Anticuerpos Monoclonales: estructura, desarrollo y usos

Los anticuerpos o inmunoglobulinas son un tipo de proteínas denominadas glicoproteínas. Funcionan como la parte específica del complejo receptor de células B, reconociendo al antígeno a nivel de la membrana del linfocito B y desencadenando una respuesta de varias células inmunes que lo atacan. Además, funcionan como moléculas circulantes secretadas por las células plasmáticas provenientes de la activación, la proliferación y la diferenciación de células B. En la actualidad, la integración de las técnicas de biología molecular e ingeniería genética y proteica permitieron expandir el horizonte de la generación de anticuerpos monoclonales y sus usos, y se han encontrado técnicas como la hibridación, la quimerización, la humanización y la producción de anticuerpos monoclonales plenamente humanos. En el mercado se hallan alrededor de 29 anticuerpos monoclonales aprobados por la Food and Drug Administration (FDA) de USA para uso en humanos. Los anticuerpos monoclonales se diseñan especialmente para actuar ante dianas específicas, con el propósito de interrumpir un proceso patológico concreto, excitar una acción celular definida o desviar un mecanismo celular hacia una vía de interés

Lifting velocity predicts the maximum number of repetitions to failure with comparable accuracy during the Smith machine and free-weight prone bench pull exercises

This study compared the accuracy of the fastest mean velocity from set (MVfastest) to predict the maximum number of repetitions to failure (RTF) between 2 variants of prone bench pull (PBP) exercise (Smith machine and free-weight) and 3 methods (generalized, individualized multiplepoint, and individualized 2-point). Twenty-three resistance-trained males randomly performed 2 sessions during Smith machine PBP and 2 sessions during free-weight PBP in different weeks. The first weekly session determined the RTF-MVfastest relationships and subjects completed single sets of repetitions to failure against 60-70-80-90%1RM. The second weekly session explored the accuracy of RTFs prediction under fatigue conditions and subjects completed 2 sets of 65%1RM and 2 sets of 85%1RM with 2 min of rest. The MVfastest associated with RTFs from 1 to 15 were greater for Smith machine compared to free-weight PBP (F ≥ 42.9; P < 0.001) and for multiplepoint compared to 2-point method (F ≥ 4.6; P ≤ 0.043). The errors when predicting RTFs did not differ between methods and PBP variants, whereas all RTF-MVfastest relationships overestimated the RTF under fatigue conditions. These results suggest that RTF–MVfastest relationships present similar accuracy during Smith machine and free-weight PBP exercises and it should be constructed under similar training conditions.The Biomedicine Doctoral Studies of the University of Granada, SpainSpanish Ministry of University under a predoctoral grant (FPU19/01137)Spanish Ministry of Science and Innovation [PID2019- 110074GBI00/SRA/10.13039/501100011033)

Changes in physiological activities and root exudation profile of two grapevine rootstocks reveal common and specific strategies for Fe acquisition

In several cultivation areas, grapevine can suffer from Fe chlorosis due to the calcareous and alkaline nature of soils. This plant species has been described to cope with Fe deficiency by activating Strategy I mechanisms, hence increasing root H+ extrusion and ferric-chelate reductase activity. The degree of tolerance exhibited by the rootstocks has been reported to depend on both reactions, but to date, little emphasis has been given to the role played by root exudate extrusion. We studied the behaviour of two hydroponically-grown, tolerant grapevine rootstocks (Ramsey and 140R) in response to Fe deficiency. Under these experimental conditions, the two varieties displayed differences in their ability to modulate morpho-physiological parameters, root acidification and ferric chelate reductase activity. The metabolic profiling of root exudates revealed common strategies for Fe acquisition, including ones targeted at reducing microbial competition for this micronutrient by limiting the exudation of amino acids and sugars and increasing instead that of Fe(III)-reducing compounds. Other modifications in exudate composition hint that the two rootstocks cope with Fe shortage via specific adjustments of their exudation patterns. Furthermore, the presence of 3-hydroxymugenic acid in these compounds suggests that the responses of grapevine to Fe availability are rather diverse and much more complex than those usually described for Strategy I plants

Exploring the Interplay between Metabolic Pathways and Taxane Production in Elicited Taxus baccata Cell Suspensions

Taxus cell cultures are a reliable biotechnological source of the anticancer drug paclitaxel. However, the interplay between taxane production and other metabolic pathways during elicitation remains poorly understood. In this study, we combined untargeted metabolomics and elicited Taxus baccata cell cultures to investigate variations in taxane-associated metabolism under the influence of 1 µM coronatine (COR) and 150 µM salicylic acid (SA). Our results demonstrated pleiotropic effects induced by both COR and SA elicitors, leading to differential changes in cell growth, taxane content, and secondary metabolism. Metabolite annotation revealed significant effects on N-containing compounds, phenylpropanoids, and terpenoids. Multivariate analysis showed that the metabolomic profiles of control and COR-treated samples are closer to each other than to SA-elicited samples at different time points (8, 16, and 24 days). The highest level of paclitaxel content was detected on day 8 under SA elicitation, exhibiting a negative correlation with the biomarkers kauralexin A2 and taxusin. Our study provides valuable insights into the intricate metabolic changes associated with paclitaxel production, aiding its potential optimization through untargeted metabolomics and an evaluation of COR/SA elicitor effects

Incidence and genetic diversity of cucurbit viruses in Spain

[EN] Several viral diseases affect cucurbits, with different economic effects depending on the region and the year. However, there are not recent studies on the incidence of specific viruses. During the 2018 summer season, surveys were carried out in open field melon (Cucumis melo), squash (Cucurbita spp.) and watermelon (Citrullus lanatus) crops in most of the main producer areas under commercial (AGL2017-85563-C2 1R and 2R) and organic farming (PROMETEO/2017/078). Samples from plants with virus-like symptoms were analyzed by RT-PCR/PCR with specific primers, hybridization and/or ELISA, to detect Cucumber mosaic virus (CMV), Zucchini yellow mosaic virus (ZYMV), Watermelon mosaic virus (WMV), Moroccan watermelon mosaic virus (MWMV), Cucurbit yellow stunting disorder virus (CYSDV), Cucurbit chlorotic yellows virus (CCYV), Cucumber green mottle mosaic virus (CGMMV) and Tomato leaf curl New Delhi virus (ToLCNDV). Samples from fields in Murcia (south-eastern Spain), Castilla-La Mancha (central Spain) and Comunidad Valenciana (eastern Spain) were analyzed. At least one of these viruses was detected in approximately 80% of the samples. WMV was the most frequently detected in samples of the three crops. ZYMV, CMV, CYSDV and ToLCNDV were present with lower incidence, mainly identified in mixed infections with WMV.This study was partially supported by the Spanish Ministerio de Ciencia, Innovación y Universidades grants AGL2017-85563-C2 (1-R and 2-R) and RTA2017-00061-C03-03 (INIA) cofounded with FEDER funds, and by the PROMETEO project 2017/078 (to promote excellence groups) by the Conselleria d'Educació , Investigació , Cultura i Esports (Generalitat Valenciana). C. Sáez is a recipient of a predoctoral fellowship (ACIF/2016/188) from Generalitat Valenciana, cofunded by the Operational Program of the European Social Fund (FSECV 2014-2020).Pérez De Castro, AM.; Martínez De Alba, AE.; Sáez-Sánchez, C.; Flores-León, A.; Sifres Cuerda, AG.; Gómez-Guillamón, ML.; López Del Rincón, C.... (2020). Incidence and genetic diversity of cucurbit viruses in Spain. Acta Horticulturae. 1294:203-210. https://doi.org/10.17660/ActaHortic.2020.1294.25S203210129

Maximal and submaximal intended velocity squat sets: Do they selectively impact mechanical performance in paired multijoint upper‐body exercise sets?

This study aimed to investigate how squat protocols performed at maximal and submaximal intended velocities during interset periods of paired upper‐body exercises that impact the mechanical performance of these multijoint upper‐body exercises. Twenty‐one young and healthy adults (seven women) completed three experimental sessions, each comprising four sets of five repetitions at 75% of their 1‐repetition maximum, with a 4‐min break between sets using the bench press and bench pull exercises. The experimental sessions differed in the protocol utilized during the interset periods: (i) Passive—no physical exercise was performed; (ii) SQfast—5 repetitions of the squat exercise at maximal intended velocity against the load associated with a mean velocity (MV) of 0.75 m s−1; and (iii) SQslow—5 repetitions of the squat exercise at submaximal velocity (intended MV of 0.50 m s−1) against the load associated with an MV of 0.75 m s−1. Level of significance was p ≤ 0.05. The main findings revealed negligible differences (effect size [ES] < 0.20) among the exercise protocols (passive vs. SQfast vs. SQslow) for all mechanical variables during the bench pull, whereas during the bench press, small differences (ES from 0.23 to 0.31) emerged favoring the passive protocol over SQfast and SQslow in terms of mean set velocity and fastest MV of the set. The absence of significant differences between the SQfast and SQslow protocols, irrespective of the particular upper‐body exercise, implies that the intended lifting velocity does not influence the potential interference effect during paired set training procedures.National Natural Science Foundation of China under grant 12250410237Funding for open access charge: Universidad de Granada/CBU

Combining Molecular Weight Fractionation and Metabolomics to Elucidate the Bioactivity of Vegetal Protein Hydrolysates in Tomato Plants

The comprehension of the bioactive fractions involved in the biostimulant activity of plant derived protein hydrolysates (PH) is a complex task, but it can also lead to significant improvements in the production of more effective plant biostimulants. The aim of this work is to shed light onto the bioactivity of different PH dialysis fractions (PH1 &lt; 0.5\u20131 kDa; PH2 &gt; 0.5\u20131 kDa; PH3 &lt; 8\u201310 kDa; PH4 &gt; 8\u201310 kDa) of a commercial PH-based biostimulant through a combined in vivo bioassay and metabolomics approach. A first tomato rooting bioassay investigated the auxin-like activity of PH and its fractions, each of them at three nitrogen levels (3, 30, and 300 mg L 121 of N) in comparison with a negative control (water) and a positive control (indole-3-butyric acid, IBA). Thereafter, a second experiment was carried out where metabolomics was applied to elucidate the biochemical changes imposed by the PH and its best performing fraction (both at 300 mg L 121 of N) in comparison to water and IBA. Overall, both the PH and its fractions increased the root length of tomato cuttings, compared to negative control. Moreover, the highest root length was obtained in the treatment PH1 following foliar application. Metabolomics allowed highlighting a response to PH1 that involved changes at phytohormones and secondary metabolite level. Notably, such metabolic reprogramming supported the effect on rooting of tomato cuttings, being shared with the response induced by the positive control IBA. Taken together, the outcome of in vivo assays and metabolomics indicate an auxin-like activity of the selected PH1 fraction

Intraocular pressure responses to a virtual reality shooting simulation in active-duty members of the Spanish Army: The influence of task complexity

Ocular physiology is sensitive to cognitively demanding tasks. However, it is unknown whether the intraocular pressure is also affected by the cognitive demands of military operations. The main objective was to determine the impact of a virtual reality shooting simulation with two levels of complexity on intraocular pressure levels in military personnel. Eighteen active-duty members of the Spanish Army and eighteen civilians performed two 4 min simulated shooting tasks with two levels of complexity using a virtual reality. In the “easy” task participants performed a simulated shoot when the stimulus (military with a rifle) appeared, while in the “difficult” task the stimulus randomly was a military with a rifle or with his hands on the air and participants were instructed to respond only when the military with a rifle appeared. Intraocular pressure was measured with a rebound tonometer before and immediately after each task. Complementarily, perceived levels of mental load and shooting performance (reaction time) were assessed. Intraocular pressure was greater after completing the more complex task in both military personnel (p-value < 0.01, Cohen´s d = 1.19) and civilians (p-value < 0.01, Cohen´s d = 1.16). Also, perceived levels of task load and reaction time were higher in the difficult compared to the easy shooting tasks (both p < 0.001). The rise in intraocular pressure is positively associated with the cognitive demands of simulated military operations. The potential application of this finding is the development of objective tools based on intraocular pressure for the evaluation of the mental state in real-world contexts, permitting to improve soldiers´safety and performance.CEMIX (Centro Mixto UGR-MADOC, Army of Spain) 5/4/20 TR-COMBAT

Exploring the interplay between metabolic pathways and taxane production in elicited Taxus baccata cell suspensions

Taxus cell cultures are a reliable biotechnological source of the anticancer drug paclitaxel. However, the interplay between taxane production and other metabolic pathways during elicitation remains poorly understood. In this study, we combined untargeted metabolomics and elicited Taxus baccata cell cultures to investigate variations in taxane-associated metabolism under the influence of 1 µM coronatine (COR) and 150 µM salicylic acid (SA). Our results demonstrated pleiotropic effects induced by both COR and SA elicitors, leading to differential changes in cell growth, taxane content, and secondary metabolism. Metabolite annotation revealed significant effects on N-containing compounds, phenylpropanoids, and terpenoids. Multivariate analysis showed that the metabolomic profiles of control and COR-treated samples are closer to each other than to SA-elicited samples at different time points (8, 16, and 24 days). The highest level of paclitaxel content was detected on day 8 under SA elicitation, exhibiting a negative correlation with the biomarkers kauralexin A2 and taxusin. Our study provides valuable insights into the intricate metabolic changes associated with paclitaxel production, aiding its potential optimization through untargeted metabolomics and an evaluation of COR/SA elicitor effects.Agencia Estatal de Investigación | Ref. PID2020-113438RB-I00Agència de Gestió d’Ajuts Universitaris i de Recerca | Ref. 2021 SGR00693Ministerio de Ciencia, Innovación y Universidades | Ref. FPU18/00850Ministerio de Universidades | Ref. 33.50.460A.75

Metabolomic Responses of Maize Shoots and Roots Elicited by Combinatorial Seed Treatments With Microbial and Non-microbial Biostimulants

Microbial and non-microbial plant biostimulants have been successfully used to improve agriculture productivity in a more sustainable manner. Since the mode of action of biostimulants is still largely unknown, the present work aimed at elucidating the morpho-physiological and metabolomic changes occurring in maize (Zea mays L.) leaves and roots following seed treatment with (i) a consortium of two beneficial fungi [arbuscular mycorrhizal fungi (AMF) and Trichoderma koningii TK7] and rhizobacteria, (ii) a protein hydrolyzate-based biostimulant (PH) alone, or (iii) in combination with a consortium of T. koningii TK7 and rhizobacteria. The application of PH alone or in combination with Trichoderma elicited significant increases (+16.6%) in the shoot biomass compared to untreated maize plants, whereas inoculation with AMF + Trichoderma elicited significant increases in root dry biomass (+48.0%) compared to untreated plants. Distinctive metabolomic signatures were achieved from the different treatments, hence suggesting that different molecular processes were involved in the plants response to the biostimulants. The metabolic reprogramming triggered by the treatments including the protein hydrolyzate was hierarchically more pronounced than the application of microorganisms alone. Most of the differential metabolites could be ascribed to the secondary metabolism, with phenylpropanoids and terpenes being the most represented compounds. The application of PH triggered an accumulation of secondary metabolites, whereas the opposite trend of accumulation was seen in the case of microorganisms alone. The increase in biomass could be related to two processes, namely the modulation of the multilayer phytohormone interaction network and a possible increase in nitrogen use efficiency via the GS-GOGAT system