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Xanthomonas citri subsp. citri (Xcc) is a bacterium that causes citrus canker, an economically important disease that results in premature fruit drop and reduced yield of fresh fruit. In this study, we demonstrated the involvement of XanB, an enzyme with phosphomannose isomerase (PMI) and guanosine diphosphate-mannose pyrophosphorylase (GMP) activities, in Xcc pathogenicity. Additionally, we found that XanB inhibitors protect the host against Xcc infection. Besides being deficient in motility, biofilm production, and ultraviolet resistance, the xanB deletion mutant was unable to cause disease, whereas xanB complementation restored wild-type phenotypes. XanB homology modeling allowed in silico virtual screening of inhibitors from databases, three of them being suitable in terms of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, which inhibited GMP (but not PMI) activity of the Xcc recombinant XanB protein in more than 50%. Inhibitors reduced citrus canker severity up to 95%, similarly to copper-based treatment. xanB is essential for Xcc pathogenicity, and XanB inhibitors can be used for the citrus canker control. IMPORTANCE: Xcc causes citrus canker, a threat to citrus production, which has been managed with copper, being required a more sustainable alternative for the disease control. XanB was previously found on the surface of Xcc, interacting with the host and displaying PMI and GMP activities. We demonstrated by xanB deletion and complementation that GMP activity plays a critical role in Xcc pathogenicity, particularly in biofilm formation. XanB homology modeling was performed, and in silico virtual screening led to carbohydrate-derived compounds able to inhibit XanB activity and reduce disease symptoms by 95%. XanB emerges as a promising target for drug design for control of citrus canker and other economically important diseases caused by Xanthomonas sp.

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CONTEXT: The advancement in the development of second-generation drugs in the field of antihistamines represents a significant milestone in the management of allergic diseases, targeting the effects of histamine. The efficacy of bilastine in treating allergic disorders has sparked interest in investigating its polymorphism, a crucial property that impacts quality, safety, and effectiveness as per regulatory guidelines. This study examines the polymorphism of bilastine, focusing on two crystalline forms labeled as Form I and Form II. Utilizing advanced analytical techniques, the research explores the structural characteristics and molecular interactions within these forms. Geometric parameters, such as bond lengths, bond angles, and torsion angles, are examined to comprehend molecular conformations and crystal packing arrangements. Hydrogen bonding, covalent bonds, and van der Waals forces contribute to the unique supramolecular arrangements in these forms. This study provides a significant contribution to understanding bilastine's polymorphism, offering critical insights to researchers and regulatory bodies to ensure the quality, efficacy, and safety of antihistamine products. METHODS: The molecular conformation of two bilastine forms was obtained through DFT with the exchange-correlation functional M06-2X and the 6-311 + + G(d,p) basis set, and the results were compared with the experimental X-ray. The atomic coordinates were obtained directly from the crystalline structures, and charge transfer was also investigated using frontier molecular orbitals (HOMO and LUMO), and MEP map in order to evaluate the energies associated with charge transfers and regions of high electron affinity. The geometric and topological parameters and intermolecular interactions in the crystals were analyzed using Hirshfeld Surface.

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l-Ascorbic acid (AsA, vitamin C) is a pivotal dietary nutrient with multifaceted importance in living organisms. In plants, the Smirnoff-Wheeler pathway is the primary route for AsA biosynthesis, and understanding the mechanistic details behind its component enzymes has implications for plant biology, nutritional science, and biotechnology. As part of an initiative to determine the structures of all six core enzymes of the pathway, the present study focuses on three of them in the model species Myrciaria dubia (camu-camu): GDP-d-mannose 3',5'-epimerase (GME), l-galactose dehydrogenase (l-GalDH), and l-galactono-1,4-lactone dehydrogenase (l-GalLDH). We provide insights into substrate and cofactor binding and the conformational changes they induce. The MdGME structure reveals a distorted substrate in the active site, pertinent to the catalytic mechanism. Mdl-GalDH shows that the way in which NAD+ association affects loop structure over the active site is not conserved when compared with its homologue in spinach. Finally, the structure of Mdl-GalLDH is described for the first time. This allows for the rationalization of previously identified residues which play important roles in the active site or in the formation of the covalent bond with FAD. In conclusion, this study enhances our understanding of AsA biosynthesis in plants, and the information provided should prove useful for biotechnological applications.

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Research output provides an insight into the development of the scientific capability of a country. Budget allocation for research and development (R&D) is directly proportional to the research output of a country. Bibliometric analysis of South American countries has not been done in many studies. The purpose of this paper was to analyse research outputs from South American countries on various metrics. An analysis was done for a period of 11 years from 2010 to 2020. The analysis revealed that Brazil with highest percentage of research spend has lowest Field Weighted Citation Impact (FWCI). This contrasts with Uruguay, whose FWCI is high despite comparatively lower spend on R&D and lower publication output. Although Argentina has the highest percentage of researchers per million population (1202), it has the least papers per researchers (0.3 per year) among the countries studied. A huge disparity in terms of percentage of research spent, research output, papers per researcher, and output with national and international co-authorship was observed.

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Opioid receptors, particularly the µ-opioid receptor (µOR), play a pivotal role in mediating the analgesic and addictive effects of opioid drugs. G protein signaling is an important pathway of µOR function, usually associated with painkilling effects. However, the molecular mechanisms underlying the interaction between the µOR and G protein remain poorly understood. In this study, we employed classical all-atom molecular dynamics simulations to investigate the structural changes occurring with the µOR-G protein complex under two different conditions: with the G protein in the apo form (open) and with the GDP bound G protein (closed, holo form). The receptor was in the apo form and active conformation in both cases, and the simulation time comprised 1µs for each system. In order to assess the effect of the G protein coupling on the receptor activation state, three parameters were monitored: the correlation of the distance between TM3 and TM6 and the RMSD of the NPxxYA motif; the universal activation index (A100); and the χ2 dihedral distribution of residue W2936.48. When complexed with the open G protein, receptor conformations with intermediate activation state prevailed throughout the molecular dynamics, whereas in the condition with the closed G protein, mostly inactive conformations of the receptor were observed. The major effect of the G protein in the receptor conformation comes from a steric hindrance involving an intracellular loop of the receptor and a ß-sheet region of the G protein. This suggests that G-protein precoupling is essential for receptor activation, but this fact is not sufficient for complete receptor activation.

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Political doctrines determine the formation of territorial units or geopolitical models more adequate to generate public value in subnational organizations, with positive results in the HDI, productivity indicators and national competitiveness oriented to improve the quality of public service for citizens who participate in democratic electoral processes with identity and that promote a decentralized State that does not generate development obstacles as an effect of geographical limits by departments and regional governments with inequalities in natural resources and comparative advantages, but that projects integration, better economic performance, sustainability, and sustainability for regional and national development and as an alternative to achieve political stability in Peru. The aim of this article is to explore whether the contribution of natural regions and macro-regions to sustainable development is unequal. Information from official web pages. The disparity index, analysis of variance (ANOVA) and Tukey's analysis were used. The GDP per capita of the coastal departments is 64% higher than that of the Andes and 136% higher than those of the Amazon; the HDI of the coast exceeds those regions by 31 and 19%; 44% of the urban population residing in marginal neighborhoods are on the coast, 67% in the Andes and 69% in the Amazon. The percentage of corruption is highest on the coast, followed by the Amazon. At the regional macro level, the primacy in GDP per capita and the HDI moves to the south, although the superiority of the corruption index persists in the center, followed by the south; both significantly higher than the east and north. This fact would reveal the possibility of a regional macro development without Lima and through axes of various development nodes, feasible in the era of globalization.

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O processo de glicosilação de proteínas nos seres vivos é uma etapa pós-traducional de extrema importância, dado que é a partir dela que muitas proteínas adquirem características estruturais essenciais para o seu funcionamento. A L-fucose é um açúcar muito importante nesses processos e compõe inúmeros oligossacarídeos fucosilados que estão anexados às proteínas de seres vivos. Para tanto, a L-fucose estará pronta para compor glicanos apenas em sua forma nucleotídeo ativada - GDP-fucose. Para síntese deste açúcar há duas vias enzimáticas conhecidas em organismos, são chamadas de via salvage - que apresenta as enzimas fucose- quinase (FK) e GDP-fucose pirofosforilase (PP) - e via de novo - que apresenta as enzimas GDP-manose 4,6 desidratase (GMD) e GDP-fucose sintase (FX). Este trabalho realiza investigações destas vias de produção de GDP-fucose em Arthropoda, partindo da espécie de aranha N. cruentata e estendendo para os demais grupos do Filo. Análises de alinhamentos das sequências de aminoácidos das enzimas FK, PP, GMD e FX foram realizadas, buscando observar a preservação ou substituição de resíduos de atividade catalítica e de ligação ao substrato e cofatores. A árvore de máxima verossimilhança a partir das enzimas da via salvage, mostra a proximidade filogenética das FKs com a enzima única de dupla função, fucose-quinase/GDP-fucose pirofosforilase (FKP), da bactéria B. fragilis, o que traz indícios de como se deu a evolução dessa rota enzimática nos seres vivos. Os resultados mostram que a via salvage de produção de GDP-fucose encontra-se ausente no subfilo Hexapoda, mas presente em Arachnida e Crustacea. Já a via de novo está presente em todos os grupos de Arthropoda cujas informações de transcriptomas encontram-se depositadas nos bancos de dados públicos.

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OBJECTIVE: The countries of the Community of Latin American and Caribbean States (CELAC, by its initials in Spanish) have been some of the most affected by COVID-19. This paper analyzes whether, in the 33 CELAC countries, population density, together with other economic variables, such as gross domestic product (GDP) at purchasing power parity (PPP) values or the Human Development Index (HDI), were significantly associated with the coronavirus mortality rate. METHODS: A correlation analysis and an ordinary least squares regression model were used to analyze the effects of different variables on the COVID-19 mortality rate. RESULTS: The results showed that countries with higher numbers of inhabitants per square kilometer had lower death rates. Gross domestic product was not associated with the number of deaths, while the HDI had a positive impact on that number. CONCLUSION: Countries with high population density are not more vulnerable to COVID-19, as population density allows for economic development and better-designed institutions.

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Hazardous alcohol consumption causes approximately 4% of deaths globally, constituting one of the leading risk factors for the burden of the disease worldwide. Alcohol has several health consequences, such as alcohol-associated liver disease, hepatocellular carcinoma, nonliver neoplasms, physical injury, cardiac disease, and psychiatric disorders. Alcohol misuse significantly affects workforce productivity, with elevated direct and indirect economic costs. Due to the high impact of alcohol consumption on the population, public health has led to the development of a range of strategies to reduce its harmful effects. Regulatory public health policies (PHP) for alcohol can exist at the global, regional, international, national, or subnational levels. Effective strategies incorporate a multilevel, multicomponent approach, targeting multiple determinants of drinking and alcohol-related harms. The World Health Organization categorizes the PHP into eight categories: national plan to fight the harmful consequences of alcohol, national license and production and selling control, taxes control and pricing policies, limiting drinking age, restrictions on alcohol access, driving-related alcohol policies, control over advertising and promotion, and government monitoring systems. These policies are supported by evidence from different populations, demonstrating that determinants of alcohol use depend on several factors such as socioeconomic level, age, sex, ethnicity, production, availability, marketing, and others. Although most policies have a significant individual effect, a higher number of PHP are associated with a lower burden of disease due to alcohol. The excessive consequences of alcohol constitute a call for action, and clinicians should advocate for developing and implementing a new PHP on alcohol consumption.

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We evaluated the influence of population size (POP), HDI (Human Development Index) and GDP (gross domestic product) on the COVID-19 pandemic in the Southeast region of Brazil, between February 2020 and May 2021. METHODS: Cases, deaths, incidence coefficient, mortality rate and lethality rate were compared among states. The cities were divided into strata according to POP, GDP, and HDI. Data were compared by Welch's ANOVA, nonlinear polynomial regression, and Spearman's correlation test (rS). RESULTS: The highest incidence coefficient (p < 0.0001) and mortality rate (p < 0.05) were observed in the states of Espírito Santo and Rio de Janeiro, respectively. Until the 45th week, the higher the POP, the higher the mortality rate (p < 0.01), with no differences in the remaining period (p > 0.05). There was a strong positive correlation between POP size and the number of cases (rS = 0.92, p < 0.0001) and deaths (rS = 0.88, p < 0.0001). The incidence coefficient and mortality rate were lower (p < 0.0001) for low GDP cities. Both coefficients were higher in high- and very high HDI cities (p < 0.0001). The lethality rate was higher in the state of Rio de Janeiro (p < 0.0001), in large cities (p < 0.0001), in cities with medium GDP (p < 0.0001), and in those with high HDI (p < 0.05). CONCLUSIONS: Both incidence and mortality were affected by time, with minimal influence of POP, GDP and HDI.

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Angiotensin-converting enzyme (ACE) inhibitors are one of the most active classes for cardiovascular diseases and hypertension treatment. In this regard, developing active and non-toxic ACE inhibitors is still a continuous challenge. Furthermore, the literature survey shows that oxidative stress plays a significant role in the development of hypertension. Herein, glutathione's molecular structure and supramolecular arrangements are evaluated as a potential ACE inhibitor. The tripeptide molecular modeling by density functional theory, the electronic structure by the frontier molecular orbitals, and the molecular electrostatic potential map to understand the biochemical processes inside the cell were analyzed. The supramolecular arrangements were studied by Hirshfeld surfaces, quantum theory of atoms in molecules, and natural bond orbital analyses. They showed distinct patterns of intermolecular interactions in each polymorph, as well as distinct stabilizations of these. Additionally, the molecular docking study presented the interactions between the active site residues of the ACE and glutathione via seven hydrogen bonds. The pharmacophore design indicated that the hydrogen bond acceptors are necessary for the interaction of this ligand with the binding site. The results provide useful information for the development of GSH analogs with higher ACE inhibitor activity.

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The COVID-19 pandemic has caused a pause in people's activities and a socio-economic crisis worldwide due to confinement. This situation is an unprecedented opportunity to understand how these changes may impact biodiversity and its conservation, as well as to study human-nature interaction. Biodiversity plays an essential role in conservation and economic activities, and in countries with greater inequality and low gross domestic product (GDP), biodiversity could have a low priority. Moreover, how biodiversity is prioritized in a society impacts how the citizens view it, and digital news tends to shape biodiversity narratives. The aim of this work was to determine the main trends in biodiversity-related news categories during the COVID-19 pandemic in countries with terrestrial and marine hotspots and relate them to the socioeconomic and public health context of each country. For this, we searched for news on biodiversity and Covid-19 in the first 6 months of the pandemic and related them to GDP, Gini-index, deaths, and infections by Covid-19. Results showed that conservation, public policies, and use of natural resources stood out as the main news categories across countries, with a positive narrative and mostly related to terrestrial rather than marine environments. On the other hand, the socio-economic and public health characteristics of each country had an influence on which aspect of the biodiversity was reflected in the media. For example, countries with greater inequality were associated with tourism news, additionally, countries with low GDP, high cases, and deaths by Covid-19 were associated with news about cultural diversity. In contrast, countries with high GDP and low inequality were associated with news about zoonosis, research and development, public policies, and alien and invasive species.

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The emergence of the COVID-19 pandemic reinforced the central role of the One Health (OH) approach, as a multisectoral and multidisciplinary perspective, to tackle health threats at the human-animal-environment interface. This study assessed Brazilian preparedness and response to COVID-19 and zoonoses with a focus on the OH approach and equity dimensions. We conducted an environmental scan using a protocol developed as part of a multi-country study. The article selection process resulted in 45 documents: 79 files and 112 references on OH; 41 files and 81 references on equity. The OH and equity aspects are poorly represented in the official documents regarding the COVID-19 response, either at the federal and state levels. Brazil has a governance infrastructure that allows for the response to infectious diseases, including zoonoses, as well as the fight against antimicrobial resistance through the OH approach. However, the response to the pandemic did not fully utilize the resources of the Brazilian state, due to the lack of central coordination and articulation among the sectors involved. Brazil is considered an area of high risk for emergence of zoonoses mainly due to climate change, large-scale deforestation and urbanization, high wildlife biodiversity, wide dry frontier, and poor control of wild animals' traffic. Therefore, encouraging existing mechanisms for collaboration across sectors and disciplines, with the inclusion of vulnerable populations, is required for making a multisectoral OH approach successful in the country.

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This paper proposes a time-series stochastic socioeconomic model for analyzing the impact of the pandemic on the regulated distribution electricity market. The proposed methodology combines the optimized tariff model (socioeconomic market model) and the random walk concept (risk assessment technique) to ensure robustness/accuracy. The model enables both a past and future analysis of the impact of the pandemic, which is essential to prepare regulatory agencies beforehand and allow enough time for the development of efficient public policies. By applying it to six Brazilian concession areas, results demonstrate that consumers have been/will be heavily affected in general, mainly due to the high electricity tariffs that took place with the pandemic, overcoming the natural trend of the market. In contrast, the model demonstrates that the pandemic did not/will not significantly harm power distribution companies in general, mainly due to the loan granted by the regulator agency, named COVID-account. Socioeconomic welfare losses averaging 500 (MR$/month) are estimated for the equivalent concession area, i.e., the sum of the six analyzed concession areas. Furthermore, this paper proposes a stochastic optimization problem to mitigate the impact of the pandemic on the electricity market over time, considering the interests of consumers, power distribution companies, and the government. Results demonstrate that it is successful as the tariffs provided by the algorithm compensate for the reduction in demand while increasing the socioeconomic welfare of the market.

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This study analyzes the causal associations between economic growth (GDP) and biomass energy consumption (BIO) in the US, UK, and BRICS countries for the period 1990 to 2020 in time-frequency space. The use of wavelets is what distinguishes our approach, i.e., cross wavelet transform, wavelet coherence, and the wavelet-based Granger causality method proposed by Olayeni (2016), which quantifies the causal associations in the time-frequency space. The results uncover that the causal relationships between GDP and BIO are not uniform across time and frequency. In fact, there is a positive relationship between GDP and BIO indicators in the BRICS countries in the medium and long term and in the USA and UK in the short term throughout the research period. In addition, a bidirectional causal effect between GDP and BIO exists in China, Brazil, and India, while there is no long-run causal relationship between GDP and BIO in India and South Africa. The causal impacts of economic growth on biomass energy usage are more pronounced in these countries than in the opposite direction, especially over longer time horizons. The key conclusion is that these countries should boost their biomass energy consumption to promote economic growth and reduce energy reliance.

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OBJECTIVE: Although there has been increased utilization of assisted reproductive technologies (ART) in the world, there is no conclusive definition about the relationship between the success rate of ART and national wealth. METHODS: In this study, using the data from the International Committee for Monitoring Assisted Reproductive Technologies (ICMART), we sought to determine whether there is a correlation between the success rate of ART (represented by pregnancy and delivery rates) and national wealth represented by the gross domestic product (GDP) per capita. Moreover, to further understand the effect of GDP per capita on ART effectiveness, we analyzed the association between ART success rate and GDP per capita in 50 US states. RESULTS: Our data showed that the number of ART treatment cycles increased as the GDP per capita increased. However, we found a negative correlation between ART success rates and GDP per capita in ICMART countries, although no correlation was seen in the US states. Using rough estimation, we derived that the success rate of ART was not related to GDP per capita in the ICMART countries with a GDP per capita greater than USD 13,000. CONCLUSIONS: In conclusion, for the first time, we showed that when the GDP per capita of an economic territory reaches (or exceeds) USD 13,000, ART pregnancy and delivery rates were not associated with GDP per capita, and ART success rates remained stable.

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This paper aims to validate the hypothesis of an Environmental Kuznets Curve (EKC) for Colombia, introducing the Economic Complexity Index (ECI) into the analysis as a differentiating element of production volumes. We use a Vector Error Correction Model (VECM) to corroborate if there is a long-term relationship between the variables covering the period between 1971-2014. Also, we test the robustness of the results using three different techniques: Dynamic Least Squares, Fully Modified Least Squares, and Canonical Cointegration Regression. The results show that for a developing country like Colombia, the EKC does not exist, and does not yet benefit from increases in economic complexity. Arguably, the country has several hurdles to overcome before achieving the environmental benefits of increased product sophistication. Some of them could be related to the country's own productive and institutional rigidities, which opens the space for public policy intervention.

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Chalcones (E)-1,3-diphenyl-2-propene-1-ones, a class of biosynthetic precursor molecules of flavonoids, have a wide variety of biological applications. Besides the natural products, many synthetic derivatives and analogs became an object of continued interest in academia and industry. In this work, a synthesis and an extensive structural study were performed on a sulfonamide chalcone 1-Benzenesulfonyl-3-(4-bromobenzylidene)-2-(2-chlorophenyl)-2,3-dihydro-1H-quinolin-4-one with potential antineoplastic application. In addition, in silico experiments have shown that the sulfonamide chalcone fits well in the ligand-binding site of EGFR with seven µ-alkyl binding energy interactions on the ligand-binding site. Finally, the kinetic stability and the pharmacophoric analysis for EGFR indicated the necessary spatial characteristics for potential activity of sulfonamide chalcone as an antagonist.

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This review commemorates the 50th anniversary of the Nobel Prize in Chemistry awarded to Luis F. Leloir 'for his discovery of sugar-nucleotides and their role in the biosynthesis of carbohydrates'. He and his co-workers discovered that activated forms of simple sugars, such as UDP-glucose and UDP-galactose, are essential intermediates in the interconversion of sugars. They elucidated the biosynthetic pathways for sucrose and starch, which are the major end-products of photosynthesis, and for trehalose. Trehalose 6-phosphate, the intermediate of trehalose biosynthesis that they discovered, is now a molecule of great interest due to its function as a sugar signalling metabolite that regulates many aspects of plant metabolism and development. The work of the Leloir group also opened the doors to an understanding of the biosynthesis of cellulose and other structural cell wall polysaccharides (hemicelluloses and pectins), and ascorbic acid (vitamin C). Nucleotide-sugars also serve as sugar donors for a myriad of glycosyltransferases that conjugate sugars to other molecules, including lipids, phytohormones, secondary metabolites, and proteins, thereby modifying their biological activity. In this review, we highlight the diversity of nucleotide-sugars and their functions in plants, in recognition of Leloir's rich and enduring legacy to plant science.

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