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INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and imposes a high burden on the healthcare system. A nurse-led AF outpatient clinic may alleviate the burden on the cardiology outpatient clinic by triaging patients who need care by a cardiologist or general practitioner (GP). However, care and referral patterns after initial assessment in a nurse-led AF outpatient clinic are unknown. We examined the proportion of AF patients assessed in a nurse-led clinic without outpatient follow-up by a cardiologist. METHODS: All patients with AF referred to our tertiary medical centre underwent cardiac work-up in the nurse-led AF outpatient clinic and were prospectively followed. Data on patient characteristics, rhythm monitoring and echocardiography were collected and described. Odds ratio (OR) for continuing care in the nurse-led AF outpatient clinic was calculated. RESULTS: From 2014 to 2018, 478 consecutive individual patients were referred to the nurse-led AF outpatient clinic. After the initial cardiac work-up, 139 patients (29.1%) remained under nurse-led care and 121 (25.3%) were referred to a cardiologist and 218 (45.6%) to a GP. Patients who remained under nurse-led care were significantly younger, were more symptomatic, more often had paroxysmal AF and had less comorbidities than the other two groups. After multivariable testing, CHA2DS2-VASc score ≥â¯2 was associated with discontinued nurse-led care (OR 0.57, 95% confidence interval 0.34-0.95). CONCLUSION: After initial cardiac assessment in the nurse-led outpatient clinic, about half of the newly referred AF patients were referred back to their GP. This strategy may reduce the burden of AF patients on secondary or tertiary cardiology outpatient clinics.
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BACKGROUND: Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. METHODS: We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1year follow-up data were gathered. RESULTS: At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). CONCLUSIONS: Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.
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BACKGROUND AND AIM: Obesity is a recognized risk factor for new-onset atrial fibrillation (AF). The association between body fat distribution, which is measured by body mass index (BMI) and waist-hip ratio (WHR), its changes, and new-onset AF is conflicting. METHODS AND RESULTS: Participants of the European Prospective Investigation into Cancer and Nutrition in Norfolk cohort study were included, with exclusion criteria of prevalent AF, rheumatic heart disease, and cancer. AF was confirmed by the International Classification of Diseases-10 hospital discharge code I48. Adjusted sex-specific Cox proportional hazards models were used to quantify the AF risk per 1 standard deviation increase and for quintiles of adiposity indices. A total of 10,885 men and 12,857 women were followed up for a median of 19 years, yielding 451,098 person-years. New-onset AF was diagnosed in 1408 (12.9%) men and 1102 (8.6%) women. Multivariable analyses showed that BMI predicted new-onset AF in all, while WHR predicted only in men. New-onset AF risk gradually increased across the range of adiposity indices: for men in the highest BMI quintile, HR: 1.59 (CI 1.32-1.91, p for trend<0.001), whereas for women in the highest BMI quintile, HR: 1.52 (CI 1.23-1.88, p for trend<0.001). Further, for men in the highest WHR quintile, HR: 1.31 (CI 1.09-1.57, p for trend: 0.01), whereas for women in the highest WHR quintile, HR: 1.12 (CI 0.90-1.41, p for trend: 0.17). The change in BMI and WHR was similar in participants with or without new-onset AF. CONCLUSIONS: An increased body mass, as measured by BMI, is associated with an increased risk of developing new-onset AF. More abdominal fat distribution, as measured by WHR, is associated with an increased risk of developing new-onset AF in men but not in women.
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Adiposidade , Fibrilação Atrial/epidemiologia , Índice de Massa Corporal , Obesidade/epidemiologia , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Inglaterra/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/fisiopatologia , Prevalência , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Relação Cintura-QuadrilRESUMO
BACKGROUND: Monosodium glutamate (MSG), also referred to as Vetsin or E621, is a flavour enhancer frequently used in Asian cuisine and abundantly present in the famous Chinese dish Peking duck. MSG is notorious for triggering the onset of the so-called 'Chinese restaurant syndrome' (CRS), a complex of unpleasant symptoms, which might include flushing, sweating and the onset of atrial fibrillation (AF). This study aims to determine the effects of MSG on the occurrence of AF. METHODS: We conducted a placebo self-controlled single-arm study in the Academic Medical Centre in Amsterdam. We included paroxysmal AF patients who reported a consistent onset of AF upon MSG intake. During three admissions, participants were subsequently administered: placebo, 1.5 g and 3 g MSG. If AF was recorded after the dose of 1.5 g MSG, patients were given another placebo instead of 3 g MSG. The primary outcome was the onset of AF registered by 24-hour Holter monitoring. The secondary outcomes were any other arrhythmia and the onset of CRS defined as two or more symptoms of CRS after MSG intake. RESULTS: Six men participated in the study. Both 1.5 g and 3 g MSG were unrelated to CRS, arrhythmias or AF occurrence. CONCLUSION: Peking duck can be put on the Christmas menu without risking guests to be admitted to the emergency department with new episodes of AF.
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OBJECTIVES: To determine the association between left atrial epicardial conduction time (LAECT), fibrosis and atrial fibrillation (AF) recurrence after thoracoscopic surgical ablation of persistent AF. SETTING: Single tertiary care centre in the Netherlands. PARTICIPANTS: Patients with persistent AF from the randomised Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT)-trial were included. Patients eligible for thoracoscopic AF ablation were included, full inclusion and exclusion criteria were previously published. All patients underwent thoracoscopic ablation, encompassing pulmonary vein isolation with an additional roof and trigone lesion. In patients with conduction block across the roof and trigone lesion, LAECT was measured. LAECT was defined as the time to local activation at one side of the roofline on pacing from the opposite side. Collagen fibre density was quantified from left atrial appendage histology. OUTCOME MEASURES: Primary outcome: AF recurrence during 2 years of follow-up. RESULTS: 121 patients were included, of whom 35(29%) were women, age was 60.4±7.8 and 51% (62) had at least one AF recurrence during 2 years of follow-up. LAECT was longer in patients with versus without AF recurrence (182±43 ms vs 147±29 ms, p<0.001). LAECT was longer in older patients, in patients with a higher body mass index (BMI) and in patients using class IC antiarrhythmic drugs. LAECT was shorter in patients with higher collagen fibre density. A previously failed catheter ablation, LAECT and BMI were independently associated with AF recurrence. CONCLUSION: LAECT is correlated with collagen fibre density and BMI and is independently associated with AF recurrence in patients with persistent AF. In these patients, LAECT appears to reflect substrate characteristics beyond clinical AF type and left atrial volume. TRIAL REGISTRATION NUMBER: NCT01091389.
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Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Idoso , Apêndice Atrial/cirurgia , Fibrilação Atrial/etiologia , Ablação por Cateter/efeitos adversos , Pré-Escolar , Colágeno , Feminino , Fibrose , Átrios do Coração , Humanos , Masculino , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: Despite advances in therapeutic interventions AF remains a progressive and symptomatic disease. Therefore, novel therapeutic interventions targeting the underlying arrhythmogenic substrate for AF is needed. Atrial fibrosis is an important component of the arrhythmogenic substrate of AF and may be initiated by aldosterone binding to the mineralocorticoid receptor. We hypothesized that aldosterone pathway blockade with mineralocorticoid receptor antagonists (MRA) reduces atrial fibrosis, and thus AF. METHODS: We searched OVID MEDLINE, OVID EMBASE and the Cochrane Central Register of Controlled Trials from inception to June 10th, 2016 for randomized controlled trials (RCT) and observational studies addressing MRA and providing information on AF occurrence. Two independent reviewers selected and appraised the data. We performed random-effects meta-analyses. Summary odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: We included 14 studies, 5 RCT and 9 observational cohorts, with a cumulative number of 5332 patients (male: 74.9%, age: 65.3years); 2397 (45.0%) received an MRA (spironolactone or eplerenone). During follow-up, 204 (8.5%) patients treated with MRAs, developed AF, compared to 547 (18.6%) patients, without MRA treatment. Meta-analyses showed a significant overall reduction of AF risk in MRA treated patients (OR: 0.48 CI: 0.38-0.60 p<0.001), including a reduction of new-onset AF (OR: 0.52 CI: 0.37-0.74 p<0.001) and recurrent AF (OR: 0.37 CI: 0.24-0.57 p<0.001), but not post-operative AF (POAF) (OR: 0.60 CI: 0.33-1.09 p=0.09). CONCLUSIONS: MRAs significantly reduce new-onset AF and recurrent AF, but not POAF. MRA treatment can be considered an additive therapeutic strategy in AF.
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Aldosterona/metabolismo , Fibrilação Atrial/prevenção & controle , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Fibrilação Atrial/metabolismo , HumanosRESUMO
Phenotypic screening is in a renaissance phase and is expected by many academic and industry leaders to accelerate the discovery of new drugs for new biology. Given that phenotypic screening is per definition target agnostic, the emphasis of in silico and in vitro follow-up work is on the exploration of possible molecular mechanisms and efficacy targets underlying the biological processes interrogated by the phenotypic screening experiments. Herein, we present six exemplar computational protocols for the interpretation of cellular phenotypic screens based on the integration of compound, target, pathway, and disease data established by the IMI Open PHACTS project. The protocols annotate phenotypic hit lists and allow follow-up experiments and mechanistic conclusions. The annotations included are from ChEMBL, ChEBI, GO, WikiPathways and DisGeNET. Also provided are protocols which select from the IUPHAR/BPS Guide to PHARMACOLOGY interaction file selective compounds to probe potential targets and a correlation robot which systematically aims to identify an overlap of active compounds in both the phenotypic as well as any kinase assay. The protocols are applied to a phenotypic pre-lamin A/C splicing assay selected from the ChEMBL database to illustrate the process. The computational protocols make use of the Open PHACTS API and data and are built within the Pipeline Pilot and KNIME workflow tools.
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Evolutionary trees based on partial small ribosomal subunit RNA sequences of 22 metazoa species have been published [(1988) Science 239, 748-753]. In these trees, cnidarians (Radiata) seemed to have evolved independently from the Bilateria, which is in contradiction with the general evolutionary view. In order to further investigate this problem, the complete srRNA sequence of the sea anemone Anemonia sulcata was determined and evolutionary trees were constructed using a matrix optimization method. In the tree thus obtained the sea anemone and Bilateria together form a monophyletic cluster, with the sea anemone forming the first line of the metazoan group.
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Evolução Biológica , Cnidários/genética , RNA Ribossômico 18S/genética , RNA Ribossômico/genética , Anêmonas-do-Mar/genética , Animais , Sequência de Bases , DNA Ribossômico/genética , DNA Ribossômico/isolamento & purificação , Modelos Moleculares , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Especificidade da EspécieRESUMO
To date, seven different human histone deacetylases (HDACs) have been identified, which fall into two distinct classes. We have isolated and characterized a cDNA encoding a novel human HDAC, which we name HDAC8. HDAC8 shows a high degree of sequence similarity to HDAC1 and HDAC2 and thus belongs to the class I of HDACs. HDAC8 is expressed in a variety of tissues. Human cells overexpressing HDAC8 localize the protein in sub-nuclear compartments whereas HDAC1 shows an even nuclear distribution. In addition, the HDAC8 gene is localized on the X chromosome at position q13, which is close to the XIST gene and chromosomal breakpoints associated with preleukemia.
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Histona Desacetilases/genética , Histona Desacetilases/metabolismo , RNA não Traduzido , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Sequência de Aminoácidos , Linhagem Celular , Núcleo Celular/química , Quebra Cromossômica/genética , Clonagem Molecular , Etiquetas de Sequências Expressas , Perfilação da Expressão Gênica , Histona Desacetilases/química , Histona Desacetilases/classificação , Histonas/metabolismo , Humanos , Hibridização in Situ Fluorescente , Leucemia/genética , Dados de Sequência Molecular , Filogenia , Mapeamento Físico do Cromossomo , Lesões Pré-Cancerosas/genética , RNA Longo não Codificante , RNA Mensageiro/análise , RNA Mensageiro/genética , Proteínas Repressoras/química , Proteínas Repressoras/classificação , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/genética , Transfecção , Cromossomo X/genéticaRESUMO
The authors previously reported that one of the cAMP-response elements (CREs) of the human beta3-AR gene, beta3CRE2, interacts with a nuclear factor which is distinct from CREB/ATF family. We named this factor WATSF-1 (white adipose tissue specific factor-1) since it is preferentially expressed in WAT. In this work, we have shown the absence of DNA binding or transcriptional activity of this factor in several non-adipose cells tested. By computer analysis, beta3CRE2 was found to constitute an octameric element that is highly homologous to the binding site for some members of the nuclear hormone receptor superfamily. Using the response elements of other adipocyte-specific nuclear receptors as competitors, a 'cross-talk' between WATSF-1 and these response elements has been demonstrated. However, the affinity of WATSF-1 for these response elements differs from that for beta3CRE2 (self), implying that WATSF-1 is distinct from these adipocyte-specific nuclear receptors. Furthermore the DNA-binding activity of WATSF-1 was shown to be enhanced by phosphatase treatment, suggesting that phosphorylation may play an important role in the functional modulation of this factor. In an effort to prove that it is indeed an adipocyte-specific factor, we used 3T3-L1 cells, a cellular model of WAT, that can undergo differentiation into adipocytes. The DNA binding and transcriptional activity of this factor appeared during differentiation of the cells. Taken together, these results demonstrate that WATSF-1 is a putative white adipocyte-specific nuclear orphan receptor induced during adipogenesis and is a transcriptional activator through one of the CREs of the human beta3-AR gene. Targeting this factor may be a novel therapeutic approach to stimulation of the beta3-AR signal transduction pathway in adipose tissues.
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Tecido Adiposo/metabolismo , Receptores Adrenérgicos beta 3/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Células 3T3 , Adipócitos/citologia , Adipócitos/metabolismo , Animais , Sequência de Bases , Sítios de Ligação/genética , Diferenciação Celular , AMP Cíclico/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , DNA/genética , DNA/metabolismo , Primers do DNA/genética , Humanos , Técnicas In Vitro , Camundongos , Obesidade/terapia , Fosforilação , Receptor Cross-Talk , Receptores Citoplasmáticos e Nucleares/genética , Transcrição GênicaRESUMO
Eukaryotic small ribosomal subunit RNAs contain an area of variable structure, V4, which comprises about 250 nucleotides in most species, whereas the corresponding area in bacterial small ribosomal subunit RNAs consists of about 64 nucleotides folded into a single hairpin. There is no consensus on the secondary structure of area V4 in eukaryotes, about 10 different models having been proposed. The prediction of a model on a comparative basis poses special problems because, due to the variability of the area in length as well as sequence, a dependable alignment is very difficult to achieve. A new model was derived by systematic examination of all combinations of helices that have been hitherto proposed, plus some new ones. The following properties of the helices were examined: transposability to all presently known sequences, presence of compensating substitutions, and thermodynamic stability. A model was selected by ranking all possible combinations of transposable helices according to the number of compensating substitutions scored. The optimal model comprises a pseudoknot and four hairpin structures. Certain species contain additional hairpins inserted between these structural elements, while in others the structure is partially or entirely deleted.
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Conformação de Ácido Nucleico , RNA Ribossômico/química , Animais , Sequência de Bases , Elementos de DNA Transponíveis , Humanos , Modelos Moleculares , Dados de Sequência Molecular , TermodinâmicaRESUMO
The 16S rRNA sequence of Trichodesmium sp. strain NIBB 1067 was determined and used for the construction of a distance tree and bootstrap analysis. The tree shows that, among the available cyanobacterial 16S rRNA sequences, Trichodesmium NIBB 1067 has Oscillatoria PCC 7515 as its closest relative, presenting 94.9% of sequence similarity with the latter strain. This is in contrast to a difference of 9 mol% G+C in mean genomic DNA base composition between the two organisms. Nevertheless, the genotypic heterogeneity presented by a number of strains assigned to the genus Oscillatoria hinders a taxonomic decision on the separate existence of the genera Trichodesmium and Oscillatoria. The sequence of the internal transcribed spacer (ITS) between the 16S and 23S rRNA genes was also determined, as a possible marker to study inter- and intraspecific variability. The ITS contains the genes coding for tRNA(Ile) and tRNA(Ala) and its total length is 547 nucleotides. In six out of eight sequenced clones, there is a duplication of 29 nucleotides, surrounding the 5' end of the tRNA(Ile).
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Cianobactérias/genética , DNA Bacteriano/genética , DNA Ribossômico/genética , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Sequência de Bases , Cianobactérias/classificação , Dados de Sequência Molecular , Fixação de Nitrogênio , Filogenia , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico , Especificidade da EspécieRESUMO
A tree was constructed from a structurally conserved area in an alignment of 83 small ribosomal subunit sequences of eukaryotic, archaebacterial, eubacterial, plastidial, and mitochondrial origin. The algorithm involved computation and optimization of a dissimilarity matrix. According to the tree, only plant mitochondria belong to the eubacterial primary kingdom, whereas animal, fungal, algal, and ciliate mitochondria branch off from an internal node situated between the tree primary kingdoms. This result is at variance with a parsimony tree of similar size published by Cedergren et al. (J Mol Evol 28:98-112, 1988), which postulates the mitochondria to be monophyletic and to belong to the eubacterial primary kingdom. The discrepancy does not follow from the use of conflicting sequence alignments, hence it must be due to the use of different treeing algorithms. We tested our algorithm on a set of sequences resulting from a simulated evolution and found it capable of faithfully reconstructing a branching topology that involved very unequal evolutionary rates. The use of more limited or more extended areas of the complete sequence alignment, comprising only very conserved or also more variable portions of the small ribosomal subunit structure, does have some influence on the tree topology. In all cases, however, the nonplant mitochondria seem to branch off before the emergence of eubacteria, and the differences are limited to the branching pattern among different types of mitochondria.
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Bactérias/genética , Evolução Biológica , Mitocôndrias/análise , RNA Ribossômico , Rana catesbeiana/genética , Algoritmos , Animais , Brucella abortus/genética , Mutação , Conformação de Ácido Nucleico , RNA Ribossômico/análise , Thermoplasma/genéticaRESUMO
The nucleotide sequence of the gene coding for small ribosomal subunit RNA in the basidiomycete Ustilago maydis was determined. It revealed the presence of a group I intron with a length of 411 nucleotides. This is the third occurrence of such an intron discovered in a small subunit rRNA gene encoded by a eukaryotic nuclear genome. The other two occurrences are in Pneumocystis carinii, a fungus of uncertain taxonomic status, and Ankistrodesmus stipitatus, a green alga. The nucleotides of the conserved core structure of 101 group I intron sequences present in different genes and genome types were aligned and their evolutionary relatedness was examined. This revealed a cluster including all group I introns hitherto found in eukaryotic nuclear genes coding for small and large subunit rRNAs. A secondary structure model was designed for the area of the Ustilago maydis small ribosomal subunit RNA precursor where the intron is situated. It shows that the internal guide sequence pairing with the intron boundaries fits between two helices of the small subunit rRNA, and that minimal rearrangement of base pairs suffices to achieve the definitive secondary structure of the 18S rRNA upon splicing.
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Íntrons , RNA Ribossômico/genética , Ustilago/genética , Sequência de Bases , DNA Ribossômico/genética , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Precursores de RNA/genética , RNA Fúngico/genética , RNA Ribossômico 18S/genéticaRESUMO
The detailed descriptions now available for the secondary structure of small-ribosomal-subunit RNA, including areas of highly variable primary structure, facilitate the alignment of nucleotide sequences. However, for optimal exploitation of the information contained in the alignment, a method must be available that takes into account the local sequence variability in the computation of evolutionary distance. A quantitative definition for the variability of an alignment position is proposed in this study. It is a parameter in an equation which expresses the probability that the alignment position contains a different nucleotide in two sequences, as a function of the distance separating these sequences, i.e., the number of substitutions per nucleotide that occurred during their divergence. This parameter can be estimated from the distance matrix resulting from the conversion of pairwise sequence dissimilarities into pairwise distances. Alignment positions can then be subdivided into a number of sets of matching variability, and the average variability of each set can be derived. Next, the conversion of dissimilarity into distance can be recalculated for each set of alignment positions separately, using a modified version of the equation that corrects for multiple substitutions and changing for each set the parameter that reflects its average variability. The distances computed for each set are finally averaged, giving a more precise distance estimation. Trees constructed by the algorithm based on variability calibration have a topology markedly different from that of trees constructed from the same alignments in the absence of calibration. This is illustrated by means of trees constructed from small-ribosomal-subunit RNA sequences of Metazoa. A reconstruction of vertebrate evolution based on calibrated alignments matches the consensus view of paleontologists, contrary to trees based on uncalibrated alignments. In trees derived from sequences covering several metazoan phyla, artefacts in topology that are probably due to a high clock rate in certain lineages are avoided.
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Evolução Biológica , Células Eucarióticas/metabolismo , RNA Ribossômico/genética , Algoritmos , Animais , Sequência de Bases , Variação Genética , Conformação de Ácido Nucleico , Filogenia , RNA Ribossômico/química , Software , Vertebrados/classificação , Vertebrados/genéticaRESUMO
Histamine H1 receptor expression has been reported to change in disorders such as allergic rhinitis, autoimmune myocarditis, rheumatoid arthritis and atherosclerosis. Here we report the isolation and characterization of genomic clones containing the 5' flanking (regulatory) region of the human histamine H1 receptor gene. An intron of approx. 5.8 kb was identified in the 5' untranslated region, which suggests that an entire subfamily of G-protein-coupled receptors may contain an intron immediately upstream of the start codon. The transcription initiation site was mapped by 5' rapid amplification of cDNA ends to a region 6.2 kb upstream of the start codon. Immediately upstream of the transcription start site a fragment of 1.85 kb was identified that showed promoter activity when placed upstream of a luciferase reporter gene and transiently transfected into cells expressing the histamine H1 receptor. The promoter sequence shares a number of characteristics with the promoter sequences of other G-protein-coupled receptor encoding genes, including binding sites for several transcription factors, and the absence of TATA and CAAT sequences at the appropriate locations. The promoter sequence described here differs from that reported previously [Fukui, Fujimoto, Mizuguchi, Sakamoto, Horio, Takai, Yamada and Ito (1994) Biochem. Biophys. Res. Commun. 201, 894-901] because the reported genomic clone was chimaeric. Furthermore our study provides evidence that the 3' untranslated region of the H1 receptor mRNA is much longer than previously accepted. Together, these findings provide a complete view of the structure of the human histamine H1 receptor gene. Both the coding region of the H1 receptor gene and its promoter region were independently mapped to chromosome 3p25.
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Cromossomos Humanos Par 3 , Receptores Histamínicos H1/genética , Regiões 5' não Traduzidas , Animais , Sequência de Bases , Sítios de Ligação , Bovinos , Mapeamento Cromossômico , Clonagem Molecular , Códon , DNA/química , DNA/genética , Primers do DNA , DNA Complementar , Biblioteca Genômica , Cobaias , Humanos , Íntrons , Camundongos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Regiões Promotoras Genéticas , Ratos , Sequências Reguladoras de Ácido Nucleico , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Fator de Transcrição AP-1/metabolismoRESUMO
The database on small ribosomal subunit RNA structure contained 1804 nucleotide sequences on April 23, 1993. This number comprises 365 eukaryotic, 65 archaeal, 1260 bacterial, 30 plastidial, and 84 mitochondrial sequences. These are stored in the form of an alignment in order to facilitate the use of the database as input for comparative studies on higher-order structure and for reconstruction of phylogenetic trees. The elements of the postulated secondary structure for each molecule are indicated by special symbols. The database is available on-line directly from the authors by ftp and can also be obtained from the EMBL nucleotide sequence library by electronic mail, ftp, and on CD ROM disk.
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Bases de Dados Factuais , RNA Ribossômico/genética , Animais , Sequência de Bases , Humanos , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Filogenia , Alinhamento de SequênciaRESUMO
The complete small ribosomal subunit RNA (srRNA) sequence was determined for the red alga Porphyra umbilicalis and the basidiomycete Leucosporidium scottii, representing two taxa for which no srRNA sequences were hitherto known. These sequences were aligned with other published complete srRNA sequences of 58 eukaryotes. Evolutionary trees were reconstructed by a matrix optimization method from a dissimilarity matrix based on sections of the alignment that correspond to structurally conservative areas of the molecule that can be aligned unambiguously. The overall topology of the eukaryotic tree thus constructed is as follows: first there is a succession of early diverging branches, leading to a diplomonad, a microsporidian, a euglenoid plus kinetoplastids, an amoeba, and slime molds. Later, a nearly simultaneous radiation seems to occur into a number of taxa comprising the metazoa, the red alga, the sporozoa, the higher fungi, the ciliates, the green plants, plus some other less numerous groups. Because the red alga diverges late in the evolutionary tree, it does not seem to represent a very primitive organism as proposed on the basis of morphological and 5S rRNA sequence data. Asco- and basidiomycetes do not share a common ancestor in our tree as is generally accepted on the basis of conventional criteria. In contrast, when all alignment positions, rather than the more conservative ones, are used to construct the evolutionary tree, higher fungi do form a monophyletic cluster. The hypothesis that higher fungi and red algae might have shared a common origin has been put forward. Although the red alga and fungi seem to diverge at nearly the same time, no such relationship can be detected. The newly determined sequences can be fitted into a secondary structure model for srRNA, which is now relatively well established with the exception of uncertainties in a number of eukaryote-specific expansion areas. A specific structural model featuring a pseudoknot is proposed for one of these areas.