Cardiovascular RNA markers and artificial intelligence may improve COVID-19 outcome: a position paper from the EU-CardioRNA COST Action CA17129.

The coronavirus disease 2019 (COVID-19) pandemic has been as unprecedented as unexpected, affecting more than 105 million people worldwide as of 8 February 2020 and causing more than 2.3 million deaths according to the World Health Organization (WHO). Not only affecting the lungs but also provoking acute respiratory distress, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is able to infect multiple cell types including cardiac and vascular cells.

A Year in the Life of the EU-CardioRNA COST Action: CA17129 Catalysing Transcriptomics Research in Cardiovascular Disease.

The EU-CardioRNA Cooperation in Science and Technology (COST) Action is a European-wide consortium established in 2018 with 31 European country members and four associate member countries to build bridges between translational researchers from academia and industry who conduct research on non-coding RNAs, cardiovascular diseases and similar research areas. EU-CardioRNA comprises four core working groups (WG1-4). In the first year since its launch, EU-CardioRNA met biannually to exchange and discuss recent findings in related fields of scientific research, with scientific sessions broadly divided up according to WG.

Structure and mode of action of a mosquitocidal holotoxin.

The crystal structure of the full mosquitocidal toxin from Bacillus sphaericus (MTX(holo)) has been determined at 2.5 A resolution by the molecular replacement method. The resulting structure revealed essentially the complete chain consisting of four ricin B-type domains curling around the catalytic domain in a hedgehog-like assembly.

Bacillus sphaericus mosquitocidal toxin (MTX) and pierisin: the enigmatic offspring from the family of ADP-ribosyltransferases.

The mosquitocidal toxin (MTX) from Bacillus sphaericus and the apoptosis-inducing pierisin-1 from the cabbage butterfly Pieris rapae are two of the most intriguing members of the family of ADP-ribosyltransferases. They are both approximately 100 kDa proteins, composed of an N-terminal ADP-ribosyltransferase (approximately 27 kDa) and a C-terminal putative binding and translocation domain (approximately 70 kDa) consisting of four ricin-B-like domains. While they both share structural homologies, with an overall amino acid sequence identity of approximately 30% that becomes approximately 50% at the level of the catalytic core, and functional similarities, notably in terms of enzyme regulation, they seem to largely differ with regard to their targets or cell internalization mechanisms.

Structure of the mosquitocidal toxin from Bacillus sphaericus.

The catalytic domain of a mosquitocidal toxin prolonged by a C-terminal 44 residue linker connecting to four ricin B-like domains was crystallized. Three crystal structures were established at resolutions between 2.5A and 3.

Deletion of peroxisome proliferator-activated receptor-alpha induces an alteration of cardiac functions.

The peroxisome proliferator-activated receptor-alpha (PPARalpha) plays a major role in the control of cardiac energy metabolism. The role of PPARalpha on cardiac functions was evaluated by using PPARalpha knockout (PPARalpha -/-) mice. Hemodynamic parameters by sphygmomanometric measurements show that deletion of PPARalpha did not affect systolic blood pressure and heart rate.

Two-site autoinhibition of the ADP-ribosylating mosquitocidal toxin (MTX) from Bacillus sphaericus by its 70-kDa ricin-like binding domain.

The mosquitocidal toxin (MTX) from Bacillus sphaericus SSII-1 is an approximately 97-kDa arginine-specific ADP-ribosyltransferase that is activated by proteolytic cleavage, thereby releasing the active 27-kDa enzyme (MTX(30-264)) and a 70-kDa C-terminal fragment (MTX(265-870)). In solution, the cleaved 70-kDa fragment is still a potent inhibitor of the ADP-ribosyltransferase activity of MTX. Here we studied the interaction of the 70-kDa fragment with the enzyme domain of MTX.

Activation of the peroxisome proliferator-activated receptor alpha protects against myocardial ischaemic injury and improves endothelial vasodilatation.

Background: The peroxisome proliferator-activated receptor alpha (PPARalpha) plays an important role in the metabolism of lipoproteins and fatty acids, and seems to protect against the development of atherosclerosis. To evaluate the possible protective role of PPARalpha on cardiovascular function, the effect of the PPARalpha agonist, fenofibrate was assessed with respect to ischaemia/reperfusion injury and endothelial function in mice.

Results: Fenofibrate treatment reduces myocardial infarction size and improves post-ischaemic contractile dysfunction.