In the last decade, geopolitical instability across the globe has increased the risk of a large-scale radiological event, when radiation biomarkers would be needed for an effective triage of an irradiated population. Ionizing radiation elicits a complex response in the proteome, genome, and metabolome and hence can be leveraged as rapid and sensitive indicators of irradiation-induced damage. We analyzed the plasma of total-body irradiated (TBI) leukemia patients (n = 24) and nonhuman primates (NHPs; n = 10) before and 24 h after irradiation, and we performed a global metabolomic study aiming to provide plasma metabolites as candidate radiation biomarkers for biological dosimetry. Peripheral blood samples were collected according to the appropriate ethical approvals, and metabolites were extracted and analyzed by liquid chromatography mass spectrometry. We identified an array of metabolites significantly altered by irradiation, including bilirubin, cholesterol, and 18-hydroxycorticosterone, which were detected in leukemia patients and NHPs. Pathway analysis showed overlapping perturbations in steroidogenesis, porphyrin metabolism, and steroid hormone biosynthesis and metabolism. Additionally, we observed dysregulation in bile acid biosynthesis and tyrosine metabolism in the TBI patient cohort. This investigation is, to our best knowledge, among the first to provide valuable insights into a comparison between human and NHP irradiation models. The findings from this study could be leveraged for translational biological dosimetry.

• MeSH
• biologické markery krev   MeSH
• celotělové ozáření * MeSH
• dospělí MeSH
• ionizující záření MeSH
• leukemie krev   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• Macaca mulatta MeSH
• metabolom * MeSH
• metabolomika metody   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Sensory processing is influenced by neuromodulators such as serotonin, thought to relay behavioural state. Recent work has shown that the modulatory effect of serotonin itself differs with the animal's behavioural state. In primates, including humans, the serotonin system is anatomically important in the primary visual cortex (V1). We previously reported that in awake fixating macaques, serotonin reduces the spiking activity by decreasing response gain in V1. But the effect of serotonin on the local network is unknown. Here, we simultaneously recorded single-unit activity and local field potentials (LFPs) while iontophoretically applying serotonin in V1 of alert monkeys fixating on a video screen for juice rewards. The reduction in spiking response we observed previously is the opposite of the known increase of spiking activity with spatial attention. Conversely, in the local network (LFP), the application of serotonin resulted in changes mirroring the local network effects of previous reports in macaques directing spatial attention to the receptive field. It reduced the LFP power and the spike-field coherence, and the LFP became less predictive of spiking activity, consistent with reduced functional connectivity. We speculate that together, these effects may reflect the sensory side of a serotonergic contribution to quiet vigilance: The lower gain reduces the salience of stimuli to suppress an orienting reflex to novel stimuli, whereas at the network level, visual processing is in a state comparable to that of spatial attention.

• MeSH
• akční potenciály fyziologie   MeSH
• lidé MeSH
• Macaca mulatta MeSH
• serotonin MeSH
• světelná stimulace MeSH
• zraková percepce fyziologie   MeSH
• zrakové evokované potenciály * MeSH
• zrakové korové centrum * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH

Natural antibodies (Abs) can target host glycans on the surface of pathogens. We studied the evolution of glycan-reactive B cells of rhesus macaques and humans using glycosylated HIV-1 envelope (Env) as a model antigen. 2G12 is a broadly neutralizing Ab (bnAb) that targets a conserved glycan patch on Env of geographically diverse HIV-1 strains using a unique heavy-chain (VH) domain-swapped architecture that results in fragment antigen-binding (Fab) dimerization. Here, we describe HIV-1 Env Fab-dimerized glycan (FDG)-reactive bnAbs without VH-swapped domains from simian-human immunodeficiency virus (SHIV)-infected macaques. FDG Abs also recognized cell-surface glycans on diverse pathogens, including yeast and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike. FDG precursors were expanded by glycan-bearing immunogens in macaques and were abundant in HIV-1-naive humans. Moreover, FDG precursors were predominately mutated IgM+IgD+CD27+, thus suggesting that they originated from a pool of antigen-experienced IgM+ or marginal zone B cells.

• MeSH
• B-lymfocyty imunologie   MeSH
• COVID-19 imunologie   MeSH
• dimerizace MeSH
• epitopy imunologie   MeSH
• genové produkty env - virus lidské imunodeficience chemie   genetika   imunologie   MeSH
• glykoprotein S, koronavirus imunologie   MeSH
• glykosylace MeSH
• HIV infekce imunologie   MeSH
• HIV protilátky imunologie   MeSH
• HIV-1 imunologie   MeSH
• imunoglobuliny - Fab fragmenty chemie   imunologie   MeSH
• lidé MeSH
• Macaca mulatta MeSH
• neutralizující protilátky imunologie   MeSH
• polysacharidy chemie   imunologie   MeSH
• receptory antigenů B-buněk chemie   MeSH
• SARS-CoV-2 imunologie   MeSH
• široce neutralizující protilátky imunologie   MeSH
• vakcíny imunologie   MeSH
• virus opičí imunodeficience genetika   imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Color perception and color signaling play an important role in various aspects of animal behavior. However, in mammals, trichromatic vision characterized by three retinal photopigments tuned to peak short, middle and long wavelengths is limited only to some primate species. In Old and New World primates a second photopigment has appeared repeatedly during phylogeny, allowing red colors to be distinguished from yellows and greens. Several hypotheses aspire to explain the adaptive benefits of trichromatic vision for primates. The predominant one is foraging adaptation for facilitation visual detection of fruits or young leaves. Alternative explanations are based on the function of red color in aposematic signaling or its role in socio-sexual communication. We tested spontaneous color preference in macaque monkeys (Macaca mulatta) for both food and non-food objects in a laboratory environment. We hypothesized that preference for or avoidance of red color together with the context of such behavior may help us to understand what the adaptive advantage leading to a rapid expansion of a gene for a second pigment in the long-wavelength region was. We found neither preference nor avoidance toward red color in non-food objects, but we found a significant preference for red color in food; therefore, we suggest that the results support the foraging hypothesis in macaque monkeys.

• MeSH
• Macaca mulatta * MeSH
• ovoce MeSH
• vidění barevné * MeSH
• výběrové chování * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Peptide immunogens provide an approach to focus antibody responses to specific neutralizing sites on the HIV envelope protein (Env) trimer or on other pathogens. However, the physical characteristics of peptide immunogens can limit their pharmacokinetic and immunological properties. Here, we have designed synthetic "star" nanoparticles based on biocompatible N-[(2-hydroxypropyl)methacrylamide] (HPMA)-based polymer arms extending from a poly(amidoamine) (PAMAM) dendrimer core. In mice, these star nanoparticles trafficked to lymph nodes (LNs) by 4 hours following vaccination, where they were taken up by subcapsular macrophages and then resident dendritic cells (DCs). Immunogenicity optimization studies revealed a correlation of immunogen density with antibody titers. Furthermore, the co-delivery of Env variable loop 3 (V3) and T-helper peptides induced titers that were 2 logs higher than if the peptides were given in separate nanoparticles. Finally, we performed a nonhuman primate (NHP) study using a V3 glycopeptide minimal immunogen that was structurally optimized to be recognized by Env V3/glycan broadly neutralizing antibodies (bnAbs). When administered with a potent Toll-like receptor (TLR) 7/8 agonist adjuvant, these nanoparticles elicited high antibody binding titers to the V3 site. Similar to human V3/glycan bnAbs, certain monoclonal antibodies (mAbs) elicited by this vaccine were glycan dependent or targeted the GDIR peptide motif. To improve affinity to native Env trimer affinity, nonhuman primates (NHPs) were boosted with various SOSIP Env proteins; however, significant neutralization was not observed. Taken together, this study provides a new vaccine platform for administration of glycopeptide immunogens for focusing immune responses to specific bnAb epitopes.

• MeSH
• epitopy imunologie   MeSH
• HIV infekce imunologie   MeSH
• HIV obalový protein gp120 chemie   MeSH
• HIV séropozitivita imunologie   MeSH
• HIV-1 imunologie   MeSH
• Macaca mulatta MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nanočástice chemie   terapeutické užití   MeSH
• neutralizující protilátky imunologie   MeSH
• peptidy MeSH
• primáti MeSH
• tvorba protilátek imunologie   MeSH
• vakcíny proti AIDS imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH

Animals' reactions to novel objects vary not only with zoological taxa and their ecology but also in the types of presented stimuli, the context, and individual characteristics. Behavioral reactions can vary from extremely neophobic (avoiding novel objects) to extremely neophilic (intense exploration of novel objects); most often, a mixture of these behavioral patterns appears. In primates, reactions toward novel objects vary according to species, age, sex, population, and the types of objects. Most experiments in this field have used a free exploration design with food or non-food objects. Here, we tested the reactions of captive male rhesus macaques using various stimuli, motivation levels, rewards, and time limits. We found that the monkeys explored and manipulated novel objects in various contexts, with little evidence of a neophobic response; however, environment, types of stimuli, and other parameters of the test can significantly affect monkeys' reactions.

• MeSH
• chování zvířat * MeSH
• Macaca mulatta fyziologie   MeSH
• odměna MeSH
• pátrací chování * MeSH
• zvířata v ZOO MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Helicobacter suis is the second most prevalent Helicobacter species in the stomach of humans suffering from gastric disease. This bacterium mainly inhabits the stomach of domesticated pigs, in which it causes gastric disease, but it appears to be absent in wild boars. Interestingly, it also colonizes the stomach of asymptomatic rhesus and cynomolgus monkeys. The origin of modern human-, pig- or non-human primate-associated H. suis strains in these respective host populations was hitherto unknown. Here we show that H. suis in pigs possibly originates from non-human primates. Our data suggest that a host jump from macaques to pigs happened between 100 000 and 15 000 years ago and that pig domestication has had a significant impact on the spread of H. suis in the pig population, from where this pathogen occasionally infects humans. Thus, in contrast to our expectations, H. suis appears to have evolved in its main host in a completely different way than its close relative Helicobacter pylori in humans.

• MeSH
• fylogeneze MeSH
• Helicobacter heilmannii klasifikace   genetika   růst a vývoj   izolace a purifikace   MeSH
• hospodářská zvířata mikrobiologie   MeSH
• infekce vyvolané Helicobacter pylori mikrobiologie   veterinární   MeSH
• lidé MeSH
• Macaca fascicularis mikrobiologie   MeSH
• Macaca mulatta mikrobiologie   MeSH
• nemoci prasat mikrobiologie   MeSH
• prasata MeSH
• žaludek mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The ability to decode antigen specificities encapsulated in the sequences of rearranged T-cell receptor (TCR) genes is critical for our understanding of the adaptive immune system and promises significant advances in the field of translational medicine. Recent developments in high-throughput sequencing methods (immune repertoire sequencing technology, or RepSeq) and single-cell RNA sequencing technology have allowed us to obtain huge numbers of TCR sequences from donor samples and link them to T-cell phenotypes. However, our ability to annotate these TCR sequences still lags behind, owing to the enormous diversity of the TCR repertoire and the scarcity of available data on T-cell specificities. In this paper, we present VDJdb, a database that stores and aggregates the results of published T-cell specificity assays and provides a universal platform that couples antigen specificities with TCR sequences. We demonstrate that VDJdb is a versatile instrument for the annotation of TCR repertoire data, enabling a concatenated view of antigen-specific TCR sequence motifs. VDJdb can be accessed at https://vdjdb.cdr3.net and https://github.com/antigenomics/vdjdb-db.

• MeSH
• analýza jednotlivých buněk MeSH
• anotace sekvence * MeSH
• antigeny chemie   imunologie   metabolismus   MeSH
• databáze proteinů * MeSH
• hlavní histokompatibilní komplex genetika   imunologie   MeSH
• interakční proteinové domény a motivy MeSH
• internet MeSH
• lidé MeSH
• Macaca mulatta MeSH
• molekulární modely MeSH
• myši MeSH
• receptory antigenů T-buněk chemie   imunologie   metabolismus   MeSH
• sekundární struktura proteinů MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční seřazení MeSH
• software * MeSH
• T-lymfocyty cytologie   imunologie   MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

2-(Phosphonomethyl)pentanedioic acid (2-PMPA) is a potent and selective inhibitor of glutamate carboxypeptidase-II (GCPII) with efficacy in multiple neurological and psychiatric disease models, but its clinical utility is hampered by low brain penetration due to the inclusion of multiple acidic functionalities. We recently reported an improvement in the brain-to-plasma ratio of 2-PMPA after intranasal (IN) dosing in both rodents and primates. Herein, we describe the synthesis of several 2-PMPA prodrugs with further improved brain delivery of 2-PMPA after IN administration by masking of the γ-carboxylate. When compared to IN 2-PMPA in rats at 1 h post dose, γ-(4-acetoxybenzyl)-2-PMPA (compound 1) resulted in significantly higher 2-PMPA delivery to both plasma (4.1-fold) and brain (11-fold). Subsequent time-dependent evaluation of 1 also showed high brain as well as plasma 2-PMPA exposures with brain-to-plasma ratios of 2.2, 0.48, and 0.26 for olfactory bulb, cortex, and cerebellum, respectively, as well as an improved sciatic nerve to plasma ratio of 0.84. In contrast, IV administration of compound 1 resulted in similar plasma exposure of 2-PMPA versus the IN route (AUCIV: 76 ± 9 h·nmol/mL versus AUCIN: 99 ± 24 h·nmol/mL); but significantly lower nerve and brain tissue exposures with tissue-to-plasma ratios of 0.21, 0.03, 0.04, and 0.04 in nerve, olfactory bulb, cortex, and cerebellum, respectively. In primates, IN administration of 1 more than doubled 2-PMPA concentrations in the cerebrospinal fluid relative to previously reported levels following IN 2-PMPA. The results of these experiments provide a promising strategy for testing GCPII inhibition in neurological and psychiatric disorders.

• MeSH
• aplikace intranazální MeSH
• estery analýza   chemie   farmakologie   MeSH
• glutamátkarboxypeptidasa II antagonisté a inhibitory   MeSH
• hematoencefalická bariéra účinky léků   MeSH
• intravenózní podání MeSH
• krysa rodu rattus MeSH
• Macaca mulatta MeSH
• mozek účinky léků   MeSH
• mozkomíšní mok účinky léků   MeSH
• neuroprotektivní látky analýza   chemie   farmakologie   MeSH
• organofosforové sloučeniny analýza   chemie   farmakologie   MeSH
• potkani Wistar MeSH
• prekurzory léčiv analýza   chemie   farmakologie   MeSH
• tkáňová distribuce MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Visual attention modulates the firing rate of neurons in many primate cortical areas. In V4, a cortical area in the ventral visual pathway, spatial attention has also been shown to reduce the tendency of neurons to fire closely separated spikes (burstiness). A recent model proposes that a single mechanism accounts for both the firing rate enhancement and the burstiness reduction in V4, but this has not been empirically tested. It is also unclear if the burstiness reduction by spatial attention is found in other visual areas and for other attentional types. We therefore recorded from single neurons in the medial superior temporal area (MST), a key motion-processing area along the dorsal visual pathway, of two rhesus monkeys while they performed a task engaging both spatial and feature-based attention. We show that in MST, spatial attention is associated with a clear reduction in burstiness that is independent of the concurrent enhancement of firing rate. In contrast, feature-based attention enhances firing rate but is not associated with a significant reduction in burstiness. These results establish burstiness reduction as a widespread effect of spatial attention. They also suggest that in contrast to the recently proposed model, the effects of spatial attention on burstiness and firing rate emerge from different mechanisms.

• MeSH
• biologické hodiny fyziologie   MeSH
• Macaca mulatta MeSH
• mozkové vlny fyziologie   MeSH
• nervová síť fyziologie   MeSH
• pozornost fyziologie   MeSH
• vnímání prostoru fyziologie   MeSH
• zraková pole fyziologie   MeSH
• zrakové korové centrum fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH