VACCINATION AND REDUCED COHORT DURATION CAN DRIVE VIRULENCE EVOLUTION: MAREK’S DISEASE VIRUS AND INDUSTRIALIZED AGRICULTURE

Marek’s disease virus (MDV), a commercially important disease of poultry, has become substantially more virulent over the last 60 years. This evolution was presumably a consequence of changes in virus ecology associated with the intensification of the poultry industry. Here, we assess whether vaccination or reduced host life span could have generated natural selection, which favored more virulent strains. Using previously published experimental data, we estimated viral fitness under a range of cohort durations and vaccine treatments on broiler farms. We found that viral fitness maximized at intermediate virulence, as a result of a trade‐off between virulence and transmission previously reported. Our results suggest that vaccination, acting on this trade‐off, could have led to the evolution of increased virulence. By keeping the host alive, vaccination prolongs infectious periods of virulent strains. Improvements in host genetics and nutrition, which reduced broiler life spans below 50 days, could have also increased the virulence of the circulating MDV strains because shortened cohort duration reduces the impact of host death on viral fitness. These results illustrate the dramatic impact anthropogenic change can potentially have on pathogen virulence.     

‘Manipulation’ without the parasite: altered feeding behaviour of mosquitoes is not dependent on infection with malaria parasites

Previous studies have suggested that Plasmodium parasites can manipulate mosquito feeding behaviours such as probing, persistence and engorgement rate in order to enhance transmission success. Here, we broaden analysis of this ‘manipulation phenotype’ to consider proximate foraging behaviours, including responsiveness to host odours and host location. Using Anopheles stephensi and Plasmodium yoelii as a model system, we demonstrate that mosquitoes with early stage infections (i.e. non-infectious oocysts) exhibit reduced attraction to a human host, whereas those with late-stage infections (i.e. infectious sporozoites) exhibit increased attraction. These stage-specific changes in behaviour were paralleled by changes in the responsiveness of mosquito odourant receptors, providing a possible neurophysiological mechanism for the responses. However, we also found that both the behavioural and neurophysiological changes could be generated by immune challenge with heat-killed Escherichia coli and were thus not tied explicitly to the presence of malaria parasites. Our results support the hypothesis that the feeding behaviour of female mosquitoes is altered by Plasmodium, but question the extent to which this is owing to active manipulation by malaria parasites of host behaviour.     

Social encounter networks: characterizing Great Britain

A major goal of infectious disease epidemiology is to understand and predict the spread of infections within human populations, with the intention of better informing decisions regarding control and intervention. However, the development of fully mechanistic models of transmission requires a quantitative understanding of social interactions and collective properties of social networks. We performed a cross-sectional study of the social contacts on given days for more than 5000 respondents in England, Scotland and Wales, through postal and online survey methods. The survey was designed to elicit detailed and previously unreported measures of the immediate social network of participants relevant to infection spread. Here, we describe individual-level contact patterns, focusing on the range of heterogeneity observed and discuss the correlations between contact patterns and other socio-demographic factors. We find that the distribution of the number of contacts approximates a power-law distribution, but postulate that total contact time (which has a shorter-tailed distribution) is more epidemiologically relevant. We observe that children, public-sector and healthcare workers have the highest number of total contact hours and are therefore most likely to catch and transmit infectious disease. Our study also quantifies the transitive connections made between an individual''s contacts (or clustering); this is a key structural characteristic of social networks with important implications for disease transmission and control efficacy. Respondents'' networks exhibit high levels of clustering, which varies across social settings and increases with duration, frequency of contact and distance from home. Finally, we discuss the implications of these findings for the transmission and control of pathogens spread through close contact.     

VOCAL REPERTOIRE OF WILD BREEDING ORANGE-WINGED PARROTS AMAZONA AMAZONICA IN AMAZONIA

ABSTRACT

The vocal repertoire of Amazona amazonica during its breeding season has been recorded from wild individuals in Santa Bárbara do Pará, Pará State, Brazil. At individual nests, we continuously recorded vocalizations and behaviour for four hours in the early morning and three hours in the late afternoon, three times a week throughout the breeding season. We identified nine vocalizations that we classified in three behavioural categories: (1) Flight call—emitted when parrots arrive in the nest area; (2) Perched contact calls—two different vocalizations, one of them related to feeding, were emitted when the pair was perched in the nest area and interacted socially between themselves or with other individuals; (3) Aggressive calls—emitted when birds were in a dangerous situation, i.e. alarm (three types of calls), agonistic contact and distress calls (two types of call). The Orange-winged Parrot is a highly social species and the complexity of its social interactions is reflected in the diversity of its vocal repertoire.     

120 例初治、年轻、中高/ 高危弥漫大B细胞淋巴瘤的临床分析

目的:探讨初治、年轻、中高/高危弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的临床特征、治疗措施及预后影响因素。方法:回顾性分析2006年1月至2014年5月军事医学科学院附属医院淋巴瘤科收治的年龄≤60岁、年龄调整的国际预后指数(aa IPI)评分≥2分的初治DLBCL病例,进行疗效及预后相关因素的分析。结果:共收集到资料完整的DLBCL病例120例,中位随访28(4-106)个月,3年PFS率53.25%,OS率61.52%。单因素分析结果显示B症状、治疗方案及近期疗效、自体移植对无进展生存(PFS)及总体生存(OS)率的影响有统计学意义。多因素分析结果显示治疗方案、自体造血干细胞移植是影响PFS、OS率的独立影响因素。结论:年轻、中高/高危DLBCL具有高度异质性,病理细胞来源、Ki-67等在本组病例中未见显著预后意义,有待临床进一步探索。     

Quantifying Transmission Investment in Malaria Parasites

Many microparasites infect new hosts with specialized life stages, requiring a subset of the parasite population to forgo proliferation and develop into transmission forms. Transmission stage production influences infectivity, host exploitation, and the impact of medical interventions like drug treatment. Predicting how parasites will respond to public health efforts on both epidemiological and evolutionary timescales requires understanding transmission strategies. These strategies can rarely be observed directly and must typically be inferred from infection dynamics. Using malaria as a case study, we test previously described methods for inferring transmission stage investment against simulated data generated with a model of within-host infection dynamics, where the true transmission investment is known. We show that existing methods are inadequate and potentially very misleading. The key difficulty lies in separating transmission stages produced by different generations of parasites. We develop a new approach that performs much better on simulated data. Applying this approach to real data from mice infected with a single Plasmodium chabaudi strain, we estimate that transmission investment varies from zero to 20%, with evidence for variable investment over time in some hosts, but not others. These patterns suggest that, even in experimental infections where host genetics and other environmental factors are controlled, parasites may exhibit remarkably different patterns of transmission investment.     

MTH1 Substrate Recognition—An Example of Specific Promiscuity

MTH1 (NUDT1) is an oncologic target involved in the prevention of DNA damage. We investigate the way MTH1 recognises its substrates and present substrate-bound structures of MTH1 for 8-oxo-dGTP and 8-oxo-rATP as examples of novel strong and weak binding substrate motifs. Investigation of a small set of purine-like fragments using 2D NMR resulted in identification of a fragment with weak potency. The protein-ligand X-Ray structure of this fragment provides insight into the role of water molecules in substrate selectivity. Wider fragment screening by NMR resulted in three new protein structures exhibiting alternative binding configurations to the key Asp-Asp recognition element of the protein. These inhibitor binding modes demonstrate that MTH1 employs an intricate yet promiscuous mechanism of substrate anchoring through its Asp-Asp pharmacophore. The structures suggest that water-mediated interactions convey selectivity towards oxidized substrates over their non-oxidised counterparts, in particular by stabilization of a water molecule in a hydrophobic environment through hydrogen bonding. These findings may be useful in the design of inhibitors of MTH1.     

Smartphone-Based Distributed Data Collection Enables Rapid Assessment of Shorebird Habitat Suitability

Understanding and managing dynamic coastal landscapes for beach-dependent species requires biological and geological data across the range of relevant environments and habitats. It is difficult to acquire such information; data often have limited focus due to resource constraints, are collected by non-specialists, or lack observational uniformity. We developed an open-source smartphone application called iPlover that addresses these difficulties in collecting biogeomorphic information at piping plover (Charadrius melodus) nest sites on coastal beaches. This paper describes iPlover development and evaluates data quality and utility following two years of collection (n = 1799 data points over 1500 km of coast between Maine and North Carolina, USA). We found strong agreement between field user and expert assessments and high model skill when data were used for habitat suitability prediction. Methods used here to develop and deploy a distributed data collection system have broad applicability to interdisciplinary environmental monitoring and modeling.     

Accounting for the nested nature of genetic variation across levels of organization improves our understanding of biodiversity and community ecology

Recent work has demonstrated that the presence or abundance of specific genotypes, populations, species and phylogenetic clades may influence community and ecosystem properties such as resilience or productivity. Many ecological studies, however, use simple linear models to test for such relationships, including species identity as the predictor variable and some measured trait or function as the response variable without accounting for the nestedness of genetic variation across levels of organization. This omission may lead to incorrect inference about which source of variation influences community and ecosystem properties. Here, we explicitly compare this common approach to alternative ways of modeling variation in trait data, using simulated trait data and empirical results of common‐garden trials using multiple levels of genetic variation within Eucalyptus, Populus and Picea. We show that: 1) when nested variation is ignored, an incorrect conclusion of species effect is drawn in up to 20% of cases; 2) overestimation of the species effect increases – up to 60% in some scenarios – as the nested term explains more of the variation; and 3) the sample sizes needed to overcome these potential problems associated with aggregating nested hierarchical variation may be impractically large. In common‐garden trials, incorporating nested models increased explanatory power twofold for mammal browsing rate in Eucalyptus, threefold for leaf area in Populus, and tenfold for branch number in Picea. Thoroughly measuring intraspecific variation and characterizing hierarchical genetic variation beyond the species level has implications for developing more robust theory in community ecology, managing invaded natural systems, and improving inference in biodiversity–ecosystem functioning research. Synthesis Until recently, ecologists acknowledged the ubiquity of within‐species trait variation, but paid scant attention to how much it affects communities and ecosystems. Here, the authors used simulated trait data and common‐garden studies to demonstrate that we ignore intraspecific trait variation at our peril. In both simulated and experimental systems, in many cases ignoring intraspecific variation led to incorrect statistical inferences and inflated the effect size of species identity. This study shows that ecologists must characterize hierarchically nested genetic and phenotypic variation to fully understand the links between individual traits, community structure and ecosystem functioning.     

Too hot to handle? Balancing increased trapability with capture mortality in hot weather pitfall trapping

Trapping at air temperatures close to, or exceeding, critical thermal maxima is important for comprehensive sampling of vertebrate assemblages and collection of sufficient data for impact assessment. However, pitfall trapping on hot days also potentially exposes trapped animals to stress or death through overheating or desiccation. We investigate causes of mortality from 14 305 captures over a 22‐year pitfall trap study in arid South Australia and compared mortality rates with maximum temperatures, solar radiation and rainfall. Overall mortality rate was 3.2% with chewing by rodents and handling accidents the most influential cause of death recorded. The highest mortality rates were experienced by the tiny skink, Lerista labialis, which was difficult to detect in traps each day and hence problematic to assess the effect of weather variables on capture mortality. For all other abundant species, high maximum temperature was only a significant explanatory variable for increased death rates of the house mouse Mus domesticus, and increased solar radiation was positively related to capture mortality for the house mouse, the frog Neobatrachus sudelli and the small skink Ctenotus schomburgkii. However, capture rates for these taxa and eight other common species would have been significantly lower if trapping did not occur on days of 40 °C or more. We conclude that trapping in hot weather is both desirable and justifiable and suggest techniques for further reducing mortality rates in pitfall studies.