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  1 / 36573 MEDLINE  
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PMID:28924008
Autor:Kajikawa Y; Smiley JF; Schroeder CE
Endereço:Translational Neuroscience Division, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962, ykajikawa@nki.rfmh.org.
Título:Primary Generators of Visually Evoked Field Potentials Recorded in the Macaque Auditory Cortex.
Fonte:J Neurosci; 37(42):10139-10153, 2017 Oct 18.
ISSN:1529-2401
País de publicação:United States
Idioma:eng
Resumo:Prior studies have reported "local" field potential (LFP) responses to faces in the macaque auditory cortex and have suggested that such face-LFPs may be substrates of audiovisual integration. However, although field potentials (FPs) may reflect the synaptic currents of neurons near the recording electrode, due to the use of a distant reference electrode, they often reflect those of synaptic activity occurring in distant sites as well. Thus, FP recordings within a given brain region (e.g., auditory cortex) may be "contaminated" by activity generated elsewhere in the brain. To determine whether face responses are indeed generated within macaque auditory cortex, we recorded FPs and concomitant multiunit activity with linear array multielectrodes across auditory cortex in three macaques (one female), and applied current source density (CSD) analysis to the laminar FP profile. CSD analysis revealed no appreciable local generator contribution to the visual FP in auditory cortex, although we did note an increase in the amplitude of visual FP with cortical depth, suggesting that their generators are located below auditory cortex. In the underlying inferotemporal cortex, we found polarity inversions of the main visual FP components accompanied by robust CSD responses and large-amplitude multiunit activity. These results indicate that face-evoked FP responses in auditory cortex are not generated locally but are volume-conducted from other face-responsive regions. In broader terms, our results underscore the caution that, unless far-field contamination is removed, LFPs in general may reflect such "far-field" activity, in addition to, or in absence of, local synaptic responses. Field potentials (FPs) can index neuronal population activity that is not evident in action potentials. However, due to volume conduction, FPs may reflect activity in distant neurons superimposed upon that of neurons close to the recording electrode. This is problematic as the default assumption is that FPs originate from local activity, and thus are termed "local" (LFP). We examine this general problem in the context of previously reported face-evoked FPs in macaque auditory cortex. Our findings suggest that face-FPs are indeed generated in the underlying inferotemporal cortex and volume-conducted to the auditory cortex. The note of caution raised by these findings is of particular importance for studies that seek to assign FP/LFP recordings to specific cortical layers.
Tipo de publicação: JOURNAL ARTICLE


  2 / 36573 MEDLINE  
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PMID:28628616
Autor: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
Endereço:Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, United States of America.
Título:Therapeutic administration of a recombinant human monoclonal antibody reduces the severity of chikungunya virus disease in rhesus macaques.
Fonte:PLoS Negl Trop Dis; 11(6):e0005637, 2017 Jun.
ISSN:1935-2735
País de publicação:United States
Idioma:eng
Resumo: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.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies, Monoclonal); 0 (Antibodies, Viral); 0 (Immunologic Factors)


  3 / 36573 MEDLINE  
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PMID:28381592
Autor:Medalla M; Gilman JP; Wang JY; Luebke JI
Endereço:Boston University School of Medicine, Boston, Massachusetts 02118 mmedalla@bu.edu.
Título:Strength and Diversity of Inhibitory Signaling Differentiates Primate Anterior Cingulate from Lateral Prefrontal Cortex.
Fonte:J Neurosci; 37(18):4717-4734, 2017 May 03.
ISSN:1529-2401
País de publicação:United States
Idioma:eng
Resumo:The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) of the primate play distinctive roles in the mediation of complex cognitive tasks. Compared with the LPFC, integration of information by the ACC can span longer timescales and requires stronger engagement of inhibitory processes. Here, we reveal the synaptic mechanism likely to underlie these differences using patch-clamp recordings of synaptic events and multiscale imaging of synaptic markers in rhesus monkeys. Although excitatory synaptic signaling does not differ, the level of synaptic inhibition is much higher in ACC than LPFC layer 3 pyramidal neurons, with a significantly higher frequency (∼6×) and longer duration of inhibitory synaptic currents. The number of inhibitory synapses and the ratio of cholecystokinin to parvalbumin-positive inhibitory inputs are also significantly higher in ACC compared with LPFC neurons. Therefore, inhibition is functionally and structurally more robust and diverse in ACC than in LPFC, resulting in a lower excitatory: inhibitory ratio and a greater dynamic range for signal integration and network oscillation by the ACC. These differences in inhibitory circuitry likely underlie the distinctive network dynamics in ACC and LPC during normal and pathological brain states. The lateral prefrontal cortex (LPFC) and anterior cingulate cortex (ACC) play temporally distinct roles during the execution of cognitive tasks (rapid working memory during ongoing tasks and long-term memory to guide future action, respectively). Compared with LPFC-mediated tasks, ACC-mediated tasks can span longer timescales and require stronger engagement of inhibition. This study shows that inhibitory signaling is much more robust and diverse in the ACC than in the LPFC. Therefore, there is a lower excitatory: inhibitory synaptic ratio and a greater dynamic range for signal integration and oscillatory behavior in the ACC. These significant differences in inhibitory synaptic transmission form an important basis for the differential timing of cognitive processing by the LPFC and ACC in normal and pathological brain states.
Tipo de publicação: JOURNAL ARTICLE


  4 / 36573 MEDLINE  
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PMID:29024670
Autor:Loonis RF; Brincat SL; Antzoulatos EG; Miller EK
Endereço:The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Anatomy and Neurobiology, Boston University, Boston MA, 02118, USA.
Título:A Meta-Analysis Suggests Different Neural Correlates for Implicit and Explicit Learning.
Fonte:Neuron; 96(2):521-534.e7, 2017 Oct 11.
ISSN:1097-4199
País de publicação:United States
Idioma:eng
Resumo:A meta-analysis of non-human primates performing three different tasks (Object-Match, Category-Match, and Category-Saccade associations) revealed signatures of explicit and implicit learning. Performance improved equally following correct and error trials in the Match (explicit) tasks, but it improved more after correct trials in the Saccade (implicit) task, a signature of explicit versus implicit learning. Likewise, error-related negativity, a marker for error processing, was greater in the Match (explicit) tasks. All tasks showed an increase in alpha/beta (10-30 Hz) synchrony after correct choices. However, only the implicit task showed an increase in theta (3-7 Hz) synchrony after correct choices that decreased with learning. In contrast, in the explicit tasks, alpha/beta synchrony increased with learning and decreased thereafter. Our results suggest that explicit versus implicit learning engages different neural mechanisms that rely on different patterns of oscillatory synchrony.
Tipo de publicação: JOURNAL ARTICLE; META-ANALYSIS


  5 / 36573 MEDLINE  
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PMID:28535861
Autor:Wooddell LJ; Kaburu SS; Suomi SJ; Dettmer AM
Endereço:Eunice Kennedy Shriver National Institute for Child Health and Human Development, NIH, Poolesville, Maryland;, Email: ljwooddell@ucdavis.edu.
Título:Elo-rating for Tracking Rank Fluctuations after Demographic Changes Involving Semi-free-ranging Rhesus Macaques ( ).
Fonte:J Am Assoc Lab Anim Sci; 56(3):260-268, 2017 May 01.
ISSN:1559-6109
País de publicação:United States
Idioma:eng
Resumo:Rhesus macaques (Macaca mulatta) are gregarious primates that form despotic societies characterized by frequent and intense aggression. Within long-term social groups, demographic changes may influence hierarchical stability, potentially resulting in conflict and violently abrupt hierarchical changes. This conflict can result in serious implications for animal welfare, and thus, predictive tools would be invaluable to captive managers in determining social instabilities. Using the method Elo-rating to track rank changes and dominance stability, we predicted that demographic changes to a population of semi-free ranging rhesus macaques would result in changes in hierarchical stability. Over a 3 y period, dominance data were recorded on all troop members to track the hierarchy. Throughout the 3 y, significant changes occurred to the population (mainly due to health and colony management reasons; no changes specifically occurred for this study) including permanent removal of a large group of natal males, temporary and permanent removal of top-ranking females, and depositions of top-ranking families. Our retrospective study suggests that removing natal males was beneficial in promoting overall troop stability (that is, stability of dominance relationships), although remaining males opportunistically attempted to increase in rank, perhaps due to limited competition. Our results also suggest that removing top-ranking females, even temporarily, destabilized dominance relationships; consequently adjacently ranked females opportunistically increased in Elo-rating, both before and after the depositions of the α families. Thus, these challenges to the established hierarchy can be predicted by increases in Elo-rating within the ß families after demographic changes to the α families. Our results suggest that the presence of natal males and the removal of top-ranking females should be minimized to maintain stable dominance relationships. In addition, longitudinal data reflecting dominance ranks, collected by using Elo-rating, may help managers of captive colonies in predicting dominance instabilities before they occur.
Tipo de publicação: JOURNAL ARTICLE


  6 / 36573 MEDLINE  
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PMID:29020058
Autor:McCurley NP; Domi A; Basu R; Saunders KO; LaBranche CC; Montefiori DC; Haynes BF; Robinson HL
Endereço:GeoVax Inc., Smyrna, GA, United States of America.
Título:HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site.
Fonte:PLoS One; 12(10):e0177863, 2017.
ISSN:1932-6203
País de publicação:United States
Idioma:eng
Resumo:Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines, both with and without co-delivery of directed-lineage gp120 boosts, failed to elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (Antigens, CD4); 0 (HIV Antigens); 0 (Vaccines, DNA); 0 (env Gene Products, Human Immunodeficiency Virus)


  7 / 36573 MEDLINE  
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Rizzo, Luiz Vicente
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PMID:28939444
Autor:Carvalho de Freitas R; Lonien SCH; Malvezi AD; Silveira GF; Wowk PF; da Silva RV; Yamauchi LM; Yamada-Ogatta SF; Rizzo LV; Bordignon J; Pinge-Filho P
Endereço:Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, 86051-970, Londrina, Paraná, Brazil.
Título:Trypanosoma cruzi: Inhibition of infection of human monocytes by aspirin.
Fonte:Exp Parasitol; 182:26-33, 2017 Nov.
ISSN:1090-2449
País de publicação:United States
Idioma:eng
Resumo:Cell invasion by Trypanosoma cruzi and its intracellular replication are essential for progression of the parasite life cycle and development of Chagas disease. Prostaglandin E2 (PGE ) and other eicosanoids potently modulate host response and contribute to Chagas disease progression. In this study, we evaluated the effect of aspirin (ASA), a non-selective cyclooxygenase (COX) inhibitor on the T. cruzi invasion and its influence on nitric oxide and cytokine production in human monocytes. The pretreatment of monocytes with ASA or SQ 22536 (adenylate-cyclase inhibitor) induced a marked inhibition of T. cruzi infection. On the other hand, the treatment of monocytes with SQ 22536 after ASA restored the invasiveness of T. cruzi. This reestablishment was associated with a decrease in nitric oxide and PGE production, and also an increase of interleukin-10 and interleukin-12 by cells pre-treated with ASA. Altogether, these results reinforce the idea that the cyclooxygenase pathway plays a fundamental role in the process of parasite invasion in an in vitro model of T. cruzi infection.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Adenylyl Cyclase Inhibitors); 0 (Cyclooxygenase Inhibitors); 0 (Cytokines); 17318-31-9 (9-(tetrahydro-2-furyl)-adenine); 31C4KY9ESH (Nitric Oxide); E0399OZS9N (Cyclic AMP); EC 4.6.1.1 (Adenylyl Cyclases); JAC85A2161 (Adenine); K7Q1JQR04M (Dinoprostone); R16CO5Y76E (Aspirin)


  8 / 36573 MEDLINE  
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PMID:28333316
Autor:Sweeney CG; Rando JM; Panas HN; Miller GM; Platt DM; Vallender EJ
Endereço:Division of Neuroscience, New England Primate Research Center, Harvard Medical School, Southborough, MA.
Título:Convergent Balancing Selection on the Mu-Opioid Receptor in Primates.
Fonte:Mol Biol Evol; 34(7):1629-1643, 2017 Jul 01.
ISSN:1537-1719
País de publicação:United States
Idioma:eng
Resumo:The mu opioid receptor is involved in many natural processes including stress response, pleasure, and pain. Mutations in the gene also have been associated with opiate and alcohol addictions as well as with responsivity to medication targeting these disorders. Two common and mutually exclusive polymorphisms have been identified in humans, A118G (N40D), found commonly in non-African populations, and C17T (V6A), found almost exclusively in African populations. Although A118G has been studied extensively for associations and in functional assays, C17T is much less well understood. In addition to a parallel polymorphism previously identified in rhesus macaques (Macaca mulatta), C77G (P26R), resequencing in additional non-human primate species identifies further common variation: C140T (P47L) in cynomolgus macaques (Macaca fascicularis), G55C (D19H) in vervet monkeys (Chlorocebus aethiops sabeus), A111T (L37F) in marmosets (Callithrix jacchus), and C55T (P19S) in squirrel monkeys (Saimiri boliviensis peruviensis). Functional effects on downstream signaling are observed for each of these variants following treatment with the endogenous agonist ß-endorphin and the exogenous agonists morphine, DAMGO ([d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin), and fentanyl. In addition to demonstrating the importance of functional equivalency in reference to population variation for minority health, this also shows how common evolutionary pressures have produced similar phenotypes across species, suggesting a shared response to environmental needs and perhaps elucidating the mechanism by which these organism-environment interactions are mediated physiologically and molecularly. These studies set the stage for future investigations of shared functional polymorphisms across species as a new genetic tool for translational research.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (OPRM1 protein, human); 0 (Receptors, Opioid, mu)


  9 / 36573 MEDLINE  
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PMID:28895116
Autor:Pittet F; Johnson C; Hinde K
Endereço:Brain, Mind, and Behavior Unit, California National Primate Research Center, Davis, California.
Título:Age at reproductive debut: Developmental predictors and consequences for lactation, infant mass, and subsequent reproduction in rhesus macaques (Macaca mulatta).
Fonte:Am J Phys Anthropol; 164(3):457-476, 2017 Nov.
ISSN:1096-8644
País de publicação:United States
Idioma:eng
Resumo:OBJECTIVES: The age at which females initiate their reproductive career is a critical life-history parameter with potential consequences on their residual reproductive value and lifetime fitness. The age at reproductive debut may be intimately tied to the somatic capacity of the mother to rear her young, but relatively little is known about the influence of age of first birth on milk synthesis within a broader framework of reproductive scheduling, infant outcomes, and other life-history tradeoffs. MATERIAL AND METHODS: Our study investigated the predictors of age at first reproduction among 108 captive rhesus macaque (Macaca mulatta) females, and associations with their milk synthesis at peak lactation, infant mass, and ability to subsequently conceive and reproduce. RESULTS: The majority of females reproduced in their fourth year (typical breeders); far fewer initiated their reproductive career one year earlier or one year later (respectively early and late breeders). Early breeders (3-year-old) benefited from highly favorable early life development (better juvenile growth, high dominance rank) to accelerate reproduction, but were impaired in milk synthesis due to lower somatic resources and their own continued growth. Comparatively, late breeders suffered from poor developmental conditions, only partially compensated by their delayed reproduction, and evinced compromised milk synthesis. Typical breeders not only produced higher available milk energy but also had best reproductive performance during the breeding and birth seasons following primiparity. DISCUSSION: Here, we refine and extend our understanding of how life-history tradeoffs manifest in the magnitude, sources, and consequences of variation in age of reproductive debut. These findings provide insight into primate reproductive flexibility in the context of constraints and opportunities.
Tipo de publicação: JOURNAL ARTICLE


  10 / 36573 MEDLINE  
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PMID:28832918
Autor:Seil SK; Hannibal DL; Beisner BA; McCowan B
Endereço:Department of Population Health & Reproduction, School of Veterinary Medicine, UC Davis, Davis, California, 95616.
Título:Predictors of insubordinate aggression among captive female rhesus macaques.
Fonte:Am J Phys Anthropol; 164(3):558-573, 2017 Nov.
ISSN:1096-8644
País de publicação:United States
Idioma:eng
Resumo:OBJECTIVES: Cercopithicine primates tend to have nepotistic hierarchies characterized by predictable, kinship-based dominance. Although aggression is typically directed down the hierarchy, insubordinate aggression does occur. Insubordination is important to understand because it can precipitate social upheaval and undermine group stability; however, the factors underlying it are not well understood. We test whether key social and demographic variables predict insubordination among captive female rhesus macaques. MATERIALS AND METHODS: To identify factors influencing insubordination, multivariate analyses of 10,821 dyadic conflicts among rhesus macaque females were conducted, using data from six captive groups. A segmented regression analysis was used to identify dyads with insubordination. Negative binomial regression analyses and an information theoretic approach were used to assess predictors of insubordination among dyads. RESULTS: In the best models, weight difference (w = 1.0; IRR = 0.930), age (dominant: w = 1.0, IRR = 0.681; subordinate: w = 1.0, IRR = 1.069), the subordinate's total number of allies (w = 0.727, IRR = 1.060) or non-kin allies (w = 0.273, IRR = 1.165), the interaction of the dominant's kin allies and weight difference (w = 0.938, IRR = 1.046), violation of youngest ascendancy (w = 1.0; IRR = 2.727), and the subordinate's maternal support (w = 1.0; IRR = 2.928), are important predictors of insubordination. DISCUSSION: These results show that both intrinsic and social factors influence insubordinate behavior. This adds to evidence of the importance of intrinsic factors and flexibility in a social structure thought to be rigid and predetermined by external factors. Further, because insubordination can precipitate social overthrow, determining predictors of insubordination will shed light on mechanisms underlying stability in nepotistic societies.
Tipo de publicação: JOURNAL ARTICLE



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