Electron Glass Phase with Resilient Zhang-Rice Singlets in LiCu_{3}O_{3}.

LiCu_{3}O_{3} is an antiferromagnetic mixed valence cuprate where trilayers of edge-sharing Cu(II)O (3d^{9}) are sandwiched in between planes of Cu(I) (3d^{10}) ions, with Li stochastically substituting Cu(II). Angle-resolved photoemission spectroscopy (ARPES) and density functional theory reveal two insulating electronic subsystems that are segregated in spite of sharing common oxygen atoms: a Cu d_{z^{2}}/O p_{z} derived valence band (VB) dispersing on the Cu(I) plane, and a Cu 3d_{x^{2}-y^{2}}/O 2p_{x,y} derived Zhang-Rice singlet (ZRS) band dispersing on the Cu(II)O planes. First-principle analysis shows the Li substitution to stabilize the insulating ground state, but only if antiferromagnetic correlations are present. Li further induces substitutional disorder and a 2D electron glass behavior in charge transport, reflected in a large 530 meV Coulomb gap and a linear suppression of VB spectral weight at E_{F} that is observed by ARPES. Surprisingly, the disorder leaves the Cu(II)-derived ZRS largely unaffected. This indicates a local segregation of Li and Cu atoms onto the two separate corner-sharing Cu(II)O_{2} sub-lattices of the edge-sharing Cu(II)O planes, and highlights the ubiquitous resilience of the entangled two hole ZRS entity against impurity scattering.

ABHD6 suppression promotes anti-inflammatory polarization of adipose tissue macrophages via 2-monoacylglycerol/PPAR signaling in obese mice.

OBJECTIVE: Pro-inflammatory polarization of adipose tissue macrophages (ATMs) plays a critical role in the pathogenesis of obesity-associated chronic inflammation. However, little is known about the role of lipids in the regulation of ATMs polarity and inflammation in response to metabolic stress. Deletion of α/ß-hydrolase domain-containing 6 (ABHD6), a monoacylglycerol (MAG) hydrolase, has been shown to protect against diet-induced obesity and insulin resistance. METHODS: Here we investigated the immunometabolic role of macrophage ABHD6 in response to nutrient excess using whole-body ABHD6-KO mice and human and murine macrophage cell-lines treated with KT203, a selective and potent pharmacological ABHD6 inhibitor. RESULTS: KO mice on high-fat diet showed lower susceptibility to systemic diet-induced inflammation. Moreover, in the setting of overnutrition, stromal vascular cells from gonadal fat of KO vs. control mice contained lower number of M1 macrophages and exhibited enhanced levels of metabolically activated macrophages (MMe) and M2 markers, oxygen consumption, and interleukin-6 (IL-6) release. Likewise, under in vitro nutri-stress condition, inhibition of ABHD6 in MMe-polarized macrophages attenuated the expression and release of pro-inflammatory cytokines and M1 markers and induced the upregulation of lipid metabolism genes. ABHD6-inhibited MMe macrophages showed elevated levels of peroxisome proliferator-activated receptors (PPARs) and 2-MAG species. Notably, among different MAG species, only 2-MAG treatment led to increased levels of PPAR target genes in MMe macrophages. CONCLUSIONS: Collectively, our findings identify ABHD6 as a key component of pro-inflammatory macrophage activation in response to excess nutrition and implicate an endogenous macrophage lipolysis/ABHD6/2-MAG/PPARs cascade, as a lipid signaling and immunometabolic pathway, which favors the anti-inflammatory polarization of ATMs in obesity.

Immune checkpoint inhibitor-induced neurotoxicity is not associated with seroprevalence of neurotropic infections.

BACKGROUND: Immune checkpoint inhibitors (ICI) substantially improve outcome for patients with cancer. However, the majority of patients develops immune-related adverse events (irAEs), which can be persistent and significantly reduce quality of life. Neurological irAEs occur in 1-5% of patients and can induce severe, permanent sequelae or even be fatal. In order to improve the diagnosis and treatment of neurological irAEs and to better understand their pathogenesis, we assessed whether previous neurotropic infections are associated with neurological irAEs. METHODS: Neurotropic infections that might predispose to ICI-induced neurological irAEs were analyzed in 61 melanoma patients from 3 countries, the Netherlands, Australia and Germany, including 24 patients with neurotoxicity and 37 control patients. In total, 14 viral, 6 bacterial, and 1 protozoal infections previously reported to trigger neurological pathologies were assessed using routine serology testing. The Dutch and Australian cohorts (NL) included pre-treatment plasma samples of patients treated with neoadjuvant ICI therapy (OpACIN-neo and PRADO trials; NCT02977052). In the Dutch/Australian cohort a total of 11 patients with neurological irAEs were compared to 27 control patients (patients without neurological irAEs). The German cohort (LMU) consisted of serum samples of 13 patients with neurological irAE and 10 control patients without any documented irAE under ICI therapy. RESULTS: The association of neurological irAEs with 21 possible preceding infections was assessed by measuring specific antibodies against investigated agents. The seroprevalence of all the tested viral (cytomegalovirus, Epstein-Barr-Virus, varicella-zoster virus, measles, rubella, influenza A and B, human herpes virus 6 and 7, herpes simplex virus 1 and 2, parvovirus B19, hepatitis A and E and human T-lymphotropic virus type 1 and 2), bacterial (Borrelia burgdorferi sensu lato, Campylobacter jejuni, Mycoplasma pneumoniae, Coxiella burnetti, Helicobacter pylori, Yersinia enterocolitica and Y. pseudotuberculosis) and protozoal (Toxoplasma gondii) infections was similar for patients who developed neurological irAEs as compared to control patients. Thus, the analysis provided no evidence for an association of described agents tested for seroprevalence with ICI induced neurotoxicity. CONCLUSION: Previous viral, bacterial and protozoal neurotropic infections appear not to be associated with the development of neurological irAEs in melanoma patients who underwent therapy with ICI across 3 countries. Further efforts are needed to unravel the factors underlying neurological irAEs in order to identify risk factors for these toxicities, especially with the increasing use of ICI in earlier stage disease.

Blood Variation Implicates Respiratory Limits on Elevational Ranges of Andean Birds.

AbstractThe extent to which species ranges reflect intrinsic physiological tolerances is a major question in evolutionary ecology. To date, consensus has been hindered by the limited tractability of experimental approaches across most of the tree of life. Here, we apply a macrophysiological approach to understand how hematological traits related to oxygen transport shape elevational ranges in a tropical biodiversity hot spot. Along Andean elevational gradients, we measured traits that affect blood oxygen-carrying capacity-total and cellular hemoglobin concentration and hematocrit, the volume percentage of red blood cells-for 2,355 individuals of 136 bird species. We used these data to evaluate the influence of hematological traits on elevational ranges. First, we asked whether the sensitivity of hematological traits to changes in elevation is predictive of elevational range breadth. Second, we asked whether variance in hematological traits changed as a function of distance to the nearest elevational range limit. We found that birds showing greater hematological sensitivity had broader elevational ranges, consistent with the idea that a greater acclimatization capacity facilitates elevational range expansion. We further found reduced variation in hematological traits in birds sampled near their elevational range limits and at high absolute elevations, patterns consistent with intensified natural selection, reduced effective population size, or compensatory changes in other cardiorespiratory traits. Our findings suggest that constraints on hematological sensitivity and local genetic adaptation to oxygen availability promote the evolution of the narrow elevational ranges that underpin tropical montane biodiversity.

[Adverse effects of licorice consumed as food: An update]. / Toxicités de l'exposition alimentaire à la réglisse : mise au point.

The word "licorice" refers to the plant, its root, and its aromatic extract. From a commercial point of view, Glycyrrhiza glabra is the most important species with a wide range of uses (herbal medicine, tobacco industry, cosmetics, food and pharmaceutical). Glycyrrhizin is one of the main constituents of licorice. Glycyrrhizin is hydrolyzed in the intestinal lumen by bacterial ß-glucuronidases to 3ß-monoglucuronyl-18ß-glycyrrhetinic acid (3MGA) and 18ß-glycyrrhetinic acid (GA), which are metabolized in the liver. Plasma clearance is slow due to enterohepatic cycling. 3MGA and GA can bind to mineralocorticoid receptors with very low affinity, and 3MGA induces apparent mineralocorticoid excess syndrome through dose-dependent inhibition of 11ß-hydroxysteroid dehydrogenase type 2 in renal tissue. The cases of apparent mineralocorticoid excess syndrome reported in the literature are numerous and sometimes severe, even fatal, most often in cases of chronic high dose consumption. Glycyrrhizin poisonings are characterized by hypertension, fluid retention, and hypokalemia with metabolic alkalosis and increased kaliuresis. Toxicity depends on the dose, the type of product consumed, the mode of consumption (acute or chronic) and a very large inter-individual variability. The diagnosis of glycyrrhizin-induced apparent mineralocorticoid excess syndrome is based on the history, clinical examination, and biochemical analysis. Management is primarily based on symptomatic care and stopping licorice consumption.

Emission of coherent THz magnons in an antiferromagnetic insulator triggered by ultrafast spin-phonon interactions.

Antiferromagnetic materials have been proposed as new types of narrowband THz spintronic devices owing to their ultrafast spin dynamics. Manipulating coherently their spin dynamics, however, remains a key challenge that is envisioned to be accomplished by spin-orbit torques or direct optical excitations. Here, we demonstrate the combined generation of broadband THz (incoherent) magnons and narrowband (coherent) magnons at 1 THz in low damping thin films of NiO/Pt. We evidence, experimentally and through modeling, two excitation processes of spin dynamics in NiO: an off-resonant instantaneous optical spin torque in (111) oriented films and a strain-wave-induced THz torque induced by ultrafast Pt excitation in (001) oriented films. Both phenomena lead to the emission of a THz signal through the inverse spin Hall effect in the adjacent heavy metal layer. We unravel the characteristic timescales of the two excitation processes found to be < 50 fs and > 300 fs, respectively, and thus open new routes towards the development of fast opto-spintronic devices based on antiferromagnetic materials.

Passerine birds.

Passeriformes, more commonly known as perching birds or passerines, are the most species-rich group of birds. Totaling nearly 6500 species, approximately two out of every three bird species is a passerine. Passerines are globally distributed and are among the most abundant birds at nearly every terrestrial location on Earth. Owing to their diversity, abundance and cosmopolitan distribution, passerines are among the most familiar of all birds and have figured prominently in both human culture and science. For example, humans have long been captivated by the beautiful songs of many passerines (such as the Common Nightingale (Luscinia megarhynchos) in Europe and the Wood Thrush (Hylocichla mustelina) of North America), and it is common in some cultures - although globally discouraged as ecologically damaging, especially when birds are captured directly from the wild - to keep passerines as pets. Nevertheless, the vocal prowess and frequent ability to thrive in captivity have made passerines important models for lab-based research ranging from neurobiology to genetics. In contrast, the diversity and accessibility of many passerine birds in the wild continue to make them among the best animal models for field-based studies of behavioral ecology, evolution, mating systems, life history, disease resistance, ecological and evolutionary responses to climate change, among many other fields.

Anisotropic long-range spin transport in canted antiferromagnetic orthoferrite YFeO3.

In antiferromagnets, the efficient transport of spin-waves has until now only been observed in the insulating antiferromagnet hematite, where circularly (or a superposition of pairs of linearly) polarized spin-waves diffuse over long distances. Here, we report long-distance spin-transport in the antiferromagnetic orthoferrite YFeO3, where a different transport mechanism is enabled by the combined presence of the Dzyaloshinskii-Moriya interaction and externally applied fields. The magnon decay length is shown to exceed hundreds of nanometers, in line with resonance measurements that highlight the low magnetic damping. We observe a strong anisotropy in the magnon decay lengths that we can attribute to the role of the magnon group velocity in the transport of spin-waves in antiferromagnets. This unique mode of transport identified in YFeO3 opens up the possibility of a large and technologically relevant class of materials, i.e., canted antiferromagnets, for long-distance spin transport.

Prevalence of severe cardiovascular disease in patients with schizophrenia.

OBJECTIVES: We assessed the prevalence of severe cardiovascular (CV) disease requiring hospitalization among patients with schizophrenia in France. METHOD: We included patients hospitalized with schizophrenia or psychotic disorder during 2015, in five French psychiatric hospitals. Patients with CV disease were defined as those with a correspondent ICD-10 code during a hospital stay in any general hospital, five years before or three years after the psychiatric hospitalization. CV disease included myocardial infarction (MI), stroke, heart failure (HF), coronary artery disease (CAD) or peripheral artery disease. Risk factors such as hypertension, obesity and diabetes were recorded. RESULTS: In total, 4424 patients with schizophrenia were included. Overall, 203 (4,6%) patients were diagnosed with CV disease, 93 (2.1%) with CAD, 86 (1.9%) with HF and 49 (1.1%) with stroke. The prevalence of hypertension, obesity and diabetes was 11.3%, 9.7% and 7.8%. The median (interquartile range) age of patients with MI and diabetes was 57 (49-70) and 56 (48-66) years. CONCLUSION: Patients with schizophrenia develop severe CV disease requiring hospitalization at an early age. These severe events are associated with a high prevalence of risk factors. Early screening and treatment of CV disease and risk factors is important to improve life expectancy and quality of life of these patients.

Experimental Evidence for Common Driving Effects in Low-Energy Fission from Sublead to Actinides.

Isotopic distributions of fragments from fission of the neutron-deficient ^{178}Hg nuclide are reported. This experimental observable is obtained for the first time in the region around lead using an innovative approach based on inverse kinematics and the coincidence between the large acceptance magnetic spectrometer VAMOS++ and a new detection arm close to the target. The average fragment N/Z ratio and prompt neutron M_{n} multiplicity are derived and compared with current knowledge from actinide fission. A striking consistency emerges, revealing the unexpected dominant role of the proton subsystem with atomic number between the Z=28 and 50 magic numbers. The origin of nuclear charge polarization in fission and fragment deformation at scission are discussed.

Contrasting drivers of diversity in hosts and parasites across the tropical Andes.

Geographic turnover in community composition is created and maintained by eco-evolutionary forces that limit the ranges of species. One such force may be antagonistic interactions among hosts and parasites, but its general importance is unknown. Understanding the processes that underpin turnover requires distinguishing the contributions of key abiotic and biotic drivers over a range of spatial and temporal scales. Here, we address these challenges using flexible, nonlinear models to identify the factors that underlie richness (alpha diversity) and turnover (beta diversity) patterns of interacting host and parasite communities in a global biodiversity hot spot. We sampled 18 communities in the Peruvian Andes, encompassing ∼1,350 bird species and ∼400 hemosporidian parasite lineages, and spanning broad ranges of elevation, climate, primary productivity, and species richness. Turnover in both parasite and host communities was most strongly predicted by variation in precipitation, but secondary predictors differed between parasites and hosts, and between contemporary and phylogenetic timescales. Host communities shaped parasite diversity patterns, but there was little evidence for reciprocal effects. The results for parasite communities contradicted the prevailing view that biotic interactions filter communities at local scales while environmental filtering and dispersal barriers shape regional communities. Rather, subtle differences in precipitation had strong, fine-scale effects on parasite turnover while host-community effects only manifested at broad scales. We used these models to map bird and parasite turnover onto the ecological gradients of the Andean landscape, illustrating beta-diversity hot spots and their mechanistic underpinnings.

Term newborns at risk for early-onset neonatal sepsis: Clinical surveillance versus systematic paraclinical test.

INTRODUCTION: Early-onset neonatal sepsis is a rare but potentially lethal infection that is very often suspected in daily practice. Previous national guidelines recommended the use of systematic paraclinical tests for healthy term newborns with suspected infection. These guidelines were updated in 2017 by the French Health Authority (Haute Autorité de santé), and promote initial clinical monitoring taking into account the infectious risk level for term and near-term born infants. OBJECTIVES: To assess the impact of the new recommendations on antibiotic therapy prescription and invasive tests, and on the outcomes of infants born from 36weeks' gestation. MATERIALS AND METHODS: This study compared the management and the outcome of neonates born from 36weeks' gestation at the level III University Hospital of Nancy, according to their infectious risk level during two periods, before and after the update of national recommendations: from July 1 to December 31, 2017, versus July 1 to December 31, 2018. Data were retrospectively collected from the infants' files. This study compared the number and length of antibiotic treatment and the number of invasive tests, the number of documented infections, the number and length of hospitalization, and mortality between the two periods. RESULTS: During the first period, among 1248 eligible newborns, 643 presented an infectious risk factor, versus 1152 newborns with 343 having an infectious risk factor during the second period. Antibiotic treatment was initiated for 18 newborns during the first period (1.4%) and for nine during the second (0.8%) (P=0.13). The mean (SD) duration of the antibiotic treatment was longer in the first than in the second period: 6.3±2days vs. 3.1±2.3days (P=0.003). There was no death related to neonatal infection. A total of 1052 blood samples were collected during the first period versus 51 during the second (P<0.01). There was no documented infection. In the first period, there were 18 newborns (1.4%) hospitalized for suspected infection versus nine (0.8%) in the second period (P=0.13). The duration of hospitalization was 5.7±1.7days in the first period versus 5.2±3days in the second (P=0.33). CONCLUSION: In this study, the application of the new guidelines enabled a reduction of antibiotic exposure and a reduction of invasive tests without additional risk.

Floristic evidence for alternative biome states in tropical Africa.

The idea that tropical forest and savanna are alternative states is crucial to how we manage these biomes and predict their future under global change. Large-scale empirical evidence for alternative stable states is limited, however, and comes mostly from the multimodal distribution of structural aspects of vegetation. These approaches have been criticized, as structure alone cannot separate out wetter savannas from drier forests for example, and there are also technical challenges to mapping vegetation structure in unbiased ways. Here, we develop an alternative approach to delimit the climatic envelope of the two biomes in Africa using tree species lists gathered for a large number of forest and savanna sites distributed across the continent. Our analyses confirm extensive climatic overlap of forest and savanna, supporting the alternative stable states hypothesis for Africa, and this result is corroborated by paleoecological evidence. Further, we find the two biomes to have highly divergent tree species compositions and to represent alternative compositional states. This allowed us to classify tree species as forest vs. savanna specialists, with some generalist species that span both biomes. In conjunction with georeferenced herbarium records, we mapped the forest and savanna distributions across Africa and quantified their environmental limits, which are primarily related to precipitation and seasonality, with a secondary contribution of fire. These results are important for the ongoing efforts to restore African ecosystems, which depend on accurate biome maps to set appropriate targets for the restored states but also provide empirical evidence for broad-scale bistability.

Extreme and variable torpor among high-elevation Andean hummingbird species.

Torpor is thought to be particularly important for small endotherms occupying cold environments and with limited fat reserves to fuel metabolism, yet among birds deep torpor is both rare and variable in extent. We investigated torpor in hummingbirds at approximately 3800 m.a.s.l. in the tropical Andes by monitoring body temperature (Tb) in 26 individuals of six species held captive overnight and experiencing natural air temperature (Ta) patterns. All species used pronounced torpor, with one Metallura phoebe reaching a minimum Tb of 3.26°C, the lowest yet reported for any bird or non-hibernating mammal. The extent and duration of torpor varied among species, with overnight body mass (Mb) loss negatively correlated with both minimum Tb and bout duration. We found a significant phylogenetic signal for minimum Tb and overnight Mb loss, consistent with evolutionarily conserved thermoregulatory traits. Our findings suggest deep torpor is routine for high Andean hummingbirds, but evolved species differences affect its depth.

Efficient Spin Torques in Antiferromagnetic CoO/Pt Quantified by Comparing Field- and Current-Induced Switching.

We achieve current-induced switching in collinear insulating antiferromagnetic CoO/Pt, with fourfold in-plane magnetic anisotropy. This is measured electrically by spin Hall magnetoresistance and confirmed by the magnetic field-induced spin-flop transition of the CoO layer. By applying current pulses and magnetic fields, we quantify the efficiency of the acting current-induced torques and estimate a current-field equivalence ratio of 4×10^{-11} T A^{-1} m^{2}. The Néel vector final state (n⊥j) is in line with a thermomagnetoelastic switching mechanism for a negative magnetoelastic constant of the CoO.

The German CPU registry: Comparison of smokers and nonsmokers.

BACKGROUND: Chest pain is a major reason for admission to an internal emergency department, and smoking is a well-known risk factor for coronary artery disease (CAD) and acute coronary syndrome (ACS). The aim of this analysis is to illustrate the differences between smokers and nonsmokers presenting to German chest pain units (CPU) in regard to patient characteristics, CAD manifestation, treatment strategy, and prognosis. METHODS: From December 2008 to March 2014, 13,902 patients who had a complete 3­month follow-up were enrolled in the German CPU registry. The analysis comprised 5796 patients with ACS and documented smoking status. RESULTS: Of all the patients in the CPU registry, 35.2% were smokers. Compared with nonsmokers, they were 13.5 years younger (58.2 vs. 71.7 years, p < 0.001), predominantly men (77.1% vs. 65.2%, p < 0.001), and were more frequently diagnosed with single-vessel disease (32.1% vs. 25.2%) as well as ST-elevation myocardial infarction (STEMI; 23.8% vs. 15.5%, p < 0.001). Although the Global Registry of Acute Coronary Events (GRACE) Risk Score for hospital mortality was lower in the group of smokers (106.1 vs. 123.3, p < 0.001), we did not observe any differences in CPU death (0.4% vs. 0.4%, p = 0.69) and CPU major adverse cardiac event (MACE) rates (3.8% vs 2.9%, p = 0.073) between the groups. In the 3­month follow-up, we documented higher mortality rates in the nonsmoker group (1.9% vs. 2.9%, p = 0.035) in correlation with the GRACE Risk Score (80.3 vs. 105.2, p < 0.001). MACE rates were similar during the follow-up (3.1% vs. 4.1%, p = 0.065). CONCLUSION: Observations from the German CPU registry demonstrate that smoking is a strong predictor of acute CAD manifestation early in life, especially STEMI. In spite of a lower GRACE Risk Score and fewer comorbidities, smokers had a rate of hospital mortality similar to the older group of nonsmokers.

Developmental toxicity in embryo-larval zebrafish (Danio rerio) exposed to strobilurin fungicides (azoxystrobin and pyraclostrobin).

Azoxystrobin and pyraclostrobin are broad spectrum strobilurin fungicides that have been measured in the aquatic environment. Strobilurins inhibit mitochondrial respiration by binding to the mitochondrial respiratory complex III. The goal of this study was to investigate mitochondrial dysfunction and oxidative stress in the developing zebrafish from exposure to azoxystrobin and pyraclostrobin. Exposure studies were performed where zebrafish embryos were exposed to azoxystrobin and pyraclostrobin at 0.1, 10, 100 µg/L from 4 hpf to 48 hpf to measure mitochondrial dysfunction and oxidative stress mRNA transcripts, and 5 dpf to measure movement, growth, oxygen consumption, enzymatic activities, and mRNA transcripts. Results from this study indicated that there was a significant reduction in both basal and maximal respiration at 48 hpf in zebrafish exposed to 100 µg/L of pyraclostrobin. There was no difference in oxidative stress or apoptotic mRNA transcripts at 48 hpf, indicating that the two strobilurins were acting first on mitochondrial function and not directly through oxidative stress. At 5 dpf, standard body length was significantly reduced with exposure to pyraclostrobin and azoxystrobin exposure as compared to the control. These reductions in apical endpoints corresponded with increases in oxidative stress and apoptotic mRNA transcripts in treatment groups at 5 dpf indicating that strobilurins' exposure followed the adverse outcome pathway for mito-toxicants. Our results indicate that strobilurins can decrease mitochondrial function, which in turn lead to diminished growth and movement.