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1.
Mol Ecol ; 2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37837272

RESUMO

Syngameons represent networks of otherwise distinct species connected by limited gene exchange. Although most studies have focused on how species maintain their cohesiveness despite gene flow, there are additional relevant questions regarding the evolutionary dynamics of syngameons and their drivers, as well as the success of their members and the network as a whole. Using a ddRADseq approach, we analysed the genetic structure, genomic clines and demographic history of a coastal hybrid zone involving two species of the Armeria (Plumbaginaceae) syngameon in southern Spain. We inferred that a peripheral population of the sand dune-adapted A. pungens diverged from the rest of the conspecific populations and subsequently hybridized with a locally more abundant pinewood congener, A. macrophylla. Both species display extensive plastid DNA haplotype sharing. Genomic cline analysis identified bidirectional introgression, but more outlier loci with excess A. pungens than A. macrophylla ancestry, suggesting the possibility of selection for A. pungens alleles. This is consistent with the finding that the A. pungens phenotype is selected for in open habitats, and with the strong correlation found between ancestry and phenotype. Taken together, our analyses suggest an intriguing scenario in which bidirectional introgression may, on the one hand, help to avoid reduced levels of genetic diversity due to the small size and isolated location of the A. pungens range-edge population, thereby minimizing demographic risks of stochastic extinction. On the other hand, the data also suggest that introgression into A. macrophylla may allow individuals to grow in open, highly irradiated, deep sandy, salt-exposed habitats.

2.
Heredity (Edinb) ; 131(5-6): 307-315, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37884616

RESUMO

An interesting conundrum was recently revealed by R. Abbott when he found that the number of hybrid zones reported in the literature for plants is very low, given the propensity of plants to hybridise. In another literature survey on hybrid zones performed over the period 1970-2022, we found that the number of hybrid zones reported for vertebrates was 2.3 times greater than that reported for vascular plants, even though there are about six times more vascular plant species than vertebrates. Looking at the number of papers reporting hybrid zones, there are 4.9 times more on vertebrates than on vascular plants. These figures support the relevance of this conundrum. In this paper we aim to shed light on this question by providing a structured discussion of the causes that may underlie this conundrum. We propose six non-mutually exclusive factors, namely lack or deficit of spatial structure, lack or deficit of genetic structure, effects of hybridisation between non-closely related species, lability of plant hybrid zones over time, botanists' perception of hybridisation, and deficit of population genetic data. There does not appear to be a single factor that explains our puzzle, which applies to all cases of plants where hybridisation is detected but no hybrid zone is reported. It is argued that some plant features suggest that the puzzle is not, at least entirely, due to insufficient knowledge of the specific cases, a hypothesis that should be addressed with a wider range of empirical data across different taxonomic groups.


Assuntos
Hibridização Genética , Plantas , Masculino , Animais , Plantas/genética , Genética Populacional
3.
Am J Bot ; 110(2): e16121, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36541247

RESUMO

PREMISE: The interfertile species Anacyclus clavatus, A. homogamos, and A. valentinus represent a plant complex coexisting in large anthropic areas of the western Mediterranean Basin with phenotypically mixed populations exhibiting a great floral variation. The goal of this study was to estimate the genetic identity of each species, to infer the role of hybridization in the observed phenotypic diversity, and to explore the effect of climate on the geographic distribution of species and genetic clusters. METHODS: We used eight nuclear microsatellites to genotype 585 individuals from 31 populations of three Anacyclus species for population genetic analyses by using clustering algorithms based on Bayesian models and ordination methods. In addition, we used ecological niche models and niche overlap analyses for both the species and genetic clusters. We used an expanded data set, including 721 individuals from 129 populations for ecological niche models of the genetic clusters. RESULTS: We found a clear correspondence between species and genetic clusters, except for A. clavatus that included up to three genetic clusters. We detected individuals with admixed genetic ancestry in A. clavatus and in mixed populations. Ecological niche models predicted similar distributions for species and genetic clusters. For the two specific genetic clusters of A. clavatus, ecological niche models predicted remarkably different areas. CONCLUSIONS: Gene flow between Anacyclus species likely explains phenotypic diversity in contact areas. In addition, we suggest that introgression could be involved in the origin of one of the two A. clavatus genetic clusters, which also showed ecological differentiation.


Assuntos
Ecossistema , Deriva Genética , Teorema de Bayes , Clima , Análise por Conglomerados , Variação Genética
4.
J Environ Manage ; 345: 118696, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37549639

RESUMO

Invasive alien species have widespread impacts on native biodiversity and ecosystem services. Since the number of introductions worldwide is continuously rising, it is essential to prevent the entry, establishment and spread of new alien species through a systematic examination of future potential threats. Applying a three-step horizon scanning consensus method, we evaluated non-established alien species that could potentially arrive, establish and cause major ecological impact in Spain within the next 10 years. Overall, we identified 47 species with a very high risk (e.g. Oreochromis niloticus, Popillia japonica, Hemidactylus frenatus, Crassula helmsii or Halophila stipulacea), 61 with high risk, 93 with moderate risk, and 732 species with low risk. Many of the species categorized as very high or high risk to Spanish biodiversity are either already present in Europe and neighbouring countries or have a long invasive history elsewhere. This study provides an updated list of potential invasive alien species useful for prioritizing efforts and resources against their introduction. Compared to previous horizon scanning exercises in Spain, the current study screens potential invaders from a wider range of terrestrial, freshwater, and marine organisms, and can serve as a basis for more comprehensive risk analyses to improve management and increase the efficiency of the early warning and rapid response framework for invasive alien species. We also stress the usefulness of measuring agreement and consistency as two different properties of the reliability of expert scores, in order to more easily elaborate consensus ranked lists of potential invasive alien species.


Assuntos
Ecossistema , Espécies Introduzidas , Espanha , Reprodutibilidade dos Testes , Biodiversidade
5.
J Vet Pharmacol Ther ; 45(3): 235-244, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35038171

RESUMO

Enflicoxib is approved for the treatment of pain and inflammation in canine osteoarthritis. The objective of this work was to assess the mechanistic basis of enflicoxib therapy investigating the COX inhibitory activity of enflicoxib (racemate), its enantiomers and its main metabolites using the canine whole blood assay. The (R)-(+)-Enflicoxib enantiomer and metabolite M8 (hydroxylated pyrazoline) did not induce significant COX inhibition. Enflicoxib and its (S)-(-)-Enflicoxib enantiomer inhibited COX-1 and COX-2 with variable degree of preferential isoform inhibition, but no significant therapeutic effect is anticipated in vivo. The pyrazol metabolite showed the highest COX-2 inhibition and was the most selective (IC50 COX-1/ COX-2 ratio: 19.45). As the pyrazol metabolite shows saturable binding to red blood cells, its in vivo concentrations in plasma are lower than in whole blood. Accordingly, when applying the red blood cell partitioning, the respective IC50 and IC80 for COX-2 inhibition decreased from 2.8 µM (1129 ng/ml) and 13.4 µM (5404 ng/ml) to 0.2 µM (80.7 ng/ml) and 1.2 µM (484 ng/ml) and the selectivity ratio increased to close to 55. The corrected pyrazol metabolite IC50 and IC80 are well within the plasma levels described in treated dogs.


Assuntos
Doenças do Cão , Osteoartrite , Animais , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2/farmacologia , Doenças do Cão/tratamento farmacológico , Cães , Osteoartrite/veterinária , Pirazóis , Sulfonamidas
6.
Sensors (Basel) ; 21(3)2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33498693

RESUMO

In recent years the Time-Sensitive Networking (TSN) Task Group (TG) has been working on proposing a series of standards to provide Ethernet with hard real-time guarantees, online management of the traffic and fault tolerance mechanisms. In this way the TG expects to create the network technology of future novel applications with real-time and reliability requirements. TSN proposes using spatial redundancy to increase the reliability of Ethernet networks, but using spatial redundancy to tolerate temporary faults is not a cost-effective solution. For this reason, we propose to use time redundancy to tolerate temporary faults in the links of TSN-based networks. Specifically, we have proposed the Proactive Transmission of Replicated Frames (PTRF) mechanism, which consists in transmitting several copies of each frame in a preventive manner. In this article we present for the first time a detailed description of the mechanism, with the three different approaches we have designed. We also present the implementation of PTRF in a real TSN prototype. Furthermore, we carry out a qualitative comparison of the different approaches of the mechanism and we experimentally evaluate the approaches of the mechanism in a quantitative manner from three perspectives: the end-to-end delay, the jitter and the bandwidth consumption.

7.
Sensors (Basel) ; 21(24)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34960521

RESUMO

The Time-Sensitive Networking (TSN) Task Group has standardised different mechanisms to provide Ethernet with hard real-time guarantees and reliability in layer 2 of the network architecture. Specifically, TSN proposes using space redundancy to increase the reliability of Ethernet networks, but using space redundancy to tolerate temporary faults is not a cost-effective solution. For this reason, we propose to use time redundancy to tolerate temporary faults in the links of TSN-based networks. Specifically, in previous works we proposed the Proactive Transmission of Replicated Frames (PTRF) mechanism to tolerate temporary faults in the links. Now, in this work we present a series of models of TSN and PTRF developed using PRISM, a probabilistic model checker that can be used to evaluate the reliability of systems. After that, we carry out a parametric sensitivity analysis of the reliability achievable by TSN and PTRF and we show that we can increase the reliability of TSN-based networks using PTRF to tolerate temporary faults in the links of TSN networks. This is the first work that presents a quantitative analysis of the reliability of TSN networks.


Assuntos
Redes Locais , Redes Locais/normas , Reprodutibilidade dos Testes
8.
Ann Bot ; 125(4): 611-623, 2020 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-31697800

RESUMO

BACKGROUND AND AIMS: Changes in the amount of repetitive DNA (dispersed and tandem repeats) are considered the main contributors to genome size variation across plant species in the absence of polyploidy. However, the study of repeatome dynamism in groups showing contrasting genomic features and complex evolutionary histories is needed to determine whether other processes underlying genome size variation may have been overlooked. The main aim here was to elucidate which mechanism best explains genome size evolution in Anacyclus (Asteraceae). METHODS: Using data from Illumina sequencing, we analysed the repetitive DNA in all species of Anacyclus, a genus with a reticulate evolutionary history, which displays significant genome size and karyotype diversity albeit presenting a stable chromosome number. KEY RESULTS: By reconstructing ancestral genome size values, we inferred independent episodes of genome size expansions and contractions during the evolution of the genus. However, analysis of the repeatome revealed a similar DNA repeat composition across species, both qualitative and quantitative. Using comparative methods to study repeatome dynamics in the genus, we found no evidence for repeat activity causing genome size variation among species. CONCLUSIONS: Our results, combined with previous cytogenetic data, suggest that genome size differences in Anacyclus are probably related to chromosome rearrangements involving losses or gains of chromosome fragments, possibly associated with homoploid hybridization. These could represent balanced rearrangements that do not disrupt gene dosage in merged genomes, for example via chromosome segment exchanges.


Assuntos
Asteraceae/genética , DNA de Plantas , Evolução Molecular , Tamanho do Genoma , Genoma de Planta , Humanos , Poliploidia
9.
Am J Bot ; 107(1): 116-125, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31903550

RESUMO

PREMISE: Gynomonoecy is an infrequent sexual system in angiosperms, although widely represented within the Asteraceae family. Currently, the hypothesis of two nuclear loci controling gynomonoecy is the most accepted. However, the genic interactions are still uncertain. Anacyclus clavatus, A. homogamos, and A. valentinus differ in their sexual system and floral traits. Here, we investigate the inheritance of gynomonoecy in this model system to understand its prevalence in the family. METHODS: We selected six natural populations (two per species) for intra- and interspecific experimental crosses, and generated a total of 1123 individuals from the F1 generation, F2 , and backcrosses for sexual system characterization. The frequency of gynomonoecy observed for each cross was tested to fit different possible hypotheses of genic interaction. Additionally, the breeding system and the degree of reproductive isolation between these species were assessed. RESULTS: Complementary epistasis, in which two dominant alleles are required for trait expression, explained the frequencies of gynomonoecy observed across all generations. The heterozygosity inferred in Anacyclus valentinus, as well as its lower and variable seed set, is congruent with its hybrid origin. CONCLUSIONS: In our model system gynomonoecy is controlled by complementary epistasis of two genes. A common origin of this sexual system in Asteraceae, in which genic duplications, mutations, and hybridization between lineages played a key role, is hypothesized whereas independent evolutionary pathways and possibly diverse underlying genetic factors are suggested for gynomonoecy expression in other angiosperm families.


Assuntos
Asteraceae , Evolução Biológica , Cruzamento , Flores , Fenótipo , Sementes
10.
Am J Bot ; 106(2): 231-243, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30801674

RESUMO

PREMISE OF THE STUDY: Ray flowers commonly observed in daisies' flowering heads are a well-known example of advertising structures for enhancing pollinator attraction. Despite this, ray loss has occurred in multiple lineages, which still rely on pollinators, suggesting that rayless phenotypes could also be adaptive for animal-pollination. Here, we investigate the benefits and costs of these specialized floral advertising structures by comparing rayed and rayless phenotypes in two hybridizing closely related species. METHODS: We assessed the advantages and costs of ray production in terms of floral visitor's attraction, pollen limitation, and female reproductive success using the broad natural variation on ray size and number at the contact zone of A. clavatus (rayed) and A. valentinus (rayless). In addition, we experimentally explored the effect of rays under controlled neighborhoods and the effect of ray removal on fruit production. KEY RESULTS: In sympatry, rayed phenotypes attracted significantly more visitors than rayless plants, in which seed production was pollen limited. However, rayed phenotypes did not show higher fruit set or seed production than rayless phenotypes. Fruit set and seed production benefited from denser neighborhood displays and larger individual floral displays, respectively. The removal of ray florets did not appear to enable resource reallocation to fruit production. CONCLUSIONS: Rayless heads compensated their lower visitation rate by means of a higher number of flowers per head achieving similar fecundity levels to rayed plants. The larger size of rayless heads might thus indicate an inflorescence-level trade-off between attraction and fertility.


Assuntos
Asteraceae/fisiologia , Flores/fisiologia , Aptidão Genética , Animais , Asteraceae/anatomia & histologia , Flores/anatomia & histologia , Frutas/crescimento & desenvolvimento , Fenótipo
11.
J Labelled Comp Radiopharm ; 62(8): 354-379, 2019 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-30850991

RESUMO

Because of their neuroprotective potential, GluN2B-selective ligands are of great interest for the treatment of various neurological and neurodegenerative disorders. Fluorinated benzo[7]annulen-7-amines, capable for PET, were synthesized by combining fluorinated phenylalkylamines with differently substituted ketones. Relationships between substitution pattern and GluN2B affinity as well as selectivity towards σ1 and σ2 receptors were investigated. Two promising ligands (18a and 20c) were selected for further pharmacological evaluation. Besides a slight serotonin transporter (SERT), norepinephrine transporter (NET), and hERG affinity, they did not show interaction with other targets. Furthermore, the pKa value of a set fluorinated ligands, bearing the fluorine atom in different positions, was determined.


Assuntos
Aminas/síntese química , Aminas/farmacologia , Halogenação , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Aminas/química , Aminas/metabolismo , Técnicas de Química Sintética , Receptores de N-Metil-D-Aspartato/metabolismo , Especificidade por Substrato
12.
Ann Bot ; 122(3): 387-395, 2018 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-29800070

RESUMO

Background and Aims: Interstitial telomeric repeat (ITR) sites, consisting of tandem repeats of telomeric motifs localized at intrachromosomal sites, have been reported in a few unrelated organisms including plants. However, the causes for the occurrence of ITRs outside of the chromosomal termini are not fully understood. One possible explanation are the chromosomal rearrangements involving telomeric sites, which could also affect the location of other structural genome elements, such as the 45S rDNA. Taking advantage of the high dynamism in 45S rDNA loci previously found in Anacyclus (Asteraceae, Anthemideae), the occurrence and patterns of variation of ITRs were explored in this genus with the aim of finding common underlying causes. Methods: In total, 132 individuals from 44 populations of nine species were analysed by fluorescence in situ hybridization using an Arabidopsis-type telomeric sequence as a probe. Key results: Variable presence of ITR sites was detected in six out of nine species of Anacyclus, ranging from two to 45 sites and showing contrasting chromosomal locations and a differential presence of the ITR site on homologous chromosome pairs. At the intraspecific level, the ranges were as large as 0-12 ITR sites. Although only 26 % of the total observed ITR sites were localized in chromosomes bearing 45S rDNA loci, all cases of interstitial 45S rDNA reported in a previous work co-occurred with ITRs in close proximity in the same chromosome arms. Conclusions: High levels of ITR polymorphism within a single species have not been previously reported in plants and suggest that this pattern might have been overlooked due to insufficient sampling. Although ancient Robertsonian translocations or the amplification of terminal 45S rDNA sites cannot, on their own, explain all of the levels of variability in ITRs reported here, there are suggestions that they may have been involved in the evolutionary history of this genus or its ancestors in Anthemideae.


Assuntos
Asteraceae/genética , Variação Genética/genética , Telômero/genética , DNA de Plantas/genética , DNA Ribossômico/genética , Loci Gênicos/genética , Genética Populacional , Cariótipo , Motivos de Nucleotídeos , Polimorfismo Genético/genética , RNA Ribossômico/genética , Sequências de Repetição em Tandem/genética
13.
Mol Phylogenet Evol ; 82 Pt A: 118-30, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25281923

RESUMO

The present study provides results of multi-species coalescent species tree analyses of DNA sequences sampled from multiple nuclear and plastid regions to infer the phylogenetic relationships among the members of the subtribe Leucanthemopsidinae (Compositae, Anthemideae), to which besides the annual Castrilanthemum debeauxii (Degen, Hervier & É.Rev.) Vogt & Oberp., one of the rarest flowering plant species of the Iberian Peninsula, two other unispecific genera (Hymenostemma, Prolongoa), and the polyploidy complex of the genus Leucanthemopsis belong. Based on sequence information from two single- to low-copy nuclear regions (C16, D35, characterised by Chapman et al. (2007)), the multi-copy region of the nrDNA internal transcribed spacer regions ITS1 and ITS2, and two intergenic spacer regions of the cpDNA gene trees were reconstructed using Bayesian inference methods. For the reconstruction of a multi-locus species tree we applied three different methods: (a) analysis of concatenated sequences using Bayesian inference (MrBayes), (b) a tree reconciliation approach by minimizing the number of deep coalescences (PhyloNet), and (c) a coalescent-based species-tree method in a Bayesian framework ((∗)BEAST). All three species tree reconstruction methods unequivocally support the close relationship of the subtribe with the hitherto unclassified genus Phalacrocarpum, the sister-group relationship of Castrilanthemum with the three remaining genera of the subtribe, and the further sister-group relationship of the clade of Hymenostemma+Prolongoa with a monophyletic genus Leucanthemopsis. Dating of the (∗)BEAST phylogeny supports the long-lasting (Early Miocene, 15-22Ma) taxonomical independence and the switch from the plesiomorphic perennial to the apomorphic annual life-form assumed for the Castrilanthemum lineage that may have occurred not earlier than in the Pliocene (3Ma) when the establishment of a Mediterranean climate with summer droughts triggered evolution towards annuality.


Assuntos
Asteraceae/classificação , Filogenia , Asteraceae/genética , Teorema de Bayes , DNA de Cloroplastos/genética , DNA de Plantas/genética , DNA Espaçador Ribossômico/genética , Europa (Continente) , Fósseis , Modelos Genéticos , Poliploidia , Análise de Sequência de DNA
14.
Ann Bot ; 112(8): 1597-612, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23287557

RESUMO

BACKGROUND AND AIMS: Most of the diversity in the pseudanthia of Asteraceae is based on the differential symmetry and sexuality of its flowers. In Anacyclus, where there are (1) homogamous capitula, with bisexual, mainly actinomorphic and pentamerous flowers; and (2) heterogamous capitula, with peripheral zygomorphic, trimerous and long-/short-rayed female flowers, the floral ontogeny was investigated to infer their origin. METHODS: Floral morphology and ontogeny were studied using scanning electron microscope and light microscope techniques. KEY RESULTS: Disc flowers, subtended by paleae, initiate acropetally. Perianth and androecium initiation is unidirectional/simultaneous. Late zygomorphy occurs by enlargement of the adaxial perianth lobes. In contrast, ray flowers, subtended by involucral bracts, initiate after the proximal disc buds, breaking the inflorescence acropetal pattern. Early zygomorphy is manifested through the fusion of the lateral and abaxial perianth lobes and the arrest of the adaxials. We report atypical phenotypes with peripheral 'trumpet' flowers from natural populations. The peripheral 'trumpet' buds initiate after disc flowers, but maintain an actinomorphic perianth. All phenotypes are compared and interpreted in the context of alternative scenarios for the origin of the capitulum and the perianth identity. CONCLUSIONS: Homogamous inflorescences display a uniform floral morphology and development, whereas the peripheral buds in heterogamous capitula display remarkable plasticity. Disc and ray flowers follow different floral developmental pathways. Peripheral zygomorphic flowers initiate after the proximal actinomorphic disc flowers, behaving as lateral independent units of the pseudanthial disc from inception. The perianth and the androecium are the most variable whorls across the different types of flowers, but their changes are not correlated. Lack of homology between hypanthial appendages and a calyx, and the perianth double-sided structure are discussed for Anacyclus together with potential causes of its ray flower plasticity.


Assuntos
Asteraceae/anatomia & histologia , Asteraceae/crescimento & desenvolvimento , Evolução Biológica , Flores/anatomia & histologia , Flores/crescimento & desenvolvimento , Asteraceae/citologia , Asteraceae/ultraestrutura , Flores/citologia , Flores/ultraestrutura , Inflorescência/anatomia & histologia , Inflorescência/citologia , Inflorescência/crescimento & desenvolvimento , Inflorescência/ultraestrutura , Fenótipo
15.
Sci Total Environ ; 874: 162416, 2023 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-36858222

RESUMO

The northwestern coast of the Iberian Peninsula is a region characterized by pronounced hydrologic and biogeochemical activity, resulting in important fish and shellfish resources whose exploitation has a strong local socioeconomic impact. This high biological diversity is strongly dependent on coastal upwelling induced by favourable winds, which presents seasonal variability. This motivates the present study, which aims to understand the relation between local circulation, hydrography and Chl-a concentration under summer upwelling events of different intensities and clarify their effects in the region. To achieve this purpose, a coupled physical-biological model was developed and validated for the northwestern coast of the Iberian Peninsula, based on the use of MOHID modelling system and the application of a nested domains methodology. Comparison of predictions with observations demonstrated the model's accuracy in reproducing the physical and biogeochemical properties of the study region, both at the surface and along the water column. The study of different summer upwelling events shows that the local phytoplankton patterns are dependent on the characteristics of the event. Results show that under high upwelling favourable winds, a surface southwestward flow and an equatorward flow through the water column develop near the coast, inducing offshore advection of nutrient and phytoplankton-rich waters. Otherwise, under light upwelling favourable winds, surface currents are weak, a poleward flow develops, and phytoplankton is retained near the coast.


Assuntos
Fitoplâncton , Vento , Animais , Estações do Ano , Biodiversidade , Água
16.
Arch Bronconeumol ; 59(8): 497-501, 2023 Aug.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37321904

RESUMO

INTRODUCTION: Patients with obesity hypoventilation syndrome (OHS) need treatment with positive pressure either with continuous (CPAP) or double pressure (NIV). The apnea-hypopnea index (AHI) is considered a key data for making therapeutic decisions. We hypothesized that HR may be an useful tool to establish different phenotypes and individualize treatment in patients with OHS. Our objective was to analyze the role of the respiratory center response to hypercapnia (HR) in the adequacy of positive airway pressure therapy. METHOD: We included subjects with OHS treated with CPAP or NIV according to AHI and baseline pCO2. We analyzed therapeutic effectiveness and treatment changes prioritizing CPAP if AHI>30/h. Therapy was considered adequate if it was effective after two years. HR was measured with the p0.1/pEtCO2 ratio and its capability to select therapy was analyzed. The statistical study was performed by means comparison (Student's t) and multivariate analysis (logistic regression). RESULTS: 67 subjects were included of 68(11) years old, 37 (55%) males, initially 45 (67%) treated with NIV and 22 (33%) with CPAP, one case was excluded and in 25 (38%) the treatment was changed. Finally, CPAP was adequate for 29 subjects (44%) and NIV for 37 (56%). The CPAP group showed AHI 57/h (24) and p0.1/pEtCO2 0.37cmH2O/mmHg (0.23), NIV group AHI 43/h (35) and p0.1/pEtCO2 0.24 (0.15) with p=0.049 and 0.006. In multivariate analysis, p0.1/pEtCO2 (p=0.033) and AHI>30 (p=0.001) were predictors of adequate therapy. CONCLUSION: Measuring the RH of the respiratory center helps to select the most appropriate treatment for patients with OHS.


Assuntos
Ventilação não Invasiva , Síndrome de Hipoventilação por Obesidade , Masculino , Feminino , Humanos , Síndrome de Hipoventilação por Obesidade/terapia , Centro Respiratório , Pressão Positiva Contínua nas Vias Aéreas , Fenômenos Fisiológicos Respiratórios , Hipercapnia/etiologia , Hipercapnia/terapia
17.
J Med Chem ; 66(17): 12499-12519, 2023 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-37607512

RESUMO

The synthesis and pharmacological activity of a new series of isoxazolylpyrimidines as sigma-2 receptor (σ2R) ligands are reported. Modification of a new hit retrieved in an HTS campaign allowed the identification of the compound WLB-89462 (20c) with good σ2R affinity (Ki = 13 nM) and high selectivity vs both the σ1R (Ki = 1777 nM) and a general panel of 180 targets. It represents one of the first σ2R ligands with drug-like properties, linked to a good physicochemical and ADMET profile (good solubility, no CYP inhibition, good metabolic stability, high permeability, brain penetration, and high oral exposure in rodents). Compound 20c shows neuroprotective activity in vitro and improves short-term memory impairment induced by hippocampal injection of amyloid ß peptide in rats. Together with the promising effects in the chronic models where 20c is currently being evaluated, these results pave the way toward its clinical development as a neuroprotective agent.


Assuntos
Peptídeos beta-Amiloides , Fármacos Neuroprotetores , Animais , Ratos , Ligantes , Neuroproteção , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
18.
Am J Bot ; 99(2): e74-7, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22301891

RESUMO

PREMISE OF THE STUDY: The development of three low-copy nuclear markers for low taxonomic level phylogenies in Asteraceae with emphasis on the subtribe Hieraciinae is reported. METHODS AND RESULTS: Marker candidates were selected by comparing a Lactuca complementary DNA (cDNA) library with public DNA sequence databases. Interspecific variation and phylogenetic signal of the selected genes were investigated for diploid taxa from the subtribe Hieraciinae and compared to a reference phylogeny. Their ability to cross-amplify was assessed for other Asteraceae tribes. All three markers had higher variation (2.1-4.5 times) than the internal transcribed spacer (ITS) in Hieraciinae. Cross-amplification was successful in at least seven other tribes of the Asteraceae. Only three cases indicating the presence of paralogs or pseudogenes were detected. CONCLUSIONS: The results demonstrate the potential of these markers for phylogeny reconstruction in the Hieraciinae as well as in other Asteraceae tribes, especially for very closely related species.


Assuntos
Asteraceae/genética , Núcleo Celular/genética , Genes de Plantas , Asteraceae/classificação , Sequência de Bases , Cromossomos de Plantas/genética , Biologia Computacional , Primers do DNA/genética , DNA Intergênico/genética , DNA de Plantas/genética , Diploide , Dosagem de Genes , Biblioteca Gênica , Marcadores Genéticos , Variação Genética , Filogenia , Pseudogenes , Análise de Sequência de DNA
19.
Cryobiology ; 64(1): 50-9, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21985768

RESUMO

BACKGROUND: There is an urgent need of vascular substitutes (VS) to be used in lower limb revascularization procedures when autologous veins are not available and synthetic prosthesis are contraindicated. Since the mechanical differences with respect to native vessels are determinants of the VS failure, the substitutes should have mechanical properties similar to those of the recipient vessels. The use of cryopreserved arteries (cryografts) could overcome limitations of available VS. These work aims were to characterize (a) native vessels/implanted cryografts mechanical and geometrical coupling, (b) cryografts capability to ensure mismatch levels lesser than those expected for expanded polytetrafluoroethylene (ePTFE), (c) cryografts functional properties considering their histological and ultra-structural characteristics. METHODS: Instantaneous pressure (mechano-transducers) and diameter (B-mode echography) were obtained in implanted femoro-popliteal, ileo-femoro-popliteal and axilo-humeral cryografts (n=8), in femoral arteries from recipients (n=8), recipient-like (n=15) and multiorgan donors-like (n=15) subjects, and in ePTFE segments (n=10). Calculus: (a) Mechanical parameters: elastic modulus, arterial compliance, distensibility and characteristic impedance; (b) Arterial remodeling: diameter, wall thickness, cross-sectional area and wall-to-lumen ratio; (c) Native vessels/VS coupling. Histological and structural analysis were done in explanted femoro-popliteal and axilo-humeral cryografts (n=7). RESULTS: Post-implant the cryografts remodeled. Their stiffness increased and the conduit function diminished. Remodeling resulted in an improvement in native vessels/cryograft coupling, which was always better than native vessels/ePTFE coupling. CONCLUSIONS: Post-implant cryograft remodeling improved native vessels/cryografts coupling. Cryografts would have mechanical and geometrical advantages over ePTFE. Anastomotic cryograft remodeling differed from that expected only due to haemodynamic factors. The structural properties of the remodeled cryografts contribute to explain their functional characteristics.


Assuntos
Implante de Prótese Vascular/métodos , Criocirurgia/métodos , Artéria Femoral/transplante , Idoso , Anastomose Cirúrgica/métodos , Prótese Vascular , Criopreservação , Feminino , Artéria Femoral/fisiopatologia , Artéria Femoral/cirurgia , Humanos , Extremidade Inferior/fisiopatologia , Extremidade Inferior/cirurgia , Masculino , Pessoa de Meia-Idade
20.
Respir Care ; 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35610030

RESUMO

BACKGROUND: The ventilatory mechanics of patients with COPD and obesity-hypoventilation syndrome (OHS) are changed when there is air trapping and auto-PEEP, which increase respiratory effort. P0.1 measures the ventilatory drive and, indirectly, respiratory effort. The aim of the study was to measure P0.1 in subjects with COPD or OHS on treatment with positive pressure and to analyze their changes in P0.1 after treatment. METHODS: With a prospective design, subjects with COPD and OHS were studied in whom positive airway pressure was applied in their treatment. P0.1 was determined at study inclusion and after 6 months of treatment. RESULTS: A total of 88 subjects were analyzed: 56% were males, and the mean age of 65 ± 9 y old. Fifty-four (61%) had OHS, and 34 (39%) had COPD. Fifty (56%) had air trapping, with an initial P0.1 value of 3.0 ± 1.3 cm H2O compared with 2.1 ± 0.7 cm H2O for subjects who did not have air trapping (P = .001). After 6 months of treatment, subjects who had air trapping had similar P0.1 as those who did not: 2.3 ± 1.1 and 2.1 ± 1 cm H2O, respectively (P = .53). In subjects with COPD, initial P0.1 was 2.9 ± 1.4 cm H2O and at 6 months 2.2 ± 1.1 cm H2O (P = .02). In subjects with OHS, initial P0.1 was 2.4 ± 1.1 cm H2O and at 6 months 2.2 ± 1.0 cm H2O (P = .28). CONCLUSIONS: COPD and air trapping were associated with greater P0.1 as a marker of respiratory effort. A decrease in P0.1 indicates less respiratory effort after treatment.

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