Emergence, spread, persistence and fade-out of sylvatic plague in Kazakhstan

Predicting the dynamics of zoonoses in wildlife is important not only for prevention of transmission to humans, but also for improving the general understanding of epidemiological processes. A large dataset on sylvatic plague in the Pre-Balkhash area of Kazakhstan (collected for surveillance purposes) provides a rare opportunity for detailed statistical modelling of an infectious disease. Previous work using these data has revealed a host abundance threshold for epizootics, and climatic influences on plague prevalence. Here, we present a model describing the local space-time dynamics of the disease at a spatial scale of 20 × 20 km(2) and a biannual temporal scale, distinguishing between invasion and persistence events. We used a Bayesian imputation method to account for uncertainties resulting from poor data in explanatory variables and response variables. Spatial autocorrelation in the data was accounted for in imputations and analyses through random effects. The results show (i) a clear effect of spatial transmission, (ii) a high probability of persistence compared with invasion, and (iii) a stronger influence of rodent abundance on invasion than on persistence. In particular, there was a substantial probability of persistence also at low host abundance.     

Lack of CCR7 induces pulmonary hypertension involving perivascular leukocyte infiltration and inflammation

The chemokine receptor CCR7 regulates lymphocyte trafficking, and CCR7 deficiency induces infiltration of T and B cells adjacent to vessels in mouse lungs. Perivascular infiltration of T and B cells has also been found in human pulmonary arterial hypertension, and downregulation of the CCR7 receptor in circulating leukocytes of such patients has been observed. To investigate whether changes in the CCR7 system contribute to the pathogenesis of pulmonary hypertension, we utilized mice deficient of the CCR7 receptor. The cardiopulmonary and inflammatory responses of CCR7 depletion were evaluated in CCR7-deficient and wild-type mice. Measurements of cytokines upregulated in the animal model were also performed in patients with pulmonary hypertension and controls and in vascular smooth muscle cells. We found that mice lacking CCR7 had increased right ventricular systolic pressure, reduced pulmonary artery acceleration time, increased right ventricular/tibial length ratio, Rho kinase-mediated pulmonary vasoconstriction, and increased muscularization of distal arteries, indicating pulmonary hypertension. These mice also showed increased perivascular infiltration of leukocytes, consisting mainly of T and B cells, and increased mRNA levels of the inflammatory cytokines interleukin-12 and CX3CL1 within pulmonary tissue. Increased serum levels of interleukin-12 and CX3CL1 were also observed in patients with pulmonary hypertension, particularly in those with pulmonary hypertension associated with connective tissue disorder. In smooth muscle cells, interleukin-12 induced secretion of the angiogenic cytokine interleukin-8. We conclude that these results suggest a role for CCR7 in the development of pulmonary arterial hypertension, at least in some subgroups, possibly via pulmonary infiltration of lymphocytes and secretion of interleukin-12 and CX3CL1.     

Moose recruitment in relation to bilberry production and bank vole numbers along a summer temperature gradient in Norway

The plant stress hypothesis states that plant stress factors other than herbivory improve herbivore performance due to changes in the content of nutritive or defensive compounds in the plants. In Norway, the bilberry (Vaccinium myrtillus) is important forage for the bank vole (Myodes glareolus) in winter and for the moose (Alces alces) in summer and autumn. The observed peaks in bank vole numbers after years with high production of bilberries are suggested to be caused by increased winter survival of bank voles due to improved forage quality. High production of bilberries should also lead to higher recruitment rates in moose in the following year. We predict, however, that there is an increasing tendency for a 1-year delay of moose indices relative to vole indices with decreasing summer temperatures, because low temperatures prolong the period needed by plants to recover in the vole peak year, and thus positively affect moose reproduction also in the succeeding year. In eight out of nine counties in south-eastern Norway, there was a positive relationship between the number of calves observed per female moose during hunting and a bilberry seed production index or an autumn bank vole population index. When dividing the study area into regions, there was a negative relationship between a moose-vole time-lag index and the mean summer temperature of the region. These patterns suggest that annual fluctuations in the production of bilberries affect forage quality, but that the effect on moose reproduction also depends on summer temperatures.     

Multiplexed immuno-precipitation with 1725 commercially available antibodies to cellular proteins

Antibody array analysis of complex samples requires capture reagents with exceptional specificity. The frequency of antibodies with label-based detection may be as low as 5%. Here, however, we show that as many as 25% of commercially available antibodies are useful when biotinylated cellular proteins are fractionated by size exclusion chromatography (SEC) first. A microsphere multiplex with 1725 antibodies to cellular proteins was added to 24 SEC fractions, labelled with streptavidin and analyzed by flow cytometry (microsphere-based affinity proteomics, MAP) The SEC-MAP approach resolved different targets captured by each antibody as reactivity peaks across the separation range of the SEC column (10-670kDa). Complex reactivity profiles demonstrated that most antibodies bound more than one target. However, specific binding was readily detected as reactivity peaks common for different antibodies to the same protein. We optimized sample preparation and found that amine-reactive biotin rarely inhibited antibody binding when the biotin to lysine ratio was kept below 1:1 during labelling. Moreover, several epitopes that were inaccessible to antibodies in native proteins were unmasked after heat denaturation with 0.1% of SDS. The SEC-MAP format should allow researchers to build multiplexed assays with antibodies purchased for use in e.g. Western blotting.     

Real-time ichthyoplankton drift in Northeast Arctic cod and Norwegian spring-spawning herring

Background

Individual-based biophysical larval models, initialized and parameterized by observations, enable numerical investigations of various factors regulating survival of young fish until they recruit into the adult population. Exponentially decreasing numbers in Northeast Arctic cod and Norwegian Spring Spawning herring early changes emphasizes the importance of early life history, when ichthyoplankton exhibit pelagic free drift. However, while most studies are concerned with past recruitment variability it is also important to establish real-time predictions of ichthyoplankton distributions due to the increasing human activity in fish habitats and the need for distribution predictions that could potentially improve field coverage of ichthyoplankton.

Methodology/Principal Findings

A system has been developed for operational simulation of ichthyoplankton distributions. We have coupled a two-day ocean forecasts from the Norwegian Meteorological Institute with an individual-based ichthyoplankton model for Northeast Arctic cod and Norwegian Spring Spawning herring producing daily updated maps of ichthyoplankton distributions. Recent years observed spawning distribution and intensity have been used as input to the model system. The system has been running in an operational mode since 2008. Surveys are expensive and distributions of early stages are therefore only covered once or twice a year. Comparison between model and observations are therefore limited in time. However, the observed and simulated distributions of juvenile fish tend to agree well during early fall. Area-overlap between modeled and observed juveniles September 1^st range from 61 to 73%, and 61 to 71% when weighted by concentrations.

Conclusions/Significance

The model system may be used to evaluate the design of ongoing surveys, to quantify the overlap with harmful substances in the ocean after accidental spills, as well as management planning of particular risky operations at sea. The modeled distributions are already utilized during research surveys to estimate coverage success of sampled biota and immediately after spills from ships at sea.     

Modulation of prolactin but not corticosterone responses to stress in relation to parental effort in a long-lived bird

We tested the hypothesis that parental effort modulates the magnitude of corticosterone and prolactin responses to stress in a long-lived bird, the Black-legged kittiwake (Rissa tridactyla). To do so, we compared corticosterone and prolactin responses to capture/restraint stress between chick-rearing birds and failed breeders (no parental effort). We predicted that (1) the increase in plasma corticosterone levels in response to stress should be lower in chick-rearing birds, (2) the decrease in plasma prolactin levels in response to stress should be lower in chick-rearing birds, and (3) as both sexes care for the chick, there should be no sex difference in the hormonal response to stress. Baseline plasma corticosterone and prolactin levels were higher in chick-rearing birds and were not influenced by body condition. Failed breeders were in better condition than chick-rearing individuals. Corticosterone response to stress was unaffected by parental effort as both chick-rearing and failed birds exhibited a robust corticosterone increase. Prolactin response to stress was however clearly influenced by parental effort: chick-rearing birds showed a modest 9% prolactin decrease whereas in failed birds prolactin concentrations fell by 41%. Body condition did not influence hormonal responses to stress. When facing stressful condition, breeding kittiwakes attenuate their prolactin response to stress while enhancing their secretion of corticosterone. Increasing corticosterone secretion triggers foraging efforts and diminishes nest attendance whereas an attenuation of prolactin response to stress maintains parental behavior. We suggest that this hormonal mechanism facilitates a flexible time-budget that has been interpreted as a buffer against environmental variability.     

AtNAP1 represents an atypical SufB protein in Arabidopsis plastids

The assembly of iron-sulfur (Fe-S) clusters involves several pathways and in prokaryotes the mobilization of the sulfur (SUF) system is paramount for Fe-S biogenesis and repair during oxidative stress. The prokaryotic SUF system consists of six proteins: SufC is an ABC/ATPase that forms a complex with SufB and SufD, SufA acts as a scaffold protein, and SufE and SufS are involved in sulfur mobilization from cysteine. Despite the importance of Fe-S proteins in higher plant plastids, little is known regarding plastidic Fe-S cluster assembly. We have recently shown that Arabidopsis harbors an evolutionary conserved plastidic SufC protein (AtNAP7) capable of hydrolyzing ATP and interacting with the SufD homolog AtNAP6. Based on this and the prokaryotic SUF system we speculated that a SufB-like protein may exist in plastids. Here we demonstrate that the Arabidopsis plastid-localized SufB homolog AtNAP1 can complement SufB deficiency in Escherichia coli during oxidative stress. Furthermore, we demonstrate that AtNAP1 can interact with AtNAP7 inside living chloroplasts suggesting the presence of a plastidic AtNAP1.AtNAP6.AtNAP7 complex and remarkable evolutionary conservation of the SUF system. However, in contrast to prokaryotic SufB proteins with no associated ATPase activity we show that AtNAP1 is an iron-stimulated ATPase and that AtNAP1 is capable of forming homodimers. Our results suggest that AtNAP1 represents an atypical plastidic SufB-like protein important for Fe-S cluster assembly and for regulating iron homeostasis in Arabidopsis.     

The plastid division protein AtMinD1 is a Ca2+-ATPase stimulated by AtMinE1

Bacteria and plastids divide symmetrically through binary fission by accurately placing the division site at midpoint, a process initiated by FtsZ polymerization, which forms a Z-ring. In Escherichia coli precise Z-ring placement at midcell depends on controlled oscillatory behavior of MinD and MinE: In the presence of ATP MinD interacts with the FtsZ inhibitor MinC and migrates to the membrane where the MinD-MinC complex recruits MinE, followed by MinD-mediated ATP hydrolysis and membrane release. Although correct Z-ring placement during Arabidopsis plastid division depends on the precise localization of the bacterial homologs AtMinD1 and AtMinE1, the underlying mechanism of this process remains unknown. Here we have shown that AtMinD1 is a Ca2+-dependent ATPase and through mutation analysis demonstrated the physiological importance of this activity where loss of ATP hydrolysis results in protein mislocalization within plastids. The observed mislocalization is not due to disrupted AtMinD1 dimerization, however; the active site AtMinD1(K72A) mutant is unable to interact with the topological specificity factor AtMinE1. We have shown that AtMinE1, but not E. coli MinE, stimulates AtMinD1-mediated ATP hydrolysis, but in contrast to prokaryotes stimulation occurs in the absence of membrane lipids. Although AtMinD1 appears highly evolutionarily conserved, we found that important biochemical and cell biological properties have diverged. We propose that correct intraplastidic AtMinD1 localization is dependent on AtMinE1-stimulated, Ca2+-dependent AtMinD1 ATP hydrolysis, ultimately ensuring precise Z-ring placement and symmetric plastid division.