bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short‐Period Heart Rate Variability in the General Population as Compared to Patients with Acute Myocardial Infarction from the Same Source Population
Authors: Kuch Bernhard , Parvanov Toma , Hense Hans W. , Axmann Joerg , Bolte Heinz D. 
Published: April 2004

Background: Our aim was to compare the distribution and determinants of heart rate variability (HRV) measures in a middle‐aged population with patients of the same sex and age after an acute myocardial infarction (AMI), and to show, whether HRV values defined as abnormal from the general population are indicative for a worse prognosis even in AMI patients. Methods: HRV was studied in a random sample of 149 middle‐aged men and 137 women from the general population (45–65 years) as well as 129 consecutive AMI patients (25–74 years). Spectral analysis was used to compute low frequency (LF), high frequency (HF), and total frequency power. To the AMI population of age 45–65 years (N = 85) a sample out of the general population was matched by age and sex by 2:1 matching (N = 149). All AMI patients were followed for a median of 43 months (range 1–47) for death or malignant arrhythmia. Results: All measures of HRV were significantly and substantially lower in AMI patients than the general population (P < 0.001). Expression in relative terms revealed that the proportionate contributions of HF and LF to total power were significantly different in the two populations with relatively lower LF power in AMI patients (P < 0.01). The negative correlation with heart rate and HRV measures was significantly more pronounced in AMI patients (P < 0.01). The 2.5th percentile of the LF power distribution in the general population (3.08 ln ms2) corresponds to the 25th percentile in the AMI population. Subjects of the whole AMI population with values below this LF cutpoint revealed a significant increased risk of death or malignant arrhythmia during follow‐up (odds ratio 5.1; 95% confidence interval: 1.3; 23). Conclusions: AMI patients had strongly diminished HRV compared to the general population. The relatively lower LF power indicates an alteration of the sympathico‐vagal balance, and the significantly stronger correlation of heart rate with HRV may be indicative for a more pronounced effect of sympathetic activation on autonomic modulation in the case of myocardial infarction. Finally, a value below the 2.5th percentile of the population LF power distribution may identify subjects at risk and warrant further testing.
Cardiac Autonomic Modulation by Estrogen in Female Mice Undergoing Ambulatory Monitoring and In Vivo Electrophysiologic Testing
Authors: Saba Samir , Shusterman Vladimir , Usiene Irmute , London Barry 
Published: April 2004

Introduction: Estrogen is an important modulator of cardiovascular risk, but its mechanism of action is not fully understood. We investigated the effect of ovariectomy and its timing on the cardiac electrophysiology in mice. Methods: Thirty female mice (age 18.8 ± 3.1 weeks) underwent in vivo electrophysiologic testing before and after autonomic blockade. Fifteen mice were ovariectomized prepuberty (PRE) and ten postpuberty (POST), 2 weeks prior to electrophysiologic testing. Five age‐matched sham‐operated female mice (Control) served as controls. A subset of 13 mice (5 PRE, 3 POST, and 5 Controls) underwent 24‐hour ambulatory monitoring. Results: With ambulatory monitoring, the average (668 ± 28 vs 769 ± 52 b/min, P = 0.008) and minimum (485 ± 47 vs 587 ± 53 b/min, P = 0.02) heart rates were significantly slower in the ovariectomized mice (PRE and POST groups) compared to the Control group. At baseline electrophysiologic testing, there were no significant differences among the ovariectomized and intact mice in any of the measured parameters. With autonomic blockade, the Control group had a significantly larger change (▵) in the atrioventricular (AV) nodal Wenckebach (AVW) periodicity (▵AVW = 11.3 ± 2.9 vs 2.1 ± 7.3 ms, P = 0.05) and functional refractory period (▵FRP = 11.3 ± 2.1 vs 1.25 ± 6.8 ms, P = 0.02) compared to the ovariectomized mice. These results were not altered by the time of ovariectomy (PRE vs POST groups). Conclusion: Our results suggest that estrogen modulates the autonomic inputs into the murine sinus and AV nodes. These findings, if replicated in humans, might underlie the observed clustering of certain arrhythmias around menstruation and explain the higher incidence of arrhythmias in men and postmenopausal women.
Sex Steroids and Heart Rate Variability in Patients after Myocardial Infarction
Authors: Wranicz Jerzy Krzysztof , Rosiak Marcin , Cygankiewicz Iwona , Kula Piotr , Kula Krzysztof , Zareba Wojciech 
Published: April 2004

Background: Although the relationship between sex steroid levels and coronary artery disease (CAD) has been the subject of many studies there are still controversies concerning the role of sex steroids in CAD. In patients with CAD, especially after a myocardial infarction, there is evidence for autonomic nervous system dysfunction. However, there is no data detailing the relationship between sex steroids and cicardian autonomic activity in patients with CAD. The aim of the study was to evaluate the association between sex steroids and heart rate variability (HRV) parameters in postinfarction patients. Methods: In 88 postinfarction men (aged 36–73, average 53 years), 24‐hour Holter monitoring was performed to assess HRV parameters: SDNN, SDNNI, SDANN, rMSSD, pNN50, and levels of the following hormones were measured: testosterone, estradiol, free testosterone index, and estradiol/testosterone ratio. Univariate and multivariate regression analyses were used to investigate the relationship between HRV parameters and levels of tested hormones. Results: Increased testosterone levels were associated with increased SDNN (r = 0.38, P = 0.03), increased rMSSD (r = 0.51, P = 0.002), and increased pNN50 (r = 0.45, P = 0.007). These associations remained significance after adjustment for age, ejection fraction, and other relevant clinical covariates. There was no significant association between estradiol and HRV parameters. Conclusion: In men with a history of myocardial infarction, higher levels of testosterone are associated with higher HRV measures of parasympathetic activity. These findings suggest that testosterone beneficially influences autonomic regulation of the heart.
A preliminary investigation into the ultrastructure of dental calculus and associated bacteria
Authors: Tan B. , Gillam David G. , Mordan N. J. , Galgut P. N. 
Published: April 2004

AbstractIntroduction: Though dental calculus is generally recognised as comprising mineralised bacteria, areas of non‐mineralised bacteria may be present.Aim: To investigate the ultrastructure of non‐decalcified young and mature supragingival calculus and subgingival calculus, and the possible presence of internal viable bacteria.Materials and methods: Supragingival calculus was harvested from five patients, 9–10 weeks after scaling and root debridement. Five samples of mature supragingival and subgingival calculus were taken from patients presenting with adult periodontitis. Specimens were fixed and embedded for transmission electron microscopy.Results: The ultrastructure of young and mature supragingival calculus was similar with various large and small crystal types. Non‐mineralised channels were observed extending into the calculus, often joining extensive lacunae, both containing intact non‐mineralised coccoid and rod‐shaped microorganisms. Subgingival calculus possessed more uniform mineralisation without non‐mineralised channels and lacunae.Conclusion: Supragingival calculus contains non‐mineralised areas which contain bacteria and other debris. The viability of the bacteria, and their identification could not be determined in this preliminary investigation. As viable bacteria within these lacunae may provide a source of re‐infection, further work needs to be done to identify the bacteria in the lacunae, and to determine their viability.
Defects in the N-Linked Oligosaccharide Biosynthetic Pathway in a
Trypanosoma brucei
Glycosylation Mutant
Authors: Acosta-Serrano Alvaro , O'Rear Jessica , Quellhorst George , Lee Soo Hee , Hwa Kuo-Yuan , Krag Sharon S. , Englund Paul T. 
Published: April 2004

ABSTRACT

Concanavalin A (ConA) kills the procyclic (insect) form of
Trypanosoma brucei
by binding to its major surface glycoprotein, procyclin. We previously isolated a mutant cell line, ConA 1-1, that is less agglutinated and more resistant to ConA killing than are wild-type (WT) cells. Subsequently we found that the ConA resistance phenotype in this mutant is due to the fact that the procyclin either has no N-glycan or has an N-glycan with an altered structure. Here we demonstrate that the alteration in procyclin N-glycosylation correlates with two defects in the N-linked oligosaccharide biosynthetic pathway. First, ConA 1-1 has a defect in activity of polyprenol reductase, an enzyme involved in synthesis of dolichol. Metabolic incorporation of [
3
H]mevalonate showed that ConA 1-1 synthesizes equal amounts of dolichol and polyprenol, whereas WT cells make predominantly dolichol. Second, we found that ConA 1-1 synthesizes and accumulates an oligosaccharide lipid (OSL) precursor that is smaller in size than that from WT cells. The glycan of OSL in WT cells is apparently Man
9
GlcNAc
2
, whereas that from ConA 1-1 is Man
7
GlcNAc
2
. The smaller OSL glycan in the ConA 1-1 explains how some procyclin polypeptides bear a Man
4
GlcNAc
2
modified with a terminal
N
-acetyllactosamine group, which is poorly recognized by ConA.
Plasmodium falciparum
Histone Acetyltransferase, a Yeast GCN5 Homologue Involved in Chromatin Remodeling
Authors: Fan Qi , An Lijia , Cui Liwang 
Published: April 2004

ABSTRACT

The yeast transcriptional coactivator GCN5 (yGCN5), a histone acetyltransferase (HAT), is part of large multimeric complexes that are required for chromatin remodeling and transcriptional activation. Like other eukaryotes, the malaria parasite DNA is organized into nucleosomes and the genome encodes components of chromatin-remodeling complexes. Here we show that GCN5 is conserved in
Plasmodium
species and that the most homologous regions are within the HAT domain and the bromodomain. The
Plasmodium falciparum GCN5
homologue (
PfGCN5
) is spliced with three introns, encoding a protein of 1,464 residues. Mapping of the ends of the
PfGCN5
transcript suggests that the mRNA is 5.2 to 5.4 kb, consistent with the result from Northern analysis. Using free core histones, we determined that recombinant PfGCN5 proteins have conserved HAT activity with a substrate preference for histone H3. Using substrate-specific antibodies, we determined that both Lys-8 and -14 of H3 were acetylated by the recombinant PfGCN5. In eukaryotes, GCN5 homologues interact with yeast ADA2 homologues and form large multiprotein HAT complexes. We have identified an ADA2 homologue in
P. falciparum
, PfADA2. Yeast two-hybrid and in vitro binding assays verified the interactions between PfGCN5 and PfADA2, suggesting that they may be associated with each other in vivo. The conserved function of the HAT domain in PfGCN5 was further illustrated with yeast complementation experiments, which showed that the PfGCN5 region corresponding to the full-length yGCN5 could partially complement the
yGCN5
deletion mutation. Furthermore, a chimera comprising the PfGCN5 HAT domain fused to the remainder of yeast GCN5 (yGCN5) fully rescued the
yGCN5
deletion mutant. These data demonstrate that PfGCN5 is an authentic GCN5 family member and may exist in chromatin-remodeling complexes to regulate gene expression in
P. falciparum
.
YBP1 and Its Homologue YBP2/YBH1 Influence Oxidative-Stress Tolerance by Nonidentical Mechanisms in
Saccharomyces cerevisiae
Authors: Gulshan Kailash , Rovinsky Sherry A. , Moye-Rowley W. Scott 
Published: April 2004

ABSTRACT

In the yeast
Saccharomyces cerevisiae
, the transcription factor Yap1p is a central determinant of resistance to oxidative stress. Previous work has demonstrated that Yap1p is recruited from the cytoplasm to the nucleus upon exposure to the oxidants diamide and H
2
O
2
in a process that requires the transient covalent linkage of the glutathione peroxidase Gpx3p to Yap1p. Genetic and biochemical analyses indicate that while both oxidants trigger nuclear accumulation of Yap1p, the function and regulation of this transcription factor is different under these two different oxidative stresses. Ybp1p (Yap1p-binding protein) has recently been demonstrated to be required for Yap1p-mediated H
2
O
2
resistance but not diamide resistance. A Ybp1p homologous protein (Ybh1p/Ybp2p) was also detected in the
S. cerevisiae
genome. Here we compare the actions of these two closely related proteins and provide evidence that while both factors influence H
2
O
2
tolerance, they do so by nonidentical mechanisms. A double mutant strain lacking both
YBP1
and
YBH1
genes is more sensitive to H
2
O
2
and more defective in activation of Yap1p-dependent gene expression than either single mutant. Ybp1p has a more pronounced effect on these phenotypes than does Ybh1p. Protein-protein interactions between Yap1p and Ybp1p could be detected by either the yeast two-hybrid or coimmunoprecipitation approach while neither technique could demonstrate Yap1p-Ybh1p interactions. Overexpression experiments indicated that high levels of Ybh1p but not Ybp1p could bypass the H
2
O
2
hypersensitivity of a
gpx3
Δ strain. Together, these data argue that these two homologous proteins act as parallel positive regulators of H
2
O
2
tolerance.
Identification, Mutational Analysis, and Coactivator Requirements of Two Distinct Transcriptional Activation Domains of the
Saccharomyces cerevisiae
Hap4 Protein
Authors: Stebbins John L. , Triezenberg Steven J. 
Published: April 2004

ABSTRACT

The Hap4 protein of the budding yeast
Saccharomyces cerevisiae
activates the transcription of genes that are required for growth on nonfermentable carbon sources. Previous reports suggested the presence of a transcriptional activation domain within the carboxyl-terminal half of Hap4 that can function in the absence of Gcn5, a transcriptional coactivator protein and histone acetyltransferase. The boundaries of this activation domain were further defined to a region encompassing amino acids 359 to 476. Within this region, several clusters of hydrophobic amino acids are critical for transcriptional activity. This activity does not require
GCN5
or two other components of the SAGA coactivator complex,
SPT3
and
SPT8
, but it does require
SPT7
and
SPT20
. Contrary to previous reports, a Hap4 fragment comprising amino acids 1 to 330 can support the growth of yeast on lactate medium, and when tethered to
lexA
, can activate a reporter gene with upstream
lexA
binding sites, demonstrating the presence of a second transcriptional activation domain. In contrast to the C-terminal activation domain, the transcriptional activity of this N-terminal region depends on
GCN5
. We conclude that the yeast Hap4 protein has at least two transcriptional activation domains with strikingly different levels of dependence on specific transcriptional coactivator proteins.
Novel P-Type ATPases Mediate High-Affinity Potassium or Sodium Uptake in Fungi
Authors: Benito Begoña , Garciadeblás Blanca , Schreier Peter , Rodríguez-Navarro Alonso 
Published: April 2004

ABSTRACTFungi have an absolute requirement for K+, but K+may be partially replaced by Na+. Na+uptake inUstilago maydisandPichia sorbitophilawas found to exhibit a fast rate, lowKm, and apparent independence of the membrane potential. Searches of sequences with similarity to P-type ATPases in databases allowed us to identify three genes in these species,Umacu1,Umacu2, andPsACU1, that could encode P-type ATPases of a novel type. Deletion of theacu1andacu2genes proved that they encoded the transporters that mediated the high-affinity Na+uptake ofU. maydis. Heterologous expressions of theUmacu2gene in K+transport mutants ofSaccharomyces cerevisiaeand transport studies in the single and double Δacu1and Δacu2mutants ofU. maydisrevealed that theacu1andacu2genes encode transporters that mediated high-affinity K+uptake in addition to Na+uptake. Other fungi also have genes or pseudogenes whose translated sequences show high similarity to the ACU proteins ofU. maydisandP. sorbitophila. In the phylogenetic tree of P-type ATPases all the identified ACU ATPases define a new cluster, which shows the lowest divergence with type IIC, animal Na+,K+-ATPases. The fungal high-affinity Na+uptake mediated by ACU ATPases is functionally identical to the uptake that is mediated by some plant HKT transporters.
Cryptococcus neoformans CAP59
(or Cap59p) Is Involved in the Extracellular Trafficking of Capsular Glucuronoxylomannan
Authors: García-Rivera Javier , Chang Yun C. , Kwon-Chung K. J. , Casadevall Arturo 
Published: April 2004

ABSTRACT

Several genes are essential for
Cryptococcus neoformans
capsule synthesis, but their functions are unknown. We examined the localization of glucuronoxylomannan (GXM) in strain B-3501 and in
cap59
mutants B-4131 and C536. Wild-type strain B-3501 showed a visible capsule by India ink staining and immunofluorescence with anticapsular monoclonal antibodies (MAbs) 12A1 and 18B7. B-4131, a mutant containing a missense mutation in
CAP59
, showed no capsule by India ink staining but revealed the presence of capsular polysaccharide on the cell surface by immunofluorescence. The
cap59
gene deletion mutant (C536), however, did not show a capsule by either India ink staining or immunofluorescence. Analysis of cell lysates for GXM by enzyme-linked immunosorbent assay revealed GXM in C536 samples. Furthermore, the epitopes recognized by MAbs 12A1, 2D10, 13F1, and 18B7 were each detected in the cytoplasm of all strains by immunogold electron microscopy, although there were differences in location consistent with differences in epitope synthesis and/or transport. In addition, the cells of B-3501 and B-4131, but not those of the
cap59
deletant, assimilated raffinose or urea. Hence, the missense mutation of
CAP59
in B-4131 partially hampered the trafficking of GXM but allowed the secretion of enzymes involved in hydrolysis of raffinose or urea. Furthermore, the cell diameter and volume for strain C536 are higher than those for strain B-3501 or B-4131 and may suggest the accumulation of cellular material in the cytoplasm. Our results suggest that
CAP59
is involved in capsule synthesis by participating in the process of GXM (polysaccharide) export.
A Paradoxical Mutant GATA Factor
Authors: Muro-Pastor M. Isabel , Strauss Joseph , Ramón Ana , Scazzocchio Claudio 
Published: April 2004

ABSTRACT

The
niiA
(nitrite reductase) and
niaD
(nitrate reductase) genes of
Aspergillus nidulans
are subject to both induction by nitrate and repression by ammonium or glutamine. The intergenic region between these genes functions as a bidirectional promoter. In this region, nucleosomes are positioned under nonexpression conditions. On nitrate induction under derepressing conditions, total loss of positioning occurs. This is independent of transcription and of the NirA-specific transcription factor but absolutely dependent on the wide-domain GATA-binding AreA factor. We show here that a 3-amino-acid deletion in the basic carboxy-terminal sequence of the DNA-binding domain results in a protein with paradoxical properties. Its weak DNA binding is consistent with its loss-of-function phenotype on most nitrogen sources. However, it results in constitutive expression and superinducibility of
niiA
and
niaD
. Nucleosome loss of positioning is also constitutive. The mutation partially suppresses null mutations in the transcription factor NirA. AreA binds NirA in vitro, and the mutation does not affect this interaction. The in vivo methylation pattern of the promoter is drastically altered, suggesting the recruitment of one or more unknown transcription factors and/or a local distortion on the DNA double helix.
Cell Division Defects of
Schizosaccharomyces pombe liz1
−
Mutants Are Caused by Defects in Pantothenate Uptake
Authors: Stolz Jürgen , Caspari Thomas , Carr Antony M. , Sauer Norbert 
Published: April 2004

ABSTRACT

The

liz1
+

gene of the fission yeast
Schizosaccharomyces pombe
was previously identified by complementation of a mutation that causes abnormal mitosis when ribonucleotide reductase is inhibited. Liz1 has similarity to transport proteins from
Saccharomyces cerevisiae
, but the potential substrate and its connection to the cell division cycle remain elusive. We report here that

liz1
+

encodes a plasma membrane-localized active transport protein for the vitamin pantothenate, the precursor of coenzyme A (CoA). Liz1 is required for pantothenate uptake at low extracellular concentrations. A lack of pantothenate uptake results in three phenotypes: (i) slow growth, (ii) delayed septation, and (iii) aberrant mitosis in the presence of hydroxyurea (HU). All three phenotypes are suppressed by high extracellular concentrations of pantothenate, where pantothenate uptake occurs by passive diffusion.
liz1
Δ mutants are viable because they can synthesize pantothenate from uracil as an endogenous source. The use of uracil for both pantothenate biosynthesis and deoxyribonucleotide generation provides an explanation for the aberrant mitosis in the presence of HU. HU blocks ribonucleotide reductase, and we propose that the accumulation of ribonucleotides reduces uracil biosynthesis by feedback inhibition of aspartate transcarbamoylase. Thus, the addition of HU to
liz1
Δ mutants results in a shortage of pantothenate. Because
liz1
Δ mutants show striking similarities to mutants with defects in fatty acid biosynthesis, we propose that the shortage of pantothenate compromises fatty acid synthesis, resulting in slow growth and mitotic defects.
Challenge of
Drosophila melanogaster
with
Cryptococcus neoformans
and Role of the Innate Immune Response
Authors: Apidianakis Yiorgos , Rahme Laurence G. , Heitman Joseph , Ausubel Frederick M. , Calderwood Stephen B. , Mylonakis Eleftherios 
Published: April 2004

ABSTRACT

We found that the ingestion of
Cryptococcus neoformans
by
Drosophila melanogaster
resulted in the death of the fly but that the ingestion of
Saccharomyces cerevisiae
or the nonpathogenic
Cryptococcus kuetzingii
or
Cryptococcus laurentii
did not. The
C. neoformans
protein kinase A and RAS signal transduction pathways, previously shown to be involved in virulence in mammals, also played a role in killing
Drosophila
. Mutation of the Toll immune response pathway, the predominant antifungal pathway of the fly, did not play a role in
Drosophila
defense following ingestion of the yeast. However, the Toll pathway was necessary for the clearance of
C. neoformans
introduced directly into the hemolymph of
D. melanogaster
and for the survival of systemically infected flies.