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Dominance hierarchies are widespread in animal social groups and often have measureable effects on individual health and reproductive success. Dominance ranks are not static individual attributes, however, but instead are influenced by two independent processes: 1) changes in hierarchy membership and 2) successful challenges of higher-ranking individuals. Understanding which of these processes dominates the dynamics of rank trajectories can provide insights into fitness benefits of within-sex competition. This question has yet to be examined systematically in a wide range of taxa due to the scarcity of long-term data and a lack of appropriate methodologies for distinguishing between alternative causes of rank changes over time. Here, we expand on recent work and develop a new likelihood-based Elo rating method that facilitates the systematic assessment of rank dynamics in animal social groups, even when interaction data are sparse. We apply this method to characterize long-term rank trajectories in wild eastern chimpanzees ( Pan troglodytes schweinfurthii ) and find remarkable sex differences in rank dynamics, indicating that females queue for social status while males actively challenge each other to rise in rank. Further, our results suggest that natal females obtain a head start in the rank queue if they avoid dispersal, with potential fitness benefits.

Humans and other primates are distinct among placental mammals in having exceptionally slow rates of growth, reproduction, and aging. Primates’ slow life history schedules are generally thought to reflect an evolved strategy of allocating energy away from growth and reproduction and toward somatic investment, particularly to the development and maintenance of large brains. Here we examine an alternative explanation: that primates’ slow life histories reflect low total energy expenditure (TEE) (kilocalories per day) relative to other placental mammals. We compared doubly labeled water measurements of TEE among 17 primate species with similar measures for other placental mammals. We found that primates use remarkably little energy each day, expending on average only 50% of the energy expected for a placental mammal of similar mass. Such large differences in TEE are not easily explained by differences in physical activity, and instead appear to reflect systemic metabolic adaptation for low energy expenditures in primates. Indeed, comparisons of wild and captive primate populations indicate similar levels of energy expenditure. Broad interspecific comparisons of growth, reproduction, and maximum life span indicate that primates’ slow metabolic rates contribute to their characteristically slow life histories.

Dogs live in the dynamic human social networks full of strangers, yet they form strong and selective bonds with familiar caretakers. Little is known about how a bond is initially formed between a dog and a complete stranger. The first-impression hypothesis suggests that interacting with strangers can present an opportunity to form a mutualistic partnership. It predicts that dogs should respond positively toward a complete stranger to facilitate bonding (Prediction 1) and adjust their preferences in response to the perceived risk and benefit of interacting with strangers (Prediction 2). We examine the social preferences of pet dogs toward a complete stranger whom they have never met before and several other potential partners – the owner with whom subjects have had a positive, long-term bond (Experiment 1 ), and an exposed stranger with whom they have had a positive short-term interaction (Experiment 2 ) or a negative one (Experiment 3 ). In support of Prediction 1, subjects were exceptionally trusting across contexts. Mixed results were found with regard to Prediction 2. Subjects preferred their owner over a stranger when following social cues and (to a lesser degree) when approaching and feeding in close proximity. However, relative to a complete stranger, subjects did not consistently prefer the positively exposed stranger or avoid the negatively exposed one. The lack of clear selectivity might be due to pet dogs’ high baseline level of trust of complete strangers or reflect the strength of their existing bonds that negated the need for another positive bond with a new human partner.

In humans and other social mammals, more socially connected females often have higher fitness. Yet evidence linking female sociality to offspring survival remains inconsistent, and is limited to a handful of primate species in which females depend on close female kin for social status. Here we examine the relationship between female social integration and offspring survival in eastern chimpanzees. We find that females that were more socially integrated with other females in the year before giving birth had higher offspring survival to age 1 (the period of highest mortality) and age 5 (the approximate age of weaning). Furthermore, social integration remained a strong predictor of offspring survival among females without close female kin. Our results thus add to a small set of studies linking sociality with offspring survival, here in the dispersing sex. As in humans, more socially connected female chimpanzees have higher offspring survival, despite primarily residing with non-kin.

Navigating social systems efficiently is critical to our species. Humans appear endowed with a cognitive system that has formed to meet the unique challenges that emerge for highly social species. Bullshitting, communication characterised by an intent to be convincing or impressive without concern for truth, is ubiquitous within human societies. Across two studies (N = 1,017), we assess participants’ ability to produce satisfying and seemingly accurate bullshit as an honest signal of their intelligence. We find that bullshit ability is associated with an individual’s intelligence and individuals capable of producing more satisfying bullshit are judged by second-hand observers to be more intelligent. We interpret these results as adding evidence for intelligence being geared towards the navigation of social systems. The ability to produce satisfying bullshit may serve to assist individuals in negotiating their social world, both as an energetically efficient strategy for impressing others and as an honest signal of intelligence.

Interleukin-2 (IL-2) has an essential role in the expansion and function of CD4+ regulatory T cells (Tregs). Tregs reduce tissue damage by limiting the immune response following infection and regulate autoreactive CD4+ effector T cells (Teffs) to prevent autoimmune diseases, such as type 1 diabetes (T1D). Genetic susceptibility to T1D causes alterations in the IL-2 pathway, a finding that supports Tregs as a cellular therapeutic target. Aldesleukin (Proleukin; recombinant human IL-2), which is administered at high doses to activate the immune system in cancer immunotherapy, is now being repositioned to treat inflammatory and autoimmune disorders at lower doses by targeting Tregs. To define the aldesleukin dose response for Tregs and to find doses that increase Tregs physiologically for treatment of T1D, a statistical and systematic approach was taken by analysing the pharmacokinetics and pharmacodynamics of single doses of subcutaneous aldesleukin in the Adaptive Study of IL-2 Dose on Regulatory T Cells in Type 1 Diabetes (DILT1D), a single centre, non-randomised, open label, adaptive dose-finding trial with 40 adult participants with recently diagnosed T1D. The primary endpoint was the maximum percentage increase in Tregs (defined as CD3+CD4+CD25highCD127low) from the baseline frequency in each participant measured over the 7 d following treatment. There was an initial learning phase with five pairs of participants, each pair receiving one of five pre-assigned single doses from 0.04 × 106 to 1.5 × 106 IU/m2, in order to model the dose-response curve. Results from each participant were then incorporated into interim statistical modelling to target the two doses most likely to induce 10% and 20% increases in Treg frequencies. Primary analysis of the evaluable population (n = 39) found that the optimal doses of aldesleukin to induce 10% and 20% increases in Tregs were 0.101 × 106 IU/m2 (standard error [SE] = 0.078, 95% CI = -0.052, 0.254) and 0.497 × 106 IU/m2 (SE = 0.092, 95% CI = 0.316, 0.678), respectively. On analysis of secondary outcomes, using a highly sensitive IL-2 assay, the observed plasma concentrations of the drug at 90 min exceeded the hypothetical Treg-specific therapeutic window determined in vitro (0.015-0.24 IU/ml), even at the lowest doses (0.040 × 106 and 0.045 × 106 IU/m2) administered. A rapid decrease in Treg frequency in the circulation was observed at 90 min and at day 1, which was dose dependent (mean decrease 11.6%, SE = 2.3%, range 10.0%-48.2%, n = 37), rebounding at day 2 and increasing to frequencies above baseline over 7 d. Teffs, natural killer cells, and eosinophils also responded, with their frequencies rapidly and dose-dependently decreased in the blood, then returning to, or exceeding, pretreatment levels. Furthermore, there was a dose-dependent down modulation of one of the two signalling subunits of the IL-2 receptor, the β chain (CD122) (mean decrease = 58.0%, SE = 2.8%, range 9.8%-85.5%, n = 33), on Tregs and a reduction in their sensitivity to aldesleukin at 90 min and day 1 and 2 post-treatment. Due to blood volume requirements as well as ethical and practical considerations, the study was limited to adults and to analysis of peripheral blood only. The DILT1D trial results, most notably the early altered trafficking and desensitisation of Tregs induced by a single ultra-low dose of aldesleukin that resolves within 2-3 d, inform the design of the next trial to determine a repeat dosing regimen aimed at establishing a steady-state Treg frequency increase of 20%-50%, with the eventual goal of preventing T1D. ISRCTN Registry ISRCTN27852285; ClinicalTrials.gov NCT01827735.

Zika virus infection of pregnant nonhuman primates results in the loss of fetal neuronal progenitor cells, even in the absence of overt microcephaly. Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque ( Macaca nemestrina ) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

To map the 2021 American Association of Colleges of Nursing Essentials to the American Nurses Association Essentials of Genomic Nursing for all nurses and provide resources for nursing faculty to support the seamless integration of genomics into existing undergraduate curricula. Since the completion of the Human Genome Project in 2003, rapid advancements in genomic science leading to practical applications of genomics have revolutionized all areas of healthcare. Nursing is built on foundational life sciences, including genomics. As the largest segment of the healthcare workforce, who spend the most time with patients and families, nurses play a critical role in healthcare teams integrating genomic knowledge into patient care to improve health and well-being. Consequently, nurses must be equipped with foundational genomic knowledge and skills during their undergraduate education. However, there is wide variability in whether and how nursing programs have incorporated genomics into their curricula. Additionally, nursing faculty may have limited knowledge of foundational genomic concepts and lack confidence in teaching genomics. Discussion paper We aligned domains from the American Association of Colleges of Nursing Essentials and American Nurses Association Essentials of Genomic Nursing. A map illustrating alignment in multiple areas, which provide examples of ways to integrate genomics into existing nursing curricula. Although based on domains developed in the United States, the map, curricular resources, example learning outcomes, and clinical vignettes can be used by nursing faculty globally to prepare future nurses who are competent in providing genomics-informed nursing care on entry-to-practice.

Background Multiple marker screening is offered to pregnant individuals in many jurisdictions to screen for trisomies 21 and 18. On occasion, the result is ‘double-positive’—a screening result that is unexpectedly positive for both aneuploidies. Although this occurs rarely, the paucity of available evidence about the outcomes of these pregnancies hinders patient counselling. This study aimed to investigate the association of double-positive results with preterm birth and other adverse perinatal outcomes. Methods We conducted a population-based retrospective cohort study of pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, using province-wide perinatal registry data in Ontario, Canada. Pregnancies with double-positive screening results where trisomies 21 and 18 were ruled-out were compared to pregnancies with screen negative results for both aneuploidies. We used modified Poisson regression models with robust variance estimation to examine the association of double positive results with preterm birth and secondary outcomes. Results From 429 540 pregnancies with multiple marker screening, 863 (0.2%) had a double-positive result; trisomies 21 and 18 were ruled out in 374 pregnancies, 203 of which resulted in a live birth. Among the pregnancies in the double-positive group resulting in a live birth, the risk of preterm birth was increased compared to pregnancies with a screen negative result: adjusted risk ratio (aRR) 2.6 (95%CI 2.0-3.6), adjusted risk difference (aRD) 10.5% (95%CI 5.4–15.7). In a sensitivity analysis excluding all diagnosed chromosomal abnormalities, the risk of preterm birth remained elevated to a similar degree: aRR 2.6 (95%CI 1.9–3.7), aRD 10.0% (95%CI 4.8–15.3). The risk of other adverse perinatal outcomes was also higher, including the risk of chromosomal abnormalities other than trisomies 21 and 18: aRR 81.1 (95%CI 69.4–94.8), aRD 34.0% (95%CI 29.2–38.8). Pregnancies with double-positive results were also less likely to result in a live birth, even when excluding all diagnosed chromosomal abnormalities; and at increased risk of adverse perinatal outcomes for those resulting in a live birth. Conclusion Although rare, double-positive multiple marker screening results are associated with an increased risk of preterm birth and other adverse perinatal outcomes, even when excluding all identified chromosomal abnormalities.