Financial regulations and bank credit to the real economy

We present a new agent-based model focusing on the linkage between the interbank market and the real economy with a stylised central bank acting as lender of last resort. Using this model we address the tradeoff between stability and economic performance for different structures of the interbank market. We also explore the efficacy of recent regulatory reforms using our richer model. Our results suggest that the effects of regulatory leverage ratios on the banking sector's performance can vary in a complex and non-monotonic way with the state of the economy, the degree of connectivity of the interbank market and the amount of information available to market participants on bank risks

Ice volume distribution and implications on runoff projections in a glacierized catchment

A dense network of helicopter-based ground-penetrating radar (GPR) measurements was used to determine the ice-thickness distribution in the Mauvoisin region. The comprehensive set of ice-thickness measurements was combined with an ice-thickness estimation approach for an accurate determination of the bedrock. A total ice volume of 3.69 ± 0.31 km<sup>3</sup> and a maximum ice thickness of 290 m were found. The ice-thickness values were then employed as input for a combined glacio-hydrological model forced by most recent regional climate scenarios. This model provided glacier evolution and runoff projections for the period 2010–2100. Runoff projections of the measured initial ice volume distribution show an increase in annual runoff of 4% in the next two decades, followed by a persistent runoff decrease until 2100. Finally, we checked the influence of the ice-thickness distribution on runoff projections. Our analyses revealed that reliable estimates of the ice volume are essential for modelling future glacier and runoff evolution. Wrong estimations of the total ice volume might even lead to deviations of the predicted general runoff trend

The impact of Saharan dust and black carbon on albedo and long-term mass balance of an Alpine glacier

Light-absorbing impurities in snow and ice control glacier melt as shortwave radiation represents the main component of the surface energy balance. Here, we investigate the long-term effect of snow impurities, i.e., mineral dust and black carbon (BC), on albedo and glacier mass balance. The analysis was performed over the period 1914–2014 for two sites on Claridenfirn, Swiss Alps, where an outstanding 100-year record of seasonal mass balance measurements is available. Information on atmospheric deposition of mineral dust and BC over the last century was retrieved from two firn/ice cores of high-alpine sites. A combined mass balance and snow/firn layer model was employed to assess the effects of melt and accumulation processes on the impurity concentration at the surface and thus on albedo and glacier mass balance. Compared to pure snow conditions, the presence of Saharan dust and BC lowered the mean annual albedo by 0.04–0.06 depending on the location on the glacier. Consequently, annual melt was increased by 15–19 %, and the mean annual mass balance was reduced by about 280–490 mm w.e. BC clearly dominated absorption which is about 3 times higher than that of mineral dust. The upper site has experienced mainly positive mass balances and impurity layers were continuously buried whereas at the lower site, surface albedo was more strongly influenced by re-exposure of dust and BC-enriched layers due to frequent years with negative mass balances

The polymorphism L412F in TLR3 inhibits autophagy and is a marker of severe COVID-19 in males

The polymorphism L412F in TLR3 has been associated with several infectious diseases. However, the mechanism underlying this association is still unexplored. Here, we show that the L412F polymorphism in TLR3 is a marker of severity in COVID-19. This association increases in the sub-cohort of males. Impaired macroautophagy/autophagy and reduced TNF/TNFα production was demonstrated in HEK293 cells transfected with TLR3L412F-encoding plasmid and stimulated with specific agonist poly(I:C). A statistically significant reduced survival at 28 days was shown in L412F COVID-19 patients treated with the autophagy-inhibitor hydroxychloroquine (p = 0.038). An increased frequency of autoimmune disorders such as co-morbidity was found in L412F COVID-19 males with specific class II HLA haplotypes prone to autoantigen presentation. Our analyses indicate that L412F polymorphism makes males at risk of severe COVID-19 and provides a rationale for reinterpreting clinical trials considering autophagy pathways.publishedVersio

Milk production and hematological and antioxidant profiles of dairy cows supplemented with oregano and green tea extracts as feed additives.

We aimed to evaluate the effects of the addition of oregano (Origanum vulgare) or green tea (Camellia sinensis L.) extracts (separately and associated) on feed intake, milk production, and hematological and antioxidant profiles of dairy cows. For that purpose, 16 Holstein and 16 Holstein-Gyr cows with 526.3±10.2 kg and within the first third of lactation were distributed according to a complete block design with measurements repeated in time. Treatments were control (CON), addition of 0.056% of oregano extract (OR), addition of 0.028% of green tea extract (GT), addition of a mixture of OR and GT extract (0.056% each) in the diet (MIX). Hematological and antioxidant profiles were monitored. Data were subjected to ANOVA, with block, treatment, days, and their interactions considered as fixed effects and animal and the residue as random effects. In Holstein cows, GT increased feed intake and milk yield compared with CON; in Holstein-Gyr crossbred cows, OR showed increased intake and GT increased milk yield compared with CON. Compared with CON, GT and OR decreased eosinophils concentration; OR showed the highest neutrophils concentration and neutrophils to leukocyte ratio. Compared with CON, OR presented increased catalase (CAT) activity, while GT increased the reduced glutathione concentration. The MIX treatment reduced CAT activity compared with OR, presented the lowest concentration of oxidized dichlorofluorescein in the erythrocytes (DCFER) and plasma (DCFPLA), and increased eosinophils concentration compared with GT and OR. Extracts differently affected feed intake and milk yield depending on genetic group. Feeding green tea and oregano extracts separately or associated distinctly affects the antioxidant indicators of lactating dairy cows

Non-genomic effects of nuclear receptors: insights from the anucleate platelet

Nuclear receptors have the ability to elicit two different kinds of responses, genomic and non-genomic. While genomic responses control gene expression by influencing the rate of transcription, non-genomic effects occur rapidly and independently of transcriptional regulation. Due to their anucleate nature and mechanistically well-characterised and rapid responses, platelets provide a model system for the study of any non-genomic effects of the nuclear receptors. Several nuclear receptors have been found to be expressed in human platelets, and multiple nuclear receptor agonists have been shown to elicit anti-platelet effects by a variety of mechanisms. The non-genomic functions of NRs vary, including the regulation of kinase and phosphatase activity, ion channel function, intracellular calcium levels and production of second messengers. Recently, the characterisation of mechanisms and identification of novel binding partners of nuclear receptors have further strengthened the prospects of developing their ligands into potential therapeutics that offer cardio-protective properties in addition to their other defined genomic effects

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 hospitalization2–4 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

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types