bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Validation of a High-Sensitivity Cardiac Troponin I Assay
Authors: Sörensen Nils A , Goßling Alina , Neumann Johannes T , Hartikainen Tau S , Haller Paul M , Scharlemann Lea , Lehmacher Jonas , Ziegler Andreas , Blankenberg Stefan , Zeller Tanja , Nordholt Gerhard , Renné Thomas , Westermann Dirk 
Published: April 2021

Abstract

Background
Emergency departments worldwide are increasingly adopting rapid diagnosis of patients with suspected myocardial infarction (MI) based on high-sensitivity troponin. We set out to assess the diagnostic accuracy of a high-sensitivity cardiac troponin I (hs-cTnI) assay in a prospective study.

Methods
In a cohort study including 1800 patients presenting with suspected acute MI, we developed and temporally validated a 0/1 h diagnostic algorithm using the Siemens Atellica IM hs-cTnI assay. The algorithm was established in the first 928 patients and validated in the following 872 patients.

Results
The derived algorithm consisted of a baseline rule-out of non–ST-segment elevation MI using a cutoff &lt;3 ng/L in patients with symptom onset ≥3 h or an admission troponin I level &lt;6 ng/L with a Δ change of &lt;3 ng/L from 0 h to 1 h. For rule-in, an admission troponin I level ≥120 ng/L or an increase within the first hour ≥12 ng/L was required. Application of the algorithm to the validation cohort showed a negative predictive value of 99.8% (95% CI, 98.7%–100.0%), sensitivity of 99.1% (95% CI, 95.1%–100.0%), and 48.3% of patients ruled out, whereas 15.1% were ruled in with a positive predictive value of 68.0% (95% CI, 59.1%–75.9%) and specificity of 94.4% (95% CI, 92.5%–96.0%). The diagnostic performance was comparable to guideline-recommended application of an established hs-cTnI assay in a rapid 0/1 h strategy.

Conclusions
The Siemens hs-cTnI assay is well suited for application in rapid diagnostic stratification of patients with suspected MI.

Study Registration
www.clinicaltrials.gov (NCT02355457)
The role of autophagy in cardiovascular pathology
Authors: Gatica Damián , Chiong Mario , Lavandero Sergio , Klionsky Daniel J 
Published: April 2021

AbstractMacroautophagy/autophagy is a conserved catabolic recycling pathway in which cytoplasmic components are sequestered, degraded, and recycled to survive various stress conditions. Autophagy dysregulation has been observed and linked with the development and progression of several pathologies, including cardiovascular diseases, the leading cause of death in the developed world. In this review, we aim to provide a broad understanding of the different molecular factors that govern autophagy regulation and how these mechanisms are involved in the development of specific cardiovascular pathologies, including ischemic and reperfusion injury, myocardial infarction, cardiac hypertrophy, cardiac remodelling, and heart failure.
Prognostic implications of left ventricular myocardial work index in patients with ST-segment elevation myocardial infarction and reduced left ventricular ejection fraction
Authors: Butcher Steele C , Lustosa Rodolfo P , Abou Rachid , Marsan Nina Ajmone , Bax Jeroen J , Delgado Victoria 
Published: April 2021

Abstract

Aims
This study aimed to determine whether lower values of left ventricular (LV) global work index (GWI) at baseline were associated with a reduction in LV functional recovery and poorer long-term prognosis in patients with reduced LV ejection fraction (LVEF ≤40%) following ST-segment elevation myocardial infarction (STEMI).

Methods and results
A total of 197 individuals (62 ± 12 years, 75% male) with STEMI treated with primary percutaneous coronary intervention and reduced LVEF were evaluated. All patients were followed up for the occurrence of all-cause mortality and the presence of LVEF normalization at 6 months (LVEF ≥50%). The median LVEF was 36% (interquartile range 32–38) and the mean value of LV GWI was 1041 ± 404 mmHg% at baseline. At 6-month follow-up, 41% of patients had normalized LVEF. On multivariable logistic regression, higher values of LV GWI were independently associated with LVEF normalization at 6 months of follow-up (odds ratio 1.32 per 250 mmHg%, P = 0.038). Over a median follow-up of 112 months, 40 patients (20%) died. LV GWI &lt;750 mmHg% was independently associated with all-cause mortality (HR 3.85, P &lt; 0.001) and was incremental to LV global longitudinal strain (P = 0.039) and LVEF (P &lt; 0.001).

Conclusion
In individuals with an LVEF ≤40% following STEMI, higher values of LV GWI were associated with a greater probability of LVEF normalization at 6-month follow-up. In addition, lower values of LV GWI were independently associated with increased all-cause mortality at long-term follow-up, providing incremental prognostic value over LVEF and minor incremental prognostic value over LV global longitudinal strain.
Sex differences on new-onset heart failure in patients with known or suspected coronary artery disease
Authors: Núñez Julio , Lorenzo Miguel , Miñana Gema , Palau Patricia , Monmeneu Jose V , López-Lereu Maria P , Gavara Jose , Marcos-Garcés Victor , Ríos-Navarro Cesar , Pérez Nerea , de Dios Elena , Núñez Eduardo , Sanchis Juan , Chorro Francisco J , Bayés-Genís Antoni , Bodí Vicent 
Published: April 2021

Abstract

Aims
The impact of sex in patients with CAD has been widely reported, but little is known about the influence of sex on the risk of new-onset HF in patients with known or suspected CAD. We aimed to examine sex-related differences and new-onset heart failure (HF) risk in patients with known or suspected coronary artery disease (CAD) undergoing vasodilator stress cardiac magnetic resonance (CMR).

Methods and results
We prospectively evaluated 5899 consecutive HF-free patients submitted to stress CMR for known or suspected CAD. Ischaemic burden (number of segments with stress-induced perfusion deficit) and left ventricular ejection fraction (LVEF) were assessed by CMR. The association between sex and new-onset HF (including outpatient diagnosis or acute HF hospitalization) was evaluated using a Cox proportional hazards regression model adjusted for competing events [death, myocardial infarction (MI), and revascularization]. A total of 2289 (38.8%) patients were women. During a median follow-up of 4.5 years, 610 (10.3%) patients died, 191 (3.2%) suffered an MI, 905 (15.3%) underwent revascularization, and 314 (5.3%) developed new-onset HF. Unadjusted new-onset HF rates were higher in women than in men (1.25 vs. 0.83 per 100 person-years, P = 0.001). After comprehensive multivariate adjustment, women showed an increased risk of new-onset HF (hazard ratio 1.58, 95% confidence interval 1.18–2.10; P = 0.002). We found a sex-differential effect along the continuum of LVEF (P-value for interaction = 0.007). At lower LVEF, there was an increased risk in both sexes. However, compared with men, the risk of new-onset HF was higher in women with LVEF &gt;55%.

Conclusion
Women with known or suspected CAD are at a higher risk of new-onset HF. Further studies are needed to unravel the mechanisms behind these sex-related differences.
Prediction, enrichment and isolation identify a responsive, competitive community of cellulolytic microorganisms from a municipal landfill
Authors: Co Rebecca , Hug Laura A 
Published: April 2021

ABSTRACT
Landfills are engineered, heterogeneously contaminated sites containing large reservoirs of paper waste. Cellulose degradation is an important process within landfill microbial ecology, and these anoxic, saturated environments are prime locations for discovery of cellulases that may offer improvements on industrial cellulose degradation efforts. We sampled leachate from three locations within a municipal landfill, a leachate collection cistern, and groundwater from an adjacent aquifer to identify cellulolytic populations and their associated cellulases. Metagenomic sequencing identified wide-spread and taxonomically diverse cellulolytic potential, with a notable scarcity of predicted exocellulases. 16S rRNA amplicon sequencing detected nine landfill microorganisms enriched in a customized leachate medium amended with microcrystalline cellulose or common paper stocks. Paper-enrichment cultures showed competition dynamics in response to the specific composition (lignin: hemi-cellulose: cellulose) of the different paper stocks. From leachate biomass, four novel cellulolytic bacteria were isolated, including two with the capacity for cellulolysis at industrially relevant temperatures. None of the isolates demonstrated exocellulase activity, consistent with the metagenome-based predictions. However, there was very little overlap between metagenome-derived predicted cellulolytic organisms, organisms enriched on paper sources, or the isolates, suggesting the landfill cellulolytic community is at low abundance but able to rapidly respond to introduced substrates.
Characterization of the Aspergillus nidulans Septin (asp) Gene Family
Authors: Momany Michelle , Zhao Jiong , Lindsey Rebecca , Westfall Patrick J 
Published: April 2021

Abstract
Members of the septin gene family are involved in cytokinesis and the organization of new growth in organisms as diverse as yeast, fruit fly, worm, mouse, and human. Five septin genes have been cloned and sequenced from the model filamentous fungus A. nidulans. As expected, the A. nidulans septins contain the highly conserved GTP binding and coiled-coil domains seen in other septins. On the basis of hybridization of clones to a chromosome-specific library and correlation with an A. nidulans physical map, the septins are not clustered but are scattered throughout the genome. In phylogenetic analysis most fungal septins could be grouped with one of the prototypical S. cerevisiae septins, Cdc3, Cdc10, Cdc11, and Cdc12. Intron-exon structure was conserved within septin classes. The results of this study suggest that most fungal septins belong to one of four orthologous classes.
Selective Sweeps in the Presence of Interference Among Partially Linked Loci
Authors: Kim Yuseob , Stephan Wolfgang 
Published: April 2021

Abstract
Recurrent directional selection on a partially recombining chromosome may cause a substantial reduction of standing genetic variation in natural populations. Previous studies of this effect, commonly called selective sweeps, assumed that at most one beneficial allele is on the way to fixation at a given time. However, for a high rate of selected substitutions and a low recombination rate, this assumption can easily be violated. We investigated this problem using full-forward simulations and analytical approximations. We found that interference between linked beneficial alleles causes a reduction of their fixation probabilities. The hitchhiking effect on linked neutral variation for a given substitution also slightly decreases due to interference. As a result, the strength of recurrent selective sweeps is weakened. However, this effect is significant only in chromosomal regions of relatively low recombination rates where the level of variation is greatly reduced. Therefore, previous results on recurrent selective sweeps although derived for a restricted parameter range are still valid. Analytical approximations are obtained for the case of complete linkage for which interference between competing beneficial alleles is maximal.
Phospholipase C-γ Contains Introns Shared by src Homology 2 Domains in Many Unrelated Proteins
Authors: Manning Charlene M , Mathews Wendy R , Fico Leah P , Thackeray Justin R 
Published: April 2021

Abstract
Many proteins with novel functions were created by exon shuffling around the time of the metazoan radiation. Phospholipase C-γ (PLC-γ) is typical of proteins that appeared at this time, containing several different modules that probably originated elsewhere. To gain insight into both PLC-γ evolution and structure-function relationships within the Drosophila PLC-γ encoded by small wing (sl), we cloned and sequenced the PLC-γ homologs from Drosophila pseudoobscura and D. virilis and compared their gene structure and predicted amino acid sequences with PLC-γ homologs in other animals. PLC-γ has been well conserved throughout, although structural differences suggest that the role of tyrosine phosphorylation in enzyme activation differs between vertebrates and invertebrates. Comparison of intron positions demonstrates that extensive intron loss has occurred during invertebrate evolution and also reveals the presence of conserved introns in both the N- and C-terminal PLC-γ SH2 domains that are present in SH2 domains in many other genes. These and other conserved SH2 introns suggest that the SH2 domains in PLC-γ are derived from an ancestral domain that was shuffled not only into PLC-γ, but also into many other unrelated genes during animal evolution.
A Large Rearrangement Involving Genes and Low-Copy DNA Interrupts the Microcollinearity Between Rice and Barley at the Rph7 Locus
Authors: Brunner S , Keller B , Feuillet C 
Published: April 2021

Abstract
Grass genomes differ greatly in chromosome number, ploidy level, and size. Despite these differences, very good conservation of the marker order (collinearity) was found at the genetic map level between the different grass genomes. Collinearity is particularly good between rice chromosome 1 and the group 3 chromosomes in the Triticeae. We have used this collinearity to saturate the leaf rust resistance locus Rph7 on chromosome 3HS in barley with ESTs originating from rice chromosome 1S. Chromosome walking allowed the establishment of a contig of 212 kb spanning the Rph7 resistance gene. Sequencing of the contig showed an average gene density of one gene/20 kb with islands of higher density. Comparison with the orthologous rice sequence revealed the complete conservation of five members of the HGA gene family whereas intergenic regions differ greatly in size and composition. In rice, the five genes are closely associated whereas in barley intergenic regions are &gt;38-fold larger. The size difference is due mainly to the presence of six additional genes as well as noncoding low-copy sequences. Our data suggest that a major rearrangement occurred in this region since the Triticeae and rice lineage diverged.
Spectrum of Chemically Induced Mutations From a Large-Scale Reverse-Genetic Screen in Arabidopsis
Authors: Greene Elizabeth A , Codomo Christine A , Taylor Nicholas E , Henikoff Jorja G , Till Bradley J , Reynolds Steven H , Enns Linda C , Burtner Chris , Johnson Jessica E , Odden Anthony R , Comai Luca , Henikoff Steven 
Published: April 2021

Abstract
Chemical mutagenesis has been the workhorse of traditional genetics, but it has not been possible to determine underlying rates or distributions of mutations from phenotypic screens. However, reverse-genetic screens can be used to provide an unbiased ascertainment of mutation statistics. Here we report a comprehensive analysis of ∼1900 ethyl methanesulfonate (EMS)-induced mutations in 192 Arabidopsis thaliana target genes from a large-scale TILLING reverse-genetic project, about two orders of magnitude larger than previous such efforts. From this large data set, we are able to draw strong inferences about the occurrence and randomness of chemically induced mutations. We provide evidence that we have detected the large majority of mutations in the regions screened and confirm the robustness of the high-throughput TILLING method; therefore, any deviations from randomness can be attributed to selectional or mutational biases. Overall, we detect twice as many heterozygotes as homozygotes, as expected; however, for mutations that are predicted to truncate an encoded protein, we detect a ratio of 3.6:1, indicating selection against homozygous deleterious mutations. As expected for alkylation of guanine by EMS, &gt;99% of mutations are G/C-to-A/T transitions. A nearest-neighbor bias around the mutated base pair suggests that mismatch repair counteracts alkylation damage.
Genetic Variability at Neutral Markers, Quantitative Trait Loci and Trait in a Subdivided Population Under Selection
Authors: Le Corre Valérie , Kremer Antoine 
Published: April 2021

Abstract
Genetic variability in a subdivided population under stabilizing and diversifying selection was investigated at three levels: neutral markers, QTL coding for a trait, and the trait itself. A quantitative model with additive effects was used to link genotypes to phenotypes. No physical linkage was introduced. Using an analytical approach, we compared the diversity within deme (HS) and the differentiation (FST) at the QTL with the genetic variance within deme (VW) and the differentiation (QST) for the trait. The difference between FST and QST was shown to depend on the relative amounts of covariance between QTL within and between demes. Simulations were used to study the effect of selection intensity, variance of optima among demes, and migration rate for an allogamous and predominantly selfing species. Contrasting dynamics of the genetic variability at markers, QTL, and trait were observed as a function of the level of gene flow and diversifying selection. The highest discrepancy among the three levels occurred under highly diversifying selection and high gene flow. Furthermore, diversifying selection might cause substantial heterogeneity among QTL, only a few of them showing allelic differentiation, while the others behave as neutral markers.
The Schizosaccharomyces pombe cdt2+ Gene, a Target of G1-S Phase-Specific Transcription Factor Complex DSC1, Is Required for Mitotic and Premeiotic DNA Replication
Authors: Yoshida Shu-hei , Al-Amodi Hiba , Nakamura Taro , McInerny Christopher J , Shimoda Chikashi 
Published: April 2021

Abstract
We have defined five sev genes by genetic analysis of Schizosaccharomyces pombe mutants, which are defective in both proliferation and sporulation. sev1+/cdt2+ was transcribed during the G1-S phase of the mitotic cell cycle, as well as during the premeiotic S phase. The mitotic expression of cdt2+ was regulated by the MCB-DSC1 system. A mutant of a component of DSC1 affected cdt2+ expression in vivo, and a cdt2+ promoter fragment containing MCB motifs bound DSC1 in vitro. Cdt2 protein also accumulated in S phase and localized to the nucleus. cdt2 null mutants grew slowly at 30° and were unable to grow at 19°. These cdt2 mutants were also medially sensitive to hydroxyurea, camptothecin, and 4-nitroquinoline-1-oxide and were synthetically lethal in combination with DNA replication checkpoint mutations. Flow cytometry analysis and pulsed-field gel electrophoresis revealed that S-phase progression was severely retarded in cdt2 mutants, especially at low temperatures. Under sporulation conditions, premeiotic DNA replication was impaired with meiosis I blocked. Furthermore, overexpression of suc22+, a ribonucleotide reductase gene, fully complemented the sporulation defect of cdt2 mutants and alleviated their growth defect at 19°. These observations suggest that cdt2+ plays an important role in DNA replication in both the mitotic and the meiotic life cycles of fission yeast.
Identification of Quantitative Trait Loci Influencing Wood Property Traits in Loblolly Pine (Pinus taeda L.). III. QTL Verification and Candidate Gene Mapping
Authors: Brown Garth R , Bassoni Daniel L , Gill Geoffrey P , Fontana Joseph R , Wheeler Nicholas C , Megraw Robert A , Davis Mark F , Sewell Mitchell M , Tuskan Gerald A , Neale David B 
Published: April 2021

Abstract
A long-term series of experiments to map QTL influencing wood property traits in loblolly pine has been completed. These experiments were designed to identify and subsequently verify QTL in multiple genetic backgrounds, environments, and growing seasons. Verification of QTL is necessary to substantiate a biological basis for observed marker-trait associations, to provide precise estimates of the magnitude of QTL effects, and to predict QTL expression at a given age or in a particular environment. Verification was based on the repeated detection of QTL among populations, as well as among multiple growing seasons for each population. Temporal stability of QTL was moderate, with approximately half being detected in multiple seasons. Fewer QTL were common to different populations, but the results are nonetheless encouraging for restricted applications of marker-assisted selection. QTL from larger populations accounted for less phenotypic variation than QTL detected in smaller populations, emphasizing the need for experiments employing much larger families. Additionally, 18 candidate genes related to lignin biosynthesis and cell wall structure were mapped genetically. Several candidate genes colocated with wood property QTL; however, these relationships must be verified in future experiments.
Schizosaccharomyces pombe Ras1 Effector, Scd1, Interacts With Klp5 and Klp6 Kinesins to Mediate Cytokinesis
Authors: Li Yingchun , Chang Eric C 
Published: April 2021

Abstract
Fission yeast Scd1 is an exchange factor for Cdc42 and an effector of Ras1. In a screen for scd1 interacting genes, we isolated klp5 and klp6, which encode presumptive kinesins. Klp5 and Klp6 form a complex to control the same processes, which so far include microtubule dynamics and chromosome segregation. We showed that klp5 or klp6 inactivation in combination with the scd1 deletion (scd1Δ) created a synthetic temperature-dependent growth defect. Further genetic analysis demonstrated that Klp5 and Klp6 interacted specifically with the Ras1-Scd1 pathway, but not with the Ras1-Byr2 pathway. In addition, Klp5 and Klp6 can stably associate with Scd1 and Cdc42. A deletion in the Scd1 C terminus, which contains the PB1 domain, prevented Scd1 binding to Klp5/6 and caused a growth defect in Klp5/6 mutant cells that is indistinguishable from that induced by scd1Δ. Analysis of the double-mutant phenotype indicated that at the nonpermissive temperature, cells failed to undergo cytokinesis efficiently. These cells contained abnormal contractile rings in which F-actin and Mid1, a key regulator of F-actin ring formation and positioning, are mispositioned and fragmented. These data suggest that Klp5/6 cooperate with the Ras1-Scd1 pathway to influence proper formation of the contractile ring for cytokinesis.
A Novel Step in β-Tubulin Folding Is Important for Heterodimer Formation in Saccharomyces cerevisiae
Authors: Lacefield Soni , Solomon Frank 
Published: April 2021

Abstract
Undimerized β-tubulin is toxic in the yeast S. cerevisiae. It can arise if levels of β-tubulin and α-tubulin are unbalanced or if the tubulin heterodimer dissociates. We are using the toxicity of β-tubulin to understand early steps in microtubule morphogenesis. We find that deletion of PLP1 suppresses toxic β-tubulin formed by disparate levels of α- and β-tubulin. That suppression occurs either when α-tubulin is modestly underexpressed relative to β-tubulin or when β-tubulin is inducibly and strongly overexpressed. Plp1p does not affect tubulin expression. Instead, a significant proportion of the undimerized β-tubulin in plp1Δ cells is less toxic than that in wild-type cells. It is also less able to combine with α-tubulin to form a heterodimer. As a result, plp1Δ cells have lower levels of heterodimer. Importantly, plp1Δ cells that also lack Pac10, a component of the GimC/PFD complex, are even less affected by free β-tubulin. Our results suggest that Plp1p defines a novel early step in β-tubulin folding.