Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 135

Publication Record

Connections

Prefrontal Control of Visual Distraction.
Cosman JD, Lowe KA, Zinke W, Woodman GF, Schall JD
(2018) Curr Biol 28: 414-420.e3
MeSH Terms: Animals, Attention, Evoked Potentials, Macaca mulatta, Male, Prefrontal Cortex, Visual Cortex, Visual Perception
Show Abstract · Added March 15, 2018
Avoiding distraction by conspicuous but irrelevant stimuli is critical to accomplishing daily tasks. Regions of prefrontal cortex control attention by enhancing the representation of task-relevant information in sensory cortex, which can be measured in modulation of both single neurons and event-related electrical potentials (ERPs) on the cranial surface [1, 2]. When irrelevant information is particularly conspicuous, it can distract attention and interfere with the selection of behaviorally relevant information. Such distraction can be minimized via top-down control [3-5], but the cognitive and neural mechanisms giving rise to this control over distraction remain uncertain and debated [6-9]. Bridging neurophysiology to electrophysiology, we simultaneously recorded neurons in prefrontal cortex and ERPs over extrastriate visual cortex to track the processing of salient distractors during a visual search task. Critically, when the salient distractor was successfully ignored, but not otherwise, we observed robust suppression of salient distractor representations. Like target selection, the distractor suppression was observed in prefrontal cortex before it appeared over extrastriate cortical areas. Furthermore, all prefrontal neurons that showed suppression of the task-irrelevant distractor also contributed to selecting the target. This suggests a common prefrontal mechanism is responsible for both selecting task-relevant and suppressing task-irrelevant information in sensory cortex. Taken together, our results resolve a long-standing debate over the mechanisms that prevent distraction, and provide the first evidence directly linking suppressed neural firing in prefrontal cortex with surface ERP measures of distractor suppression.
Copyright © 2017 Elsevier Ltd. All rights reserved.
0 Communities
1 Members
0 Resources
8 MeSH Terms
Vaccine Induction of Heterologous Tier 2 HIV-1 Neutralizing Antibodies in Animal Models.
Saunders KO, Verkoczy LK, Jiang C, Zhang J, Parks R, Chen H, Housman M, Bouton-Verville H, Shen X, Trama AM, Scearce R, Sutherland L, Santra S, Newman A, Eaton A, Xu K, Georgiev IS, Joyce MG, Tomaras GD, Bonsignori M, Reed SG, Salazar A, Mascola JR, Moody MA, Cain DW, Centlivre M, Zurawski S, Zurawski G, Erickson HP, Kwong PD, Alam SM, Levy Y, Montefiori DC, Haynes BF
(2017) Cell Rep 21: 3681-3690
MeSH Terms: AIDS Vaccines, Amino Acid Sequence, Animals, Antibodies, Neutralizing, Disease Models, Animal, Epitopes, HIV Antibodies, HIV-1, Immunization, Macaca mulatta, Mice, Polysaccharides, Protein Multimerization, Rabbits, env Gene Products, Human Immunodeficiency Virus
Show Abstract · Added March 14, 2018
The events required for the induction of broad neutralizing antibodies (bnAbs) following HIV-1 envelope (Env) vaccination are unknown, and their induction in animal models as proof of concept would be critical. Here, we describe the induction of plasma antibodies capable of neutralizing heterologous primary (tier 2) HIV-1 strains in one macaque and two rabbits. Env immunogens were designed to induce CD4 binding site (CD4bs) bnAbs, but surprisingly, the macaque developed V1V2-glycan bnAbs. Env immunization of CD4bs bnAb heavy chain rearrangement (VDJ) knockin mice similarly induced V1V2-glycan neutralizing antibodies (nAbs), wherein the human CD4bs V chains were replaced with mouse rearrangements bearing diversity region (D)-D fusions, creating antibodies with long, tyrosine-rich HCDR3s. Our results show that Env vaccination can elicit broad neutralization of tier 2 HIV-1, demonstrate that V1V2-glycan bnAbs are more readily induced than CD4bs bnAbs, and define V replacement and diversity region fusion as potential mechanisms for generating V1V2-glycan bnAb site antibodies.
Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Gene Regulatory Enhancers with Evolutionarily Conserved Activity Are More Pleiotropic than Those with Species-Specific Activity.
Fish A, Chen L, Capra JA
(2017) Genome Biol Evol 9: 2615-2625
MeSH Terms: Animals, Callithrix, Cats, Cattle, Conserved Sequence, Databases, Genetic, Dogs, Enhancer Elements, Genetic, Evolution, Molecular, Genetic Pleiotropy, Histones, Humans, Macaca mulatta, Mice, Rabbits, Rats, Swine
Show Abstract · Added March 14, 2018
Studies of regulatory activity and gene expression have revealed an intriguing dichotomy: There is substantial turnover in the regulatory activity of orthologous sequences between species; however, the expression level of orthologous genes is largely conserved. Understanding how distal regulatory elements, for example, enhancers, evolve and function is critical, as alterations in gene expression levels can drive the development of both complex disease and functional divergence between species. In this study, we investigated determinants of the conservation of regulatory enhancer activity for orthologous sequences across mammalian evolution. Using liver enhancers identified from genome-wide histone modification profiles in ten diverse mammalian species, we compared orthologous sequences that exhibited regulatory activity in all species (conserved-activity enhancers) to shared sequences active only in a single species (species-specific-activity enhancers). Conserved-activity enhancers have greater regulatory potential than species-specific-activity enhancers, as quantified by both the density and diversity of transcription factor binding motifs. Consistent with their greater regulatory potential, conserved-activity enhancers have greater regulatory activity in humans than species-specific-activity enhancers: They are active across more cellular contexts, and they regulate more genes than species-specific-activity enhancers. Furthermore, the genes regulated by conserved-activity enhancers are expressed in more tissues and are less tolerant of loss-of-function mutations than those targeted by species-specific-activity enhancers. These consistent results across various stages of gene regulation demonstrate that conserved-activity enhancers are more pleiotropic than their species-specific-activity counterparts. This suggests that pleiotropy is associated with the conservation of regulatory across mammalian evolution.
© The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Broadly neutralizing antibodies targeting the HIV-1 envelope V2 apex confer protection against a clade C SHIV challenge.
Julg B, Tartaglia LJ, Keele BF, Wagh K, Pegu A, Sok D, Abbink P, Schmidt SD, Wang K, Chen X, Joyce MG, Georgiev IS, Choe M, Kwong PD, Doria-Rose NA, Le K, Louder MK, Bailer RT, Moore PL, Korber B, Seaman MS, Abdool Karim SS, Morris L, Koup RA, Mascola JR, Burton DR, Barouch DH
(2017) Sci Transl Med 9:
MeSH Terms: Amino Acid Sequence, Animals, Antibodies, Neutralizing, CD4-Positive T-Lymphocytes, Female, HIV Envelope Protein gp120, HIV-1, Macaca mulatta, Male, Neutralization Tests, Sequence Alignment, Simian Acquired Immunodeficiency Syndrome, Simian Immunodeficiency Virus, Viral Load
Show Abstract · Added March 14, 2018
Neutralizing antibodies to the V2 apex antigenic region of the HIV-1 envelope (Env) trimer are among the most prevalent cross-reactive antibodies elicited by natural infection. Two recently described V2-specific antibodies, PGDM1400 and CAP256-VRC26.25, have demonstrated exquisite potency and neutralization breadth against HIV-1. However, little data exist on the protective efficacy of V2-specific neutralizing antibodies. We created a novel SHIV-325c viral stock that included a clade C HIV-1 envelope and was susceptible to neutralization by both of these antibodies. Rhesus macaques received a single infusion of either antibody at three different concentrations (2, 0.4, and 0.08 mg/kg) before challenge with SHIV-325c. PGDM1400 was fully protective at the 0.4 mg/kg dose, whereas CAP256-VRC26.25-LS was fully protective even at the 0.08 mg/kg dose, which correlated with its greater in vitro neutralization potency against the challenge virus. Serum antibody concentrations required for protection were <0.75 μg/ml for CAP256-VRC26.25-LS. These data demonstrate unprecedented potency and protective efficacy of V2-specific neutralizing antibodies in nonhuman primates and validate V2 as a potential target for the prevention of HIV-1 infection in passive immunization strategies in humans.
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
0 Communities
1 Members
0 Resources
14 MeSH Terms
Decreased Rhes mRNA levels in the brain of patients with Parkinson's disease and MPTP-treated macaques.
Napolitano F, Booth Warren E, Migliarini S, Punzo D, Errico F, Li Q, Thiolat ML, Vescovi AL, Calabresi P, Bezard E, Morelli M, Konradi C, Pasqualetti M, Usiello A
(2017) PLoS One 12: e0181677
MeSH Terms: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Aged, Aged, 80 and over, Animals, Bipolar Disorder, Brain Chemistry, Case-Control Studies, Female, GTP-Binding Proteins, Humans, Macaca mulatta, Male, Middle Aged, Parkinson Disease, Putamen, RNA, Messenger, Schizophrenia
Show Abstract · Added March 14, 2018
In rodent and human brains, the small GTP-binding protein Rhes is highly expressed in virtually all dopaminoceptive striatal GABAergic medium spiny neurons, as well as in large aspiny cholinergic interneurons, where it is thought to modulate dopamine-dependent signaling. Consistent with this knowledge, and considering that dopaminergic neurotransmission is altered in neurological and psychiatric disorders, here we sought to investigate whether Rhes mRNA expression is altered in brain regions of patients with Parkinson's disease (PD), Schizophrenia (SCZ), and Bipolar Disorder (BD), when compared to healthy controls (about 200 post-mortem samples). Moreover, we performed the same analysis in the putamen of non-human primate Macaca Mulatta, lesioned with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Overall, our data indicated comparable Rhes mRNA levels in the brain of patients with SCZ and BD, and their respective healthy controls. In sharp contrast, the putamen of patients suffering from PD showed a significant 35% reduction of this transcript, compared to healthy subjects. Interestingly, in line with observations obtained in humans, we found 27% decrease in Rhes mRNA levels in the putamen of MPTP-treated primates. Based on the established inhibitory influence of Rhes on dopamine-related responses, we hypothesize that its striatal downregulation in PD patients and animal models of PD might represent an adaptive event of the dopaminergic system to functionally counteract the reduced nigrostriatal innervation.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Noise-induced cochlear synaptopathy in rhesus monkeys (Macaca mulatta).
Valero MD, Burton JA, Hauser SN, Hackett TA, Ramachandran R, Liberman MC
(2017) Hear Res 353: 213-223
MeSH Terms: Animals, Auditory Fatigue, Auditory Threshold, Cochlea, Cochlear Diseases, Disease Models, Animal, Evoked Potentials, Auditory, Brain Stem, Hair Cells, Auditory, Hearing, Hearing Loss, Noise-Induced, Macaca mulatta, Noise, Otoacoustic Emissions, Spontaneous, Synapses, Synaptic Transmission, Time Factors
Show Abstract · Added April 3, 2018
Cochlear synaptopathy can result from various insults, including acoustic trauma, aging, ototoxicity, or chronic conductive hearing loss. For example, moderate noise exposure in mice can destroy up to ∼50% of synapses between auditory nerve fibers (ANFs) and inner hair cells (IHCs) without affecting outer hair cells (OHCs) or thresholds, because the synaptopathy occurs first in high-threshold ANFs. However, the fiber loss likely impairs temporal processing and hearing-in-noise, a classic complaint of those with sensorineural hearing loss. Non-human primates appear to be less vulnerable to noise-induced hair-cell loss than rodents, but their susceptibility to synaptopathy has not been studied. Because establishing a non-human primate model may be important in the development of diagnostics and therapeutics, we examined cochlear innervation and the damaging effects of acoustic overexposure in young adult rhesus macaques. Anesthetized animals were exposed bilaterally to narrow-band noise centered at 2 kHz at various sound-pressure levels for 4 h. Cochlear function was assayed for up to 8 weeks following exposure via auditory brainstem responses (ABRs) and otoacoustic emissions (OAEs). A moderate loss of synaptic connections (mean of 12-27% in the basal half of the cochlea) followed temporary threshold shifts (TTS), despite minimal hair-cell loss. A dramatic loss of synapses (mean of 50-75% in the basal half of the cochlea) was seen on IHCs surviving noise exposures that produced permanent threshold shifts (PTS) and widespread hair-cell loss. Higher noise levels were required to produce PTS in macaques compared to rodents, suggesting that primates are less vulnerable to hair-cell loss. However, the phenomenon of noise-induced cochlear synaptopathy in primates is similar to that seen in rodents.
Copyright © 2017 Elsevier B.V. All rights reserved.
0 Communities
1 Members
0 Resources
16 MeSH Terms
Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques.
Broeckel R, Fox JM, Haese N, Kreklywich CN, Sukulpovi-Petty S, Legasse A, Smith PP, Denton M, Corvey C, Krishnan S, Colgin LMA, Ducore RM, Lewis AD, Axthelm MK, Mandron M, Cortez P, Rothblatt J, Rao E, Focken I, Carter K, Sapparapau G, Crowe JE, Diamond MS, Streblow DN
(2017) PLoS Negl Trop Dis 11: e0005637
MeSH Terms: Animals, Antibodies, Monoclonal, Antibodies, Viral, B-Lymphocytes, Chikungunya Fever, Chikungunya virus, Disease Models, Animal, Drug Evaluation, Preclinical, Immunologic Factors, Macaca mulatta, T-Lymphocytes, Treatment Outcome
Show Abstract · Added March 14, 2018
Chikungunya virus (CHIKV) is a mosquito-borne virus that causes a febrile syndrome in humans associated with acute and chronic debilitating joint and muscle pain. Currently no licensed vaccines or therapeutics are available to prevent or treat CHIKV infections. We recently isolated a panel of potently neutralizing human monoclonal antibodies (mAbs), one (4N12) of which exhibited prophylactic and post-exposure therapeutic activity against CHIKV in immunocompromised mice. Here, we describe the development of an engineered CHIKV mAb, designated SVIR001, that has similar antigen binding and neutralization profiles to its parent, 4N12. Because therapeutic administration of SVIR001 in immunocompetent mice significantly reduced viral load in joint tissues, we evaluated its efficacy in a rhesus macaque model of CHIKV infection. Rhesus macaques that were treated after infection with SVIR001 showed rapid elimination of viremia and less severe joint infiltration and disease compared to animals treated with SVIR002, an isotype control mAb. SVIR001 reduced viral burden at the site of infection and at distant sites and also diminished the numbers of activated innate immune cells and levels of pro-inflammatory cytokines and chemokines. SVIR001 therapy; however, did not substantively reduce the induction of CHIKV-specific B or T cell responses. Collectively, these results show promising therapeutic activity of a human anti-CHIKV mAb in rhesus macaques and provide proof-of-principle for its possible use in humans to treat active CHIKV infections.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation.
Zhou T, Doria-Rose NA, Cheng C, Stewart-Jones GBE, Chuang GY, Chambers M, Druz A, Geng H, McKee K, Kwon YD, O'Dell S, Sastry M, Schmidt SD, Xu K, Chen L, Chen RE, Louder MK, Pancera M, Wanninger TG, Zhang B, Zheng A, Farney SK, Foulds KE, Georgiev IS, Joyce MG, Lemmin T, Narpala S, Rawi R, Soto C, Todd JP, Shen CH, Tsybovsky Y, Yang Y, Zhao P, Haynes BF, Stamatatos L, Tiemeyer M, Wells L, Scorpio DG, Shapiro L, McDermott AB, Mascola JR, Kwong PD
(2017) Cell Rep 19: 719-732
MeSH Terms: Animals, Antibodies, Neutralizing, Antibody Specificity, Binding Sites, CD4 Antigens, Crystallography, X-Ray, Epitopes, Glycosylation, Guinea Pigs, HIV Antibodies, HIV-1, Humans, Immunization, Macaca mulatta, Molecular Dynamics Simulation, Polysaccharides, Protein Structure, Quaternary, env Gene Products, Human Immunodeficiency Virus
Show Abstract · Added May 3, 2017
While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.
Published by Elsevier Inc.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Therapeutic treatment of Marburg and Ravn virus infection in nonhuman primates with a human monoclonal antibody.
Mire CE, Geisbert JB, Borisevich V, Fenton KA, Agans KN, Flyak AI, Deer DJ, Steinkellner H, Bohorov O, Bohorova N, Goodman C, Hiatt A, Kim DH, Pauly MH, Velasco J, Whaley KJ, Crowe JE, Zeitlin L, Geisbert TW
(2017) Sci Transl Med 9:
MeSH Terms: Animals, Antibodies, Monoclonal, Cross Protection, Filoviridae, Filoviridae Infections, Guinea Pigs, Humans, Macaca fascicularis, Macaca mulatta, Marburg Virus Disease, Marburgvirus, Pilot Projects
Show Abstract · Added April 13, 2017
As observed during the 2013-2016 Ebola virus disease epidemic, containment of filovirus outbreaks is challenging and made more difficult by the lack of approved vaccine or therapeutic options. Marburg and Ravn viruses are highly virulent and cause severe and frequently lethal disease in humans. Monoclonal antibodies (mAbs) are a platform technology in wide use for autoimmune and oncology indications. Previously, we described human mAbs that can protect mice from lethal challenge with Marburg virus. We demonstrate that one of these mAbs, MR191-N, can confer a survival benefit of up to 100% to Marburg or Ravn virus-infected rhesus macaques when treatment is initiated up to 5 days post-inoculation. These findings extend the small but growing body of evidence that mAbs can impart therapeutic benefit during advanced stages of disease with highly virulent viruses and could be useful in epidemic settings.
Copyright © 2017, American Association for the Advancement of Science.
0 Communities
1 Members
0 Resources
12 MeSH Terms
Mimicry of an HIV broadly neutralizing antibody epitope with a synthetic glycopeptide.
Alam SM, Aussedat B, Vohra Y, Meyerhoff RR, Cale EM, Walkowicz WE, Radakovich NA, Anasti K, Armand L, Parks R, Sutherland L, Scearce R, Joyce MG, Pancera M, Druz A, Georgiev IS, Von Holle T, Eaton A, Fox C, Reed SG, Louder M, Bailer RT, Morris L, Abdool-Karim SS, Cohen M, Liao HX, Montefiori DC, Park PK, Fernández-Tejada A, Wiehe K, Santra S, Kepler TB, Saunders KO, Sodroski J, Kwong PD, Mascola JR, Bonsignori M, Moody MA, Danishefsky S, Haynes BF
(2017) Sci Transl Med 9:
MeSH Terms: Animals, Antibodies, Neutralizing, Antibody Specificity, B-Lymphocytes, Cell Lineage, Cell Separation, Clone Cells, Epitopes, Glycopeptides, HIV Antigens, HIV Envelope Protein gp120, HIV-1, Macaca mulatta, Molecular Mimicry, Protein Domains, Protein Multimerization
Show Abstract · Added May 3, 2017
A goal for an HIV-1 vaccine is to overcome virus variability by inducing broadly neutralizing antibodies (bnAbs). One key target of bnAbs is the glycan-polypeptide at the base of the envelope (Env) third variable loop (V3). We have designed and synthesized a homogeneous minimal immunogen with high-mannose glycans reflective of a native Env V3-glycan bnAb epitope (Man-V3). V3-glycan bnAbs bound to Man-V3 glycopeptide and native-like gp140 trimers with similar affinities. Fluorophore-labeled Man-V3 glycopeptides bound to bnAb memory B cells and were able to be used to isolate a V3-glycan bnAb from an HIV-1-infected individual. In rhesus macaques, immunization with Man-V3 induced V3-glycan-targeted antibodies. Thus, the Man-V3 glycopeptide closely mimics an HIV-1 V3-glycan bnAb epitope and can be used to isolate V3-glycan bnAbs.
Copyright © 2017, American Association for the Advancement of Science.
0 Communities
1 Members
0 Resources
16 MeSH Terms