The Great Lakes region of Central Africa is a major producer of common beans in Africa. The region is known for high population density and small average farm size. The common bean represents the ...most important legume crop of the region, grown on over a third of the cultivated land area, and the per capita consumption is among the highest in the world for the food crop. The objective of this study was to evaluate the genetic diversity in a collection of 365 genotypes from the Great Lakes region of Central Africa, including a large group of landraces from Rwanda as well as varieties from primary centers of diversity and from neighboring countries of Central Africa, such as the Democratic Republic of Congo and Uganda, using 30 fluorescently labeled microsatellite markers and automated allele detection. In addition, the landraces were evaluated for their seed iron and zinc concentration to determine if genetic diversity influenced nutritional quality. Principal coordinate and neighbor-joining analyses allowed the separation of the landraces into 132 Andean and 195 Mesoamerican (or Middle American) genotypes with 32 landraces and 6 varieties intermediate between the gene pools and representing inter-gene pool introgression in terms of seed characteristics and alleles. Genetic diversity and the number of alleles were high for the collection, reflecting the preference for a wide range of seed types in the region and no strong commercial class preference, although red, red mottled and brown seeded beans were common. Observed heterozygosity was also high and may be explained by the common practice of maintaining seed and plant mixtures, a coping strategy practiced by Central African farmers to reduce the effects of abiotic and biotic stresses. Finally, nutritional quality differed between the gene pools with respect to seed iron and zinc concentration, while genotypes from the intermediate group were notably high in both minerals. In conclusion, this study has shown that Central African varieties of common bean are a source of wide genetic diversity with variable nutritional quality that can be used in crop improvement programs for the region.
A convenient regioselective synthesis of allyl- and vinylsilyl alcohols, from a common precursor, was described, by selecting the appropriate reaction conditions. Allyl- and vinylsilyl alcohols were ...tested in silyl-Prins cyclizations for the preparation of disubstituted oxygenated heterocycles in a one-pot sequential reaction. The methodology was sensitive to the structure of the starting alkenylsilyl alcohol and reaction conditions, with competitive pathways observed (particularly for allylsilyl alcohols), such as Peterson elimination and oxonia-Cope reactions. However, the use of vinylsilyl alcohols allowed the preparation of differently disubstituted
-2,6-dihydropyrans in moderate to good yields. Computational studies support the proposed mechanism.
We herein present a selective methodology for the synthesis of disubstituted dihydropyrans by silyl-Prins cyclization of
Z
-vinylsilyl alcohols mediated by trimethylsilyl trifluoromethanesulfonate ...(TMSOTf). The reaction features broad substrate scope, short reaction times and ease of process scale-up. Moreover, to showcase the applicability of the proposed method, we also report a facile and linear synthesis of analogues of rhopaloic acid and natural doremox fragrance.
Selective methodology to access disubstituted dihydropyrans by silyl-Prins cyclization of
Z
-vinylsilyl alcohols mediated by TMSOTf. The reaction features broad substrate scope, short reaction times and ease of process scale-up.
In this perspective, we showcase the benefits of continuous flow chemistry and photochemistry and how these valuable tools have contributed to the synthesis of organic scaffolds from the marine ...environment. These technologies have not only facilitated previously described synthetic pathways, but also opened new opportunities in the preparation of novel organic molecules with remarkable pharmacological properties which can be used in drug discovery programs.
In this work, one of the most prevalent polypharmacology drug-drug interaction events that occurs between two widely used beta-blocker drugs-i.e., acebutolol and propranolol-with the most abundant ...blood plasma fibrinogen protein was evaluated. Towards that end, molecular docking and Density Functional Theory (DFT) calculations were used as complementary tools. A fibrinogen crystallographic validation for the three best ranked binding-sites shows 100% of conformationally favored residues with total absence of restricted flexibility. From those three sites, results on both the binding-site druggability and ligand transport analysis-based free energy trajectories pointed out the most preferred biophysical environment site for drug-drug interactions. Furthermore, the total affinity for the stabilization of the drug-drug complexes was mostly influenced by steric energy contributions, based mainly on multiple hydrophobic contacts with critical residues (THR22: P and SER50: Q) in such best-ranked site. Additionally, the DFT calculations revealed that the beta-blocker drug-drug complexes have a spontaneous thermodynamic stabilization following the same affinity order obtained in the docking simulations, without covalent-bond formation between both interacting beta-blockers in the best-ranked site. Lastly, experimental ultrasound density and velocity measurements were performed and allowed us to validate and corroborate the computational obtained results.
Analyses of protein structures have shown the existence of molecular channels in enzymes from Prokaryotes. Those molecular channels suggest a critical role of spatial voids in proteins, above all, in ...those enzymes functioning under high temperature. It is expected that these spaces within the protein structure are required to access the active site and to maximize availability and thermal stability of their substrates and cofactors. Interestingly, numerous substrates and cofactors have been reported to be highly temperature-sensitive biomolecules. Methanogens represent a singular phylogenetic group of Archaea that performs anaerobic respiration producing methane during growth. Methanogens inhabit a variety of environments including the full range of temperatures for the known living forms. Herein, we carry out a dimensional analysis of molecular tunnels in key enzymes of the methanogenic pathway from methanogenic Archaea growing optimally over a broad temperature range. We aim to determine whether the dimensions of the molecular tunnels are critical for those enzymes from thermophiles. Results showed that at increasing growth temperature the dimensions of molecular tunnels in the enzymes methyl-coenzyme M reductase and heterodisulfide reductase become increasingly restrictive and present strict limits at the highest growth temperatures, i.e., for hyperthermophilic methanogens. However, growth at lower temperature allows a wide dimensional range for the molecular spaces in these enzymes. This is in agreement with previous suggestions on a potential major role of molecular tunnels to maintain biomolecule stability and activity of some enzymes in microorganisms growing at high temperatures. These results contribute to better understand archaeal growth at high temperatures. Furthermore, an optimization of the dimensions of molecular tunnels would represent an important adaptation required to maintain the activity of key enzymes of the methanogenic pathway for those methanogens growing optimally at high temperatures.
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases in the elderly. The key histopathological features of these diseases are the presence of ...abnormal protein aggregates and the progressive and irreversible loss of neurons in specific brain regions. The exact mechanisms underlying the etiopathogenesis of AD or PD remain unknown, but there is extensive evidence indicating that excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS), along with a depleted antioxidant system, mitochondrial dysfunction, and intracellular Ca
dyshomeostasis, plays a vital role in the pathophysiology of these neurological disorders. Due to an improvement in life expectancy, the incidence of age-related neurodegenerative diseases has significantly increased. However, there is no effective protective treatment or therapy available but rather only very limited palliative treatment. Therefore, there is an urgent need for the development of preventive strategies and disease-modifying therapies to treat AD/PD. Because dysregulated Ca
metabolism drives oxidative damage and neuropathology in these diseases, the identification or development of compounds capable of restoring Ca
homeostasis and signaling may provide a neuroprotective avenue for the treatment of neurodegenerative diseases. In addition, a set of strategies to control mitochondrial Ca
homeostasis and signaling has been reported, including decreased Ca
uptake through voltage-operated Ca
channels (VOCCs). In this article, we review the modulatory effects of several heterocyclic compounds on Ca
homeostasis and trafficking, as well as their ability to regulate compromised mitochondrial function and associated free-radical production during the onset and progression of AD or PD. This comprehensive review also describes the chemical synthesis of the heterocycles and summarizes the clinical trial outcomes.
Although intermittent calorie restriction (ICR) has become popular as an alternative weight loss strategy to continuous calorie restriction (CCR), there is insufficient evidence on diet quality ...during ICR and on its feasibility over longer time periods. Thus, we compared dietary composition and adherence between ICR and CCR in a follow-up analysis of a randomized trial. A total of 98 participants with overweight or obesity BMI (kg/m
) 25-39.9, 35-65 years, 49% females were randomly assigned to ICR, operationalized as a "5:2 diet" (energy intake: ~100% on five non-restricted (NR) days, ~25% on two restricted (R) days), or CCR (daily energy intake: ~80%). The trial included a 12-week (wk) intervention phase, and follow-up assessments at wk24, wk50 and wk102. Apart from a higher proportion of energy intake from protein with ICR vs. CCR during the intervention (wk2:
< 0.001; wk12:
= 0.002), there were no significant differences with respect to changes in dietary composition over time between the groups, while overall adherence to the interventions appeared to be good. No significant difference between ICR and CCR regarding weight change at wk102 was observed (
= 0.63). However, self-reported adherence was worse for ICR than CCR, with 71.1% vs. 32.5% of the participants reporting not to or only rarely have followed the regimen to which they were assigned between wk50 and wk102. These results indicate that within a weight management setting, ICR and CCR were equivalent in achieving modest weight loss over two years while affecting dietary composition in a comparable manner.
Small scale fisheries are critically important for the provision of food security, livelihoods, and economic development for billions of people. Yet, most of these fisheries appear to not be ...achieving either fisheries or conservation goals, with respect to creating healthier oceans that support more fish, feed more people and improve livelihoods. Research and practical experience have elucidated many insights into how to improve the performance of small-scale fisheries. Here, we present lessons learned from five case studies of small-scale fisheries in Cuba, Mexico, the Philippines, and Belize. The major lessons that arise from these cases are: 1) participatory processes empower fishers, increase compliance, and support integration of local and scientific knowledge; 2) partnership across sectors improves communication and community buy-in; 3) scientific analysis can lead fishery reform and be directly applicable to co-management structures. These case studies suggest that a fully integrated approach that implements a participatory process to generate a scientific basis for fishery management (e.g., data collection, analysis, design) and to design management measures among stakeholders will increase the probability that small-scale fisheries will implement science-based management and improve their performance.
Antecedentes: La expresión de empatía mejora la calidad de la atención a la salud, y por ello se sugiere su instrucción durante los años de formación académica de estudiantes de medicina. No ...obstante, la expresión de empatía también puede ocasionar ansiedad y perjudicar el bienestar psicológico. Objetivo: Identificar perfiles que describan la relación entre empatía, ansiedad y bienestar psicológico en estudiantes mexicanos de medicina. Método: Estudio transversal en estudiantes mexicanos de medicina que completaron la Escala Multidimensional de Empatía, el Inventario de Ansiedad de Beck y la Escala de Bienestar Psicológico para Adultos. Resultados: Las mujeres presentaron mayor empatía y ansiedad, y menor bienestar psicológico (p < 0.01). La ansiedad en estudiantes del último año de formación fue menor que en los estudiantes de primer y segundo año (p < 0.01). Se detectaron cuatro perfiles: 1) hombres, ansiedad mínima, empatía baja; 2) estudiantes de primer año de formación, ansiedad moderada a grave, bienestar psicológico bajo, empatía alta; 3) último año de formación, ansiedad leve, bienestar psicológico adecuado, empatía media; 4) mujeres, segundo y tercer años de formación, muy alta empatía. Conclusiones: Los estudiantes de medicina del primer año de formación constituyen una población de riesgo. Son necesarias estrategias de atención para este grupo estudiantil.
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