Electrical activity in the heart exhibits 24-hour rhythmicity, and potentially fatal arrhythmias are more likely to occur at specific times of day. Here, we demonstrate that circadian clocks within ...the brain and heart set daily rhythms in sinoatrial (SA) and atrioventricular (AV) node activity, and impose a time-of-day dependent susceptibility to ventricular arrhythmia. Critically, the balance of circadian inputs from the autonomic nervous system and cardiomyocyte clock to the SA and AV nodes differ, and this renders the cardiac conduction system sensitive to decoupling during abrupt shifts in behavioural routine and sleep-wake timing. Our findings reveal a functional segregation of circadian control across the heart's conduction system and inherent susceptibility to arrhythmia.
This study sought to evaluate the effects of beta-blocker withdrawal in acute decompensated heart failure (ADHF).
Published reports showed trends for either no harm or increased risk of in-hospital ...mortality, short-term mortality, and rehospitalization rates in patients admitted for ADHF that discontinued beta-blockers; however, a comprehensive analysis has not been conducted.
Relevant studies from January 2000 through January 2015 were identified in the PubMed, EMBASE, and COCHRANE electronic databases. Where appropriate data were available, weighted relative risks were estimated using random-effects meta-analysis techniques.
Five observational studies and 1 randomized clinical trial (n = 2,704 patients who continued beta-blocker therapy and n = 439 patients who discontinued beta-blocker therapy) that reported the short-term effects of beta-blocker withdrawal in ADHF were included in the analyses. In 2 studies, beta-blocker withdrawal significantly increased risk of in-hospital mortality (risk ratio: 3.72; 95% confidence interval CI: 1.51 to 9.14). Short-term mortality (relative risk: 1.61; 95% CI: 1.04 to 2.49; 4 studies) and combined short-term rehospitalization or death (relative risk: 1.59; 95% CI: 1.03 to 2.45; 4 studies) were also significantly increased.
Discontinuation of beta-blockers in patients admitted with ADHF was associated with significantly increased in-hospital mortality, short-term mortality, and the combined endpoint of short-term rehospitalization or mortality. These data suggest beta-blockers should be continued in ADHF patients if their clinical picture allows.
Yeast physiology is temporally regulated, this becomes apparent under nutrient-limited conditions and results in respiratory oscillations (YROs). YROs share features with circadian rhythms and ...interact with, but are independent of, the cell division cycle. Here, we show that YROs minimise energy expenditure by restricting protein synthesis until sufficient resources are stored, while maintaining osmotic homeostasis and protein quality control. Although nutrient supply is constant, cells sequester and store metabolic resources via increased transport, autophagy and biomolecular condensation. Replete stores trigger increased H
export which stimulates TORC1 and liberates proteasomes, ribosomes, chaperones and metabolic enzymes from non-membrane bound compartments. This facilitates translational bursting, liquidation of storage carbohydrates, increased ATP turnover, and the export of osmolytes. We propose that dynamic regulation of ion transport and metabolic plasticity are required to maintain osmotic and protein homeostasis during remodelling of eukaryotic proteomes, and that bioenergetic constraints selected for temporal organisation that promotes oscillatory behaviour.
Bovine viral diarrhea virus (BVDV), a ubiquitous pathogen of cattle, causes subclinical to severe acute disease. Two species of BVDV are recognized, BVDV1 and BVDV2 with BVDV1 divided into at least ...21 subgenotypes and BVDV2 into 3–4 subgenotypes, most commonly using sequences from the 5’ untranslated region (5’ UTR). We report genomic sequencing of 8 BVDV2 isolates that did not segregate into the 2a subgenotype; but represented two additional BVDV2 subgenotypes. One BVDV2 subgenotype was previously recognized only in Asia. The other seven viruses fell into a second subgenotype that was first reported in Brazil and the U.S. in 2002. Neutralization assays using antiserum raised against vaccine strain BVDV2a 296c revealed varying degrees of neutralization of genetically diverse BVDV2 isolates. Neutralization titers decreased from 1.8 to more than a four log(2) decrease. This study illustrated the considerable genetic and antigenic diversity in BVDV2 circulating in the U.S.
•Thirty-five BVDV2 genomes were sequenced in this study.•The 35 sequences were used in a phylogenetic analysis with 68 other BVDV sequences.•Three subgenotypes of BVDV2 were identified in the United States.•Antiserum raised against vaccine strain 296c was used in virus neutralization assays.•VN assays indicated antigenic differences increased with increasing genetic distance.
•A method for deriving multiple RNA virus genomic sequences is described.•Twenty RNA virus genomes were routinely sequenced simultaneously.•The sequencing protocol is rapid and accurate.•Bovine viral ...diarrhea virus and bovine coronaviruses genomes were sequenced.•Sequence coverage of >99% was obtained for 35 of 40 viruses sequenced.
Comparing sequences of archived viruses collected over many years to the present allows the study of viral evolution and contributes to the design of new vaccines. However, the difficulty, time and expense of generating full-length sequences individually from each archived sample have hampered these studies. Next generation sequencing technologies have been utilized for analysis of clinical and environmental samples to identify viral pathogens that may be present. This has led to the discovery of many new, uncharacterized viruses from a number of viral families. Use of these sequencing technologies would be advantageous in examining viral evolution. In this study, a sequencing procedure was used to sequence simultaneously and rapidly multiple archived samples using a single standard protocol. This procedure utilized primers composed of 20 bases of known sequence with 8 random bases at the 3′-end that also served as an identifying barcode that allowed the differentiation each viral library following pooling and sequencing. This conferred sequence independence by random priming both first and second strand cDNA synthesis. Viral stocks were treated with a nuclease cocktail to reduce the presence of host nucleic acids. Viral RNA was extracted, followed by single tube random-primed double-stranded cDNA synthesis. The resultant cDNAs were amplified by primer-specific PCR, pooled, size fractionated and sequenced on the Ion Torrent PGM platform. The individual virus genomes were readily assembled by both de novo and template-assisted assembly methods. This procedure consistently resulted in near full length, if not full-length, genomic sequences and was used to sequence multiple bovine pestivirus and coronavirus isolates simultaneously.
Bovine viral diarrhea virus (BVDV) is one of the most economically important viruses of cattle, but this pathogen is also able to infect pigs, camelids, and a wide range of domestic and wild ...ruminants. BVDV isolates circulating in animal populations are genetically and antigenically highly diverse. Acute BVDV infections in cattle cause the introduction of many substitutions in the viral genome. Serial infection of pregnant sheep with a BVDV-1b isolate of bovine origin was also associated with great numbers of substitutions. To our knowledge, genomic changes arising during BVDV infections in swine have not been investigated. The purpose of this study was to investigate the changes occurring in the open reading frame (ORF) of BVDV during serial infection of pregnant swine with a BVDV isolate of bovine origin. The BVDV-1b isolate AU526 was serially passaged in six pregnant gilts, two of which gave birth to live piglets congenitally infected with BVDV. The complete ORF sequences of 14 BVDV isolates obtained from pregnant gilts and their piglets were determined. Their analysis revealed that serial transmission of AU526 in pregnant swine resulted in many genomic changes. All isolates of porcine origin shared 32 nucleotide and 12 amino acid differences with the virus inoculum AU526. These changes were detected after a single passage in pregnant swine and were conserved during the subsequent five passages. Amino acid changes occurred primarily in genomic regions encoding the BVDV structural proteins E2 and E
rns
. These results suggest that BVDV infections in pregnant swine may contribute significantly to the genetic variability of BVDV and lead to the appearance of adaptive changes.
Bovine viral diarrhea viruses (BVDV) are a common global viral pathogen of ruminants. Considerable genetic variability is found amongst BVDV1 isolates, with at least 21 subgenotypes being described. ...In the United States, BVDV1a and 1b are the only subgenotypes described to date. Here, the genomic sequence of CA2005, a cytopathic BVDV1, was determined. This virus, isolated in California, did not segregate into either BVDV1a or 1b subgenotypes. BLAST analysis showed CA2005 was most closely related to BVDV1i isolates. CA2005 was also the first cytopathic BVDV1i and one of few non-1a, non-1b cytopathic viruses reported. The genomic sequence was 15,752 nucleotides in length. Cytopathogenicity was conferred by duplication of the NS3 protein with a small ubiquitin B insertion at the border of the NS2/NS3 proteins. Virus neutralization assays using antisera against BVDV1a vaccine viruses revealed variable neutralization, suggesting modified live vaccines may not be totally protective against CA2005 and similar viruses.
•Cytopathic BVDV1 (CA2005) isolated from cow in 2005.•5′ UTR sequence analysis showed this virus did not segregate with BVDV1a or 1b•Genomic sequencing showed this virus to be BVDV1i with genomic rearrangement.•Virus neutralization assays showed limited cross-reaction with BVDV1a vaccine strains.•CA2005 is the first BVDV1i reported in the United States.
•Quasispecies composition in ‘HoBi’-like PI animals compared temporally.•Genetic variability in viral mutant clouds increased along time.•Absence of a putative N-glycosylation site represented an ...advantage in viral variants.•Variations in viral swarm occurred over time and were dependent on host factor.
‘HoBi’-like virus is an atypical group within the Pestivirus genus that is implicated in economic losses for cattle producers due to both acute and persistent infections. Pestivirus strains exist as quasispecies (swarms of individual viruses) in infected animals and the viral populations making up the quasispecies differ widely in size and diversity in each animal. In the present study the viral quasispecies circulating in persistently infected (PI) calves, generated and maintained under experimental conditions using two different ‘HoBi’-like strains, was observed over time. An increase in genetic variability and the development of certain mutations was observed over time. Mutations observed included the loss of a putative N-linked glycosylation site in the E2 region and the change of specific residues in E1/E2. It is hypothesized that these changes may be the results on continued adaption of the pestivirus to individual hosts. This is the first study characterizing variation in the viral swarms of animals persistently infected with HoBi-like viruses over time. Studies of the shifts in PI viral swarms will contribute to our understanding of the host and viral mechanisms that function in the maintenance of pestivirus persistent infections.
The International Federation of Accountants (IFAC) has issued a revised "Code of Ethics for Professional Accountants" (IFAC Code). The IFAC Code is intended to be a model code of ethics for national ...accounting organizations throughout the world. Prior research demonstrates that approximately 50% of IFAC member organizations have adopted the IFAC Code as their organizational code of conduct. There is therefore empirical evidence that international convergence of accounting ethical standards is occurring. We employ Hofstede's (2008, http://www. geert-hofstede. com/hofs tede_ dimensions. php) cultural dimensions in an attempt to empirically explain accounting organizations' decisions about whether to adopt the IFAC Code or to retain their organization-specific code. Our results indicate that accounting organizations in cultures with high levels of Individualism and Uncertainty Avoidance are less likely to adopt the model IFAC Code. Organizations in high Individualism and Uncertainty Avoidance societies are therefore less likely to surrender the setting of ethical standards to an outside, international organization.
Proper ultrasound examination and interpretation hinges on thorough knowledge of the relevant anatomy, artifacts, and technique. This book provides an excellent foundation by going beyond pathology ...and concentrating on these fundamentals. Basic physics and artifact recognition and prevention are outlined. Chapters review essential anatomy and include images and tables that highlight relevant bones, ligaments, tendons, muscles, and nerves. Sites of attachment and the best positions for examination are also noted. Technique is presented via a three-tiered approach and photographs of patients in the transducer position are matched with the resulting ultrasound images and complementary anatomical overlays.
PDF
