Present situation and progress of xenotransplantation at home and abroad / 器官移植

Organ shortage has become one of the major challenges hindering the development of organ transplantation. Xenotransplantation is one of the most valuable methods to resolve global organ shortage. In recent years, the development of genetic engineering technique and research and development of new immunosuppressant have provided novel theoretical basis for xenotransplantation. International scholars have successively carried out researches on xenotransplantation in genetically modified pigs to non-human primates or brain death recipients, making certain substantial progresses. However, most of the researches are still in the preclinical stage, far from clinical application. Therefore, according to the latest preclinical experimental research progress at home and abroad, the history of xenotransplantation, the development of gene modification technology, xenotransplantation rejection and immunosuppression regimens were reviewed, aiming to provide reference for subsequent research of xenotransplantation, promote clinical application of xenotransplantation and bring benefits to more patients with end-stage diseases.

Application of xenotransplantation in clinical practice / 器官移植

Organ transplantation is the optimal treatment for end-stage organ failure. Nevertheless, organ shortage is a global problem, which limits further development of organ transplantation. Recent research shows that genetically modified pig may become a realistic alternative source of clinical organ transplantation donor. Xenotransplantation may serve as one of the effective measures to resolve the problem of organ shortage. Since 2021, 2 cases of living xenotransplantation and 6 cases of xenotransplantation in brain death recipients have been performed worldwide, and phase Ⅰ clinical trial of xenotransplantation has been launched, and the results have exceeded expectations. Therefore, in this article, recent clinical trial results of xenotransplantation in living and brain death recipients were retrospectively analyzed, and scientific, technical and ethical issues related to clinical research of xenotransplantation were illustrated, hoping to provide reference for clinical research of xenotransplantation in China and promote the development of xenotransplantation in clinical practice.

Progress in subclinical research of kidney xenotransplantation / 器官移植

Xenotransplantation is an efficient pathway to solve the problem of transplant organ source deficiency in clinical settings. With the increasing progress of gene editing technique and immune suppression regimen, important development has been achieved on researches regarding pig to non-human primate kidney xenotransplantation, which provides a good condition for the introduction of the technique in the clinical application. In view of the substantial difference between human and non-human primate, and to meet the needs of current ethic requirements, it is necessary to perform subclinical studies for pig to human kidney xenotransplantation. In recent years, such subclinical studies with regard to the genetically modified pig to brain death recipient kidney xenotransplantation had been performed, indicating that kidney xenotransplantation gradually began to transit to the clinical development stage. However, donor/recipient selection and immune suppression regimen has not reached a consensus yet, and has to be clarified in subclinical studies. In this article, the current status and confronted problems of donor/recipient selection, immune suppression regimen and post transplantation management in the subclinical studies of kidney xenotransplantation were reviewed, aiming to promote the clinical transformation of kidney xenotransplantation to the clinical application.

Neural Correlates of Spatial Navigation in Primate Hippocampus / 神经科学通报·英文版

The hippocampus has been extensively implicated in spatial navigation in rodents and more recently in bats. Numerous studies have revealed that various kinds of spatial information are encoded across hippocampal regions. In contrast, investigations of spatial behavioral correlates in the primate hippocampus are scarce and have been mostly limited to head-restrained subjects during virtual navigation. However, recent advances made in freely-moving primates suggest marked differences in spatial representations from rodents, albeit some similarities. Here, we review empirical studies examining the neural correlates of spatial navigation in the primate (including human) hippocampus at the levels of local field potentials and single units. The lower frequency theta oscillations are often intermittent. Single neuron responses are highly mixed and task-dependent. We also discuss neuronal selectivity in the eye and head coordinates. Finally, we propose that future studies should focus on investigating both intrinsic and extrinsic population activity and examining spatial coding properties in large-scale hippocampal-neocortical networks across tasks.

Single-nucleus transcriptomics reveals a gatekeeper role for FOXP1 in primate cardiac aging

Aging poses a major risk factor for cardiovascular diseases, the leading cause of death in the aged population. However, the cell type-specific changes underlying cardiac aging are far from being clear. Here, we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age. We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profiles. Via transcription regulatory network analysis, we identified FOXP1, a core transcription factor in organ development, as a key downregulated factor in aged cardiomyocytes, concomitant with the dysregulation of FOXP1 target genes associated with heart function and cardiac diseases. Consistently, the deficiency of FOXP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes. Altogether, our findings depict the cellular and molecular landscape of ventricular aging at the single-cell resolution, and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.

Single-nucleus profiling unveils a geroprotective role of the FOXO3 in primate skeletal muscle aging

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia, and increases the risk of many aging-related metabolic diseases. Here, we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging. A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types, indicating a higher susceptibility of skeletal muscle fiber to aging. We found a downregulation of FOXO3 in aged primate skeletal muscle, and identified FOXO3 as a hub transcription factor maintaining skeletal muscle homeostasis. Through the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model, we revealed that silence of FOXO3 accelerates human myotube senescence, whereas genetic activation of endogenous FOXO3 alleviates human myotube aging. Altogether, based on a combination of monkey skeletal muscle and human myotube aging research models, we unraveled the pivotal role of the FOXO3 in safeguarding primate skeletal muscle from aging, providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-related disorders.

Kidney xenotransplantation: status quo and development trend of physiological research / 器官移植

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D3 of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

A non-human primate derived anti-P-selectin glycoprotein ligand-1 antibody curtails acute pancreatitis by alleviating the inflammatory responses

Acute pancreatitis (AP) is a devastating disease characterized by an inflammatory disorder of the pancreas. P-selectin glycoprotein ligand-1 (PSGL-1) plays a crucial role in the initial steps of the adhesive at process to inflammatory sites, blockade of PSGL-1 might confer potent anti-inflammatory effects. In this study, we generated two non-human primate derived monoclonal antibodies capable of efficiently targeting human PSGL-1, RH001-6 and RH001-22, which were screened from immunized rhesus macaques. We found that RH001-6, can effectively block the binding of P-selectin to PSGL-1, and abolish the adhesion of leukocytes to endothelial cells in vitro. In vivo, we verified that RH001-6 relieved inflammatory responses and pancreatic injury in both caerulein and l-arginine induced AP models. We also evaluated the safety profile after RH001-6 treatment in mice, and verified that RH001-6 did not cause any significant pathological damages in vivo. Taken together, we developed a novel non-human primate derived PSGL-1 blocking antibody with high-specificity, named RH001-6, which can interrupt the binding of PSGL-1 and P-selectin and attenuate inflammatory responses during AP. Therefore, RH001-6 is highly potential to be further developed into therapeutics against acute inflammatory diseases, such as AP.

A single-nucleus transcriptomic atlas of primate testicular aging reveals exhaustion of the spermatogonial stem cell reservoir and loss of Sertoli cell homeostasis

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases.

Genetic Approaches for Neural Circuits Dissection in Non-human Primates / 神经科学通报·英文版

Genetic tools, which can be used for the morphology study of specific neurons, pathway-selective connectome mapping, neuronal activity monitoring, and manipulation with a spatiotemporal resolution, have been widely applied to the understanding of complex neural circuit formation, interactions, and functions in rodents. Recently, similar genetic approaches have been tried in non-human primates (NHPs) in neuroscience studies for dissecting the neural circuits involved in sophisticated behaviors and clinical brain disorders, although they are still very preliminary. In this review, we introduce the progress made in the development and application of genetic tools for brain studies on NHPs. We also discuss the advantages and limitations of each approach and provide a perspective for using genetic tools to study the neural circuits of NHPs.

Comparative study between S-(+)-ketamine­midazolam and fentanyl­droperidol in black-tufted marmosets (Callithrix penicillata) / Estudo comparativo entre S-(+)cetamina-midazolam e fentanil-droperidol em saguis-de-tufo-preto (Callithrix penicillata)

Sedative and antinociceptive effects of two anesthetic protocols in black-tufted marmosets were compared in this study. Twenty-six marmosets underwent chemical immobilization for physical examination, blood sampling, tattooing, and microchipping. Animals were randomly treated with S-(+)-ketamine (10 mg/kg) and midazolam (1 mg/kg) (KM) or fentanyl (12.5 µg/kg) and droperidol (625 µg/kg) (FD) given by intramuscular injection. Heart and respiratory rates were recorded. Sedation, antinociception, muscle relaxation, posture, auditory, and visual responses were evaluated using a scoring system. Sedation in KM was achieved faster (p < 0.001) and lasted for a shorter period of time (p = 0.0009). KM was similar to FD in its cardiorespiratory effects, auditory and visual responses. Both protocols promoted adequate sedation to allow manipulation. Animals in KM assumed lateral recumbency while animals in FD maintained a quadrupedal posture during evaluation. FD produced less intense sedation and muscle relaxation but a higher degree of antinociception compared to KM and is suitable for procedures that require analgesia in black-tufted marmosets.(AU)

O presente estudo comparou os efeitos cardiorrespiratórios, sedativos e antinociceptivos de dois protocolos anestésicos em saguis-de-tufo-preto (Callithrix penicillata). Vinte e seis saguis foram submetidos à contenção química para exame físico, coleta de sangue, tatuagem de identificação e microchip. Os animais foram tratados aleatoriamente com a associação de S-(+)-cetamina (10 mg/kg) e midazolam (1 mg/kg) (KM) ou fentanil (12,5 µg/kg) e droperidol (625 µg/kg) (FD), administrados por injeção intramuscular. Foram avaliadas frequência cardíaca, frequência respiratória, sedação, antinocicepção, relaxamento muscular, postura e resposta ao estímulo auditivo e visual. A sedação em KM foi alcançada mais rapidamente (p <0,001) e teve um tempo hábil mais curto (p = 0,0009). KM foi semelhante a FD nos efeitos cardiorrespiratórios, respostas auditivas e visuais. Os dois protocolos promoveram sedação adequada para manipulação. Os animais do grupo KM permaneceram em decúbito lateral durante a avaliação, enquanto os animais em FD mantiveram postura quadrupedal. FD resultou em sedação e relaxamento muscular de menor intensidade, porém com maior escore de antinocicepção em comparação com KM, sendo adequada para procedimentos que requerem analgesia em saguis-de-tufo-preto.(AU)

Fast surveillance response reveals the introduction of a new yellow fever virus sub-lineage in 2021, in Minas Gerais, Brazil

BACKGROUND In Brazil, the yellow fever virus (YFV) is maintained in a sylvatic cycle involving wild mosquitoes and non-human primates (NHPs). The virus is endemic to the Amazon region; however, waves of epidemic expansion reaching other Brazilian states sporadically occur, eventually causing spillovers to humans. OBJECTIVES To report a surveillance effort that led to the first confirmation of YFV in NHPs in the state of Minas Gerais (MG), Southeast region, in 2021. METHODS A surveillance network was created, encompassing the technology of smartphone applications and coordinated actions of several research institutions and health services to monitor and investigate NHP epizootics. FINDINGS When alerts were spread through the network, samples from NHPs were collected and YFV infection confirmed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and genome sequencing at an interval of only 10 days. Near-complete genomes were generated using the Nanopore MinION sequencer. Phylogenetic analysis indicated that viral genomes were related to the South American genotype I, clustering with a genome detected in the Amazon region (state of Pará) in 2017, named YFVPA/MG sub-lineage. Fast YFV confirmation potentialised vaccination campaigns. MAIN CONCLUSIONS A new YFV introduction was detected in MG 6 years after the beginning of the major outbreak reported in the state (2015-2018). The YFV strain was not related to the sub-lineages previously reported in MG. No human cases have been reported, suggesting the importance of coordinated surveillance of NHPs using available technologies and supporting laboratories to ensure a quick response and implementation of contingency measures to avoid YFV spillover to humans.

Estado actual de Cheracebus sp. (Primates: Pitheciidae) y de su hábitat entrelos ríos Tigre y Nanay, Amazonía peruana / Current status of Cheracebus sp. (Primates: Pitheciidae) and of its habitat between the Tigre and Nanay rivers, Peruvian Amazon

Resumen Con excepción de los bosques de la cuenca del río Itaya, área de influencia de la carretera Iquitos-Nauta y cuenca media de los ríos Nanay y Tigre, no hay información sobre el estado actual de la población y hábitat de Cheracebus sp., lo que motivó el desarrollo de este estudio cuyos objetivos estuvieron orientados a obtener más información sobre el estado actual de esta especie. Para ello, de mayo a noviembre del 2019 se realizaron censos por transecto lineal en bosques de las cuencas de los ríos Itaya, Nanay y Tigre. En 1659 km de longitud recorrida se avistaron 32 grupos de Cheracebus sp., de ellos, 17 correspondieron a la cuenca del río Nanay. Grupos con cuatro individuos se avistaron con más frecuencia en la cuenca del río Nanay; la abundancia relativa y la densidad poblacional fue ligeramente mayor en la cuenca del río Itaya con 0.3 grupos/10 km y 4.2 individuos/km2. En el área de estudio, los bosques están muy perturbados desde las orillas de los ríos y quebradas hasta aproximadamente 0.7 km al interior. La baja densidad poblacional de Cheracebus sp. es consecuencia de la alta presión de caza, en particular en la cuenca del río Tigre; a ella se suma la alta perturbación de los bosques por la extracción de árboles maderables y otros recursos, lo que estaría ocasionando escasez de recursos alimenticios para éste y otros primates.

Abstract With the exception of the forests of the Itaya river basin, the area of influence of the Iquitos-Nauta highway and the middle basin of the Nanay and Tigre rivers, there is no information on the current status of Cheracebus sp. populations and habitat, which motivated this study. The objectives were aimed at obtaining more information on Cheracebus sp. and the state of its populations. Linear transect censuses were conducted from May to November 2019 in forests of the Itaya, Nanay and Tigre river basins. In 1659 km of covered length, 32 groups were sighted; of them, 17 corresponded to the Nanay river basin. Groups with four individuals were seen more frequently in the Nanay river basin; relative abundance and population density were slightly higher in the Itaya river basin with 0.3 groups/ 10 km and 4.2 individuals/ km2. In the study area, forests are highly disturbed from the banks of rivers and streams up to approximately 0.7 km inland. The low population density of Cheracebus sp. is a consequence of high hunting pressure, particularly in the Tigre river basin; added to this is the high disturbance of the forests due to the extraction of timber trees and other resources; which would be causing a shortage of food resources for this and other primates.

Single-nucleus transcriptomic landscape of primate hippocampal aging

The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

Endometritis supurativa en una tití gris (Saguinus leucopus) en cautiverio: / Suppurative endometritis in a captive white-footed tamarin (Saguinus leucopus):

Resumen La endometritis es la inflamación del revestimiento interno del útero producida por distintos agentes infecciosos. Puede presentarse de forma clínica o subclínica, y tener curso agudo o crónico. Este documento describe el caso de una hembra de tití gris (Saguinus leucopus) en proceso de rehabilitación en la Unidad de Rescate y Rehabilitación de Animales Silvestres (URRAS), que manifestó enfermedad uterina, y cuyos hallazgos fueron compatibles con endometritis supurativa. No se conocen otros reportes de la patología en calitrícidos. Por tal motivo, se propone adelantar investigaciones que determinen los factores de riesgo en la presentación de estas enfermedades reproductivas, y para estandarizar pruebas paraclínicas que mejoren su diagnóstico en pequeños primates, teniendo en cuenta la escasa información disponible para la especie afectada y las repercusiones en su conservación.

Abstract Endometritis is inflammation of the intern uterus lining caused by different infectious microorganisms, and it can be clinical or subclinical and have an acute or chronic path. This paper describes the case of a female white-footed tamarin (Saguinus leucopus) in rehabilitation from the Unidad de Rescate y Rehabilitacion de Animales Silvestres (URRAS), that presented a uterus disease and the pathological findings were compatible with suppurative endometritis. There are no reports of endometritis in Callitrichidae, suggesting that more studies need to be done to determine the risk factors in the presentation of these reproductive diseases and to standardize paraclinical tests that improve their diagnosis in small primates, taking into account the limited information available for the affected species and the implications for its conservation.

Vascularization of the Alouatta belzebul brain base / Vascularização da base do encéfalo de Alouatta belzebul

We studied the arterial circle in the brain of five specimens of the Alouatta belzebul primate. The material had the arterial system perfused (water at 40°C), injected with stained latex (Neoprene 650), fixed in aqueous formaldehyde solution (10%) and dissected for vessel verification. The arterial circle of this primate is composed of two vascular systems: the vertebra-basilar and the carotid ones, which anastomose to close the arterial circuit. In the caudal portion of the arterial circle, there are the vertebral arteries and their branches: the rostral spinal artery and the caudal inferior cerebellar artery. The anastomosis of the vertebral arteries gives rise to the basilar artery. It presented an anatomical variation at the beginning of its path, forming a double basilar artery, called arterial island. In its course, it emitted branches giving rise to the rostral inferior cerebellar artery, the pontine arteries, the rostral cerebellar arteries, the satellite rostral cerebellar arteries and its terminal branch, the caudal cerebral artery, which presented itself in two segments: the pre-communicating one and post-communicating, joining the internal carotid artery and originating the caudal communicating artery. This group of arteries and anastomoses enclose the caudal portion of the arterial circle. From the right and left internal carotid arteries begins the rostral portion of the arterial circle, which consists of the right and left rostral cerebral arteries and the right and left middle cerebral arteries. The rostral cerebral arteries anastomose into a single trunk, giving rise to the interhemispheric artery, and in A. belzebul and Sapajus libidinosus, the rostral communicating artery is absent. The interhemispheric artery goes to the midbrain region and the corpus callosum knee divides into pericalous artery and callosarginal artery, which will supply the pre and post-central regions of the cerebral hemispheres of this species, as well as other non-human and human primates. It is noted that in the first part of the left rostral cerebral artery, there is a direct inosculation between the recurrent branch of the rostral cerebral artery and left middle cerebral artery to supply the entorhinal region. This fact also occurs in Pongo spp. The middle cerebral artery travels along the lateral sulcus where it emits several superficial branches to irrigate the superior and inferior lateral cortical regions of the frontal, parietal and temporal lobes. It is not part of the arterial circle but is the terminal branch of the internal carotid artery. A. belzebul can be considered to depend on two sources of supply to the brain: the vertebra-basilar and carotid systems, contributing to the intervention of veterinarians during clinical and surgical procedures in other primates, as well as the preservation of wild animals.(AU)

Estudamos o círculo arterial no encéfalo de cinco espécimes do primata Alouatta belzebul. O material teve o sistema arterial perfundido (água a 40°C), injetado com látex corado (Neoprene 650), fixado em solução aquosa de formaldeído (10%) e dissecado para verificação dos vasos. O círculo arterial deste primata é composto por dois sistemas vasculares: vértebro-basilar e o sistema carotídeo, que se anastomosam para fechar o circuito arterial. Na porção caudal do círculo arterial encontra-se as artérias vertebrais e seus ramos: artéria espinal rostral e a cerebelar inferior caudal. A anastomose das artérias vertebrais dá origem a artéria basilar. Esta apresentou uma variação anatômica no início do seu trajeto, formando uma dupla artéria basilar, denominada ilha arterial. Em seu trajeto emitiu ramos dando origem a artéria cerebelar inferior rostral, as artérias pontinas, as artérias cerebelares rostrais, as artérias cerebelares rostrais satélites e o seu ramo terminal, a artéria cerebral caudal, que apresentou-se em dois segmentos: o pré-comunicante e pós-comunicante, unindo-se a artéria carótida interna e originando a artéria comunicante caudal. Este grupo de artérias e anastomoses encerram a porção caudal do círculo arterial. Das artérias carótidas internas direita e esquerda, inicia-se a porção rostral do círculo arterial, ao qual é constituído pelas artérias cerebrais rostrais direita e esquerda e as artérias cerebrais médias direita e esquerda. As artérias cerebrais rostrais se anastomosam em um tronco único dando origem a artéria inter-hemisférica e em A. belzebul e Sapajus libidinosus, a artéria comunicante rostral se encontra ausente. A artéria inter-hemisférica segue para região média do encéfalo e no joelho do corpo caloso se divide em artéria pericalosa e artéria calosomarginal, que vão suprir as regiões pré e pós-central dos hemisférios cerebrais desta espécie, assim como outros primatas não humanos e humano. Nota-se que na primeira parte da artéria cerebral rostral esquerda, ocorre uma inosculação direta entre o ramo recorrente da artéria cerebral rostral e artéria cerebral média esquerda para suprir a região entorrinal, esse fato também ocorre em Pongo spp. A artéria cerebral média segue seu trajeto pelo sulco lateral onde emite vários ramos superficiais para irrigar as regiões corticais supero e ínfero lateral do lobo frontal, parietal e temporal, esta não faz parte do círculo arterial mas é o ramo terminal da artéria carótida interna. Pode-se considerar que A. belzebul depende de duas fontes de suprimento para o encéfalo: os sistemas vértebro-basilar e carotídeo, contribuindo na intervenção de médicos veterinários durante os procedimentos clínicos e cirúrgicos em outros primatas, assim como na preservação de animais silvestres.(AU)

Fragment shape and size, landscape permeability and fragmentation level as predictors of primate occupancy in a region of Brazilian Cerrado

Human activities result in the formation of a mosaic of forest patches within a non-habitat matrix. The response of the local biodiversity to changes in land-use may occur at different scales. It is important to evaluate the effects of the attributes of both the patches and the surrounding landscape on the occupancy of forest patches by animal populations. Here, we assessed the predictive potential of local (basal area, tree density), patch (size, shape) and landscape scale (total area of forest, number of patches, matrix permeability, patch proximity) variables on the occupancy of forest patches by the syntopic primates Alouatta caraya, Sapajus libidinosus and Callithrix penicillata in the city of Goiânia in the Cerrado region of central Brazil. We used playback to survey primate populations in 22 focal patches and assessed the landscape within a 1000 m buffer zone around each site. In A. caraya, occupancy was influenced by the shape of the focal patches, the amount of forest and fragmentation level of the landscape. Focal patch size and the permeability of the matrix were the principal determinants of the occupancy of S. libidinosus. None of the predictors influenced patch occupancy in C. penicillata, and the structure of the vegetation did not influence occupancy in any of the species. The preservation of as many forest patches as possible, both large and small, as well as gallery forests, and the enhancement of matrix permeability will be essential for the long-term conservation of the syntopic primates of the Cerrado of central Brazil.

Generation of a Hutchinson-Gilford progeria syndrome monkey model by base editing

Many human genetic diseases, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by single point mutations. HGPS is a rare disorder that causes premature aging and is usually caused by a de novo point mutation in the LMNA gene. Base editors (BEs) composed of a cytidine deaminase fused to CRISPR/Cas9 nickase are highly efficient at inducing C to T base conversions in a programmable manner and can be used to generate animal disease models with single amino-acid substitutions. Here, we generated the first HGPS monkey model by delivering a BE mRNA and guide RNA (gRNA) targeting the LMNA gene via microinjection into monkey zygotes. Five out of six newborn monkeys carried the mutation specifically at the target site. HGPS monkeys expressed the toxic form of lamin A, progerin, and recapitulated the typical HGPS phenotypes including growth retardation, bone alterations, and vascular abnormalities. Thus, this monkey model genetically and clinically mimics HGPS in humans, demonstrating that the BE system can efficiently and accurately generate patient-specific disease models in non-human primates.

Acute effects of ayahuasca in a juvenile non-human primate model of depression

Objective: The incidence rate of major depression in adolescents reaches approximately 14%. This disorder is usually recurrent, without remission of symptoms even after pharmacological treatment, and persists throughout adult life. Since the effects of antidepressants take approximately 2 weeks to begin, new pharmacological therapies are under continuous exploration. Recent evidence suggests that psychedelics could produce rapid antidepressant effects. In this study, we evaluated the potential antidepressant effects of ayahuasca in a juvenile non-human primate model of depression. Methods: While living with their families, juvenile marmosets (8 males; 7 females) were observed on alternate days for four weeks during a baseline phase. This was followed by 8 weeks of an induced depressive state protocol, the social isolated context (IC), in which the animals were monitored in the first and last weeks. Subsequently, five males and four females were randomly selected for treatment, first with a single administration of saline vehicle (1.67 mL/300 g of body weight, via gavage), followed by a single dose of ayahuasca (1.67 mL/300 g of body weight, via gavage). Both phases lasted 1 week and the animals were monitored daily. A third week of sampling was called the tardive-pharmacological effects phase. In all phases the marmosets were assessed for behavior, fecal cortisol levels, and body weight. Results: After IC, the animals presented typical hypocortisolemia, but cortisol recovered to baseline levels 24 h after an acute dose of ayahuasca; this recovery was not observed in vehicle-treated animals. Additionally, in males, ayahuasca, but not the vehicle, reduced scratching, a stereotypic behavior, and increased feeding. Ayahuasca treatment also improved body weight to baseline levels in both sexes. The ayahuasca-induced behavioral response had long-term effects (14 days). Thus, in this translational juvenile animal model of depression, ayahuasca presented beneficial effects. Conclusions: These results can contribute to the validation of ayahuasca as an antidepressant drug and encourage new studies on psychedelic drugs as a tool for treating mood disorders, including for adolescents with early-onset depression.

First report of Gongylonema sp. in a free ranging callitrichid from the Brazilian Atlantic Forest: case report / Primeiro relato de Gongylonema sp. em um calitriquídeo de vida livre proveniente da Mata Atlântica brasileira: relato de caso

This is the first report of parasitism by Gongylonema sp. in a free-ranging callitrichid from the Atlantic forest of Espírito Santo, Brazil. A juvenile male of Geoffroy's marmoset (Callithrix geoffroyi) was euthanized due to poor prognosis, then necropsied. Samples of the tongue were collected for routine histological processing. Microscopically, there were transversal sections of adult nematodes within the epithelial layer of the mucosa of the tongue. Lingual scraping demonstrated a small number of oval embryonated eggs with a thick capsule. The morphology of the adult parasites and the eggs, associated with its location, were compatible with the Spirurida nematode of the genus Gongylonema. Further studies are needed to evaluate the impact of this parasite on free-ranging callitrichid populations.(AU)

Este é o primeiro relato de parasitismo por Gongylonema sp. em um calitriquídeo de vida livre proveniente da Mata Atlântica do Espírito Santo, Brasil. Um sagui-da-cara-branca (Callithrix geoffroyi), macho, jovem, foi eutanasiado, devido a prognóstico desfavorável, e necropsiado. Fragmentos de língua foram coletados para processamento histológico de rotina. Microscopicamente, havia cortes transversais de nematoides adultos na mucosa da língua. Na raspagem da mucosa da língua, foi observada pequena quantidade de ovos larvados ovais com cápsula espessa. A morfologia do parasita adulto e dos ovos, associada à localização do agente, é compatível com nematoide Spirurida do gênero Gongylonema. São necessários estudos adicionais para avaliar o impacto desse parasito nas populações de calitriquídeos de vida livre.(AU)