Effects of inbreeding on fitness‐related traits in a small isolated moose population

Inbreeding can affect fitness‐related traits at different life history stages and may interact with environmental variation to induce even larger effects. We used genetic parentage assignment based on 22 microsatellite loci to determine a 25 year long pedigree for a newly established island population of moose with 20–40 reproducing individuals annually. We used the pedigree to calculate individual inbreeding coefficients and examined for effects of individual inbreeding (f) and heterozygosity on fitness‐related traits. We found negative effects of f on birth date, calf body mass and twinning rate. The relationship between f and calf body mass and twinning rate were found to be separate but weaker after accounting for birth date. We found no support for an inbreeding effect on the age‐specific lifetime reproductive success of females. The influence of f on birth date was related to climatic conditions during the spring prior to birth, indicating that calves with a low f were born earlier after a cold spring than calves with high f. In years with a warm spring, calf f did not affect birth date. The results suggest that severe inbreeding in moose has both indirect effects on fitness through delayed birth and lower juvenile body mass, as well as separate direct effects, as there still was a significant relationship between f and twinning rate after accounting for birth date and body mass as calf. Consequently, severe inbreeding as found in the study population may have consequences for population growth and extinction risk.     

Dataset size and composition impact the reliability of performance benchmarks for peptide-MHC binding predictions

Background

It is important to accurately determine the performance of peptide:MHC binding predictions, as this enables users to compare and choose between different prediction methods and provides estimates of the expected error rate. Two common approaches to determine prediction performance are cross-validation, in which all available data are iteratively split into training and testing data, and the use of blind sets generated separately from the data used to construct the predictive method. In the present study, we have compared cross-validated prediction performances generated on our last benchmark dataset from 2009 with prediction performances generated on data subsequently added to the Immune Epitope Database (IEDB) which served as a blind set.

Results

We found that cross-validated performances systematically overestimated performance on the blind set. This was found not to be due to the presence of similar peptides in the cross-validation dataset. Rather, we found that small size and low sequence/affinity diversity of either training or blind datasets were associated with large differences in cross-validated vs. blind prediction performances. We use these findings to derive quantitative rules of how large and diverse datasets need to be to provide generalizable performance estimates.

Conclusion

It has long been known that cross-validated prediction performance estimates often overestimate performance on independently generated blind set data. We here identify and quantify the specific factors contributing to this effect for MHC-I binding predictions. An increasing number of peptides for which MHC binding affinities are measured experimentally have been selected based on binding predictions and thus are less diverse than historic datasets sampling the entire sequence and affinity space, making them more difficult benchmark data sets. This has to be taken into account when comparing performance metrics between different benchmarks, and when deriving error estimates for predictions based on benchmark performance.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2105-15-241) contains supplementary material, which is available to authorized users.     

The interactions of calreticulin with immunoglobulin G and immunoglobulin Y

Calreticulin is a chaperone of the endoplasmic reticulum (ER) assisting proteins in achieving the correctly folded structure. Details of the binding specificity of calreticulin are still a matter of debate. Calreticulin has been described as an oligosaccharide-binding chaperone but data are also accumulating in support of calreticulin as a polypeptide binding chaperone. In contrast to mammalian immunoglobulin G (IgG), which has complex type N-glycans, chicken immunoglobulin Y (IgY) possesses a monoglucosylated high mannose N-linked glycan, which is a ligand for calreticulin. Here, we have used solid and solution-phase assays to analyze the in vitro binding of calreticulin, purified from human placenta, to human IgG and chicken IgY in order to compare the interactions. In addition, peptides from the respective immunoglobulins were included to further probe the binding specificity of calreticulin. The experiments demonstrate the ability of calreticulin to bind to denatured forms of both IgG and IgY regardless of the glycosylation state of the proteins. Furthermore, calreticulin exhibits binding to peptides (glycosylated and non-glycosylated) derived from trypsin digestion of both immunoglobulins. Additionally, calreticulin peptide binding was examined with synthetic peptides covering the IgG Cγ2 domain demonstrating interaction with approximately half the peptides. Our results show that the dominant binding activity of calreticulin in vitro is toward the polypeptide moieties of IgG and IgY even in the presence of the monoglucosylated high mannose N-linked oligosaccharide on IgY.     

miRdentify: high stringency miRNA predictor identifies several novel animal miRNAs

During recent years, miRNAs have been shown to play important roles in the regulation of gene expression. Accordingly, much effort has been put into the discovery of novel uncharacterized miRNAs in various organisms. miRNAs are structurally defined by a hairpin-loop structure recognized by the two-step processing apparatus, Drosha and Dicer, necessary for the production of mature ∼22-nucleotide miRNA guide strands. With the emergence of high-throughput sequencing applications, tools have been developed to identify miRNAs and profile their expression based on sequencing reads. However, as the read depth increases, false-positive predictions increase using established algorithms, underscoring the need for more stringent approaches. Here we describe a transparent pipeline for confident miRNA identification in animals, termed miRdentify. We show that miRdentify confidently discloses more than 400 novel miRNAs in humans, including the first male-specific miRNA, which we successfully validate. Moreover, novel miRNAs are predicted in the mouse, the fruit fly and nematodes, suggesting that the pipeline applies to all animals. The entire software package is available at www.ncrnalab.dk/mirdentify.     

Removal of snow cover inhibits spring growth of Arctic ice algae through physiological and behavioral effects

The snow cover of Arctic sea ice has recently decreased, and climate models forecast that this will continue and even increase in future. We therefore tested the effect of snow cover on the optical properties of sea ice and the biomass, photobiology, and species composition of sea ice algae at Kangerlussuaq, West Greenland, during March 2011, using a snow-clearance experiment. Sea ice algae in areas cleared of snow was compared with control areas, using imaging variable fluorescence of photosystem II in intact, unthawed ice sections. The study coincided with the onset of spring growth of ice algae, mainly an increase in two pennate diatoms (Achnanthes taeniata and Navicula directa), as temperature increased and ice thickness and brine volume stabilized. The increase in biomass was accompanied by an increase in minimum variable fluorescence (F _o) and the maximum quantum yield of PSII (F _v /F _m) and filling of brine channels with fluorescing cells. In contrast, in the minus snow area, PAR transmittance increased sixfold and there was an exponential decrease in chl-a and no increase in F _o, and the area of fluorescing biomass declined to become undetectable. This study suggests that the onset of the spring bloom is predominantly due to temperature effects on brine channel volume, and that the algal decline after snow removal was primarily due to emigration rather than photodamage.     

Herbarium specimens reveal a historical shift in phylogeographic structure of common ragweed during native range disturbance

Invasive plants provide ample opportunity to study evolutionary shifts that occur after introduction to novel environments. However, although genetic characters pre‐dating introduction can be important determinants of later success, large‐scale investigations of historical genetic structure have not been feasible. Common ragweed (Ambrosia artemisiifolia L.) is an invasive weed native to North America that is known for its allergenic pollen. Palynological records from sediment cores indicate that this species was uncommon before European colonization of North America, and ragweed populations expanded rapidly as settlers deforested the landscape on a massive scale, later becoming an aggressive invasive with populations established globally. Towards a direct comparison of genetic structure now and during intense anthropogenic disturbance of the late 19th century, we sampled 45 natural populations of common ragweed across its native range as well as historical herbarium specimens collected up to 140 years ago. Bayesian clustering analyses of 453 modern and 473 historical samples genotyped at three chloroplast spacer regions and six nuclear microsatellite loci reveal that historical ragweed's spatial genetic structure mirrors both the palaeo‐record of Ambrosia pollen deposition and the historical pattern of agricultural density across the landscape. Furthermore, for unknown reasons, this spatial genetic pattern has changed substantially in the intervening years. Following on previous work relating morphology and genetic expression between plants collected from eastern North America and Western Europe, we speculate that the cluster associated with humans’ rapid transformation of the landscape is a likely source of these aggressive invasive populations.     

Feasibility of Progressive Strength Training Implemented in the Acute Ward after Hip Fracture Surgery

Importance

Patients with a hip fracture lose more than 50% knee-extension strength in the fractured limb within one week of surgery. Hence, immediate progressive strength training following hip fracture surgery may be rational, but the feasibility unknown.

Objective

To examine the feasibility of in-hospital progressive strength training implemented in the acute ward following hip fracture surgery, based on pre-specified criteria for feasibility.

Design, Setting and Patients

A prospective cohort study conducted in an acute orthopedic hip fracture unit at a university hospital. A consecutive sample of 36 patients, 18 with a cervical and 18 with a trochanteric hip fracture (27 women and 9 men, mean (SD) age of 79.4 (8.3) years) were included between June and December 2012.

Intervention

A daily (on weekdays) program of progressive knee-extension strength training for the fractured limb, using ankle weight cuffs in 3 sets of 10 repetition maximum loadings.

Main outcomes and Measures

The primary outcome was the change in training load (kg) during the knee-extension strength training. The secondary outcomes were changes in hip fracture-related pain and maximal isometric knee-extension strength.

Results

The strength training was commenced at a mean of 2.4 (0.7) days after surgery. The training loads (kilograms lifted) increased from 1.6 (0.8) to 4.3 (1.7) kg over 4.3 (2.2) training sessions (P<.001). The maximal isometric knee-extension strength of the fractured limb increased from 0.37 (0.2) to 0.61 (0.3) Nm/kg (P<.001), while the average strength deficit in the fractured limb decreased from 50% to 32% (% non-fractured, P<.001). Only 3 of 212 sessions were not performed because of severe hip fracture-related pain.

Conclusion and Relevance

Progressive knee-extension strength training of the fractured limb commenced in the acute ward seems feasible, and may reduce strength asymmetry between limbs without hip pain interfering. The clinical efficacy needs confirmation in a randomized controlled design.

Trial Registration

ClinicalTrials.gov ID: NCT01616030