An analysis of risk factors for spontaneously occurring type 2 diabetes mellitus in rhesus macaques (Macaca mulatta).

BACKGROUND: Type 2 Diabetes Mellitus (T2D) is a chronic disease with a high prevalence worldwide. Human literature suggests factors beyond well-known risk factors (e.g., age, body mass index) for T2D: cytomegalovirus serostatus, season of birth, maternal age, birth weight, and depression. Nothing is known, however, about whether these variables are influential in primate models of T2D. METHODS: Using a retrospective methodology, we identified 22 cases of spontaneously occurring T2D among rhesus monkeys at our facility. A control sample of n = 1199 was identified. RESULTS: Animals born to mothers that were ≤5.5 years of age, and animals that showed heightened Activity and Emotionality in response to brief separation in infancy, had a greater risk for development of T2D in adulthood. CONCLUSIONS: Knowledge of additional risk factors for T2D could help colony managers better identify at-risk animals and enable diabetes researchers to select animals that might be more responsive to their manipulations.

Repeatability of measures of behavioral organization over two years in captive infant rhesus macaques, Macaca mulatta.

Individual differences of infant temperament have been associated with future health outcomes that provide explanatory power beyond adult personality. Despite the importance of such a metric, our developmental understanding of personality-like traits is poor. Therefore, we examined whether young primates show consistency in personality traits throughout development. We replicated a Biobehavioral Assessment (BBA) at three time periods: 3-4 months, 1 year, and 2 years of age in 47 rhesus macaque (Macaca mulatta) subjects from large mixed-sex outdoor social housing units at the California National Primate Research Center. We report results for tests focused on responses and adaptation to the temporary separation and relocation, responses to a threatening stimulus, and ratings of overall temperament. We found consistently repeatable associations in measures of Emotionality; these associations were stronger in males, but also present in females, and broadly consistent between Years 1 and 2. We also explored whether behavioral responses to this experimental relocation might be influenced by their experience being relocated for other reasons (i.e., hospitalizations) as individuals' responses might be influenced by similar experiences to the BBA procedure. Only locomotion, during one of the assessments, was associated with past hospitalization events. Overall, repeatability in Emotionality-associated behaviors was evident across the 2 years, in both sexes. We did, however, find evidence of the emergence of sex differences via differentiated expression of behavioral responses during the BBA. We emphasize that there is likely contextual nuance in the use of these BBA factor-associated behaviors. Further research is required to determine whether and how shifts occur in underlying factor structure and the expression of associated behaviors.

Naturally occurring low sociality in female rhesus monkeys: A tractable model for autism or not?

BACKGROUND: Autism spectrum disorder (ASD) is characterized by persistent social interaction impairments and is male-biased in prevalence. We have established naturally occurring low sociality in male rhesus monkeys as a model for the social features of ASD. Low-social male monkeys exhibit reduced social interactions and increased autistic-like trait burden, with both measures highly correlated and strongly linked to low cerebrospinal fluid (CSF) arginine vasopressin (AVP) concentration. Little is known, however, about the behavioral and neurochemical profiles of female rhesus monkeys, and whether low sociality in females is a tractable model for ASD. METHODS: Social behavior assessments (ethological observations; a reverse-translated autistic trait measurement scale, the macaque Social Responsiveness Scale-Revised [mSRS-R]) were completed on N = 88 outdoor-housed female rhesus monkeys during the non-breeding season. CSF and blood samples were collected from a subset of N = 16 monkeys across the frequency distribution of non-social behavior, and AVP and oxytocin (OXT) concentrations were quantified. Data were analyzed using general linear models. RESULTS: Non-social behavior frequency and mSRS-R scores were continuously distributed across the general female monkey population, as previously found for male monkeys. However, dominance rank significantly predicted mSRS-R scores in females, with higher-ranking individuals showing fewer autistic-like traits, a relationship not previously observed in males from this colony. Females differed from males in several other respects: Social behavior frequencies were unrelated to mSRS-R scores, and AVP concentration was unrelated to any social behavior measure. Blood and CSF concentrations of AVP were positively correlated in females; no significant relationship involving any OXT measure was found. LIMITATIONS: This study sample was small, and did not consider genetic, environmental, or other neurochemical measures that may be related to female mSRS-R scores. CONCLUSIONS: Dominance rank is the most significant predictor of autistic-like traits in female rhesus monkeys, and CSF neuropeptide concentrations are unrelated to measures of female social functioning (in contrast to prior CSF AVP findings in male rhesus monkeys and male and female autistic children). Although preliminary, this evidence suggests that the strong matrilineal organization of this species may limit the usefulness of low sociality in female rhesus monkeys as a tractable model for ASD.

Hair and plasma cortisol throughout the first 3 years of development in infant rhesus macaques, Macaca mulatta.

Cortisol expression has been demonstrated to have variation across development in rhesus macaques (Macaca mulatta). There exists contradictory evidence for the nature of this change, and age at which it occurs, across biological sample types. Consequently, we lack a cohesive understanding for cortisol concentrations across the development of a major human health translational model. We examined hair cortisol concentrations over the first 3 years of life for 49 mother-reared infant macaques from mixed-sex outdoor units at the California National Primate Research Center. For 48 of these subjects at infancy, 1 year, and 2 years, we obtained plasma cortisol samples for response to a stressor, adjustment to prolonged stress, and response to dexamethasone injection. Hair cortisol concentrations decreased dramatically between 3 and 10 months, followed by relative stability up to the final sampling event at around 34 months of age. Plasma cortisol showed within-year consistency, and consistency between infancy and year 1. We document variability in the infant plasma cortisol samples, especially in percent change between samples 1 and 2. Our plasma cortisol results indicate that infants possess the physiological capacity to effectively inhibit the release of cortisol when stimulated, as effectively as later responses in juveniles. Age-related changes in hair cortisol parallel findings indicating a large decline in the weeks following postparturation.

Rhesus macaque social functioning is paternally, but not maternally, inherited by sons: potential implications for autism.

BACKGROUND: Quantitative autistic traits are common, heritable, and continuously distributed across the general human population. Patterns of autistic traits within families suggest that more complex mechanisms than simple Mendelian inheritance-in particular, parent of origin effects-may be involved. The ideal strategy for ascertaining parent of origin effects is by half-sibling analysis, where half-siblings share one, but not both, parents and each individual belongs to a unique combination of paternal and maternal half-siblings. While this family structure is rare in humans, many of our primate relatives, including rhesus macaques, have promiscuous breeding systems that consistently produce paternal and maternal half-siblings for a given index animal. Rhesus macaques, like humans, also exhibit pronounced variation in social functioning. METHODS: Here we assessed differential paternal versus maternal inheritance of social functioning in male rhesus macaque offspring (N = 407) using ethological observations and ratings on a reverse-translated quantitative autistic trait measurement scale. Restricted Maximum Likelihood mixed models with unbounded variance estimates were used to estimate the variance components needed to calculate the genetic contribution of parents as the proportion of phenotypic variance (σ2P) between sons that could uniquely be attributed to their shared genetics (σ2g), expressed as σ2g/σ2P (or the proportion of phenotypic variance attributable to genetic variance), as well as narrow sense heritability (h2). RESULTS: Genetic contributions and heritability estimates were strong and highly significant for sons who shared a father but weak and non-significant for sons who shared a mother. Importantly, these findings were detected using the same scores from the same sons in the same analysis, confirmed when paternal and maternal half-siblings were analyzed separately, and observed with two methodologically distinct behavioral measures. Finally, genetic contributions were similar for full-siblings versus half-siblings that shared only a father, further supporting a selective paternal inheritance effect. LIMITATIONS: These data are correlational by nature. A larger sample that includes female subjects, enables deeper pedigree assessments, and supports molecular genetic analyses is warranted. CONCLUSIONS: Rhesus macaque social functioning may be paternally, but not maternally, inherited by sons. With continued investigation, this approach may yield important insights into sex differences in autism's genetic liability.

Variation in the serotonin transporter genotype is associated with maternal restraint and rejection of infants: A nonhuman primate (Macaca mulatta) model.

Studies show that maternal behaviors are mediated by the bivariate serotonin transporter (5-HTT) genotype, although the findings are mixed, with some studies showing that mothers with the s allele exhibit increased maternal sensitivity, while other studies show that mothers with the s allele show decreased maternal sensitivity. Nonhuman primate studies offer increased control over extraneous variables and may contribute to a better understanding of the effects of the 5-HTT genotype on maternal sensitivity. This study assesses the influence of 5-HTT genotype variation on maternal sensitivity in parenting in 125 rhesus macaque mothers (Macaca mulatta) during the first three-months of their infants' lives, an age well before typical infants undergo weaning. Mothers were genotyped for the 5-HTT genotype and maternal behaviors were collected, including neglectfulness, sensitivity, and premature rejections during undisturbed social interactions. Results showed that mothers homozygous for the s allele rejected their infants the most and restrained their infants the least, an indication that mothers with the s allele are more likely to neglect their infants' psychological and physical needs. These findings suggest that, at an age when an infant's needs are based on warmth, security, and protection, mothers with an s allele exhibit less sensitive maternal behaviors. High rates of rejections and low rates of restraints are behaviors that typically characterize premature weaning and are inappropriate for their infant's young age. This study is an important step in understanding the etiology of variability in maternal warmth and care, and further suggests that maternal 5-HTT genotype should be examined in studies assessing genetic influences on variation in maternal sensitivity, and ultimately, mother-infant attachment quality.

Effect of Pochonia chlamydosporia Endophytism and Meloidogyne incognita Parasitism on WRKYs and Defense Gene Expression in Tomato Roots.

The expression of WRKY transcription factors and plant defense-related genes was studied in the roots of Apulian tomato (Solanum lycopersicum) cv Regina di Fasano (accessions MRT and PLZ) endophytically colonized by Pochonia chlamydosporia and parasitized or not by the root-knot nematode (RKN) Meloidogyne incognita. The effect on plant growth, nematode parasitism and histological aspect of the interaction were considered. The association of P. chlamydosporia with RKN-parasitized MRT plants increased the total biomass and shoot fresh weight in comparison with healthy plants and with those only parasitized by RKN, without the endophyte. However, the PLZ accession showed no significant difference in the observed biometric parameters. The number of RKN-induced galls per plant was not affected by endophytism eight days after inoculation. No histological changes were observed in the nematode feeding sites in the presence of the fungus. Gene expression analysis showed an accession-specific response to P. chlamydosporia with differential activation of WRKY-related genes. No significant change was found for WRKY76 expression in nematode-parasitized plants compared with control roots, confirming cultivar susceptibility. Data indicate genotype-specific responses of the WRKY genes to parasitism examined in roots with nematodes and/or endophytic P. chlamydosporia. At 25 days post-inoculation with P. chlamydosporia, no significant difference was observed in the expression of defense-related genes in both accessions, suggesting that salicylic acid (SA) (PAL and PR1) and jasmonate (JA) related genes (Pin II) are not active during endophytism.

Responses to Drought Stress in Poplar: What Do We Know and What Can We Learn?

Poplar (Populus spp.) is a high-value crop for wood and biomass production and a model organism for tree physiology and genomics. The early release, in 2006, of the complete genome sequence of P. trichocarpa was followed by a wealth of studies that significantly enriched our knowledge of complex pathways inherent to woody plants, such as lignin biosynthesis and secondary cell wall deposition. Recently, in the attempt to cope with the challenges posed by ongoing climate change, fundamental studies and breeding programs with poplar have gradually shifted their focus to address the responses to abiotic stresses, particularly drought. Taking advantage from a set of modern genomic and phenotyping tools, these studies are now shedding light on important processes, including embolism formation (the entry and expansion of air bubbles in the xylem) and repair, the impact of drought stress on biomass yield and quality, and the long-term effects of drought events. In this review, we summarize the status of the research on the molecular bases of the responses to drought in poplar. We highlight how this knowledge can be exploited to select more tolerant genotypes and how it can be translated to other tree species to improve our understanding of forest dynamics under rapidly changing environmental conditions.

Variation in infant rhesus monkeys' (Macaca mulatta) neutrophil-to-lymphocyte ratio is associated with environmental conditions, emotionality, and cortisol concentrations, and predicts disease-related outcomes.

The neutrophil-to-lymphocyte ratio (NLR) is a predictor of morbidity for a variety of medical conditions, but little is known about how variation in NLR arises. We examined variation in this measure in a sample of 4577 infant rhesus monkeys (54.8 % female), who participated in the BioBehavioral Assessment program at the California National Primate Research Center at 3-4 months of age. Lower values for NLR were seen for animals reared indoors, for animals that were raised to be free of specific pathogens, and for males. In addition lower NLR was associated with higher stress values of cortisol and with greater emotionality in response to an acute stressor. Finally, lower NLR in infancy was associated with greater risk for developing airways hyperresponsiveness (a hallmark of asthma); with display of diarrhea up to 3.97 years later; and with greater viral load when infected with the simian immunodeficiency virus at a mean of 6.1 years of age. Infant NLR was a better predictor of viral load than was a contemporaneously obtained measure of NLR. Infant and adult values of NLR were only modestly correlated; one reason may be that the infant measure was obtained during stressful conditions and the adult measure was obtained under baseline conditions. We propose that NLR is an integrated outcome measure reflecting organization and interaction of stress-response and immune systems. As such, assessment of NLR under conditions of stress may be a particularly useful marker of individual differences in morbidity, especially for conditions in which stress plays an important role, as in asthma, diarrhea/colitis, and AIDS.

Sustainable strategies for management of the "false root-knot nematode" Nacobbus spp.

The genus Nacobbus, known as the false root-knot nematode, is native to the American continent and comprises polyphagous species adapted to a wide range of climatic conditions. Alone or in combination with other biotic and abiotic factors, Nacobbus spp. can cause significant economic yield losses on main food crops such as potato, sugar beet, tomato, pepper and bean, in South and North America. Although the genus distribution is restricted to the American continent, it has quarantine importance and is subject to international legislation to prevent its spread to other regions, such as the European Union. The management of Nacobbus spp. remains unsatisfactory due to the lack of information related to different aspects of its life cycle, survival stages in the soil and in plant material, a rapid and reliable diagnostic method for its detection and the insufficient source of resistant plant genotypes. Due to the high toxicity of chemical nematicides, the search for alternatives has been intensified. Therefore, this review reports findings on the application of environmentally benign treatments to manage Nacobbus spp. Biological control strategies, such as the use of different organisms (mainly bacteria, fungi and entomopathogenic nematodes) and other eco-compatible approaches (such as metabolites, essential oils, plant extracts, phytohormones and amendments), either alone or as part of a combined control strategy, are discussed. Knowledge of potential sources of resistance for genetic improvement for crops susceptible to Nacobbus spp. are also reported. The sustainable strategies outlined here offer immediate benefits, not only to counter the pathogen, but also as good alternatives to improve crop health and growth.

Rhesus monkey sociality is stable across time and linked to variation in the initiation but not receipt of prosocial behavior.

Rhesus monkeys and humans are highly social primates, yet both species exhibit pronounced variation in social functioning, spanning a spectrum of sociality. Naturally occurring low sociality in rhesus monkeys may be a promising construct by which to model social impairments relevant to human autism spectrum disorder (ASD), particularly if low sociality is found to be stable across time and associated with diminished social motivation. Thus, to better characterize variation in sociality and social communication profiles, we performed quantitative social behavior assessments on N = 95 male rhesus macaques (Macaca mulatta) housed in large, outdoor groups. In Study 1, we determined the social classification of our subjects by rank-ordering their total frequency of nonsocial behavior. Monkeys with the greatest frequency of nonsocial behavior were classified as low-social (n = 20) and monkeys with the lowest frequency of nonsocial behavior were classified as high-social (n = 21). To assess group differences in social communication profiles, in Study 2, we quantified the rates of transient social communication signals, and whether these social signals were initiated by or directed towards the focal subject. Finally, in Study 3, we assessed the within-individual stability of sociality in a subset of monkeys (n = 11 low-social, n = 11 high-social) two years following our initial observations. Nonsocial behavior frequency significantly correlated across the two timepoints (Studies 1 and 3). Likewise, low-social versus high-social classification accurately predicted classification two years later. Low-social monkeys initiated less prosocial behavior than high-social monkeys, but groups did not differ in receipt of prosocial behavior, nor did they differ in threat behavior. These findings indicate that sociality is a stable, trait-like characteristic and that low sociality is linked to diminished initiation of prosocial behavior in rhesus macaques. This evidence also suggests that low sociality may be a useful construct for gaining mechanistic insight into the social motivational deficits often observed in people with ASD.

Multi-omic brain and behavioral correlates of cell-free fetal DNA methylation in macaque maternal obesity models.

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

Advanced Breeding for Biotic Stress Resistance in Poplar.

Poplar is one of the most important forest trees because of its high economic value. Thanks to the fast-growing rate, easy vegetative propagation and transformation, and availability of genomic resources, poplar has been considered the model species for forest genetics, genomics, and breeding. Being a field-growing tree, poplar is exposed to environmental threats, including biotic stresses that are becoming more intense and diffused because of global warming. Current poplar farming is mainly based on monocultures of a few elite clones and the expensive and long-term conventional breeding programmes of perennial tree species cannot face current climate-change challenges. Consequently, new tools and methods are necessary to reduce the limits of traditional breeding related to the long generation time and to discover new sources of resistance. Recent advances in genomics, marker-assisted selection, genomic prediction, and genome editing offer powerful tools to efficiently exploit the Populus genetic diversity and allow enabling molecular breeding to support accurate early selection, increasing the efficiency, and reducing the time and costs of poplar breeding, that, in turn, will improve our capacity to face or prevent the emergence of new diseases or pests.

In vitro compatibility of Brassicaceae extracts with nematophagous fungi and their effects against Nacobbus celatus.

Nacobbus celatus sp. n. is one of the main root-knot nematodes in the field destined for horticultural production of the central region of Argentine due to its ability to infect several host plants. The lack of new and safe active ingredients against this nematode has restricted control alternatives for growers. Egg-parasitic fungi and biofumigation with brassicaceae have been considered as potential candidates for the development of bionematicides. Nematicidal effects of Brassica oleracea var. italica (broccoli) and Brassica oleracea var. capitata (cabbage) aqueous extracts (AEs) against second-stage juveniles (J2) of N. celatus were evaluated in vitro. Fisher LSD tests evidenced significant nematicidal (α = 0.05) effects of the two AEs tested, with LD100 of 250 and 500 µL mL-1 for broccoli and cabbage, respectively. Compatibility assays between AEs and five nematophagous fungi were performed on soil extract medium conditioned at 0.99 water activity and incubated at 30, 25 and 20 °C. Purpureocillium lilacinum SR14 was the fungal strain that showed compatibility at levels of spore viability, growth rate and conidia productions at LD50 (125 µL mL-1) and LD25 (60 µL mL-1) of broccoli aqueous extract (BAE) and enhanced the nematophagous effect. Moreover, phytotoxic studies revealed that 125 µL mL-1 of BAE applied at the transplantation time could be safely used without affecting tomato culture. In conclusion, the integrated application of BAE with P. lilacinum SR14, which combines two action mechanisms, represents a promising integrated strategy to management phytoparasitic nematodes.

Rhizosphere 16S-ITS Metabarcoding Profiles in Banana Crops Are Affected by Nematodes, Cultivation, and Local Climatic Variations.

Agriculture affects soil and root microbial communities. However, detailed knowledge is needed on the effects of cropping on rhizosphere, including biological control agents (BCA) of nematodes. A metabarcoding study was carried out on the microbiota associated with plant parasitic and other nematode functional groups present in banana farms in Tenerife (Canary Islands, Spain). Samples included rhizosphere soil from cv Pequeña Enana or Gruesa and controls collected from adjacent sites, with the same agroecological conditions, without banana roots. To characterize the bacterial communities, the V3 and V4 variable regions of the 16S rRNA ribosomal gene were amplified, whereas the internal transcribed spacer (ITS) region was used for the fungi present in the same samples. Libraries were sequenced with an Illumina MiSeq™ in paired ends with a 300-bp read length. For each sample, plant parasitic nematodes (PPN) and other nematodes were extracted from the soil, counted, and identified. Phytoparasitic nematodes were mostly found in banana rhizosphere. They included Pratylenchus goodeyi, present in northern farms, and Helicotylenchus spp., including H. multicinctus, found in both northern and southern farms. Metabarcoding data showed a direct effect of cropping on microbial communities, and latitude-related factors that separated northern and southern controls from banana rizosphere samples. Several fungal taxa known as nematode BCA were identified, with endophytes, mycorrhizal species, and obligate Rozellomycota endoparasites, almost only present in the banana samples. The dominant bacterial phyla were Proteobacteria, Actinobacteria, Planctomycetes, Bacteroidetes, Chloroflexi, and Acidobacteria. The ITS data showed several operational taxonomic units (OTUs) belonging to Sordariomycetes, including biocontrol agents, such as Beauveria spp., Arthrobotrys spp., Pochonia chlamydosporia, and Metarhizium anisopliae. Other taxa included Trichoderma harzianum, Trichoderma longibrachiatum, Trichoderma virens, and Fusarium spp., together with mycoparasites such as Acrostalagmus luteoalbus. However, only one Dactylella spp. showed a correlation with predatory nematodes. Differences among the nematode guilds were found, as phytoparasitic, free-living, and predatory nematode groups were correlated with specific subsets of other bacteria and fungi. Crop cultivation method and soil texture showed differences in taxa representations when considering other farm and soil variables. The data showed changes in the rhizosphere and soil microbiota related to trophic specialization and specific adaptations, affecting decomposers, beneficial endophytes, mycorrhizae, or BCA, and plant pathogens.

Water Stress Differentially Modulates the Expression of Tomato Cell Wall Metabolism-Related Genes in Meloidogyne incognita Feeding Sites.

Microscopic observations and transcriptomic RNA-Seq analyses were applied to investigate the effect of water stress during the formation of tomato galls formation 1 and 2 weeks after inoculation with the root-knot nematode Meloidogyne incognita. Water stress affected root growth and the nematode ability to mount an efficient parasitism. The effects of water stress on the feeding site development were already observed at 1 week after nematode inoculation, with smaller giant cells, delayed development, and thinner cell walls. These features suggested changes in the expression levels of genes involved in the feeding site formation and maintenance. Gene Ontology (GO) enrichment and expression patterns were used to characterize differentially expressed genes. Water stress modified the expression profile of genes involved in the synthesis, degradation, and remodeling of the cell wall during the development of nematode feeding site. A comparison of gene expression with unstressed galls revealed that water stress intensified the up or downregulation of most genes. However, it particularly influenced the expression pattern of expansin A11 (Solyc04g081870.4.1), expansin-like B1(Solyc08g077910.3.1), a pectin acetylesterase (Solyc08g005800.4.1), and the pectin methylesterase pmeu1 (Solyc03g123630.4.1) which were upregulated in unstressed galls and repressed by water stress, at both sampling times. The expression of most members of the genes involved in cell wall metabolism, i.e., those coding for Csl, fasciclin, and COBRA proteins, were negatively influenced. Interestingly, alteration in the expression profiles of most dirigent protein genes (DIRs) and upregulation of five gene coding for Casparian strip domain protein (CASP)-like proteins were found. Gene expression analysis of galls from water stressed plants allowed us to better understand the molecular basis of M. incognita parasitism in tomato. Specific genes, including those involved in regulation of cellulose synthesis and lignification process, require further study to develop defense strategies against root-knot nematodes.

Adverse biobehavioral effects in infants resulting from pregnant rhesus macaques' exposure to wildfire smoke.

As wildfires across the world increase in number, size, and intensity, exposure to wildfire smoke (WFS) is a growing health problem. To date, however, little is known for any species on what might be the behavioral or physiological consequences of prenatal exposure to WFS. Here we show that infant rhesus monkeys exposed to WFS in the first third of gestation (n = 52) from the Camp Fire (California, November, 2018) show greater inflammation, blunted cortisol, more passive behavior, and memory impairment compared to animals conceived after smoke had dissipated (n = 37). Parallel analyses, performed on a historical control cohort (n = 2490), did not support the alternative hypothesis that conception timing alone could explain the results. We conclude that WFS may have a teratogenic effect on the developing fetus and speculate on mechanisms by which WFS might affect neural development.

The relationship of maternal rank, 5-HTTLPR genotype, and MAOA-LPR genotype to temperament in infant rhesus monkeys (Macaca mulatta).

Temperament is a construct whose manifestations are quantifiable from an early age, and whose origins have been proposed as "biological." Our goal was to determine whether maternal rank and infant genotype are associated with five measures of temperament in 3- to 4-month old rhesus monkeys (Macaca mulatta), all of whom were born and reared by their mothers in large, outdoor, half-acre cages. Maternal rank was defined as the proportion of animals outranked by each female, and the two genes of interest to us were monoamine oxidase and serotonin transporter, both of which are polymorphic in their promoter regions (MAOA-LPR and 5-HTTLPR, respectively), with one allele of each gene considered a "plasticity" allele, conferring increased sensitivity to environmental events. Our large sample size (n = 2014-3140) enabled us to examine the effects of individual genotypes rather than combining genotypes as is often done. Rank was positively associated with Confident temperament, but only for animals with the 5-repeat allele for MAOA-LPR. Rank had no other effect on temperament. In contrast, genotype had many different effects, with 5-HTTLPR associated with behavioral inhibition, and MAOA-LPR associated with ratings-based measures of temperament. We also examined the joint effect of the two genotypes and found some evidence for a dose-response: animals with the plasticity alleles for both genes were more likely to be behaviorally inhibited. Our results suggest phenotypic differences between animals possessing alleles for MAOA-LPR that show functional equivalence based on in vitro tests, and our data for 5-HTTLPR revealed differences between short/short homozygotes and long/short heterozygotes, strongly suggesting that combining genotypes for statistical analysis should be avoided if possible. Our analysis also provides evidence of sex differences in temperament, and, to our knowledge, the only evidence of differences in temperament based on specific pathogen-free status. We suggest several directions for future research.

Juliano Moreira: the black Brazilian who greatly influenced the modern school of Neurology in Brazil.

Juliano Moreira was a black Brazilian physician, well recognized for his role in the foundation of scientific psychiatry in Brazil; however, little is known about his influences on modern Neurology. Our aim is to highlight Moreira's importance in the field of Neurology and his role in the development of scientific and medical societies in Brazil. We describe his contributions from his doctoral thesis in 1891 to his 27-year tenure as the director of the National Hospice for the Insane. We also review Moreira's role in the foundation of societies including the Brazilian Academy of Sciences and the first Brazilian journal dedicated to Neuropsychiatry, concluding that Moreira was one of the most important influential figures for the development of Neurology in Brazil. In addition to his influences on various medical fields, Moreira distinguished himself as an impactful citizen who fought against racist and xenophobic medical theories of his time.

The Type I interferon antiviral gene program is impaired by lockdown and preserved by caregiving.

Previous research has linked perceived social isolation (loneliness) to reduced antiviral immunity, but the immunologic effects of the objective social isolation imposed by pandemic "shelter in place" (SIP) policies is unknown. We assessed the immunologic impact of SIP by relocating 21 adult male rhesus macaques from 2,000-m2 field cage communities of 70 to 132 other macaques to 2 wk of individual housing in indoor shelters. SIP was associated with 30% to 50% reductions in all circulating immune cell populations (lymphocytes, monocytes, and granulocytes), down-regulation of Type I interferon (IFN) antiviral gene expression, and a relative up-regulation of CD16- classical monocytes. These effects emerged within the first 48 h of SIP, persisted for at least 2 wk, and abated within 4 wk of return to social housing. A subsequent round of SIP in the presence of a novel juvenile macaque showed comparable reductions in circulating immune cell populations but reversal of Type I IFN reductions and classical monocyte increases observed during individual SIP. Analyses of lymph node tissues showed parallel up-regulation of Type I IFN genes and enhanced control of viral gene expression during juvenile-partnered SIP compared to isolated SIP. These results identify a significant adverse effect of SIP social isolation on antiviral immune regulation in both circulating immune cells and lymphoid tissues, and they suggest a potential behavioral strategy for ameliorating gene regulatory impacts (but not immune cell declines) by promoting prosocial engagement during SIP.