The epidemiology underlying age‐related avian malaria infection in a long‐lived host: the mute swan Cygnus olor

Quantifying the factors that predict parasite outbreak and persistence is a major challenge for both applied and fundamental biology. Key to understanding parasite prevalence and disease outbreaks is determining at what age individuals show signs of infection, and whether or not they recover. Age‐dependent patterns of the infection of a host population by parasites can indicate among‐individual heterogeneities in their susceptibility to, or rate of recovery from, parasite infections. Here, we present a cross‐sectional study of avian malaria in a long‐lived bird species, the mute swan Cygnus olor, examining age‐related patterns of parasite prevalence and modelling patterns of infection and recovery. One‐hundred and fifteen swans, ranging from one to nineteen years old, were screened for infection with Plasmodium, Haemoproteus and Leucocytozoon parasites. Infections with three cytochrome‐b lineages of Haemoproteus were found (pooled prevalence 67%), namely WW1 (26%), which is common in passerine birds, and two new lineages closely related to WW1: MUTSW1 (25%) and MUTSW2 (16%). We found evidence for age‐related infection in one lineage, MUTSW1. Catalytic models examining patterns of infection and recovery in the population suggested that infections in this population were not life‐long – recovery of individuals was included in the best fitting models. These findings support the results of recent studies that suggest hosts can clear infections, although patterns of infection‐related mortality in older birds remain to be studied in more detail.     

Differential Phosphorylation of Smad1 Integrates BMP and Neurotrophin Pathways through Erk/Dusp in Axon Development

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Resistance Development of Cystic Fibrosis Respiratory Pathogens When Exposed to Fosfomycin and Tobramycin Alone and in Combination under Aerobic and Anaerobic Conditions

Although antibiotics from different classes are frequently prescribed in combination to prevent the development of resistance amongst Cystic Fibrosis (CF) respiratory pathogens, there is a lack of data as to the efficacy of this approach. We have previously shown that a 4∶1 (w/w) combination of fosfomycin and tobramycin (F∶T) has excellent activity against CF pathogens with increased activity under physiologically relevant anaerobic conditions. Therefore, the aim of this study was to determine whether F∶T could delay or prevent the onset of resistance compared to either fosfomycin or tobramycin alone under aerobic and anaerobic conditions. The frequency of spontaneous mutants arising following exposure to fosfomycin, tobramycin and F∶T was determined for clinical Pseudomonas aeruginosa and MRSA isolates under aerobic and anaerobic conditions. The effect of sub-inhibitory concentrations of fosfomycin, tobramycin and F∶T on the induction of resistance was also investigated, with the stability of resistance and fitness cost associated with resistance assessed if it developed. P. aeruginosa and MRSA isolates had a lower frequency of spontaneous mutants to F∶T compared to fosfomycin and tobramycin under both aerobic and anaerobic conditions. There was a maximum two-fold increase in F∶T MICs when P. aeruginosa and MRSA isolates were passaged in sub-inhibitory F∶T for 12 days. In contrast, sequential resistance to fosfomycin and tobramycin developed quickly (n = 3 days for both) after passage in sub-inhibitory concentrations. Once developed, both fosfomycin and tobramycin resistance was stable and not associated with a biological fitness cost to either P. aeruginosa or MRSA isolates. The results of this study suggest that F∶T may prevent the development of resistance compared to fosfomycin or tobramycin alone under aerobic and physiologically relevant anaerobic conditions. F∶T may be a potential treatment option in CF patients chronically colonised by MRSA and/or P. aeruginosa.     

Ability of Innate Defence Regulator Peptides IDR-1002, IDR-HH2 and IDR-1018 to Protect against Mycobacterium tuberculosis Infections in Animal Models

Tuberculosis is an ongoing threat to global health, especially with the emergence of multi drug-resistant (MDR) and extremely drug-resistant strains that are motivating the search for new treatment strategies. One potential strategy is immunotherapy using Innate Defence Regulator (IDR) peptides that selectively modulate innate immunity, enhancing chemokine induction and cell recruitment while suppressing potentially harmful inflammatory responses. IDR peptides possess only modest antimicrobial activity but have profound immunomodulatory functions that appear to be influential in resolving animal model infections. The IDR peptides HH2, 1018 and 1002 were tested for their activity against two M. tuberculosis strains, one drug-sensitive and the other MDR in both in vitro and in vivo models. All peptides showed no cytotoxic activity and only modest direct antimicrobial activity versus M. tuberculosis (MIC of 15–30 µg/ml). Nevertheless peptides HH2 and 1018 reduced bacillary loads in animal models with both the virulent drug susceptible H37Rv strain and an MDR isolate and, especially 1018 led to a considerable reduction in lung inflammation as revealed by decreased pneumonia. These results indicate that IDR peptides have potential as a novel immunotherapy against TB.     

On the selection of thresholds for predicting species occurrence with presence‐only data

Presence‐only data present challenges for selecting thresholds to transform species distribution modeling results into binary outputs. In this article, we compare two recently published threshold selection methods (maxSSS and maxF_pb) and examine the effectiveness of the threshold‐based prevalence estimation approach. Six virtual species with varying prevalence were simulated within a real landscape in southeastern Australia. Presence‐only models were built with DOMAIN, generalized linear model, Maxent, and Random Forest. Thresholds were selected with two methods maxSSS and maxF_pb with four presence‐only datasets with different ratios of the number of known presences to the number of random points (KP–RP_ratio). Sensitivity, specificity, true skill statistic, and F measure were used to evaluate the performance of the results. Species prevalence was estimated as the ratio of the number of predicted presences to the total number of points in the evaluation dataset. Thresholds selected with maxF_pb varied as the KP–RP_ratio of the threshold selection datasets changed. Datasets with the KP–RP_ratio around 1 generally produced better results than scores distant from 1. Results produced by We conclude that maxF_pb had specificity too low for very common species using Random Forest and Maxent models. In contrast, maxSSS produced consistent results whichever dataset was used. The estimation of prevalence was almost always biased, and the bias was very large for DOMAIN and Random Forest predictions. We conclude that maxF_pb is affected by the KP–RP_ratio of the threshold selection datasets, but maxSSS is almost unaffected by this ratio. Unbiased estimations of prevalence are difficult to be determined using the threshold‐based approach.     

Assessing Disease and Mortality among Small Cetaceans Stranded at a World Heritage Site in Southern Brazil

Cetaceans are considered environmental sentinels and their health often reflects either anthropogenic or natural spatio-temporal disturbances. This study investigated the pathological findings and mortality of small cetaceans with the aim of detecting hazards and monitoring health trends in a high-biodiversity area. Between 2007 and 2012, 218 stranded cetaceans were recorded on the Paraná coast, southern Brazil. Fifty-seven (26.1%) of these animals, including 50 Sotalia guianensis, 2 Pontoporia blainvillei, 2 Stenella frontalis, 1 Stenella longirostris, 1 Tursiops truncatus and 1 Globicephala melas were necropsied and samples were collected for histopathology. Causes of death were determined in 46 of the 57 (80.7%) animals and most (30 or 65.2%) were ascribed to anthropogenic activities, including fisheries bycatch (28/30) and trauma (2/30). The remaining 16 fatalities were considered natural, and attributed to pneumonia (10/16), emaciation (3/16), septicemia (1/16), neonatal pathology (1/16) and choking via food obstruction (1/16). Irrespective of the cause, bronchointerstitial pneumonia, associated with parasitism, lymphadenitis and membranous glomerulonephritis were common findings among all fatalities. These results suggest, that while anthropogenic activities are a leading cause of cetacean strandings in Paraná, underlying pre-existing diseases may contribute towards deaths. Although the studied area is considered a biosphere reserve by UNESCO, complex anthropogenic and natural interactions might be occurring, increasing cetacean susceptibility to hazards. This study may help facilitate developing an effective conservation plan for coastal cetaceans focusing on reducing fisheries interactions, habitat degradation and pollution as mechanisms for ultimately increasing species resilience.     

Mosaicism in a new Eocene pufferfish highlights rapid morphological innovation near the origin of crown tetraodontiforms

Tetraodontiformes (pufferfishes and kin) is a taxonomically and structurally diverse, widely‐distributed clade of acanthomorphs, whose members often serve as models for genomics and, increasingly, macroevolutionary studies. Morphologically disparate Palaeogene fossils suggest considerable early experimentation, but these flattened specimens often preserve limited information. We present a three‐dimensionally preserved beaked tetraodontiform from the early Eocene (c. 53 Ma) London Clay Formation, UK. Approximately coeval with the oldest crown tetraodontiforms, ?Ctenoplectus williamsi gen. et sp. nov. presents an unprecedented combination of characters, pairing a fused beak‐like dentition with prominent dorsal‐fin spines that insert atop transversely‐expanded pterygiophores roofing the skull. Bayesian total‐evidence tip‐dating analysis indicates that ?Ctenoplectus represents the sister lineage of Triodontidae and highlights considerable levels of homoplasy in early tetraodontiform evolution. According to our dataset, rates of morphological character evolution were elevated at the origin of crown Tetraodontiformes, especially within gymnodonts, but declined after the principal body plans were established. Such ‘early burst’ patterns are regarded as a hallmark of adaptive radiations, but are typically associated with diversification at smaller spatiotemporal scales. However, denser sampling of Neogene and Recent taxa is needed to confirm this pattern.