RESUMO
The development of new compounds to treat Chagas disease is imperative due to the adverse effects of current drugs and their low efficacy in the chronic phase. This study aims to investigate nitroisoxazole derivatives that produce oxidative stress while modifying the compounds' lipophilicity, affecting their ability to fight trypanosomes. The results indicate that these compounds are more effective against the epimastigote form of T. cruzi, with a 52 ± 4% trypanocidal effect for compound 9. However, they are less effective against the trypomastigote form, with a 15 ± 3% trypanocidal effect. Additionally, compound 11 interacts with a higher number of amino acid residues within the active site of the enzyme cruzipain. Furthermore, it was also found that the presence of a nitro group allows for the generation of free radicals; likewise, the large size of the compound enables increased interaction with aminoacidic residues in the active site of cruzipain, contributing to trypanocidal activity. This activity depends on the size and lipophilicity of the compounds. The study recommends exploring new compounds based on the nitroisoxazole skeleton, with larger substituents and lipophilicity to enhance their trypanocidal activity.
Assuntos
Isoxazóis , Tripanossomicidas , Trypanosoma cruzi , Trypanosoma cruzi/efeitos dos fármacos , Tripanossomicidas/farmacologia , Tripanossomicidas/química , Tripanossomicidas/síntese química , Isoxazóis/química , Isoxazóis/farmacologia , Proteínas de Protozoários/metabolismo , Proteínas de Protozoários/química , Proteínas de Protozoários/antagonistas & inibidores , Relação Estrutura-Atividade , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Cisteína Endopeptidases/química , Cisteína Endopeptidases/metabolismo , Animais , Domínio Catalítico , Estrutura MolecularRESUMO
BACKGROUND: Veterinary antibiotics are chemical compounds used to kill or inhibit the growth of pathogenic bacteria associated with animal diseases. These molecules can be defined by their retention times (tR) in liquid chromatography-mass spectrometry (LC-MS). One strategy to predict the tR of new veterinary antibiotics is the development of predictive quantitative structure-property relationships (QSPRs), which were used in this study. RESULTS: A database of 122 antibiotics was selected in which the tR was measured using a Hypersil GOLD column. An optimal three-feature model was developed by integrating the unsupervised variable reduction, replacement method variable subset selection, and multiple linear regression. The negligible differences among the coefficient of determination and the root-mean-square error for the training set (R2 = 0.902 and RMSEC = 0.871) and test set (Q2 = 0.854 and RMSEP = 1.064) indicate a stable and predictive model. In a further step, a more in-depth explanation of the mechanism of action of each descriptor in predicting the tR is provided, with the construction of the theoretical chemical space for accurate predictions of new antibiotics. CONCLUSION: The in silico model developed in this work identified three molecular descriptors associated with aqueous solubility, octanol-water partition coefficient, and the presence of negative and lipophilic atom pairs. The QSPR developed here could be implemented by agricultural and food chemists to identify and monitor existing and new antibiotics within the framework of LC-MS. The computational model was developed in accordance with five principles outlined by the Organization for Economic Co-operation and Development. © 2024 Society of Chemical Industry.
Assuntos
Antibacterianos , Espectrometria de Massas , Relação Quantitativa Estrutura-Atividade , Drogas Veterinárias , Antibacterianos/química , Antibacterianos/análise , Drogas Veterinárias/análise , Drogas Veterinárias/química , Cromatografia Líquida , Animais , Cromatografia Líquida de Alta Pressão , Simulação por Computador , Espectrometria de Massa com Cromatografia LíquidaRESUMO
We report Sporothrix brasiliensis infection in three cats from Santiago, Chile. Recently, S. brasiliensis was reported in cats from the southernmost region of Chile located 2,190 km from Santiago. Our findings emphasize the emergence of S. brasiliensis in the Chilean context, reflecting its rapid expansion across South America in recent years. Veterinarians should include S. brasiliensis in the differential diagnosis of skin conditions in cats.
RESUMO
RESUMEN Las enfermedades cardiovasculares y el cáncer corresponden a la primera y segunda causa de muerte a nivel mundial, respectivamente. Comparten factores de riesgo comunes: envejecimiento, estilos de vida no saludables, entre otros; con la atenuante que los pacientes con cáncer o sobrevivientes a este, por sus tratamientos, pueden desarrollar cardiotoxici- dad. Por lo tanto, las estrategias de prevención y tratamiento en algunos de sus abordajes también son similares. Pueden considerarse enfermedades simultáneas o consecutivas, pueden coexistir en un mismo paciente, corresponde entonces un abordaje multidisciplinario, basado en evaluación del riesgo, entrenamiento físico, optimización de terapia farmacoló- gica, consejería de estilos de vida saludable, control de factores de riesgo cardiovascular, apoyo psicológico, adherencia a un estilo de vida más activo con la consecuente mejora en la capacidad cardiopulmonar y por lo tanto funcional. Este documento tiene la intención de plantear una propuesta de protocolo para la prescripción de ejercicio en paciente on- cológico o sobreviviente de cáncer para la prevención de enfermedad cardiovascular, basado en recomendaciones de los consensos internacionales.
ABSTRACT Protocol proposal for exercise prescription in cancer patients or cancer survivors for the prevention of cardiovascular disease Cardiovascular diseases and cancer correspond to the first and second causes of death worldwide. They share common risk factors: aging, unhealthy lifestyles, among others; with the attenuating circumstance that cancer patients or survivors may develop cardiotoxicity due to their treatment. Therefore, the prevention and treatment strategies in some of its approaches are also similar. Diseases can be considered simultaneous or consecutive, they can coexist in the same patient, so a multidisciplinary approach is appropriate, based on risk assessment, physical training, optimization of drug therapy, healthy lifestyle counseling, control of cardiovascular risk factors, psychological support, adherence to a more active lifestyle with the consequent improvement in cardiopulmonary and therefore functional capacity. This document intends to propose a protocol proposal for the prescription of exercise in cancer patients or cancer survivors for the prevention of cardiovascular disease, based on international consensus recommendations.
Assuntos
Humanos , Doenças Cardiovasculares/terapia , Protocolos Clínicos , Terapia por Exercício , Cardio-Oncologia/educação , Costa Rica , Reabilitação Cardíaca , Fatores de Risco de Doenças CardíacasRESUMO
Most human cystic echinococcosis (CE) cases worldwide are attributed to Echinococcus granulosus sensu stricto (s.s), followed by the G6 and G7 genotypes. While E. granulosus s.s. has a cosmopolitan distribution, the G6 genotype is restricted to areas where camels and goats are present. Goats are the primary livestock in the Neuquén province in Argentina where the G6 genotype has been reported to be responsible for a significant percentage of CE human cysts genotyped. In the present study, we genotyped 124 Echinococcus cysts infecting 90 CE-confirmed patients. Echinococcus granulosus s.s. was identified in 51 patients (56.7%) with 81 cysts and the G6 genotype in 39 patients (43.3%) harbouring 43 cysts. Most CE cases ≤18 years were male suggesting pastoral work could be a risk factor for the infection. Echinococcus granulosus s.s. was significantly found more frequently in the liver (32/51 patients) and the G6 genotype in the lungs and extrahepatic localizations (27/39). The patients infected with E. granulosus s.s., presented up to 6 cysts while patients infected with G6 presented a maximum of 2. The diameter of lung cysts attributed to E. granulosus s.s. was significantly larger compared to lung cysts from G6. Following the WHO ultrasound classification of liver cysts, we observed inactive cysts in 55.6% of G6 cysts and only 15.3% of E. granulosus s.s cysts. In conclusion, we provide evidence of differences in clinical aspects of CE caused by E. granulosus s.s. and the G6 genotype of E. granulosus s.l. complex infecting humans.
Assuntos
Cistos , Equinococose , Echinococcus granulosus , Animais , Humanos , Masculino , Feminino , Echinococcus granulosus/genética , Argentina/epidemiologia , Equinococose/epidemiologia , Equinococose/veterinária , Genótipo , Cabras , CamelusRESUMO
BACKGROUND: Antioxidants are chemicals used to protect foods from deterioration by neutralizing free radicals and inhibiting the oxidative process. One approach to investigate the antioxidant activity is to develop quantitative structure-activity relationships (QSARs). RESULTS: A curated database of 165 structurally heterogeneous phenolic compounds with the Trolox equivalent antioxidant capacity (TEAC) was developed. Molecular geometries were optimized by means of the GFN2-xTB semiempirical method and diverse molecular descriptors were obtained afterwards. For model development, V-WSP unsupervised variable reduction was used before performing the genetic algorithms-variable subset selection (GAs-VSS) to construct the best five-descriptor multiple linear regression model. The coefficient of determination and the root mean square error were used to measure the performance in calibration (R2 = 0.789 and RMSEC = 0.381), and test set prediction (Q2 = 0.748 and RMSEP = 0.416), along several cross-validation criteria. To thoroughly understand the TEAC prediction, a fully explained mechanism of action of the descriptors is provided. In addition, the applicability domain of the model defined a theoretical chemical space for reliable predictions of new phenolic compounds. CONCLUSION: This in silico model conforms to the five principles stated by the Organisation for Economic Co-operation and Development. The model might be useful for virtual screening of the antioxidant chemical space and for identifying the most potent molecules related to an experimental measurement of TEAC activity. In addition, the model could assist chemists working on computer-aided drug design for the synthesis of new targets with improved activity and potential uses in food science. © 2023 Society of Chemical Industry.
Assuntos
Antioxidantes , Quimioinformática , Antioxidantes/química , Relação Quantitativa Estrutura-Atividade , Análise Multivariada , Radicais Livres , FenóisRESUMO
We report a case of Dirofilaria immitis nematode infection in a dog imported from Venezuela that had been living for 2 years in Santiago, Chile, where this parasite had not been reported before. Our findings warrant surveillance for all dogs imported to Chile, given that suitable conditions exist for establishing this parasite.
Assuntos
Dirofilaria immitis , Dirofilaria repens , Dirofilariose , Doenças do Cão , Animais , Cães , Dirofilariose/diagnóstico , Dirofilariose/epidemiologia , Dirofilariose/parasitologia , Chile/epidemiologia , Venezuela/epidemiologia , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologiaRESUMO
Climate change, competent vectors, and reservoir animals are the main factors for developing vector-borne zoonotic diseases. These diseases encompass a significant and widespread category of pathogens (e.g., viruses, bacteria, protozoa, and helminths) transmitted by blood-feeding arthropods, including ticks, fleas, lice, triatomines, mosquitoes, sandflies, and blackflies. In Chile, several studies have explored the role of dogs as reservoirs of vector-borne pathogens; however, there is a lack of research investigating the presence of pathogens in arthropods. Specifically, within the order Diptera, limited knowledge exists regarding their roles as carriers of pathogens. This study aimed to examine the presence of zoonotic filarial nematodes in mosquitoes and dogs within a previously unstudied semi-rural area of Central Chile. Two hundred samples of dog blood and seven hundred and twenty-four mosquitoes were collected during 2021-2022 and studied for filarial nematodes by PCR. The prevalence of microfilaremic dogs detected by Knott's test was 7.5%, with Acanthocheilonema reconditum being the only species identified. Aedes (Ochlerotatus) albifasciatus was the most abundant mosquito species collected, and 15 out of 65 pools were positive for filarial nematodes. Among these pools, 13 tested positive for Acanthocheilonema reconditum, and two tested positive for Setaria equina through PCR. Additionally, five Culex pipiens specimens were positive for Acanthocheilonema reconditum. Despite the absence of zoonotic filarial species, these findings underscore the significance of monitoring pathogens in mosquitoes and animal hosts and continued research into the dynamics of vector-borne diseases, particularly in unexplored regions.
RESUMO
BACKGROUND: Substance use is highly prevalent among children and adolescents in Chile, and it is known how it impacts their health and social adjustment. The call for effective prevention of substance use among children adolescents has resulted in numerous school-based programs, and particularly, the Social Competence Promotion Program among Young Adolescents (SCPP-YA) has been proved to be successful for promoting social and problem-solving skills in addition to preventing substance abuse in the US population. The purpose of this study is to test the effectiveness of the Social Competence Promotion Program among Young Adolescents (SCPP-YA) in Chile ("Mi Mejor Plan"). METHODS: This is a cluster randomized controlled trial, parallel-group type, where "Mi Mejor Plan" is compared to standard school preventive curricula in control schools. A total of 10 schools and 600 adolescents are expected to be recruited and randomized with 1:1 allocation. During formative work, the SCPP-YA program was culturally adapted to Chile. The effectiveness of this program will be assessed using the European Drug Addiction Prevention Trial Questionnaire (EU-Dap), measuring substance use prevalence and risk and protective factors in baseline, post-intervention, and 4 months after the end of the intervention. DISCUSSION: The proposed study will be the first to test the effectiveness of the Social Competence Promotion Program among Young Adolescents (SCPP-YA) in Chile in a cluster randomized control trial and also the first study evaluating this program in Spanish-speaking Latin America. SCPP-YA has been implemented successfully in the USA. Thus, if the effects of the program are positive, wide implementation in Chile and Latin American countries is possible soon. TRIAL REGISTRATION: Clinical Trials NCT04236947 . Registered on January 22, 2020.
Assuntos
Habilidades Sociais , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Criança , Chile , Humanos , Avaliação de Programas e Projetos de Saúde , Ensaios Clínicos Controlados Aleatórios como Assunto , Serviços de Saúde Escolar , Instituições Acadêmicas , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle , Inquéritos e QuestionáriosRESUMO
The purpose of this work is the creation of a chemical database named ChemTastesDB that includes both organic and inorganic tastants. The creation, curation pipeline and the main features of the database are described in detail. The database includes 2944 verified and curated compounds divided into nine classes, which comprise the five basic tastes (sweet, bitter, umami sour and salty) along with four additional categories: tasteless, non-sweet, multitaste and miscellaneous. ChemTastesDB provides the following information for each tastant: name, PubChem CID, CAS registry number, canonical SMILES, class taste and references to the scientific sources from which data were retrieved. The molecular structure in the HyperChem (.hin) format of each chemical is also made available. In addition, molecular fingerprints were used for characterizing and analyzing the chemical space of tastants by means of unsupervised machine learning. ChemTastesDB constitutes a useful tool to the scientific community to expand the information of taste molecules and to assist in silico studies for the taste prediction of unevaluated and as yet unsynthetized compounds, as well as the analysis of the relationships between molecular structure and taste. The database is freely accessible at https://doi.org/10.5281/zenodo.5747393.
RESUMO
Pro-social behavior is crucial to the sustainable governance of common-pool resources such as fisheries. Here, we investigate how key socioeconomic characteristics influence fishers' pro-social and bargaining behavior in three types of experimental economic games (public goods, trust, and trade) conducted in fishing associations in Chile. Our games revealed high levels of cooperation in the public goods game, a high degree of trust, and that sellers rather than buyers had more bargaining power, yet these results were strongly influenced by participants' socioeconomic characteristics. Specifically, gender, having a secondary income source, age, and being the main income provider for the household all had a relationship to multiple game outcomes. Our results highlight that engagement in pro-social behaviors such as trust and cooperation can be influenced by people's socioeconomic context.
RESUMO
OBJECTIVE: To characterise community mental health consultations in a primary care centre in Cali, Colombia. METHODS: Observational, descriptive, cross-sectional study. A secondary database was used, systematically recording patients seen in the community outpatient clinic, and a description of the information recorded therein was prepared. All the records available in the database were used. The data were processed using Microsoft Excel and the program SPSS 25 was used for the statistical analysis. RESULTS: 481 consultations were conducted, of which 272 were first time consultations; in total 383 patients were seen, which indicates that 1.26 consultations were carried out per patient. The average age of the patients who consulted was 43.5±21.7 years. Sixty-one point five percent of the consultations were for women, while adulthood was the stage of life in which the highest percentage (51.8%) attended. The most common socioeconomic stratum was 1, which indicates that this institution serves above all the low-income population. CONCLUSIONS: The results of this study allowed us to recognise the main reasons for consultation in the community mental health service, a necessary input to design and develop preventive programmes that promote and strengthen community-based rehabilitation strategies.
RESUMO
Viable eggs of the canine intestinal tapeworm Echinococcus granulosus sensu lato (s.l.) infect various intermediate hosts causing cystic echinococcosis (CE). Furthermore, CE represents a serious zoonosis causing a significant global burden of disease. CE is highly endemic in South America, including Argentina, Brazil, Chile, Uruguay, and Peru. For Bolivia, no official data concerning the incidence in humans or the number of livestock and dogs infected are available. However, it is well known that CE occurs in Bolivia. We aim here to fill the gap in the current knowledge of the epidemiological situation of CE in Bolivia, providing a historical overview of documents published within the country, which have never been comprehensively reviewed. The very first documentation of E. granulosus infection in animals dates in 1910, while the first human case was reported in 1913. In total, 876 human CE cases have been reported in the scientific literature, with an apparent increase since the 1970s. In the absence of other epidemiological studies, the highest prevalence in human comes from Tupiza, Potosí Department, where 4.1% (51/1,268) of the population showed signs of CE at mass ultrasound screening in 2011. In the same report, 24% of dog faecal samples were positive for coproantigens of E. granulosus s.l. in ELISA. The highest prevalence in intermediate hosts reported at abattoir reached 37.5% in cattle from Potosí, followed by 26.9% in llamas from Oruro, 2.4% in pigs and 1.4% in sheep from La Paz. Finally, Echinococcus granulosus sensu stricto (s.s.), Echinococcus ortleppi (G5), and Echinococcus intermedius (G7) have been identified in Bolivia. Data reviewed here confirm that E. granulosus s.l. is circulating in Bolivia and that a proper prospective nationwide epidemiological study of CE is urgently needed to define transmission patterns as a basis for the planning and implementation of future control measurements.
Assuntos
Equinococose/veterinária , Echinococcus granulosus/genética , Zoonoses/parasitologia , Animais , Bolívia/epidemiologia , Equinococose/epidemiologia , Humanos , Vigilância da População , Zoonoses/epidemiologiaRESUMO
Actualmente hay una alta incidencia de accidentes de tránsito en el mundo, muchos de ellos provocan una discapacidad grave en las personas. Estas lesiones en las extremidades provocan alta morbilidad llegando incluso a una amputación. Esto se agrava en pacientes VIH/SIDA, sobre todo en el tratamiento y la evolución. Se presenta un caso clínico de un paciente con lesión severa del mediopie que termina en amputación y se hace una revisión del manejo quirúrgico del paciente traumatológico con VIH/SIDA
Currently there is a high incidence of traffic accidents in the world, many of them cause severe disability in people. These limb injuries cause high morbidity even reaching an amputation. This is aggravated in HIV/AIDS patients, especially in treatment and evolution. A clinical case of a patient with severe midfoot injury that ends in amputation is presented and a surgical management review of the trauma patient with HIV/AIDS is made.
RESUMO
Cystic echinococcosis is a disease that affects both humans and animals, caused by cryptic species complex belonging to the platyhelminth Echinococcus granulosus sensu lato (s.l.). This disease is distributed worldwide, with E. granulosus sensu stricto (s.s.) being the most widespread of the species. High genetic variability has been demonstrated within E. granulosus s.s. studying single cyst per infected animal identifying a number of different haplotypes. However, few studies have addressed the genetic diversity of this parasite within a single intermediate host with multiple Echinococcus cysts. To date, it remains unknown if specific haplotypes of E. granulosus s.s. produce differences in biological features of the cyst. Here, we use the full length of the mitochondrial gene cox1 to determine E. granulosus s.s. haplotypes in samples from both cattle and sheep which harboured more than one cyst in different areas in Chile, where this parasite is endemic. We found 16 different haplotypes in 66 echinococcal cysts from 10 animals, and both cattle and sheep can harbour up to five different haplotypes of E. granulosus s.s. in the same animal. Regarding cyst fertility, five animals had both fertile and infertile Echinococcus cysts in both single and multiple haplotype infections. There was no association between haplotype and cyst fertility, size, or adventitial layer characteristics. Sampling and sequencing every Echinococcus cyst found in the intermediate host reveals a high molecular variability. We speculate that multiple haplotype infections could also suggest that intermediate hosts come from hyperendemic areas.
Assuntos
Doenças dos Bovinos/parasitologia , Equinococose/veterinária , Echinococcus granulosus/classificação , Doenças dos Ovinos/parasitologia , Animais , Bovinos , Chile , Ciclo-Oxigenase 1/genética , Equinococose/parasitologia , Echinococcus granulosus/genética , Echinococcus granulosus/isolamento & purificação , Fertilidade , Genes Mitocondriais/genética , Variação Genética/genética , Genótipo , Haplótipos , Humanos , Ovinos/genéticaRESUMO
The aim of this work was the foodinformatic (chemoinformatic) modeling of volatile organic compounds (VOCs) of different samples of peppers based on a quantitative structure-property relationship (QSPR) for the retention indices of 273 identified compounds. The experimental retention indices were measured by means of comprehensive two-dimensional gas chromatography combined with quadrupole-mass spectrometry (GC × GC/qMS) using the BPX5 and BP20 column coupled system. All the VOCs were represented by means of both conformation-independent molecular descriptors and molecular fingerprints calculated in the Dragon and PaDEL-Descriptor software. The dataset was divided into training, validation and test sets of molecules according to the Balanced Subsets Method (BSM). Subsequently, the V-WSP unsupervised variable reduction method was used to reduce the presence of multicollinearity, redundancy, and noise in the initial pool of 4,336 molecular descriptors and fingerprints. Using this method, a reduced pool of 1,664 was submitted to the supervised selection by means of the replacement method (RM) variable subset selection in order to define a four-descriptor model. The quality of the model was measured by means of the coefficient of determination and the root-mean-square deviation in fitting ( R train 2 = 0 . 879 and RMSD train = 72.1 ), validation ( R val 2 = 0 . 832 and RMSD val = 91.7 ), and prediction ( R test 2 = 0 . 915 and RMSD test = 55.4 ). The negligible differences among the parameters in the three sets indicate a stable and predictive QSPR model. This quantitative structure-activity relationship was developed keeping in mind the five principles defined by the Organization for Economic Co-operation and Development (OECD) to make it applicable. PRACTICAL APPLICATION: This predictive mathematical model developed from the retention indices of 273 volatile organic compounds (VOCs) detected in pepper samples could be useful for chromatographers working on the identification of other common VOCs in peppers or other foods by means of comprehensive two-dimensional gas chromatography combined with quadrupole-mass spectrometry (GC × GC/qMS) using a bi-dimensional stationary phase coupled system (BPX5 and BP20).
Assuntos
Capsicum/química , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química , Cromatografia Gasosa-Espectrometria de Massas , Relação Quantitativa Estrutura-AtividadeRESUMO
BACKGROUND: The most common infusion in southern Latin-American countries is prepared with dried leaves of Ilex paraguariensis A. St.-Hil., an aboriginal ancestral beverage known for its high polyphenols concentration currently consumed in > 90% of homes in Argentina, in Paraguay and Uruguay. The economy of entire provinces heavily relies on the production, collection and manufacture of Ilex paraguariensis, the fifth plant species with highest antioxidant activity. Polyphenols are associated to relevant health benefits including strong antioxidant properties. Despite its regional relevance and potential biotechnological applications, little is known about functional genomics and genetics underlying phenotypic variation of relevant traits. By generating tissue specific transcriptomic profiles, we aimed to comprehensively annotate genes in the Ilex paraguariensis phenylpropanoid pathway and to evaluate differential expression profiles. RESULTS: In this study we generated a reliable transcriptome assembly based on a collection of 15 RNA-Seq libraries from different tissues of Ilex paraguariensis. A total of 554 million RNA-Seq reads were assembled into 193,897 transcripts, where 24,612 annotated full-length transcripts had complete ORF. We assessed the transcriptome assembly quality, completeness and accuracy using BUSCO and TransRate; consistency was also evaluated by experimentally validating 11 predicted genes by PCR and sequencing. Functional annotation against KEGG Pathway database identified 1395 unigenes involved in biosynthesis of secondary metabolites, 531 annotated transcripts corresponded to the phenylpropanoid pathway. The top 30 differentially expressed genes among tissue revealed genes involved in photosynthesis and stress response. These significant differences were then validated by qRT-PCR. CONCLUSIONS: Our study is the first to provide data from whole genome gene expression profiles in different Ilex paraguariensis tissues, experimentally validating in-silico predicted genes key to the phenylpropanoid (antioxidant) pathway. Our results provide essential genomic data of potential use in breeding programs for polyphenol content. Further studies are necessary to assess if the observed expression variation in the phenylpropanoid pathway annotated genes is related to variations in leaves' polyphenol content at the population scale. These results set the current reference for Ilex paraguariensis genomic studies and provide a substantial contribution to research and biotechnological applications of phenylpropanoid secondary metabolites.
Assuntos
Genoma de Planta , Ilex paraguariensis/genética , Especificidade de Órgãos/genética , Análise de Sequência de RNA/métodos , Transcriptoma/genética , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Genes de Plantas , Anotação de Sequência Molecular , Folhas de Planta/genética , Raízes de Plantas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Metabolismo Secundário/genéticaRESUMO
BACKGROUND: Local classification models were used to establish Quantitative Structure- Activity Relationships (QSARs) of bioactive di-, tri- and tetrapeptides, with their capacity to inhibit Angiotensin Converting Enzyme (ACE). These discrete models can thus predict this activity for other peptides obtained from functional foods. These types of peptides allow some foods to be considered nutraceuticals. METHOD: A database of 313 molecules of di-, tri- and tetrapeptides was investigated and antihypertensive activities of peptides, expressed as log (1/IC50), were separated into two qualitative classes: low activity (inactive) was associated with experimental values under the 66th percentile and active peptides with values above this threshold. Chemicals were divided into a training set, including 70% of the peptides, and a test set for external validation. Genetic algorithms-variable subset selection coupled with the kNN and N3 local classifiers were applied to select the best subset of molecular descriptors from a pool of 953 Dragon descriptors. Both models were validated on the test peptides. RESULTS: The N3 model turned out to be superior to the kNN model when the classification focused on identifying the most active peptides.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Oligopeptídeos/química , Oligopeptídeos/farmacologia , Peptidil Dipeptidase A/metabolismo , Relação Quantitativa Estrutura-Atividade , Bases de Dados de Proteínas , Concentração Inibidora 50 , Modelos EstatísticosRESUMO
Cystic echinococcosis (CE), a parasitic disease caused by the cestode Echinococcus granulosus sensu lato (s.l.), is a worldwide zoonotic infection. Although endemic in Chile, information on the molecular characteristics of CE in livestock remains scarce. Therefore we aimed to describe the status of infection with E. granulosus s.l. in cattle from central Chile and also to contribute to the study of the molecular epidemiology of this parasite. According to our results, the prevalence of CE is 18.84% in cattle, similar to previous reports from Chile, suggesting that the prevalence in Santiago Metropolitan area has not changed in the last 30 years. Most of the cysts were found only in lungs (51%), followed by concurrent infection in liver and lungs (30%), and only liver (19%). Molecular characterization of the genetic diversity and population structure of E. granulosus s.l. from cattle in central Chile was performed using a section of the cytochrome c oxidase subunit 1 (cox1) mitochondrial gene. E. granulosus sensu stricto (s.s.) (G1-G3 genotypes) was confirmed by RFLP-PCR to be the dominant species affecting cattle (284 samples/290 samples); we also report for the first time in Chile the presence of E. ortleppi (G5 genotype) (2 samples/61 samples). The Chilean E. granulosus s.s. parsimony network displayed 1 main haplotype. Additional studies using isolates from many locations across Chile and different intermediate hosts will provide more data on the molecular structure of E. granulosus s.s. within this region. Likewise, investigations of the importance of E. ortleppi in human infection in Chile deserve future attention.
Assuntos
Doenças dos Bovinos/parasitologia , Equinococose/veterinária , Echinococcus/isolamento & purificação , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Chile/epidemiologia , DNA de Helmintos/análise , Equinococose/epidemiologia , Equinococose/parasitologia , Echinococcus/classificação , Echinococcus/fisiologia , Feminino , Fertilidade , Genes de Helmintos , Genes Mitocondriais , Haplótipos , Masculino , Mutação , Especificidade de Órgãos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prevalência , Alinhamento de SequênciaRESUMO
This work describes a novel approach based on advanced molecular similarity to predict the sweetness of chemicals. The proposed Quantitative Structure-Taste Relationship (QSTR) model is an expert system developed keeping in mind the five principles defined by the Organization for Economic Co-operation and Development (OECD) for the validation of (Q)SARs. The 649 sweet and non-sweet molecules were described by both conformation-independent extended-connectivity fingerprints (ECFPs) and molecular descriptors. In particular, the molecular similarity in the ECFPs space showed a clear association with molecular taste and it was exploited for model development. Molecules laying in the subspaces where the taste assignation was more difficult were modeled trough a consensus between linear and local approaches (Partial Least Squares-Discriminant Analysis and N-nearest-neighbor classifier). The expert system, which was thoroughly validated through a Monte Carlo procedure and an external set, gave satisfactory results in comparison with the state-of-the-art models. Moreover, the QSTR model can be leveraged into a greater understanding of the relationship between molecular structure and sweetness, and into the design of novel sweeteners.