ABSTRACT
Background: Despite growing interest in understanding the challenges faced by multidisciplinary health teams during the COVID-19 pandemic, there is a lack of studies specifically focusing on changes in pharmacist interventions and drug-related problems. Objectives: To analyze and compare the interventions performed by pharmacists during comprehensive medication management in the adult intensive care unit and general internal medicine ward of the University Hospital of the University of São Paulo, Brazil, for defined periods before the onset of the COVID-19 pandemic and during the pandemic itself. Methods: All pharmacist interventions performed in relation to inpatient prescriptions from March to December 2019 (before the pandemic) and from March to December 2021 (during the pandemic) were collected and tabulated. These interventions were then classified according to the Pharmaceutical Care Network Europe (PCNE) system, version 9.1, and categorized based on first-level codes of the Anatomical Therapeutic Chemical classification system. Results: The analysis revealed substantial changes in the patterns of pharmacist interventions and the therapeutic classes of drugs for COVID-19-positive and COVID-19-negative patients during the pandemic relative to patients in the pre-pandemic period. Among COVID-19-positive patients, interventions were predominantly related to enhancing patient safety (PCNE code P2), drug selection (C1), dose selection (C3), prescribing and dispensing processes (C5), the drug-use process (C6), and patient transfers between different levels of care (C8). The drug-related problems addressed by pharmacist interventions primarily involved COVID-19-positive patients in the pandemic period and were related to systemic hormonal preparations (excluding sex hormones and insulins), anti-infective agents for systemic use, nervous system and drugs for the blood and blood-forming organs. Conclusion: The results of this study highlight the adaptability and competence of pharmacists in responding to critical scenarios such as the COVID-19 pandemic. These scenarios are characterized by new work dynamics, the hiring of additional professionals, an increase in the number of beds, the rapid evolution of evidence-based information, and drug shortages that necessitate the use of alternative medications. Pharmacists play a crucial role in ensuring patient safety during these difficult times.
Contexte: Malgré un intérêt croissant pour la compréhension des défis auxquels les équipes de santé multidisciplinaires ont été confrontées pendant la pandémie de COVID-19, peu d'études portent sur les changements chez les interventions des pharmaciens et les problèmes liés aux médicaments en particulier. Objectifs: Analyser et comparer les interventions réalisées par les pharmaciens lors de la gestion globale des médicaments dans l'unité de soins intensifs pour adultes et le service de médecine interne générale de l'hôpital universitaire de l'Université de São Paulo, Brésil, pendant des périodes définies avant le début de la pandémie de COVID-19 et pendant la pandémie elle-même. Méthodologie: Toutes les interventions des pharmaciens réalisées en lien avec les prescriptions hospitalières de mars à décembre 2019 (avant la pandémie) et de mars à décembre 2021 (pendant la pandémie) ont été collectées et compilées. Ces interventions ont ensuite été classées selon le système du Pharmaceutical Care Network Europe (PCNE), version 9.1, et catégorisées sur la base des codes de premier niveau du système de classification anatomique, thérapeutique et chimique. Résultats: L'analyse a révélé des changements substantiels dans les types d'intervention des pharmaciens et dans les classes thérapeutiques de médicaments pour les patients positifs pour la COVID-19 et négatifs pour la COVID-19 pendant la pandémie par rapport aux patients d'avant la pandémie. Parmi les patients positifs pour la COVID-19, les interventions étaient principalement liées à l'amélioration de la sécurité des patients (code PCNE P2), au choix des médicaments (C1), à la sélection des doses (C3), au processus de prescription et de délivrance (C5), au processus d'utilisation des médicaments (C6), et aux transferts de patients entre différents niveaux de soins (C8). Les problèmes liés aux médicaments traités par les interventions des pharmaciens concernaient principalement les patients positifs pour la COVID-19 pendant la période de la pandémie et se rapportaient aux préparations hormonales systémiques (à l'exclusion des hormones sexuelles et des insulines), aux agents anti-infectieux à usage systémique, au système nerveux ainsi qu'au sang et aux organes hématopoïétiques. Conclusion: Les résultats de cette étude mettent en évidence l'adaptabilité et la compétence des pharmaciens pour répondre à des scénarios critiques tels que la pandémie de COVID-19. Ces scénarios se caractérisent par une nouvelle dynamique de travail, l'embauche de professionnels supplémentaires, une augmentation du nombre de lits, l'évolution rapide des informations fondées sur des données probantes et des pénuries de médicaments nécessitant le recours à des médicaments alternatifs. Les pharmaciens jouent un rôle crucial pour assurer la sécurité des patients pendant ces périodes difficiles.
ABSTRACT
Anthracnose, white mold, powdery mildew, and root rot caused by Colletotrichum lindemuthianum, Scletorinia sclerotiorum, Erysiphe spp., and Pythium ultimum, respectively, are among the most frequent diseases that cause significant production losses worldwide in common bean (Phaseolus vulgaris L.). Reactions against these four fungal diseases were investigated under controlled conditions using a diversity panel of 311 bean lines for snap consumption (Snap bean Panel). The genomic regions involved in these resistance responses were identified based on a genome-wide association study conducted with 16,242 SNP markers. The highest number of resistant lines was observed against the three C. lindemuthianum isolates evaluated: 156 lines were resistant to CL124 isolate, 146 lines resistant to CL18, and 109 lines were resistant to C531 isolate. Two well-known anthracnose resistance clusters were identified, the Co-2 on chromosome Pv11 for isolates CL124 and CL18, and the Co-3 on chromosome Pv04 for isolates CL124 and C531. In addition, other lesser-known regions of anthracnose resistance were identified on chromosomes Pv02, Pv06, Pv08, and Pv10. For the white mold isolate tested, 24 resistant lines were identified and the resistance was localized to three different positions on chromosome Pv08. For the powdery mildew local isolate, only 12 resistant lines were identified, and along with the two previous resistance genes on chromosomes Pv04 and Pv11, a new region on chromosome Pv06 was also identified. For root rot caused by Pythium, 31 resistant lines were identified and two main regions were located on chromosomes Pv04 and Pv05. Relevant information for snap bean breeding programs was provided in this work. A total of 20 lines showed resistant or intermediate responses against four or five isolates, which can be suitable for sustainable farm production and could be used as resistance donors. Potential genes and genomic regions to be considered for targeted improvement were provided, including new or less characterized regions that should be validated in future works. Powdery mildew disease was identified as a potential risk for snap bean production and should be considered a main goal in breeding programs.
ABSTRACT
KEY MESSAGE: Association analysis, colocation study with previously reported QTL, and differential expression analyses allowed the identification of the consistent QTLs and main candidate genes controlling seed traits. Common beans show wide seed variations in shape, size, water uptake, and coat proportion. This study aimed to identify consistent genomic regions and candidate genes involved in the genetic control of seed traits by combining association and differential expression analyses. In total, 298 lines from the Spanish Diversity Panel were genotyped with 4,658 SNP and phenotyped for seven seed traits in three seasons. Thirty-eight significant SNP-trait associations were detected, which were grouped into 23 QTL genomic regions with 1,605 predicted genes. The positions of the five QTL regions associated with seed weight were consistent with previously reported QTL. HCPC analysis using the SNP that tagged these five QTL regions revealed three main clusters with significantly different seed weights. This analysis also separated groups that corresponded well with the two gene pools described: Andean and Mesoamerican. Expression analysis was performed on the seeds of the cultivar 'Xana' in three seed development stages, and 1,992 differentially expressed genes (DEGs) were detected, mainly when comparing the early and late seed development stages (1,934 DEGs). Overall, 91 DEGs related to cell growth, signaling pathways, and transcriptomic factors underlying these 23 QTL were identified. Twenty-two DEGs were located in the five QTL regions associated with seed weight, suggesting that they are the main set of candidate genes controlling this character. The results confirmed that seed weight is the sum of the effects of a complex network of loci, and contributed to the understanding of seed phenotype control.
Subject(s)
Phaseolus , Phenotype , Polymorphism, Single Nucleotide , Quantitative Trait Loci , Seeds , Seeds/genetics , Seeds/growth & development , Phaseolus/genetics , Phaseolus/growth & development , Genotype , RNA-Seq , Genetic Association Studies , Genes, Plant , Chromosome Mapping , Gene Expression Regulation, Plant , Genome-Wide Association StudyABSTRACT
Indoor air quality is crucial for human health due to the significant time people spend at home, and it is mainly affected by internal sources such as solid fuel combustion for heating. This study investigated the indoor air quality and health implications associated with residential coal burning covering gaseous pollutants (CO, CO2 and total volatile organic compounds), particulate matter, and toxicity. The PM10 chemical composition was obtained by ICP-MS/OES (elements), ion chromatography (water-soluble ions) and thermal-optical analysis (organic and elemental carbon). During coal combustion, PM10 levels were higher (up to 8.8 times) than background levels and the indoor-to-outdoor ratios were, on average, greater than unity, confirming the existence of a significant indoor source. The chemical characterisation of PM10 revealed increased concentrations of organic carbon and elemental carbon during coal combustion as well as arsenic, cadmium and lead. Carcinogenic risks associated with exposure to arsenic exceeded safety thresholds. Indoor air quality fluctuated during the study, with varying toxicity levels assessed using the Aliivibrio fischeri bioluminescence inhibition assay. These findings underscore the importance of mitigating indoor air pollution associated with coal burning and highlight the potential health risks from long-term exposure. Effective interventions are needed to improve indoor air quality and reduce health risks in coal-burning households.
Subject(s)
Air Pollutants , Air Pollution, Indoor , Arsenic , Air Pollutants/analysis , Air Pollution, Indoor/analysis , Arsenic/analysis , Carbon/analysis , Coal/analysis , Environmental Monitoring , Particulate Matter/analysisABSTRACT
KEY MESSAGE: QTL mapping, association analysis, and colocation study with previously reported QTL revealed three main regions controlling pod morphological traits and two loci for edible pod characteristics on the common bean chromosomes Pv01 and Pv06. Bean pod phenotype is a complex characteristic defined by the combination of different traits that determine the potential use of a genotype as a snap bean. In this study, the TUM RIL population derived from a cross between 'TU' (dry) and 'Musica' (snap) was used to investigate the genetic control of pod phenotype. The character was dissected into pod morphological traits (PMTs) and edible pod characteristics (EPC). The results revealed 35 QTL for PMTs located on seven chromosomes, suggesting a strong QTL colocation on chromosomes Pv01 and Pv06. Some QTL were colocated with previously reported QTL, leading to the mapping of 15 consensus regions associated with bean PMTs. Analysis of EPC of cooked beans revealed that two major loci with epistatic effect, located on chromosomes Pv01 and Pv06, are involved in the genetic control of this trait. An association study using a subset of the Spanish Diversity Panel (snap vs. non-snap) detected 23 genomic regions, with three regions being mapped at a position similar to those of two loci identified in the TUM population. The results demonstrated the relevant roles of Pv01 and Pv06 in the modulation of bean pod phenotype. Gene ontology enrichment analysis revealed a significant overrepresentation of genes regulating the phenylpropanoid metabolic process and auxin response in regions associated with PMTs and EPC, respectively. Both biological functions converged in the lignin biosynthetic pathway, suggesting the key role of the pathway in the genetic control of bean pod phenotype.
Subject(s)
Phaseolus , Quantitative Trait Loci , Phaseolus/genetics , Chromosome Mapping , Phenotype , GenotypeABSTRACT
The Fabada market class within the dry beans has a well-differentiated seed phenotype with very large white seeds. This work investigated the genetic diversity maintained in the seed collections within this market class and possible genetic erosion over the last 30 years. A panel with 100 accessions was maintained in seed collections for 30 years, 57 accessions collected from farmers in 2021, six cultivars developed in SERIDA, and 16 reference cultivars were gathered and genotyped with 108,585 SNPs using the genotyping-by-sequencing method. Filtering based on genotypic and phenotypic data was carried out in a staggered way to investigate the genetic diversity among populations. The dendrogram generated from genotyping revealed 90 lines forming 16 groups with identical SNP profiles (redundant lines) from 159 lines classified as market-class Fabada according to their passport data. Seed phenotyping indicated that 19 lines were mistakenly classified as Fabada (homonymies), which was confirmed in the dendrogram built without redundant lines. Moreover, this study provides evidence of genetic erosion between the population preserved for 30 years and the currently cultivated population. The conserved population contains 54.6% segregation sites and 41 different SNP profiles, whereas the cultivated population has 19.6% segregation sites and 26 SNP profiles. The loss of genetic variability cannot be attributed to the diffusion of modern cultivars, which increase genetic diversity (six new SNP profiles). The results allow for the more efficient preservation of plant genetic resources in genebanks, minimizing redundant accessions and incorporating new variations based on genotypic and phenotypic data.
Subject(s)
Fabaceae , Genotype , Phenotype , Polymorphism, Single NucleotideABSTRACT
Mining is an economic activity that entails the production and displacement of significant amounts of atmospheric particulate matter (PM) during operations involving intense earthcrushing or earthmoving. As high concentrations of PM may have adverse effects on human health, it is necessary to monitor and control the fugitive emissions of this pollutant. This paper presents an innovative methodology for the online monitoring of PM10 concentrations in air using a low-cost sensor (LCS, <300 USD) onboard an unmanned aerial vehicle. After comprehensive calibration, the LCS was horizontally flown over seven different areas of the large Riotinto copper mine (Huelva, Spain) at different heights to study the PM10 distribution at different longitudes and altitudes. The flights covered areas of zero activity, intense mining, drilling, ore loading, waste discharge, open stockpiling, and mineral processing. In the zero-activity area, the resuspension of PM10 was very low, with a weak wind speed (3.6 m/s). In the intense-mining area, unhealthy concentrations of PM10 (>51 µgPM10/m3) could be released, and the PM10 can reach surrounding populations through long-distance transport driven by several processes being performed simultaneously. Strong dilution was also observed at high altitudes (> 50 m). Mean concentrations were found to be 22-89 µgPM10/m3, with peaks ranging from 86 to 284 µgPM10/m3. This study demonstrates the potential applicability of airborne LCSs in the high-resolution online monitoring of PM in mining, thus supporting environmental managers during decision-making against fugitive emissions in a cost-effective manner.
ABSTRACT
Domesticated crops have been disseminated by humans over vast geographic areas. Common bean (Phaseolus vulgaris L.) was introduced in Europe after 1492. Here, by combining whole-genome profiling, metabolic fingerprinting and phenotypic characterisation, we show that the first common bean cultigens successfully introduced into Europe were of Andean origin, after Francisco Pizarro's expedition to northern Peru in 1529. We reveal that hybridisation, selection and recombination have shaped the genomic diversity of the European common bean in parallel with political constraints. There is clear evidence of adaptive introgression into the Mesoamerican-derived European genotypes, with 44 Andean introgressed genomic segments shared by more than 90% of European accessions and distributed across all chromosomes except PvChr11. Genomic scans for signatures of selection highlight the role of genes relevant to flowering and environmental adaptation, suggesting that introgression has been crucial for the dissemination of this tropical crop to the temperate regions of Europe.
Subject(s)
Phaseolus , Humans , Phaseolus/genetics , Genetic Variation , Genotype , Biological Evolution , Hybridization, GeneticABSTRACT
BACKGROUND: A large variation in seed coat colors and seed phenolic metabolites is present in common bean (Phaseolus vulgaris L.). The study of the relationships between seed coat color phenotype and the phenolic profile is an important step in the elucidation of the gene network involved in the phenylpropanoid biosynthetic pathway. However, this relationship is still poorly understood in this species. RESULTS: A genome-wide association study (GWAS) was used to investigate the genomic regions associated with the synthesis of 10 flavonoids (5 anthocyanins and 5 flavonols) and with 10 seed coat color traits using a set of 308 common bean lines of the Spanish Diversity Panel (SDP) which have been genotyped with 11,763 SNP markers.. A total of 31 significant SNP-trait associations (QTNs) were identified, grouped in 20 chromosome regions: 6 for phenolic metabolites on chromosomes Pv01, Pv02, Pv04, Pv08, and Pv09, 13 for seed coat color on chromosomes Pv01, Pv02, Pv06, Pv07, and Pv10, and 1 including both types of traits located on chromosome Pv08. In all, 58 candidate genes underlying these regions have been proposed, 31 of them previously described in the phenylpropanoid pathway in common bean, and 27 of them newly proposed in this work based on the association study and their homology with Arabidopsis anthocyanin genes. CONCLUSIONS: Chromosome Pv08 was identified as the main chromosome involved in the phenylpropanoid pathway and in consequence in the common bean seed pigmentation, with three independent chromosome regions identified, Phe/C_Pv08(2.7) (expanding from 2.71 to 4.04 Mbp), C_Pv08(5.8) (5.89-6.59 Mbp), and Phe_Pv08(62.5) (62.58 to 63.28 Mbp). Candidate genes previously proposed by other authors for the color genes V and P were validated in this GWAS. Candidate genes have been tentatively proposed from this study for color genes B and Rk on Pv02, Asp on Pv07, and complex C on Pv08. These results help to clarify the complex network of genes involved in the genetic control of phenolic compounds and seed color in common bean and provide the opportunity for future validation studies.
Subject(s)
Phaseolus , Phenols , Anthocyanins/genetics , Chromosome Mapping , Genome-Wide Association Study , Phaseolus/genetics , Seeds/geneticsABSTRACT
Particulate matter (PM2.5) samples were collected in the vicinity of an industrial chemical pole and analysed for organic and elemental carbon (OC and EC), 47 trace elements and around 150 organic constituents. On average, OC and EC accounted for 25.2% and 11.4% of the PM2.5 mass, respectively. Organic compounds comprised polycyclic aromatic hydrocarbons (PAHs), alkylated PAHs, anhydrosugars, phenolics, aromatic ketones, glycerol derivatives, aliphatic alcohols, sterols, and carboxyl groups, including aromatic, carboxylic and dicarboxylic acids. Enrichment factors > 100 were obtained for Pb, Cd, Zn, Cu, Sn, B, Se, Bi, Sb and Mo, showing the contribution of industrial emissions and nearby major roads. Principal component analysis revealed that vehicle, industrial and biomass burning emissions accounted for 66%, 11% and 9%, respectively, of the total PM2.5-bound PAHs. Some of the detected organic constituents are likely associated with plasticiser ingredients and thermal stabilisers used in the manufacture of PVC and other plastics in the industrial complex. Photooxidation products of both anthropogenic (e.g., toluene) and biogenic (e.g., isoprene and pinenes) precursors were also observed. It was estimated that biomass burning accounted for 13.8% of the PM2.5 concentrations and that secondary OC represented 37.6% of the total OC. The lifetime cancer risk from inhalation exposure to PM2.5-bound PAHs was found to be negligible, but it exceeded the threshold of 10-6 for metal(loi)s, mainly due to Cr and As.
Subject(s)
Air Pollutants , Polycyclic Aromatic Hydrocarbons , Trace Elements , Air Pollutants/analysis , Alcohols , Cadmium/analysis , Carbon/analysis , Dicarboxylic Acids/analysis , Environmental Monitoring , Ketones , Lead/analysis , Particulate Matter/analysis , Polycyclic Aromatic Hydrocarbons/analysis , Polyvinyl Chloride/analysis , Seasons , Sterols/analysis , Toluene/analysis , Trace Elements/analysis , Vehicle Emissions/analysisABSTRACT
Anthracnose is responsible for large yield losses in common bean crops. RNA-sequencing was used to investigate the differentially expressed genes (DEGs) in response to race 38 of Colletotrichum lindemuthianum in two near-isogenic lines (A25 and A4804) that differ in the presence of a resistance gene located in the cluster Co-2. Their responses were analyzed at different hours after inoculation (0, 24, and 48) and within and between genotypes. In all, 2,850 DEGs were detected, with 2,373 assigned to at least one functional GO term. Enriched GO terms in the resistant genotype were mainly related to functions as a response to stimulus, hormone signaling, cellular component organization, phosphorylation activities, and transcriptional regulation. The region containing the Co-2 cluster was delimited at the end of chromosome Pv11 (46.65-48.65 Mb) through a comparison with the SNP genotypes, obtained using 'Genotyping by Sequencing,' among seven resistant lines harboring the Co-2 gene and the susceptible line A25. The delimited region contained 23 DEGs, including 8 typical R genes, that showed higher expression levels in the resistant genotype and non-changes in the susceptible genotype after inoculation. Six R genes encoding protein kinases and an LRR domain formed a cluster in a core region between 46.98 and 47.04 Mb. The alignment of the raw transcriptome reads in the core region revealed structural changes that were used to design four potential breeder-friendly DNA markers, and it revealed some alignments with the intergenic regions, suggesting the presence of genes in addition to those annotated in the reference genome.
ABSTRACT
Trace element concentrations within PM10, gaseous pollutants (NO2 and SO2), and PM10 levels were studied during the Covid-19 lockdown at a regional level in Southern Spain (Andalusia). Pollutant concentrations were compared considering different mobility periods (pre-lockdown, lockdown, and relaxation) in 2020 and previous years (2013-2016). An acute decrease in NO2 levels (<50%) was observed as a consequence of traffic diminution during the confinement period. Moreover, a lower reduction in PM10 levels and a non-clear pattern for SO2 levels were observed. During the lockdown period, PM10 elements released from traffic emissions (Sn and Sb) showed the highest concentration diminution in the study area. Regarding the primary industrial sites, there were no significant differences in V, Ni, La, and Cr concentration reduction during 2020 associated with industrial activity (stainless steel and oil refinery) in Algeciras Bay. Similarly, concentrations of Zn showed the same behaviour at Cordoba, indicating that the Zn-smelter activity was not affected by the lockdown. Nevertheless, stronger reductions of Cu, Zn, and As in Huelva during the confinement period indicated a decrease in the nearby Cu-smelter emissions. Brick factories in Bailen were also influenced by the confinement measures, as corroborated by the marked decrease in concentrations of Ni, V, Cu, and Zn during the lockdown compared to that from previous years. This work has shown the baseline concentrations of trace elements of PM10, which is of great value to air quality managers in order to minimise pollution levels by applying the confinement of the population, affecting both traffic and industrial anthropogenic activities.
Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Environmental Pollutants , Trace Elements , Air Pollutants/analysis , Air Pollution/analysis , COVID-19/epidemiology , Cities , Communicable Disease Control , Environmental Monitoring , Gases , Humans , Nitrogen Dioxide/analysis , Particulate Matter/analysis , SARS-CoV-2 , SpainABSTRACT
In the course of infection and intense endotoxemia processes, induction of a catabolic state leading to weight loss is observed in mice and humans. However, the late effects of acute inflammation on energy homeostasis, regulation of body weight and glucose metabolism are yet to be elucidated. Here, we addressed whether serial intense endotoxemia, characterized by an acute phase response and weight loss, could be an aggravating or predisposing factor to weight gain and associated metabolic complications. Male Swiss Webster mice were submitted to 8 consecutive doses of lipopolysaccharide (10 mg/kg LPS), followed by 10 weeks on a high-fat diet (HFD). LPS-treated mice did not show changes in weight when fed standard chow. However, when challenged by a high-fat diet, LPS-treated mice showed greater weight gain, with larger fat depot areas, increased serum leptin and insulin levels and impaired insulin sensitivity when compared to mice on HFD only. Acute endotoxemia caused a long-lasting increase in mRNA expression of inflammatory markers such as TLR-4, CD14 and serum amyloid A (SAA) in the adipose tissue, which may represent the key factors connecting inflammation to increased susceptibility to weight gain and impaired glucose homeostasis. In an independent experimental model, and using publicly available microarray data from adipose tissue from mice infected with Gram-negative bacteria, we performed gene set enrichment analysis and confirmed upregulation of a set of genes responsible for cell proliferation and inflammation, including TLR-4 and SAA. Together, we showed that conditions leading to intense and recurring endotoxemia, such as common childhood bacterial infections, may resound for a long time and aggravate the effects of a western diet. If confirmed in humans, infections should be considered an additional factor contributing to obesity and type 2 diabetes epidemics.
ABSTRACT
Snap beans are a group of bean cultivars grown for their edible immature pods. The objective of this work was to characterize the diversity of pod phenotypes in a snap bean panel (SBP), comprising 311 lines collected in Europe, and establish a core set (Core-SBP) with the maximum diversity of pod phenotypes. Phenotyping of the SBP was carried out over two seasons based on 14 quantitative pod dimension traits along with three qualitative traits: pod color, seed coat color, and growth habit. Phenotypes were grouped into 54 classes using a hierarchical method, and a Core-SBP with one line per phenotype class was established. A further field-based evaluation of the Core-SBP revealed higher diversity index values than those obtained for the SBP. The Core-SBP was also genotyped using 24 breeder-friendly DNA markers tagging 21 genomic regions previously associated with pod trait control. Significant marker-trait associations were found for 11 of the 21 analyzed regions as well as the locus fin. The established Core-SBP was a first attempt to classify snap bean cultivars based on pod morphology and constituted a valuable source of characteristics for future breeding programs and genetic analysis.
ABSTRACT
BACKGROUND: The dominant effect of age on COVID-19 mortality obscures the impact of other risk factors. Although the elderly is at a greater risk of severe disease and death due to COVID-19, the interaction of obesity and age was not carefully assessed. This analysis is especially critical for prioritizing groups to receive COVID-19 vaccination. METHODS: Starting with 1,120,767 unvaccinated individuals registered in a Brazilian surveillance system, we selected 313,898 hospitalized COVID-19 patients aged 20 to 89 who had a BMI ≥ 25 kg/m2 and cardiovascular diseases (CVD) or diabetes, as well as individuals with no risk factors associated with severe COVID-19. Patient data were stratified by age, obesity, BMI, and comorbidities, and subsequently, subjected to crude and adjusted odds ratio, hazard ratio, and Kaplan-Meier curves. Disease outcomes were invasive and non-invasive ventilatory support, intensive care unit (ICU) admission, and death. FINDINGS: Obesity alone is a risk factor for in-hospital mortality and is more significant than cardiovascular disease and diabetes. Furthermore, obesity, cardiovascular disease, and diabetes increase the risk of severity and death by COVID-19 more significantly in young adults than in the elderly. When categorizing patients by obesity classes, the severity of obesity was found to be associated with a higher risk of admission to the ICU and death from COVID-19 than the non-obese young adults or elderly population. INTERPRETATION: Our findings highlight the increased risk of severe COVID-19 on the Brazilian obese youth. As SARS-CoV-2 may become a recurrent seasonal infection, future vaccination campaigns against COVID-19 should prioritize obese young individuals. FUNDINGS: This work was supported by the Brazilian National Council for Scientific and Technological Development (grant number 313662/2017-7 and 307356/2017-5; the São Paulo Research Foundation (grant numbers 2018/14933-2); and CAPES.
ABSTRACT
Kynurenine (KYN), the most abundant metabolite of tryptophan, is classically associated with immune tolerance and tumor immune escape. In the last years, KYN is in the spotlight in other biological processes. Here, we showed that KYN inhibited tyrosinase expression and melanin content in primary human melanocyte and keratinocyte co-cultures. Furthermore, KYN decreased melanosome content in a 3D human skin reconstruction model. In these experiments, we used tyrosine + NH4 Cl to induce pigmentation. We compared the inhibitory effect of KYN on melanogenesis with the already known inhibitory effect promoted by IFN-γ. Since increased KYN production depends on the IFN-γ-inducible enzyme indoleamine-2,3-dioxygenase (IDO), we propose that part of the effect of IFN-γ on melanogenesis involves KYN production. From that, we tested if, during melanogenesis, changes in tryptophan metabolism would occur. For this purpose, we measured tryptophan, KYN and downstream products along with pigmentation. There were no significant changes in Trp metabolism, except for the high consumption of kynurenic acid. Our data identify the skin as a potential target for the action of KYN relevant for skin physiology and pigmentation. The results are discussed concerning the high production of KYN in skin inflammatory disorders and cancer.
Subject(s)
Kynurenine , Tryptophan , Coculture Techniques , Humans , Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism , Keratinocytes/metabolism , Kynurenine/metabolism , Melanocytes/metabolism , Tryptophan/pharmacologyABSTRACT
The influence of North African (NAF) dust events on the air quality at the regional level (12 representative monitoring stations) in Southern Europe during a long time series (2007-2014) was studied. PM10 levels and chemical composition were separated by Atlantic (ATL) and NAF air masses. An increase in the average PM10 concentrations was observed on sampling days with NAF dust influence (42 µg m-3) when compared to ATL air masses (29 µg m-3). Major compounds such as crustal components and secondary inorganic compounds (SIC), as well as toxic trace elements derived from industrial emissions, also showed higher concentrations of NAF events. A source contribution analysis using positive matrix factorisation (PMF) 5.0 of the PM10 chemical data, discriminating ATL and NAF air mass origins, allowed the identification of five sources: crustal, sea salt, traffic, regional, and industrial. A higher contribution (74%) of the natural sources to PM10 concentrations was confirmed under NAF episodes compared with ATL. Furthermore, there was an increase in anthropogenic sources during these events (51%), indicating the important influence of the NAF air masses on these sources. The results of this study highlight that environmental managers should take appropriate actions to reduce local emissions during NAF events to ensure good air quality.
Subject(s)
Air Pollutants , Dust , Air Pollutants/analysis , Dust/analysis , Environmental Monitoring , Europe , Particle Size , Particulate Matter/analysisABSTRACT
KEY MESSAGE: Three genes associated with the seed coat color in a TU/Musica RIL population were located on a genetic map, and two candidate genes proposed to control black seed coat in the TU genotype were characterized. Seed coat color is an important characteristic of common bean (Phaseolus vulgaris L.) associated with the marketability of dry bean cultivars, quality and nutritional characteristics of seed, as well as response to pathogens. In this study, the genetic control of seed coat color in a recombinant inbred line population (175 lines) obtained from the cross 'TU' × 'Musica' was investigated. Phenotypic segregation fitted 1:1 for white vs. nonwhite, and 3:1 for brown versus black, indicating the involvement of three independent genes, one controlling white color and two (with epistatic interaction) controlling black color. Using a genetic map built with 842 SNPs, the gene responsible for the white seed coat was mapped on the linkage group Pv07, in the position previously described for the P gene. For the black seed coat phenotype, two genes were mapped to the beginning of chromosomes Pv06 and Pv08, in the positions estimated for the V gene and the complex C locus, respectively, by classical studies. The involvement of these two genomic regions was verified through two crosses between three selected RILs exhibiting complementary and dominant inheritance, in which the TU alleles for both genes resulted in a black phenotype. Two genes involved in the anthocyanin biosynthesis pathway were proposed as candidate genes: Phvul.006G018800 encoding a flavonoid 3'5'hydroxylase and Phvul.008G038400 encoding MYB113 transcription factor. These findings add knowledge to the complex network of genes controlling seed coat color in common bean as well as providing genetic markers to be used in future genetic analysis or plant breeding.
Subject(s)
Phaseolus/genetics , Pigmentation/genetics , Seeds , Alleles , Chromosome Mapping , Color , Crosses, Genetic , Genes, Plant , Genetic Linkage , Genotype , Phenotype , Polymorphism, Single NucleotideABSTRACT
BACKGROUND: Common bean (Phaseolus vulgaris L.) is an important legume species which can be consumed as immature pods and dry seeds after re-hydration and cooking. Many genes and QTL, and epistatic interactions among them, condition pod morphological traits. However, not all them have been mapped or validated nor candidate genes proposed. We sought to investigate the genomic regions conditioning pod morphological and color characters through GWAS. RESULTS: Single and multi-locus genome wide association analysis was used to investigate pod traits for a set of 301 bean lines of the Spanish Diversity Panel (SDP). The SDP was genotyped with 32,812 SNPs obtained from Genotyping by Sequencing. The panel was grown in two seasons and phenotypic data were recorded for 17 fresh pods traits grouped in four pod characters: pod length, pod cross-section, pod color, and number of seeds per pod. In all, 23 QTL for pod length, 6 for cross-section, 18 for pod color, 6 for number of seeds per pod and 9 associated to two or more pod characters were detected. Most QTL were located in the telomeric region of chromosomes Pv01, Pv02, Pv04, Pv08, Pv09 and Pv10. Eighteen detected QTL co-localized with 28 previously reported QTL. Twenty-one potential candidate genes involving developmental processes were detected underlying 11 QTL for pod morphological characters, four of them homologous to A. thaliana genes FIS2, SPL10, TTG2 and AML4 affecting silique size. Eight potential candidate genes involved in pigment synthesis, were found underlying five QTL for pod color. CONCLUSIONS: GWAS for pod morphological and color characters in the bean Spanish Diversity Panel revealed 62 QTL, 18 co-localized with previously reported QTL, and 16 QTL were underlain by 25 candidate genes. Overall 44 new QTL identified and 18 existing QTL contribute to a better understanding of the complex inheritance of pod size and color traits in common bean and open the opportunity for future validation works.
Subject(s)
Genome-Wide Association Study , Phaseolus/genetics , Phenotype , Plant Proteins/genetics , Seeds/physiology , Color , Plant Proteins/metabolism , Polymorphism, Single Nucleotide , Seeds/geneticsABSTRACT
In legumes, pod shattering occurs when mature pods dehisce along the sutures, and detachment of the valves promotes seed dispersal. In Phaseolus vulgaris (L)., the major locus qPD5.1-Pv for pod indehiscence was identified recently. We developed a BC4/F4 introgression line population and narrowed the major locus down to a 22.5 kb region. Here, gene expression and a parallel histological analysis of dehiscent and indehiscent pods identified an AtMYB26 orthologue as the best candidate for loss of pod shattering, on a genomic region ~11 kb downstream of the highest associated peak. Based on mapping and expression data, we propose early and fine up-regulation of PvMYB26 in dehiscent pods. Detailed histological analysis establishes that pod indehiscence is associated with the lack of a functional abscission layer in the ventral sheath, and that the key anatomical modifications associated with pod shattering in common bean occur early during pod development. We finally propose that loss of pod shattering in legumes resulted from histological convergent evolution and that it is the result of selection at orthologous loci.