrosequencing, Sandra Gonzalez, Damien C. Tully, Clement Gondwe, Charles Wood
Nebraska Center for Virology: Faculty Publications
Given the recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, we sought to determine how often and at what levels do drug-resistant mutant variants exist in ART-naïve HIV subtype C infected individuals. Samples from 10 ART-naïve Zambian individuals were subjected to ultra-deep pyrosequencing (UDPS) to characterize the frequency of low-abundance drug resistance mutations in the pol gene. Low-abundance clinically relevant variants were detected for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in eight of the ten subjects. Intermediate to high-level resistance was predicted for the majority of NRTIs. Mutations conferring resistance to …
Clade C Hiv-1 Isolates Circulating In Southern
Africa Exhibit A Greater Frequency Of Dicysteine
Motif-Containing Tat Variants Than Those In
Southeast Asia And Cause Increased
Neurovirulence,
2013
Albert Einstein College of Medicine
Clade C Hiv-1 Isolates Circulating In Southern Africa Exhibit A Greater Frequency Of Dicysteine Motif-Containing Tat Variants Than Those In Southeast Asia And Cause Increased Neurovirulence, Vasudev R. Rao, Ujjwal Neogi, Joshua S, Talboom, Ligia Padilla, Mustafizur Rahman, Cari Fritz-French, Sandra Gonzalez-Ramirez, Anjali Verma, Charles Wood, Ruth M. Ruprecht, Udaykumar Ranga, Tasnim Azim, Vinayaka R. Prasad
Nebraska Center for Virology: Faculty Publications
Background: HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. …
Global Neuroaids Roundtable,
2013
National Institutes of Health
Global Neuroaids Roundtable, Jeymohan Joseph, Cristian L. Achim, Michael J. Boivin, Bruce J. Brew, David B. Clifford, Deborah A. Colosi, Ronald J. Ellis, Robert K. Heaton, Amadou Gallo-Diop, Igor Grant, Georgette D. Kanmogne, Mahendra Kumar, Scott Letendre, Thomas D. Marcotte, Avindra Nath, Carlos A. Pardo, Robert H. Paul, Lynn Pulliam, Kevin Robertson, Walter Royal Iii, Ned Sacktor, Pasiri Sithinamsuwan, Davey M. Smith, Victor Valcour, Brian Wigdahl, Charles Wood
Nebraska Center for Virology: Faculty Publications
In May 2012, the Division of AIDS Research at the National Institute of Mental Health (NIMH) organized the “Global NeuroAIDS Roundtable” in conjunction with the 11th International Symposium on Neurovirology and the 2012 Conference on HIV in the Nervous System. The meeting was held in New York, NY, USA and brought together NIMH-funded investigators who are currently working on projects related to the neurological complications of AIDS (NeuroAIDS) in Africa, Asia, Eastern Europe, and Latin America in order to provide an opportunity to share their recent findings and discuss the challenges encountered within each country. The major goals of the …
Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model,
2013
Liberty University
Aβ Alters The Dna Methylation Status Of Cell-Fate Genes In An Alzheimer’S Disease Model, Gary D. Isaacs, Noor Taher, Courtney Mckenzie, Rebecca Garrett, Matthew Baker, Nena Fox
Faculty Publications and Presentations
Alzheimer’s disease (AD) is characterized by neurofibrillary tangles and extracellular amyloid-β plaques (Aβ). Despite ongoing research, some ambiguity remains surrounding the role of Aβ in the pathogenesis of this neurodegenerative disease. While several studies have focused on the mutations associated with AD, our understanding of the epigenetic contributions to the disease remains less clear. To that end, we determined the changes in DNA methylation in differentiated human neurons with and without Aβ treatment. We isolated the DNA from neurons treated with Aβ or vehicle, and digested the two samples with either a methylation-sensitive (HpaII) or a methylation-insensitive (MspI) restriction endonuclease. …
Different Mechanisms Of Inflammation Induced In Virus And Autoimmune-Mediated Models Of Multiple Sclerosis In C57bl6 Mice.,
2013
Indian Institute of Science Education and Research-Kolkata, Mohanpur, Nadia West Bengal 741252, India
Different Mechanisms Of Inflammation Induced In Virus And Autoimmune-Mediated Models Of Multiple Sclerosis In C57bl6 Mice., Abhinoy Kishore, Anurag Kanaujia, Soma Nag, A M Rostami, Lawrence C. Kenyon, Kenneth S Shindler, Jayasri Das Sarma
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS). Neurotropic demyelinating strain of MHV (MHV-A59 or its isogenic recombinant strain RSA59) induces MS-like disease in mice mediated by microglia, along with a small population of T cells. The mechanism of demyelination is at least in part due to microglia-mediated myelin stripping, with some direct axonal injury. Immunization with myelin oligodendrocyte glycoprotein (MOG) induces experimental autoimmune encephalomyelitis (EAE), a mainly CD4(+) T-cell-mediated disease, although CD8(+) T cells may play a significant role in demyelination. It is possible that both autoimmune and nonimmune mechanisms such as …
Neisseria Oralis Sp. Nov., Isolated From Healthy Gingival Plaque And Clinical Samples,
2013
New York State Department of Health
Neisseria Oralis Sp. Nov., Isolated From Healthy Gingival Plaque And Clinical Samples, William J. Wolfgang, Teresa V. Passaretti, Reashma Jose, Jocelyn Cole, An Coorevits, Andrea N. Carpenter, Sherly Jose, Anita Van Landschoot, Jacques Izard, Donna J. Kohlerschmidt, Peter Vandamme, Floyd E. Dewhirst, Mark A. Fisher, Kimberlee A. Musser
Department of Food Science and Technology: Faculty Publications
A polyphasic analysis was undertaken of seven independent isolates of gram-negative cocci collected from pathological clinical samples from New York, Louisiana, Florida, and Illinois and healthy subgingival plaque from a patient in Virginia, USA. The 16S rRNA gene sequence similarity among these isolates was 99.7–100 %, and the closest species with a validly published name was Neisseria lactamica (96.9 % similarity to the type strain). DNA–DNA hybridization confirmed that these isolates are of the same species and are distinct from their nearest phylogenetic neighbor, N. lactamica. Phylogenetic analysis of 16S and 23S rRNA gene sequences indicated that the …
Towards Defining The Chloroviruses: A Genomic
Journey Through A Genus Of Large Dna Viruses,
2013
Aix-Marseille Université
Towards Defining The Chloroviruses: A Genomic Journey Through A Genus Of Large Dna Viruses, Adrien Jeanniard, David D. Dunigan, James Gurnon, Irina V. Agarkova, Ming Kang, Jason Vitek, Garry Duncan, O William Mcclung, Megan Larsen, Jean-Michel Claverie, James L. Van Etten, Guillaume Blanc
Nebraska Center for Virology: Faculty Publications
Background: Giant viruses in the genus Chlorovirus (family Phycodnaviridae) infect eukaryotic green microalgae. The prototype member of the genus, Paramecium bursaria chlorella virus 1, was sequenced more than 15 years ago, and to date there are only 6 fully sequenced chloroviruses in public databases. Presented here are the draft genome sequences of 35 additional chloroviruses (287 – 348 Kb/319 – 381 predicted protein encoding genes) collected across the globe; they infect one of three different green algal species. These new data allowed us to analyze the genomic landscape of 41 chloroviruses, which revealed some remarkable features about these viruses. …
Evaluation Of Higher Plant Virus Resistance Genes In The Green
Alga, Chlorella Variabilis Nc64a, During The Early Phase Of
Infection With Paramecium Bursaria Chlorella Virus-1,
2013
University of California - Irvine
Evaluation Of Higher Plant Virus Resistance Genes In The Green Alga, Chlorella Variabilis Nc64a, During The Early Phase Of Infection With Paramecium Bursaria Chlorella Virus-1, Janet M. Rowe, David D. Dunigan, Guillaume Blanc, James R. Gurnon, Yuannan Xia, James L. Van Etten
Nebraska Center for Virology: Faculty Publications
With growing industrial interest in algae plus their critical roles in aquatic systems, the need to understand the effects of algal pathogens is increasing. We examined a model algal host–virus system, Chlorella variabilis NC64A and virus, PBCV-1. C. variabilis encodes 375 homologs to genes involved in RNA silencing and in response to virus infection in higher plants. Illumina RNA-Seq data showed that 325 of these homologs were expressed in healthy and early PBCV-1 infected (≤60 min) cells. For each of the RNA silencing genes to which homologs were found, mRNA transcripts were detected in healthy and infected cells. C. variabilis …
A Twin-Cysteine Motif In The V2 Region Of Gp120 Is
Associated With Siv Envelope Trimer Stabilization,
2013
University of Nebraska-Lincoln
A Twin-Cysteine Motif In The V2 Region Of Gp120 Is Associated With Siv Envelope Trimer Stabilization, Christopher Bohl, Dane Bowder, Jesse Thompson, Levon Abrahamyan, Sandra Gonzalez-Ramirez, Youdong Mao, Joseph Sodroski, Charles Wood, Shi-Hua Xiang
Nebraska Center for Virology: Faculty Publications
The V1 and V2 variable regions of the primate immunodeficiency viruses contribute to the trimer association domain of the gp120 exterior envelope glycoprotein. A pair of V2 cysteine residues at 183 and 191 (‘‘twin cysteines’’) is present in several simian immunodeficiency viruses, human immunodeficiency virus type 2 (HIV-2) and some SIVcpz lineages, but not in HIV-1. To examine the role of this potentially disulfide-bonded twin-cysteine motif, the cysteine residues in the SIVmac239 envelope glycoproteins were individually and pairwise substituted by alanine residues. All of the twin-cysteine mutants exhibited decreases in gp120 association with the Env trimer, membrane-fusing activity, and …
Hiv-1 Env C2-V4 Diversification In A Slow-Progressor
Infant Reveals A Flat But Rugged Fitness Landscape,
2013
University of Oklahoma Health Sciences Center
Hiv-1 Env C2-V4 Diversification In A Slow-Progressor Infant Reveals A Flat But Rugged Fitness Landscape, S. Abigail Smith, Charles Wood, John T. West
Nebraska Center for Virology: Faculty Publications
Human immunodeficiency virus type-1 (HIV-1) fitness has been associated with virus entry, a process mediated by the envelope glycoprotein (Env). We previously described Env genetic diversification in a Zambian, subtype C infected, slow-progressor child (1157i) in parallel with an evolving neutralizing antibody response. Because of the role the Variable-3 loop (V3) plays in transmission, cell tropism, neutralization sensitivity, and fitness, longitudinally isolated 1157i C2-V4 alleles were cloned into HIV-1NL4-3-eGFP and -DsRed2 infectious molecular clones. The fluorescent reporters allowed for dual-infection competitions between all patient-derived C2-V4 chimeras to quantify the effect of V3 diversification and selection on fitness. ‘Winners’ …
‘‘Megavirales’’, A Proposed New Order For Eukaryotic
Nucleocytoplasmic Large Dna Viruses,
2013
Aix-Marseille Universite
‘‘Megavirales’’, A Proposed New Order For Eukaryotic Nucleocytoplasmic Large Dna Viruses, Philippe Colson, Xavier De Lamballerie, Natalya Yutin, Sassan Asgari, Yves Bigot, Dennis K. Bideshi, Xiao-Wen Cheng, Brian A. Federici, James L. Van Etten, Eugene V. Koonin, Bernard La Scola, Didier Raoult
Nebraska Center for Virology: Faculty Publications
The nucleocytoplasmic large DNA viruses (NCLDVs) comprise a monophyletic group of viruses that infect animals and diverse unicellular eukaryotes. The NCLDV group includes the families Poxviridae, Asfarviridae, Iridoviridae, Ascoviridae, Phycodnaviridae, Mimiviridae and the proposed family ‘‘Marseilleviridae’’. The family Mimiviridae includes the largest known viruses, with genomes in excess of one megabase, whereas the genome size in the other NCLDV families varies from 100 to 400 kilobase pairs. Most of the NCLDVs replicate in the cytoplasm of infected cells, within so-called virus factories. The NCLDVs share a common ancient origin, as demonstrated by evolutionary reconstructions that trace approximately 50 genes encoding …
Recent Advances On The Use Of Structural Biology For The
Design Of Novel Envelope Immunogens Of Hiv-1,
2013
University of Nebraska-Lincoln
Recent Advances On The Use Of Structural Biology For The Design Of Novel Envelope Immunogens Of Hiv-1, Shi-Hua Xiang
Nebraska Center for Virology: Faculty Publications
Many efforts have been made in the worldwide quest for a prophylactic HIV vaccine to end the AIDS pandemic, but none has yet succeeded. The lessons learned have repeatedly informed us that the traditional or conventional approaches directly using the pathogens or subunits will not be sufficient for an effective HIV/AIDS vaccine. Recent advances in structure-based technology have shown some promise in the quest for a better immunogen in HIV vaccine development. According to the basic binding structural relationship of an antigen and an antibody, structure-based antigen design could bring some hope for the development of an effective vaccine against …
