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

Cell migration leads to spatially distinct but clonally related airway cancer precursors

Background Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related. Methods Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship. Results We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12 years. Conclusions Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree

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

A latent trait approach to measuring HIV/AIDS related stigma in healthcare professionals: application of mokken scaling technique

The attitudes of healthcare professionals towards HIV positive patients and high risk groups are central to the quality of care and therefore to the management of HIV/AIDS related stigma in health settings. Extant HIV/AIDS stigma scales that measure stigmatising attitudes towards people living with HIV/AIDS have been developed using scaling techniques such as principal component analysis. This approach has resulted in instruments that are often long. Mokken scale analysis is a nonparametric hierarchical scaling technique that can be used to develop unidimensional cumulative scales. This technique is advantageous over the other approaches; as the scales are usually shorter, while retaining acceptable psychometric properties. Moreover, Mokken scales also make no distributional assumptions about the underlying data, other than that the data are capable of being ordered by item and by person. In this study we aimed at developing a precise and concise measure of HIV/AIDS related stigma among health care professionals, using Mokken scale analysis

Association of childhood trauma with cognitive function in healthy adults: a pilot study

BACKGROUND: Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults. METHODS: In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB) and the Wide-Range-Achievement-Test (WRAT-3) to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ). Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales) and potential confounders (age, sex, education, income). RESULTS: Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p < 0.01. CONCLUSIONS: Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology

Common marmoset (Callithrix jacchus) personality, subjective well-being, hair cortisol level and AVPR1a, OPRM1, and DAT genotypes

We studied personality, subjective well-being, and hair cortisol level, in common marmosets Callithrix jacchus, a small, cooperatively breeding New World monkey, by examining their associations with one another and genotypes. Subjects were 68 males and 9 females that lived in the RIKEN Center for Life Science Technologies. Personality and subjective well-being were assessed by keeper ratings on two questionnaires, hair samples were obtained to assay cortisol level and buccal swabs were used to assess AVPR1a, OPRM1 and DAT genotypes. Three personality domains—Dominance, Sociability, and Neuroticism—were identified. Consistent with findings in other species, Sociability and Neuroticism were related to higher and lower subjective well-being, respectively. Sociability was also associated with higher hair cortisol levels. The personality domains and hair cortisol levels were heritable and associated with genotypes: the short form of AVPR1a was associated with lower Neuroticism and the AA genotype of the A111T SNP of OPRM1 was related to lower Dominance, lower Neuroticism, and higher hair cortisol level. Some genetic associations were not in directions that one would expect given findings in other species. These findings provide insights into the proximate and ultimate bases of personality in common marmosets, other primates and humans

Personality of wild male crested macaques (Macaca nigra).

Animal personalities, i.e. consistent differences in behavior across time and/or context, have received increased attention of behavioral biologists over the last years. Recent research shows that personalities represent traits on which natural and sexual selection work and which can have substantial fitness consequences. The aim of this study is to establish the personality structure of crested macaque (Macaca nigra) males as foundation for future studies on its adaptive value. We collected behavioral data through focal animal sampling and additionally conducted two sets of playback experiments. Results of a factor analysis on the behavioral data revealed a four factor structure with components we labeled Anxiety, Sociability, Connectedness and Aggressiveness. Results from the experiments revealed an additional and independent Boldness factor but the absence of Neophilia. Overall, this structure resembles other macaque and animal species with the exception of Connectedness, which might be a consequence of the species' tolerant social style. Our results thus not only form the basis for future studies on the adaptive value of personality in crested macaques but also contribute an important data point for investigating the evolution of personality structure from a comparative perspective by refining, for example, which personality factors characterized the last common ancestor of hominids and macaques

Involvement in surface antigen expression by a moonlighting FG-repeat nucleoporin in trypanosomes

Components of the nuclear periphery coordinate a multitude of activities, including macromolecular transport, cell-cycle progression, and chromatin organization. Nuclear pore complexes (NPCs) mediate nucleocytoplasmic transport, mRNA processing, and transcriptional regulation, and NPC components can define regions of high transcriptional activity in some organisms at the nuclear periphery and nucleoplasm. Lineage-specific features underpin several core nuclear functions and in trypanosomatids, which branched very early from other eukaryotes, unique protein components constitute the lamina, kinetochores, and parts of the NPCs. Here we describe a phenylalanine-glycine (FG)-repeat nucleoporin, TbNup53b, that has dual localizations within the nucleoplasm and NPC. In addition to association with nucleoporins, TbNup53b interacts with a known trans-splicing component, TSR1, and has a role in controlling expression of surface proteins including the nucleolar periphery-located, procyclin genes. Significantly, while several nucleoporins are implicated in intranuclear transcriptional regulation in metazoa, TbNup53b appears orthologous to components of the yeast/human Nup49/Nup58 complex, for which no transcriptional functions are known. These data suggest that FG-Nups are frequently co-opted to transcriptional functions during evolution and extend the presence of FG-repeat nucleoporin control of gene expression to trypanosomes, suggesting that this is a widespread and ancient eukaryotic feature, as well as underscoring once more flexibility within nucleoporin function

An exploration of the relationships among facial dimensions, age, sex, dominance status and personality in rhesus macaques (Macaca mulatta)

Aspects of personality in nonhuman primates have been linked to health, social relationships, and life history outcomes. In humans as well as nonhuman primates, facial morphology is associated with assertiveness, aggression, and measures of dominance status. In this study we aimed to examine the relationship among facial morphology, age, sex, dominance status, and ratings on the personality dimensions Confidence, Openness, Assertiveness, Friendliness, Activity, and Anxiety in rhesus macaques (Macaca mulatta). We measured facial width-to-height ratio (fWHR) and lower-height/full-height ratio (fLHFH) using photographs from 109 captive rhesus macaques, which observers also assessed for dominance status and personality, and explored the associations among facial morphology, age, sex, dominance status, and personality. fWHR and fLHFH personality associations depended on age category: Assertiveness was associated with higher fWHR and fLHFH, and Confidence was associated with lower fWHR and fLHFH, but all these associations were consistent only in individuals &lt;8 yr. of age. We found fWHR and fLHFH to not be consistently associated with sex or dominance status; compared to younger individuals, we found few associations with fWHR and fLHFH for individuals older than 8 yr., which may be due to limited sample size. Our results indicate that in macaques &lt;8 yr. old, facial morphology is associated with the Assertiveness and Confidence personality dimensions, which is consistent with results suggesting a relationship between fWHR and trait aggression in humans and assertiveness in brown capuchins, all of which implies that fWHR might be a cue to assertive and aggressive traits

Does true Gleason pattern 3 merit its cancer descriptor?

Nearly five decades following its conception, the Gleason grading system remains a cornerstone in the prognostication and management of patients with prostate cancer. In the past few years, a debate has been growing whether Gleason score 3 + 3 = 6 prostate cancer is a clinically significant disease. Clinical, molecular and genetic research is addressing the question whether well characterized Gleason score 3 + 3 = 6 disease has the ability to affect the morbidity and quality of life of an individual in whom it is diagnosed. The consequences of treatment of Gleason score 3 + 3 = 6 disease are considerable; few men get through their treatments without sustaining some harm. Further modification of the classification of prostate cancer and dropping the label cancer for Gleason score 3 + 3 = 6 disease might be warranted