RESUMO
BACKGROUND: Algorithms to monitor pump parameters are needed to further improve outcomes after left ventricular assist device (LVAD) implantation. Previous research showed a restored circadian rhythm in pump parameters in patients on HeartWare (HVAD) support. Circadian patterns in HeartMate3 (HM3) were not studied before, but this is important for the development of LVAD monitoring algorithms. Hence, we aimed to describe circadian patterns in HM3 parameters and their relation to patterns in heart rate (HR). METHODS: 18 HM3 patients were included in this study. HM3 data were retrieved at a high frequency (one sample per 1 or 2 h) for 1-2 weeks. HR was measured using a wearable biosensor. To study overall patterns in HM3 parameters and HR, a heatmap was created. A 24-h cosine was fitted on power and HR separately. The relationship between the amplitude of the fitted cosines of power and HR was calculated using Spearman correlation. RESULTS: A lower between patient variability was found in power compared with flow and PI. 83% of the patients showed a significant circadian rhythmicity in power (p < 0.001-0.04), with a clear morning increase. All patients showed significant circadian rhythmicity in HR (p < 0.001-0.02). The amplitudes of the circadian rhythm in power and HR were not correlated (Spearman correlation of 0.32, p = 0.19). CONCLUSIONS: A circadian rhythm of pump parameters is present in the majority of HM3 patients. Higher frequency pump parameter data should be collected, to enable early detection of complications in the future development of predictive algorithms.
Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Humanos , Coração Auxiliar/efeitos adversos , Estudos Retrospectivos , Ritmo Circadiano , Algoritmos , Diagnóstico Precoce , Insuficiência Cardíaca/cirurgia , Resultado do TratamentoRESUMO
Functional mitral regurgitation (FMR) is characterized by a dilatation of the mitral valve annulus resulting in an insufficient adaptation of the anterior and posterior mitral valve leaflets and/or severe tethering of the leaflets due to dilatation of the left ventricle. The Cardioband® system was introduced in 2015 and is a catheter-based direct mitral valve annuloplasty procedure for treatment of FMR. In the European CE approval study 60 patients with moderate or severe FMR were analyzed per protocol. There were no device or procedure-related deaths. The technical success rate of the procedure, defined as successful implantation and tightening was 97%. At 1 year, the overall survival and survival free of hospital readmission for heart failure were 87% and 66%, respectively. Currently, various interventional treatment procedures are available, such as the edge-to-edge technique as well as direct and indirect annuloplasty. In summary, patients with FMR as a result of a dilatation of the mitral valve annulus appear to be suitable for direct annuloplasty with the Cardioband® system.
Assuntos
Implante de Prótese de Valva Cardíaca , Anuloplastia da Valva Mitral , Insuficiência da Valva Mitral , Ventrículos do Coração , Humanos , Valva Mitral , Insuficiência da Valva Mitral/cirurgia , Resultado do TratamentoRESUMO
Iron is essential for all organisms but can be toxic in excess. Iron homeostasis is typically regulated by cytoplasmic iron binding proteins, but here we describe a signal transduction system (PmrA/PmrB) that responds to extracytoplasmic ferric iron. Iron promoted transcription of PmrA-activated genes and resistance to the antibiotic polymyxin in Salmonella. The PmrB protein bound iron via its periplasmic domain which harbors two copies of the sequence ExxE, a motif present in the Saccharomyces FTR1 iron transporter and in mammalian ferritin light chain. A pmrA mutant was hypersensitive to killing by iron but displayed wild-type resistance to a variety of oxidants, suggesting PmrA/PmrB controls a novel pathway mediating the avoidance of iron toxicity.
Assuntos
Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Espaço Extracelular/metabolismo , Ferro/metabolismo , Ferro/farmacologia , Salmonella enterica/efeitos dos fármacos , Transdução de Sinais/fisiologia , Proteínas de Bactérias/genética , Sítios de Ligação/efeitos dos fármacos , Sítios de Ligação/genética , Resistência Microbiana a Medicamentos/genética , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/genética , Proteínas de Ligação ao Ferro , Fenótipo , Polimixinas/farmacologia , Estrutura Terciária de Proteína/genética , Salmonella enterica/genética , Salmonella enterica/metabolismo , Fatores de Transcrição/genética , Transcrição Gênica/genética , Proteínas de Ligação a TransferrinaRESUMO
The PmrA-PmrB two-component system of Salmonella enterica controls resistance to the peptide antibiotic polymyxin B and to several antimicrobial proteins from human neutrophils. Transcription of PmrA-activated genes is induced by high iron, but can also be promoted by growth in low magnesium in a process that requires another two-component system, PhoP-PhoQ. Here, we define the genetic basis for the interaction between the PhoP-PhoQ and PmrA-PmrB systems. We have identified pmrD as a PhoP-activated gene that mediates the transcriptional activation of PmrA-regulated genes during growth in low magnesium. When transcription of pmrD is driven from a heterologous promoter, expression of PmrA-activated genes occurs even at repressing magnesium concentrations and becomes independent of the phoP and phoQ genes. The PmrD effect is specific for PmrA-regulated genes and requires functional PmrA and PmrB proteins. A pmrD mutant is sensitive to polymyxin if grown in low magnesium, but resistant if grown in high iron. The PmrD protein controls the activity of the PmrA-PmrB system at a post-transcriptional level.
Assuntos
Proteínas de Bactérias/metabolismo , Salmonella enterica/química , Fatores de Transcrição/metabolismo , Antibacterianos/metabolismo , Proteínas de Bactérias/genética , Sequência de Bases , Resistência Microbiana a Medicamentos , Ferro/metabolismo , Magnésio/metabolismo , Modelos Biológicos , Dados de Sequência Molecular , Mutagênese , Mutação , Fosforilação , Plasmídeos , Polimixinas/metabolismo , Ligação Proteica , Processamento Pós-Transcricional do RNA , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Endonucleases Específicas para DNA e RNA de Cadeia Simples/metabolismo , Fatores de Transcrição/genética , Transcrição GênicaRESUMO
The two-component system PmrA/PmrB of Salmonella enterica controls expression of several loci including those mediating modifications in the lipopolysaccharide that result in polymyxin resistance. To gain insight in the regulation of polymyxin resistance, we mapped the transcription start sites of the PmrA-regulated genes pmrC, pmrG, pbgPE, and ugd and identified a conserved sequence in the promoter region of the first three genes. His-tagged PmrA protein could gel shift DNA fragments containing the promoters of the pmrC, pmrG, and pbgPE genes but not the udg promoter. DNase I footprinting analysis of the pmrC, pmrG, and pbgPE promoters indicate that phosphorylated as well as unphosphorylated PmrA bind to a 16-base pair imperfect inverted repeat sequence (5'-TTAAKTTCTTAAKGTT-3'), which is found 40, 80, and 38 nucleotides upstream from the transcription start sites of the pmrC, pmrG, and pbgPE genes, respectively. Our data suggest that a PmrA dimer activates transcription of the divergent pmrG and pbgPE promoters by binding to a single site in the pmrG-pbgPE intergenic region and that the ugd gene is regulated by the PmrA/PmrB system only indirectly.
Assuntos
Proteínas de Bactérias/genética , Regulon/genética , Salmonella typhimurium/genética , Sequência de Bases , Mapeamento Cromossômico , Eletroforese em Gel de Poliacrilamida , Modelos Químicos , Dados de Sequência Molecular , Regiões Promotoras Genéticas , Transcrição GênicaRESUMO
The initiation of transcription is the most important step for gene regulation in eubacteria. To initiate transcription, RNA polymerase has to associate with a small protein, known as a sigma-factor. The sigma-factor directs RNA polymerase to a specific class of promoter sequences. Most bacterial species synthesize several different sigma-factors that recognize different consensus sequences. This variety in sigma-factors provides bacteria with the opportunity to maintain basal gene expression as well as for regulation of gene expression in response to altered environmental or developmental signals. This review focuses on the function, regulation and distribution of the 14 different classes of sigma-factors that are presently known.
Assuntos
Fenômenos Fisiológicos Bacterianos , Fator sigma/fisiologia , Transcrição Gênica/genética , Cianobactérias/fisiologia , Flagelos/fisiologia , Bactérias Gram-Positivas/fisiologia , Proteínas de Choque Térmico/fisiologia , Filogenia , Regiões Promotoras Genéticas/genética , Fator sigma/química , Fator sigma/classificação , EsporosRESUMO
The rpoD gene encoding the primary sigma-factor of Campylobacter jejuni was amplified from genomic DNA with degenerate oligonucleotide primers. The complete gene encodes a polypeptide of 622 amino acids and has a deduced M(r) of 72.6 kDa. This polypeptide is 40% identical to the RpoD (sigma 70) protein of Escherichia coli and has 66% identity with the Helicobacter pylori RpoD protein. A C. jejuni sigma 70 promoter, not recognized by the E. coli sigma 70 factor, could be activated in this bacterium in the presence of the cloned C. jejuni RpoD protein.
Assuntos
Campylobacter jejuni/genética , RNA Polimerases Dirigidas por DNA/genética , Genes Bacterianos/genética , Fator sigma/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , RNA Polimerases Dirigidas por DNA/fisiologia , Regulação Bacteriana da Expressão Gênica/genética , Dados de Sequência Molecular , Regiões Promotoras Genéticas/genética , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Fator sigma/fisiologia , Ativação TranscricionalRESUMO
A promoterless lacZ shuttle vector, which allowed screening of promoters by beta-galactosidase activity in Campylobacter jejuni and Escherichia coli, was developed. Chromosomal DNA fragments from C. jejuni were cloned into this vector; 125 of 1,824 clones displayed promoter activity in C. jejuni. Eleven clones with strong promoter activity in C. jejuni were further characterized. Their nucleotide sequences were determined, and the transcriptional start sites of the putative promoters in C. jejuni were determined by primer extension. Only 6 of these 11 promoters were functional in E. coli. The 11 newly characterized and 10 previously characterized C. jejuni promoters were used to establish a consensus sequence for C. jejuni promoters. The 21 promoters were found to be very similar. They contain three conserved regions, located approximately 10, 16, and 35 bp upstream of the transcriptional start point. The -10 region resembles that of a typical sigma70 E. coli promoter, but the -35 region is completely different. In addition a -16 region typical for gram-positive bacteria was identified.
Assuntos
Campylobacter jejuni/genética , DNA Bacteriano/genética , Regiões Promotoras Genéticas , Sequência de Bases , Sítios de Ligação , Clonagem Molecular , Sequência Consenso , RNA Polimerases Dirigidas por DNA/genética , Biblioteca Gênica , Vetores Genéticos , Dados de Sequência Molecular , Iniciação Traducional da Cadeia Peptídica , RNA Bacteriano , RNA Mensageiro , Análise de Sequência de DNA , Homologia de Sequência do Ácido Nucleico , Fator sigma/genética , Transcrição GênicaRESUMO
LytB of Escherichia coli is an essential gene involved in penicillin tolerance and the stringent response. The lytB gene of Campylobacter jejuni was cloned and characterized. It could complement a temperature-sensitive E. coli lytB mutant. The C. jejuni lytB gene encodes a protein of 277 amino acids that has 34, 36 and 40% amino acid identity with the LytB proteins of E. coli, Haemophilus influenzae, and Synechocystis sp. PCC6803, respectively. The lytB gene is situated between the aroA gene and a gene that encodes ribosomal protein S1.
Assuntos
Proteínas de Bactérias/genética , Campylobacter jejuni/genética , Proteínas de Escherichia coli , Oxirredutases , Proteoglicanas/genética , Proteínas de Bactérias/química , Campylobacter jejuni/efeitos dos fármacos , Clonagem Molecular , Regulação Bacteriana da Expressão Gênica , Teste de Complementação Genética , Dados de Sequência Molecular , Resistência às Penicilinas , Proteoglicanas/química , Análise de Sequência de DNA , Homologia de Sequência de AminoácidosRESUMO
The gene for 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase (aroA) cloned from Campylobacter jejuni (Cj) strain 81116 was identified by complementation of an Escherichia coli (Ec) auxotrophic aroA mutant. The Cj aroA gene has been sequenced. It encodes an enzyme of 428 amino acids (aa), that is homologous to other bacterial EPSP synthases, especially that of Bacillus subtilis with which it has a 39% aa identity. The transcriptional start point was mapped. It is present in an upstream open reading frame (ORF) that has a strong homology to the gene encoding phenylalanine tRNA synthetase (pheS). Downstream from aroA another ORF is present which is homologous to the lytB gene of Ec. The stop codon of the aroA gene overlaps the start codon of lytB.
