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1.
J Immunol Res ; 2022: 3883822, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36093436

RESUMO

Monkeypox virus (MPV) is a smallpox-like virus belonging to the genus Orthopoxvirus of the family Poxviridae. Unlike smallpox with no animal reservoir identified and patients suffering from milder symptoms with less mortality, several animals were confirmed to serve as natural hosts of MPV. The reemergence of a recently reported monkeypox epidemic outbreak in nonendemic countries has raised concerns about a global outburst. Since the underlying mechanism of animal-to-human transmission remains largely unknown, comprehensive analyses to discover principal differences in gene signatures during disease progression have become ever more critical. In this study, two MPV-infected in vitro models, including human immortal epithelial cancer (HeLa) cells and rhesus monkey (Macaca mulatta) kidney epithelial (MK2) cells, were chosen as the two subjects to identify alterations in gene expression profiles, together with co-regulated genes and pathways that are affected during monkeypox disease progression. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and MetaCore analyses, we discovered that elevated expression of genes associated with interleukins (ILs), G protein-coupled receptors (GPCRs), heat shock proteins (HSPs), Toll-like receptors (TLRs), and metabolic-related pathways play major roles in disease progression of both monkeypox-infected monkey MK2 and human HeLa cell lines. Interestingly, our analytical results also revealed that a cluster of differentiation 40 (CD40), plasmin, and histamine served as major regulators in the monkeypox-infected monkey MK2 cell line model, while interferons (IFNs), macrophages, and neutrophil-related signaling pathways dominated the monkeypox-infected human HeLa cell line model. Among immune pathways of interest, apart from traditional monkeypox-regulated signaling pathways such as nuclear factor- (NF-κB), mitogen-activated protein kinases (MAPKs), and tumor necrosis factors (TNFs), we also identified highly significantly expressed genes in both monkey and human models that played pivotal roles during the progression of monkeypox infection, including CXCL1, TNFAIP3, BIRC3, IL6, CCL2, ZC3H12A, IL11, CSF2, LIF, PTX3, IER3, EGR1, ADORA2A, and DUOX1, together with several epigenetic regulators, such as histone cluster family gene members, HIST1H3D, HIST1H2BJ, etc. These findings might contribute to specific underlying mechanisms related to the pathophysiology and provide suggestions regarding modes of transmission, post-infectious sequelae, and vaccine development for monkeypox in the future.


Assuntos
Varíola dos Macacos , Varíola , Animais , Progressão da Doença , Células HeLa , Humanos , Macaca mulatta , Varíola dos Macacos/patologia , Vírus da Varíola dos Macacos/genética , Transcriptoma
2.
Sci Transl Med ; 14(661): eabo5598, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36070369

RESUMO

A successful HIV-1 vaccine will require induction of a polyclonal neutralizing antibody (nAb) response, yet vaccine-mediated induction of such a response in primates remains a challenge. We found that a stabilized HIV-1 CH505 envelope (Env) trimer formulated with a Toll-like receptor 7/8 agonist induced potent HIV-1 polyclonal nAbs that correlated with protection from homologous simian-human immunodeficiency virus (SHIV) infection. The serum dilution that neutralized 50% of virus replication (ID50 titer) required to protect 90% of macaques was 1:364 against the challenge virus grown in primary rhesus CD4+ T cells. Structural analyses of vaccine-induced nAbs demonstrated targeting of the Env CD4 binding site or the N156 glycan and the third variable loop base. Autologous nAb specificities similar to those elicited in macaques by vaccination were isolated from the human living with HIV from which the CH505 Env immunogen was derived. CH505 viral isolates were isolated that mutated the V1 to escape both the infection-induced and vaccine-induced antibodies. These results define the specificities of a vaccine-induced nAb response and the protective titers of HIV-1 vaccine-induced nAbs required to protect nonhuman primates from low-dose mucosal challenge by SHIVs bearing a primary transmitted/founder Env.


Assuntos
Vacinas contra a AIDS , Doenças Transmissíveis , HIV-1 , Vírus da Imunodeficiência Símia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Imunização , Macaca mulatta , Vacinação
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2022: 3123-3126, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36086028

RESUMO

A better understanding of reward signaling in the sensorimotor cortices can aid in developing Reinforcement Learning-based Brain-Computer Interfaces (RLBCI) for restoration of movement functions with fewer implants. Brain-computer interfaces (BCIs) using local field potentials (LFPs) have recently achieved performance comparable to spike-BCIs [1]. With superior stability over time, LFPs may be the preferred signal for BCIs. We show that sensorimotor LFPs can provide reward level information (R1 - R3) like spikes[2]. We used a cued reward-level reaching task in which reward information was temporally dissociated from movement information. This allowed the study of reward- and movement-related modulations in LFPs. We recorded simultaneously from contralateral primary -somatosensory (S1), -motor (M1), and the dorsal premotor (PMd) cortices in a female Macaca Mulatta. We found that all three cortices' average beta band (14-30 Hz) amplitude showed robust modulation with reward levels during the cue presentation period. Such modulation was consistently observed after controlling for cue color, differences in behavioral variables, and electromyogram (EMG) activity. Statistical amplitude analysis showed that reward level could be extracted from the simple LFP feature of beta band amplitude, even before a reaching target appeared, and no specific reach plan could be developed. Clinical Relevance - The availability of reward-related signals in the sensorimotor cortical (S1, M1,and PMd) LFPs' prior to movement planning opens new avenues to build RLBCIs with fewer implants recording fewer sites among different cortices Reward and motivational representations derived from LFPs compared to spikes allow the development of long-term clinical applications given LFP's stability and ease of recording over long periods.


Assuntos
Córtex Motor , Potenciais de Ação , Animais , Braço , Feminino , Macaca mulatta , Movimento , Recompensa
4.
Transl Vis Sci Technol ; 11(9): 6, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36074454

RESUMO

Purpose: The purpose of this study was to assess ocular coat mechanical behavior using controlled ocular microvolumetric injections (MVI) of 15 µL of balanced salt solution (BSS) infused over 1 second into the anterior chamber (AC) via a syringe pump. Methods: Intraocular pressure (IOP) was continuously recorded at 200 Hz with a validated implantable IOP telemetry system in 7 eyes of 7 male rhesus macaques (nonhuman primates [NHPs]) during 5 MVIs in a series at native (3 trials), 15 and 20 mm Hg baseline IOPs, repeated in 2 to 5 sessions at least 2 weeks apart. Ocular rigidity coefficients (K) and ocular pulse volume (PV) were calculated for each trial. Data were averaged across sessions within eyes; PV was analyzed with a three-level nested ANOVA, and parameter relationships were analyzed with Pearson Correlation and linear regression. Results: After MVI at native baseline IOP of 10.4 ± 1.6 mm Hg, IOP increased by 9.1 ± 2.8 mm Hg (∆IOP) at a 9.6 ± 2.7 mm Hg/s slope, ocular pulse amplitude (OPA) was 0.70 ± 0.13 mm Hg on average; the average K was 0.042 ± 0.010 µL-1 and average PV was 1.16 ± 0.43 µL. PV varied significantly between trials, days, and eyes (P ≤ 0.05). OPA was significantly correlated with K at native IOP: Pearson coefficients ranged from 0.71 to 0.83 (P ≤ 0.05) and R2 ranged from 0.50 to 0.69 (P ≤ 0.05) during the first trial. Conclusions: The MVI-driven ∆IOP and slope can be used to assess ocular coat mechanical behavior and measure ocular rigidity. Translational Relevance: Importantly, OPA at native IOP is correlated with ocular rigidity despite the significant variability in PV between heartbeats.


Assuntos
Oftalmopatias , Pressão Intraocular , Animais , Câmara Anterior , Frequência Cardíaca , Macaca mulatta , Masculino , Tonometria Ocular
5.
Nat Commun ; 13(1): 5538, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36130949

RESUMO

Maternal obesity during pregnancy is associated with neurodevelopmental disorder (NDD) risk. We utilized integrative multi-omics to examine maternal obesity effects on offspring neurodevelopment in rhesus macaques by comparison to lean controls and two interventions. Differentially methylated regions (DMRs) from longitudinal maternal blood-derived cell-free fetal DNA (cffDNA) significantly overlapped with DMRs from infant brain. The DMRs were enriched for neurodevelopmental functions, methylation-sensitive developmental transcription factor motifs, and human NDD DMRs identified from brain and placenta. Brain and cffDNA methylation levels from a large region overlapping mir-663 correlated with maternal obesity, metabolic and immune markers, and infant behavior. A DUX4 hippocampal co-methylation network correlated with maternal obesity, infant behavior, infant hippocampal lipidomic and metabolomic profiles, and maternal blood measurements of DUX4 cffDNA methylation, cytokines, and metabolites. We conclude that in this model, maternal obesity was associated with changes in the infant brain and behavior, and these differences were detectable in pregnancy through integrative analyses of cffDNA methylation with immune and metabolic factors.


Assuntos
Ácidos Nucleicos Livres , Obesidade Materna , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Ácidos Nucleicos Livres/metabolismo , Citocinas/metabolismo , DNA/metabolismo , Metilação de DNA , Epigênese Genética , Feminino , Humanos , Lactente , Macaca mulatta/genética , Gravidez , Fatores de Transcrição/metabolismo
6.
Sci Rep ; 12(1): 15763, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36131114

RESUMO

Serum N-glycan profiling studies during the past decades have shown robust associations between N-glycan changes and various biological conditions, including infections, in humans. Similar studies are scarcer for other mammals, despite the tremendous potential of serum N-glycans as biomarkers for infectious diseases in animal models of human disease and in the veterinary context. To expand the knowledge of serum N-glycan profiles in important mammalian model systems, in this study, we combined MALDI-TOF-MS analysis and HILIC-UPLC profiling of released N-glycans together with glycosidase treatments to characterize the glycan structures present in rhesus macaque serum. We used this baseline to monitor changes in serum N-glycans during infection with Brugia malayi, a parasitic nematode of humans responsible for lymphatic filariasis, in a longitudinal cohort of infected rhesus macaques. Alterations of the HILIC-UPLC profile, notably of abundant structures, became evident as early as 5 weeks post-infection. Given its prominent role in the immune response, contribution of immunoglobulin G to serum N-glycans was investigated. Finally, comparison with similar N-glycan profiling performed during infection with the dog heartworm Dirofilaria immitis suggests that many changes observed in rhesus macaque serum N-glycans are specific for lymphatic filariasis.


Assuntos
Brugia Malayi , Dirofilaria immitis , Filariose Linfática , Animais , Biomarcadores , Dirofilaria immitis/fisiologia , Cães , Filariose Linfática/parasitologia , Glicosídeo Hidrolases , Humanos , Imunoglobulina G , Macaca mulatta , Mamíferos , Polissacarídeos
8.
Proc Natl Acad Sci U S A ; 119(40): e2202564119, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36161937

RESUMO

A large body of recent work suggests that neural representations in prefrontal cortex (PFC) are changing over time to adapt to task demands. However, it remains unclear whether and how such dynamic coding schemes depend on the encoded variable and are influenced by anatomical constraints. Using a cued attention task and multivariate classification methods, we show that neuronal ensembles in PFC encode and retain in working memory spatial and color attentional instructions in an anatomically specific manner. Spatial instructions could be decoded both from the frontal eye field (FEF) and the ventrolateral PFC (vlPFC) population, albeit more robustly from FEF, whereas color instructions were decoded more robustly from vlPFC. Decoding spatial and color information from vlPFC activity in the high-dimensional state space indicated stronger dynamics for color, across the cue presentation and memory periods. The change in the color code was largely due to rapid changes in the network state during the transition to the delay period. However, we found that dynamic vlPFC activity contained time-invariant color information within a low-dimensional subspace of neural activity that allowed for stable decoding of color across time. Furthermore, spatial attention influenced decoding of stimuli features profoundly in vlPFC, but less so in visual area V4. Overall, our results suggest that dynamic population coding of attentional instructions within PFC is shaped by anatomical constraints and can coexist with stable subspace coding that allows time-invariant decoding of information about the future target.


Assuntos
Atenção , Córtex Pré-Frontal , Animais , Atenção/fisiologia , Macaca mulatta , Memória de Curto Prazo/fisiologia , Dinâmica Populacional , Córtex Pré-Frontal/fisiologia
9.
Front Immunol ; 13: 960411, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36131913

RESUMO

Fc mediated effector functions of antibodies play important roles in immunotherapies and vaccine efficacy but assessing those functions in animal models can be challenging due to species differences. Rhesus macaques, Macaca mulatta (Mm) share approximately 93% sequence identity with humans but display important differences in their adaptive immune system that complicates their use in validating therapeutics and vaccines that rely on Fc effector functions. In contrast to humans, macaques only have one low affinity FcγRIII receptor, CD16, which shares a polymorphism at position 158 with human FcγRIIIa with Ile158 and Val158 variants. Here we describe structure-function relationships of the Ile/Val158 polymorphism in Mm FcγRIII. Our data indicate that the affinity of the allelic variants of Mm FcγRIII for the macaque IgG subclasses vary greatly with changes in glycan composition both on the Fc and the receptor. However, unlike the human Phe/Val158 polymorphism in FcγRIIIa, the higher affinity variant corresponds to the larger, more hydrophobic side chain, Ile, even though it is not directly involved in the binding interface. Instead, this side chain appears to modulate glycan-glycan interactions at the Fc/FcγRIII interface. Furthermore, changes in glycan composition on the receptor have a greater effect for the Val158 variant such that with oligomannose type glycans and with glycans only on Asn45 and Asn162, Val158 becomes the variant with higher affinity to Fc. These results have implications not only for the better interpretation of nonhuman primate studies but also for studies performed with human effector cells carrying different FcγRIIIa alleles.


Assuntos
Imunoglobulina G , Polissacarídeos , Animais , Humanos , Fragmentos Fc das Imunoglobulinas/imunologia , Macaca mulatta , Polissacarídeos/metabolismo , Receptores de IgG/imunologia
11.
Nat Commun ; 13(1): 5592, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36151142

RESUMO

Humans and other primates recognize one another in part based on unique structural details of the face, including both local features and their spatial configuration within the head and body. Visual analysis of the face is supported by specialized regions of the primate cerebral cortex, which in macaques are commonly known as face patches. Here we ask whether the responses of neurons in anterior face patches, thought to encode face identity, are more strongly driven by local or holistic facial structure. We created stimuli consisting of recombinant photorealistic images of macaques, where we interchanged the eyes, mouth, head, and body between individuals. Unexpectedly, neurons in the anterior medial (AM) and anterior fundus (AF) face patches were predominantly tuned to local facial features, with minimal neural selectivity for feature combinations. These findings indicate that the high-level structural encoding of face identity rests upon populations of neurons specialized for local features.


Assuntos
Face , Imageamento por Ressonância Magnética , Animais , Mapeamento Encefálico , Córtex Cerebral , Humanos , Macaca mulatta , Neurônios/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa
12.
Transl Vis Sci Technol ; 11(9): 23, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36156731

RESUMO

Purpose: To define the normal range of central corneal thickness (CCT) and corneal endothelial cell density (ECD) in rhesus macaques (Macaca mulatta) and the effects of age, body weight, sex, and intraocular pressure (IOP) on these parameters. Methods: Ophthalmic examinations were performed on 144 rhesus macaques without anterior segment pathology. The CCT was measured via ultrasound pachymetry (USP) and specular microscopy, and the ECD was semiautomatically and manually counted using specular microscopy. Rebound tonometry was used to measure IOP. Linear regression and mixed-effects linear regression models were used to evaluate the effects of age, body weight, sex, and IOP on CCT and ECD. Results: We included 98 females and 46 males with an age range of 0.2 to 29.4 years. The mean CCT by USP and specular microscopy were 483 ± 39 and 463 ± 33 µm, respectively, and were statistically different (P < 0.001). The ECDs were 2717 ± 423 and 2747 ± 438 cells/mm2 by semiautomated and manual analysis, respectively. Corneal endothelial degeneration was identified in one aged rhesus macaque. Conclusions: The mean USP and specular microscopy CCT values differed significantly, whereas the semiautomatic and manual ECD did not. The CCT was associated with the IOP and sex, whereas the ECD was associated with body weight and age (P < 0.05). As in humans, corneal disease in rhesus macaques is uncommon. Translational Relevance: Establishing reference values is fundamental to use rhesus macaques as a model for corneal disease or to identify toxicity in studies of ocular drugs or devices.


Assuntos
Córnea , Distrofias Hereditárias da Córnea , Adolescente , Adulto , Idoso , Animais , Peso Corporal , Criança , Pré-Escolar , Córnea/anatomia & histologia , Córnea/patologia , Distrofias Hereditárias da Córnea/patologia , Células Endoteliais , Feminino , Humanos , Lactente , Macaca mulatta , Masculino , Reprodutibilidade dos Testes , Adulto Jovem
13.
Nat Commun ; 13(1): 5207, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064848

RESUMO

Although the current hepatitis B (HB) vaccine comprising small-HBs antigen (Ag) is potent and safe, attenuated prophylaxis against hepatitis B virus (HBV) with vaccine-escape mutations (VEMs) has been reported. We investigate an HB vaccine consisting of large-HBsAg that overcomes the shortcomings of the current HB vaccine. Yeast-derived large-HBsAg is immunized into rhesus macaques, and the neutralizing activities of the induced antibodies are compared with those of the current HB vaccine. Although the antibodies induced by the current HB vaccine cannot prevent HBV infection with VEMs, the large-HBsAg vaccine-induced antibodies neutralize those infections. The HBV genotypes that exhibited attenuated neutralization via these vaccines are different. Here, we show that the HB vaccine consisting of large-HBsAg is useful to compensate for the shortcomings of the current HB vaccine. The combined use of these HB vaccines may induce antibodies that can neutralize HBV strains with VEMs or multiple HBV genotypes.


Assuntos
Vacinas contra Hepatite B , Hepatite B , Animais , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B/genética , Vacinas contra Hepatite B/uso terapêutico , Vírus da Hepatite B/genética , Macaca mulatta , Mutação
14.
Nat Commun ; 13(1): 5236, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068229

RESUMO

SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.


Assuntos
Infecções por HIV , Síndrome de Imunodeficiência Adquirida dos Símios , Vírus da Imunodeficiência Símia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Infecções por HIV/prevenção & controle , Humanos , Macaca mulatta , Polissacarídeos
15.
Genes (Basel) ; 13(9)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36140683

RESUMO

Spontaneous type 2 diabetes mellitus (T2DM) macaques are valuable resources for our understanding the pathological mechanism of T2DM. Based on one month's fasting blood glucose survey, we identified seven spontaneous T2DM macaques and five impaired glucose regulation (IGR) macaques from 1408 captive individuals. FPG, HbA1c, FPI and IR values were significant higher in T2DM and IGR than in controls. 16S rRNA sequencing of fecal microbes showed the significantly greater abundance of Oribacterium, bacteria inhibiting the production of secondary bile acids, and Phascolarctobacterium, bacteria producing short-chain fatty acids was significantly lower in T2DM macaques. In addition, several opportunistic pathogens, such as Mogibacterium and Kocuria were significantly more abundant in both T2DM and IGR macaques. Fecal metabolites analysis based on UHPLC-MS identified 50 differential metabolites (DMs) between T2DM and controls, and 26 DMs between IGR and controls. The DMs were significantly enriched in the bile acids metabolism, fatty acids metabolism and amino acids metabolism pathways. Combining results from physiochemical parameters, microbiota and metabolomics, we demonstrate that the imbalance of gut microbial community leading to the dysfunction of glucose, bile acids, fatty acids and amino acids metabolism may contribute to the hyperglycaemia in macaques, and suggest several microbes and metabolites are potential biomarkers for T2DM and IGR macaques.


Assuntos
Diabetes Mellitus Tipo 2 , Microbiota , Estado Pré-Diabético , Aminoácidos , Animais , Ácidos e Sais Biliares , Glicemia , Ácidos Graxos Voláteis , Glucose , Hemoglobina A Glicada , Macaca mulatta , Microbiota/genética , Estado Pré-Diabético/genética , RNA Ribossômico 16S/genética
16.
Nat Commun ; 13(1): 5479, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123363

RESUMO

Optic flow is a powerful cue for inferring self-motion status which is critical for postural control, spatial orientation, locomotion and navigation. In primates, neurons in extrastriate visual cortex (MSTd) are predominantly modulated by high-order optic flow patterns (e.g., spiral), yet a functional link to direct perception is lacking. Here, we applied electrical microstimulation to selectively manipulate population of MSTd neurons while macaques discriminated direction of rotation around line-of-sight (roll) or direction of linear-translation (heading), two tasks which were orthogonal in 3D spiral coordinate using a four-alternative-forced-choice paradigm. Microstimulation frequently biased animal's roll perception towards coded labeled-lines of the artificial-stimulated neurons in either context with spiral or pure-rotation stimuli. Choice frequency was also altered between roll and translation flow-pattern. Our results provide direct causal-link evidence supporting that roll signals in MSTd, despite often mixed with translation signals, can be extracted by downstream areas for perception of rotation relative to gravity-vertical.


Assuntos
Percepção de Movimento , Fluxo Óptico , Córtex Visual , Animais , Macaca mulatta , Percepção de Movimento/fisiologia , Estimulação Luminosa/métodos , Córtex Visual/fisiologia
17.
FASEB J ; 36(10): e22536, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36070186

RESUMO

The liver is an essential multifunctional organ and constantly communicates with nearly all the tissues in the body. Spaceflight or simulated microgravity has a significant impact on the livers of rodent models, including lipid accumulation and inflammatory cell infiltration. Whether similar liver lipotoxicity could occur in humans is not known, even though altered circulating cholesterol profile has been reported in astronauts. Using a 42-day head-down bed rest (HDBR) model in rhesus macaques, the present study investigated whether simulated microgravity alters the liver of non-human primates at the transcriptome and metabolome levels. Its association with stress and intestinal changes was also explored. Compared to the controls, the HDBR monkeys showed mild liver injury, elevated ANGPTL3 level in the plasma, and accumulation of fat vacuoles and inflammatory cells in the liver. Altered transcriptome signatures with up-regulation of genes in lipid metabolisms and down-regulation of genes in innate immune defense were also found in HDBR group-derived liver samples. The metabolic profiling of the liver revealed mildly disturbed fatty acid metabolism in the liver of HDBR monkeys. The intestinal dysbiosis, its associated endotoxemia and changes in the composition of bile acids, and elevated stress hormone in HDBR monkeys may contribute to the altered lipid metabolisms in the liver. These data indicate that liver metabolic functions and gut-liver axis should be closely monitored in prolonged spaceflight to facilitate strategy design to improve and maintain metabolic homeostasis.


Assuntos
Ausência de Peso , Animais , Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , Lipídeos , Fígado/metabolismo , Macaca mulatta , Ausência de Peso/efeitos adversos
18.
PLoS Biol ; 20(9): e3001798, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36103550

RESUMO

Sensory pathways provide complex and multifaceted information to the brain. Recent advances have created new opportunities for applying our understanding of the brain to sensory prothesis development. Yet complex sensor physiology, limited numbers of electrodes, and nonspecific stimulation have proven to be a challenge for many sensory systems. In contrast, the vestibular system is uniquely suited for prosthesis development. Its peripheral anatomy allows site-specific stimulation of 3 separate sensory organs that encode distinct directions of head motion. Accordingly, here, we investigated whether implementing natural encoding strategies improves vestibular prosthesis performance. The eye movements produced by the vestibulo-ocular reflex (VOR), which plays an essential role in maintaining visual stability, were measured to quantify performance. Overall, implementing the natural tuning dynamics of vestibular afferents produced more temporally accurate VOR eye movements. Exploration of the parameter space further revealed that more dynamic tunings were not beneficial due to saturation and unnatural phase advances. Trends were comparable for stimulation encoding virtual versus physical head rotations, with gains enhanced in the latter case. Finally, using computational methods, we found that the same simple model explained the eye movements evoked by sinusoidal and transient stimulation and that a stimulation efficacy substantially less than 100% could account for our results. Taken together, our results establish that prosthesis encodings that incorporate naturalistic afferent dynamics and account for activation efficacy are well suited for restoration of gaze stability. More generally, these results emphasize the benefits of leveraging the brain's endogenous coding strategies in prosthesis development to improve functional outcomes.


Assuntos
Membros Artificiais , Vestíbulo do Labirinto , Animais , Movimentos Oculares , Macaca mulatta , Reflexo Vestíbulo-Ocular/fisiologia , Vestíbulo do Labirinto/fisiologia
19.
BMC Genomics ; 23(1): 647, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096729

RESUMO

BACKGROUND: Cynomolgus macaque (Macaca fascicularis) is an attractive animal model for the study of human disease and is extensively used in biomedical research. Cynomolgus macaques share behavioral, physiological, and genomic traits with humans and recapitulate human disease manifestations not observed in other animal species. To improve the use of the cynomolgus macaque model to investigate immune responses, we defined and characterized the T cell receptor (TCR) repertoire. RESULT: We identified and analyzed the alpha (TRA), beta (TRB), gamma (TRG), and delta (TRD) TCR loci of the cynomolgus macaque. The expressed repertoire was determined using 22 unique lung samples from Mycobacterium tuberculosis infected cynomolgus macaques by single cell RNA sequencing. Expressed TCR alpha (TRAV) and beta (TRBV) variable region genes were enriched and identified using gene specific primers, which allowed their functional status to be determined. Analysis of the primers used for cynomolgus macaque TCR variable region gene enrichment showed they could also be used to amplify rhesus macaque (M. mulatta) variable region genes. CONCLUSION: The genomic organization of the cynomolgus macaque has great similarity with the rhesus macaque and they shared > 90% sequence similarity with the human TCR repertoire. The identification of the TCR repertoire facilitates analysis of T cell immunity in cynomolgus macaques.


Assuntos
Genoma , Mycobacterium tuberculosis , Animais , Genômica , Humanos , Macaca fascicularis/genética , Macaca mulatta/genética , Mycobacterium tuberculosis/genética
20.
Elife ; 112022 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-36097816

RESUMO

Theta-burst transcranial magnetic stimulation (TBS) has become a standard non-invasive technique to induce offline changes in cortical excitability in human volunteers. Yet, TBS suffers from a high variability across subjects. A better knowledge about how TBS affects neural activity in vivo could uncover its mechanisms of action and ultimately allow its mainstream use in basic science and clinical applications. To address this issue, we applied continuous TBS (cTBS, 300 pulses) in awake behaving rhesus monkeys and quantified its after-effects on neuronal activity. Overall, we observed a pronounced, long-lasting, and highly reproducible reduction in neuronal excitability after cTBS in individual parietal neurons, with some neurons also exhibiting periods of hyperexcitability during the recovery phase. These results provide the first experimental evidence of the effects of cTBS on single neurons in awake behaving monkeys, shedding new light on the reasons underlying cTBS variability.


Assuntos
Excitabilidade Cortical , Gastrópodes , Animais , Voluntários Saudáveis , Humanos , Macaca mulatta , Neurônios , Estimulação Magnética Transcraniana/métodos
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