• Species distribution is strongly driven by local and global gradients in water availability but the underlying mechanisms are not clear. Vulnerability to xylem embolism (P50) is a key trait that ...indicates how species cope with drought and might explain plant distribution patterns across environmental gradients. Here we address its role on species sorting along a hydrotopographical gradient in a central Amazonian rainforest and examine its variance at the community scale.
• We measured P50 for 28 tree species, soil properties and estimated the hydrological niche of each species using an indicator of distance to the water table (HAND).
• We found a large hydraulic diversity, covering as much as 44% of the global angiosperm variation in P50. We show that P50: contributes to species segregation across a hydrotopographic gradient in the Amazon, and thus to species coexistence; is the result of repeated evolutionary adaptation within closely related taxa; is associated with species tolerance to P-poor soils, suggesting the evolution of a stress-tolerance syndrome to nutrients and drought; and is higher for trees in the valleys than uplands.
• The large observed hydraulic diversity and its association with topography has important implications for modelling and predicting forest and species resilience to climate change.
Extensive research within the last two decades revealed that most chronic illnesses, including cancer, neurological, autoimmune and cardiovascular diseases are mediated through chronic inflammation. ...Thus, suppressing chronic inflammation has the potential to delay, prevent, and treat those diseases. However, side effects and high costs of current anti-inflammatory drugs force the development of new drugs. Natural products represent an important source of new bioactive compounds. Among them, phenolic compounds, which are widely distributed in plants, have been described as having many therapeutic effects. Several reviews have addressed the anti-inflammatory activity of phenols, attributing their properties not only to the antioxidant capacity, but also to inflammatory mediators' modulation, namely cytokines and pro-inflammatory proteins, such as inducible nitric oxide synthase and cyclooxygenase-2. Signal transduction pathways precede changes in inflammatory mediators' expression. However, only a restricted number of studies have addressed the effect of phenols on a specific signal transduction pathway. The present review attempts to summarize and highlight a broad range of inflammation-associated signaling pathways modulated by phenols namely: nuclear factor (NF)-κB, activator protein (AP)-1, peroxisome proliferator-activated receptor (PPAR) and nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factors; mitogen-activated protein kinases (MAPKs); protein tyrosine kinases (PTKs); tyrosine phosphatidylinositol 3-kinase (PI3K)/Akt and ubiquitin-proteasome system. As a consequence of phenols effect on signaling pathways, described above, their action on inflammatory mediators' production is mentioned. Finally, it is established that the structure-activity relationships of phenolic compounds are a valuable information source on the development of new anti-inflammatory drugs from natural products.
This study presents fuzzy versions of Jensen inequalities type integral for convex and concave fuzzy-interval-valued functions. To this end, the concepts of fuzzy inclusion order relation, convexity, ...and concavity for fuzzy-interval-valued functions are used. Some examples showing the applicability of the theory developed in this study are presented. Since the fuzzy results are obtained through level sets of fuzzy-interval elements, the versions of these results in the interval context are presented here for the first time.
The complexity of the electrocatalytic reduction of CO to CH4 and C2H4 on copper electrodes prevents a straightforward elucidation of the reaction mechanism and the design of new and better ...catalysts. Although structural and electrolyte effects have been separately studied, there are no reports on structure-sensitive cation effects on the catalyst’s selectivity over a wide potential range. Therefore, we investigated CO reduction on Cu(100), Cu(111), and Cu(polycrystalline) electrodes in 0.1 M alkaline hydroxide electrolytes (LiOH, NaOH, KOH, RbOH, CsOH) between 0 and −1.5 V vs RHE. We used online electrochemical mass spectrometry and high-performance liquid chromatography to determine the product distribution as a function of electrode structure, cation size, and applied potential. First, cation effects are potential dependent, as larger cations increase the selectivity of all electrodes toward ethylene at E > −0.45 V vs RHE, but methane is favored at more negative potentials. Second, cation effects are structure-sensitive, as the onset potential for C2H4 formation depends on the electrode structure and cation size, whereas that for CH4 does not. Fourier Transform infrared spectroscopy (FTIR) and density functional theory help to understand how cations favor ethylene over methane at low overpotentials on Cu(100). The rate-determining step to methane and ethylene formation is CO hydrogenation, which is considerably easier in the presence of alkaline cations for a CO dimer compared to a CO monomer. For Li+ and Na+, the stabilization is such that hydrogenated dimers are observable with FTIR at low overpotentials. Thus, potential-dependent, structure-sensitive cation effects help steer the selectivity toward specific products.
Out‐of‐hospital cardiac arrest (OHCA) is a major health problem that affects approximately four hundred and thousand patients annually in the United States alone. It is a major challenge for the ...emergency medical system as decreased survival rates are directly proportional to the time delay from collapse to defibrillation. Historically, defibrillation has only been performed by physicians and in‐hospital. With the development of automated external defibrillators (AEDs), rapid defibrillation by nonmedical professionals and subsequently by trained or untrained lay bystanders has become possible. Much hope has been put to the concept of Public Access Defibrillation with a massive dissemination of public available AEDs throughout most Western countries. Accordingly, current guidelines recommend that AEDs should be deployed in places with a high likelihood of OHCA. Despite these efforts, AED use is in most settings anecdotal with little effect on overall OHCA survival. The major reasons for low use of public AEDs are that most OHCAs take place outside high incidence sites of cardiac arrest and that most OHCAs take place in residential settings, currently defined as not suitable for Public Access Defibrillation. However, the use of new technology for identification and recruitment of lay bystanders and nearby AEDs to the scene of the cardiac arrest as well as new methods for strategic AED placement redefines and challenges the current concept and definitions of Public Access Defibrillation. Existing evidence of Public Access Defibrillation and knowledge gaps and future directions to improve outcomes for OHCA are discussed. In addition, a new definition of the different levels of Public Access Defibrillation is offered as well as new strategies for increasing AED use in the society.
The transition from enucleated reticulocytes to mature normocytes is marked by substantial remodeling of the erythrocytic cytoplasm and membrane. Despite conspicuous changes, most studies describe ...the maturing reticulocyte as a homogenous erythropoietic cell type. While reticulocyte staging based on fluorescent RNA stains such as thiazole orange have been useful in a clinical setting; these 'sub-vital' stains may confound delicate studies on reticulocyte biology and may preclude their use in heamoparasite invasion studies.
Here we use highly purified populations of reticulocytes isolated from cord blood, sorted by flow cytometry into four sequential subpopulations based on transferrin receptor (CD71) expression: CD71high, CD71medium, CD71low and CD71negative. Each of these subgroups was phenotyped in terms of their, morphology, membrane antigens, biomechanical properties and metabolomic profile.
Superficially CD71high and CD71medium reticulocytes share a similar gross morphology (large and multilobular) when compared to the smaller, smooth and increasingly concave reticulocytes as seen in the in the CD71low and CD71negativesamples. However, between each of the four sample sets we observe significant decreases in shear modulus, cytoadhesive capacity, erythroid receptor expression (CD44, CD55, CD147, CD235R, and CD242) and metabolite concentrations. Interestingly increasing amounts of boric acid was found in the mature reticulocytes.
Reticulocyte maturation is a dynamic and continuous process, confounding efforts to rigidly classify them. Certainly this study does not offer an alternative classification strategy; instead we used a nondestructive sampling method to examine key phenotypic changes of in reticulocytes. Our study emphasizes a need to focus greater attention on reticulocyte biology.
We address the problem of separating stars from galaxies in future large photometric surveys. We focus our analysis on simulations of the Dark Energy Survey (DES). In the first part of the paper, we ...derive the science requirements on star/galaxy separation, for measurement of the cosmological parameters with the gravitational weak lensing and large-scale structure probes. These requirements are dictated by the need to control both the statistical and systematic errors on the cosmological parameters, and by point spread function calibration. We formulate the requirements in terms of the completeness and purity provided by a given star/galaxy classifier. In order to achieve these requirements at faint magnitudes, we propose a new method for star/galaxy separation in the second part of the paper. We first use principal component analysis to outline the correlations between the objects parameters and extract from it the most relevant information. We then use the reduced set of parameters as input to an Artificial Neural Network. This multiparameter approach improves upon purely morphometric classifiers (such as the classifier implemented in SExtractor), especially at faint magnitudes: it increases the purity by up to 20 per cent for stars and by up to 12 per cent for galaxies, at i-magnitude fainter than 23.
Inflammation is a predominant aspect of neurodegenerative diseases and experimental studies performed in animal models of Parkinson’s disease (PD) suggesting that a sustained neuroinflammation ...exacerbates the nigrostriatal degeneration pathway. The central role of microglia in neuroinflammation has been studied as a target for potential neuroprotective drugs for PD, for example nonsteroidal anti-inflammatory drugs (NSAIDs) and matrix metalloproteinases (MMP) inhibitors that regulates microglial activation and migration. The aim of this study was to investigate the neuroprotective response of the iminosugar 1-deoxynojirimycin (1-DNJ) and compare its effect with a combined treatment with ibuprofen. MPTP-treated mice were orally dosed with ibuprofen and/or 1-DNJ 1. Open-field test was used to evaluate behavioral changes. Immunohistochemistry for dopaminergic neurons marker (TH
+
) and microglia markers (Iba-1
+
; CD68
+
) were used to investigate neuronal integrity and microglial activation in the substantia nigra pars compacta (SNpc). The pro-inflammatory cytokines TNF-α and IL-6 were analysed by qPCR. Treatments with either 1-DNJ or Ibuprofen alone did not reduce the damage induced by MPTP intoxication. However, combined treatment with 1-DNJ and ibuprofen prevents loss of mesencephalic dopaminergic neurons, decreases the number of CD68
+
/ Iba-1
+
cells, the microglia/neurons interactions, and the pro-inflammatory cytokines, and improves behavioral changes when compared with MPTP-treated animals. In conclusion, these data demonstrate that the combined treatment with a MMPs inhibitor (1-DNJ) plus an anti-inflammatory drug (ibuprofen) has neuroprotective effects open for future therapeutic interventions.
Graphical Abstract
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a protoxicant that, after crossing the Blood Brain Barrier, is metabolized by astrocytic MAO-B to MPDP+, a pyridinium intermediate, which undergoes further two-electron oxidation to yield the toxic metabolite MPP+ (methyl-phenyltetrahydropyridinium) that is then selectively transported into nigral neurons via the mesencephalic dopamine transporter. In this study, we demonstrated that MPTP induced death of dopaminergic neurons, microgliosis, increase of gliapses, motor impairment and neuroinflammation in mice, which were inhibited by combined 1-deoxynojirimycin and ibuprofen treatment.
Malaria is an infectious disease that affects over 216 million people worldwide, killing over 445,000 patients annually. Due to the constant emergence of parasitic resistance to the current ...antimalarial drugs, the discovery of new drug candidates is a major global health priority. Aiming to make the drug discovery processes faster and less expensive, we developed binary and continuous Quantitative Structure-Activity Relationships (QSAR) models implementing deep learning for predicting antiplasmodial activity and cytotoxicity of untested compounds. Then, we applied the best models for a virtual screening of a large database of chemical compounds. The top computational predictions were evaluated experimentally against asexual blood stages of both sensitive and multi-drug-resistant Plasmodium falciparum strains. Among them, two compounds, LabMol-149 and LabMol-152, showed potent antiplasmodial activity at low nanomolar concentrations (EC50 <500 nM) and low cytotoxicity in mammalian cells. Therefore, the computational approach employing deep learning developed here allowed us to discover two new families of potential next generation antimalarial agents, which are in compliance with the guidelines and criteria for antimalarial target candidates.
We present a detailed analysis of a recent, 2013 Suzaku campaign on the nearby (z = 0.184) luminous (L
bol ∼ 1047 erg s−1) quasar PDS 456. This consisted of three observations, covering a total ...duration of ∼1 Ms and a net exposure of 455 ks. During these observations, the X-ray flux was unusually low, suppressed by a factor of >10 in the soft X-ray band when compared to previous observations. We investigated the broad-band continuum by constructing a spectral energy distribution (SED), making use of the optical/UV photometry and hard X-ray spectra from the later simultaneous XMM–Newton and NuSTAR campaign in 2014. The high-energy part of this low-flux SED cannot be accounted for by physically self-consistent accretion disc and corona models without attenuation by absorbing gas, which partially covers a substantial fraction of the line of sight towards the X-ray continuum. At least two layers of absorbing gas are required, of column density log (N
H,low/cm−2) = 22.3 ± 0.1 and log (N
H,high/cm−2) = 23.2 ± 0.1, with average line-of-sight covering factors of ∼80 per cent (with typical ∼5 per cent variations) and 60 per cent (±10–15 per cent), respectively. During these observations PDS 456 displays significant short-term X-ray spectral variability, on time-scales of ∼100 ks, which can be accounted for by variable covering of the absorbing gas along the line of sight. The partial covering absorber prefers an outflow velocity of
$v_{\rm pc} = 0.25^{+0.01}_{-0.05}\,c$
at the >99.9 per cent confidence level over the case where v
pc = 0. This is consistent with the velocity of the highly ionized outflow responsible for the blueshifted iron K absorption profile. We therefore suggest that the partial covering clouds could be the denser, or clumpy part of an inhomogeneous accretion disc wind. Finally estimates are placed upon the size-scale of the X-ray emission region from the source variability. The radial extent of the X-ray emitter is found to be of the order ∼15–20R
g, although the hard X-ray (>2 keV) emission may originate from a more compact or patchy corona of hot electrons, which is typically ∼6–8R
g in size.
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