Evidence for a Kernel of Truth in Children’s Facial Impressions of Children’s Niceness, but not Shyness

Acknowledgements: We are grateful to the parents and children who helped make this research possible. We would like to thank Romina Palermo for providing us the opportunity to contact her sample of participants and to use some existing data. We also thank Lou Ewing for sharing the Zeb the Alien Scientist testing materials, and Saba Siddique for comments regarding a manuscript draft. Finally, we would like to thank Kaitlyn Turbett, Dielle Horne, Saba Siddique, Chloe Giffard, and Maira Vicente Braga, for help testing participants. JC, LJ, GR, and CS conceived the study and helped to draft and edit the manuscript. JC programmed the experiment, collected most participant data, performed the statistical analyses and drafted the first manuscript draft. EB coordinated image collection and testing schedules. All authors participated in the study design, and read, provided critical revisions and approved the final manuscript. The study methods, hypotheses and analyses were pre-registered(https://osf.io/kjtva/registrations). Funding: This research was supported by an APR Internship Academic Mentor Grant to CS, an Australian Research Council (ARC) Centre of Excellence Grant award to GR [CE110001021], ARC Discovery Early Career Research Award to CS [DE190101043], ARC Discovery Grant to GR and CS [DP170104602], ARC Discovery Grant to LJ [140101743], and a Research Training Program stipend to JC.Peer reviewedPostprin

Funerary Artifacts, Social Status, and Atherosclerosis in Ancient Peruvian Mummy Bundles

Background: Evidence of atherosclerotic plaques in ancient populations has led to the reconsideration of risk factors for heart disease and of the common belief that it is a disease of modern times. Methods: Fifty-one wrapped mummy bundles excavated from the sites of Huallamarca, Pedreros, and Rinconada La Molina from the Puruchuco Museum collection in Lima, Peru, were scanned using computed tomography to investigate the presence of atherosclerosis. Funerary artifacts contained within the undisturbed mummy bundles were analyzed as an attempt to infer the social status of the individuals to correlate social status with evidence of heart disease in this ancient Peruvian group. This work also provides an inventory of the museum mummy collection to guide and facilitate future research. Results: Statistical analysis concluded that there is little association between the types of grave goods contained within the bundles when the groups are pooled together. However, some patterns of artifact type, material, atherosclerosis, and sex emerge when the 3 excavation sites are analyzed separately. Conclusions: From the current sample, it would seem that social class is difficult to discern, but those from Huallamarca have the most markers of elite status. We had hypothesized that higher-status individuals may have had lifestyles that would place them at a higher risk for atherogenesis. There seems to be some indication of this within the site of Huallamarca, but it is inconclusive in the other 2 archeological sites. It is possible that a larger sample size in the future could reveal more statistically significant results

Genomic Correlates of Atherosclerosis in Ancient Humans

Paleogenetics offers a unique opportunity to study human evolution, population dynamics, and disease evolution in situ. Although histologic and computed x-ray tomographic investigations of ancient mummies have clearly shown that atherosclerosis has been present in humans for more than 5,000 years, limited data are available on the presence of genetic predisposition for cardiovascular disease in ancient human populations. In a previous whole-genome study of the Tyrolean Iceman, a 5,300-year-old glacier mummy from the Alps, an increased risk for coronary heart disease was detected. The Iceman’s genome revealed several single nucleotide polymorphisms that are linked with cardiovascular disease in genome-wide association studies. Future genetic studies of ancient humans from various geographic origins and time periods have the potential to provide more insights into the presence and possible changes of genetic risk factors in our ancestors. The study of ancient humans and a better understanding of the interaction between environmental and genetic influences on the development of heart diseases may lead to a more effective prevention and treatment of the most common cause of death in the modern world

Coronary Atherosclerosis in Indigenous South American Tsimane: A Cross-Sectional Cohort Study

Background—Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. Methods—We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. Findings—Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1–100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0-0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2.35 mmol/L (91 mg/dL) and 1.0 mmol/L (39.5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High- sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3.0 mg/dL in 360 (51%) Tsimane participants. Interpretation—Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined

The impact of islet mass, number of transplants, and time between transplants on graft function in a national islet transplant program

The UK islet allotransplant program is nationally funded to deliver one or two transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus two transplants; time between two transplants and graft survival (stimulated C-peptide >50 pmol/L) and function. In total, 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23 (68%) single and 47 (94%) (p =.002) two transplant recipients (separated by [median (IQR)] 6 (3–8) months). 64% recipients of one or two transplants with uninterrupted function at 12 months sustained graft function at 6 years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p <.01). Despite 1.9-fold greater transplanted mass in recipients of two versus one islet infusion (12 218 [9291–15 417] vs. 6442 [5156–7639] IEQ/kg; p <.0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta −0.35; p =.02). Graft survival over the first 12 months was greater in recipients of two versus one islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function

Dynamic changes in the brain protein interaction network correlates with progression of A?42 pathology in Drosophila

Alzheimer’s disease (AD), the most prevalent form of dementia, is a progressive and devastating neurodegenerative condition for which there are no effective treatments. Understanding the molecular pathology of AD during disease progression may identify new ways to reduce neuronal damage. Here, we present a longitudinal study tracking dynamic proteomic alterations in the brains of an inducible Drosophila melanogaster model of AD expressing the Arctic mutant Aβ42 gene. We identified 3093 proteins from flies that were induced to express Aβ42 and age-matched healthy controls using label-free quantitative ion-mobility data independent analysis mass spectrometry. Of these, 228 proteins were significantly altered by Aβ42 accumulation and were enriched for AD-associated processes. Network analyses further revealed that these proteins have distinct hub and bottleneck properties in the brain protein interaction network, suggesting that several may have significant effects on brain function. Our unbiased analysis provides useful insights into the key processes governing the progression of amyloid toxicity and forms a basis for further functional analyses in model organisms and translation to mammalian systems

Efficient Gene Targeting by Homologous Recombination in Rat Embryonic Stem Cells

The rat is the preferred experimental animal in many biological studies. With the recent derivation of authentic rat embryonic stem (ES) cells it is now feasible to apply state-of-the art genetic engineering in this species using homologous recombination. To establish whether rat ES cells are amenable to in vivo recombination, we tested targeted disruption of the hypoxanthine phosphoribosyltransferase (hprt) locus in ES cells derived from both inbred and outbred strains of rats. Targeting vectors that replace exons 7 and 8 of the hprt gene with neomycinR/thymidine kinase selection cassettes were electroporated into male Fisher F344 and Sprague Dawley rat ES cells. Approximately 2% of the G418 resistant colonies also tolerated selection with 6-thioguanine, indicating inactivation of the hprt gene. PCR and Southern blot analysis confirmed correct site-specific targeting of the hprt locus in these clones. Embryoid body and monolayer differentiation of targeted cell lines established that they retained differentiation potential following targeting and selection. This report demonstrates that gene modification via homologous recombination in rat ES cells is efficient, and should facilitate implementation of targeted, genetic manipulation in the rat

Prevalence of Dementia and Mild Cognitive Impairment in Indigenous Bolivian Forager-Horticulturalists

Introduction We evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle. Methods Participants from population-based samples ≥ 60 years of age (n = 623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans. Results Tsimane exhibited five cases of dementia (among n = 435; crude prevalence = 1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n = 169; crude prevalence = 0.6%, 95% CI: 0.0, 3.2), all age ≥ 80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia. Discussion The prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer\u27s disease (AD) dementia phenotype