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1.
Molecules ; 29(12)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38930828

ABSTRACT

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.


Subject(s)
Isoxazoles , Trypanocidal Agents , Trypanosoma cruzi , Trypanosoma cruzi/drug effects , Trypanocidal Agents/pharmacology , Trypanocidal Agents/chemistry , Trypanocidal Agents/chemical synthesis , Isoxazoles/chemistry , Isoxazoles/pharmacology , Protozoan Proteins/metabolism , Protozoan Proteins/chemistry , Protozoan Proteins/antagonists & inhibitors , Structure-Activity Relationship , Chagas Disease/drug therapy , Chagas Disease/parasitology , Cysteine Endopeptidases/chemistry , Cysteine Endopeptidases/metabolism , Animals , Catalytic Domain , Molecular Structure
2.
J Sci Food Agric ; 104(11): 6724-6732, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38551410

ABSTRACT

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.


Subject(s)
Anti-Bacterial Agents , Mass Spectrometry , Quantitative Structure-Activity Relationship , Veterinary Drugs , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/analysis , Veterinary Drugs/analysis , Veterinary Drugs/chemistry , Chromatography, Liquid , Animals , Chromatography, High Pressure Liquid , Computer Simulation , Liquid Chromatography-Mass Spectrometry
3.
Emerg Infect Dis ; 29(2)2023 02.
Article in English | MEDLINE | ID: mdl-36692864

ABSTRACT

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.


Subject(s)
Dirofilaria immitis , Dirofilaria repens , Dirofilariasis , Dog Diseases , Animals , Dogs , Dirofilariasis/diagnosis , Dirofilariasis/epidemiology , Dirofilariasis/parasitology , Chile/epidemiology , Venezuela/epidemiology , Dog Diseases/diagnosis , Dog Diseases/epidemiology , Dog Diseases/parasitology
4.
Parasitology ; 150(7): 599-605, 2023 06.
Article in English | MEDLINE | ID: mdl-37203451

ABSTRACT

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.


Subject(s)
Cysts , Echinococcosis , Echinococcus granulosus , Animals , Humans , Male , Female , Echinococcus granulosus/genetics , Argentina/epidemiology , Echinococcosis/epidemiology , Echinococcosis/veterinary , Genotype , Goats , Camelus
5.
J Sci Food Agric ; 103(10): 4867-4875, 2023 Aug 15.
Article in English | MEDLINE | ID: mdl-36929660

ABSTRACT

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.


Subject(s)
Antioxidants , Cheminformatics , Antioxidants/chemistry , Quantitative Structure-Activity Relationship , Multivariate Analysis , Free Radicals , Phenols
6.
Infect Immun ; 90(8): e0017422, 2022 08 18.
Article in English | MEDLINE | ID: mdl-35862712

ABSTRACT

The larval stage of the helminthic cestode Echinococcus multilocularis can inflict tumor-like hepatic lesions that cause the parasitic disease alveolar echinococcosis in humans, with high mortality in untreated patients. Opportunistic properties of the disease have been established based on the increased incidence in immunocompromised patients and mouse models, indicating that an appropriate adaptive immune response is required for the control of the disease. However, cellular interactions and the kinetics of the local hepatic immune responses during the different stages of infection with E. multilocularis remain unknown. In a mouse model of oral infection that mimics the normal infection route in human patients, the networks of the hepatic immune response were assessed using single-cell RNA sequencing (scRNA-seq) of isolated hepatic CD3+ T cells at different infection stages. We observed an early and sustained significant increase in natural killer T (NKT) cells and regulatory T cells (Tregs). Early tumor necrosis factor (TNF)- and integrin-dependent interactions between these two cell types promote the formation of hepatic lesions. At late time points, downregulation of programmed cell death protein 1 (PD-1) and ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)-dependent signaling suppress the resolution of parasite-induced pathology. The obtained data provide fresh insight into the adaptive immune responses and local regulatory pathways at different infection stages of E. multilocularis in mice.


Subject(s)
Echinococcosis , Echinococcus multilocularis , Natural Killer T-Cells , T-Lymphocytes, Regulatory , Animals , Humans , Liver/physiology , Mice
7.
Conserv Biol ; 35(3): 816-823, 2021 06.
Article in English | MEDLINE | ID: mdl-32779761

ABSTRACT

Markets are increasingly being incorporated into many aspects of daily life and are becoming an important part of the conservation solution space. Although market-based solutions to environmental problems can result in improvements to conservation, a body of social science research highlights how markets may also have unforeseen consequences by crowding out or displacing 3 key types of behaviors potentially relevant to conservation, including people's willingness to engage in collective action and civic duty; tolerance for inflicting harm on others (third-party externalities); and desire for equity. Better understanding of the contexts and mechanisms through which this crowding out occurs and whether specific market-based instruments are more prone to different types of crowding out will be crucial to developing novel conservation initiatives that can reduce or prevent crowding out.


Los Mercados y el Desplazamiento del Comportamiento Relevante para la Conservación Resumen Los mercados cada vez están más incorporados dentro de muchos aspectos de la vida diaria y se están transformando en una parte importante del espacio de las soluciones de conservación. Aunque las soluciones basadas en los mercados para los problemas ambientales pueden resultar en mejoras para la conservación, una parte de los estudios sociales resaltan cómo los mercados también pueden tener consecuencias imprevistas al desplazar o excluir tres tipos importantes de comportamiento potencialmente relevantes para la conservación: la disposición de las personas a participar en acciones colectivas y deberes cívicos, la tolerancia a infligir daño a otros (efectos externos de terceros) y el anhelo por la equidad. Un mejor entendimiento de los contextos y los mecanismos mediante los cuales ocurre este desplazamiento y si los instrumentos basados en los mercados son más susceptibles a los diferentes tipos de desplazamiento serán elementos cruciales para desarrollar iniciativas de conservación novedosas que puedan reducir o prevenir el desplazamiento.


Subject(s)
Conservation of Natural Resources , Humans
8.
Parasitol Res ; 120(10): 3451-3459, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34462804

ABSTRACT

The diagnosis of human taeniosis can be achieved through coproscopy, ELISA or PCR. An important limitation of these methods is the high turnaround time for stool sample collection and preparation, indicating the need for a straightforward sampling strategy. Due to the high metabolic activity and reproductive potential of Taenia spp., we hypothesise that parasite DNA (cells and eggs) present in the peri-anal region of the host can be exploited as a target for molecular diagnosis. We evaluated the feasibility of recovering parasite DNA from the peri-anal area of foxes naturally infected with Taenia spp. Before necropsy, cotton swabs were rubbed at the peri-anal region of foxes. DNA was extracted using alkaline lysis coupled with a commercial DNA isolation kit (method A) or alkaline lysis alone (method B). DNA was used in the multiplex-PCR assay (previously described and called here swab-PCR) and a novel LAMP assay detecting Taenia spp. commonly found in foxes (swab-LAMP). The results of these assays from 105 foxes were compared with the presence of intestinal helminths determined at necropsy and by the sedimentation and counting technique (SCT). The sensitivity of swab-PCR for detecting Taenia (n = 68) was 89.8% (95% CI, 77.7-96.6) and 89.5% (66.9-98.7) using methods A and B, respectively. The sensitivity of the swab-LAMP assay was 83.7% (70.3-92.7) using method A and 89.5% (66.9-98.7) with method B. We postulate that peri-anal swab sampling followed by simplified DNA extraction and LAMP might be a suitable strategy for surveillance of human taeniosis in resource-limited settings in the future.


Subject(s)
Cestoda , Foxes , Animals , DNA, Helminth/genetics , Humans , Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Polymerase Chain Reaction , Sensitivity and Specificity
9.
Parasitology ; 147(9): 1048-1054, 2020 08.
Article in English | MEDLINE | ID: mdl-32364108

ABSTRACT

The metacestode of Echinococcus multilocularis is the etiological agent of alveolar echinococcosis. The metacestode stage used for research is maintained in rodents by serial passages. In order to determine whether cryopreservation of E. multilocularis metacestodes would be suitable for long-term maintenance and replace serial passages, isolates of different geographic origin were cryopreserved in 1984-1986. The aim of the current study was to test the viability of cryopreserved isolates following long-term cryopreservation (up to 35 years) and to determine the phylogenetic clades these isolates belonged to. Cryopreserved isolates were tested for viability in vitro and in vivo in gerbils. In vitro results of 5 isolates indicated protoscolex survival in 13 of 17 experiments (76%) and metacestode survival in 5 of 12 (42%) in vivo experiments. In vivo results showed 'abortive lesions' in 13 of the 36 animals, 15 were negative and 8 harboured proliferating metacestode tissue containing protoscoleces. Genetic analysis confirmed the isolates belonged to European, Asian and North-American clades. In conclusion, the results of the current study indicate that metacestodes of E. multilocularis are able to survive long-term cryopreservation. Therefore, cryopreservation is a suitable method for long-term storage of E. multilocularis metacestode isolates and reduces the number of experimental animals.


Subject(s)
Cryopreservation/statistics & numerical data , Echinococcus multilocularis/physiology , Gerbillinae/parasitology , Animals , Echinococcus multilocularis/growth & development , Larva/growth & development , Larva/physiology , Seasons
10.
Parasitol Res ; 119(2): 763-770, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31863181

ABSTRACT

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.


Subject(s)
Cattle Diseases/parasitology , Echinococcosis/veterinary , Echinococcus granulosus/classification , Sheep Diseases/parasitology , Animals , Cattle , Chile , Cyclooxygenase 1/genetics , Echinococcosis/parasitology , Echinococcus granulosus/genetics , Echinococcus granulosus/isolation & purification , Fertility , Genes, Mitochondrial/genetics , Genetic Variation/genetics , Genotype , Haplotypes , Humans , Sheep/genetics
11.
Ecotoxicol Environ Saf ; 171: 47-53, 2019 Apr 30.
Article in English | MEDLINE | ID: mdl-30594756

ABSTRACT

Water solubility is a key physicochemical parameter in pesticide control and regulation, although sometimes its experimental determination is not an easy task. In this study, we present Quantitative Structure-Property Relationships (QSPRs) for predicting the water solubility at 20 °C of 1211 approved heterogeneous pesticide compounds, collected from the online Pesticides Properties Data Base (PPDB). Validated and generally applicable Multivariable Linear Regression (MLR) models were established, including molecular descriptors carrying constitutional and topological aspects of the analyzed compounds. The most representative descriptors were selected from the exploration of a large number of about 18,000 structural variables. A hybrid approach that involves a molecular descriptor, a fingerprint, and a flexible descriptor showed the best predictive performance.


Subject(s)
Molecular Conformation , Pesticides/chemistry , Quantitative Structure-Activity Relationship , Water/chemistry , Linear Models , Solubility
12.
BMC Genomics ; 19(1): 891, 2018 Dec 07.
Article in English | MEDLINE | ID: mdl-30526481

ABSTRACT

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.


Subject(s)
Genome, Plant , Ilex paraguariensis/genetics , Organ Specificity/genetics , Sequence Analysis, RNA/methods , Transcriptome/genetics , Gene Expression Regulation, Plant , Gene Ontology , Genes, Plant , Molecular Sequence Annotation , Plant Leaves/genetics , Plant Roots/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reproducibility of Results , Secondary Metabolism/genetics
13.
Parasitology ; 145(6): 807-813, 2018 05.
Article in English | MEDLINE | ID: mdl-29173204

ABSTRACT

Echinococcus granulosus is an important zoonotic parasite that is distributed worldwide. The EG95 vaccine was developed to assist with control of E. granulosus transmission through the parasite's livestock intermediate hosts. The vaccine is based on a recombinant antigen encoded by a gene which is a member of a multi-gene family. With the recent availability of two E. granulosus draft genomes, we sought to map the eg95 gene family to the genomes. We were unable to map unequivocally any of the eg95 gene family members which had previously been characterized by cloning and sequencing both strands of genomic DNA fragments. Our inability to map EG95-related genes to the genomes has revealed limitations in the assembled sequence data when utilized for gene family analyses. This study contrasts with the expectations expressed in often high-profile publications describing draft genomes of parasitic organisms, highlighting deficiencies in currently available genomic resources for E. granulosus and provides a cautionary note for research which seeks to utilize these genome datasets.


Subject(s)
Antigens, Helminth/immunology , Echinococcus granulosus/genetics , Genome, Helminth , Helminth Proteins/genetics , Animals , Antigens, Helminth/genetics , Cloning, Molecular , DNA, Complementary , Echinococcosis/immunology , Echinococcosis/parasitology , Echinococcosis/prevention & control , Echinococcus granulosus/immunology , Helminth Proteins/immunology , Humans , Vaccines/genetics , Vaccines/immunology
14.
Immunogenetics ; 67(9): 515-30, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26123975

ABSTRACT

The viability of coral reefs worldwide has been seriously compromised in the last few decades due in part to the emergence of coral diseases of infectious nature. Despite important efforts to understand the etiology and the contribution of environmental factors associated to coral diseases, the mechanisms of immune response in corals are just beginning to be studied systematically. In this study, we analyzed the set of conserved immune response genes of the Caribbean reef-building coral Pseudodiploria strigosa by Illumina-based transcriptome sequencing and annotation of healthy colonies challenged with whole live Gram-positive and Gram-negative bacteria. Searching the annotated transcriptome with immune-related terms yielded a total of 2782 transcripts predicted to encode conserved immune-related proteins that were classified into three modules: (a) the immune recognition module, containing a wide diversity of putative pattern recognition receptors including leucine-rich repeat-containing proteins, immunoglobulin superfamily receptors, representatives of various lectin families, and scavenger receptors; (b) the intracellular signaling module, containing components from the Toll-like receptor, transforming growth factor, MAPK, and apoptosis signaling pathways; and (3) the effector module, including the C3 and factor B complement components, a variety of proteases and protease inhibitors, and the melanization-inducing phenoloxidase. P. strigosa displays a highly variable and diverse immune recognition repertoire that has likely contributed to its resilience to coral diseases.


Subject(s)
Anthozoa/genetics , Anthozoa/immunology , MAP Kinase Signaling System/genetics , Mitogen-Activated Protein Kinases/genetics , Toll-Like Receptors/genetics , Animals , Anthozoa/microbiology , Apoptosis/genetics , Apoptosis/immunology , Base Sequence , Caribbean Region , Coral Reefs , Gram-Negative Bacteria/immunology , Gram-Positive Bacteria/immunology , Monophenol Monooxygenase/genetics , Sequence Analysis, DNA , Toll-Like Receptors/immunology , Transcriptome/genetics , Transforming Growth Factors/genetics
15.
BMC Genomics ; 15: 766, 2014 Sep 06.
Article in English | MEDLINE | ID: mdl-25194793

ABSTRACT

BACKGROUND: Small RNA (sRNA) has been described as a regulator of gene expression. In order to understand the role of maize sRNA (Zea mays-hybrid UENF 506-8) during association with endophytic nitrogen-fixing bacteria, we analyzed the sRNA regulated by its association with two diazotrophic bacteria, Herbaspirillum seropedicae and Azospirillum brasilense. RESULTS: Deep sequencing analysis was done with RNA extracted from plants inoculated with H. seropedicae, allowing the identification of miRNA and siRNA. A total of 25 conserved miRNA families and 15 novel miRNAs were identified. A dynamic regulation in response to inoculation was also observed. A hypothetical model involving copper-miRNA is proposed, emphasizing the fact that the up-regulation of miR397, miR398, miR408 and miR528, which is followed by inhibition of their targets, can facilitate association with diazotrophic bacteria. Similar expression patterns were observed in samples inoculated with A. brasilense. Moreover, novel miRNA and siRNA were classified in the Transposable Elements (TE) database, and an enrichment of siRNA aligned with TE was observed in the inoculated samples. In addition, an increase in 24-nt siRNA mapping to genes was observed, which was correlated with an increase in methylation of the coding regions and a subsequent reduction in transcription. CONCLUSION: Our results show that maize has RNA-based silencing mechanisms that can trigger specific responses when plants interact with beneficial endophytic diazotrophic bacteria. Our findings suggest important roles for sRNA regulation in maize, and probably in other plants, during association with diazotrophic bacteria, emphasizing the up-regulation of Cu-miRNA.


Subject(s)
Bacteria , Endophytes , MicroRNAs/genetics , RNA, Plant/genetics , RNA, Small Interfering/genetics , Zea mays/genetics , Zea mays/microbiology , Bacteria/metabolism , Chromosome Mapping , Computational Biology , DNA Transposable Elements , Databases, Nucleic Acid , Endophytes/metabolism , Gene Expression Regulation, Plant , Gene Library , Genome-Wide Association Study , Methylation , Nitrogen Fixation , Phenotype , RNA Splicing , Symbiosis , Zea mays/growth & development
16.
Neuropediatrics ; 45(6): 354-61, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25098832

ABSTRACT

BACKGROUND: Preterm babies treated with synthetic glucocorticoids (sGC) in utero exhibit behavioral alterations and disturbances in brain maturation during infancy. However, the effects on dentate granule cell morphology and spatial memory in rats that were given clinically equivalent doses of antenatal betamethasone remain unclear. METHODS: Pregnant rats were randomly divided into the following two experimental groups: control (CON) and betamethasone-treated (BET) groups. At gestational day 20 (G20), BET dams were subcutaneously injected with a 0.17 mg/kg betamethasone solution, and CON animals received a similar volume of saline. At postnatal days 22 (P22) and P52, BET and CON offsprings were behaviorally evaluated in the Y-Maze test, and the dentate gyrus granular neurons were histologically analyzed. RESULTS: Animals prenatally treated with a single course of betamethasone exhibit a significant decrement in the dendritic outgrowth of dentate granule cells along with impaired spatial memory when evaluated at P52. Moreover, the body and brain weight of the BET group was significantly lower than the CON group at P0, P22, and P52. CONCLUSION: The current results indicate that a single course of betamethasone in pregnant rats produces significant neuronal and behavioral impairments of the offspring at adolescence along with a decrement in somatic and brain weights at each of the three ages evaluated.


Subject(s)
Betamethasone/toxicity , Dendrites/drug effects , Dentate Gyrus/drug effects , Neurons/drug effects , Prenatal Exposure Delayed Effects , Spatial Memory/drug effects , Animals , Betamethasone/administration & dosage , Dentate Gyrus/growth & development , Dentate Gyrus/pathology , Female , Neurons/pathology , Pregnancy , Rats
17.
Med Mycol Case Rep ; 43: 100624, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38222925

ABSTRACT

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.

18.
Matrix Biol ; 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39153517

ABSTRACT

Skeletal muscle fibrosis is defined as the excessive accumulation of extracellular matrix (ECM) components and is a hallmark of muscular dystrophies. Fibro-adipogenic progenitors (FAPs) are the main source of ECM, and thus have been strongly implicated in fibrogenesis. In skeletal muscle fibrotic models, including muscular dystrophies, FAPs undergo dysregulations in terms of proliferation, differentiation, and apoptosis, however few studies have explored the impact of FAPs migration. Here, we studied fibroblast and FAPs migration and identified lysophosphatidic acid (LPA), a signaling lipid central to skeletal muscle fibrogenesis, as a significant migration inductor. We identified LPA receptor 1 (LPA1) mediated signaling as crucial for this effect through a mechanism dependent on the Hippo pathway, another pathway implicated in fibrosis across diverse tissues. This cross-talk favors the activation of the Yes-associated protein 1 (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ), leading to increased expression of fibrosis-associated genes. This study reveals the role of YAP in LPA-mediated fibrotic responses as inhibition of YAP transcriptional coactivator activity hinders LPA-induced migration in fibroblasts and FAPs. Moreover, we found that FAPs derived from the mdx4cv mice, a murine model of Duchenne muscular dystrophy, display a heightened migratory phenotype due to enhanced LPA signaling compared to wild-type FAPs. Remarkably, we found that the inhibition of LPA1 or YAP transcriptional coactivator activity in mdx4cv FAPs reverts this phenotype. In summary, the identified LPA-LPA1-YAP pathway emerges as a critical driver of skeletal muscle FAPs migration and provides insights into potential novel targets to mitigate fibrosis in muscular dystrophies.

19.
Food Res Int ; 171: 113036, 2023 09.
Article in English | MEDLINE | ID: mdl-37330849

ABSTRACT

The capacity to discriminate safe from dangerous compounds has played an important role in the evolution of species, including human beings. Highly evolved senses such as taste receptors allow humans to navigate and survive in the environment through information that arrives to the brain through electrical pulses. Specifically, taste receptors provide multiple bits of information about the substances that are introduced orally. These substances could be pleasant or not according to the taste responses that they trigger. Tastes have been classified into basic (sweet, bitter, umami, sour and salty) or non-basic (astringent, chilling, cooling, heating, pungent), while some compounds are considered as multitastes, taste modifiers or tasteless. Classification-based machine learning approaches are useful tools to develop predictive mathematical relationships in such a way as to predict the taste class of new molecules based on their chemical structure. This work reviews the history of multicriteria quantitative structure-taste relationship modelling, starting from the first ligand-based (LB) classifier proposed in 1980 by Lemont B. Kier and concluding with the most recent studies published in 2022.


Subject(s)
Taste Buds , Taste , Humans , Taste/physiology , Taste Perception
20.
Front Vet Sci ; 10: 1334832, 2023.
Article in English | MEDLINE | ID: mdl-38260205

ABSTRACT

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.

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