Equal nonbreeding period survival in adults and juveniles of a long‐distant migrant bird

In migrant birds, survival estimates for the different life‐history stages between fledging and first breeding are scarce. First‐year survival is shown to be strongly reduced compared with annual survival of adult birds. However, it remains unclear whether the main bottleneck in juvenile long‐distant migrants occurs in the postfledging period within the breeding ranges or en route. Quantifying survival rates during different life‐history stages and during different periods of the migration cycle is crucial to understand forces driving the evolution of optimal life histories in migrant birds. Here, we estimate survival rates of adult and juvenile barn swallows (Hirundo rustica L.) in the breeding and nonbreeding areas using a population model integrating survival estimates in the breeding ranges based on a large radio‐telemetry data set and published estimates of demographic parameters from large‐scale population‐monitoring projects across Switzerland. Input parameters included the country‐wide population trend, annual productivity estimates of the double‐brooded species, and year‐to‐year survival corrected for breeding dispersal. Juvenile survival in the 3‐week postfledging period was low (S = 0.32; SE = 0.05), whereas in the rest of the annual cycle survival estimates of adults and juveniles were similarly high (S > 0.957). Thus, the postfledging period was the main survival bottleneck, revealing the striking result that nonbreeding period mortality (including migration) is not higher for juveniles than for adult birds. Therefore, focusing future research on sources of variation in postfledging mortality can provide new insights into determinants of population dynamics and life‐history evolution of migrant birds.     

Flowering phenology of a palm community in a central Amazon forest

The flowering phenology of 27 taxa of palms in a lowland moist forest in the central Amazon was recorded over a 40 month period. Phenological data were transformed into measures, of synchrony, regularity, and duration. Flowering was observed at all times of year and there was no correlation with rainfall either for the current month or for any monthly lag interval. The 27 taxa were divided into three pollination groups—weevil, bee/fly, or beetle—based on their behavior at anthesis. Phenology was significantly correlated with pollination groups. Weevilpollinated palms had higher synchrony and shorter duration of flowering than other groups. Bee/fly-pollinated palms had lower synchrony and longer duration of flowering. The beetle-pollinated palms were intermediate between the two other groups. Seasonal regularity of flowering was similar in all three groups. We suggest that, at least inBactris, taxa exhibit staggered flowering.     

The FgfrL1 receptor is required for development of slow muscle fibers

FgfrL1, which interacts with Fgf ligands and heparin, is a member of the fibroblast growth factor receptor (Fgfr) family. FgfrL1-deficient mice show two significant alterations when compared to wildtype mice: They die at birth due to a malformed diaphragm and they lack metanephric kidneys. Utilizing gene arrays, qPCR and in situ hybridization we show here that the diaphragm of FgfrL1 knockout animals lacks any slow muscle fibers at E18.5 as indicated by the absence of slow fiber markers Myh7, Myl2 and Myl3. Similar lesions are also found in other skeletal muscles that contain a high proportion of slow fibers at birth, such as the extraocular muscles. In contrast to the slow fibers, fast fibers do not appear to be affected as shown by expression of fast fiber markers Myh3, Myh8, Myl1 and MylPF. At early developmental stages (E10.5, E15.5), FgfrL1-deficient animals express slow fiber genes at normal levels. The loss of slow fibers cannot be attributed to the lack of kidneys, since Wnt4 knockout mice, which also lack metanephric kidneys, show normal expression of Myh7, Myl2 and Myl3. Thus, FgfrL1 is specifically required for embryonic development of slow muscle fibers.     

Generalized arterial calcification of infancy and pseudoxanthoma elasticum can be caused by mutations in either ENPP1 or ABCC6

Spontaneous pathologic arterial calcifications in childhood can occur in generalized arterial calcification of infancy (GACI) or in pseudoxanthoma elasticum (PXE). GACI is associated with biallelic mutations in ENPP1 in the majority of cases, whereas mutations in ABCC6 are known to cause PXE. However, the genetic basis in subsets of both disease phenotypes remains elusive. We hypothesized that GACI and PXE are in a closely related spectrum of disease. We used a standardized questionnaire to retrospectively evaluate the phenotype of 92 probands with a clinical history of GACI. We obtained the ENPP1 genotype by conventional sequencing. In those patients with less than two disease-causing ENPP1 mutations, we sequenced ABCC6. We observed that three GACI patients who carried biallelic ENPP1 mutations developed typical signs of PXE between 5 and 8 years of age; these signs included angioid streaks and pseudoxanthomatous skin lesions. In 28 patients, no disease-causing ENPP1 mutation was found. In 14 of these patients, we detected pathogenic ABCC6 mutations (biallelic mutations in eight patients, monoallelic mutations in six patients). Thus, ABCC6 mutations account for a significant subset of GACI patients, and ENPP1 mutations can also be associated with PXE lesions in school-aged children. Based on the considerable overlap of genotype and phenotype of GACI and PXE, both entities appear to reflect two ends of a clinical spectrum of ectopic calcification and other organ pathologies, rather than two distinct disorders. ABCC6 and ENPP1 mutations might lead to alterations of the same physiological pathways in tissues beyond the artery.     

Therapeutic Use of a Selective S1P1 Receptor Modulator Ponesimod in Autoimmune Diabetes

In the present study, we investigated the therapeutic potential of a selective S1P₁ receptor modulator, ponesimod, to protect and reverse autoimmune diabetes in non-obese diabetic (NOD) mice. Ponesimod was administered orally to NOD mice starting at 6, 10, 13 and 16 weeks of age up to 35 weeks of age or to NOD mice showing recent onset diabetes. Peripheral blood and spleen B and T cell counts were significantly reduced after ponesimod administration. In pancreatic lymph nodes, B lymphocytes were increased and expressed a transitional 1-like phenotype. Chronic oral ponesimod treatment efficiently prevented autoimmune diabetes in 6, 10 and 16 week-old pre-diabetic NOD mice. Treatment withdrawal led to synchronized disease relapse. Ponesimod did not inhibit the differentiation of autoreactive T cells as assessed by adoptive transfer of lymphocytes from treated disease-free NOD mice. In addition, it did not affect the migration, proliferation and activation of transgenic BDC2.5 cells into the target tissue. However, ponesimod inhibited spreading of the T cell responses to islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). Treatment of diabetic NOD mice with ponesimod induced disease remission. However, here again, upon treatment cessation, the disease rapidly recurred. This recurrence was effectively prevented by combination treatment with a CD3 antibody leading to the restoration of self-tolerance. In conclusion, treatment with a selective S1P₁ modulator in combination with CD3 antibody represents a promising therapeutic approach for the treatment of autoimmune diabetes.     

A predictive framework to assess spatio‐temporal variability of infestations by the European spruce bark beetle

Natural disturbances are key factors for the development of forest ecosystems. In forests of central Europe and Scandinavia, the European spruce bark beetle Ips typographus is the most devastating biotic disturbance agent in Norway spruce Picea abies, but our understanding of the factors determining its spatio‐temporal dynamics is still quite limited. To quantify the drivers of bark beetle dynamics, we analyzed a survey dataset with annual resolution that covers 17 yr and 469 forest districts (10 860 km² of forest area) all over Switzerland. We used Poisson log‐normal models in a Bayesian framework to analyze the spatio‐temporal dynamics of bark beetle infestation spots at the forest district level. Bark beetle infestations increased with increasing heat sum (> 8.3°C), volume of standing Norway spruce stock, and the number of infestation spots of the previous year. Precipitation tended to slightly affect the risk of bark beetle infestations. Two major storm events further increased the spatio‐temporal variability of bark beetle infestations. Spruce abundance, storm damage and temperature are known to be important factors influencing the population dynamics of the European spruce bark beetle. Our study is the first to quantify the combined effects of spruce abundance and heat sum, whereby the heat sum turned out to be the most important and consistent predictor. Because our study area encompasses large ecological and climatological gradients, our model is likely to be applicable to Norway spruce forests in other regions of central Europe and Scandinavia.     

EUROCarbDB: An open-access platform for glycoinformatics

The EUROCarbDB project is a design study for a technical framework, which provides sophisticated, freely accessible, open-source informatics tools and databases to support glycobiology and glycomic research. EUROCarbDB is a relational database containing glycan structures, their biological context and, when available, primary and interpreted analytical data from high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance experiments. Database content can be accessed via a web-based user interface. The database is complemented by a suite of glycoinformatics tools, specifically designed to assist the elucidation and submission of glycan structure and experimental data when used in conjunction with contemporary carbohydrate research workflows. All software tools and source code are licensed under the terms of the Lesser General Public License, and publicly contributed structures and data are freely accessible. The public test version of the web interface to the EUROCarbDB can be found at http://www.ebi.ac.uk/eurocarb.     

Diffusional mobility of parvalbumin in spiny dendrites of cerebellar Purkinje neurons quantified by fluorescence recovery after photobleaching

Ca(2+)-binding proteins (CaBPs) represent key factors for the modulation of cellular Ca(2+) dynamics. Especially in thin extensions of nerve cells, Ca(2+) binding and buffered diffusion of Ca(2+) by CaBPs is assumed to effectively control the spatio-temporal extend of Ca(2+) signals. However, no quantitative data about the mobility of specific CaBPs in the neuronal cytosol are available. We quantified the diffusion of the endogenous CaPB parvalbumin (PV) in spiny dendrites of cerebellar Purkinje neurons with two-photon fluorescence recovery after photobleaching. Fluorescently labeled PV diffused readily between spines and dendrites with a median time constant of 49 ms (37-61 ms, interquartile range). Based on published data on spine geometry, this value corresponds to an apparent diffusion coefficient of 43 microm(2) s(-1) (34-56 microm(2) s(-1)). The absence of large or immobile binding partners for PV was confirmed in PV null-mutant mice. Our data validate the common but so far unproven assumption that PV is highly mobile in neurons and will facilitate simulations of neuronal Ca(2+) buffering. Our experimental approach represents a versatile tool for quantifying the mobility of proteins in neuronal dendrites.     

Identification of specificity-defining amino acids of the wheat immune receptor Pm2 and powdery mildew effector AvrPm2

Plant nucleotide-binding leucine-rich repeat receptors (NLRs) act as intracellular sensors for pathogen-derived effector proteins and trigger an immune response, frequently resulting in the hypersensitive cell death response (HR) of the infected host cell. The wheat (Triticum aestivum) NLR Pm2 confers resistance against the fungal pathogen Blumeria graminis f. sp. tritici (Bgt) if the isolate contains the specific RNase-like effector AvrPm2. We identified and isolated seven new Pm2 alleles (Pm2e–i) in the wheat D-genome ancestor Aegilops tauschii and two new natural AvrPm2 haplotypes from Bgt. Upon transient co-expression in Nicotiana benthamiana, we observed a variant-specific HR of the Pm2 variants Pm2a and Pm2i towards AvrPm2 or its homolog from the AvrPm2 effector family, BgtE-5843, respectively. Through the introduction of naturally occurring non-synonymous single nucleotide polymorphisms and structure-guided mutations, we identified single amino acids in both the wheat NLR Pm2 and the fungal effector proteins AvrPm2 and BgtE-5843 responsible for the variant-specific HR of the Pm2 variants. Exchanging these amino acids led to a modified HR of the Pm2–AvrPm2 interaction and allowed the identification of the effector head epitope, a 20-amino-acid long unit of AvrPm2 involved in the HR. Swapping of the AvrPm2 head epitope to the non-HR-triggering AvrPm2 family member BgtE-5846 led to gain of a HR by Pm2a. Our study presents a molecular approach to identify crucial effector surface structures involved in the HR and demonstrates that natural and induced diversity in an immune receptor and its corresponding effectors can provide the basis for understanding and modifying NLR–effector specificity.