Investigation of excited 0+ states in 160Er populated via the (p, t) two-neutron transfer reaction

Many efforts have been made in nuclear structure physics to interpret the nature of low-lying excited 0+ states in well-deformed rare-earth nuclei. However, one of the difficulties in resolving the nature of these states is that there is a paucity of data. In this work, excited 0+ states in the N = 92 nucleus 160Er were studied via the 162Er(p, t)160Er two-neutron transfer reaction, which is ideal for probing 0+ → 0+ transitions, at the Maier-Leibnitz-Laboratorium in Garching, Germany. Reaction products were momentum-analyzed with a Quadrupole-3-Dipole magnetic spectrograph. The 0+2 state was observed to be strongly populated with 18% of the ground state strength

Global maps of soil temperature.

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km <sup>2</sup> resolution for 0-5 and 5-15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km <sup>2</sup> pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (-0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

Delayed mucosal antiviral responses despite robust peripheral inflammation in fatal COVID-19

Background While inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished coronavirus disease 2019 (COVID-19) severity categories, and relate these to disease progression and peripheral inflammation. Methods We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalized with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0–5 days after symptom onset) or late (6–20 days after symptom onset) phase. Results Patients that survived severe COVID-19 showed interferon (IFN)-dominated mucosal immune responses (IFN-γ, CXCL10, and CXCL13) early in infection. These early mucosal responses were absent in patients who would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by interleukin 2 (IL-2), IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease. Conclusions Defective early mucosal antiviral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Novel pharmacological approaches to airway and pulmonary vascular disease

Asthma and chronic obstructive pulmonary disease (COPD) remain major clinical problems with significant unmet needs. This issue of Current Opinion in Pharmacology discusses some of the advances being made in our understanding of the pathogenesis of asthma and COPD, along with providing state-of-the-art reviews on some of the new approaches being taken to combat these conditions. There is an increasing awareness that neuronal pathways may play a role in the airways and, in particular, that sensory nerve pathways may be involved in the pathogenesis of the bronchial hyperresponsiveness that so characterises patients with asthma as reviewed by Spina, and this subject is expanded in the overview of TRPV1 receptors in the airways by Lee. The genetic approaches to the treatment of asthma are reviewed by Ian Hall, and the implication of this research for more patient selective treatment is discussed. The role of Ach, long recognised as an important bronchoconstrictor substance in the airway, is discussed by Trevethick, and other actions of this substance in the airways are reviewed. There is also an excellent overview of the role of purinergic receptors in the airway and the role they play in the regulation of airway epithelial function discussed by Boucher. Finally a major problem in pulmonary pharmacology remains the suitability of animal models, particularly those used in the selection of new drugs. Mary Fitzgerald critically reviews this controversial area and the progress being made to find animal models more representative of the clinical situation

Serotonin and pulmonary hypertension—from bench to bedside?

The serotonin hypothesis of pulmonary arterial hypertension (PAH) arose owing to anorexigens, acting as indirect serotinergic agonists, causing PAH. However, it is now thought that serotonin plays an important role in the pathobiology of PAH per se. The rate-limiting enzyme in the synthesis of peripheral serotonin is tryptophan hydroxylase 1 (TPH1), serotonin can mediate pulmonary arterial smooth muscle cell proliferation via the serotonin transporter (SERT) and serotonin can induce pulmonary vasoconstriction via the 5-HT1B receptor in man. There is evidence that TPH1, SERT and 5-HT1B expression/activity can be upregulated in clinical PAH. This review discusses recent evidence implicating serotonin in the development of experimental and clinical PAH and suggests potential therapeutic target