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1.
Proc Natl Acad Sci U S A ; 121(12): e2318176121, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38483994

RESUMO

Endogenous retroviruses (ERVs) are frequently reactivated in mammalian placenta. It has been proposed that ERVs contribute to shaping the gene regulatory network of mammalian trophoblasts, dominantly acting as species- and placental-specific enhancers. However, whether and how ERVs control human trophoblast development through alternative pathways remains poorly understood. Besides the well-recognized function of human endogenous retrovirus-H (HERVH) in maintaining pluripotency of early human epiblast, here we present a unique role of HERVH on trophoblast lineage development. We found that the LTR7C/HERVH subfamily exhibits an accessible chromatin state in the human trophoblast lineage. Particularly, the LTR7C/HERVH-derived Urothelial Cancer Associated 1 (UCA1), a primate-specific long non-coding RNA (lncRNA), is transcribed in human trophoblasts and promotes the proliferation of human trophoblast stem cells (hTSCs), whereas its ectopic expression compromises human trophoblast syncytialization coinciding with increased interferon signaling pathway. Importantly, UCA1 upregulation is detectable in placental samples from early-onset preeclampsia (EO-PE) patients and the transcriptome of EO-PE placenta exhibits considerable similarities to that of the syncytiotrophoblasts differentiated from UCA1-overexpressing hTSCs, supporting up-regulated UCA1 as a potential biomarker of this disease. Altogether, our data shed light on the versatile regulatory role of HERVH in early human development and provide a unique mechanism whereby ERVs exert a function in human placentation and placental syndromes.


Assuntos
Retrovirus Endógenos , RNA Longo não Codificante , Animais , Humanos , Gravidez , Feminino , Retrovirus Endógenos/genética , Retrovirus Endógenos/metabolismo , Placenta/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Trofoblastos/metabolismo , Placentação , Primatas/genética , Mamíferos/genética
2.
Cereb Cortex ; 34(2)2024 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-38425213

RESUMO

The size and shape of the cerebral cortex have changed dramatically across evolution. For some species, the cortex remains smooth (lissencephalic) throughout their lifetime, while for other species, including humans and other primates, the cortex increases substantially in size and becomes folded (gyrencephalic). A folded cortex boasts substantially increased surface area, cortical thickness, and neuronal density, and it is therefore associated with higher-order cognitive abilities. The mechanisms that drive gyrification in some species, while others remain lissencephalic despite many shared neurodevelopmental features, have been a topic of investigation for many decades, giving rise to multiple perspectives of how the gyrified cerebral cortex acquires its unique shape. Recently, a structurally unique germinal layer, known as the outer subventricular zone, and the specialized cell type that populates it, called basal radial glial cells, were identified, and these have been shown to be indispensable for cortical expansion and folding. Transcriptional analyses and gene manipulation models have provided an invaluable insight into many of the key cellular and genetic drivers of gyrification. However, the degree to which certain biomechanical, genetic, and cellular processes drive gyrification remains under investigation. This review considers the key aspects of cerebral expansion and folding that have been identified to date and how theories of gyrification have evolved to incorporate this new knowledge.


Assuntos
Córtex Cerebral , Neurônios , Animais , Humanos , Córtex Cerebral/metabolismo , Neurônios/metabolismo , Ventrículos Laterais/metabolismo , Primatas
3.
Anim Cogn ; 27(1): 5, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38429436

RESUMO

Humans and many other animal species act in ways that benefit others. Such prosocial behaviour has been studied extensively across a range of disciplines over the last decades, but findings to date have led to conflicting conclusions about prosociality across and even within species. Here, we present a conceptual framework to study the proximate regulation of prosocial behaviour in humans, non-human primates and potentially other animals. We build on psychological definitions of prosociality and spell out three key features that need to be in place for behaviour to count as prosocial: benefitting others, intentionality, and voluntariness. We then apply this framework to review observational and experimental studies on sharing behaviour and targeted helping in human children and non-human primates. We show that behaviours that are usually subsumed under the same terminology (e.g. helping) can differ substantially across and within species and that some of them do not fulfil our criteria for prosociality. Our framework allows for precise mapping of prosocial behaviours when retrospectively evaluating studies and offers guidelines for future comparative work.


Assuntos
Altruísmo , Comportamento Social , Humanos , Animais , Estudos Retrospectivos , Primatas
4.
Zool Res ; 45(2): 275-283, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38485497

RESUMO

Huntington's disease (HD) is a hereditary neurodegenerative disorder for which there is currently no effective treatment available. Consequently, the development of appropriate disease models is critical to thoroughly investigate disease progression. The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin ( HTT) gene, leading to the expansion of a polyglutamine repeat in the HTT protein. Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain, which precipitate selective neuronal loss in specific brain regions. Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets. Due to the marked species differences between rodents and larger animals, substantial efforts have been directed toward establishing large animal models for HD research. These models are pivotal for advancing the discovery of novel therapeutic targets, enhancing effective drug delivery methods, and improving treatment outcomes. We have explored the advantages of utilizing large animal models, particularly pigs, in previous reviews. Since then, however, significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD. In the current review, we provide a comprehensive overview of large animal models of HD, incorporating recent findings regarding the establishment of HD knock-in (KI) pigs and their genetic therapy. We also explore the utilization of large animal models in HD research, with a focus on sheep, non-human primates (NHPs), and pigs. Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.


Assuntos
Doença de Huntington , Doenças dos Ovinos , Doenças dos Suínos , Animais , Ovinos , Suínos , Doença de Huntington/genética , Doença de Huntington/terapia , Doença de Huntington/metabolismo , Doença de Huntington/veterinária , Modelos Animais de Doenças , Primatas/genética , Encéfalo/metabolismo , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Doenças dos Ovinos/metabolismo , Doenças dos Ovinos/patologia , Doenças dos Suínos/metabolismo , Doenças dos Suínos/patologia
5.
Zool Res ; 45(2): 292-298, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38485499

RESUMO

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys ( Macaca fascicularis) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. The successful establishment of this non-human primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.


Assuntos
Doenças Mitocondriais , Doenças dos Roedores , Camundongos , Humanos , Feminino , Animais , Doenças Mitocondriais/genética , Doenças Mitocondriais/prevenção & controle , Doenças Mitocondriais/veterinária , Haplorrinos/genética , Mitocôndrias/genética , DNA Mitocondrial/genética , Primatas/genética
6.
Zool Res ; 45(2): 429-438, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38485510

RESUMO

The Chinese tree shrew ( Tupaia belangeri chinensis), a member of the mammalian order Scandentia, exhibits considerable similarities with primates, including humans, in aspects of its nervous, immune, and metabolic systems. These similarities have established the tree shrew as a promising experimental model for biomedical research on cancer, infectious diseases, metabolic disorders, and mental health conditions. Herein, we used meta-transcriptomic sequencing to analyze plasma, as well as oral and anal swab samples, from 105 healthy asymptomatic tree shrews to identify the presence of potential zoonotic viruses. In total, eight mammalian viruses with complete genomes were identified, belonging to six viral families, including Flaviviridae, Hepeviridae, Parvovirinae, Picornaviridae, Sedoreoviridae, and Spinareoviridae. Notably, the presence of rotavirus was recorded in tree shrews for the first time. Three viruses - hepacivirus 1, parvovirus, and picornavirus - exhibited low genetic similarity (<70%) with previously reported viruses at the whole-genome scale, indicating novelty. Conversely, three other viruses - hepacivirus 2, hepatovirus A and hepevirus - exhibited high similarity (>94%) to known viral strains. Phylogenetic analyses also revealed that the rotavirus and mammalian orthoreovirus identified in this study may be novel reassortants. These findings provide insights into the diverse viral spectrum present in captive Chinese tree shrews, highlighting the necessity for further research into their potential for cross-species transmission.


Assuntos
Tupaia , Vírus , Humanos , Animais , Tupaia/fisiologia , Tupaiidae , Musaranhos , Filogenia , Primatas
7.
Nat Commun ; 15(1): 2319, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485931

RESUMO

Monoclonal antibodies are an increasingly important tool for prophylaxis and treatment of acute virus infections like SARS-CoV-2 infection. However, their use is often restricted due to the time required for development, variable yields and high production costs, as well as the need for adaptation to newly emerging virus variants. Here we use the genetically modified filamentous fungus expression system Thermothelomyces heterothallica (C1), which has a naturally high biosynthesis capacity for secretory enzymes and other proteins, to produce a human monoclonal IgG1 antibody (HuMab 87G7) that neutralises the SARS-CoV-2 variants of concern (VOCs) Alpha, Beta, Gamma, Delta, and Omicron. Both the mammalian cell and C1 produced HuMab 87G7 broadly neutralise SARS-CoV-2 VOCs in vitro and also provide protection against VOC Omicron in hamsters. The C1 produced HuMab 87G7 is also able to protect against the Delta VOC in non-human primates. In summary, these findings show that the C1 expression system is a promising technology platform for the development of HuMabs in preventive and therapeutic medicine.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Cricetinae , Humanos , SARS-CoV-2/genética , COVID-19/prevenção & controle , Primatas , Imunoglobulina G , Anticorpos Monoclonais , Fungos , Anticorpos Neutralizantes , Glicoproteína da Espícula de Coronavírus , Anticorpos Antivirais , Mamíferos
8.
Cell ; 187(6): 1547-1562.e13, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38428424

RESUMO

We sequenced and assembled using multiple long-read sequencing technologies the genomes of chimpanzee, bonobo, gorilla, orangutan, gibbon, macaque, owl monkey, and marmoset. We identified 1,338,997 lineage-specific fixed structural variants (SVs) disrupting 1,561 protein-coding genes and 136,932 regulatory elements, including the most complete set of human-specific fixed differences. We estimate that 819.47 Mbp or ∼27% of the genome has been affected by SVs across primate evolution. We identify 1,607 structurally divergent regions wherein recurrent structural variation contributes to creating SV hotspots where genes are recurrently lost (e.g., CARD, C4, and OLAH gene families) and additional lineage-specific genes are generated (e.g., CKAP2, VPS36, ACBD7, and NEK5 paralogs), becoming targets of rapid chromosomal diversification and positive selection (e.g., RGPD gene family). High-fidelity long-read sequencing has made these dynamic regions of the genome accessible for sequence-level analyses within and between primate species.


Assuntos
Genoma , Primatas , Animais , Humanos , Sequência de Bases , Primatas/classificação , Primatas/genética , Evolução Biológica , Análise de Sequência de DNA , Variação Estrutural do Genoma
10.
Nat Aging ; 4(3): 396-413, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38503993

RESUMO

Adrenal glands, vital for steroid secretion and the regulation of metabolism, stress responses and immune activation, experience age-related decline, impacting systemic health. However, the regulatory mechanisms underlying adrenal aging remain largely uninvestigated. Here we established a single-nucleus transcriptomic atlas of both young and aged primate suprarenal glands, identifying lipid metabolism and steroidogenic pathways as core processes impacted by aging. We found dysregulation in centripetal adrenocortical differentiation in aged adrenal tissues and cells in the zona reticularis region, responsible for producing dehydroepiandrosterone sulfate (DHEA-S), were highly susceptible to aging, reflected by senescence, exhaustion and disturbed hormone production. Remarkably, LDLR was downregulated in all cell types of the outer cortex, and its targeted inactivation in human adrenal cells compromised cholesterol uptake and secretion of dehydroepiandrosterone sulfate, as observed in aged primate adrenal glands. Our study provides crucial insights into endocrine physiology, holding therapeutic promise for addressing aging-related adrenal insufficiency and delaying systemic aging.


Assuntos
Glândulas Suprarrenais , Envelhecimento , Animais , Humanos , Idoso , Sulfato de Desidroepiandrosterona/metabolismo , Glândulas Suprarrenais/metabolismo , Envelhecimento/genética , Zona Reticular , Primatas/metabolismo
11.
Cell ; 187(6): 1360-1362, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38490180

RESUMO

The mpox outbreak in 2022 launched a vaccination campaign employing an existing vaccine with moderate protection, highlighting the lack of scalable Orthopoxvirus vaccines with optimal protection. In this issue of Cell, Zuiani et al. report pre-clinical findings of an mRNA-based mpox vaccine, paving the way for Phase I/II clinical trials.


Assuntos
Vacina Antivariólica , Vacinas Virais , Vacinas de mRNA , Animais , Vírus da Varíola dos Macacos/imunologia , Vacinas de mRNA/imunologia , Primatas , Vacina Antivariólica/imunologia , Vacinas Virais/imunologia
12.
Commun Biol ; 7(1): 329, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38485764

RESUMO

Optogenetics has transformed studies of neural circuit function, but remains challenging to apply to non-human primates (NHPs). A major challenge is delivering intense, spatiotemporally-precise, patterned photostimulation across large volumes in deep tissue. Such stimulation is critical, for example, to modulate selectively deep-layer corticocortical feedback circuits. To address this need, we have developed the Utah Optrode Array (UOA), a 10×10 glass needle waveguide array fabricated atop a novel opaque optical interposer, and bonded to an electrically addressable µLED array. In vivo experiments with the UOA demonstrated large-scale, spatiotemporally precise, activation of deep circuits in NHP cortex. Specifically, the UOA permitted both focal (confined to single layers/columns), and widespread (multiple layers/columns) optogenetic activation of deep layer neurons, as assessed with multi-channel laminar electrode arrays, simply by varying the number of activated µLEDs and/or the irradiance. Thus, the UOA represents a powerful optoelectronic device for targeted manipulation of deep-layer circuits in NHP models.


Assuntos
Neurônios , Optogenética , Animais , Eletrodos , Neurônios/fisiologia , Primatas/fisiologia , Utah
13.
Nat Commun ; 15(1): 2519, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514616

RESUMO

Consensus is rapidly building to support a role for the cerebellum beyond motor function, but its contributions to non-motor learning remain poorly understood. Here, we provide behavioral, anatomical and computational evidence to demonstrate a causal role for the primate posterior lateral cerebellum in learning new visuomotor associations. Reversible inactivation of the posterior lateral cerebellum of male monkeys impeded the learning of new visuomotor associations, but had no effect on movement parameters, or on well-practiced performance of the same task. Using retrograde transneuronal transport of rabies virus, we identified a distinct cerebro-cerebellar network linking Purkinje cells in the posterior lateral cerebellum with a region of the prefrontal cortex that is critical in learning visuomotor associations. Together, these results demonstrate a causal role for the primate posterior lateral cerebellum in non-motor, reinforcement learning.


Assuntos
Cerebelo , Aprendizagem , Animais , Masculino , Cerebelo/fisiologia , Aprendizagem/fisiologia , Células de Purkinje , Córtex Pré-Frontal , Primatas
14.
Sci Rep ; 14(1): 6839, 2024 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-38514646

RESUMO

Light is known to induce retinal damage affecting photoreceptors and retinal pigment epithelium. For polychromatic light, the blue part of the spectrum is thought to be the only responsible for photochemical damage, leading to the establishment of a phototoxicity threshold for blue light (445 nm). For humans it corresponds to a retinal dose of 22 J/cm2. Recent studies on rodents and non-human primates suggested that this value is overestimated. In this study, we aim at investigating the relevance of the current phototoxicity threshold and at providing new hints on the role of the different components of the white light spectrum on phototoxicity. We use an in vitro model of human induced pluripotent stem cells (hiPSC)-derived retinal pigment epithelial (iRPE) cells and exposed them to white, blue and red lights from LED devices at doses below 22 J/cm2. We show that exposure to white light at a dose of 3.6 J/cm2 induces an alteration of the global cellular structure, DNA damage and an activation of cellular stress pathways. The exposure to blue light triggers DNA damage and the activation of autophagy, while exposure to red light modulates the inflammatory response and inhibits autophagy.


Assuntos
Células-Tronco Pluripotentes Induzidas , Epitélio Pigmentado da Retina , Animais , Humanos , Epitélio Pigmentado da Retina/metabolismo , Retina , Primatas
15.
Elife ; 132024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426402

RESUMO

Investigating how, when, and what subjects learn during decision-making tasks requires tracking their choice strategies on a trial-by-trial basis. Here, we present a simple but effective probabilistic approach to tracking choice strategies at trial resolution using Bayesian evidence accumulation. We show this approach identifies both successful learning and the exploratory strategies used in decision tasks performed by humans, non-human primates, rats, and synthetic agents. Both when subjects learn and when rules change the exploratory strategies of win-stay and lose-shift, often considered complementary, are consistently used independently. Indeed, we find the use of lose-shift is strong evidence that subjects have latently learnt the salient features of a new rewarded rule. Our approach can be extended to any discrete choice strategy, and its low computational cost is ideally suited for real-time analysis and closed-loop control.


Assuntos
Comportamento de Escolha , Aprendizagem , Humanos , Ratos , Animais , Teorema de Bayes , Recompensa , Primatas
16.
Mil Med Res ; 11(1): 17, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475827

RESUMO

BACKGROUND: Tactile and mechanical pain are crucial to our interaction with the environment, yet the underpinning molecular mechanism is still elusive. Endophilin A2 (EndoA2) is an evolutionarily conserved protein that is documented in the endocytosis pathway. However, the role of EndoA2 in the regulation of mechanical sensitivity and its underlying mechanisms are currently unclear. METHODS: Male and female C57BL/6 mice (8-12 weeks) and male cynomolgus monkeys (7-10 years old) were used in our experiments. Nerve injury-, inflammatory-, and chemotherapy-induced pathological pain models were established for this study. Behavioral tests of touch, mechanical pain, heat pain, and cold pain were performed in mice and nonhuman primates. Western blotting, immunostaining, co-immunoprecipitation, proximity ligation and patch-clamp recordings were performed to gain insight into the mechanisms. RESULTS: The results showed that EndoA2 was primarily distributed in neurofilament-200-positive (NF200+) medium-to-large diameter dorsal root ganglion (DRG) neurons of mice and humans. Loss of EndoA2 in mouse NF200+ DRG neurons selectively impaired the tactile and mechanical allodynia. Furthermore, EndoA2 interacted with the mechanically sensitive ion channel Piezo2 and promoted the membrane trafficking of Piezo2 in DRG neurons. Moreover, as an adaptor protein, EndoA2 also bound to kinesin family member 5B (KIF5B), which was involved in the EndoA2-mediated membrane trafficking process of Piezo2. Loss of EndoA2 in mouse DRG neurons damaged Piezo2-mediated rapidly adapting mechanically activated currents, and re-expression of EndoA2 rescued the MA currents. In addition, interference with EndoA2 also suppressed touch sensitivity and mechanical hypersensitivity in nonhuman primates. CONCLUSIONS: Our data reveal that the KIF5B/EndoA2/Piezo2 complex is essential for Piezo2 trafficking and for sustaining transmission of touch and mechanical hypersensitivity signals. EndoA2 regulates touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking in sensory neurons. Our findings identify a potential new target for the treatment of mechanical pain.


Assuntos
Aciltransferases , Hiperalgesia , Canais Iônicos , Tato , Animais , Feminino , Masculino , Camundongos , Hiperalgesia/patologia , Canais Iônicos/metabolismo , Cinesinas/metabolismo , Mecanotransdução Celular/fisiologia , Camundongos Endogâmicos C57BL , Dor , Primatas , Tato/fisiologia , Aciltransferases/metabolismo
17.
Nat Commun ; 15(1): 2171, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38462641

RESUMO

A central challenge of neuroscience is to elucidate how brain function supports consciousness. Here, we combine the specificity of focal deep brain stimulation with fMRI coverage of the entire cortex, in awake and anaesthetised non-human primates. During propofol, sevoflurane, or ketamine anaesthesia, and subsequent restoration of responsiveness by electrical stimulation of the central thalamus, we investigate how loss of consciousness impacts distributed patterns of structure-function organisation across scales. We report that distributed brain activity under anaesthesia is increasingly constrained by brain structure across scales, coinciding with anaesthetic-induced collapse of multiple dimensions of hierarchical cortical organisation. These distributed signatures are observed across different anaesthetics, and they are reversed by electrical stimulation of the central thalamus, coinciding with recovery of behavioural markers of arousal. No such effects were observed upon stimulating the ventral lateral thalamus, demonstrating specificity. Overall, we identify consistent distributed signatures of consciousness that are orchestrated by specific thalamic nuclei.


Assuntos
Anestésicos , Propofol , Animais , Estado de Consciência/fisiologia , Encéfalo/diagnóstico por imagem , Propofol/farmacologia , Córtex Cerebral , Primatas , Tálamo/diagnóstico por imagem , Anestésicos/farmacologia
18.
J Med Primatol ; 53(2): e12694, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38454198

RESUMO

BACKGROUND: Animal models of respiratory viral infections are essential for investigating disease pathogenesis and the efficacy of antivirals and vaccine candidates. A major limitation in the research of respiratory diseases in animal models is correlating clinically relevant changes in pulmonary physiology with cellular and molecular mechanistic studies. Few animal models have captured and correlated physiologic changes in lung function and immune response within same experiment, which is critical given the heterogeneous nature of lung disease due to viral infections. In ventilated human patients, pulmonary physiology testing can be used to not only capture oxygenation, ventilation, but also pulmonary mechanics to yield quantitative measures of lung function and scalar tracings of flow-volume and pressure-volume loops. Application of this protocol during mechanical ventilation in non-human (NHP) models would represent a major advance in respiratory viral disease research. METHODS: We have applied and optimized a human pulmonary physiology testing protocol to ventilated pigtail macaques (Macaca nemestrina) at baseline and 5 days after influenza A (IAV) viral inoculation. RESULTS: The NHPs manifested clinical disease with hypothermia and loss of body weight. Declines in lung function were striking with a 66%-81% decline in P/F ratio, a measure of oxygenation reflecting the ratio of partial pressure of oxygen in arterial blood (PaO2 ) to the fraction of inspiratory oxygen concentration (FiO2 ). There was also a 16%-45% decline in lung compliance. CONCLUSION: We describe a new approach to performing pulmonary physiology testing protocol in non-human primates to better capture quantitative correlates of respiratory disease and demonstrate protection by therapeutics and vaccines.


Assuntos
Pulmão , Viroses , Humanos , Animais , Respiração Artificial/métodos , Oxigênio , Primatas
19.
Adv Neurobiol ; 36: 241-258, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38468036

RESUMO

The evolution of the brain in mammals is characterized by changes in size, architecture, and internal organization. Consequently, the geometry of the brain, and especially the size and shape of the cerebral cortex, has changed notably during evolution. Comparative studies of the cerebral cortex suggest that there are general architectural principles governing its growth and evolutionary development. In this chapter, some of the design principles and operational modes that underlie the fractal geometry and information processing capacity of the cerebral cortex in primates, including humans, will be explored. It is shown that the development of the cortex coordinates folding with connectivity in a way that produces smaller and faster brains.


Assuntos
Evolução Biológica , Fractais , Animais , Humanos , Encéfalo , Primatas , Córtex Cerebral , Mamíferos
20.
Front Immunol ; 15: 1359679, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529287

RESUMO

Understanding the immunological control of pathogens requires a detailed evaluation of the mechanistic contributions of individual cell types within the immune system. While knockout mouse models that lack certain cell types have been used to help define the role of those cells, the biological and physiological characteristics of mice do not necessarily recapitulate that of a human. To overcome some of these differences, studies often look towards nonhuman primates (NHPs) due to their close phylogenetic relationship to humans. To evaluate the immunological role of select cell types, the NHP model provides distinct advantages since NHP more closely mirror the disease manifestations and immunological characteristics of humans. However, many of the experimental manipulations routinely used in mice (e.g., gene knock-out) cannot be used with the NHP model. As an alternative, the in vivo infusion of monoclonal antibodies that target surface proteins on specific cells to either functionally inhibit or deplete cells can be a useful tool. Such depleting antibodies have been used in NHP studies to address immunological mechanisms of action. In these studies, the extent of depletion has generally been reported for blood, but not thoroughly assessed in tissues. Here, we evaluated four depleting regimens that primarily target T cells in NHP: anti-CD4, anti-CD8α, anti-CD8ß, and immunotoxin-conjugated anti-CD3. We evaluated these treatments in healthy unvaccinated and IV BCG-vaccinated NHP to measure the extent that vaccine-elicited T cells - which may be activated, increased in number, or resident in specific tissues - are depleted compared to resting populations in unvaccinated NHPs. We report quantitative measurements of in vivo depletion at multiple tissue sites providing insight into the range of cell types depleted by a given mAb. While we found substantial depletion of target cell types in blood and tissue of many animals, residual cells remained, often residing within tissue. Notably, we find that animal-to-animal variation is substantial and consequently studies that use these reagents should be powered accordingly.


Assuntos
Anticorpos Monoclonais , Linfócitos T , Animais , Humanos , Camundongos , Filogenia , Anticorpos Monoclonais/farmacologia , Primatas
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