Explore the vast range of titles available.

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (bodymass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use.

Comparative studies have identified a wide range of behavioural and ecological correlates of relative brain size, with results differing between taxonomic groups, and even within them. In primates for example, recent studies contradict one another over whether social or ecological factors are critical. A basic assumption of such studies is that with sufficiently large samples and appropriate analysis, robust correlations indicative of selection pressures on cognition will emerge. We carried out a comprehensive re-examination of correlates of primate brain size using two large comparative datasets and phylogenetic comparative methods. We found evidence in both datasets for associations between brain size and ecological variables (home range size, diet and activity period), but little evidence for an effect of social group size, a correlation which has previously formed the empirical basis of the Social Brain Hypothesis. However, reflecting divergent results in the literature, our results exhibited instability across datasets, even when they were matched for species composition and predictor variables. We identify several potential empirical and theoretical difficulties underlying this instability and suggest that these issues raise doubts about inferring cognitive selection pressures from behavioural correlates of brain size.

Rationale: Zolpidem is a positive allosteric modulator of gamma -aminobutyric acid (GABA) with preferential binding affinity and efficacy for alpha 1-subunit containing GABA sub(A) receptors ( alpha 1-GABA sub(A)Rs). Over the last three decades, a variety of animal models and experimental procedures have been used in an attempt to relate the behavioral profile of zolpidem and classic benzodiazepines (BZs) to their interaction with alpha 1-GABA sub(A)Rs. Objectives: This paper reviews the results of rodent and non-human primate studies that have evaluated the effects of zolpidem on motor behaviors, anxiety, memory, food and fluid intake, and electroencephalogram (EEG) sleep patterns. Also included are studies that examined zolpidem's discriminative, reinforcing, and anticonvulsant effects as well as behavioral signs of tolerance and withdrawal. Results: The literature reviewed indicates that alpha 1-GABA sub(A)Rs play a principle role in mediating the hypothermic, ataxic-like, locomotor- and memory-impairing effects of zolpidem and BZs. Evidence also suggests that alpha 1-GABA sub(A)Rs play partial roles in the hypnotic, EEG sleep, anticonvulsant effects, and anxiolytic-like of zolpidem and diazepam. These studies also indicate that alpha 1-GABA sub(A)Rs play a more prominent role in mediating the discriminative stimulus, reinforcing, hyperphagic, and withdrawal effects of zolpidem and BZs in primates than in rodents. Conclusions: The psychopharmacological data from both rodents and non-human primates suggest that zolpidem has a unique pharmacological profile when compared with classic BZs. The literature reviewed here provides an important framework for studying the role of different GABA sub(A)R subtypes in the behavioral effects of BZ-type drugs and helps guide the development of new pharmaceutical agents for disorders currently treated with BZ-type drugs.

Sterile alpha motif domain-containing proteins 9 and 9-like (SAMD9/9L) are associated with life-threatening genetic diseases in humans and are restriction factors of poxviruses. Yet, their cellular function and the extent of their antiviral role are poorly known. Here, we found that interferon-stimulated human SAMD9L restricts HIV-1 in the late phases of replication, at the posttranscriptional and prematuration steps, impacting viral translation and, possibly, endosomal trafficking. Surprisingly, the paralog SAMD9 exerted an opposite effect, enhancing HIV-1. More broadly, we showed that SAMD9L restricts primate lentiviruses, but not a gammaretrovirus (MLV), nor 2 RNA viruses (arenavirus MOPV and rhabdovirus VSV). Using structural modeling and mutagenesis of SAMD9L, we identified a conserved Schlafen-like active site necessary for HIV-1 restriction by human and a rodent SAMD9L. By testing a gain-of-function constitutively active variant from patients with SAMD9L-associated autoinflammatory disease, we determined that SAMD9L pathogenic functions also depend on the Schlafen-like active site. Finally, we found that the constitutively active SAMD9L strongly inhibited HIV, MLV, and, to a lesser extent, MOPV. This suggests that the virus-specific effect of SAMD9L may involve its differential activation/sensing and the virus ability to evade from SAMD9L restriction. Overall, our study identifies SAMD9L as an HIV-1 antiviral factor from the cell autonomous immunity and deciphers host determinants underlying the translational repression. This provides novel links and therapeutic avenues against viral infections and genetic diseases.

After administration of the super(99m)Tc complex with N,N'-1,2-ethylenediylbis-L-cysteine diethyl ester ( super(99m)Tc-ECD), a brain perfusion imaging agent, the radioactive metabolite is trapped in primate brain, but not in mouse and rat. Here, we investigate the involvement of metabolite extrusion by organic anion transporter 3 (OAT3), which is highly expressed at the blood-brain barrier in mice, in this species difference. The efflux rate of radioactivity in the cerebrum of Oat3 super(-/-) mice at later phase was 20% of that of control mice. Thus, organic anion transporters in mouse brain would be involved in the low brain retention of radioactivity after super(99m)Tc-ECD administration.

Nipah virus (NiV) is an emerging highly lethal zoonotic disease that, like SARS-CoV-2, can be transmitted via respiratory droplets. Single-injection vaccines that rapidly control NiV outbreaks are needed. To assess the ability of a vaccine to induce fast-acting protection, we immunized African green monkeys with a recombinant vesicular stomatitis virus (VSV) expressing the Bangladesh strain glycoprotein (NiVBG) of NiV (rVSV-ΔG-NiVBG). Monkeys were challenged 3 or 7 d later with a lethal dose of NiVB. All monkeys vaccinated with rVSV-ΔG-NiVBG 7 d prior to NiVB exposure were protected from lethal disease, while 67% of animals vaccinated 3 d before NiVB challenge survived. Vaccine protection correlated with natural killer cell and cytotoxic T cell transcriptional signatures, whereas lethality was linked to sustained interferon signaling. NiV G-specific antibodies in vaccinated survivors corroborated additional transcriptomic findings, supporting activation of humoral immunity. This study demonstrates that rVSV-based vaccines may have utility in rapidly protecting humans against NiV infection.

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species.

Some non-selective serotonin2C (5-HT sub(2C)) agonists or inverse agonists enhance the product of the proto-oncogene c-Fos within the basal ganglia, a group of brain regions involved in motor behavior and in the ability of these drugs to promote abnormal movements. The role of 5-HT sub(2C) receptors in these effects is unclear. The 5-HT sub(2C) antagonist SB243,213 (1 mg/kg), which enhanced Fos per se in the striatum and the subthalamic nucleus (STN) only, was used to study the implication of 5-HT sub(2C) receptors. The agonists Ro 60-0175 (3 mg/kg) and m-CPP (1 mg/kg) and the inverse agonist SB206,553 (10 mg/kg) enhanced Fos expression in the STN and faintly in the entopeduncular nucleus (EPN, the internal globus pallidus in primate). The effects of these drugs differed mainly in the striatum regarding the magnitude (m-CPP > Ro 60-0175> SB243,213 > SB206,553) or the striatal quadrants (faint to no labeling in lateral striatum) and in the substantia nigra. None of these compounds enhanced Fos expression by themselves in the globus pallidus or in the EPN when combined with SB243,213. Their Fos effect in the STN was reduced significantly by SB243,213 only in the case of m-CPP. In the ventromedial striatum, SB243,213 reduced the effects of m-CPP while SB206,553 reduced the effects of SB243,213. The results show that opposite pharmacological agents alter similarly Fos expression in the EPN or the STN. Although some of the effects of 5-HT agents are related to targets other than 5-HT sub(2C) receptors, the study confirms the existence of multiple 5-HT sub(2C) receptor-dependent controls recruited by these drugs upon basal ganglia activity.

Lesions of nigrostriatal dopaminergic neurons as seen in Parkinson's disease (PD) increase orofacial responses to serotonergic (5-HT) agonists in rodents. Although this response to 5-HT agonists has been related to aberrant signalling in the basal ganglia, a group a subcortical structures involved in the control of motor behaviours, it deserves additional studies with respect to the specific loci involved. Using measurements of orofacial activity, as well as single-cell recordings in vivo, we have studied the role of the entopeduncular nucleus (EPN; equivalent to the internal globus pallidus of primates), an output structure of basal ganglia, in the hypersensitized responses to a 5-HT agonist in sham- or unilaterally dopamine-depleted rats. Intra-EPN injections of Ro 60-0175 (0.3 and 1 mu g/100 nl) promoted robust oral movements in 6-OHDA rats without affecting oral activity in sham-depleted rats. Peripheral administration of Ro 60-0175 (3 mg/kg ip) decreased EPN neuronal firing rate in 6-OHDA rats compared to sham-depleted rats. Such an effect was also observed when the agonist (0.2 mu g/20 nl) was locally applied onto EPN neurons. These data demonstrate the contribution of EPN to hypersensitized responses to 5-HT agonists in a rat model of PD.

Purpose: [ super(11)C]AZ10419369 is a recently developed 5-HT sub(1B) receptor radioligand that is sensitive to changes in endogenous serotonin concentrations in the primate brain. Thus, [ super(11)C] AZ10419369 may serve as a useful tool in clinical studies of the pathophysiology and pharmacological treatment of diseases related to the serotonin system, such as depression and anxiety disorders. The aim of this study was to evaluate the test-retest reliability of [ super(11)C]AZ10419369. Methods: Eight men were examined with PET and [ super(11)C] AZ10419369 twice on the same day. The binding potentials (BP sub(ND)) of [ super(11)C]AZ10419369 in selected serotonergic projection areas and in the raphe nuclei (RN) were determined using the simplified reference tissue model, and for comparison also using a wavelet-aided parametric imaging approach. The BP sub(ND) values obtained from the first and second PET scans were compared by means of descriptive statistics, difference, absolute variability and intraclass correlation coefficient. Results: Similar BP sub(ND) values were obtained with the two methods. The absolute mean differences in BP sub(ND) between PET 1 and PET 2 were less than 3 % in all serotonergic projection regions. Absolute variabilities were low in cortical regions (5 - 7 %), low to moderate (7 - 14 %) in subcortical regions, but higher (20 %) in the RN. Conclusion: The BP sub(ND) of [ super(11)C]AZ10419369 is highly reproducible in cortical regions and satisfactory in subcortical projection areas. The variability in the RN is higher. Thus larger sample sizes or larger divergences are required to assess a potential difference between subjects or between experimental conditions in this region.