Systematic identification of stem-loop containing sequence families in bacterial genomes

<p>Abstract</p> <p>Background</p> <p>Analysis of non-coding sequences in several bacterial genomes brought to the identification of families of repeated sequences, able to fold as secondary structures. These sequences have often been claimed to be transcribed and fulfill a functional role. A previous systematic analysis of a representative set of 40 bacterial genomes produced a large collection of sequences, potentially able to fold as stem-loop structures (SLS). Computational analysis of these sequences was carried out by searching for families of repetitive nucleic acid elements sharing a common secondary structure.</p> <p>Results</p> <p>The initial clustering procedure identified clusters of similar sequences in 29 genomes, corresponding to about 1% of the whole population. Sequences selected in this way have a substantially higher aptitude to fold into a stable secondary structure than the initial set. Removal of redundancies and regrouping of the selected sequences resulted in a final set of 92 families, defined by HMM analysis. 25 of them include all well-known SLS containing repeats and others reported in literature, but not analyzed in detail. The remaining 67 families have not been previously described. Two thirds of the families share a common predicted secondary structure and are located within intergenic regions.</p> <p>Conclusion</p> <p>Systematic analysis of 40 bacterial genomes revealed a large number of repeated sequence families, including known and novel ones. Their predicted structure and genomic location suggest that, even in compact bacterial genomes, a relatively large fraction of the genome consists of non-protein-coding sequences, possibly functioning at the RNA level.</p

In Silico approaches applied to the study of peptide analogs of ile-pro-ile in relation to their dipeptidyl peptidase IV inhibitory properties

peer-reviewedInhibition of dipeptidyl peptidase IV (DPP-IV) may be exploited to maintain the incretin effect during the postprandial phase. As a result, glycemic regulation and energy homeostasis may be improved. Food protein-derived peptides have been identified as natural agents capable of inhibiting DPP-IV. Ile-Pro-Ile is the most potent DPP-IV inhibitory peptide identified to date. A minimum analog peptide set approach was used to study peptide analogs of Ile-Pro-Ile. The DPP-IV half maximal inhibitory concentration (IC50) values of the 25 peptides evaluated ranged from 3.9 ± 1.0 μM (Ile-Pro-Ile) to 247.0 ± 32.7 μM (Phe-Pro-Phe). The presence of Pro at position 2 of tripeptides was required to achieve high DPP-IV inhibition. Most peptides behaved as competitive inhibitors of DPP-IV with the exception of peptides with a N-terminal Trp, which were mixed-type inhibitors. While possessing the structure of preferred DPP-IV substrates, most peptides studied were particularly stable during 30 min incubation with DPP-IV. Molecular docking revealed that Ile-Pro-Ile and its peptide analogs interacted in a very similar manner with the active site of DPP-IV. In addition, no correlation was found between the Hydropathic INTeraction score and the DPP-IV IC50 values of the peptides studied. This outcome suggests that free energy may not be directly responsible for enzyme inhibition by the peptides. Finally, novel DPP-IV inhibitory peptides were identified using the strategy employed herein. These results may be relevant for the development of food protein-derived peptides with serum glucose lowering and food intake regulatory properties in humans

Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial

: As lactoferrin is a nutritional supplement with proven antiviral and immunomodulatory abilities, it may be used to improve the clinical course of COVID-19. The clinical efficacy and safety of bovine lactoferrin were evaluated in the LAC randomized double-blind placebo-controlled trial. A total of 218 hospitalized adult patients with moderate-to-severe COVID-19 were randomized to receive 800 mg/die oral bovine lactoferrin (n = 113) or placebo (n = 105), both given in combination with standard COVID-19 therapy. No differences in lactoferrin vs. placebo were observed in the primary outcomes: the proportion of death or intensive care unit admission (risk ratio of 1.06 (95% CI 0.63-1.79)) or proportion of discharge or National Early Warning Score 2 (NEWS2) ≤ 2 within 14 days from enrollment (RR of 0.85 (95% CI 0.70-1.04)). Lactoferrin showed an excellent safety and tolerability profile. Even though bovine lactoferrin is safe and tolerable, our results do not support its use in hospitalized patients with moderate-to-severe COVID-19

An econometric analysis of emission allowance prices

Knowledge of the statistical distribution of the prices of emission allowances, and their forecastability, are crucial in constructing, among other things, purchasing and risk management strategies in the emissions-constrained markets. This paper analyzes the two emission permits markets, CO2 in Europe, and SO2 in the US, and investigates a model for dealing with the unique stylized facts of this type of data. Its effectiveness in terms of model fit and out-of-sample value-at-risk-forecasting, as compared to models commonly used in risk-forecasting contexts, is demonstrated

An econometric analysis of emission allowance prices

Knowledge of the statistical distribution of the prices of emission allowances, and their forecastability, are crucial in constructing, among other things, purchasing and risk management strategies in the emissions-constrained markets. This paper analyzes the two emission permits markets, CO2 in Europe, and SO2 in the US, and investigates a model for dealing with the unique stylized facts of this type of data. Its effectiveness in terms of model fit and out-of-sample value-at-risk-forecasting, as compared to models commonly used in risk-forecasting contexts, is demonstrated.C16 C32 C51 C52 C53 Emission allowances GARCH Greenhouse gases Mixture models Value-at-risk