On the key role of droughts in the dynamics of summer fires in Mediterranean Europe

Summer fires frequently rage across Mediterranean Europe, often intensified by high temperatures and droughts. According to the state-of-the-art regional fire risk projections, in forthcoming decades climate effects are expected to become stronger and possibly overcome fire prevention efforts. However, significant uncertainties exist and the direct effect of climate change in regulating fuel moisture (e.g. warmer conditions increasing fuel dryness) could be counterbalanced by the indirect effects on fuel structure (e.g. warmer conditions limiting fuel amount), affecting the transition between climate-driven and fuel-limited fire regimes as temperatures increase. Here we analyse and model the impact of coincident drought and antecedent wet conditions (proxy for the climatic factor influencing total fuel and fine fuel structure) on the summer Burned Area (BA) across all eco-regions in Mediterranean Europe. This approach allows BA to be linked to the key drivers of fire in the region. We show a statistically significant relationship between fire and same-summer droughts in most regions, while antecedent climate conditions play a relatively minor role, except in few specific eco-regions. The presented models for individual eco-regions provide insights on the impacts of climate variability on BA, and appear to be promising for developing a seasonal forecast system supporting fire management strategies.We thank the European Forest Fire Information System-EFFIS (http://effis.jrc.ec.europa.eu) of the European Commission Joint Research Centre for the fire data. We acknowledge the SPEI data providers (http://sac.csic. es/spei/database.html). Special thanks to Joaquín Bedia, Esteve Canyameras, Xavier Castro and Andrej Ceglar for helpful discussions on the study. This work was partially funded by the Project of Interest “NextData” of the Italian Ministry for Education, University and Research and by the EU H2020 Project 641762 “ECOPOTENTIAL: Improving Future Ecosystem Benefits through Earth Observations”. Ricardo Trigo was supported by IMDROFLOOD funded by Portuguese FCT (WaterJPI/0004/2014).Peer ReviewedPostprint (published version

Detection and quantification of glenohumeral joint effusion: reliability of ultrasound

Objectives: To evaluate reliability of ultrasound for detection and quantification of glenohumeral joint effusion. Methods: With institutional review board approval and informed consent ultrasound of 30 consecutive patients before and after MR arthrography of the shoulder was performed. Presence and width of any anechoic collection was noted within various locations (biceps tendon sheath, subscapular recess (neutral position and internal rotation), posterior glenohumeral joint recess (neutral position and external rotation)). Injected fluid (8-12ml) into the glenohumeral joint served as gold-standard. Widths of anechoic collections were correlated (Spearman rank correlation) with injected fluid. Results: Glenohumeral anechoic collection was consistently seen in the posterior glenohumeral joint recess with the arm in external rotation (100%, 30/30), and in the biceps tendon sheath (97%, 29/30). Ultrasound was not sensitive at other locations (7%-17%). Mean width in anterior-posterior direction of anechoic collection in the posterior glenohumeral joint recess was 7mm (range: 3-18mm), 2mm (range: 1-7mm) in the biceps tendon sheath. Significant correlation (R = 0.390, p = 0.033) was found between width of anechoic collection and injected fluid in the posterior glenohumeral joint recess. Conclusions: Glenohumeral joint effusion can be detected and quantified most reliably in the posterior glenohumeral joint recess with the arm in external rotatio

Molecular recording of mammalian embryogenesis.

Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes

Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA

The AlkB protein is a repair enzyme that uses an α-ketoglutarate/Fe(II)-dependent mechanism to repair alkyl DNA adducts. AlkB has been reported to repair highly susceptible substrates, such as 1-methyladenine and 3-methylcytosine, more efficiently in ss-DNA than in ds-DNA. Here, we tested the repair of weaker AlkB substrates 1-methylguanine and 3-methylthymine and found that AlkB prefers to repair them in ds-DNA. We also discovered that AlkB and its human homologues, ABH2 and ABH3, are able to repair the aforementioned adducts when the adduct is present in a mismatched base pair. These observations demonstrate the strong adaptability of AlkB toward repairing various adducts in different environments. (Chemical Equation Presented)

Dynamics of myelin content decrease in the rat stroke model

A majority of studies were usually focused on neuronal death after brain ischemia, however, stroke affects all cell types including oligodendrocytes that form myelin sheath in the CNS. Our study is focused on the changes of myelin content in ischemic core and neighbor structures in early terms (1, 3 and 10 days) after stroke. Stroke modeled with middle cerebral artery occlusion (MCAo) in 15 male rats that were divided in three groups by time-points after operation. Brain sections were histologically stained with Luxol Fast Blue (LFB) for myelin quantification. The significant demyelination was found in the ischemic core, corpus callosum, anterior commissure, whereas myelin content was increased in caudoputamen, internal capsule and piriform cortex compared with the contralateral hemisphere. The motor cortex showed a significant increase of myelin content on the 1st day and a significant decrease on the 3rd and 10th days after MCAo. These results suggest stroke influences myelination not only in ischemic core but also in distant structures

Exact beta function from the holographic loop equation of large-N QCD_4

We construct and study a previously defined quantum holographic effective action whose critical equation implies the holographic loop equation of large-N QCD_4 for planar self-avoiding loops in a certain regularization scheme. We extract from the effective action the exact beta function in the given scheme. For the Wilsonean coupling constant the beta function is exacly one loop and the first coefficient agrees with its value in perturbation theory. For the canonical coupling constant the exact beta function has a NSVZ form and the first two coefficients agree with their value in perturbation theory.Comment: 42 pages, latex. The exponent of the Vandermonde determinant in the quantum effective action has been changed, because it has been employed a holomorphic rather than a hermitean resolution of identity in the functional integral. Beta function unchanged. New explanations and references added, typos correcte

Sustained Immune Complex-Mediated Reduction in CD16 Expression after Vaccination Regulates NK Cell Function

Cross-linking of FcγRIII (CD16) by immune complexes induces antibody-dependent cellular cytotoxicity (ADCC) by natural killer (NK) cells, contributing to control of intracellular pathogens; this pathway can also be targeted for immunotherapy of cancerous or otherwise diseased cells. However, downregulation of CD16 expression on activated NK cells may limit or regulate this response. Here, we report sustained downregulation of CD16 expression on NK cells in vivo after intramuscular (but not intranasal) influenza vaccination. CD16 downregulation persisted for at least 12 weeks after vaccination and was associated with robust enhancement of influenza-specific plasma antibodies after intramuscular (but not intranasal) vaccination. This effect could be emulated in vitro by co-culture of NK cells with influenza antigen and immune serum and, consistent with the sustained effects after vaccination, only very limited recovery of CD16 expression was observed during long-term in vitro culture of immune complex-treated cells. CD16 downregulation was most marked among normally CD16high CD57+ NK cells, irrespective of NKG2C expression, and was strongly positively associated with degranulation (surface CD107a expression). CD16 downregulation was partially reversed by inhibition of ADAM17 matrix metalloprotease, leading to a sustained increase in both CD107a and CD25 (IL-2Rα) expression. Both the degranulation and CD25 responses of CD57+ NK cells were uniquely dependent on trivalent influenza vaccine-specific IgG. These data support a role for CD16 in early activation of NK cells after vaccination and for CD16 downregulation as a means to modulate NK cell responses and maintain immune homeostasis of both antibody and T cell-dependent pathways

Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity.

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels

A Multiplexed Single-Cell CRISPR Screening Platform Enables Systematic Dissection of the Unfolded Protein Response

Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis. Subjecting ∼100 hits to Perturb-seq enabled high-precision functional clustering of genes. Single-cell analyses decoupled the three UPR branches, revealed bifurcated UPR branch activation among cells subject to the same perturbation, and uncovered differential activation of the branches across hits, including an isolated feedback loop between the translocon and IRE1α. These studies provide insight into how the three sensors of ER homeostasis monitor distinct types of stress and highlight the ability of Perturb-seq to dissect complex cellular responses.National Human Genome Research Institute (U.S.) (Grant P50HG006193

Electrochemical Characterization of Escherichia coli Adaptive Response Protein AidB

When exposed to known DNA-damaging alkylating agents, Escherichia coli cells increase production of four DNA repair enzymes: Ada, AlkA, AlkB, and AidB. The role of three enzymes (Ada, AlkA, and AlkB) in repairing DNA lesions has been well characterized, while the function of AidB is poorly understood. AidB has a distinct cofactor that is potentially related to the elusive role of AidB in adaptive response: a redox active flavin adenine dinucleotide (FAD). In this study, we report the thermodynamic redox properties of the AidB flavin for the first time, both for free protein and in the presence of potential substrates. We find that the midpoint reduction potential of the AidB flavin is within a biologically relevant window for redox chemistry at −181 mV, that AidB significantly stabilizes the flavin semiquinone, and that small molecule binding perturbs the observed reduction potential. Our electrochemical results combined with structural analysis allow for fresh comparisons between AidB and the homologous acyl-coenzyme A dehydrogenase (ACAD) family of enzymes. AidB exhibits several discrepancies from ACADs that suggest a novel catalytic mechanism distinct from that of the ACAD family enzymes.National Institutes of Health (U.S.) (Grant P30-ES002109)National Institutes of Health (U.S.) (Grant R01-GM69857)National Science Foundation (U.S.) (Grant MCB-0543833