RESUMO
Identifying the genetic basis of local adaptation and fitness trade-offs across environments is a central goal of evolutionary biology. Cold acclimation is an adaptive plastic response for surviving seasonal freezing, and costs of acclimation may be a general mechanism for fitness trade-offs across environments in temperate zone species. Starting with locally adapted ecotypes of Arabidopsis thaliana from Italy and Sweden, we examined the fitness consequences of a naturally occurring functional polymorphism in CBF2. This gene encodes a transcription factor that is a major regulator of cold-acclimated freezing tolerance and resides within a locus responsible for a genetic trade-off for long-term mean fitness. We estimated the consequences of alternate genotypes of CBF2 on 5-y mean fitness and fitness components at the native field sites by comparing near-isogenic lines with alternate genotypes of CBF2 to their genetic background ecotypes. The effects of CBF2 were validated at the nucleotide level using gene-edited lines in the native genetic backgrounds grown in simulated parental environments. The foreign CBF2 genotype in the local genetic background reduced long-term mean fitness in Sweden by more than 10%, primarily via effects on survival. In Italy, fitness was reduced by more than 20%, primarily via effects on fecundity. At both sites, the effects were temporally variable and much stronger in some years. The gene-edited lines confirmed that CBF2 encodes the causal variant underlying this genetic trade-off. Additionally, we demonstrated a substantial fitness cost of cold acclimation, which has broad implications for potential maladaptive responses to climate change.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Mutação , Aclimatação/genética , Proteínas de Arabidopsis/genética , Fatores de Transcrição/genética , Temperatura Baixa , Aptidão GenéticaRESUMO
There is considerable evidence for local adaptation in nature, yet important questions remain regarding its genetic basis. How many loci are involved? What are their effect sizes? What is the relative importance of conditional neutrality versus genetic trade-offs? Here we address these questions in the self-pollinating, annual plant Arabidopsis thaliana. We used 400 recombinant inbred lines (RILs) derived from two locally adapted populations in Italy and Sweden, grew the RILs and parents at the parental locations, and mapped quantitative trait loci (QTL) for mean fitness (fruits/seedling planted). We previously published results from the first 3 years of the study, and here add five additional years, providing a unique opportunity to assess how temporal variation in selection might affect QTL detection and classification. We found 10 adaptive and one maladaptive QTL in Italy, and six adaptive and four maladaptive QTL in Sweden. The discovery of maladaptive QTL at both sites suggests that even locally adapted populations are not always at their genotypic optimum. Mean effect sizes for adaptive QTL, 0.97 and 0.55 fruits in Italy and Sweden, respectively, were large relative to the mean fitness of the RILs (approximately 8 fruits/seedling planted at both sites). Both genetic trade-offs (four cases) and conditional neutrality (seven cases) contribute to local adaptation in this system. The 8-year dataset provided greater power to detect QTL and to estimate their locations compared to our previous 3-year study, identifying one new genetic trade-off and resolving one genetic trade-off into two conditionally adaptive QTL.
Assuntos
Arabidopsis , Arabidopsis/genética , Adaptação Fisiológica/genética , Locos de Características Quantitativas/genética , Aclimatação , Genótipo , Plântula/genéticaRESUMO
PREMISE: What maintains mixed mating is an evolutionary enigma. Cleistogamy-the production of both potentially outcrossing chasmogamous and obligately selfing cleistogamous flowers on the same individual plant-is an excellent system to study the costs of selfing. Inbreeding depression can prevent the evolution of greater selfing within populations, and heterosis in crosses between populations may further tip the balance in favor of outcrossing. Few empirical estimates of inbreeding depression and heterosis in the same system exist for cleistogamous species. METHODS: We investigate the potential costs of selfing by quantifying inbreeding depression and heterosis in three populations of the cleistogamous perennial Ruellia humilis Nutt (Acanthaceae). We performed three types of hand-pollinations-self, outcross-within, and outcross-between populations-and measured seed number, germination, total flower production, and estimated cumulative fitness for the resulting progeny in a greenhouse experiment. RESULTS: We found moderate inbreeding depression for cumulative fitness (<30%) in two populations, but outbreeding depression for crosses within a third population (-26%). For between-population crosses, there was weak to modest heterosis (11-47%) in two of the population combinations, but modest to strong outbreeding depression (-21 to -71%) in the other four combinations. CONCLUSIONS: Neither inbreeding depression nor heterosis was of sufficient magnitude to explain the continued production of chasmogamous flowers given the relative energetic advantage of cleistogamous flowers previously estimated for these populations. Outbreeding depression either within or between populations makes the maintenance of chasmogamous flowers even harder to explain. More information is needed on the genetic basis of cleistogamy to resolve this conundrum.
PREMISA: Lo que mantiene los sistemas de apareamiento mixto aún es un enigma. La cleistogamia, la producción de flores con potencial de cruzamiento casmógamas, y de flores cleistógamas obligadamente autofecundadas en la misma planta, es un excelente sistema para estudiar los costos de la autofecundación. La depresión endogámica puede prevenir la evolución hacia una mayor autofecundación dentro de las poblaciones, y la heterosis de los cruces entre poblaciones puede inclinar aún más la balanza a favor del cruzamiento. Existen pocas estimaciones empíricas de depresión endogámica y heterosis en el mismo sistema para especies cleistógamas. MÉTODOS: Investigamos los costos potenciales de la autofecundación cuantificando la depresión endogámica y la heterosis en tres poblaciones de la perenne cleistógama Ruellia humilis Nutt (Acanthaceae). Realizamos autopolinizaciones manuales, y cruces dentro y entre poblaciones, Medimos el número de semillas, la germinación, la producción total de flores y estimamos la acumulación de fitness para la progenie resultante en un experimento de invernadero. RESULTADOS: Encontramos depresión endogámica moderada para fitness acumulado (<30%) en dos poblaciones, pero depresión exogámica para cruces dentro de la tercera población (-26%). Entre cruces de población, hubo heterosis de débil a modesta (11-47%) en dos de las combinaciones de poblaciones, pero depresión exogámica moderada a fuerte (-21 a -71%) en las otras cuatro combinaciones. CONCLUSIONES: Ni la depresión endogámica, ni la heterosis fueron de suficiente magnitud para explicar la producción continua de flores casmógamas dada la ventaja energética relativa de las flores cleistógamas previamente estimadas para estas poblaciones. La depresión exogámica, ya sea dentro o entre poblaciones, hace que el mantenimiento de las flores casmógamas sea aún más difícil de explicar. Se necesita más información sobre la base genética de la cleistogamia para resolver este enigma.
Assuntos
Vigor Híbrido , Depressão por Endogamia , Vigor Híbrido/genética , Endogamia , Reprodução , PolinizaçãoRESUMO
Resources allocated to survival cannot be used to increase fecundity, but the extent to which this trade-off constrains adaptation depends on overall resource status. Adaptation to local environmental conditions may therefore entail the evolution of traits that increase the amount of resources available to individuals (their resource status or 'condition'). We examined the relative contribution of trade-offs and increased condition to adaptive evolution in a recombinant inbred line population of Arabidopsis thaliana planted at the native sites of the parental ecotypes in Italy and Sweden in 2 years. We estimated genetic correlations among fitness components based on genotypic means and explored their causes with QTL mapping. The local ecotype produced more seeds per fruit than did the non-local ecotype, reflected in stronger adaptive differentiation than was previously shown based on survival and fruit number only. Genetic correlations between survival and overall fecundity, and between number of fruits and number of seeds per fruit, were positive, and there was little evidence of a trade-off between seed size and number. Quantitative trait loci for these traits tended to map to the same regions of the genome and showed positive pleiotropic effects. The results indicate that adaptive differentiation between the two focal populations largely reflects the evolution of increased ability to acquire resources in the local environment, rather than shifts in the relative allocation to different life-history traits. Differentiation both in phenology and in tolerance to cold is likely to contribute to the advantage of the local genotype at the two sites.
Assuntos
Arabidopsis , Adaptação Fisiológica/genética , Arabidopsis/genética , Aptidão Genética , Humanos , Itália , Locos de Características Quantitativas , SuéciaRESUMO
Evidence for adaptation to different climates in the model species Arabidopsis thaliana is seen in reciprocal transplant experiments, but the genetic basis of this adaptation remains poorly understood. Field-based quantitative trait locus (QTL) studies provide direct but low-resolution evidence for the genetic basis of local adaptation. Using high-resolution population genomic approaches, we examine local adaptation along previously identified genetic trade-off (GT) and conditionally neutral (CN) QTLs for fitness between locally adapted Italian and Swedish A. thaliana populations [Ågren J, et al. (2013) Proc Natl Acad Sci USA 110:21077-21082]. We find that genomic regions enriched in high FST SNPs colocalize with GT QTL peaks. Many of these high FST regions also colocalize with regions enriched for SNPs significantly correlated to climate in Eurasia and evidence of recent selective sweeps in Sweden. Examining unfolded site frequency spectra across genes containing high FST SNPs suggests GTs may be due to more recent adaptation in Sweden than Italy. Finally, we collapse a list of thousands of genes spanning GT QTLs to 42 genes that likely underlie the observed GTs and explore potential biological processes driving these trade-offs, from protein phosphorylation, to seed dormancy and longevity. Our analyses link population genomic analyses and field-based QTL studies of local adaptation, and emphasize that GTs play an important role in the process of local adaptation.
Assuntos
Adaptação Fisiológica/genética , Arabidopsis/genética , Genoma de Planta , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Itália , SuéciaRESUMO
PREMISE: Despite myriad examples of local adaptation, the phenotypes and genetic variants underlying such adaptive differentiation are seldom known. Recent work on freezing tolerance and local adaptation in ecotypes of Arabidopsis thaliana from Italy and Sweden provides an essential foundation for uncovering the genotype-phenotype-fitness map for an adaptive response to a key environmental stress. METHODS: We examined the consequences of a naturally occurring loss-of-function (LOF) mutation in an Italian allele of the gene that encodes the transcription factor CBF2, which underlies a major freezing-tolerance locus. We used four lines with a Swedish genetic background, each containing a LOF CBF2 allele. Two lines had introgression segments containing the Italian CBF2 allele, and two contained deletions created using CRISPR-Cas9. We used a growth chamber experiment to quantify freezing tolerance and gene expression before and after cold acclimation. RESULTS: Freezing tolerance was lower in the Italian (11%) compared to the Swedish (72%) ecotype, and all four experimental CBF2 LOF lines had reduced freezing tolerance compared to the Swedish ecotype. Differential expression analyses identified 10 genes for which all CBF2 LOF lines, and the IT ecotype had similar patterns of reduced cold responsive expression compared to the SW ecotype. CONCLUSIONS: We identified 10 genes that are at least partially regulated by CBF2 that may contribute to the differences in cold-acclimated freezing tolerance between the Italian and Swedish ecotypes. These results provide novel insight into the molecular and physiological mechanisms connecting a naturally occurring sequence polymorphism to an adaptive response to freezing conditions.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Aclimatação , Temperatura Baixa , Congelamento , Regulação da Expressão Gênica de Plantas , SuéciaRESUMO
The importance of genetic drift in shaping patterns of adaptive genetic variation in nature is poorly known. Genetic drift should drive partially recessive deleterious mutations to high frequency, and inter-population crosses may therefore exhibit heterosis (increased fitness relative to intra-population crosses). Low genetic diversity and greater genetic distance between populations should increase the magnitude of heterosis. Moreover, drift and selection should remove strongly deleterious recessive alleles from individual populations, resulting in reduced inbreeding depression. To estimate heterosis, we crossed 90 independent line pairs of Arabidopsis thaliana from 15 pairs of natural populations sampled across Fennoscandia and crossed an additional 41 line pairs from a subset of four of these populations to estimate inbreeding depression. We measured lifetime fitness of crosses relative to parents in a large outdoor common garden (8,448 plants in total) in central Sweden. To examine the effects of genetic diversity and genetic distance on heterosis, we genotyped parental lines for 869 SNPs. Overall, genetic variation within populations was low (median expected heterozygosity = 0.02), and genetic differentiation was high (median FST = 0.82). Crosses between 10 of 15 population pairs exhibited significant heterosis, with magnitudes of heterosis as high as 117%. We found no significant inbreeding depression, suggesting that the observed heterosis is due to fixation of mildly deleterious alleles within populations. Widespread and substantial heterosis indicates an important role for drift in shaping genetic variation, but there was no significant relationship between fitness of crosses relative to parents and genetic diversity or genetic distance between populations.
Assuntos
Arabidopsis/genética , Vigor Híbrido , Aptidão Genética , Depressão por EndogamiaRESUMO
Dysautonomia and headache are 2 common diagnoses within pediatric neurology; in the case of dysautonomia, a lack of consideration may lead to misdiagnosis. Despite being common conditions, there is a lot to learn about each individually as well as collectively. Many of the symptoms between headache and dysautonomia patients overlap making the diagnosis difficult. Migraine patients often exhibit symptoms of dysautonomia, namely postural orthostatic tachycardia syndrome (POTS); yet these symptoms are overlooked or lumped in as a part of their migraine diagnosis. The distinction or coexistence between dysautonomia and headache is identified through a thorough history, a full exam, and an open mind. This is crucial for the treatment and outcomes of these patients. Struggles arise when critical treatment differences are overlooked because dysautonomia is not considered. In this review, we will look at the epidemiology of dysautonomia and headache with focus on POTS and migraine. We will then compare the clinical features of both conditions as well as some hypothesized pathophysiology overlaps. We will conclude by summarizing the diagnostic approach and multitiered treatment options for POTS and migraine.
Assuntos
Cefaleia/epidemiologia , Disautonomias Primárias/epidemiologia , Adolescente , Idade de Início , Analgésicos/uso terapêutico , Criança , Pré-Escolar , Comorbidade , Feminino , Cefaleia/diagnóstico , Cefaleia/tratamento farmacológico , Cefaleia/fisiopatologia , Humanos , Lactente , Masculino , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/fisiopatologia , Exame Neurológico , Neurotransmissores/metabolismo , Acoplamento Neurovascular , Síndrome da Taquicardia Postural Ortostática/diagnóstico , Síndrome da Taquicardia Postural Ortostática/tratamento farmacológico , Síndrome da Taquicardia Postural Ortostática/epidemiologia , Síndrome da Taquicardia Postural Ortostática/fisiopatologia , Prevalência , Disautonomias Primárias/diagnóstico , Disautonomias Primárias/tratamento farmacológico , Disautonomias Primárias/fisiopatologia , Avaliação de Sintomas , VasodilataçãoRESUMO
Local adaptation is common, but the traits and genes involved are often unknown. Physiological responses to cold probably contribute to local adaptation in wide-ranging species, but the genetic basis underlying natural variation in these traits has rarely been studied. Using a recombinant inbred (495 lines) mapping population from locally adapted populations of Arabidopsis thaliana from Sweden and Italy, we grew plants at low temperature and mapped quantitative trait loci (QTLs) for traits related to photosynthesis: maximal quantum efficiency (Fv/Fm), rapidly reversible photoprotection (NPQfast), and photoinhibition of PSII (NPQslow) using high-throughput, whole-plant measures of chlorophyll fluorescence. In response to cold, the Swedish line had greater values for all traits, and for every trait, large effect QTLs contributed to parental differences. We found one major QTL affecting all traits, as well as unique major QTLs for each trait. Six trait QTLs overlapped with previously published locally adaptive QTLs based on fitness measured in the native environments over 3 years. Our results demonstrate that photosynthetic responses to cold can vary dramatically within a species, and may predominantly be caused by a few QTLs of large effect. Some photosynthesis traits and QTLs probably contribute to local adaptation in this system.
Assuntos
Arabidopsis/fisiologia , Temperatura Baixa , Fotossíntese/genética , Locos de Características Quantitativas , Adaptação Biológica , Arabidopsis/genética , Itália , SuéciaRESUMO
The distribution of effect sizes of adaptive substitutions has been central to evolutionary biology since the modern synthesis. Early theory proposed that because large-effect mutations have negative pleiotropic consequences, only small-effect mutations contribute to adaptation. More recent theory suggested instead that large-effect mutations could be favoured when populations are far from their adaptive peak. Here we suggest that the distributions of effect sizes are expected to differ among study systems, reflecting the wide variation in evolutionary forces and ecological conditions experienced in nature. These include selection, mutation, genetic drift, gene flow, and other factors such as the degree of pleiotropy, the distance to the phenotypic optimum, whether the optimum is stable or moving, and whether new mutation or standing genetic variation provides the source of adaptive alleles. Our goal is to review how these factors might affect the distribution of effect sizes and to identify new research directions. Until more theory and empirical work is available, we feel that it is premature to make broad generalizations about the effect size distribution of adaptive substitutions important in nature.
Assuntos
Adaptação Biológica , Evolução Biológica , Mutação , Animais , Modelos Biológicos , PlantasRESUMO
Organisms inhabiting different environments are often locally adapted, and yet despite a considerable body of theory, the genetic basis of local adaptation is poorly understood. Unanswered questions include the number and effect sizes of adaptive loci, whether locally favored loci reduce fitness elsewhere (i.e., fitness tradeoffs), and whether a lack of genetic variation limits adaptation. To address these questions, we mapped quantitative trait loci (QTL) for total fitness in 398 recombinant inbred lines derived from a cross between locally adapted populations of the highly selfing plant Arabidopsis thaliana from Sweden and Italy and grown for 3 consecutive years at the parental sites (>40,000 plants monitored). We show that local adaptation is controlled by relatively few genomic regions of small to modest effect. A third of the 15 fitness QTL we detected showed evidence of tradeoffs, which contrasts with the minimal evidence for fitness tradeoffs found in previous studies. This difference may reflect the power of our multiyear study to distinguish conditionally neutral QTL from those that reflect fitness tradeoffs. In Sweden, but not in Italy, the local genotype underlying fitness QTL was often maladaptive, suggesting that adaptation there is constrained by a lack of adaptive genetic variation, attributable perhaps to genetic bottlenecks during postglacial colonization of Scandinavia or to recent changes in selection regime caused by climate change. Our results suggest that adaptation to markedly different environments can be achieved through changes in relatively few genomic regions, that fitness tradeoffs are common, and that lack of genetic variation can limit adaptation.
Assuntos
Adaptação Biológica/genética , Arabidopsis/genética , Evolução Biológica , Meio Ambiente , Variação Genética , Locos de Características Quantitativas/genética , Análise de Variância , Arabidopsis/crescimento & desenvolvimento , Teorema de Bayes , Mapeamento Cromossômico , Cruzamentos Genéticos , Aptidão Genética/genética , Itália , Escore Lod , SuéciaRESUMO
The genetic basis of phenotypic traits is of great interest to evolutionary biologists, but their contribution to adaptation in nature is often unknown. To determine the genetic architecture of flowering time in ecologically relevant conditions, we used a recombinant inbred line population created from two locally adapted populations of Arabidopsis thaliana from Sweden and Italy. Using these RILs, we identified flowering time QTL in growth chambers that mimicked the natural temperature and photoperiod variation across the growing season in each native environment. We also compared the genomic locations of flowering time QTL to those of fitness (total fruit number) QTL from a previous three-year field study. Ten total flowering time QTL were found, and in all cases, the Italy genotype caused early flowering regardless of the conditions. Two QTL were consistent across chamber environments, and these had the largest effects on flowering time. Five of the fitness QTL colocalized with flowering time QTL found in the Italy conditions, and in each case, the local genotype was favoured. In contrast, just two flowering time QTL found in the Sweden conditions colocalized with fitness QTL and in only one case was the local genotype favoured. This implies that flowering time may be more important for adaptation in Italy than Sweden. Two candidate genes (FLC and VIN3) underlying the major flowering time QTL found in the current study are implicated in local adaptation.
Assuntos
Adaptação Fisiológica/genética , Arabidopsis/genética , Flores/fisiologia , Genética Populacional , Locos de Características Quantitativas , Arabidopsis/fisiologia , Aptidão Genética , Genótipo , Itália , Modelos Genéticos , Fenótipo , SuéciaRESUMO
Local adaptation, defined as higher fitness of local vs. nonlocal genotypes, is commonly identified in reciprocal transplant experiments. Reciprocally adapted populations display fitness trade-offs across environments, but little is known about the traits and genes underlying fitness trade-offs in reciprocally adapted populations. We investigated the genetic basis and adaptive significance of freezing tolerance using locally adapted populations of Arabidopsis thaliana from Italy and Sweden. Previous reciprocal transplant studies of these populations indicated that subfreezing temperature is a major selective agent in Sweden. We used quantitative trait locus (QTL) mapping to identify the contribution of freezing tolerance to previously demonstrated local adaptation and genetic trade-offs. First, we compared the genomic locations of freezing tolerance QTL to those for previously published QTL for survival in Sweden, and overall fitness in the field. Then, we estimated the contributions to survival and fitness across both field sites of genotypes at locally adaptive freezing tolerance QTL. In growth chamber studies, we found seven QTL for freezing tolerance, and the Swedish genotype increased freezing tolerance for five of these QTL. Three of these colocalized with locally adaptive survival QTL in Sweden and with trade-off QTL for overall fitness. Two freezing tolerance QTL contribute to genetic trade-offs across environments for both survival and overall fitness. A major regulator of freezing tolerance, CBF2, is implicated as a candidate gene for one of the trade-off freezing tolerance QTL. Our study provides some of the first evidence of a trait and gene that mediate a fitness trade-off in nature.
Assuntos
Adaptação Fisiológica/genética , Arabidopsis/genética , Congelamento , Aptidão Genética , Locos de Características Quantitativas , Arabidopsis/fisiologia , Mapeamento Cromossômico , Meio Ambiente , Genética Populacional , Itália , SuéciaRESUMO
BACKGROUND: Hemiplegic migraine (HM) is a rare type of migraine with aura that involves motor weakness. Data on conventional and advanced neuroimaging findings during prolonged attacks of HM are limited, particularly in children. CASE: A 13-year-old-female with a history of migraine had a typical attack of HM characterized by right-sided hemiplegia, deterioration of vigilance and paraphasia. MRI performed 3 hours after hemiplegia onset revealed normal diffusion tensor imaging (DTI) sequences, but perfusion weighted imaging (PWI) showed a large area of hypoperfusion within the left cerebral hemisphere and susceptibility weighted imaging (SWI) demonstrated a matching area with prominent, hypointense draining sulcal veins. Magnetic resonance angiography (MRA) revealed subtle narrowing of the left middle cerebral artery. The neuroimaging abnormalities completely resolved 24 hours after the attack onset. CONCLUSION: Multiple conventional and advanced MRI techniques including SWI play a key role in an HM attack to (1) exclude acute arterial ischemic stroke and (2) further understand the pathophysiology of HM.
Assuntos
Imageamento por Ressonância Magnética/métodos , Enxaqueca com Aura/patologia , Adolescente , Imagem de Tensor de Difusão , Feminino , Hemiplegia/etiologia , Hemiplegia/patologia , Humanos , Interpretação de Imagem Assistida por ComputadorRESUMO
Individually, childhood epilepsy and migraine are two of the most common conditions seen in pediatric neurology. What complicates matters is that there can be marked similarities between migraine and epilepsy as well as a variety of underlying conditions that predispose children to both seizures and headache. Thus, separating epilepsy from migraine may not be easy, but can be done with a detailed history as well as timely use of ancillary testing. Once children have been diagnosed with epilepsy, migraine, or both, treatment options become essential in attempts to manage these common, yet often disabling, neurological conditions. Acute interventions tend to be condition specific while preventative options may overlap for migraine and epilepsy. In the following review, we will discuss the epidemiology of childhood epilepsy and headache, the association between them, as well as how to differentiate epilepsy from migraine. Treatment strategies will follow before concluding with a discussion on prognosis.
Assuntos
Anticonvulsivantes/uso terapêutico , Dieta Cetogênica/métodos , Epilepsia/diagnóstico , GABAérgicos/uso terapêutico , Transtornos de Enxaqueca/diagnóstico , Ácido Valproico/uso terapêutico , Criança , Pré-Escolar , Comorbidade , Diagnóstico Diferencial , Epilepsia/epidemiologia , Epilepsia/terapia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Anamnese/métodos , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/terapia , Guias de Prática Clínica como Assunto , PrognósticoRESUMO
Childhood obesity and headache are both significant health concerns that often have a marked impact both personally and socially, that if not addressed can carry over into adulthood. For many individuals, these effects may be magnified when obesity and headache are seen in conjunction. It is this overlap between obesity and headache in children, as well as similarities in the known mechanism of action for feeding and headache, which led to a suspected association between the two. Unfortunately, although recent studies have supported this association, only a limited number have been conducted to directly address this. Furthermore, despite rising rates of childhood obesity and headache, the associated medical comorbidities, and the significant financial cost for these conditions, there is a relative void in studies investigating treatment options that address both underlying conditions of obesity and headache in children.
Assuntos
Cefaleia/epidemiologia , Obesidade Infantil/epidemiologia , Adolescente , Criança , Comorbidade , Feminino , Cefaleia/complicações , Humanos , MasculinoRESUMO
Traits that have lost function sometimes persist through evolutionary time. These traits may be maintained by a lack of standing genetic variation for the trait, if selection against the trait is weak relative to drift, or if they have a residual function. To determine the evolutionary processes shaping whether nonfunctional traits are retained or lost, we investigated short stamens in 16 populations of Arabidopsis thaliana along an elevational cline in the Spanish Pyrenees. We found a cline in short stamen number from retention of short stamens in high elevation populations to incomplete loss in low elevation populations. We did not find evidence that limited genetic variation constrains the loss of short stamens at high elevations nor evidence for divergent selection on short stamens between high and low elevations. Finally, we identified loci associated with short stamens in the Spanish Pyrenees that are different from loci associated with variation in short stamen number across latitudes from a previous study. Overall, we did not identify the evolutionary mechanisms maintaining an elevational cline in short stamen number but did identify different genetic loci underlying the variation in short stamen along similar phenotypic clines.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Transtornos de Enxaqueca/prevenção & controle , Guias de Prática Clínica como Assunto , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/imunologia , Adolescente , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais Humanizados/uso terapêutico , Tamanho Corporal , Peptídeo Relacionado com Gene de Calcitonina/imunologia , Peptídeo Relacionado com Gene de Calcitonina/fisiologia , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/administração & dosagem , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/efeitos adversos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/imunologia , Criança , Ensaios Clínicos como Assunto , Cefaleia Histamínica/prevenção & controle , Contraindicações de Medicamentos , Relação Dose-Resposta a Droga , Relação Dose-Resposta Imunológica , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Seleção de Pacientes , Cefaleia Pós-Traumática/prevenção & controle , Gravidez , Complicações na Gravidez/tratamento farmacológicoRESUMO
Migraine is common in children and adolescents and can cause significant disability. There are relatively limited evidence-based treatment options available, especially when compared with treatment of migraine in adults. The Pediatric Research Equity Act requires the study of a new drug or biologic in pediatric populations. As such it is mandatory that the newest migraine treatment options available for adults be evaluated in children and adolescents. It will take years before results from clinical trials in pediatric patients become available. In the meantime, there is eagerness among clinicians to seek out the existing evidence that may help provide clarity on utilization of the newer migraine therapies in children and adolescents because many of the currently available, guideline-recommended treatments do not provide benefit for all patients. In this narrative review, the literature regarding onabotulinumtoxinA, neuromodulatory devices, calcitonin gene-related peptide (CGRP) monoclonal antibodies, 5-hydroxytryptamine (1F) agonists (i.e., ditans), and CGRP small-molecule receptor antagonists (i.e., gepants) for the treatment of migraine in children and adolescents will be summarized.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Humanos , Adolescente , Criança , Peptídeo Relacionado com Gene de Calcitonina/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Receptores de Peptídeo Relacionado com o Gene de Calcitonina , Anticorpos Monoclonais/uso terapêuticoRESUMO
OBJECTIVE: There has been a rise in the prenatal detection of right sided aortic arch (RAA). When associated with a left-sided arterial duct (LD), this forms a vascular ring encircling the trachea. Infants may have symptoms or signs suggestive of tracheoesophageal compression but many are asymptomatic. The objective of this study was to investigate the relationship between symptoms and severity of tracheobronchial compression assessed by bronchoscopy. METHODS: Retrospective review of all cases of prenatally diagnosed RAA-LD in the absence of associated congenital heart disease at Evelina London Children's Hospital and Kings College Hospital over a 4-year period between April 2015-2019. Clinical records, fetal echocardiograms, and free-breathing flexible bronchoscopy (FB) data were reviewed. RESULTS: One hundred and twelve cases of isolated RAA-LD were identified of whom 82 cases (73%) underwent FB. FB was performed median age of 11 months (range 1-36 months), no complications occurred. Aberrant left subclavian artery (ALSA) was present in 86% (96/112) and mirror image branching (MIB) in 13% (15/112). 34/112 (30%) reported symptoms during follow-up. 36/77 (47%) with ALSA who underwent FB showed moderate-severe compression mostly at distal tracheal and carinal level of whom 38% had parent-reported symptoms. Moderate-severe compression was seen in 3/5 (60%) with MIB mostly at mid tracheal level; 3 were symptomatic but only 2 had tracheal compression. In total 36% (18/50) of investigated asymptomatic patients showed moderate-severe compression. Respiratory symptoms were poorly predictive of moderate-severe tracheal compression (positive predictive value 66%, negative predictive value 64%). CONCLUSION: The absence of symptoms did not exclude significant tracheal compression. The anatomical effect of the vascular ring is under appreciated when symptoms alone are used as a marker of tracheal compression.