Current status and future trends of microbial and nematode-based biopesticides for biocontrol of crop pathogens.

The increasing public demand to avoid the use of synthetic pesticides and fertilizers in agricultural production systems, causing serious environmental damages, has challenged industry to develop new and effective solutions to manage and control phytopathogens. Biopesticides, particularly microbial-based biopesticides, are a promising new alternative with high biodegradability, specificity, suitability for incorporation into integrated pest management practices, low likelihood of resistance development, and practically no known human health risks. However: expensive production methods, narrow action spectra, susceptibility to environmental conditions, short shelf life, poor storage stability, legislation registry constraints, and general lack of knowledge are slowing down their adoption. In addition to regulatory framework revisions and improved training initiatives, improved preservation methods, thoughtfully designed formulations, and field test validations are needed to offer new microbial- and nematode-based biopesticides with improved efficacy and increased shelf-life. During the last several years, substantial advancements in biopesticide production have been developed. The novelty part of this review written in 2023 is to summarize (i) mechanisms of action of beneficial microorganisms used to increase crop performance and (ii) successful formulation including commercial products for the biological control of phytopathogens based on microorganisms, nematode and/or metabolites.

Computer-aided drug design supporting sunscreen research: a showcase study using previously synthesized hybrid UV filter-antioxidant compounds.

CONTEXT: Although quantum mechanical calculations have proven effective in accurately predicting UV absorption and assessing the antioxidant potential of compounds, the utilization of computer-aided drug design (CADD) to support sustainable synthesis research of new sunscreen active ingredients remains an area with limited exploration. Furthermore, there are ongoing concerns about the safety and effectiveness of existing sunscreens. Therefore, it remains crucial to investigate photoprotection mechanisms and develop enhanced strategies for mitigating the harmful effects of UVR exposure, improving both the safety and efficacy of sunscreen products. A previous study conducted synthesis research on eight novel hybrid compounds (I-VIII) for use in sunscreen products by molecular hybridization of trans-resveratrol (RESV), avobenzone (AVO), and octinoxate (OMC). Herein, time-dependent density functional theory (TD-DFT) calculations performed in the gas phase on the isolated hybrid compounds (I-VIII) proved to reproduce the experimental UV absorption. Resveratrol-avobenzone structure-based hybrids (I-IV) present absorption maxima in the UVB range with slight differences between them, while resveratrol-OMC structure-based hybrids (V-VIII) showed main absorption in the UVA range. Among RESV-OMC hybrids, compounds V and VI exhibited higher UV absorption intensity, and compound VIII stood out for its broad-spectrum coverage in our simulations. Furthermore, both in silico and in vitro analyses revealed that compounds VII and VIII exhibited the highest antioxidant activity, with compound I emerging as the most reactive antioxidant within RESV-AVO hybrids. The study suggests a preference for the hydrogen atom transfer (HAT) mechanism over single-electron transfer followed by proton transfer (SET-PT) in the gas phase. With a strong focus on sustainability, this approach reduces costs and minimizes effluent production in synthesis research, promoting the eco-friendly development of new sunscreen active ingredients. METHODS: The SPARTAN'20 program was utilized for the geometry optimization and energy calculations of all compounds. Conformer distribution analysis was performed using the Merck molecular force field 94 (MMFF94), and geometry optimization was carried out using the parametric method 6 (PM6) followed by density functional theory (DFT/B3LYP/6-31G(d)). The antioxidant behavior of the hybrid compounds (I-VIII) was determined using the highest occupied molecular orbital (εHOMO) and the lowest unoccupied molecular orbital (εLUMO) energies, as well as the bond dissociation enthalpy (BDE), ionization potential (IP), and proton dissociation enthalpy (PDE) values, all calculated at the same level of structural optimization. TD-DFT study is carried out to calculate the excitation energy using the B3LYP functional with the 6-31G(d) basis set. The calculated transitions were convoluted with a Gaussian profile using the Gabedit program.

Can allelopathic potentialities of Mediterranean plant species reduce the spread of invasive plant species, Acacia dealbata and Ailanthus altissima?

Beyond ecological and health impacts, invasive alien plant species can generate indirect and direct costs, notably through reduced agricultural yields, restoration, and management of the invaded environment. Acacia dealbata and Ailanthus altissima are invasive plant species that cause particularly significant damage to the railway network in the Mediterranean area. The allelopathic properties of Mediterranean plant species could be used as nature-based solutions to slow down the spread of such invasive plant species along railway borders. In this context, a mesocosm experiment was set-up: (i) to test the potential allelopathic effects of Cistus ladanifer, Cistus albidus, and Cotinus coggygria leaf aqueous extracts on seed germination and seedling growth of A. dealbata and A. altissima; (ii) to evaluate whether these effects depend on the extract dose; and finally, (iii) to estimate whether these effects are modified by soil amendment. Leaf aqueous extracts of the three native plant species showed negative effects on both seed germination and seedling growth of the two invasive species. Our results show that the presence of allelochemicals induces a delay in seed germination (e.g., A. dealbata germination lasted up to 269% longer in the presence of high-dose leaf aqueous extracts of C. coggygria), which can lead to a decrease in individual recruitment. They also highlight a decrease in seedling growth (e.g., high-dose C. coggygria leaf aqueous extracts induced a 26% decrease in A. dealbata radicle growth), which can alter the competitiveness of invasive species for resource access. Our results also highlight that compost addition limits the inhibitory effect of native Mediterranean plants on the germination of invasive alien plants, suggesting that soil organic matter content can counteract allelopathic effects on invasive alien plants. Thus, our findings revealed that the allelopathic potential of certain Mediterranean plant species could be a useful tool to manage invasive plant species.

Refining the genomic profiles of North African sheep breeds through meta-analysis of worldwide genomic SNP data.

Introduction: The development of reproducible tools for the rapid genotyping of thousands of genetic markers (SNPs) has promoted cross border collaboration in the study of sheep genetic diversity on a global scale. Methods: In this study, we collected a comprehensive dataset of 239 African and Eurasian sheep breeds genotyped at 37,638 filtered SNP markers, with the aim of understanding the genetic structure of 22 North African (NA) sheep breeds within a global context. Results and discussion: We revealed asubstantial enrichment of the gene pool between the north and south shores of the Mediterranean Sea, which corroborates the importance of the maritime route in the history of livestock. The genetic structure of North African breeds mirrors the differential composition of genetic backgrounds following the breed history. Indeed, Maghrebin sheep stocks constitute a geographically and historically coherent unit with any breed-level genetic distinctness among them due to considerable gene flow. We detected a broad east-west pattern describing the most important trend in NA fat-tailed populations, exhibited by the genetic closeness of Egyptian and Libyan fat-tailed sheep to Middle Eastern breeds rather than Maghrebin ones. A Bayesian FST scan analysis revealed a set of genes with potentially key adaptive roles in lipid metabolism (BMP2, PDGFD VEGFA, TBX15, and WARS2), coat pigmentation (SOX10, PICK1, PDGFRA, MC1R, and MTIF) and horn morphology RXFP2) in Tunisian sheep. The local ancestry method detected a Merino signature in Tunisian Noire de Thibar sheep near the SULF1gene introgressed by Merino's European breeds. This study will contribute to the general picture of worldwide sheep genetic diversity.

IBD sharing patterns as intra-breed admixture indicators in small ruminants.

In this study, we investigated how IBD patterns shared between individuals of the same breed could be informative of its admixture level, with the underlying assumption that the most admixed breeds, i.e. the least genetically isolated, should have a much more fragmented genome. We considered 111 goat breeds (i.e. 2501 individuals) and 156 sheep breeds (i.e. 3304 individuals) from Europe, Africa and Asia, for which beadchip SNP genotypes had been performed. We inferred the breed's level of admixture from: (i) the proportion of the genome shared by breed's members (i.e. "genetic integrity level" assessed from ADMIXTURE software analyses), and (ii) the "AV index" (calculated from Reynolds' genetic distances), used as a proxy for the "genetic distinctiveness". In both goat and sheep datasets, the statistical analyses (comparison of means, Spearman correlations, LM and GAM models) revealed that the most genetically isolated breeds, also showed IBD profiles made up of more shared IBD segments, which were also longer. These results pave the way for further research that could lead to the development of admixture indicators, based on the characterization of intra-breed shared IBD segments, particularly effective as they would be independent of the knowledge of the whole genetic landscape in which the breeds evolve. Finally, by highlighting the fragmentation experienced by the genomes subjected to crossbreeding carried out over the last few generations, the study reminds us of the need to preserve local breeds and the integrity of their adaptive architectures that have been shaped over the centuries.

Statistical Experimental Design as a New Approach to Optimize a Solid-State Fermentation Substrate for the Production of Spores and Bioactive Compounds from Trichoderma asperellum.

Managing organic agricultural wastes is a challenge in today's modern agriculture, where the production of different agricultural goods leads to the generation of large amounts of waste, for example, olive pomace and vine shoot in Mediterranean Europe. The discovery of a cost-effective and environment-friendly way to valorize such types of waste in Mediterranean Europe is encouraged by the European Union regulation. As an opportunity, organic agricultural waste could be used as culture media for solid-state fermentation (SSF) for fungal strains. This methodology represents a great opportunity to produce secondary metabolites like 6-pentyl-alpha-pyrone (6-PP), a lactone compound with antifungal properties against phytopathogens, produced by Trichoderma spp. Therefore, to reach adequate yields of 6-PP, lytic enzymes, and spores, optimization using specific agricultural cheap local wastes from Southeastern France is in order. The present study was designed to show the applicability of an experimental admixture design to find the optimal formulation that favors the production of 6-PP. To conclude, the optimized formulation of 6-PP production by Trichoderma under SSF contains 18% wheat bran, 23% potato flakes, 20% olive pomace, 14% olive oil, 24% oatmeal, and 40% vine shoots.

Water drinking during aerobic exercise improves the recovery of non-linear heart rate dynamics in coronary artery disease: crossover clinical trial.

Introduction: The post-exercise recovery is a period of vulnerability of the cardiovascular system in which autonomic nervous system plays a key role in cardiovascular deceleration. It is already known that individuals with coronary artery disease (CAD) are at greater risk due to delayed vagal reactivation in this period. Water ingestion has been studied as a strategy to improve autonomic recovery and mitigate the risks during recovery. However, the results are preliminary and need further confirmation. Therefore, our aim was to investigate the influence of individualized water drinking on the non-linear dynamics of heart rate during and after aerobic exercise in CAD subjects. Methods: 30 males with CAD were submitted to a control protocol composed of initial rest, warming up, treadmill exercise, and passive recovery (60 min). After 48 hours they performed the hydration protocol, composed of the same activities, however, with individualized water drinking proportional to the body mass lost in the control protocol. The non-linear dynamics of heart rate were assessed by indices of heart rate variability extracted from the recurrence plot, detrended fluctuation analysis, and symbolic analysis. Results and discussion: During exercise, the responses were physiological and similar in both protocols, indicating high sympathetic activity and reduced complexity. During recovery, the responses were also physiological, indicating the rise of parasympathetic activity and the return to a more complex state. However, during hydration protocol, the return to a more complex physiologic state occurred sooner and non-linear HRV indices returned to resting values between the 5th and 20th minutes of recovery. In contrast, during the control protocol, only a few indices returned to resting values within 60 minutes. Despite that, differences between protocols were not found. We conclude that the water drinking strategy accelerated the recovery of non-linear dynamics of heart rate in CAD subjects but did not influence responses during exercise. This is the first study to characterize the non-linear responses during and after exercise in CAD subjects.

Plant biodiversity offsets negative effects of metals and metalloids soil multi-contamination on ecosystem multifunctionality.

Despite increasing metals and metalloids (MM) human-driven soil contamination, how it simultaneously alters biodiversity and ecosystem functioning remains unknown. We used a wide gradient of a 170-year-old MM soil multi-contamination in Mediterranean scrublands to assess the effects of soil multi-contamination on multiple plant biodiversity facets, microbial communities and ecosystem multifunctionality (EMF). We found an overall positive effect of plant biodiversity on EMF mediated by microbial communities, and allowing offsetting the negative impacts of MM soil multi-contamination, especially on soil water holding capacity and nitrogen content. The diversity of distant plant lineages was the key facet promoting EMF by enhancing microbial communities, whereas the subordinate species richness altered EMF. By developing a holistic approach of these complex relationships between soil multi-contamination, plant biodiversity, microbial communities and ecosystem functioning, our results reveal the potential of plant biodiversity, and especially the diversity of evolutionary distant species, to offset the alteration of ecosystem functioning by MM soil multi-contamination. In this worldwide decade of ecosystems restoration, our study helps to identify relevant facets of plant biodiversity promoting contaminated ecosystem functioning, which is crucial to guide and optimize management efforts aiming to restore ecosystems and preserve human health.

Chemical and Microbial Characterization of Fermented Forest Litters Used as Biofertilizers.

The excessive use of chemicals in intensive agriculture has had a negative impact on soil diversity and fertility. A strategy for developing sustainable agriculture could rely on the use of microbial-based fertilizers, known as biofertilizers. An alternative to marketed products could be offered to small farmers if they could produce their own biofertilizers using forest litters, which harbor one of the highest microbial diversities. The aim of this study is to characterize microbial communities of Fermented Forest Litters (FFL), assuming that the fermentation process will change both their abundance and diversity. We investigated two types of differing in the chemical composition of the initial litters used and the climatic context of the forest where they are originated from. The abundance and diversity of bacterial and fungal communities were assessed using quantitative PCR and molecular genotyping techniques. The litter chemical compositions were compared before and after fermentation using Infrared spectrometry. Results obtained showed that fermentation increased the abundance of bacteria but decreased that of fungi. Low pH and change in organic matter composition observed after fermentation also significantly reduced the α-diversity of both bacterial and fungal communities. The higher proportion of aliphatic molecules and lower C/N of the FFLs compared to initial litters indicate that FFLs should be rapidly decomposed once added into the soil. This preliminary study suggests that the agronomic interest of FFLs used as biofertilizers is probably more related to the contribution of nutrients easily assimilated by plants than to the diversity of microorganisms that compose it. Further studies must be conducted with sequencing techniques to identify precisely the microbial species likely to be beneficial to plant growth.

Is Musical Auditory Stimulation Able to Influence the Recovery of Autonomic Modulation After Exercise?

Context: The effects of musical auditory stimulation on the human body have received considerable interest, especially when related to health and wellbeing, so the objective was to verify the influence of classical music exposure on autonomic modulation in recovery after exercise. Methods: 35 healthy young men aged 21.74 ± 2.59 years were evaluated. Volunteers perform 2-day evaluations, 1 day without musical stimulus and 1 with musical stimulation through classical music during exercise and recovery. Physical exercises were performed on a treadmill with an intensity of 6.0 km/hr + 1% of inclination in the first 5 minutes for physical "warm-up", followed by 25 minutes with an intensity equivalent to 60% of the maximum velocity (Vmax), with a same slope according to the Conconi's threshold. Finally, the volunteers remain at rest for 60 minutes for recovery. Heart rate variability (HRV) was analyzed in some moments of recovery by linear (RMSSD, SDNN, LF and HF (milliseconds squared and normalized unit) and LF/HF ratio, RRtri, TINN and the Poincaré plot: SD1, SD2 and SD1/SD2) and nonlinear indexes (DFA Total, DFA Alpha 1 and Symbolic Analysis: Shannon's Entropy, 0V%, 1V%, 2LV% and 2ULV%). Results: No differences were found in the comparison between the values of the HRV indexes between protocols and interaction moments vs protocols. Differences were observed between the moments for most indexes (P < .05). Conclusions: Classical music did not significantly influence the autonomic control of heart rate in the recovery phase after submaximal exercise.

Effects of osteopathic manipulative treatment associated with pain education and clinical hypnosis in individuals with chronic low back pain: study protocol for a randomized sham-controlled clinical trial.

BACKGROUND: Patients with chronic low back pain (CLBP) suffer with functional, social, and psychological aspects. There is a growing number of studies with multimodal approaches in the management of these patients, combining physical and behavioral therapies such as osteopathic manipulative treatment, associating pain education and clinical hypnosis. The aim of the present study will be to evaluate the effects of osteopathic manipulative treatment (OMT) associated with pain neuroscience education (PNE) and clinical hypnosis (CH) on pain and disability in participants with CLBP compared to PNE, CH, and sham therapy. METHODS: A randomized controlled clinical trial will be conducted in participants aged 20-60 years with CLBP who will be divided into two groups. Group 1 will receive PNE and CH associated with OMT, and G2 will receive PNE, CH, and sham therapy. In both groups, 4 interventions of a maximum of 50 min and with an interval of 7 days will be performed. As primary outcomes, pain (numerical pain scale), pressure pain threshold (pressure algometer), and disability (Oswestry Disability Questionnaire) will be evaluated and, as a secondary outcome, global impression of improvement (Percent of Improvement Scale), central sensitization (Central Sensitization Questionnaire), biopsychosocial aspects (Start Beck Toll Questionnaire), and behavior of the autonomic nervous system (heart rate variability) will be assessed. Participants will be evaluated in the pre-intervention moments, immediately after the end of the protocol and 4 weeks after the procedures. Randomization will be created through a simple randomized sequence and the evaluator will be blinded to the allocation of intervention groups. DISCUSSION: The guidelines have been encouraging multimodal, biopsychosocial approaches for patients with CLBP; in this sense, the results of this study can help clinicians and researchers in the implementation of a model of treatment strategy for these patients. In addition, patients may benefit from approaches with minimal risk of deleterious effects and low cost. In addition, it will enable the addition of relevant elements to the literature, with approaches that interact and do not segment the body and brain of patients with CLBP, allowing new studies in this scenario. TRIALS REGISTRATION: Date: September 4, 2021/Number: NCT05042115 .

Using bibliometrics to analyze the state of art of pesticide use in vineyard agrosystems: a review.

The production of wine dates to ancient civilization and has heavily influenced different landscapes around the globe. Nowadays, wine is still an important sector in terms of land use and income source in many countries, more specifically in the European Mediterranean region. However, to control pests and regulate wine growth, the extensive use of pesticides is common. The effects and persistence of agrochemicals in the environment is well known and defined in scientific literature as well as the environmental and human health risks of these compounds. The purpose of this review was to do a state of art of worldwide production of academic literature using bibliometric principles and analysis to identify thematic areas of this type of agriculture, and its challenges in a changing world. For this review, the focus is on current practices to see what may evolve for more sustainable viticulture. It was found that the three main producers of wine, i.e., Spain, France, and Italy, are also three top producers of scientific literature on this topic. The use of bibliometric methodologies defined the main thematic areas on this subject as follows: soil-plant transfer of agrochemicals, heavy metal accumulation in vineyard soils, management practices in viticulture, water pollution transport, effects of viticulture on the living part of soil, sustainable alternatives to pesticides. We found that Spain, France, and Italy work the most on developing sustainable alternatives for agricultural practices; however, sustainable alternatives and practices were also the least developed thematic in general.

Hydration Influence on the Autonomic Recovery of the Coronary Diseases Patient: Geometric Indices Analysis.

Purpose: To evaluate the recovery period of autonomic modulation, through geometric indices of heart rate variability (HRV), on coronary artery disease (CAD) patients submitted to a cardiovascular rehabilitation session (CR), associated with hydration. Methods: Thirty male participants of a CR program, diagnosed with CAD were submitted to the control (CP) and hydration protocol (HP) characterized by a CR session. Only during HP were the participants given 8 equal portions of water. The water amount was determined through the hydric loss measured at the CP. During the protocols, the heart rate was measured beat-by-beat at rest (5-10 minutes[M1]) and at recovery (0-5 minutes [M2], 5-10 minutes [M3], 15-20 minutes [M4], 25-30 minutes [M5], 40-45 minutes [M6], 55-60 minutes [M7]) for the HRV analysis, performed by the geometric indices: TINN, RRTRI, SD1, SD2 and SD1/SD2 ratio. Results: Statistically significant differences were observed between the protocols (SD1, pvalue = 0.022), moments (TINN, pvalue = 0.001; SD1, pvalue = 0.019; SD2, pvalue = 0.001; SD1/SD2, pvalue = 0.001) and moments vs. protocol interaction (SD1, pvalue = 0.019). The SD1 index pointed to acceleration of parasympathetic recovery in the first minutes after exercising (HP recovery after M3 [86.07 ± 32.31%] vs. CP recovery after M5[86.43 ± 24.56]) and increase in global variability (TINN-HP remained increased in longer, until M5 (M1 83.10 ± 55.76 ms to M5 116.82 ± 67.54 ms) vs. CP that remained increased for a short time, until M2 (M1 77.93 ± 68.56 ms to M2 134.82 ± 56.08 ms). Conclusions: In CAD patients, hydration promoted a more efficient recovery on parasympathetic autonomic modulation and increased the global HRV in the recovery period.

Ethylhexyl methoxycinnamate and butyl methoxydibenzoylmethane: Toxicological effects on marine biota and human concerns.

Ethylhexyl methoxycinnamate (EHMC) (CAS number: 5466-77-3) and butyl methoxydibenzoylmethane (BMDM) (CAS number: 70356-09-1) are important sunscreens. However, frequent application of large amounts of these compounds may reflect serious environmental impact, once it enters the environment through indirect release via wastewater treatment or immediate release during water activities. In this article, we reviewed the toxicological effects of EHMC and BMDM on aquatic ecosystems and the human consequences. According to the literature, EHMC and BMDM have been detected in water samples and sediments worldwide. Consequently, these compounds are also present in several marine organisms like fish, invertebrates, coral reefs, marine mammals, and other species, due to its bioaccumulation potential. Studies show that these chemicals are capable of damaging the aquatic beings in different ways. Further, bioaccumulation studies have shown that EHMC biomagnifies through trophic levels, which makes human seafood consumption a concern because the higher position in the trophic chain, the more elevate levels of ultraviolet (UV) filters are detected, and it is established that EHMC present adverse effects on the human organism. In contrast, there are no studies on the BMDM bioaccumulation and biomagnification potential. Different strategies can be adopted to avoid the damage caused by sunscreens in the environment and human organism. Two of them include the use of natural photoprotectors, such as polyphenols, in association with UV filters in sunscreens and the development of new and safer UV filters. Overall, this review shows the importance of studying the impacts of sunscreens in nature and developing safer sunscreens and formulations to safeguard marine fauna, ecosystems, and humans.

Development and validation of an assay for the measurement of gentamicin concentrations in dried blood spots using UHPLC-MS/MS.

Gentamicin sulfate (GEN) is an aminoglycoside antibiotic with a narrow therapeutic range of plasma concentrations. The collection of venous blood represents a significant burden for patients, especially in neonatology. Dried blood spots (DBS) obtained from capillary blood can be an alternative for drug measurements in this particular population. This study aimed to develop and validate an assay for the quantification of GEN in DBS using UHPLC-MS/MS. Total GEN concentrations were obtained by adding the individual concentrations of the GEN forms C1, C1a, and C2. The assay used a DBS disk containing approximately 17 µL of blood for GEN quantitation in the range of 0.1-40 mg L-1. Measurement accuracy for total GEN was in the range of 102.6-108.6%, inter-assay precision was 11.3-13.1% and intra-assay precision was 9.1-12.8.% GEN was stable for 21 days at - 20 and 8 °C, but only for 24 h at room temperature. Blood Hct affected the accuracy within acceptable limits (93.8-95% at Hct% of 30, 104.3-113% at Hct% of 50). Blood spotted volume did not affect GEN measurement accuracy. Concentrations of GEN in DBS obtained after heel pricks were correlated to plasma levels in a small cohort of neonatal patients. However, percentual differences between estimated plasma concentrations and actual plasma levels presented values between - 64-35.3% (average difference of - 1.9%). The use of DBS for the measurement of GEN concentrations can increase access to TDM of this antibiotic due to the ease of sample collection and the facilitated specimen transportation logistics when testing is not available onsite.

Genomic Uniqueness of Local Sheep Breeds From Morocco.

Sheep farming is a major source of meat in Morocco and plays a key role in the country's agriculture. This study aims at characterizing the whole-genome diversity and demographic history of the main Moroccan sheep breeds, as well as to identify selection signatures within and between breeds. Whole genome data from 87 individuals representing the five predominant local breeds were used to estimate their level of neutral genetic diversity and to infer the variation of their effective population size over time. In addition, we used two methods to detect selection signatures: either for detecting selective sweeps within each breed separately or by detecting differentially selected regions by contrasting different breeds. We identified hundreds of genomic regions putatively under selection, which related to several biological terms involved in local adaptation or the expression of zootechnical performances such as Growth, UV protection, Cell maturation or Feeding behavior. The results of this study revealed selection signatures in genes that have an important role in traits of interest and increased our understanding of how genetic diversity is distributed in these local breeds. Thus, Moroccan local sheep breeds exhibit both a high genetic diversity and a large set of adaptive variations, and therefore, represent a valuable genetic resource for the conservation of sheep in the context of climate change.

Local adaptations of Mediterranean sheep and goats through an integrative approach.

Small ruminants are suited to a wide variety of habitats and thus represent promising study models for identifying genes underlying adaptations. Here, we considered local Mediterranean breeds of goats (n = 17) and sheep (n = 25) from Italy, France and Spain. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original cradle (i.e., the geographical area in which the breed has emerged), including transhumant pastoral areas. We then used the programs PCAdapt and LFMM to identify signatures of artificial and environmental selection. Considering cradles instead of current GPS coordinates resulted in a greater number of signatures identified by the LFMM analysis. The results, combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles in relation to the gradient of aridity and altitude. Some of these genes have been previously implicated in lipid metabolism (SUCLG2, BMP2), hypoxia stress/lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). Selection signatures involving the PCDH9 and KLH1 genes, as well as NBEA/NBEAL1, were identified in both species and thus could play an important adaptive role.

Sensitive determination of gentamicin in plasma using ion-exchange solid-phase extraction followed by UHPLC-MS/MS analysis.

BACKGROUND: Therapeutic drug monitoring (TDM) of gentamicin sulfate (GEN) is usually recommended, particularly in critical patients. Only a few reports had described the determination of GEN in plasma or plasma using LC-MS/MS. OBJECTIVE: This study aimed to develop and validate a sensitive ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) assay for the quantification of GEN in small volumes of human plasma. RESULTS: The use of a very low concentration of the ion-pairing agent HFBA allowed significant retention of the very polar GEN forms in a reversed phase UHPLC column. The solid-phase extraction (SPE) procedure allowed clean extracts, with no interferences detected in blank samples, and high sensitivity. The assay was linear on the range of 0.2-40 mg L-1 of GEN complex. The combined GEN complex had inter-assay CV of 8.8-10.0%, intra-assay CV of 10.2-11.0%, and accuracy of 96.8-104.0%. The assay was applied to 17 clinical samples obtained from neonate patients. Measured concentrations were in the range of 0.15-3.57 mg L-1 for GEN C1, 0.12-3.55 mg L-1 for GEN C1a, 0.20-5.77 mg L-1 for GEN C2, and 0.47-12.88 mg L-1 for the GEN complex, all within the linear range of the assay. CONCLUSION: A sensitive assay for the quantification of gentamicin in plasma using anion-exchange SPE and UHPLC-MS/MS was validated. The assay can be used for TDM of gentamicin, particularly in centers with access to proper instrumentation and with a low demand for gentamicin measurements, where immunoassays are not cost-effective.

Search for Selection Signatures Related to Trypanosomosis Tolerance in African Goats.

Livestock is heavily affected by trypanosomosis in Africa. Through strong selective pressure, several African indigenous breeds of cattle and small ruminants have acquired varying degrees of tolerance against this disease. In this study, we combined LFMM and PCAdapt for analyzing two datasets of goats from West-Central Africa and East Africa, respectively, both comprising breeds with different assumed levels of trypanotolerance. The objectives were (i) to identify molecular signatures of selection related to trypanotolerance; and (ii) to guide an optimal sampling for subsequent studies. From 33 identified signatures, 18 had been detected previously in the literature as being mainly associated with climatic adaptations. The most plausible signatures of trypanotolerance indicate the genes DIS3L2, COPS7B, PD5A, UBE2K, and UBR1. The last gene is of particular interest since previous literature has already identified E3-ubiquitin ligases as playing a decisive role in the immune response. For following-up on these findings, the West-Central African area appears particularly relevant because of (i) a clear parasitic load gradient related to a humidity gradient, and (ii) still restricted admixture levels between goat breeds. This study illustrates the importance of protecting local breeds, which have retained unique allelic combinations conferring their remarkable adaptations.

Vagal reactivation after a cardiac rehabilitation session associated with hydration in coronary artery disease patients: crossover clinical trial.

This study aimed to investigate the hydration influence on the autonomic responses of coronary artery disease subjects in the immediate recovery period after a cardiovascular rehabilitation session, in view of the risks of a delayed autonomic recovery for this population. 28 males with coronary artery disease were submitted to: (I) Maximum effort test; (II) Control protocol (CP), composed by initial rest, warm-up, exercise and passive recovery; (III) Hydration protocol (HP) similar to CP, but with rehydration during exercise. The recovery was evaluated through the heart rate (HR) variability, HR recovery and by the rate of perceived exertion and recovery. The main results revealed that the vagal reactivation occurred at the first 30 s of recovery in HP and after the first minute in CP. A better behavior of the HR at the first minute of recovery was observed in HP. The rate of perceived exertion had a significant decrease in the first minute of recovery in HP, while in CP this occurred after the third minute. In conclusion, despite an anticipated vagal reactivation found at HP, these results should be analyzed with caution as there were no significant differences between protocols for all variables and the effect sizes were small.