ABSTRACT
BACKGROUND: Malaria is a global health problem and is transmitted by the Anopheles species. Due to the epidemiological importance of the genus, studies on biological, phylogenetic, and evolutionary aspects have contributed to the understanding of adaptation, vector capacity, and resistance to insecticides. The latter may result from different causes such as mutations in the gene that encodes the sodium channel (NaV). METHODS: In this study, the NaV subunit I scaffold of 17 anopheline species was used to infer phylogenetic relationships of the genus Anopheles using Bayesian inference. The evolutionary phylogenetic tree of the NaV gene was aligned in the AliView program and analyzed utilizing Bayesian inference, using the software MrBayes. RESULTS: The anophelines were grouped into five well-supported clusters: 1 - Anopheles darlingi and Anopheles albimanus; 2 - Anopheles sinensis and Anopheles atroparvus; 3 - Anopheles dirus; 4 - Anopheles minimus, Anopheles culicifacies, Anopheles funestus, Anopheles maculatus, and Anopheles stephensi; and 5 - Anopheles christyi, Anopheles epiroticus, Anopheles merus, Anopheles melas, Anopheles gambiae, Anopheles coluzzii, and Anopheles arabiensis. CONCLUSIONS: The topology confirms the phylogenetic relationships proposed in studies based on the genome of some anophelines and reflects the current taxonomy of the genus, which suggests that NaV undergoes selection pressure during the evolution of the species. These data are useful tools for inferring their ability to resist insecticides and also help in better understanding the evolutionary processes of the genus Anopheles.
Subject(s)
Anopheles , Insecticides , Animals , Anopheles/genetics , Phylogeny , Bayes Theorem , Mosquito Vectors/genetics , Sodium Channels/geneticsABSTRACT
ABSTRACT Background: Malaria is a global health problem and is transmitted by the Anopheles species. Due to the epidemiological importance of the genus, studies on biological, phylogenetic, and evolutionary aspects have contributed to the understanding of adaptation, vector capacity, and resistance to insecticides. The latter may result from different causes such as mutations in the gene that encodes the sodium channel (NaV). Methods: In this study, the NaV subunit I scaffold of 17 anopheline species was used to infer phylogenetic relationships of the genus Anopheles using Bayesian inference. The evolutionary phylogenetic tree of the NaV gene was aligned in the AliView program and analyzed utilizing Bayesian inference, using the software MrBayes. Results: The anophelines were grouped into five well-supported clusters: 1 - Anopheles darlingi and Anopheles albimanus; 2 - Anopheles sinensis and Anopheles atroparvus; 3 - Anopheles dirus; 4 - Anopheles minimus, Anopheles culicifacies, Anopheles funestus, Anopheles maculatus, and Anopheles stephensi; and 5 - Anopheles christyi, Anopheles epiroticus, Anopheles merus, Anopheles melas, Anopheles gambiae, Anopheles coluzzii, and Anopheles arabiensis. Conclusions: The topology confirms the phylogenetic relationships proposed in studies based on the genome of some anophelines and reflects the current taxonomy of the genus, which suggests that NaV undergoes selection pressure during the evolution of the species. These data are useful tools for inferring their ability to resist insecticides and also help in better understanding the evolutionary processes of the genus Anopheles.
ABSTRACT
The genome assembly of Anopheles darlingi consists of 2221 scaffolds (N50 = 115,072 bp) and has a size spanning 136.94 Mbp. This assembly represents one of the smallest genomes among Anopheles species. Anopheles darlingi genomic DNA fragments of ~37 Kb were cloned, end-sequenced, and used as probes for fluorescence in situ hybridization (FISH) with salivary gland polytene chromosomes. In total, we mapped nine DNA probes to scaffolds and autosomal arms. Comparative analysis of the An. darlingi scaffolds with homologous sequences of the Anopheles albimanus and Anopheles gambiae genomes identified chromosomal rearrangements among these species. Our results confirmed that physical mapping is a useful tool for anchoring genome assemblies to mosquito chromosomes.
ABSTRACT
Rather than acute inflammation, long-standing multiple sclerosis (MS) course is hallmarked by relentless axonal loss and brain atrophy, both with subtle clinical expression and scarcely visible on conventional MRI studies. Brain atrophy imaging has sophisticated methodological requirements, not always practical and accessible to most centers. Corpus callosum (CC) is a major inter-hemispheric white matter bundle, grossly affected by long term MS and easily assessed by MRI. To determine whether a practical imaging method can reliably follow presumed axonal loss in patients with progressive MS, we designed a 5-year prospective open label study, enrolling 128 consecutive patients (75 relapsing-remitting (RR) and 53 secondary-progressive (SP)), on regular immunomodulatory therapy compared to control group, formed by 23 patients with MRI considered normal. On a conventional best mid-sagittal T1W, CC index (CCI) was obtained by measuring anterior, medium and posterior segments of CC, normalized to its greatest anteroposterior diameter using an orthogonal semi-automated linear system. CCI was measured at baseline and at least once yearly. Results were plotted intra-individually; baseline values were used as reference. At baseline, CCI was able to distinguish SP patients from RR and controls, and on follow-up, despite some overlap, demonstrated a progressive reduction from baseline on both RR and SP groups compared to controls. From the third year on, difference between SP and RR patients reached statistical significance, which did not correlated with disability measured by EDSS. So, a corpus callosum index proved practical and feasible to longitudinally demonstrate morphometric callosal changes with potential to be used as a tool for long-term follow-up, mostly in SP patients.
Subject(s)
Corpus Callosum/pathology , Multiple Sclerosis/pathology , Adult , Atrophy , Case-Control Studies , Disease Progression , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Prospective StudiesABSTRACT
Rather than acute inflammation, long-standing multiple sclerosis (MS) course is hallmarked by relentless axonal loss and brain atrophy, both with subtle clinical expression and scarcely visible on conventional MRI studies. Brain atrophy imaging has sophisticated methodological requirements, not always practical and accessible to most centers. Corpus callosum (CC) is a major inter-hemispheric white matter bundle, grossly affected by long term MS and easily assessed by MRI. To determine whether a practical imaging method can reliably follow presumed axonal loss in patients with progressive MS, we designed a 5-year prospective open label study, enrolling 128 consecutive patients (75 relapsing-remitting (RR) and 53 secondary-progressive (SP)), on regular immunomodulatory therapy compared to control group, formed by 23 patients with MRI considered normal. On a conventional best mid-saggital T1W, CC index (CCI) was obtained by measuring anterior, medium and posterior segments of CC, normalized to its greatest anteroposterior diameter using an orthogonal semi-automated linear system. CCI was measured at baseline and at least once yearly. Results were plotted intra-individually; baseline values were used as reference. At baseline, CCI was able to distinguish SP patients from RR and controls, and on follow-up, despite some overlap, demonstrated a progressive reduction from baseline on both RR and SP groups compared to controls. From the third year on, difference between SP and RR patients reached statistical significance, which did not correlated with disability measured by EDSS. So, a corpus callosum index proved practical and feasible to longitudinally demonstrate morphometric callosal changes with potential to be used as a tool for long-term follow-up, mostly in SP patients.
Mais do que inflamação aguda, a perda celular e conseqüente atrofia cerebral são os fatos patofisiológicos mais marcantes na fase progressiva da esclerose múltipla (EM). No entanto, correlatos clínicos e de imagem por ressonância magnética (IRM) destes eventos, requerem sofisticada tecnologia, nem sempre prática e quase nunca acessível à maioria dos centros de tratamento. Deste modo, considerando a hipótese de que esta perda celular compromete fibras associativas que compõem o corpo caloso (CC), estrutura facilmente acessível à IRM convencional, nosso grupo elaborou um estudo prospectivo aberto, atualmente com 5 anos de duração, e envolvendo 128 pacientes consecutivos, todos em acompanhamento regular em nosso centro de tratamento para a EM. A aquisição do índice de CC se deu através de um "melhor" corte meio-sagital em estudo convencional de imagem ponderada por T1, utilizando um sistema linear ortogonal semi-automatizado. Este índice foi obtido no início do seguimento e sua evolução foi acompanhada anualmente. A partir do terceiro ano deste seguimento, sua diferença entre os pacientes com a forma surto-remissiva e aqueles com a forma secundariamente progressiva alcançou significância estatística. Esta diferença não mostrou correlação com o grau de incapacidade medido pelo EDSS. Assim, um índice de CC mostrou-se uma medida prática para o seguimento de alterações morfométricas do corpo caloso, provando assim potencial para ser utilizado no acompanhamento em longo prazo de pacientes com EM, em especial aqueles com a forma progressiva.
