A genome blogger manifesto

Cheap prices for genomic testing have revolutionized consumers’ access to personal genomics. Exploration of personal genomes poses significant challenges for customers wishing to learn beyond provider customer reports. A vibrant community has spontaneously appeared blogging experiences and data as a way to learn about their personal genomes. No set of values has publicly been described to date encapsulating ideals and code of conduct for this community. Here I present a first attempt to address this vacuum based on my own personal experiences as genome blogger

An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

Prolonged injury symptoms and later visits to psychiatric care after mild traumatic brain injury in school-age

Objective To investigate demographic and pre-injury factors in Finnish school-aged children admitted to pediatric neurology services after mild traumatic brain injury (mTBI). The relation of these factors to prolonged injury symptoms and later visits into psychiatric care was assessed. Methods Demographic information, pre-injury learning status, and neuropsychological test results of 120 patients aged 7-16 years were retrospectively collected from the hospital medical records. Data were compared with self- or parent-reported injury symptoms at 1-3 months post-injury and later visits to psychiatric care. Results According to medical records, 14.2% of the children with mTBI had a diagnosed neurobehavioral or psychiatric condition pre-injury. Additionally, 53.3% of the children had some neurobehavioral or psychiatric concerns or traits prior to the injury. Over half (56.7%) of the children studied were symptomatic at 1-3 months following the injury. Female gender and presence of prolonged symptoms were predictive for later visit into psychiatric care. Conclusions Pre-injury neurobehavioral or psychiatric problems may predict prolonged injury symptoms following pediatric mTBI. In this retrospective patient series, prolonged symptoms and female gender seem to predict the need for later psychiatric care. Monitoring the recovery of children with mTBI and pre-injury risk factors is important for timely interventions.Peer reviewe

Machine Learning Interatomic Potentials as Emerging Tools for Materials Science.

Atomic-scale modeling and understanding of materials have made remarkable progress, but they are still fundamentally limited by the large computational cost of explicit electronic-structure methods such as density-functional theory. This Progress Report shows how machine learning (ML) is currently enabling a new degree of realism in materials modeling: by "learning" electronic-structure data, ML-based interatomic potentials give access to atomistic simulations that reach similar accuracy levels but are orders of magnitude faster. A brief introduction to the new tools is given, and then, applications to some select problems in materials science are highlighted: phase-change materials for memory devices; nanoparticle catalysts; and carbon-based electrodes for chemical sensing, supercapacitors, and batteries. It is hoped that the present work will inspire the development and wider use of ML-based interatomic potentials in diverse areas of materials research.Academy of Finland under project #310574. The authors are thankful for generous allocation of computational resources on the ARCHER UK National Supercomputing Service (EPSRC grants EP/K014560/1 and EP/P022596/1) and by CSC ‐ IT Center for Science, Finland, which supported some of the work discussed herein. V.L.D. and M.A.C. are grateful for mutual HPC‐Europa3 exchange visits (funded by the European Union's Horizon 2020 research and innovation programme under grant agreement No. 730897), during one of which this manuscript was finalized

Overview of farmers expected benefits of diversification. Report on national stakeholder involvement.

Seven different European countries are participating in a transnational project SUREVEG (Strip-cropping and recycling of waste for biodiverse and resoURce-Efficient intensive VEGetable production). SUREVEG focuses on developing and implementing new diversified, intensive organic cropping systems using strip-cropping and fertility strategies from plant-based fertilizers for improved resilience, system sustainability, local nutrient recycling and soil carbon storage. This study focuses on providing references concerning benefits and drawbacks of strip-cropping and plant residues for soil fertility in field vegetable production at medium sized organic farms. Specifically to identify local stakeholders’ knowledge and develop ideas in an iterative approach on benefits of diversification in space, time and genes, and plant-based fertilizers. Activities included workshops with stakeholder involvement, to increase awareness and dialogue on strip-cropping and identify local technical and practical knowledge on organic systems. A survey was developed as a tool for having a more systematic discussion with the stakeholders in the workshops. With a selection of questions to analysis the performance criteria of strip-cropping in farmers perspective a transnational comparison of the findings is presented,. The workshops and surveys were executed in six different European countries. In total approximately 140 farmers and other stakeholders were participating in the workshops and 38 farmers filled out the survey. The outcome of the survey and workshops in the different countries suggests that most farmers think fairly equally about the added values of strip-cropping. Higher resistance of crops against plagues and diseases is ranked high in all countries. This is followed by soil quality and benefits from increased agroecosystem biodiversity. Only Belgian farmers mentioned higher yield as an important added value, however certain individual farmers in different counties have ranked it high as well. Divers answers were given on the question on the most suitable width of the cropping-strips. For farmers this depends mostly on the machinery farmers have available for their daily practices. For the importance of crop traits, the efficient use of nutrients and resilience against diseases and plagues scored high throughout all countries investigated. Only Italian farmers mentioned nitrogen-fixing capacity as an important trait. The farmers in all countries thought the same about expected bottlenecks for implementing strip-cropping system: harvesting, weed control and technical problems. The information obtained by the survey and workshops in the different countries is input for the experimental design of field trials in each country. Some countries changed their set-up for following years. To conclude, in the participating countries, the use of strip-cropping is still limited. The farmers participating, consider strip-cropping a promising innovation. However, a lot of basic questions about strip-cropping still need to be answered for farmers before implementing strip-cropping. Farmers in every country will benefit from a database of best crops combinations. In Finland, the farmers explicitly mentioned the need of good companion crops for Brassicaceae and Apiaceae vegetables (suitable trap crops)

Ectopic expression of PtaRHE1, encoding a poplar RING-H2 protein with E3 ligase activity, alters plant development and induces defence-related responses

RING (really interesting new gene)-H2 domain-containing proteins are widely represented in plants and play important roles in the regulation of many developmental processes as well as in plant–environment interactions. In the present report, experiments were performed to unravel the role of the poplar gene PtaRHE1, coding for a RING-H2 protein. In vitro ubiquitination assays indicate a functional E3 ligase activity for PtaRHE1 with the specific E2 ubiquitin-conjugating enzyme UbcH5a. The overexpression of PtaRHE1 in tobacco resulted in a pleiotropic phenotype characterized by a curling of the leaves, the formation of necrotic lesions on leaf blades, growth retardation, and a delay in floral transition. The plant gene expression response to PtaRHE1 overexpression provided evidence for the up-regulation of defence- and/or programmed cell death-related genes. Moreover, genes coding for WRKY transcription factors as well as for mitogen-activated protein kinases, such as wound-induced protein kinase (WIPK), were also found to be induced in the transgenic lines as compared with the wild type. In addition, histochemical β-glucuronidase staining showed that the PtaRHE1 promoter is induced by plant pathogens and by elicitors such as salicylic acid and cellulase. Taken together, these results suggest that the E3 ligase PtaRHE1 plays a role in the ubiquitination-mediated regulation of defence response, possibly by acting upstream of WIPK and/or in the activation of WRKY factors

High throughput in vitro seed germination screen identified new ABA responsive RING-type ubiquitin E3 ligases in Arabidopsis thaliana

Seed quality is an important factor for seedling vigour as well as adult plant resilience. The key quality attributes are related to physical characteristics, physiological performance, genetic background and health status of the seeds. Many ways to address seed quality attributes have been developed and recently many of them have featured automated high throughput methods. In our study, we addressed two of the seed quality attributes, namely physiological performance and genetic background by analysing germination rates in our mutant collection. These mutants represent ubiquitin E3 ligases that transcriptionally respond to abscisic acid (ABA). This plant hormone is an important regulator of germination and seedling establishment. To facilitate in vitro germination screens of large seed collections a high throughput image-based assay was developed. As a read out of the germination on ABA treatment the cotyledon emergence was detected with top view chlorophyll fluorescence camera. By applying the ABA treatment during germination, RING-type ubiquitin E3 ligase mutants were identified, showing either resistant or sensitive responses to ABA. In conclusion, a scalable high throughput screen for in vitro germination assay was established that allowed fast screening of tens of mutants in a hormone supplemented media.Peer reviewe

Three distinct molecular surfaces in ephrin-A5 are essential for a functional interaction with EphA3

Eph receptor tyrosine kinases (Ephs) function as molecular relays that interact with cell surface-bound ephrin ligands to direct the position of migrating cells. Structural studies revealed that, through two distinct contact surfaces on opposite sites of each protein, Eph and ephrin binding domains assemble into symmetric, circular heterotetramers. However, Eph signal initiation requires the assembly of higher order oligomers, suggesting additional points of contact. By screening a random library of EphA3 binding-compromised ephrin-A5 mutants, we have now determined ephrin-A5 residues that are essential for the assembly of high affinity EphA3 signaling complexes. In addition to the two interfaces predicted from the crystal structure of the homologous EphB2 center dot ephrin-B2 complex, we identified a cluster of 10 residues on the ephrin-A5 E alpha-helix, the E-F loop, the underlying H beta-strand, as well as the nearby B - C loop, which define a distinct third surface required for oligomerization and activation of EphA3 signaling. Together with a corresponding third surface region identified recently outside of the minimal ephrin binding domain of EphA3, our findings provide experimental evidence for the essential contribution of three distinct protein-interaction interfaces to assemble functional EphA3 signaling complexes

Intermittent exposure to traces of green leaf volatiles triggers a plant response

Plants are known to mount a defensive response when exposed to volatile chemicals from other plants, but the critical concentration required for this response is not known. We showed that intermittent exposure over a period of 3 weeks to trace amounts (less than 140 pptV) of green leaf volatiles emitted by a freshly damaged Arabidopsis plant induced physiological (defensive) responses in undamaged neighbouring plants. These results demonstrated that plants can respond to long-term repeated exposures to subcritical amounts of chemical signals