RESUMO
OBJECTIVES: During the Coronavirus disease (COVID-19) pandemic, clinicians recommended awake-prone positioning (APP) to avoid the worst outcomes. The objectives of this study were to investigate if APP reduces intubation, death rates, and hospital length of stay (HLOS) in acute COVID-19. METHODS: We performed a retrospective cohort with non-mechanically ventilated patients hospitalized in a reference center in Manaus, Brazil, 2020. Participants were stratified into APP and awake-not-prone positioning (ANPP) groups. Also, we conducted a systematic review and performed a meta-analysis to understand if this intervention had different outcomes in resource-limited settings (PROSPERO CRD42023422452). RESULTS: A total of 115 participants were allocated into the groups. There was no statistical difference between both groups regarding time to intubation (HR: 0.861; 95CI: 0.474-1.1562; p=0.622) and time to death (HR: 1.666; 95CI: 0.939-2.951; p=0.081). APP was not significantly associated with reduced HLOS. A total of 86 articles were included in the systematic review, of which 76 (88,3%) show similar findings after APP. Also, low/middle, and high-income countries were similar regarding such outcomes. CONCLUSION: APP in COVID-19 does not present clinical improvement that affects mortality, intubation rate and HLOS. The lack of a prone position protocol, obtained through a controlled study, is necessary. After 3 years, APP benefits are still inconclusive.
Assuntos
COVID-19 , Posicionamento do Paciente , Humanos , COVID-19/mortalidade , COVID-19/terapia , Decúbito Ventral , Estudos Retrospectivos , Posicionamento do Paciente/métodos , Masculino , Tempo de Internação/estatística & dados numéricos , Pessoa de Meia-Idade , Feminino , Idoso , Vigília , Brasil/epidemiologia , Intubação Intratraqueal/estatística & dados numéricos , SARS-CoV-2 , Resultado do Tratamento , Respiração ArtificialRESUMO
Abstract Objectives: To determine the cut-off point of the cochlear radiation dose as a risk factor for hearing loss in patients with vestibular schwannoma treated with radiosurgery. Methods: A systematic review of the literature was performed without language or publication year restrictions in the MEDLINE/PubMed, EMBASE, Web of Science, LILACS/VHL and Cochrane Library databases. Studies that met the following criteria were included: 1) population: adults of both sexes who underwent radiosurgery for vestibular schwannoma treatment; 2) exposure: cochlear radiation; 3) outcome: hearing loss; 4) type of study: cohort. Two independent reviewers conducted the entire review process. The registration number in PROSPERO was CRD42020206128. Results: From the 333 articles identified in the searches, seven were included after applying the eligibility criteria. There was no standardization as to how to measure exposure or outcome in the included studies, and most studies did not present sufficient data to enable meta-analysis. Conclusion: It was not possible to determine a cut-off point for high cochlear dose that could be considered a risk factor for hearing loss.
RESUMO
OBJECTIVES: To determine the cut-off point of the cochlear radiation dose as a risk factor for hearing loss in patients with vestibular schwannoma treated with radiosurgery. METHODS: A systematic review of the literature was performed without language or publication year restrictions in the MEDLINE/PubMed, EMBASE, Web of Science, LILACS/VHL and Cochrane Library databases. Studies that met the following criteria were included: 1) population: adults of both sexes who underwent radiosurgery for vestibular schwannoma treatment; 2) exposure: cochlear radiation; 3) outcome: hearing loss; 4) type of study: cohort. Two independent reviewers conducted the entire review process. The registration number in PROSPERO was CRD42020206128. RESULTS: From the 333 articles identified in the searches, seven were included after applying the eligibility criteria. There was no standardization as to how to measure exposure or outcome in the included studies, and most studies did not present sufficient data to enable meta-analysis. CONCLUSION: It was not possible to determine a cut-off point for high cochlear dose that could be considered a risk factor for hearing loss.
Assuntos
Surdez , Perda Auditiva , Neuroma Acústico , Radiocirurgia , Adulto , Feminino , Humanos , Masculino , Surdez/cirurgia , Perda Auditiva/etiologia , Perda Auditiva/cirurgia , Neuroma Acústico/radioterapia , Neuroma Acústico/cirurgia , Neuroma Acústico/complicações , Doses de Radiação , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Individuals with sickle cell disease (SCD) often experience numerous vaso-occlusive crisis events throughout their lives, which can progress to severe damage of several organs, including avascular necrosis, also known as osteonecrosis (ON). Osteonecrosis is one of the most devastating musculoskeletal clinical manifestations of sickle cell disease, afflicting up to 50% of the SCD patients. Herein, a NMR-based untargeted metabolomics approach was used to assess the metabolome alterations of blood plasma and bone marrow interstitial fluid (BMIF) samples of SCD patients with osteonecrosis. Furthermore, biochemical signatures associated with different osteonecrosis stages were assessed by analysing the metabolome of blood plasma and bone marrow interstitial fluid samples of SCD patients with different stages of the disease based on the Fiat and Arlet classification (FAC). Multivariate statistical analysis allowed a clear discrimination between the studied groups and it provided important insights into the different osteonecrosis stages. Citrate was pointed out as a possible biomarker to differentiate SCD patients with and without osteonecrosis. Acetate, creatinine, histidine, tyrosine, glucose, and NI5 seems to be key metabolites associated to different stages of the disease. Although this is a pioneer exploratory study, we acknowledge that fact that it is limited by the group sizes and absence of a validation cohort. Nevertheless, multivariate statistical analyses indicated that the metabolome of blood plasma and BMIF samples encompasses a complex metabolic regulation system for osteonecrosis.
Assuntos
Anemia Falciforme , Osteonecrose , Humanos , Líquido Extracelular , Medula Óssea , Metabolômica , PlasmaRESUMO
The Senna genus has a wide diversity of species, with an interesting chemical composition of secondary metabolites and applications as medicine. The folk medicine, mainly in developing countries, uses species of Senna to treat seizures, epilepsy and constipation. Though the recognized bioactivity, some Brazilian native species of Senna remain unexplored, such as Senna cearensis, a native species of Caatinga. This is the first report about the bioactivity of the flowers of S. cearensis Afr. Fern., a native species of northeast Brazil. In this communication, flavonoids and catechins are identified in S. cearensis flowers and the chemical composition is linked with its antioxidant, anticholinesterase, and cytotoxic activities. By UPLC-QTOF, some compounds that belong to the class of flavonoids were identified. They are: catechin, epigallocatechin, guibourtinidol-(4α-8)-catechin, and cassiaflavan-(Cat)-epicatechin. The cytotoxic activity is more noticeable for the HL60 (leukemia) cell line with a cell growth inhibition (GI%) of 81.65 ± 5.65.
Assuntos
Antineoplásicos , Catequina , Gleiquênias , Antioxidantes/farmacologia , Antioxidantes/química , Flavonoides/farmacologia , Inibidores da Colinesterase/farmacologia , Catequina/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , FloresRESUMO
Results obtained from rat studies indicate that, even at low concentrations, mercurial species cause harmful effects on the kidneys, by inducing the nephrotic oxidative stress response. In the present work, Hg-associated proteins were identified as possible mercury-exposure biomarkers in rat kidneys exposed to low mercury chloride concentrations for 30 days (Hg-30) and 60 days (Hg-60), using metalloproteomic strategies. The renal proteomic profile was fractioned by two-dimensional electrophoresis and the mercury determinations in kidney samples, protein pellets and protein spots were performed using graphite furnace atomic absorption spectrometry. The characterization of Hg-associated protein spots and the analysis of differentially expressed proteins were performed by liquid chromatography, coupled with tandem mass spectrometry. Eleven Hg-associated protein spots with a concentration range of 79 ± 1 to 750 ± 9 mg kg-1 in the Hg-60 group were identified. The characterization and expression analyses allowed the identification of 53 proteins that were expressed only in the Hg-60 group, 13 "upregulated" proteins (p > 0.95) and 47 "downregulated" proteins (p < 0.05). Actin isoforms and hemoglobin subunits were identified in protein spots of the Hg-60 group, with mercury concentrations in the range of 138 to 750 mg kg-1, which qualifies these proteins as potential mercury-exposure biomarkers.
Assuntos
Desequilíbrio Ácido-Base , Mercúrio , Animais , Ratos , Proteínas de Transporte , Cloretos , Proteômica , Cloreto de Mercúrio/toxicidade , Mercúrio/toxicidade , BiomarcadoresRESUMO
The transport of substrates across the cell membrane plays an essential role in nutrient assimilation by yeasts. The establishment of an efficient microbial cell factory, based on the maximum use of available carbon sources, can generate new technologies that allow the full use of lignocellulosic constituents. These technologies are of interest because they could promote the formation of added-value products with economic feasibility. In silico analyses were performed to investigate gene sequences capable of encoding xylose transporter proteins in the Candida tropicalis genome. The current study identified 11 putative transport proteins that have not yet been functionally characterized. A phylogenetic tree highlighted the potential C. tropicalis xylose-transporter proteins CtXUT1, CtXUT4, CtSTL1, CtSTL2, and CtGXT2, which were homologous to previously characterized and reported xylose transporters. Their expression was quantified through real-time qPCR at defined times, determined through a kinetic analysis of the microbial growth curve in the absence/presence of glucose supplemented with xylose as the main carbon source. The results indicated different mRNA expression levels for each gene. CtXUT1 mRNA expression was only found in the absence of glucose in the medium. Maximum CtXUT1 expression was observed in intervals of the highest xylose consumption (21 to 36 h) that corresponded to consumption rates of 1.02 and 0.82 g/L/h in the formulated media, with xylose as the only carbon source and with glucose addition. These observations indicate that CtXUT1 is an important xylose transporter in C. tropicalis. KEY POINTS: ⢠Putative xylose transporter proteins were identified in Candida tropicalis; ⢠The glucose concentration in the cultivation medium plays a key role in xylose transporter regulation; ⢠The transporter gene CtXUT1 has an important role in xylose consumption by Candida tropicalis.
Assuntos
Candida tropicalis , Xilose , Candida tropicalis/genética , Candida tropicalis/metabolismo , Carbono/metabolismo , Proteínas de Transporte/genética , Biologia Computacional , Fermentação , Expressão Gênica , Glucose/metabolismo , Cinética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Pentoses/metabolismo , Filogenia , RNA Mensageiro/metabolismo , Xilitol , Xilose/metabolismoRESUMO
Embryo development in eggs of the spittlebug Mahanarva spectabilis (Distant) (Hemiptera: Cercopidae) passes through four phases (known as S1 to S4) being stopped at S2 during diapause. Studies about the molecular basis of diapause in spittlebugs are nonexistent. Here, we analyzed proteins from non-diapausing (ND), diapausing (D) and post-diapausing (PD) eggs of the spittlebug M. spectabilis. In total, we identified 87 proteins where 12 were in common among the developmental and diapause phases and 19 remained as uncharacterized. Non-diapausing eggs (S2ND and S4ND) showed more proteins involved in information storage and processing than the diapausing ones (S2D). Eggs in post-diapausing (S4PD) had a higher number of proteins associated with metabolism than S2D. The network of protein interactions and metabolic processes allowed the identification of different sets of molecular interactions for each developmental and diapause phases. Two heat shock proteins (Hsp65 and Hsp70) along with two proteins associated with intracellular signaling (MAP4K and a serine/threonine-protein phosphatase) were found only in diapausing and/or post-diapausing eggs and are interesting targets to be explored in future experiments. These results shine a light on one key biological process for spittlebug survival and represent the first search for proteins linked to diapause in this important group of insects.
Assuntos
Diapausa de Inseto , Diapausa , Hemípteros , Animais , Hemípteros/fisiologiaRESUMO
Emerging environmental contaminants, such as medicine waste, are of great concern to the scientific community and to the local environmental and health departments because of their potential long-term effects and ecotoxicological risk. Besides the prolonged use of medicines for the development of modern society, the elucidation of their effect on the ecosystem is relatively recent. Medicine waste and its metabolites can, for instance, cause alterations in microbial dynamics and disturb fish behavior. Bioremediation is an efficient and eco-friendly technology that appears as a suitable alternative to conventional methods of water waste and sludge treatment and has the capacity to remove or reduce the presence of emerging contaminants. Thus, this review has the objective of compiling information on environmental contamination by common medicines and their microbial biodegradation, focusing on five therapeutic classes: analgesics, antibiotics, antidepressants, non-steroidal anti-inflammatory drugs (NSAIDs), and contraceptives. Their effects in the environment will also be analyzed, as well as the possible routes of degradation by microorganisms.
Assuntos
Ecossistema , Esgotos , Animais , Biodegradação AmbientalRESUMO
In this study, we investigated the phenolic and antioxidant content, cytotoxic, and anticholinesterase activities of flower extracts of Senna spectabilis var. excelsa and Senna macranthera. The antioxidant activities performed by the DPPH and ABTS methods showed that the extracts possess good antioxidant activity, with emphasis on the S. macranthera extract, which obtained results very similar to the rutin pattern. In the evaluation of the cytotoxic activity, the species S. spectabilis var. excelsa presented expressive cytotoxicity against the cellular lines PC3 and HL60 with IC50 values 21.08 and 31.37 µg mL-1, respectively. The results of anticholinesterase activity showed that both the plants induced enzyme inhibition, reaching 14 mm of inhibition in the case of S. spectabilis var. excelsa. The good results obtained in this work may be related to the presence of compounds such as apigenin-7-apioglucoside, quercetin 3,4'-diglucoside, cassine and spectaline identified in the extracts in our previous work.
Assuntos
Antineoplásicos , Senna , Antioxidantes/química , Antioxidantes/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Flores , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Senna/químicaRESUMO
An analytical procedure for the multielement determination in enteral nutrition formulations employing slurry sampling and inductively coupled plasma optical emission spectrometry (ICP OES) is proposed. A two-level full-factorial design was applied to assess the influence of the presence of stabilizing agents (HNO3, Triton X-100 and ethanol) on the composition of the slurry. Multiple response was established as a dependent variable. The experimental conditions for the preparation of the slurry were: 2.0 mL of sample and 8.0 mL of 10% (v/v) HNO3. The limits of detection (LOD) were 5; 9; and 10 µg L-1 for Cu, Fe, Zn, respectively. For P, and K, the LOD were 8 and 24 mg L-1, respectively. The method was applied for the analysis of three enteral nutrition formulation samples and the obtained concentrations ranges were (in mg L-1): 0.41-0.43 (Cu), 2.0-2.9 (Fe), 1.7-3.1 (Zn), 682-1409 (K), and 217-344 (P).
Assuntos
Nutrição Enteral , Limite de Detecção , Análise EspectralRESUMO
This study presents a novel approach to use claw disorders in cattle as a retrospective welfare indicator characterized at the abattoir. A total of 1040 cattle (2080 front and back left claws) were analyzed from 143 batches, originating from feedlots, free-range, and dairy systems. Our results indicate that abnormal claw shapes (>55%) and fissures of the claw wall (>25%) had the highest prevalence, regardless of the system of origin. For the seven types of lesions monitored, numerous associations were found between lesions in the front and rear limbs typical of each production system. Ultimate meat pH was higher in animals with white line disease and skin wounds in feedlot and free-range cattle. We conclude that claw disorders can be used as an iceberg indicator to provide valuable information about animal fitness, and the ability to cope with the husbandry and pre-slaughter environment. These indicators can be used to improve the level of welfare of the animals.
Assuntos
Criação de Animais Domésticos/métodos , Bem-Estar do Animal , Casco e Garras/patologia , Músculo Esquelético/química , Matadouros , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Feminino , Doenças do Pé/epidemiologia , Doenças do Pé/veterinária , Concentração de Íons de Hidrogênio , Masculino , México , Estudos Retrospectivos , Pele/lesõesRESUMO
Sickle cell anaemia (SCA) is a debilitating genetic haemoglobinopathy predominantly affecting the disenfranchised strata of society in Africa and the Americas. The most common pharmacological treatment for this disease is the administration of hydroxycarbamide (HC) for which questions remain regarding its mechanism of action, efficacy and long-term toxicity specifically in paediatric individuals. A multiplatform metabolomics approach was used to assess the metabolome of plasma samples from a population of children and adolescents with SCA with and without HC treatment along with non-SCA individuals. Fifty-three metabolites were identified by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and 1 H nuclear magnetic resonance (NMR) with a predominance of membrane lipids, amino acids and organic acids. The partial least-squares discriminant analysis (PLS-DA) analysis allowed a clear discrimination between the different studied groups, revealing clear effects of the HC treatment in the patients' metabolome including rescue of specific metabolites to control levels. Increased creatine/creatinine levels under HC treatment suggests a possible increase in the arginine pool and increased NO synthesis, supporting existing models for HC action in SCA. The metabolomics results extend the current knowledge on the models for SCA pathophysiology including impairment of Lands' cycle and increased synthesis of sphingosine 1-phosphate. Putative novel biomarkers are suggested.
Assuntos
Anemia Falciforme/sangue , Antidrepanocíticos/uso terapêutico , Hidroxiureia/uso terapêutico , Metabolômica , Ácidos/sangue , Síndrome Torácica Aguda/etiologia , Adolescente , Aminoácidos/sangue , Anemia Falciforme/complicações , Anemia Falciforme/tratamento farmacológico , Antidrepanocíticos/farmacologia , Arteriopatias Oclusivas/etiologia , Biomarcadores , Butiratos/sangue , Criança , Cromatografia Líquida de Alta Pressão , Creatina/sangue , Creatinina/sangue , Feminino , Humanos , Hidroxiureia/farmacologia , Lisofosfolipídeos/sangue , Masculino , Espectrometria de Massas , Lipídeos de Membrana/sangue , Modelos Biológicos , Ressonância Magnética Nuclear Biomolecular , Esfingosina/análogos & derivados , Esfingosina/sangueRESUMO
BACKGROUND: Protein-peptide interactions play a fundamental role in a wide variety of biological processes, such as cell signaling, regulatory networks, immune responses, and enzyme inhibition. Peptides are characterized by low toxicity and small interface areas; therefore, they are good targets for therapeutic strategies, rational drug planning and protein inhibition. Approximately 10% of the ethical pharmaceutical market is protein/peptide-based. Furthermore, it is estimated that 40% of protein interactions are mediated by peptides. Despite the fast increase in the volume of biological data, particularly on sequences and structures, there remains a lack of broad and comprehensive protein-peptide databases and tools that allow the retrieval, characterization and understanding of protein-peptide recognition and consequently support peptide design. RESULTS: We introduce Propedia, a comprehensive and up-to-date database with a web interface that permits clustering, searching and visualizing of protein-peptide complexes according to varied criteria. Propedia comprises over 19,000 high-resolution structures from the Protein Data Bank including structural and sequence information from protein-peptide complexes. The main advantage of Propedia over other peptide databases is that it allows a more comprehensive analysis of similarity and redundancy. It was constructed based on a hybrid clustering algorithm that compares and groups peptides by sequences, interface structures and binding sites. Propedia is available through a graphical, user-friendly and functional interface where users can retrieve, and analyze complexes and download each search data set. We performed case studies and verified that the utility of Propedia scores to rank promissing interacting peptides. In a study involving predicting peptides to inhibit SARS-CoV-2 main protease, we showed that Propedia scores related to similarity between different peptide complexes with SARS-CoV-2 main protease are in agreement with molecular dynamics free energy calculation. CONCLUSIONS: Propedia is a database and tool to support structure-based rational design of peptides for special purposes. Protein-peptide interactions can be useful to predict, classifying and scoring complexes or for designing new molecules as well. Propedia is up-to-date as a ready-to-use webserver with a friendly and resourceful interface and is available at: https://bioinfo.dcc.ufmg.br/propedia.
Assuntos
Sistemas de Gerenciamento de Base de Dados , Bases de Dados de Proteínas , Peptídeos/química , Proteínas/química , Algoritmos , HumanosRESUMO
Insect pests such as Anticarsia gemmatalis cause defoliation and yield losses. Soybean breeding has obtained resistant genotypes, however the mechanism remains unknown. Studies indicated the presence of deterrents compounds in the resistant genotype IAC17, and their leaf metabolite profiles were compared to the susceptible genotype UFV105, which was elicited or not by caterpillar infestation. Cluster analysis indicated a significative distinction between these profiles as well as differences in plant defense pathways. Methylquercetins were constitutively present in the largest concentrations, specifically in the IAC17. Relationship between the resistance and the levels of phytohormones jasmonic acid, abscisic acid and salicylic acid was not observed. However, 1-aminocyclopropane -1carboxylic acid levels indicated that the ethylene may be involved in the constitutive biosynthesis of bioactive compounds. Extracts were added to the diets at three different concentrations to evaluate the effect on caterpillar survival. Lowest survival rates were observed when extracts from the resistant IAC 17 were used, at the lowest concentrations. Survival rates were not higher when IAC 17 infested by caterpillars were used. On the other hand, when extracts from the susceptible were used, the survival reductions were only observed in the highest extract concentrations. These supplementations of the diet reduced the digestive capacity, agreeing with the proteolytic activities, whereas malformations of the intestinal cells were dose dependent. The inhibitory effects persisted in higher dilutions only for the IAC17. Constitutive resistance was also explained by higher levels of protease inhibition. These results can be useful to elucidate the genes and cascades controlling the resistance.
Assuntos
Glycine max/genética , Lepidópteros/fisiologia , Metaboloma , Folhas de Planta/metabolismo , Animais , Digestão , Genótipo , Herbivoria , Larva/fisiologiaRESUMO
The objective of this study was to evaluate the Holopothrips fulvus Morgan (Thysanoptera: Phlaeothripidae) population dynamics and to identify dwarf cashew genotypes less infested by the pest in 2015 and 2016, under field conditions. H. fulvus population evaluations were carried out by monthly observations in the plants and using a score scale varying from 0 to 4. H. fulvus infestation occurred from October to December, and in the cashew genotypes CAP 112/8, CAP 121/1, CAP 131/2, CAP 145/2, CAP 145/7, CAP 128/2, CAP 120/4, CAP 123/6, CAP 130/1, and CAP 157/2 was dependent on the flowering period of the crop in 2015. In 2016, there was dependence in all evaluated genotypes between H. fulvus infestation and the cashew flowering period. In 2015, no significant differences were observed between the evaluated genotypes regarding H. fulvus infestation. In 2016, genotypes CAP 105/5, CAP 143/7, CAP 150/3, CAP 155/2, CAP 158/8, CAP 161/7, CAP 163/8, CAP 31, CAP 71, CAP 92, CAP 113, CAP 120, CAP 155, CAP 165, CAP 106/1, CAP 111/2, CAP 127/3, CAP 157/2, and BRS 226 were less infested. H. fulvus occurs from October to December and we could identify the dwarf cashew genotypes less infested by the pest.
Assuntos
Anacardium/genética , Anacardium/parasitologia , Tisanópteros/fisiologia , Animais , Genótipo , Dinâmica Populacional , Estações do AnoRESUMO
BACKGROUND: Protein-protein interactions (PPIs) are fundamental in many biological processes and understanding these interactions is key for a myriad of applications including drug development, peptide design and identification of drug targets. The biological data deluge demands efficient and scalable methods to characterize and understand protein-protein interfaces. In this paper, we present ppiGReMLIN, a graph based strategy to infer interaction patterns in a set of protein-protein complexes. Our method combines an unsupervised learning strategy with frequent subgraph mining in order to detect conserved structural arrangements (patterns) based on the physicochemical properties of atoms on protein interfaces. To assess the ability of ppiGReMLIN to point out relevant conserved substructures on protein-protein interfaces, we compared our results to experimentally determined patterns that are key for protein-protein interactions in 2 datasets of complexes, Serine-protease and BCL-2. RESULTS: ppiGReMLIN was able to detect, in an automatic fashion, conserved structural arrangements that represent highly conserved interactions at the specificity binding pocket of trypsin and trypsin-like proteins from Serine-protease dataset. Also, for the BCL-2 dataset, our method pointed out conserved arrangements that include critical residue interactions within the conserved motif LXXXXD, pivotal to the binding specificity of BH3 domains of pro-apoptotic BCL-2 proteins towards apoptotic suppressors. Quantitatively, ppiGReMLIN was able to find all of the most relevant residues described in literature for our datasets, showing precision of at least 69% up to 100% and recall of 100%. CONCLUSIONS: ppiGReMLIN was able to find highly conserved structures on the interfaces of protein-protein complexes, with minimum support value of 60%, in datasets of similar proteins. We showed that the patterns automatically detected on protein interfaces by our method are in agreement with interaction patterns described in the literature.
Assuntos
Mapeamento de Interação de Proteínas/métodos , Animais , Gráficos por Computador , Mineração de Dados , Complexos Multiproteicos/química , Proteínas Proto-Oncogênicas c-bcl-2/química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Tripsina/química , Tripsina/metabolismoRESUMO
Small mammals such as rodents can to carry zoonotic pathogens. Currently, there is impaired knowledge on zoonotic pathogens in rodents and insectivores in the Netherlands. This limits opportunities for preventive measures and complicates risk-assessments for zoonotic transmission to humans. Leptospira spp. and Toxoplasma gondii are present on a list of prioritized emerging pathogens in the Netherlands and were therefore the focus of this study. Both pathogens have the ability to survive under moist environmental conditions. In total, a group of 379 small mammals (rodents & insectivores) were tested on pathogenic Leptospira spp., and 312 on T. gondii. Rodents and insectivores were trapped at various sites, but mostly on pig and dairy farms throughout the country. Over five percent of the animals (5.3%, n = 379) tested positive for Leptospira DNA, and five of the animals (1.6%, n = 312) tested were positive for T. gondii DNA. The animals positive for T.gondii were all brown rats and the ones for Leptospira spp. were various species. Our results show that insectivores and rodents might be used as an indicator for the environmental contamination and/or the contamination in wildlife for Leptospira spp.
Assuntos
Reservatórios de Doenças/veterinária , Eulipotyphla , Leptospirose/veterinária , Doenças dos Roedores/epidemiologia , Roedores , Toxoplasmose Animal/epidemiologia , Zoonoses/epidemiologia , Animais , Feminino , Humanos , Leptospira/isolamento & purificação , Leptospirose/epidemiologia , Leptospirose/microbiologia , Masculino , Países Baixos/epidemiologia , Doenças dos Roedores/microbiologia , Doenças dos Roedores/parasitologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/parasitologia , Zoonoses/microbiologia , Zoonoses/parasitologiaRESUMO
BACKGROUND: Interactions between proteins and non-proteic small molecule ligands play important roles in the biological processes of living systems. Thus, the development of computational methods to support our understanding of the ligand-receptor recognition process is of fundamental importance since these methods are a major step towards ligand prediction, target identification, lead discovery, and more. This article presents visGReMLIN, a web server that couples a graph mining-based strategy to detect motifs at the protein-ligand interface with an interactive platform to visually explore and interpret these motifs in the context of protein-ligand interfaces. RESULTS: To illustrate the potential of visGReMLIN, we conducted two cases in which our strategy was compared with previous experimentally and computationally determined results. visGReMLIN allowed us to detect patterns previously documented in the literature in a totally visual manner. In addition, we found some motifs that we believe are relevant to protein-ligand interactions in the analyzed datasets. CONCLUSIONS: We aimed to build a visual analytics-oriented web server to detect and visualize common motifs at the protein-ligand interface. visGReMLIN motifs can support users in gaining insights on the key atoms/residues responsible for protein-ligand interactions in a dataset of complexes.
Assuntos
Ligantes , Proteínas/metabolismo , Interface Usuário-Computador , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligação Proteica , Proteínas/químicaRESUMO
This study investigated the chronic effect of inspiratory muscle training (IMT) on the human serum metabolome in healthy male recreational cyclists. Using a randomized, parallel group design, twenty-eight participants were randomized to three IMT groups: low intensity (LI, n = 7); moderate intensity (MI, n = 10); and high intensity (HI, n = 11). The IMT was performed for 11 weeks. Another group of participants under the same conditions, who did not perform the IMT but participated in all procedures, was included as controls (CG, n = 6). Blood samples were collected one week before and after 11 weeks of IMT and analyzed for metabolite shifts using 1H NMR. Statistical analysis included a 4 (group) × 2 (time) repeated measures ANOVA using the general linear model (GLM), and multivariate principal component analysis (PCA). Untargeted metabolomics analysis of serum samples identified 22 metabolites, including amino acids, lipids, and tricarboxylic acid cycle intermediates. Metabolites shifts did not differ between groups, indicating that IMT at three intensity levels did not alter the serum metabolome relative to the control group. These results reveal novel insights into the metabolic effects of the IMT and are consistent with the results from other studies showing negligible chronic alterations in the serum metabolome in response to physical training.