Pioneering role of RNA in the early evolution of life.

The catalytic, regulatory and structural properties of RNA, combined with their extraordinary ubiquity in cellular processes, are consistent with the proposal that this molecule played a much more conspicuous role in heredity and metabolism during the early stages of biological evolution. This review explores the pivotal role of RNA in the earliest life forms and its relevance in modern biological systems. It examines current models that study the early evolution of life, providing insights into the primordial RNA world and its legacy in contemporary biology.

Structural and Evolutionary Analysis of Proteins Endowed with a Nucleotidyltransferase, or Non-canonical Palm, Catalytic Domain.

Many polymerases and other proteins are endowed with a catalytic domain belonging to the nucleotidyltransferase fold, which has also been deemed the non-canonical palm domain, in which three conserved acidic residues coordinate two divalent metal ions. Tertiary structure-based evolutionary analyses provide valuable information when the phylogenetic signal contained in the primary structure is blurry or has been lost, as is the case with these proteins. Pairwise structural comparisons of proteins with a nucleotidyltransferase fold were performed in the PDBefold web server: the RMSD, the number of superimposed residues, and the Qscore were obtained.

Chapter 2: What Is Life?

The question "What is life?" has existed since the beginning of recorded history. However, the scientific and philosophical contexts of this question have changed and been refined as advancements in technology have revealed both fine details and broad connections in the network of life on Earth. Understanding the framework of the question "What is life?" is central to formulating other questions such as "Where else could life be?" and "How do we search for life elsewhere?" While many of these questions are addressed throughout the Astrobiology Primer 3.

Chapter 1: The Astrobiology Primer 3.0.

The Astrobiology Primer 3.0 (ABP3.0) is a concise introduction to the field of astrobiology for students and others who are new to the field of astrobiology.

Subtle structural differences of nucleotide analogs may impact SARS-CoV-2 RNA-dependent RNA polymerase and exoribonuclease activity.

The rapid spread and public health impact of the novel SARS-CoV-2 variants that cause COVID-19 continue to produce major global impacts and social distress. Several vaccines were developed in record time to prevent and limit the spread of the infection, thus playing a pivotal role in controlling the pandemic. Although the repurposing of available drugs attempts to provide therapies of immediate access against COVID-19, there is still a need for developing specific treatments for this disease.

Structural Analysis of Monomeric RNA-Dependent Polymerases Revisited.

In the past few years, our understanding of the RNA virosphere has changed dramatically due to the growth and spurt of metagenomics, exponentially increasing the number of RNA viral sequences, and providing a better understanding of their range of potential hosts. As of today, the only conserved protein among RNA viruses appears to be the monomeric RNA-dependent RNA polymerase. This enzyme belongs to the right-hand DNA-and RNA polymerases, which also includes reverse transcriptases and eukaryotic replicative DNA polymerases.

Two short low complexity regions (LCRs) are hallmark sequences of the Delta SARS-CoV-2 variant spike protein.

Low complexity regions (LCRs) are protein sequences formed by a set of compositionally biased residues. LCRs are extremely abundant in cellular proteins and have also been reported in viruses, where they may partake in evasion of the host immune system. Analyses of 28,231 SARS-CoV-2 whole proteomes and of 261,051 spike protein sequences revealed the presence of four extremely conserved LCRs in the spike protein of several SARS-CoV-2 variants.

Structural analysis of viral ExoN domains reveals polyphyletic hijacking events.

Nidoviruses and arenaviruses are the only known RNA viruses encoding a 3'-5' exonuclease domain (ExoN). The proofreading activity of the ExoN domain has played a key role in the growth of nidoviral genomes, while in arenaviruses this domain partakes in the suppression of the host innate immune signaling. Sequence and structural homology analyses suggest that these proteins have been hijacked from cellular hosts many times.

Sofosbuvir as a potential alternative to treat the SARS-CoV-2 epidemic.

As of today, there is no antiviral for the treatment of the SARS-CoV-2 infection, and the development of a vaccine might take several months or even years. The structural superposition of the hepatitis C virus polymerase bound to sofosbuvir, a nucleoside analog antiviral approved for hepatitis C virus infections, with the SARS-CoV polymerase shows that the residues that bind to the drug are present in the latter. Moreover, a multiple alignment of several SARS-CoV-2, SARS and MERS-related coronaviruses polymerases shows that these residues are conserved in all these viruses, opening the possibility to use sofosbuvir against these highly infectious pathogens.

A yellow flag on the horizon: The looming threat of yellow fever to North America.

Yellow fever virus historically was a frequent threat to American and European coasts. Medical milestones such as the discovery of mosquitoes as vectors and subsequently an effective vaccine significantly reduced its incidence, in spite of which, thousands of cases of this deathly disease still occur regularly in Sub-Saharan Africa and the Amazonian basin in South America, which are usually not reported. An urban outbreak in Angola, consecutive years of increasing incidence near major Brazilian cities, and imported cases in China, South America and Europe, have brought this virus back to the global spotlight.

Are RNA Viruses Candidate Agents for the Next Global Pandemic? A Review.

Pathogenic RNA viruses are potentially the most important group involved in zoonotic disease transmission, and they represent a challenge for global disease control. Their biological diversity and rapid adaptive rates have proved to be difficult to overcome and to anticipate by modern medical technology. Also, the anthropogenic change of natural ecosystems and the continuous population growth are driving increased rates of interspecies contacts and the interchange of pathogens that can develop into global pandemics.

Structural Analysis of Monomeric RNA-Dependent Polymerases: Evolutionary and Therapeutic Implications.

The crystal structures of monomeric RNA-dependent RNA polymerases and reverse transcriptases of more than 20 different viruses are available in the Protein Data Bank. They all share the characteristic right-hand shape of DNA- and RNA polymerases formed by the fingers, palm and thumb subdomains, and, in many cases, "fingertips" that extend from the fingers towards the thumb subdomain, giving the viral enzyme a closed right-hand appearance. Six conserved structural motifs that contain key residues for the proper functioning of the enzyme have been identified in all these RNA-dependent polymerases.

Evaluation of the endothelial function in hypertensive patients with 13N-ammonia PET.

Background: Essential hypertension is one of the main risk factors for the development of coronary artery disease (CAD). Hypertension causes endothelial dysfunction which is considered an early sign for the development of CAD. Positron emission tomography is a non-invasive imaging technique that measures myocardial blood flow (MBF), allowing us to identify patients with endothelial dysfunction.

Automatic alignment of myocardial perfusion PET and 64-slice coronary CT angiography on hybrid PET/CT.

Background: Hybrid PET/CT allows for acquisition of cardiac PET and coronary CT angiography (CCTA) in one session. However, PET and CCTA are acquired with differing breathing protocols and require software registration. We aimed to validate automatic correction for breathing misalignment between PET and CCTA acquired on hybrid scanner.

Coenzymes, viruses and the RNA world.

The results of a detailed bioinformatic search for ribonucleotidyl coenzyme biosynthetic sequences in DNA- and RNA viral genomes are presented. No RNA viral genome sequence available as of April 2011 appears to encode for sequences involved in coenzyme biosynthesis. In both single- and double-stranded DNA viruses a diverse array of coenzyme biosynthetic genes has been identified, but none of the viral genomes examined here encodes for a complete pathway.

Comparison of clinical tools for measurements of regional stress and rest myocardial blood flow assessed with 13N-ammonia PET/CT.

Unlabelled: Several models for the quantitative analysis of myocardial blood flow (MBF) at stress and rest and myocardial flow reserve (MFR) with (13)N-ammonia myocardial perfusion PET have been implemented for clinical use. We aimed to compare quantitative results obtained from 3 software tools (QPET, syngo MBF, and PMOD), which perform PET MBF quantification with either a 2-compartment model (QPET and syngo MBF) or a 1-compartment model (PMOD).

Methods: We considered 33 adenosine stress and rest (13)N-ammonia studies (22 men and 11 women).

[The importance of multi-imaging diagnosis in cardiology].

Cardiovascular imaging is one of the disciplines in cardiology with the most recent advances. This means that the teaching of Cardiology must evolve in the same way. In 2009, the American College of Cardiology published a statement, which points out that all of the cardiology residents must have basic training in every one of the cardiovascular imaging modalities available.

Functional impact of coronary stenosis observed on coronary computed tomography angiography: Comparison with ¹³N-ammonia PET.

Background And Aims: We undertook this study to evaluate the functional impact of coronary abnormalities in patients with suspected coronary artery disease (CAD) by means of integrated positron emission tomography (PET) and coronary computed tomography angiography (CCTA) scan obtained on a hybrid state-of-the-art PET/CT scanner.

Methods: We studied 29 consecutive, patients with a clinically suspected intermediate risk for CAD, using a hybrid PET/CT 64 slice scanner. During a single scanning session, CCTA was performed for coronary anatomy evaluation, and a rest/adenosine stress (13)N-ammonia PET was performed for myocardial perfusion assessment in 3D mode with CT attenuation correction.

Endothelial dysfunction in systemic lupus erythematosus: evaluation with 13N-ammonia PET.

Unlabelled: Systemic lupus erythematosus (SLE) affects multiple organs and systems, severely involving the cardiovascular system. The aim of this study was to evaluate the presence of endothelial dysfunction with (13)N-ammonia PET in asymptomatic SLE patients.

Methods: We enrolled 16 women with SLE and 16 healthy women.

Effect of ezetimibe-simvastatine over endothelial dysfunction in dyslipidemic patients: assessment by 13N-ammonia positron emission tomography.

Background: Dyslipidemias constitute an independent risk factor for the development of atherogenesis and they also predispose to the development of endothelial dysfunction (ED). Using PET with (13)N-ammonia, it is possible to quantify myocardial blood flow (MBF) in mL/min/g and to quantitatively evaluate ED. With the use of lipid lowering therapy it is possible to reduce ED and increase the MBF and the endothelial-dependent vasodilation index (ENDEVI).