Presence of Fulgencio's Mithologies in the Genealogy of the pagan gods of Boccaccio

Fulgencio Planciades escribió en el siglo V d.C. sus Mitologías, un tratado fundamental para la transmisión de los mitos clásicos en época medieval. Siglos más tarde Boccaccio escribe un extenso tratado mitológico en latín en donde podemos comprobar la enorme influencia del autor norteafricano en su forma y en su contenido. Este artículo pretende remarcar los aspectos concretos en donde podemos ver la presencia de Fulgencio como fuente e inspiración de escritor y humanista toscano.Fulgencio Planciades wrote in the V century A.D. his Mythologies, a treaty essential for the transmission of classical myths in medieval times. Centuries later Boccaccio writes an extensive mythological Latin treatise where we can see the enormous influence of the North African author in form and in content. This article aims to highlight the specific aspects where we can see the presence of Fulgencio as a source and inspiration of Tuscan writer and humanist

New Insights into the Phylogeny and Molecular Classification of Nicotinamide Mononucleotide Deamidases

Nicotinamide mononucleotide (NMN) deamidase is one of the key enzymes of the bacterial pyridine nucleotide cycle (PNC). It catalyzes the conversion of NMN to nicotinic acid mononucleotide, which is later converted to NAD+ by entering the Preiss-Handler pathway. However, very few biochemical data are available regarding this enzyme. This paper represents the first complete molecular characterization of a novel NMN deamidase from the halotolerant and alkaliphilic bacterium Oceanobacillus iheyensis (OiPncC). The enzyme was active over a broad pH range, with an optimum at pH 7.4, whilst maintaining 90 % activity at pH 10.0. Surprisingly, the enzyme was quite stable at such basic pH, maintaining 61 % activity after 21 days. As regard temperature, it had an optimum at 65 °C but its stability was better below 50 °C. OiPncC was a Michaelian enzyme towards its only substrate NMN, with a Km value of 0.18 mM and a kcat/Km of 2.1 mM-1 s-1. To further our understanding of these enzymes, a complete phylogenetic and structural analysis was carried out taking into account the two Pfam domains usually associated with them (MocF and CinA). This analysis sheds light on the evolution of NMN deamidases, and enables the classification of NMN deamidases into 12 different subgroups, pointing to a novel domain architecture never before described. Using a Logo representation, conserved blocks were determined, providing new insights on the crucial residues involved in the binding and catalysis of both CinA and MocF domains. The analysis of these conserved blocks within new protein sequences could permit the more efficient data curation of incoming NMN deamidases

Dietary α‐Linolenic Acid, Marine ω‐3 Fatty Acids, and Mortality in a Population With High Fish Consumption: Findings From the PREvención con DIeta MEDiterránea (PREDIMED) Study

Background: Epidemiological evidence suggests a cardioprotective role of α‐linolenic acid (ALA), a plant‐derived ω‐3 fatty acid. It is unclear whether ALA is beneficial in a background of high marine ω‐3 fatty acids (long‐chain n‐3 polyunsaturated fatty acids) intake. In persons at high cardiovascular risk from Spain, a country in which fish consumption is customarily high, we investigated whether meeting the International Society for the Study of Fatty Acids and Lipids recommendation for dietary ALA (0.7% of total energy) at baseline was related to all‐cause and cardiovascular disease mortality. We also examined the effect of meeting the society's recommendation for long‐chain n‐3 polyunsaturated fatty acids (≥500 mg/day). Methods and Results: We longitudinally evaluated 7202 participants in the PREvención con DIeta MEDiterránea (PREDIMED) trial. Multivariable‐adjusted Cox regression models were fitted to estimate hazard ratios. ALA intake correlated to walnut consumption (r=0.94). During a 5.9‐y follow‐up, 431 deaths occurred (104 cardiovascular disease, 55 coronary heart disease, 32 sudden cardiac death, 25 stroke). The hazard ratios for meeting ALA recommendation (n=1615, 22.4%) were 0.72 (95% CI 0.56–0.92) for all‐cause mortality and 0.95 (95% CI 0.58–1.57) for fatal cardiovascular disease. The hazard ratios for meeting the recommendation for long‐chain n‐3 polyunsaturated fatty acids (n=5452, 75.7%) were 0.84 (95% CI 0.67–1.05) for all‐cause mortality, 0.61 (95% CI 0.39–0.96) for fatal cardiovascular disease, 0.54 (95% CI 0.29–0.99) for fatal coronary heart disease, and 0.49 (95% CI 0.22–1.01) for sudden cardiac death. The highest reduction in all‐cause mortality occurred in participants meeting both recommendations (hazard ratio 0.63 [95% CI 0.45–0.87]). Conclusions: In participants without prior cardiovascular disease and high fish consumption, dietary ALA, supplied mainly by walnuts and olive oil, relates inversely to all‐cause mortality, whereas protection from cardiac mortality is limited to fish‐derived long‐chain n‐3 polyunsaturated fatty acids. Clinical Trial Registration URL: http://www.Controlled-trials.com/. Unique identifier: ISRCTN35739639

The first comprehensive phylogenetic and biochemical analysis of NADH diphosphatases reveals that the enzyme from Tuber melanosporum is highly active towards NAD+

©. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published/Accepted/Submitted Manuscript version of a Published Work that appeared in final form in [Scientific Reports]. To access the final edited and published work see[https://doi.org/10.1038/s41598-019-53138-w]Las hidrolasas Nudix (por nucleósido difosfatasas unidas a otros motivos, X) son una familia diversa de proteínas capaces de escindir una enorme variedad de sustratos, que van desde azúcares nucleotídicos hasta ARNs coronados con NAD+. Aunque todos los miembros de esta superfamilia comparten un motivo catalítico común conservado, la caja Nudix, su especificidad de sustrato radica en rasgos de secuencia específicos, que dan lugar a diferentes subfamilias. Entre ellas, las NADH pirofosfatasas o difosfatasas (NADDs) están poco estudiadas y no se sabe nada de su distribución. Para solucionar esto, diseñamos un patrón compatible con Prosite para identificar nuevas secuencias de NADDs. El escaneo in silico de la base de datos UniProtKB mostró que el 3% de las proteínas Nudix eran NADDs y mostraban 21 arquitecturas de dominio diferentes, siendo la arquitectura canónica (NUDIX-like_zf-NADH-PPase_NUDIX) la más abundante (53%). Curiosamente, las secuencias fúngicas de NADD destacaban entre los eucariotas y se distribuían en varias clases, incluyendo los Pezizomicetos. Inesperadamente, en esta última Clase de hongos, se encontró que los NADDs estaban presentes desde el ancestro reciente más común hasta las Tuberaceae, siguiendo una distribución de la filogenia molecular similar a la descrita previamente usando dos mil genes individuales concatenados. Por último, cuando se caracterizó bioquímicamente la NADD de Tuber melanosporum, formadora de trufas, ésta mostró la mayor relación de eficiencia catalítica NAD+/NADH jamás descrita. .Nudix (for nucleoside diphosphatases linked to other moieties, X) hydrolases are a diverse family of proteins capable of cleaving an enormous variety of substrates, ranging from nucleotide sugars to NAD+-capped RNAs. Although all the members of this superfamily share a common conserved catalytic motif, the Nudix box, their substrate specificity lies in specific sequence traits, which give rise to different subfamilies. Among them, NADH pyrophosphatases or diphosphatases (NADDs) are poorly studied and nothing is known about their distribution. To address this, we designed a Prosite-compatible pattern to identify new NADDs sequences. In silico scanning of the UniProtKB database showed that 3% of Nudix proteins were NADDs and displayed 21 different domain architectures, the canonical architecture (NUDIX-like_zf-NADH-PPase_NUDIX) being the most abundant (53%). Interestingly, NADD fungal sequences were prominent among eukaryotes, and were distributed over several Classes, including Pezizomycetes. Unexpectedly, in this last fungal Class, NADDs were found to be present from the most common recent ancestor to Tuberaceae, following a molecular phylogeny distribution similar to that previously described using two thousand single concatenated genes. Finally, when truffle-forming ectomycorrhizal Tuber melanosporum NADD was biochemically characterized, it showed the highest NAD+/NADH catalytic efficiency ratio ever describe

Plot of the different Pfam domain architectures found for PncC enzymes using ArchSchema.

<p>Green rectangles represent the CinA domain (Pfam ID: PF02464). Red rectangles represent the MocF domain (Pfam ID: PF00994). Other colored rectangles and squares represent other Pfam domains. Labels represent UniProt codes of enzymes belonging to each architecture. </p

Phylogenetic analysis of NMN deamidases.

<p>The structures behind each organism name represent domain composition of the enzyme: MocF domain (dark blue); functional CinA domain (green); non-functional CinA domain (red); Eukaryotic PncCs (yellow). Special domains with only MocF domain are shown in light blue. C-terminal section of the protein is the outer part of the domain representation. Branch colours represent the same phylum as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082705#pone-0082705-g004" target="_blank">Figure 4</a>. The tree was built using Archaeopteryx [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082705#B29" target="_blank">29</a>], bootstrap values were obtained after 1000 generations. The arrow and the star indicate the position of OiPncC and <i>S. oneidensis</i> PncC, respectively. Other symbols are: <i>E. coli</i> YFAY (▲), <i>E. coli</i> YDEJ (●), <i>E. coli</i> YGAD (○), <i>T. acidophilum</i> CinA (◊) and <i>A. tumefaciens</i> CinA (♦).</p

Structural analysis of MocF domain.

<p>A) Surface (subunit A) and ribbon (subunit B) representation of the dimeric <i>Thermoplasma acidophilum</i> CinA protein (PDB code: 3KBQ); conserved blocks forming the binding site are colored, and its consensus sequence shown as generated by WebLogo [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082705#B34" target="_blank">34</a>]. A Molybdenum cofactor molecule (Moco) in the proposed binding site is shown in ball and stick representation. B) Detailed view of the amino acids involved in the interaction between 3KBQ and Moco rendered by Chimera [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082705#B25" target="_blank">25</a>]. C) An ADPr molecule in the proposed binding site (subunit A) is shown in ball and stick representation. D) Detailed view of the amino acids involved in the interaction between 3KBQ and ADPr.</p

Pyridine nucleotide cycle and NAD⁺ biosynthetic routes.

<p>The routes known to be functional across diverse bacterial species are shown by solid lines. Preiss-Handler pathway is shadowed. Dashed and hollow arrows relate to uptake and <i>de </i><i>novo</i> NaMN synthesis, respectively. Blue arrow corresponds to nicotinamidase activity (PncA), Red arrow corresponds to nicotinamide mononucleotide deamidase activity (PncC) and green arrow corresponds to NAD⁺-dependent DNA ligase. Enzymes are indicated as the acronym used to identify the corresponding gene locus: NadA, quinolinate synthetase; NadB, L-aspartate oxidase; NadC, quinolinate phosphoribosyl transferase; NadD, NaMN adenylyltransferase; NadE, NAD synthetase; NadM, NMN adenyltransferase; NadR^C, NmR kinase; NadR^N, NMN adenylyltransferase; NadV, Nm phosphoribosyltransferase; PncA, Nam deamidase; PncB, Na phosphoribosyltransferase; PncC, nicotinamide mononucleotide deamidase; PncU, nucleoside permease. The gene name of the enzymes existing in <i>O. iheyensis</i> is highlighted in brown. Abbreviations: NAD, nicotinamide adenine dinucleotide; IA, α-iminosuccinate; Qa, quinolonic acid; Asp, aspartate; Trp, tryptophan; NAM, nicotinamide; NA: nicotinic acid; NMN, nicotinic acid mononucleotide; NaAD, nicotinic acid adenine dinucleotide; NmR, nicotinamide riboside; DNA, deoxyribonucleic acid.</p

Structural analysis of CinA domain.

<p>A) Surface and ribbon representation of the <i>Agrobacterium tumefaciens</i> CinA dimer (PDB code: 2A9S); conserved blocks forming the binding site are colored and its consensus sequence are shown. A NMN molecule in the proposed binding site is shown in ball and stick representation. B) Detailed view of the amino acids involved in the interaction between 2A9S and NMN. C) Logo representations of the multiple alignments of the conserved blocks of CinA domain in representative active and inactive PncCs. The key residues involved in the catalytic process are marked with a red triangle.</p

Effect of pH and temperature on OiPncC.

<p><b>A</b>) Effect of pH on OiPncC activity measured by the HPLC Assay. The buffers used were 50 mM sodium acetate (pH 5.0), 50 mM potassium phosphate buffer (pH 6.0-7.4) and glycine-NaOH (pH 8.5-10.0). <b>B</b>) pH-stability. Aliquots of enzyme incubated at different pHs were removed and relative activity was measured using the enzyme-coupled assay at different times. The buffers used (50mM) were sodium acetate pH 5.0 (●), potassium phosphate pH 6.5 (■), pH 7.0 (Δ), pH 8.0 (▲), Tris-HCl pH 9.0 (♦), glycine pH 10 (□) and pH 10.5 (◊). <b>C</b>) Effect of temperature on OiPncC activity measured by the HPLC assay. <b>D</b>) Thermostability assay. Aliquots of enzyme incubated at different temperatures [4 °C (●), 20 °C (■), 37 °C (Δ), 45 °C (▲), 50 °C (♦) and 60 °C (◊)] were removed at different times and relative activity was measured using the enzyme-coupled assay. Standard assay conditions were used in all cases.</p