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1.
Anticancer Res ; 41(11): 5343-5353, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34732404

RESUMO

Enhanced understanding of the molecular features of glioma has led to an expansion of murine glioma models and successful preclinical studies. However, clinical trials continue to have a high cost, extended production time, and low proportion of success. Studies in large-animal models of various cancer types have emerged to bridge the translational gap between in vitro and in vivo animal studies and human clinical trials. The anatomy and physiology of large animals are of more direct relevance to human disease, allowing for more rigorous testing of treatments such as surgical resection and adjuvant therapy in glioma. The recent generation of multiple porcine glioma models supports their use in high-throughput preclinical studies. The demonstration of spontaneous glioblastoma formation in canines further provides a unique avenue for the study of de novo glioma. The aim of this review was to outline the current status of large animal models of glioma and their value as a transitional step between rodent models and human clinical trials.


Assuntos
Neoplasias Encefálicas , Glioma , Pesquisa Médica Translacional , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Modelos Animais de Doenças , Cães , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Glioma/terapia , Haplorrinos , Humanos , Camundongos Transgênicos , Especificidade da Espécie , Sus scrofa
2.
BMC Ophthalmol ; 21(1): 377, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34696757

RESUMO

BACKGROUND: microRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression. They are found within cells and in body fluids. Extracellular miRNAs have been shown to associate with the surrounding tissues. Therefore, we predicted that miRNAs in tears may contribute to regulate corneal epithelial cell function. However, information on the miRNA expression profile of tears is limited and the specific functions of tear miRNAs for corneal epithelial cells are still unknown. To study the role of tear miRNAs, we determined which miRNAs are highly expressed in tears and examined the involvement of miRNAs in corneal epithelial cell viability. METHODS: miRNAs extracted from monkey tears and sera were subjected to microarray analysis. miRNAs of which expression levels were higher in tears than in sera were selected, and their expression levels were quantified by quantitative polymerase chain reaction (qPCR). To examine miRNA function, mimics and inhibitors of miRNAs were transfected into human corneal epithelial (HCE-T) cells and incubated for 24 or 48 h. After transfection of miRNA mimics and inhibitors, the viability of HCE-T cells was measured using the water soluble tetrazolium salt (WST) assay, and microarray analysis and qPCR were performed using total RNA extracted from HCE-T cells. siRNAs of the candidate targets for miR-203 were transfected into HCE-T cells and the WST assay was performed. To determine a direct target gene for miR-203, a dual luciferase reporter assay was performed in HCE-T cells using a luciferase reporter plasmid containing 3'-UTR of human IGFBP5. RESULTS: Microarray and qPCR analyses showed that miR-184 and miR-203 were expressed significantly more highly in tears than in sera (165,542.8- and 567.8-fold, respectively, p < 0.05). Of these two miRNAs, transfection of a miR-203 mimic significantly reduced the viability of HCE-T cells (p < 0.05), while a miR-203 inhibitor significantly increased this viability (p < 0.05). miR-203 mimic downregulated insulin-like growth factor-binding protein 5 (IGFBP5) and nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1), while miR-203 inhibitor upregulated these two genes. Transfection of IGFBP5-siRNA decreased the viability of HCE-T cells. miR-203 mimic significantly diminished the luciferase reporter activity. CONCLUSIONS: In this study, we identified miRNAs that are highly expressed in tears, and the inhibition of miR-203 increases the viability of corneal epithelial cells. Our results suggest that miR-203 contributes to regulating the homeostasis of corneal epithelial cells.


Assuntos
Córnea/citologia , Células Epiteliais/citologia , MicroRNAs , Animais , Células Cultivadas , Haplorrinos , Humanos , MicroRNAs/genética , Análise em Microsséries , RNA Interferente Pequeno , Lágrimas
3.
Nat Commun ; 12(1): 6057, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663796

RESUMO

Studies of sensory-evoked neuronal responses often focus on mean spike rates, with fluctuations treated as internally-generated noise. However, fluctuations of spontaneous activity, often organized as traveling waves, shape stimulus-evoked responses and perceptual sensitivity. The mechanisms underlying these waves are unknown. Further, it is unclear whether waves are consistent with the low rate and weakly correlated "asynchronous-irregular" dynamics observed in cortical recordings. Here, we describe a large-scale computational model with topographically-organized connectivity and conduction delays relevant to biological scales. We find that spontaneous traveling waves are a general property of these networks. The traveling waves that occur in the model are sparse, with only a small fraction of neurons participating in any individual wave. Consequently, they do not induce measurable spike correlations and remain consistent with locally asynchronous irregular states. Further, by modulating local network state, they can shape responses to incoming inputs as observed in vivo.


Assuntos
Modelos Neurológicos , Neurônios/fisiologia , Potenciais de Ação/fisiologia , Animais , Simulação por Computador , Feminino , Haplorrinos , Masculino , Modelos Animais , Córtex Visual/fisiologia
4.
Nat Commun ; 12(1): 5866, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620867

RESUMO

Type I interferon is promising in treating different kinds of tumors, but has been limited by its toxicity, lack of tumor targeting, and very short half-life. To target tumors, reduce systemic toxicity, and increase half-life, here we engineer a masked type I IFN-Fc (ProIFN) with its natural receptor connected by a cleavable linker that can be targeted by tumor-associated proteases. ProIFN has a prolonged serum half-life and shows an improved tumor-targeting effect. Interestingly, ProIFN-treated mice show enhanced DC cross-priming and significant increased CD8+ infiltration and effector function in the tumor microenvironment. ProIFN is able to improve checkpoint blockade efficacy in established tumors, as well as radiation efficacy for both primary and metastatic tumors. ProIFN exhibits superior long-term pharmacokinetics with minimal toxicity in monkeys. Therefore, this study demonstrates an effective tumor-activating IFN that can increase targeted immunity against primary tumor or metastasis and reduce periphery toxicity to the host.


Assuntos
Antineoplásicos/imunologia , Imunidade , Interferon Tipo I/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular Tumoral , Microscopia Crioeletrônica , Haplorrinos , Imunoterapia , Cinética , Camundongos , Microambiente Tumoral
5.
Primates ; 62(6): 879-886, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34515900

RESUMO

A recent debate on the taxonomic identification of the monkeys depicted in a fresco from Room 6 of Building Complex Beta in the Bronze Age town of Akrotiri, Thera (Greece) has triggered a multitude of different interpretations deriving from a fruitful exchange of diverse academic approaches. Thus, Pareja et al. (Primates 61:159-168, 2020a) identified those Aegean monkeys as Asian langurs (Semnopithecus spp.), whereas Urbani and Youlatos (Antiquity 94:e9, 2020a) and Binnberg et al. (J Gr Archaeol 6:in press, 2021) argued for the identification as African vervets (Chlorocebus spp.), and recently Pruetz and Greenlaw (Primates 62:703-707, 2021) introduced the African L'Hoest's monkeys (Allochrocebus lhoesti) and Diana monkeys (Cercopithecus diana) into the debate. This comment intends to present thoughts on the latter contention. In this context, our approach encompassed the morphological analysis of specific features of the face and torso, the cultural context of the use of the blue color for representing the Aegean monkeys, the detailed artistic rendering of Aegean painters, the geographical distribution ranges of the potential candidate monkey species, and the historical context of trading monkeys or exchanging monkey imageries in the eastern Mediterranean region and Africa. All this evidence supports our contention that vervets still represent the most parsimonious models for the monkeys depicted in Room 6. This debate, based on multidisciplinary research, stands as a constructive example for the perspectives that need to be followed for the development of archeoprimatology.


Assuntos
Cercopithecus , África , Animais , Grécia , Haplorrinos
6.
J Hum Evol ; 158: 103048, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34340120

RESUMO

Homo naledi fossils from the Rising Star cave system provide important insights into the diversity of hand morphology within the genus Homo. Notably, the pollical (thumb) metacarpal (Mc1) displays an unusual suite of characteristics including a median longitudinal crest, a narrow proximal base, and broad flaring intrinsic muscle flanges. The present study evaluates the affinities of H. naledi Mc1 morphology via 3D geometric morphometric analysis of shaft shape using a broader comparative sample (n = 337) of fossil hominins, recent humans, apes, and cercopithecoid monkeys than in prior work. Results confirm that the H. naledi Mc1 is distinctive from most other hominins in being narrow at the proximal end but surmounted by flaring muscle flanges distally. Only StW 418 (Australopithecus cf. africanus) is similar in these aspects of shape. The gracile proximal shaft is most similar to cercopithecoids, Pan, Pongo, Australopithecus afarensis, and Australopithecus sediba, suggesting that H. naledi retains the condition primitive for the genus Homo. In contrast, Neandertal Mc1s are characterized by wide proximal bases and shafts, pinched midshafts, and broad distal flanges, while those of recent humans generally have straight shafts, less robust muscle flanges, and wide proximal shafts/bases. Although uncertainties remain regarding character polarity, the morphology of the H. naledi thumb might be interpreted as a retained intermediate state in a transformation series between the overall gracility of the shaft and the robust shafts of later hominins. Such a model suggests that the addition of broad medial and lateral muscle flanges to a primitively slender shaft was the first modification in transforming the Mc1 into the overall more robust structure exhibited by other Homo taxa including Neandertals and recent Homo sapiens in whose shared lineage the bases and proximal shafts became expanded, possibly as an adaptation to the repeated recruitment of powerful intrinsic pollical muscles.


Assuntos
Fósseis , Hominidae/anatomia & histologia , Ossos Metacarpais/anatomia & histologia , Animais , Evolução Biológica , Cavernas , Haplorrinos/anatomia & histologia , Humanos , Homem de Neandertal/anatomia & histologia
7.
Mol Inform ; 40(9): e2100031, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34378348

RESUMO

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to be a global threat, causing millions of deaths worldwide. SARS-CoV-2 is an enveloped virus with spike (S) glycoproteins conferring binding to the host cell's angiotensin-converting enzyme 2 (ACE2), which is critical for cellular entry. The host range of the virus extends well beyond humans and non-human primates. Natural and experimental infections have confirmed the high susceptibility of cats, ferrets, and Syrian hamsters, whereas dogs, mice, rats, pigs, and chickens are refractory to SARS-CoV-2 infection. To investigate the underlying reason for the variable susceptibility observed in different species, we have developed molecular descriptors to efficiently analyse dynamic simulation models of complexes between SARS-CoV-2 S and ACE2. Our extensive analyses represent the first systematic structure-based approach that allows predictions of species susceptibility to SARS-CoV-2 infection.


Assuntos
SARS-CoV-2/química , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/metabolismo , Gatos , Cães , Furões , Haplorrinos , Humanos , Mesocricetus , Camundongos , Simulação de Dinâmica Molecular , Ratos , SARS-CoV-2/metabolismo , Especificidade da Espécie , Suínos
8.
Am J Phys Anthropol ; 176(3): 402-421, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34453450

RESUMO

OBJECTIVES: The presence of sexual dimorphism in the birth canals of anthropoid primates is well documented, and birth canal dimorphism tends to be especially robust among species that give birth to relatively large neonates. However, it is less clear whether birth canal dimorphism is accompanied by dimorphism in parts of the pelvis not directly under selection for birth, particularly including bi-iliac breadth, biactetabular breadth, lengths of the ischium and ilium, and 3D shape. This study investigates the patterns of dimorphism among anthropoid primates in those parts of the pelvis which do not directly contribute to the bony birth canal, here termed the non-obstetric pelvis. METHODS: 3D landmark data were collected on the bony pelves of 899 anthropoid primates. Specifically, landmark data were collected on parts of the pelvis not thought to be directly involved in selection for parturition, including portions of the posterior and superior ilium, acetabulum, and lateral ischium. Principal components analysis and Euclidean distance matrix analysis were used to ascertain sexual dimorphism in pelvic sizes and shapes within each species. RESULTS: Results show that dimorphism in non-obstetric pelvic size and shape exists across anthropoids, just as is seen in the birth canal. However, the magnitude of dimorphism in non-obstetric pelvic shape tends to be greater among anthropoid species that give birth to relatively large neonates compared with those birthing smaller neonates relative to maternal pelvic size. CONCLUSIONS: Though all anthropoids included in the study show some degree of sexual dimorphism in non-obstetric pelvic size and/or shape, species which give birth to large neonates relative to maternal pelvic size have the highest levels of dimorphism in pelvic shape. Moreover, the magnitude of dimorphism in certain parts of the non-obstetric pelvis mirrors patterns seen in the birth canal. The results of this study are promising for ascertaining pelvic dimorphism and relative neonate size in fossil primates, particularly in fragmentary remains which do not preserve a complete bony birth canal.


Assuntos
Ossos Pélvicos , Caracteres Sexuais , Animais , Haplorrinos , Humanos , Recém-Nascido , Pelve , Primatas
9.
Toxicol Appl Pharmacol ; 428: 115673, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364948

RESUMO

Pegbelfermin (PGBF) is a PEGylated fibroblast growth factor 21 (FGF21) analogue in development for treatment of nonalcoholic steatohepatitis (NASH). Mouse models highlight potential utility of FGF21 in NASH, but also suggest negative effects on bone, though these findings are confounded by profound FGF21-related decreases in body mass/growth. This study aimed to profile PGBF-related bone effects in adult nonhuman primates after long-term, clinically-relevant exposures. Adult male cynomolgus monkeys received weekly subcutaneous PGBF (0.3, 0.75 mg/kg) or control injections for 1 year (n = 5/group). Assessments included body weight, clinical chemistry, adiponectin levels, bone turnover biomarkers, skeletal radiography, pharmacokinetics, immunogenicity, and histopathology. Bone densitometry and body composition were evaluated in vivo and/or ex vivo with dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and biomechanical strength testing. After 1 year of PGBF administration, there was clear evidence of sustained PGBF pharmacology in monkeys (peak increase in serum adiponectin of 1.7× and 2.35× pretest at 0.3 and 0.75 mg/kg PGBF, respectively) and decreased body weight compared with control at exposures comparable to those tested in humans. At 0.75 mg/kg PGBF, pharmacologically-mediated reductions in lean mass, lean area, and fat area were observed relative to controls. There were no PGBF-related effects on bone biomarkers, radiography, densitometry, or strength. Together, these data demonstrate that PGBF did not adversely alter bone metabolism, density, or strength following 1 year of dosing at clinically relevant (0.7-2.2× human AUC[0-168 h] at 20 mg once weekly), pharmacologically-active exposures in adult monkeys, suggesting a low potential for negative effects on bone quality in adult humans.


Assuntos
Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/análogos & derivados , Polietilenoglicóis/administração & dosagem , Animais , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Esquema de Medicação , Fatores de Crescimento de Fibroblastos/administração & dosagem , Fatores de Crescimento de Fibroblastos/química , Haplorrinos , Macaca fascicularis , Masculino , Polietilenoglicóis/química , Fatores de Tempo
10.
Nat Commun ; 12(1): 5000, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404805

RESUMO

The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.


Assuntos
Enzima de Conversão de Angiotensina 2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/imunologia , Anticorpos Neutralizantes/administração & dosagem , COVID-19/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , COVID-19/mortalidade , COVID-19/virologia , Chlorocebus aethiops , Modelos Animais de Doenças , Epitopos , Feminino , Células HEK293 , Haplorrinos , Humanos , Macaca fascicularis , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pandemias , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Células Vero , Ativação Viral
12.
J Cogn Neurosci ; 33(5): 919-932, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34449845

RESUMO

The appearance of a salient stimulus evokes saccadic eye movements and pupil dilation as part of the orienting response. Although the role of the superior colliculus (SC) in saccade and pupil dilation has been established separately, whether and how these responses are coordinated remains unknown. The SC also receives global luminance signals from the retina, but whether global luminance modulates saccade and pupil responses coordinated by the SC remains unknown. Here, we used microstimulation to causally determine how the SC coordinates saccade and pupil responses and whether global luminance modulates these responses by varying stimulation frequency and global luminance in male monkeys. Stimulation frequency modulated saccade and pupil responses, with trial-by-trial correlations between the two responses. Global luminance only modulated pupil, but not saccade, responses. Our results demonstrate an integrated role of the SC on coordinating saccade and pupil responses, characterizing luminance independent modulation in the SC, together elucidating the differentiated pathways underlying this behavior.


Assuntos
Movimentos Sacádicos , Colículos Superiores , Animais , Haplorrinos , Masculino , Estimulação Luminosa , Pupila
13.
Stem Cell Res ; 55: 102497, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34411973

RESUMO

OBJECTIVE: In order to provide regenerative therapy for millions of patients suffering from corneal blindness globally, we derived corneal endothelial cell substitute (CECSi) cells from induced pluripotent stem cells (iPSCs) to treat corneal edema due to endothelial dysfunction (bullous keratopathy). METHODS AND RESULTS: We developed an efficient xeno-free protocol to produce CECSi cells from both research grade (Ff-MH09s01 and Ff-I01s04) and clinical grade (QHJI01s04) iPSCs. CECSi cells formed a hexagonal confluent monolayer with Na, K-ATPase alpha 1 subunit expression (ATP1A1), tight junctions, N-cadherin adherence junction formation, and nuclear PITX2 expression, which are all characteristics of corneal endothelial cells. CECSi cells can be cryopreserved, and thawed CECSi cell suspensions also expressed N-cadherin and ATP1A1. Residual undifferentiated iPSCs in QHJI01s04-derived CECSi cells was below 0.01%. Frozen stocks of Ff-I01s04- and QHJI01s04-derived CECSi cells were transported, thawed and transplanted into a monkey corneal edema model. CECSi-transplanted eyes significantly reduced corneal edema compared to control group. CONCLUSION: Our results show a promising approach to provide bullous keratopathy patients with an iPS-cell-based cell therapy to recover useful vision.


Assuntos
Edema da Córnea , Células-Tronco Pluripotentes Induzidas , Animais , Edema da Córnea/terapia , Células Endoteliais , Endotélio Corneano , Haplorrinos , Humanos
14.
Br J Anaesth ; 127(3): 343-345, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34272059

RESUMO

Whether anaesthesia exposure early in life leads to brain damage with long-lasting structural and behavioural consequences in primates has not been conclusively determined. A study in the British Journal of Anaesthesia by Neudecker and colleagues found that 2 yr after early anaesthesia exposure, monkeys exhibited signs of chronic astrogliosis which correlate with behavioural deficits. Given the increasing frequency of exposure to anaesthetics in infancy in humans, clinical trials are greatly needed to understand how sedative/anaesthetic agents may be impacting brain and behaviour development.


Assuntos
Anestesia , Anestésicos , Síndromes Neurotóxicas , Animais , Haplorrinos , Síndromes Neurotóxicas/etiologia , Fenótipo
15.
Behav Neurosci ; 135(3): 443-452, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34264694

RESUMO

The evolutionary and neural underpinnings of human prosociality are still being identified. A growing body of evidence suggests that some species find the sight of another individual receiving a reward reinforcing, called vicarious reinforcement, and that this capacity is supported by a network of brain areas including the anterior cingulate cortex (ACC) and the amygdala. At the same time, analyses of autonomic arousal have been increasingly used to contextualize and guide neural research, especially for studies of reward processing. Here, we characterized the autonomic pupil response of eight monkeys across two laboratories in two different versions of a vicarious reinforcement paradigm. Monkeys were cued as to whether an upcoming reward would be delivered to them, another monkey, or nobody and could accept or decline the offer. As expected, all monkeys in both laboratories showed a marked preference for juice to the self, together with a reliable prosocial preference for juice to a social partner compared to juice to nobody. However, contrary to our expectations, we found that pupils were widest in anticipation of juice to the self, moderately sized in anticipation of juice to nobody, and narrowest in anticipation of juice to a social partner. This effect was seen across both laboratories and regardless of specific task parameters. The seemingly paradoxical pupil effect can be explained by a model in which pupil size tracks outcome salience, prosocial tendencies track outcome valence, and the relation between salience and valence is U-shaped. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Assuntos
Nível de Alerta , Recompensa , Animais , Mapeamento Encefálico , Giro do Cíngulo , Haplorrinos , Imageamento por Ressonância Magnética
16.
Am J Phys Anthropol ; 176(3): 390-401, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34297357

RESUMO

OBJECTIVES: Previous studies have shown that frugivorous anthropoids have wider incisors than folivores relative to body mass, and that catarrhines have relatively wider incisors than platyrrhines. This study reexamines these contrasts using mandibular length as a biomechanical standard to quantify relative incisor width. MATERIALS AND METHODS: Dental, mandibular, and body-mass data for 86 anthropoid species were taken from the literature. Incisor width was size-adjusted using shape ratios, with mandibular length and body mass as the denominators. Dietary and phylogenetic effects were examined using phylogenetic generalized least squares. RESULTS: Mandible-based ratios provide a signal that is very similar to the one derived from ratios computed using body mass. Frugivores have relatively wider incisors than folivores, as expected. There is limited support for a stronger dietary effect in platyrrhines when mandible-based ratios are used, but neither type of ratio indicates an overall difference between platyrrhines and catarrhines. DISCUSSION: Although both ratios support a link between incisor size and diet, there is some evidence indicating that mandible-based ratios are more sensitive to dietary variation at smaller phylogenetic scales. Understanding why the signals from the two ratios diverge at such scales may help clarify the functional significance of variation in incisor width. The results of this study undermine the view that platyrrhines, as a group, tend to have narrower incisors than catarrhines, regardless of diet. Instead, the difference between the two clades noted in previous studies can be explained by greater incisor functional diversity in platyrrhines.


Assuntos
Dieta , Incisivo , Animais , Haplorrinos , Mandíbula , Filogenia
17.
Sci Rep ; 11(1): 14819, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285293

RESUMO

Blindsight is the residual visuo-motor ability without subjective awareness observed after lesions of the primary visual cortex (V1). Various visual functions are retained, however, instrumental visual associative learning remains to be investigated. Here we examined the secondary reinforcing properties of visual cues presented to the hemianopic field of macaque monkeys with unilateral V1 lesions. Our aim was to test the potential role of visual pathways bypassing V1 in reinforcing visual instrumental learning. When learning the location of a hidden area in an oculomotor search task, conditioned visual cues presented to the lesion-affected hemifield operated as an effective secondary reinforcer. We noted that not only the hidden area location, but also the vector of the saccade entering the target area was reinforced. Importantly, when the visual reinforcement signal was presented in the lesion-affected field, the monkeys continued searching, as opposed to stopping when the cue was presented in the intact field. This suggests the monkeys were less confident that the target location had been discovered when the reinforcement cue was presented in the affected field. These results indicate that the visual signals mediated by the residual visual pathways after V1 lesions can access fundamental reinforcement mechanisms but with impaired visual awareness.


Assuntos
Córtex Visual/fisiologia , Vias Visuais/fisiologia , Percepção Visual/fisiologia , Animais , Condicionamento Operante/fisiologia , Haplorrinos , Masculino
18.
Cell ; 184(16): 4203-4219.e32, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34242577

RESUMO

SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.


Assuntos
Anticorpos Neutralizantes/imunologia , SARS-CoV-2/fisiologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Antivirais/imunologia , Líquido da Lavagem Broncoalveolar/química , COVID-19/patologia , COVID-19/virologia , Citocinas/metabolismo , Feminino , Haplorrinos , Humanos , Pulmão/patologia , Pulmão/virologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Domínios Proteicos , RNA Guia/metabolismo , Receptores de IgG/metabolismo , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/química , Carga Viral , Replicação Viral
19.
Sci Rep ; 11(1): 14196, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244546

RESUMO

Life history, brain size and energy expenditure scale with body mass in mammals but there is little conclusive evidence for a correlated evolution between life history and energy expenditure (either basal/resting or daily) independent of body mass. We addressed this question by examining the relationship between primate free-living daily energy expenditure (DEE) measured by doubly labeled water method (n = 18 species), life history variables (maximum lifespan, gestation and lactation duration, interbirth interval, litter mass, age at first reproduction), resting metabolic rate (RMR) and brain size. We also analyzed whether the hypometabolic primates of Madagascar (lemurs) make distinct energy allocation tradeoffs compared to other primates (monkeys and apes) with different life history traits and ecological constraints. None of the life-history traits correlated with DEE after controlling for body mass and phylogeny. In contrast, a regression model showed that DEE increased with increasing RMR and decreasing reproductive output (i.e., litter mass/interbirth interval) independent of body mass. Despite their low RMR and smaller brains, lemurs had an average DEE remarkably similar to that of haplorhines. The data suggest that lemurs have evolved energy strategies that maximize energy investment to survive in the unusually harsh and unpredictable environments of Madagascar at the expense of reproduction.


Assuntos
Encéfalo/fisiologia , Metabolismo Energético , Animais , Metabolismo Basal , Feminino , Haplorrinos/fisiologia , Hominidae/fisiologia , Lemur/fisiologia , Traços de História de Vida , Longevidade , Masculino , Tamanho do Órgão , Primatas , Reprodução , Especificidade da Espécie
20.
Neuroimage ; 241: 118414, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34298082

RESUMO

Activity observed in biological neural networks is determined by anatomical connectivity between cortical areas. The monkey frontoparietal network facilitates cognitive functions, but the organization of its connectivity is unknown. Here, a new connectivity matrix is proposed which shows that the network utilizes a small-world architecture and the 3-node M9 motif. Its areas exhibit relatively homogeneous connectivity with no suggestion of the hubs seen in scale-free networks. Crucially, its M9 dynamical relay motif is optimally arranged for near-zero and non-zero phase synchrony to arise in support of cognition, serving as a candidate topological mechanism for previously reported findings. These results can serve as a benchmark to be used in the treatment of neurological disorders where the types of cognition the frontoparietal network supports are impaired.


Assuntos
Lobo Frontal/fisiologia , Macaca/fisiologia , Rede Nervosa/fisiologia , Redes Neurais de Computação , Lobo Parietal/fisiologia , Animais , Haplorrinos , Especificidade da Espécie
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