The positive and negative consequences of stressors during early life

We discuss the long-term effects of stress exposure in pre- and early postnal life. We present an evolutionary framework within which such effects can be viewed, and describe how the outcomes might vary with species life histories. We focus on stressors that induce increases in glucocorticoid hormones and discuss the advantages of an experimental approach. We describe a number of studies demonstrating how exposure to these hormones in early life can influence stress responsiveness and have substantial long-term, negative consequences for adult longevity. We also describe how early life exposure to mild levels of stressors can have beneficial effects on resilience to stress in later life, and discuss how the balance of costs and benefits is likely dependent on the nature of the adult environment

The utilisation of urban resources by the herring gull (larus arqentatus)

The utilisation of urban resources by the Herring Gull was studied between 1973 and 1976 in Northeast England. This involved a study of refuse tips as a winter food supply, and the use of inhabited buildings as nesting sites. The local breeding population is small, and there is an influx of gulls from east Scottish and Norwegian colonies into Northeast England during the winter months. Herring Gulls caught during winter could be sexed by bill depth alone; wing length was used as an indicator of geographical origin. Gulls fed at refuse tips in the study area throughout the winter months. There was a predominance of adults over immatures at refuse tips in winter, while immatures predominated over adults around inshore fishing vessels in the same area. There was considerable fluctuation in the number of gulls present at tips on different days, related to weather factors and feeding conditions elsewhere. Immature Herring Gulls were less constant to a particular feeding area than adults, and adult females less so than adult males. Individual Herring Gulls did not feed at refuse tips every day, and refuse did not constitute the major or necessarily the only food source for these birds in winter. There were two different feeding areas used by gulls on the refuse tips which differed in the abundance and availability of food: individual birds consistently used one or other area, and proportionally more adult females than males used the secondary area. The number of nesting pairs/ pairs and nest sites used by Herring Gulls nesting on buildings in Sunderland and South Shields were monitored. Their breeding success was higher than in more "natural" colonies, possibly due to the nature of the nesting sites. A national census of gulls nesting on buildings in Britain and Ireland was organised in 1976, to measure the growth and spread of rooftop nesting: the number of Herring Gulls nesting on buildings was found to be doubling within 5 years, and the number of Lesser Black-backs within 3 years. The potential public health hazard presented by gulls nesting on buildings was reviewed

Environmental conditions can modulate the links among oxidative stress, age, and longevity

Understanding the links between environmental conditions and longevity remains a major focus in biological research. We examined within-individual changes between early- and mid-adulthood in the circulating levels of four oxidative stress markers linked to ageing, using zebra finches (Taeniopygia guttata): a DNA damage product (8-hydroxy-2′-deoxyguanosine; 8-OHdG), protein carbonyls (PC), non-enzymatic antioxidant capacity (OXY), and superoxide dismutase activity (SOD). We further examined whether such within-individual changes differed among birds living under control (ad lib food) or more challenging environmental conditions (unpredictable food availability), having previously found that the latter increased corticosterone levels when food was absent but improved survival over a three year period. Our key findings were: (i) 8-OHdG and PC increased with age in both environments, with a higher increase in 8-OHdG in the challenging environment; (ii) SOD increased with age in the controls but not in the challenged birds, while the opposite was true for OXY; (iii) control birds with high levels of 8-OHdG died at a younger age, but this was not the case in challenged birds. Our data clearly show that while exposure to the potentially damaging effects of oxidative stress increases with age, environmental conditions can modulate the pace of this age–related change

Parental resource allocation among offspring varies with increasing brood age in Black-legged Kittiwakes Rissa tridactyla

Capsule: Black-legged Kittiwakes Rissa tridactyla breeding at a North Sea colony allocated more resources to younger chicks with increasing brood age.<p></p> Aims: Examine how feeding, attendance and resource allocation change with increasing brood age and how allocation of feeds affects growth rate and fledging success.<p></p> Methods: Broods of two were observed on Coquet Island to compare feeding rates and fledging success between chicks of different hatching order.<p></p> Results: Growth and feeding rates were similar between chicks of different hatching order. The relationship between growth and feeding rate may have differed between siblings, although this relationship was not strong. Feeding rate per brood and nest attendance decreased nonlinearly as brood age increased. First-hatched chicks were fed more frequently at the beginning of multiple feeds and received a higher proportion of feeds during early chick-rearing. However, during late chick-rearing second-hatched chicks received proportionally more feeds.<p></p> Conclusion: Parents reduced overall feeding rate as brood age increased, while increasing the proportion of resources allocated to younger offspring. This may explain general similarities in growth rate and fledging success between chicks of different hatching order. By considering resource allocation throughout development we can better understand parental investment strategies in asynchronous species.<p></p&gt

Early-life adversity accelerates cellular ageing and affects adult inflammation: experimental evidence from the European starling

Early-life adversity is associated with accelerated cellular ageing during development and increased inflammation during adulthood. However, human studies can only establish correlation, not causation, and existing experimental animal approaches alter multiple components of early-life adversity simultaneously. We developed a novel hand-rearing paradigm in European starling nestlings (Sturnus vulgaris), in which we separately manipulated nutritional shortfall and begging effort for a period of 10 days. The experimental treatments accelerated erythrocyte telomere attrition and increased DNA damage measured in the juvenile period. For telomere attrition, amount of food and begging effort exerted additive effects. Only the combination of low food amount and high begging effort increased DNA damage. We then measured two markers of inflammation, high-sensitivity C-reactive protein and interleukin-6, when the birds were adults. The experimental treatments affected both inflammatory markers, though the patterns were complex and different for each marker. The effect of the experimental treatments on adult interleukin-6 was partially mediated by increased juvenile DNA damage. Our results show that both nutritional input and begging effort in the nestling period affect cellular ageing and adult inflammation in the starling. However, the pattern of effects is different for different biomarkers measured at different time points

Real-time head nod and shake detection for continuous human affect recognition

Human affect recognition is the field of study associated with using automatic techniques to identify human emotion or human affective state. A person’s affective states is often communicated non-verbally through body language. A large part of human body language communication is the use of head gestures. Almost all cultures use subtle head movements to convey meaning. Two of the most common and distinct head gestures are the head nod and the head shake gestures. In this paper we present a robust system to automatically detect head nod and shakes. We employ the Microsoft Kinect and utilise discrete Hidden Markov Models (HMMs) as the backbone to a to a machine learning based classifier within the system. The system achieves 86% accuracy on test datasets and results are provided

Design of a Potent, Selective, and Brain-Penetrant Inhibitor of Wnt-Deactivating Enzyme Notum by Optimization of a Crystallographic Fragment Hit

Notum is a carboxylesterase that suppresses Wnt signaling through deacylation of an essential palmitoleate group on Wnt proteins. There is a growing understanding of the role Notum plays in human diseases such as colorectal cancer and Alzheimer's disease, supporting the need to discover improved inhibitors, especially for use in models of neurodegeneration. Here, we have described the discovery and profile of 8l (ARUK3001185) as a potent, selective, and brain-penetrant inhibitor of Notum activity suitable for oral dosing in rodent models of disease. Crystallographic fragment screening of the Diamond-SGC Poised Library for binding to Notum, supported by a biochemical enzyme assay to rank inhibition activity, identified 6a and 6b as a pair of outstanding hits. Fragment development of 6 delivered 8l that restored Wnt signaling in the presence of Notum in a cell-based reporter assay. Assessment in pharmacology screens showed 8l to be selective against serine hydrolases, kinases, and drug targets

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

文献目録

textabstractHuman immunodeficiency virus type I enhancer binding protein 2 (HIVEP2) has been previously associated with intellectual disability and developmental delay in three patients. Here, we describe six patients with developmental delay, intellectual disability, and dysmorphic features with de novo likely gene-damaging variants in HIVEP2 identified by whole-exome sequencing (WES). HIVEP2 encodes a large transcription factor that regulates various neurodevelopmental pathways. Our findings provide further evidence that pathogenic variants in HIVEP2 lead to intellectual disabilities and developmental delay