Motherhood and DREADD manipulation of the nucleus accumbens weaken established pair bonds in female prairie voles.

Monogamous pair bonding has evolved to enhance reproductive success and ensure offspring survival. Although the behavioral and neural mechanisms regulating the formation of pair bonds have been relatively well outlined, how these relationships are regulated and maintained across the lifetime of an individual remains relatively unexplored. One way to explore this is to study the maintenance of a social bond across a major life-history transition. The transition to motherhood is among the most poignant moments in the life history of a female, and is associated with significant neural and behavioral changes and shifting priorities. The nucleus accumbens (NAc) is known to modulate social valence and is central to mammalian pair bonding. In this study, we investigated two mechanisms driving variation in bond strength in the socially monogamous prairie vole (Microtus ochrogaster). We manipulated neural activity of the NAc at two distinct stages of life-history, before and after the birth of offspring, to assess how neural activity and social contexts modulate female pair bond strength. Our results showed DREADD (Designer Receptor Exclusively Activated by Designer Drugs) inhibition of the NAc decreases affiliative behavior towards the mating partner, whereas DREADD activation of the NAc increases affiliative behavior of strangers, thereby decreasing social selectivity. We also found a robust "birth effect" on pair bond strength, such that bonds with partners were weakened after the birth of offspring, an effect not attributable to the amount of cohabitation time with a partner. Overall, our data support the hypotheses that NAc activity modulates reward/saliency within the social brain in different ways, and that motherhood comes with a cost for the bond strength between mating partners.

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.

Adaptive developmental plasticity in rhesus macaques: the serotonin transporter gene interacts with maternal care to affect juvenile social behaviour.

Research has increasingly highlighted the role that developmental plasticity-the ability of a particular genotype to produce variable phenotypes in response to different early environments-plays as an adaptive mechanism. One of the most widely studied genetic contributors to developmental plasticity in humans and rhesus macaques is a serotonin transporter gene-linked polymorphic region (5-HTTLPR), which determines transcriptional efficiency of the serotonin transporter gene in vitro and modifies the availability of synaptic serotonin in these species. A majority of studies to date have shown that carriers of a loss-of-function variant of the 5-HTTLPR, the short (s) allele, develop a stress-reactive phenotype in response to adverse early environments compared with long (l) allele homozygotes, leading to the prevalent conceptualization of the s-allele as a vulnerability allele. However, this framework fails to address the independent evolution of these loss-of-function mutations in both humans and macaques as well as the high population prevalence of s-alleles in both species. Here we show in free-ranging rhesus macaques that s-allele carriers benefit more from supportive early social environments than l-allele homozygotes, such that s-allele carriers which receive higher levels of maternal protection during infancy demonstrate greater social competence later in life. These findings provide, to our knowledge, the first empirical support for the assertion that the s-allele grants high undirected biological sensitivity to context in primates and suggest a mechanism through which the 5-HTTLPR s-allele is maintained in primate populations.

Working in Venezuela: How the Crisis has Affected the Labor Conditions.

BACKGROUND: Venezuela, the country with the largest oil reserves in the world, is facing the worst economic, social and political crisis in its history; which has notably affected the quality of life of the workforce and the entire population. OBJECTIVES: Identify and analyze the main social factors derived from the Venezuelan crisis, which are affecting the workers' health and working conditions. METHODS: Document study. Several sources of information from the last twenty years were consulted, ranging from public statistics and reports, newspaper articles, and results of scientific research. The information gathered was carefully studied to ensure that only reliable sources were used to ultimately reach valid conclusions. RESULTS: Both workers from the formal and informal sector and their families are struggling to fulfill their basic needs. Low salaries and soaring inflation have resulted in a dramatic reduction in the purchasing power of the people. General violence and high prices of basic goods are some of the major problems affecting workers both inside and outside of their working environment. Being a formal employee is no longer a guarantee for an acceptable quality of life. As a result, over 1.6 million Venezuelans have left their country since 2015 in a migration crisis never seen before in Latin America. CONCLUSION: Quality of life and wellbeing of most of the Venezuelan population has being deteriorated in the last 5 years and Occupational Safety and Health (OSH) is not a priority for enterprises in the middle of the economic emergency and general deterioration of daily life.Despite the relevance of this problem, research on the subject is very limited. Recent and pertinent data is needed to properly identify and measure the risks and negative consequences that workers and families are exposed caused by the ongoing crisis.

Preference for novel faces in male infant monkeys predicts cerebrospinal fluid oxytocin concentrations later in life.

The ability to recognize individuals is a critical skill acquired early in life for group living species. In primates, individual recognition occurs predominantly through face discrimination. Despite the essential adaptive value of this ability, robust individual differences in conspecific face recognition exist, yet its associated biology remains unknown. Although pharmacological administration of oxytocin has implicated this neuropeptide in face perception and social memory, no prior research has tested the relationship between individual differences in face recognition and endogenous oxytocin concentrations. Here we show in a male rhesus monkey cohort (N = 60) that infant performance in a task used to determine face recognition ability (specifically, the ability of animals to show a preference for a novel face) robustly predicts cerebrospinal fluid, but not blood, oxytocin concentrations up to five years after behavioural assessment. These results argue that central oxytocin biology may be related to individual face perceptual abilities necessary for group living, and that these differences are stable traits.

Early Predictors of Impaired Social Functioning in Male Rhesus Macaques (Macaca mulatta).

Autism spectrum disorder (ASD) is characterized by social cognition impairments but its basic disease mechanisms remain poorly understood. Progress has been impeded by the absence of animal models that manifest behavioral phenotypes relevant to ASD. Rhesus monkeys are an ideal model organism to address this barrier to progress. Like humans, rhesus monkeys are highly social, possess complex social cognition abilities, and exhibit pronounced individual differences in social functioning. Moreover, we have previously shown that Low-Social (LS) vs. High-Social (HS) adult male monkeys exhibit lower social motivation and poorer social skills. It is not known, however, when these social deficits first emerge. The goals of this study were to test whether juvenile LS and HS monkeys differed as infants in their ability to process social information, and whether infant social abilities predicted later social classification (i.e., LS vs. HS), in order to facilitate earlier identification of monkeys at risk for poor social outcomes. Social classification was determined for N = 25 LS and N = 25 HS male monkeys that were 1-4 years of age. As part of a colony-wide assessment, these monkeys had previously undergone, as infants, tests of face recognition memory and the ability to respond appropriately to conspecific social signals. Monkeys later identified as LS vs. HS showed impairments in recognizing familiar vs. novel faces and in the species-typical adaptive ability to gaze avert to scenes of conspecific aggression. Additionally, multivariate logistic regression using infant social ability measures perfectly predicted later social classification of all N = 50 monkeys. These findings suggest that an early capacity to process important social information may account for differences in rhesus monkeys' motivation and competence to establish and maintain social relationships later in life. Further development of this model will facilitate identification of novel biological targets for intervention to improve social outcomes in at-risk young monkeys.

Polyphosphate kinases modulate Campylobacter jejuni outer membrane constituents and alter its capacity to invade and survive in intestinal epithelial cells in vitro.

Campylobacter jejuni is the most prevalent cause of bacterial gastroenteritis worldwide. Polyphosphate kinases 1 and 2 (PPK1 and PPK2) regulate several cellular processes, including the biosynthesis of the bacterial cell wall. Despite their importance, whether PPK1 and PPK2 modulate the composition of C. jejuni outer membrane constituents (OMCs) and consequently impact its interaction with host cells remains unknown. Our comparative analysis between C. jejuni wild type, Δppk1, and Δppk2 strains showed qualitative and quantitative differences in the total OMC composition among these strains. Importantly, these OMC variations observed on the C. jejuni polyphosphate kinase mutants are directly related to their capacity to invade, survive, and alter the immune response of intestinal epithelial cells in vitro. Specifically, sub-fractionation of the C. jejuni OMC indicated that OMC proteins are uniquely associated with bacterial invasion, whereas C. jejuni OMC proteins, lipids, and lipoglycans are all associated with C. jejuni intracellular survival. This study provides new insights regarding the function of polyphosphate kinases and their role in C. jejuni infection.

Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure.

Bisphenol A (BPA) is an estrogenic endocrine disruptor widely used in the production of plastics. Increasing evidence indicates that in utero BPA exposure affects sexual differentiation and behavior; however, the mechanisms underlying these effects are unknown. We hypothesized that BPA may disrupt epigenetic programming of gene expression in the brain. Here, we provide evidence that maternal exposure during pregnancy to environmentally relevant doses of BPA (2, 20, and 200 µg/kg/d) in mice induces sex-specific, dose-dependent (linear and curvilinear), and brain region-specific changes in expression of genes encoding estrogen receptors (ERs; ERα and ERß) and estrogen-related receptor-γ in juvenile offspring. Concomitantly, BPA altered mRNA levels of epigenetic regulators DNA methyltransferase (DNMT) 1 and DNMT3A in the juvenile cortex and hypothalamus, paralleling changes in estrogen-related receptors. Importantly, changes in ERα and DNMT expression in the cortex (males) and hypothalamus (females) were associated with DNA methylation changes in the ERα gene. BPA exposure induced persistent, largely sex-specific effects on social and anxiety-like behavior, leading to disruption of sexually dimorphic behaviors. Although postnatal maternal care was altered in mothers treated with BPA during pregnancy, the effects of in utero BPA were not found to be mediated by maternal care. However, our data suggest that increased maternal care may partially attenuate the effects of in utero BPA on DNA methylation. Overall, we demonstrate that low-dose prenatal BPA exposure induces lasting epigenetic disruption in the brain that possibly underlie enduring effects of BPA on brain function and behavior, especially regarding sexually dimorphic phenotypes.

Congestive Heart Failure home monitoring pilot study in urban Denver.

With a growing number of low-income patients developing Congestive Heart Failure in urban Denver, accessible and affordable solutions are needed to provide home management options. A multidisciplinary team evaluated currently available options for telemonitoring and developed a solution for an initial pilot study. This system is currently used in the Denver Metro area (Colorado) for 44 CHF patients. Preliminary results show this approach is effective and has reduced the patients' average length of stay at the hospital compared to historical data and control patients who do not use a remote monitoring system.