ABSTRACT
MAIN CONCLUSION: Natural selection influenced adaptive divergence between Cereus fernambucensis and Cereus insularis, revealing key genes governing abiotic stress responses and supporting neoteny in C. insularis. Uncovering the molecular mechanisms driving adaptive divergence in traits related to habitat adaptation remains a central challenge. In this study, we focused on the cactus clade, which includes Cereus sericifer F.Ritter, Cereus fernambucensis Lem., and Cereus insularis Hemsley. These allopatric species inhabit distinct relatively drier regions within the Brazilian Atlantic Forest, each facing unique abiotic conditions. We leveraged whole transcriptome data and abiotic variables datasets to explore lineage-specific and environment-specific adaptations in these species. Employing comparative phylogenetic methods, we identified genes under positive selection (PSG) and examined their association with non-synonymous genetic variants and abiotic attributes through a PhyloGWAS approach. Our analysis unveiled signatures of selection in all studied lineages, with C. fernambucensis northern populations and C. insularis showing the most PSGs. These PSGs predominantly govern abiotic stress regulation, encompassing heat tolerance, UV stress response, and soil salinity adaptation. Our exclusive observation of gene expression tied to early developmental stages in C. insularis supports the hypothesis of neoteny in this species. We also identified genes associated with abiotic variables in independent lineages, suggesting their role as environmental filters on genetic diversity. Overall, our findings suggest that natural selection played a pivotal role in the geographic range of these species in response to environmental and biogeographic transitions.
Subject(s)
Adaptation, Physiological , Cactaceae , Forests , Gene Expression Profiling , Phylogeny , Brazil , Cactaceae/genetics , Cactaceae/physiology , Adaptation, Physiological/genetics , Selection, Genetic , Transcriptome , Stress, Physiological/genetics , Gene Expression Regulation, PlantABSTRACT
Here we use population genomic data (ddRAD-Seq) and ecological niche modeling to test biogeographic hypotheses for the divergence of the island-endemic cactus species Cereus insularis Hemsl. (Cereeae; Cactaceae) from its sister species C. fernambucensis Lem. The Cereus insularis grows in the Fernando de Noronha Islands (FNI), a Neotropical archipelago located 350 km off the Brazilian Atlantic Forest (BAF) coast. Phylogeographic reconstructions support a northward expansion by the common ancestor of C. insularis and C. fernambucensis along the mainland BAF coast, with C. insularis diverging from the widespread mainland taxon C. fernambucensis after colonizing FNI in the late Pleistocene. The morphologically distinct C. insularis is monophyletic and nested within C. fernambucensis, as expected from a progenitor-derivative speciation model. We tested alternative biogeographic and demographic hypotheses for the colonization of the FNI using Approximate Bayesian Computation. We found the greatest support for a stepping-stone path that emerged during periods of decreased sea level (the "bridge" hypothesis), in congruence with historical ecological niche modeling that shows highly suitable habitats on stepping-stone islands during glacial periods. The outlier analyses reveal signatures of selection in C. insularis, suggesting a putative role of adaptation driving rapid anagenic differentiation of this species in FNI.
Subject(s)
Bayes Theorem , Cactaceae , Islands , Phylogeny , Phylogeography , Cactaceae/genetics , Brazil , Ecosystem , Genetics, PopulationABSTRACT
BACKGROUND AND AIMS: Cactaceae are succulent plants, quasi-endemic to the American continent, and one of the most endangered plant groups in the world. Molecular phylogenies have been key to unravelling phylogenetic relationships among major cactus groups, previously hampered by high levels of morphological convergence. Phylogenetic studies using plastid markers have not provided adequate resolution for determining generic relationships within cactus groups. This is the case for the tribe Cereeae s.l., a highly diverse group from tropical America. Here we aimed to reconstruct a well-resolved phylogenetic tree of tribe Cereeae and update the circumscription of suprageneric and generic groups in this tribe. METHODS: We integrated sequence data from public gene and genomic databases with new target sequences (generated using the customized Cactaceae591 probe set) across representatives of this tribe, with a denser taxon sampling of the subtribe Cereinae. We inferred concatenated and coalescent phylogenetic trees and compared the performance of both approaches. KEY RESULTS: Six well-supported suprageneric clades were identified using different datasets. However, only genomic datasets, especially the Cactaceae591, were able to resolve the contentious relationships within the subtribe Cereinae. CONCLUSIONS: We propose a new taxonomic classification within Cereeae based on well-resolved clades, including new subtribes (Aylosterinae subtr. nov., Uebelmanniinae subtr. nov. and Gymnocalyciinae subtr. nov.) and revised subtribes (Trichocereinae, Rebutiinae and Cereinae). We emphasize the importance of using genomic datasets allied with coalescent inference to investigate evolutionary patterns within the tribe Cereeae.
Subject(s)
Biological Evolution , Cactaceae , Phylogeny , Sequence Analysis, DNA , Genomics , Cactaceae/geneticsABSTRACT
PREMISE: Pilosocereus (Cactaceae) is an important dry forest element in all subregions and transitional zones of the neotropics, with the highest diversity in eastern Brazil. The genus is subdivided into informal taxonomic groups; however, most of these are not supported by recent molecular phylogenetic inferences. This lack of confidence is probably due to the use of an insufficient number of loci and the complexity of cactus diversification. Here, we explored the species relationships in Pilosocereus in more detail, integrating multilocus phylogenetic approaches with the assessment of the ancestral range and the effect of geography on diversification shifts. METHODS: We used 28 nuclear, plastid, and mitochondrial loci from 54 plant samples of 31 Pilosocereus species for phylogenetic analyses. We used concatenated and coalescent phylogenetic trees and Bayesian models to estimate the most likely ancestral range and diversification shifts. RESULTS: All Pilosocereus species were clustered in the same branch, except P. bohlei. The phylogenetic relationships were more associated with the geographic distribution than taxonomic affinities among taxa. The genus began diversifying during the Plio-Pleistocene transition in the Caatinga domain and experienced an increased diversification rate during the Calabrian age. CONCLUSIONS: We recovered a well-supported multispecies coalescent phylogeny. Our results refine the pattern of rapid diversification of Pilosocereus species across neotropical drylands during the Pleistocene and highlight the need for taxonomic rearrangements in the genus. We recovered a pulse of diversification during the Pleistocene that was likely driven by multiple dispersal and vicariance events within and among the Caatinga, Cerrado, and Atlantic Forest domains.
Subject(s)
Forests , Phylogeny , Phylogeography , Bayes Theorem , BrazilABSTRACT
Leishmaniases affect 12 million people worldwide. They are caused by Leishmania spp., protozoan parasites transmitted to mammals by female phlebotomine flies. During the life cycle, promastigote forms of the parasite live in the gut of infected sandflies and convert into amastigotes inside the vertebrate macrophages. The parasite evades macrophage's microbicidal responses due to virulence factors that affect parasite phagocytosis, survival and/or proliferation. The interaction between Leishmania and macrophage molecules is essential to phagocytosis and parasite survival. Proteins containing leucine-rich repeats (LRRs) are common in several organisms, and these motifs are usually involved in proteinprotein interactions. We have identified the LRR17 gene, which encodes a protein with 6 LRR domains, in the genomes of several Leishmania species. We show here that promastigotes of Leishmania (L.) amazonensis overexpressing LaLRR17 are more infective in vitro. We produced recombinant LaLRR17 protein and identified macrophage 78 kDa glucose-regulated protein (GRP78) as a ligand for LaLRR17 employing affinity chromatography followed by mass spectrometry. We showed that GRP78 binds to LaLRR17 and that its blocking precludes the increase of infection conferred by LaLRR17. Our results are the first to report LRR17 gene and protein, and we hope they stimulate further studies on how this protein increases phagocytosis of Leishmania.
Subject(s)
Leishmania , Leishmaniasis , Parasites , Humans , Animals , Female , Mice , Leishmania/physiology , Endoplasmic Reticulum Chaperone BiP , Macrophages/parasitology , Mice, Inbred BALB C , MammalsABSTRACT
The present paper describes a compact point of care (POC) optical device for therapeutic drug monitoring (TDM). The core of the device is a disposable plastic chip where an immunoassay for the determination of immunosuppressants takes place. The chip is designed in order to have ten parallel microchannels allowing the simultaneous detection of more than one analyte with replicate measurements. The device is equipped with a microfluidic system, which provides sample mixing with the necessary chemicals and pumping samples, reagents and buffers into the measurement chip, and with integrated thin film amorphous silicon photodiodes for the fluorescence detection. Submicrometric fluorescent magnetic particles are used as support in the immunoassay in order to improve the efficiency of the assay. In particular, the magnetic feature is used to concentrate the antibody onto the sensing layer leading to a much faster implementation of the assay, while the fluorescent feature is used to increase the optical signal leading to a larger optical dynamic change and consequently a better sensitivity and a lower limit of detection. The design and development of the whole integrated optical device are here illustrated. In addition, detection of mycophenolic acid and cyclosporine A in spiked solutions and in microdialysate samples from patient blood with the implemented device are reported.
Subject(s)
Immunosuppressive Agents , Optical Devices , Humans , Immunoassay , Microfluidics , SiliconABSTRACT
MAIN CONCLUSION: The first South American cactus nuclear genome assembly associated with comparative genomic analyses provides insights into nuclear and plastid genomic features, such as size, transposable elements, and metabolic processes related to cactus development. Here, we assembled the partial genome, plastome, and transcriptome of Cereus fernambucensis (Cereeae, Cactaceae), a representative species of the South American core Cactoideae. We accessed other genomes and transcriptomes available for cactus species to compare the heterozygosity level, genome size, transposable elements, orthologous genes, and plastome structure. These estimates were obtained from the literature or using the same pipeline adopted for C. fermabucensis. In addition to the C. fernambucensis plastome, we also performed de novo plastome assembly of Pachycereus pringlei, Stenocereus thurberi, and Pereskia humboldtii based on the sequences available in public databases. We estimated a genome size of ~ 1.58 Gb for C. fernambucensis, the largest genome among the compared species. The genome heterozygosity was 0.88% in C. fernambucensis but ranged from 0.36 (Carnegiea gigantea) to 17.4% (Lophocereus schottii) in the other taxa. The genome lengths of the studied cacti are constituted by a high amount of transposable elements, ranging from ~ 57 to ~ 67%. Putative satellite DNAs are present in all species, excepting C. gigantea. The plastome of C. fernambucensis was ~ 104 kb, showing events of translocation, inversion, and gene loss. We observed a low number of shared unique orthologs, which may suggest gene duplication events and the simultaneous expression of paralogous genes. We recovered 37 genes that have undergone positive selection along the Cereus branch that are associated with different metabolic processes, such as improving photosynthesis during drought stress and nutrient absorption, which may be related to the adaptation to xeric areas of the Neotropics.
Subject(s)
Cactaceae , Genome, Plastid , Cactaceae/genetics , DNA Transposable Elements/genetics , Evolution, Molecular , Genomics , North America , PhylogenyABSTRACT
This study points to evaluate the effects of pre-treatment with standardized dry extract of Curcuma longa (Motore™) added to the diet (0; 250; 500; and 750 mg/kg) on oxidative stress parameters, longevity, and therapeutic success in Rhamdia quelen experimentally infected with Aeromonas hydrophila (MF 372510). After treatment, the liver and kidney were collected to determine non-enzymatic oxidative parameters such as the formation of thiobarbituric acid reactive substances (TBARS), non-protein thiols (NPSH), and quantification of reactive oxygen species (ROS) levels. Also, two enzymatic antioxidant parameters were evaluated: superoxide dismutase (SOD) and catalase (CAT) activities. The results showed an increase of ROS and TBARS levels, a depletion in NPSH, and a decrease of SOD and CAT activities in infected fish compared to control. The highest Motore™ dose minimized the deleterious effect of A. hydrophila infection improving longevity, oxidative status, and survival rate. The addition of 750 mg Motore™/kg feed is recommended for silver catfish in fish farming. Serious economic losses in Rhamdia quelen culture caused by Aeromonas hydrophila infections can be prevented by the addition of Motore™ to the diet.
Subject(s)
Catfishes , Fish Diseases , Gram-Negative Bacterial Infections , Aeromonas hydrophila , Animals , Antioxidants , Dietary Supplements , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/veterinary , Oxidative StressABSTRACT
BACKGROUND: There is a lack of useful diagnostic tools to identify EGFR mutated NSCLC patients with long-term survival. This study develops a prognostic model using real world data to assist clinicians to predict survival beyond 24 months. METHODS: EGFR mutated stage IIIB and IV NSCLC patients diagnosed between January 2009 and December 2017 included in the Spanish Lung Cancer Group (SLCG) thoracic tumor registry. Long-term survival was defined as being alive 24 months after diagnosis. A multivariable prognostic model was carried out using binary logistic regression and internal validation through bootstrapping. A nomogram was developed to facilitate the interpretation and applicability of the model. RESULTS: 505 of the 961 EGFR mutated patients identified in the registry were included, with a median survival of 27.73 months. Factors associated with overall survival longer than 24 months were: being a woman (OR 1.78); absence of the exon 20 insertion mutation (OR 2.77); functional status (ECOG 0-1) (OR 4.92); absence of central nervous system metastases (OR 2.22), absence of liver metastases (OR 1.90) or adrenal involvement (OR 2.35) and low number of metastatic sites (OR 1.22). The model had a good internal validation with a calibration slope equal to 0.781 and discrimination (optimism corrected C-index 0.680). CONCLUSIONS: Survival greater than 24 months can be predicted from six pre-treatment clinicopathological variables. The model has a good discrimination ability. We hypothesized that this model could help the selection of the best treatment sequence in EGFR mutation NSCLC patients.
Subject(s)
Cancer Survivors/statistics & numerical data , Carcinoma, Non-Small-Cell Lung/mortality , Chemoradiotherapy/mortality , Lung Neoplasms/mortality , Mutation , Nomograms , Aged , Biomarkers, Tumor/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/therapy , ErbB Receptors/genetics , Female , Follow-Up Studies , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/therapy , Male , Middle Aged , Models, Statistical , Prognosis , Retrospective Studies , Survival RateABSTRACT
The aim of this study was to determine the pharmacokinetic parameters of doxycycline in dogs and assess the efficacy of an oral drug dosage regimen of 10 mg/kg daily for 28 days through Pharmacokinetic/Pharmacodynamic (PK/PD) target analysis based on Monte Carlo simulation, using previously published data for the zoonotic pathogen Staphylococcus pseudintermedius. After a multiple-dosage regimen, the accumulation index was 1.88 ± 0.82. The Cmaxss and Cminss values were 5.18 ± 1.81 µg/ml and 1.91 ± 1.35 µg/ml, respectively. There were statistically significant differences for Cmax, Cmin at 24 hr, MRTt, AUCt and AUC∞ between days 1 and 28. The Cminss value was over the MIC of the principal pathogens, and Cmaxss was higher than the resistance values (>2 µg/ml). For AUC/MIC indices of 12, 25 and 40, the cumulative fraction responses (CFR) were 94.01%, 69.55% and 60.86%, respectively; for an MIC value of 2 µg/ml, the corresponding probability of target attainment (PTA) was 99.94%, 84.78% and 45.16%, respectively. Doxycycline was used against numerous localized infections in different organs and tissues. For the strains with MIC < 1 µg/mL, PTA was close to 100%, even for the most demanding ones, specifically 94.98% for an index of 40% and 99.9% for an index of 25.
Subject(s)
Anti-Bacterial Agents , Doxycycline , Administration, Oral , Animals , Dogs , Microbial Sensitivity Tests/veterinary , Monte Carlo Method , StaphylococcusABSTRACT
Hybridization and introgression between species in contact/hybrid zones provide important insight into the genetic and ecological mechanisms of speciation. Cactaceae represents the most important radiation of true succulent angiosperms in the New World. This diversification continues to date, with species experiencing few intrinsic barriers to gene flow and the frequent occurrence of natural hybridization. Here, we used RAD-Seq single-nucleotide polymorphism (SNP) data to investigate the genetic architecture of hybridization in four hybrid zones hosting Melocactus concinnus and four congeneric species (M. ernestii, M. glaucescens, M. paucispinus, and M. zehntneri). Our results revealed that M. concinnus is highly promiscuous in sympatric areas and hybridizes with various species distributed in Morro do Chapéu (Diamantina Plateau, Bahia), eastern Brazil. However, the contemporary genomic introgression among the investigated species is very low (c. 2-5%), confirming that even in the face of hybridization, Melocactus species maintain their genetic integrity. The genomic cline approach showed a large fraction of loci deviating from a model of neutral introgression, where most of the loci are consistent with selection favoring parental genotypes. Our results suggest the occurrence of weak premating but strong postmating reproductive isolation in the analyzed cactus species. Furthermore, as most of the Melocactus species are restricted in distribution, hybridization might negatively affect their integrity if hybrids replace the parental species.
Subject(s)
Cactaceae/genetics , Hybridization, Genetic , Brazil , Gene Flow , Genetic Introgression , Polymorphism, Single Nucleotide , Reproductive Isolation , SympatryABSTRACT
The reconstruction of relationships within recently radiated groups is challenging even when massive amounts of sequencing data are available. The use of restriction site-associated DNA sequencing (RAD-Seq) to this end is promising. Here, we assessed the performance of RAD-Seq to infer the species-level phylogeny of the rapidly radiating genus Cereus (Cactaceae). To examine how the amount of genomic data affects resolution in this group, we used datasets and implemented different analyses. We sampled 52 individuals of Cereus, representing 18 of the 25 species currently recognized, plus members of the closely allied genera Cipocereus and Praecereus, and other 11 Cactaceae genera as outgroups. Three scenarios of permissiveness to missing data were carried out in iPyRAD, assembling datasets with 30% (333 loci), 45% (1440 loci), and 70% (6141 loci) of missing data. For each dataset, Maximum Likelihood (ML) trees were generated using two supermatrices, i.e., only SNPs and SNPs plus invariant sites. Accuracy and resolution were improved when the dataset with the highest number of loci was used (6141 loci), despite the high percentage of missing data included (70%). Coalescent trees estimated using SVDQuartets and ASTRAL are similar to those obtained by the ML reconstructions. Overall, we reconstruct a well-supported phylogeny of Cereus, which is resolved as monophyletic and composed of four main clades with high support in their internal relationships. Our findings also provide insights into the impact of missing data for phylogeny reconstruction using RAD loci.
Subject(s)
Biological Evolution , Cactaceae/genetics , Genome, Plant , Sequence Analysis, DNA , Base Sequence , Databases, Genetic , Genetic Loci , Genetic Speciation , Likelihood Functions , Phylogeny , Polymorphism, Single Nucleotide/genetics , Principal Component AnalysisABSTRACT
The study of transferability of simple sequence repeats (SSR) among closely related species is a well-known strategy in population genetics, however transferability among distinct genera is less common. We tested cross-genera SSR amplification in the family Cactaceae using a total of 20 heterologous primers previously developed for the genera Ariocarpus, Echinocactus, Polaskia and Pilosocereus, in four taxa of the genus Cereus: C. fernambucensis subsp. fernambucensis, C. fernambucensis subsp. sericifer, C. jamacaru and C. insularis. Nine microsatellite loci were amplified in Cereus resulting in 35.2% of success in transferability, which is higher than the average rate of 10% reported in the literature for cross-genera transferability in eudicots. The genetic variation in the transferred markers was sufficient to perform standard clustering analysis, indicating each population as a cohesive genetic cluster. Overall, the amount of genetic variation found indicates that the transferred SSR markers might be useful in large-scale population studies within the genus Cereus.
ABSTRACT
OBJECTIVE: The purpose of the report is to describe a patient with hereditary osteochondromatosis and spinal cord compression at the thoracic level. CLINICAL FEATURES: An 8-year-old patient with hereditary osteochondromatosis inherited from his father presented paraparesis in the left foot, leading to complete paralysis in both legs. INTERVENTION: In a CT scan, a bony tumor rising from the posterior wall of the T3 body narrowing the spinal canal, and the MRI spinal cord compression at the same level and the hydrosyringomyelic cavity extended to the conus medullaris; with an anterior thoracic approach to T2-T4, the fibro-cartilaginous tumor was removed, and the stabilization was completed with bone graft and a plate. Two months after surgery, the patient recovered strength in both legs. CONCLUSIONS: A detailed family history through examination-guided advanced imaging and biopsy provides useful information for diagnosis and appropriate management of occupative lesions in patients affected with multiple hereditary exostosis.
Subject(s)
Exostoses, Multiple Hereditary/diagnostic imaging , Exostoses, Multiple Hereditary/surgery , Spinal Cord Compression/diagnostic imaging , Spinal Cord Compression/surgery , Thoracic Vertebrae/diagnostic imaging , Thoracic Vertebrae/surgery , Child , Exostoses, Multiple Hereditary/complications , Humans , Male , Spinal Cord Compression/etiology , Tomography, X-Ray Computed/methodsABSTRACT
The prevalence of Clostridium difficile in 107 dogs with diverse digestive disorders attended in a Spanish veterinary teaching hospital was assessed. The microorganism was isolated from 13 dogs (12.1%) of different disease groups. Isolates belonged to PCR ribotypes 078, 106, 154 and 430 (all of them toxigenic) and 110 (non-toxigenic), and were resistant to several antimicrobial drugs. Notably, seven isolates obtained from different dogs displayed stable resistance to metronidazole. The results of this study provide further evidence that dogs can act as a reservoir of C. difficile strains of epidemic ribotypes with resistance to multiple antibiotics.
Subject(s)
Anti-Infective Agents/pharmacology , Clostridioides difficile/isolation & purification , Dog Diseases/epidemiology , Drug Resistance, Bacterial , Enterocolitis, Pseudomembranous/epidemiology , Metronidazole/pharmacology , Animals , Clostridioides difficile/genetics , Disease Reservoirs , Dog Diseases/microbiology , Dogs , Enterocolitis, Pseudomembranous/microbiology , Female , Genetic Variation , Humans , Male , Microbial Sensitivity Tests , Prevalence , RibotypingABSTRACT
BACKGROUND: Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, ß-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS: Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS: The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI.
Subject(s)
Chondroitin Sulfates/therapeutic use , Dog Diseases/therapy , Inflammatory Bowel Diseases/veterinary , Prebiotics , Animals , Chondroitin Sulfates/adverse effects , Dog Diseases/drug therapy , Dogs , Female , Inflammatory Bowel Diseases/pathology , Inflammatory Bowel Diseases/therapy , Male , Microbiota , Prebiotics/adverse effectsABSTRACT
A series of eleven novel 5-amino-N-phenylpyrazine-2-carboxamides were synthesized and evaluated for in vitro anti-infective properties. Prepared compounds were characterized by IR, 1H NMR and 13C NMR spectra, elementary analysis and melting points. Lipophilicity parameters Log P and ClogP were calculated. None of the compounds was effective against any of tested mycobacterial strains (Mycobacterium tuberculosis H37Rv, M. kansasii, M. avium) up to concentration of 100 µg/mL. 5-amino-N-(2,5-dimethylphenyl) pyrazine-2-carboxamide (3) exerted moderate antibacterial activity against Staphylococcus aureus (MIC = 62.5 µM). No antifungal activity was detected. Several compounds exerted moderate antiviral activity against influenza A viruses at the level of tens of µM.Key words: pyrazinamide antimycobacterial activity antibacterial activity antifungal activity antiviral activity.
Subject(s)
Anti-Infective Agents/chemical synthesis , Pyrazinamide/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Pyrazinamide/chemistry , Pyrazinamide/pharmacologyABSTRACT
Melipona subnitida, a tropical stingless bee, is an endemic species of the Brazilian northeast and exhibits great potential for honey and pollen production in addition to its role as one of the main pollinators of the Caatinga biome. To understand the genetic structure and better assist in the conservation of this species, we characterized the population variability of M. subnitida using geometric morphometrics of the forewing and cytochrome c oxidase I gene fragment sequencing. We collected workers from six localities in the northernmost distribution. Both methodologies indicated that the variability among the sampled populations is related both to the environment in which samples were collected and the geographical distance between the sampling sites, indicating that differentiation among the populations is due to the existence of at least evolutionary lineages. Molecular clock data suggest that this differentiation may have begun in the middle Pleistocene, approximately 396 kya. The conservation of all evolutionary lineages is important since they can present differential resistance to environmental changes, as resistance to drought and diseases.
Subject(s)
Bees , Biological Evolution , DNA, Mitochondrial/genetics , Genetic Variation , Wings, Animal/anatomy & histology , Animals , Bees/anatomy & histology , Bees/classification , Bees/genetics , Haplotypes , Molecular Sequence Data , PhylogenyABSTRACT
Objectives: The aim of this study was to determine the degree of integration of patient safety in the training of medical faculties at universities in Spain. Methods: A descriptive, cross-sectional study was conducted. An assessment was made of the curse syllabi of Spanish medical schools, summarizing the proportion of faculties that present each of the topics recommended in the WHO's curriculum guide. Results: Of the 49 faculties, access to the curse syllabus of the subjects for the academic year 2023-2024 was obtained from 38 (78%). Although 82% of the faculties integrated some patient safety topic, only 56% included between 1 and 3 of the 11 topics recommended by WHO. The maximum number of integrated topics was 7, and this was only achieved by 1 faculty. Conclusion: There is progress in the incorporation of fundamental concepts in patient safety, but the comprehensive implementation of all topics recommended by the WHO in Spanish medical schools is insufficient.
Subject(s)
Curriculum , Patient Safety , Spain , Humans , Cross-Sectional Studies , Education, Medical , Schools, Medical , World Health OrganizationABSTRACT
Biobanks are infrastructures essential for research involving multi-disciplinary teams and an increasing number of stakeholders. In the field of personalized medicine, biobanks play a key role through the provision of well-characterized and annotated samples protecting at the same time the right of donors. The Andalusian Public Health System Biobank (SSPA Biobank) has implemented a global information management system made up of different modules that allow for the recording, traceability and monitoring of all the information associated with the biobank operations. The data model, designed in a standardized and normalized way according to international initiatives on data harmonization, integrates the information necessary to guarantee the quality of results from research, benefiting researchers, clinicians and donors.