Passerines may be sufficiently plastic to track temperature‐mediated shifts in optimum lay date

Projecting the fates of populations under climate change is one of global change biology's foremost challenges. Here, we seek to identify the contributions that temperature‐mediated local adaptation and plasticity make to spatial variation in nesting phenology, a phenotypic trait showing strong responses to warming. We apply a mixed modeling framework to a Britain‐wide spatiotemporal dataset comprising >100 000 records of first egg dates from four single‐brooded passerine bird species. The average temperature during a specific time period (sliding window) strongly predicts spatiotemporal variation in lay date. All four species exhibit phenological plasticity, advancing lay date by 2–5 days °C^?1. The initiation of this sliding window is delayed further north, which may be a response to a photoperiod threshold. Using clinal trends in phenology and temperature, we are able to estimate the temperature sensitivity of selection on lay date (B), but our estimates are highly sensitive to the temporal position of the sliding window. If the sliding window is of fixed duration with a start date determined by photoperiod, we find B is tracked by phenotypic plasticity. If, instead, we allow the start and duration of the sliding window to change with latitude, we find plasticity does not track B, although in this case, at odds with theoretical expectations, our estimates of B differ across latitude vs. longitude. We argue that a model combining photoperiod and mean temperature is most consistent with current understanding of phenological cues in passerines, the results from which suggest that each species could respond to projected increases in spring temperatures through plasticity alone. However, our estimates of B require further validation.     

Functional infertility in a wild passerine bird

Information about male infertility in free‐living bird populations and its underlying causes are poorly documented in the literature. Here, we assessed sperm quality and infertility among males in a wild population of Blue Tits Cyanistes caeruleus, a socially monogamous passerine with frequent extra‐pair mating. One of 30 males (3.3%) studied across two breeding seasons had morphologically abnormal and nearly immotile spermatozoa in combination with zero annual fertilization success. Demonstration of male functional infertility suggests the possibility that socially monogamous females of the study population could obtain a direct fitness benefit by mating polyandrously to increase fertilization success, which could contribute to selection on extra‐pair mating behaviour.     

Structural correlates of antimicrobial efficacy in IL-8 and related human kinocidins

Chemokines are small (8-12 kDa) effector proteins that potentiate leukocyte chemonavigation. Beyond this role, certain chemokines have direct antimicrobial activity against human pathogenic organisms; such molecules are termed kinocidins. The current investigation was designed to explore the structure-activity basis for direct microbicidal activity of kinocidins. Amino acid sequence and 3-dimensional analyses demonstrated these molecules to contain iterations of the conserved γ-core motif found in broad classes of classical antimicrobial peptides. Representative CXC, CC and C cysteine-motif-group kinocidins were tested for antimicrobial activity versus human pathogenic bacteria and fungi. Results demonstrate that these molecules exert direct antimicrobial activity in vitro, including antibacterial activity of native IL-8 and MCP-1, and microbicidal activity of native IL-8. To define molecular determinants governing its antimicrobial activities, the IL-8 γ-core (IL-8γ) and α-helical (IL-8α) motifs were compared to native IL-8 for antimicrobial efficacy in vitro. Microbicidal activity recapitulating that of native IL-8 localized to the autonomous IL-8α motif in vitro, and demonstrated durable microbicidal activity in human blood and blood matrices ex vivo. These results offer new insights into the modular architecture, context-related deployment and function, and evolution of host defense molecules containing γ-core motifs and microbicidal helices associated with antimicrobial activity.     

Interactions of the Australian tree frog antimicrobial peptides aurein 1.2, citropin 1.1 and maculatin 1.1 with lipid model membranes: Differential scanning calorimetric and Fourier transform infrared spectroscopic studies

The interactions of the antimicrobial peptides aurein 1.2, citropin 1.1 and maculatin 1.1 with dimyristoylphosphatidylcholine (DMPC), dimyristoylphosphatidylglycerol (DMPG) and dimyristoylphosphatidylethanolamine (DMPE) were studied by differential scanning calorimetry (DSC) and Fourier-transform infrared (FTIR) spectroscopy. The effects of these peptides on the thermotropic phase behavior of DMPC and DMPG are qualitatively similar and manifested by the suppression of the pretransition, and by peptide concentration-dependent decreases in the temperature, cooperativity and enthalpy of the gel/liquid-crystalline phase transition. However, at all peptide concentrations, anionic DMPG bilayers are more strongly perturbed than zwitterionic DMPC bilayers, consistent with membrane surface charge being an important aspect of the interactions of these peptides with phospholipids. However, at all peptide concentrations, the perturbation of the thermotropic phase behavior of zwitterionic DMPE bilayers is weak and discernable only when samples are exposed to high temperatures. FTIR spectroscopy indicates that these peptides are unstructured in aqueous solution and that they fold into α-helices when incorporated into lipid membranes. All three peptides undergo rapid and extensive H-D exchange when incorporated into D₂O-hydrated phospholipid bilayers, suggesting that they are located in solvent-accessible environments, most probably in the polar/apolar interfacial regions of phospholipid bilayers. The perturbation of model lipid membranes by these peptides decreases in magnitude in the order maculatin 1.1 > aurein 1.2 > citropin 1.1, whereas the capacity to inhibit Acholeplasma laidlawii B growth decreases in the order maculatin 1.1 > aurein 1.2 ≅ citropin 1.1. The higher efficacy of maculatin 1.1 in disrupting model and biological membranes can be rationalized by its larger size and higher net charge. However, despite its smaller size and lower net charge, aurein 1.2 is more disruptive of model lipid membranes than citropin 1.1 and exhibits comparable antimicrobial activity, probably because aurein 1.2 has a higher propensity for partitioning into phospholipid membranes.     

Random effects modeling approaches for estimating ROC curves from repeated ordinal tests without a gold standard

Estimating diagnostic accuracy without a gold standard is an important problem in medical testing. Although there is a fairly large literature on this problem for the case of repeated binary tests, there is substantially less work for the case of ordinal tests. A noted exception is the work by Zhou, Castelluccio, and Zhou (2005, Biometrics 61, 600-609), which proposed a methodology for estimating receiver operating characteristic (ROC) curves without a gold standard from multiple ordinal tests. A key assumption in their work was that the test results are independent conditional on the true test result. I propose random effects modeling approaches that incorporate dependence between the ordinal tests, and I show through asymptotic results and simulations the importance of correctly accounting for the dependence between tests. These modeling approaches, along with the importance of accounting for the dependence between tests, are illustrated by analyzing the uterine cancer pathology data analyzed by Zhou et al. (2005).     

Linear measurement error models with restricted sampling

The relationship between nutrient consumption and chronic disease risk is the focus of a large number of epidemiological studies where food frequency questionnaires (FFQ) and food records are commonly used to assess dietary intake. However, these self-assessment tools are known to involve substantial random error for most nutrients, and probably important systematic error as well. Study subject selection in dietary intervention studies is sometimes conducted in two stages. At the first stage, FFQ-measured dietary intakes are observed and at the second stage another instrument, such as a 4-day food record, is administered only to participants who have fulfilled a prespecified criterion that is based on the baseline FFQ-measured dietary intake (e.g., only those reporting percent energy intake from fat above a prespecified quantity). Performing analysis without adjusting for this truncated sample design and for the measurement error in the nutrient consumption assessments will usually provide biased estimates for the population parameters. In this work we provide a general statistical analysis technique for such data with the classical additive measurement error that corrects for the two sources of bias. The proposed technique is based on multiple imputation for longitudinal data. Results of a simulation study along with a sensitivity analysis are presented, showing the performance of the proposed method under a simple linear regression model.     

Monomeric A beta and metals reduce their cytotoxicities to each other

The present study has examined the effect of metals, such as iron and copper on the cytotoxicity of amyloid beta protein 1-40 (Abeta40). First, we showed that monomeric Abeta40 has stronger cytotoxicity than various type of aggregated Abeta40. Next we showed the addition of metals into the monomeric Abeta40 reduced the cytotoxicity of either monomeric Abeta40 or metals (iron and copper) although the addition of metals into monomeric Abeta40 resulted in a marked increase of aggregated form of Abeta40, which composed of beta-sheeted Abeta40 and Abeta40 aggregation not characterized by beta-sheet fibrils (coagrated Abeta40). Taken together, the metals and monomeric Abeta40 affect on each other and cause the reduction of their cell toxicity.