Amaranth as a Source of Antihypertensive Peptides

Amaranth is an ancestral crop used by pre-Columbian cultures for 6000 to 8000 years. Its grains have a relevant chemical composition not only from a nutritional point of view but also due to the contribution of components with good techno-functional properties and important potential as bioactive compounds. Numerous studies have shown that amaranth storage proteins possess encrypted sequences that, once released, exhibit different physiological activities. One of the most studied is antihypertensive activity. This review summarizes the progress made over the last years (2008-2020) related to this topic. Studies related to inhibition of different enzymes of the Renin-Angiotensin-Aldosterone system, in particular Angiotensin Converting Enzyme (ACE) and Renin, as well as those referring to potential modulation mechanisms of tissue or local Renin-Angiotensin-Aldosterone system, are analyzed, including in silico, in vitro, in vivo, and ex vivo assays. Furthermore, the potential use of these bioactive peptides or products containing them, in the elaboration of functional food matrices is discussed. Finally, the most relevant conclusions and future requirements in research and development of food products are presented.Facultad de Ciencias ExactasCentro de Investigación y Desarrollo en Criotecnología de Alimento

Large-scale mapping of bioactive peptides in structural and sequence space

Health-enhancing potential bioactive peptide (BP) has driven an interest in food proteins as well as in the development of predictive methods. Research in this area has been especially active to use them as components in functional foods. Apparently, BPs do not have a given biological function in the containing proteins and they do not evolve under independent evolutionary constraints. In this work we performed a large-scale mapping of BPs in sequence and structural space. Using well curated BP deposited in BIOPEP database, we searched for exact matches in non-redundant sequences databases. Proteins containing BPs, were used in fold-recognition methods to predict the corresponding folds and BPs occurrences were mapped. We found that fold distribution of BP occurrences possibly reflects sequence relative abundance in databases. However, we also found that proteins with 5 or more than 5 BP in their sequences correspond to well populated protein folds, called superfolds. Also, we found that in well populated superfamilies, BPs tend to adopt similar locations in the protein fold, suggesting the existence of hotspots. We think that our results could contribute to the development of new bioinformatics pipeline to improve BP detection.Fil: Nardo, Agustina Estefania. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; ArgentinaFil: Añon, Maria Cristina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Criotecnología de Alimentos. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Criotecnología de Alimentos; ArgentinaFil: Parisi, Gustavo Daniel. Universidad Nacional de Quilmes; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Number of different structural and sequential clusters derived from CATH database.

<p>Blue dots represent proteins with less than 5 BPs and the orange ones those with 5 or more BPs. It is possible to see that proteins with more than 5 BPs are more diverse structurally and sequentially.</p

Diagram of structural mapping of the bioactive peptides on structural superfamilies.

<p>Once a BP was detected in a given protein after sequence exact searches, we identified putative folds for that sequence using fold-assignment techniques. Templates in this fold identification were those domains deposited in CATH database. We then structurally aligned the sequence putative CATH template with the corresponding representative protein of the structural superfamily again accordingly with CATH database. We finally mapped the BP occurrence to the representative template of each structural superfamily.</p

Distribution of number of GO terms associated with folds with more and less than 5 biopeptides.

<p>Distributions of different GO terms per each class (Molecular function, Cellular components and Biological process) for proteins showing less than 5 and 5 or more BP (panels a, b, and c). Panel d, shows the same distribution but now using FunTree clusters information. In all the cases it is possible to observe that proteins with more than 5 BPs are functionally more diverse than those proteins with less than 5 BPs.</p

Flowchart of main procedure followed to mapping the structural occurrence of biopeptides.

<p>Flowchart of main procedure followed to mapping the structural occurrence of biopeptides.</p

Description of the top ten most abundant superfamilies found in the assignation of structure of the sequences with at least one peptide.

<p>Description of the top ten most abundant superfamilies found in the assignation of structure of the sequences with at least one peptide.</p

Structure of dethiobiotin synthase (PDB ID 1byi) represented in cartoon representation showing mapped BPs.

<p>Red indicates ACE inhibitor BP activity (14), blue antibacterial (4), yellow inmunomodulating (3), green antioxidative (3), magenta neuropeptide (1), light grey chemotactic (1) and dark grey stimulating activities (1) (as derived from BIOPEP database). It is possible to see that different activities have similar location. BPs found in different proteins of the same superfamily have been mapped on a representative structure (1byi) accordingly to CATH (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0191063#sec002" target="_blank">Materials and methods</a>).</p

Detail of the sequence and activity of biopeptides of the first four superfamilies with the highest number of biopeptides.

<p>The activity corresponds to the classification in BIOPEP.</p