The crystal structure of the Physarum polycephalum actin-fragmin kinase: an atypical protein kinase with a specialized substrate-binding domain.

Coordinated temporal and spatial regulation of the actin cytoskeleton is essential for diverse cellular processes such as cell division, cell motility and the formation and maintenance of specialized structures in differentiated cells. In plasmodia of Physarum polycephalum, the F-actin capping activity of the actin-fragmin complex is regulated by the phosphorylation of actin. This is mediated by a novel type of protein kinase with no sequence homology to eukaryotic-type protein kinases. Here we present the crystal structure of the catalytic domain of the first cloned actin kinase in complex with AMP at 2.9 A resolution. The three-dimensional fold reveals a catalytic module of approximately 160 residues, in common with the eukaryotic protein kinase superfamily, which harbours the nucleotide binding site and the catalytic apparatus in an inter-lobe cleft. Several kinases that share this catalytic module differ in the overall architecture of their substrate recognition domain. The actin-fragmin kinase has acquired a unique flat substrate recognition domain which is supposed to confer stringent substrate specificity.     

A framework integrating physiology,dispersal and land‐use to project species ranges under climate change

To study the potential effects of climate change on species, one of the most popular approaches are species distribution models (SDMs). However, they usually fail to consider important species‐specific biological traits, such as species’ physiological capacities or dispersal ability. Furthermore, there is consensus that climate change does not influence species distributions in isolation, but together with other anthropogenic impacts such as land‐use change, even though studies investigating the relative impacts of different threats on species and their geographic ranges are still rare. Here we propose a novel integrative approach which produces refined future range projections by combining SDMs based on distribution, climate, and physiological tolerance data with empirical data on dispersal ability as well as current and future land‐use. Range projections based on different combinations of these factors show strong variation in projected range size for our study species Emberiza hortulana. Using climate and physiological data alone, strong range gains are projected. However, when we account for land‐use change and dispersal ability, future range‐gain may even turn into a future range loss. Our study highlights the importance of accounting for biological traits and processes in species distribution models and of considering the additive effects of climate and land‐use change to achieve more reliable range projections. Furthermore, with our approach we present a new tool to assess species’ vulnerability to climate change which can be easily applied to multiple species.     

Phylogenetic signals in thermal traits remain stronger in the tropics if we can believe published physiological data. A reply to McKechnie et al., “Data quality problems undermine analyses of endotherm upper critical temperatures”

Due to concerns about data quality, McKechnie, Coe, Gerson, and Wolf ( 2016 ) questioned the conclusions of our study (Khaliq et al., 2015 ) published in this journal. Here, we argue that most of the questioned data points are in fact useful for macrophysiological analyses, mostly because the vast majority of data are explicitly reported in the peer‐reviewed physiological literature. Furthermore, we show that our conclusions remain largely robust irrespective of the data inclusion criterion. While we think that constructive debates about the adequate use of primary data in meta‐studies as well as more transparency in data inclusion criteria are indeed useful, we also emphasize that data suitability should be evaluated in the light of the scope and scale of the study in which they are used. We hope that this discussion will not discourage the exchange between disciplines such as biogeography and physiology, as this integration is needed to address some of the most urgent scientific challenges.     

NT-proBNP during and after primary PCI for improved scheduling of early hospital discharge

Background

The Zwolle Risk Score (ZRS) identifies primary percutaneous coronary intervention (PPCI) patients at low mortality risk, eligible for early discharge. Recently, this score was improved by adding baseline NT-proBNP. However, the optimal timepoint for NT-proBNP measurement is unknown.

Methods

PPCI patients in the On-Time 2 study were candidates. The ZRS and NT-proBNP levels on admission, at 18–24?h, at 72–96?h, and the change in NT-proBNP from baseline to 18–24?h (delta NT-proBNP) were determined. We investigated whether addition of the different NT-proBNP measurements to the ZRS improves the prediction of 30-day mortality. Based on cut-off values reflecting zero mortality at 30?d, patients who potentially could be discharged early were identified and occurrence of major adverse cardiac events (MACE) and major bleeding until 10?d was registered.

Results

845 patients were included. On multivariate analyses, NT-proBNP at baseline (HR 2.09, 95% CI 1.59–2.74, p < 0.001), at 18–24?h (HR 6.83, 95% CI 2.94–15.84), and at 72–96?h (HR 3.32, 95% CI 1.22–9.06) independently predicted death at 30?d. Addition of NT-proBNP to the ZRS improved prediction of mortality, particularly at 18–24?h (net reclassification index 29%, p < 0.0001, integrated discrimination improvement 17%, p < 0.0001). Based on ZRS (<2) or NT-proBNP at 18–24?h (<2500?pg/ml) 75% of patients could be targeted for early discharge at 48?h, with expected re-admission rates of 1.2% due to MACE and/or major bleeding.

Conclusions

NT-proBNP at different timepoints improves prognostication of the ZRS. Particularly at 18–24?h post PPCI, the largest group of patients that potentially could be discharged early was identified.

     

Chalcone synthase gene lineage diversification confirms allopolyploid evolutionary relationships of European rostrate violets

Phylogenetic relationships among and within the subsections of the genus Viola are still far from resolved. We present the first organismal phylogeny of predominantly western European species of subsection Rostratae based on the plastid trnS-trnG intron and intergenic spacer and the nuclear low-copy gene chalcone synthase (CHS) sequences. CHS is a key enzyme in the synthesis of flavonoids, which are important for flower pigmentation. Genes encoding for CHS are members of a multigene family. In Viola, 3 different CHS copies are present. CHS gene lineages obtained confirmed earlier hypotheses about reticulate relationships between species of Viola subsection Rostratae based on karyotype data. Comparison of the CHS gene lineage tree and the plastid species phylogeny of Viola reconstructed in this study indicates that the different CHS copies present in Viola are the products of both recent and more ancient duplications.     

Bactericidal activity of LFchimera is stronger and less sensitive to ionic strength than its constituent lactoferricin and lactoferrampin peptides

The innate immunity factor lactoferrin harbours two antimicrobial moieties, lactoferricin and lactoferrampin, situated in close proximity in the N1 domain of the molecule. Most likely they cooperate in many of the beneficial activities of lactoferrin. To investigate whether chimerization of both peptides forms a functional unit we designed a chimerical structure containing lactoferricin amino acids 17-30 and lactoferrampin amino acids 265-284. The bactericidal activity of this LFchimera was found to be drastically stronger than that of the constituent peptides, as was demonstrated by the need for lower dose, shorter incubation time and less ionic strength dependency. Likewise, strongly enhanced interaction with negatively charged model membranes was found for the LFchimera relative to the constituent peptides. Thus, chimerization of the two antimicrobial peptides resembling their structural orientation in the native molecule strikingly improves their biological activity.     

No evidence for melatonin-linked immunoenhancement over the annual cycle of an avian species

The winter immunoenhancement hypothesis associates long nights and increased exposure to melatonin with enhanced immune function in winter when resource availability is low and the chances of becoming ill are high. Thus, increased exposure to melatonin in the winter could be adaptive for species facing difficult winter conditions. This idea has found some support in studies of resident mammals. In birds, the link between day length and melatonin over the annual cycle is weaker, and contributions of melatonin to seasonal timing are unclear. Furthermore, many species, especially migrants, do not experience the most difficult conditions of their annual cycle in winter. In this study, we tested whether the winter immunoenhancement hypothesis holds in an avian species, the red knot Calidris canutus. We found that melatonin duration and amplitude varied significantly over the annual cycle with the highest values occurring in winter. However, peaks did not correspond to the winter solstice or with annual variation in immune function. Our findings do not support the winter immunoenhancement hypothesis in knots and question whether the idea that immune function should be bolstered in winter can be generalized to systems where winter is not the most difficult time of the year.     

Gliotoxin in <Emphasis Type="Italic">Aspergillus fumigatus</Emphasis>: an example that mycotoxins are potential virulence factors

Moulds produce several different mycotoxins that may improve their chance of survival in particular environments. For example, Aspergillus fumigatus, an important human pathogen, produces several mycotoxins including gliotoxin. This secondary metabolite, a small lipid soluble dipeptide, exerts toxic effects on phagocytic cells and T-lymphocytes at low concentrations in vitro. A. fumigatus also produces high levels of gliotoxin in vivo, and this suggests that host defense mechanisms might be impaired by this metabolite during host infection. In the past few years, the genes responsible for the production of gliotoxin in A. fumigatus have been identified and more recently gliotoxin-minus mutants have been used in animal experiments to ascertain the biological role of this product. Mycotoxins have also been shown to act as virulence factors in some fungal infections of insects and plants.