bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of "hot spots" of aggregation in disease-linked polypeptides
Authors: de Groot Natalia Sánchez , Pallarés Irantzu , Avilés Francesc X , Vendrell Josep , Ventura Salvador 
Published: October 2005

Abstract

Background
The polypeptides involved in amyloidogenesis may be globular proteins with a defined 3D-structure or natively unfolded proteins. The first class includes polypeptides such as β2-microglobulin, lysozyme, transthyretin or the prion protein, whereas β-amyloid peptide, amylin or α-synuclein all belong to the second class. Recent studies suggest that specific regions in the proteins act as "hot spots" driving aggregation. This should be especially relevant for natively unfolded proteins or unfolded states of globular proteins as they lack significant secondary and tertiary structure and specific intra-chain interactions that can mask these aggregation-prone regions. Prediction of such sequence stretches is important since they are potential therapeutic targets.

Results
In this study we exploited the experimental data obtained in an in vivo system using β-amyloid peptide as a model to derive the individual aggregation propensities of natural amino acids. These data are used to generate aggregation profiles for different disease-related polypeptides. The approach detects the presence of "hot spots" which have been already validated experimentally in the literature and provides insights into the effect of disease-linked mutations in these polypeptides.

Conclusion
The proposed method might become a useful tool for the future development of sequence-targeted anti-aggregation pharmaceuticals.
Circadian rhythm of autonomic activity in non diabetic offsprings of type 2 diabetic patients
Authors: Fiorentini A , Perciaccante A , Paris A , Serra P , Tubani L 
Published: October 2005

AbstractThe aim of the present study was to evaluate, by heart rate variability (HRV) with 24-hours ECG Holter (HRV), the circadian autonomic activity in offspring of type 2 diabetic subjects and the relation with insulin-resistance. METHODS: 50 Caucasian offsprings of type 2 diabetic subjects were divided in two groups: insulin-resistant offsprings (IR) and non insulin-resistant offsprings (NIR). Autonomic nervous activity was studied by HRV. Time domain and spectral analysis (low frequency, LF, and high frequency, HF, provide markers of sympathetic and parasympathetic modulation when assessed in normalized units) were evaluated. RESULTS. Time domain showed a reduction of total SDNN in IR (p < 0.001) and NIR (p 0.047) versus controls. Spectral analysis showed a total and night LF higher in IR and NIR than in control group (all p < 0.001). CONCLUSION. In frequency domain, the analysis of sympathetic (LF) and parasympathetic (HF) component evidenced an association between the offspring of type 2 diabetic subjects and a sympathetic overactivity. A global reduction and alteration of circadian rhythm of autonomic activity are present in offspring of type 2 diabetic patients with and without insulin resistance. The data of our study suggested that an autonomic impairment is associated with the familiarity for type 2 diabetes independently to insulin resistance and that an impairment of autonomic system activity could precede the insulin resistance.
Effect of larval crowding on mating competitiveness of Anopheles gambiae mosquitoes
Authors: Ng'habi Kija R , John Bernadette , Nkwengulila Gamba , Knols Bart GJ , Killeen Gerry F , Ferguson Heather M 
Published: October 2005

Abstract

Background
The success of sterile or transgenic Anopheles for malaria control depends on their mating competitiveness within wild populations. Current evidence suggests that transgenic mosquitoes have reduced fitness. One means of compensating for this fitness deficit would be to identify environmental conditions that increase their mating competitiveness, and incorporate them into laboratory rearing regimes.

Methods

Anopheles gambiae larvae were allocated to three crowding treatments with the same food input per larva. Emerged males were competed against one another for access to females, and their corresponding longevity and energetic reserves measured.

Results
Males from the low-crowding treatment were much more likely to acquire the first mating. They won the first female approximately 11 times more often than those from the high-crowding treatment (Odds ratio = 11.17) and four times more often than those from the medium-crowding treatment (Odds ratio = 3.51). However, there was no overall difference in the total number of matings acquired by males from different treatments (p = 0.08). The survival of males from the low crowding treatment was lower than those from other treatments. The body size and teneral reserves of adult males did not differ between crowding treatments, but larger males were more likely to acquire mates than small individuals.

Conclusion
Larval crowding and body size have strong, independent effects on the mating competitiveness of adult male An. gambiae. Thus manipulation of larval crowding during mass rearing could provide a simple technique for boosting the competitiveness of sterile or transgenic male mosquitoes prior to release.
Synchronization analysis of the uterine magnetic activity during contractions
Authors: Ramon Ceon , Preissl Hubert , Murphy Pam , Wilson James D , Lowery Curtis , Eswaran Hari 
Published: October 2005

Abstract

Background
Our objective was to quantify and compare the extent of synchronization of the spatial-temporal myometrial activity over the human uterus before and during a contraction using transabdominal magnetomyographic (MMG) recordings. Synchronization can be an important indicator for the quantification of uterine contractions.

Methods
The spatialtermporal myometrial activity recordings were performed using a 151-channel noninvasive magnetic sensor system called SARA. This device covers the entire pregnant abdomen and records the magnetic field corresponding to the electrical activity generated in the uterine myometrium. The data was collected at 250 samples/sec and was resampled with 25 samples/sec and then filtered in the band of 0.1–0.2 Hz to study the primary magnetic activity of the uterus related to contractions. The synchronization between a channel pair was computed. It was inferred from a statistical tendency to maintain a nearly constant phase difference over a given period of time even though the analytic phase of each channel may change markedly during that time frame. The analytic phase was computed after taking Hilbert transform of the magnetic field data. The process was applied on the pairs of magnetic field traces (240 sec length) with a stepping window of 20 sec duration which is long enough to cover two cycle of the lowest frequency of interest (0.1 Hz). The analysis was repeated by stepping the window at 10 sec intervals. The spatial patterns of the synchronization indices covering the anterior transabdominal area were computed. For this, regional coil-pairs were used. For a given coil, the coil pairs were constructed with the surrounding six coils. The synchronization indices were computed for each coil pair, averaged over the 21 coil-pairs and then assigned as the synchronization index to that particular coil. This procedure was tested on six pregnant subjects at the gestational age between 29 and 40 weeks admitted to the hospital for contractions. The RMS magnetic field for each coil was also computed.

Results
The results show that the spatial patterns of the synchronization indices change and follow the periodic pattern of the uterine contraction cycle. Spatial patterns of synchronization indices and the RMS magnetic fields show similarities in few window frames and also show large differences in few other windows. For six subjects, the average synchronization indices were: 0.346 ± 0.068 for the quiescent baseline period and 0.545 ± 0.022 at the peak of the contraction.

Discussion
These results show that synchronization indices and their spatial distributions depict uterine contractions and relaxations.
A multicenter point-prevalence study: antimicrobial prescription frequencies in hospitalized patients in turkey
Authors: Usluer Gaye , Ozgunes Ilhan , Leblebicioglu Hakan ,   the Turkish Antibiotic Utilization Study Group
Published: October 2005

Abstract

Background
Accurate information about prescribing patterns in hospitals is valuable in improving the quality of antimicrobial prescriptions.

Methods
Data on the use of antimicrobial agents in eighteen tertiary care hospitals were collected on March 20th 2002.

Results
One or more antimicrobials were ordered in 2900 (30.6 %)of 9471 hospitalized patients. The reasons of hospitalization of the patients receiving antimicrobials were medical treatment (42.5 %), elective surgery (39.6 %), treatment of infectious disease (17.1 %) and emergent surgical procedures (10.4 %). The highest consumption frequencies were found in surgical (81.6 %) and medical (55.2 %) intensive care units. The 48.8 % of antimicrobials were given for treatment and 44.2 % for prophylactic use. The most common reasons for treatment were found as lower respiratory tract, urinary tract, surgical wound infections and febrile neutropenia. Antimicrobials were ordered empirically in 78.4 % of patients. The proven infection ratio was found as 30.7 %. The 56.4 % and 13.4 % of orders were evaluated as clinically and microbiologically appropriate respectively.

Conclusion
These results suggest that antimicrobial prescription and empirical treatment ratios were high and inappropriate at inpatient groups.
Postprandial lipemia in men with metabolic syndrome, hypertensives and healthy subjects
Authors: Kolovou Genovefa D , Anagnostopoulou Katherine K , Pavlidis Antonis N , Salpea Klelia D , Iraklianou Stella A , Tsarpalis Konstantinos , Damaskos Dimitris S , Manolis Athanasios , Cokkinos Dennis V 
Published: October 2005

Abstract

Background
The metabolic syndrome (MetS), as well as postprandial hypertriglyceridemia, is associated with coronary heart disease. This study aimed to evaluate the postprandial lipemia after oral fat tolerance test (OFTT) in subjects with MetS and compare them to hypertensive (HTN) and healthy subjects.

Results
OFTT was given to 33 men with MetS (defined by the Adult Treatment Panel III), 17 HTN and 14 healthy men. The MetS group was further divided according to fasting triglycerides (TG) into TG ≥ 150 [MetS+TG, (n = 22)] or <150 mg/dl [MetS-TG (n = 11)], and into those with or without hypertension [MetS+HTN (n = 24), MetS-HTN (n = 9), respectively]. TG concentrations were measured before and at 4, 6 and 8 h after OFTT and the postprandial response was quantified using the area under the curve (AUC) for TG.
The postprandial response was significantly higher in MetS compared to HTN and healthy men [AUC (SD) in mg/dl/h; 2534 ± 1016 vs. 1620 ± 494 and 1019 ± 280, respectively, p ≤ 0.001]. The TG levels were increased significantly in MetS+TG compared to MetS-TG subjects at 4 (p = 0.022), 6 (p < 0.001) and 8 hours (p < 0.001). The TG were increased significantly in MetS-TG compared to healthy subjects at 4 (p = 0.011), 6 (p = 0.001) and 8 hours (p = 0.015). In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 8.462, p < 0.001).

Conclusion
Fasting TG concentration is the main determinant of postprandial lipemia. However, an exaggeration of TG postprandialy was found in normotriglyceridemic MetS and HTN compared to healthy subjects. This suggests that intervention to lower fasting TG levels should be recommended in MetS subjects.
Potential targets of transforming growth factor-beta1 during inhibition of oocyte maturation in zebrafish
Authors: Kohli Gurneet , Clelland Eric , Peng Chun 
Published: October 2005

Abstract

Background
TGF-beta is a multifunctional growth factor involved in regulating a variety of cellular activities. Unlike mammals, the function of TGF-beta in the reproduction of lower vertebrates, such as fish, is not clear. Recently, we showed that TGF-beta1 inhibits gonadotropin- and 17alpha, 20beta-dihydroxyprogesterone (DHP)-induced maturation in zebrafish. The aim of the present study was to investigate the mechanisms underlying this action.

Method
To determine if the effect of TGF-beta1 on oocyte maturation involves transcription and/or translation, ovarian follicles were pre-treated with actinomycin D, a blocker of transcription, and cyclohexamide, an inhibitor of translation, and incubated with hCG or DHP, either alone or in combination with TGF-beta1 and oocyte maturation scored. To determine the effect of TGF-beta1 on mRNA levels of several key effectors of oocyte maturation, three sets of experiments were performed. First, follicles were treated with control medium or TGF-beta1 for 2, 6, 12, and 24 h. Second, follicles were treated with different concentrations of TGF-beta1 (0 to 10 ng/ml) for 18 h. Third, follicles were incubated with hCG in the absence or presence of TGF-beta1 for 18 h. At the end of each experiment, total RNA was extracted and reverse transcribed. PCR using primers specific for 20beta-hydroxysteroid dehydrogenase (20beta-HSD) which is involved in DHP production, follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), the two forms of membrane progestin receptor: mPR-alpha and mPR-beta, as well as GAPDH (control), were performed.

Results
Treatment with actinomycin D, a blocker of transcription, reduced the inhibitory effect of TGF-beta1 on DHP-induced oocyte maturation, indicating that the inhibitory action of TGF-beta1 is in part due to regulation of gene transcription. Treatment with TGF-beta1 caused a dose and time-dependent decrease in mRNA levels of 20beta-HSD, LHR and mPR-beta in follicles. On the other hand, TGF-beta1 had no effect on mPR-alpha mRNA expression and increased FSHR mRNA levels. Furthermore, hCG upregulated 20beta-HSD, LHR and mPR-beta mRNA levels, but this stimulatory effect was blocked by TGF-beta1.

Conclusion
These findings suggest that TGF-beta1 acts at multiple sites, including LHR, 20beta-HSD and mPR-beta, to inhibit zebrafish oocyte maturation.
Evolutionary selection across the nuclear hormone receptor superfamily with a focus on the NR1I subfamily (vitamin D, pregnane X, and constitutive androstane receptors)
Authors: Krasowski Matthew D , Yasuda Kazuto , Hagey Lee R , Schuetz Erin G 
Published: October 2005

AbstractBackgroundThe nuclear hormone receptor (NR) superfamily complement in humans is composed of 48 genes with diverse roles in metabolic homeostasis, development, and detoxification. In general, NRs are strongly conserved between vertebrate species, and few examples of molecular adaptation (positive selection) within this superfamily have been demonstrated. Previous studies utilizing two-species comparisons reveal strong purifying (negative) selection of most NR genes, with two possible exceptions being the ligand-binding domains (LBDs) of the pregnane X receptor (PXR, NR1I2) and the constitutive androstane receptor (CAR, NR1I3), two proteins involved in the regulation of toxic compound metabolism and elimination. The aim of this study was to apply detailed phylogenetic analysis using maximum likelihood methods to theentirecomplement of genes in the vertebrate NR superfamily. Analyses were carried out both across all vertebrates and limited to mammals and also separately for the two major domains of NRs, the DNA-binding domain (DBD) and LBD, in addition to the full-length sequences. Additional functional data is also reported for activation of PXR and the vitamin D receptor (VDR; NR1I1) to gain further insight into the evolution of the NR1I subfamily.ResultsThe NR genes appear to be subject to strong purifying selection, particularly in the DBDs. Estimates of the ratio of the non-synonymous to synonymous nucleotide substitution rates (the ω ratio) revealed that only the PXR LBD had a sub-population of codons with an estimated ω ratio greater than 1. CAR was also unusual in showing high relative ω ratios in both the DBD and LBD, a finding that may relate to the recent appearance of the CAR gene (presumably by duplication of a pre-mammalian PXR gene) just prior to the evolution of mammals. Functional analyses of the NR1I subfamily show that human and zebrafish PXRs show similar activation by steroid hormones and early bile salts, properties not shared by sea lamprey, mouse, or human VDRs, or byXenopus laevisPXRs.ConclusionNR genes generally show strong sequence conservation and little evidence for positive selection. The main exceptions are PXR and CAR, genes that may have adapted to cross-species differences in toxic compound exposure.
Gene expression profiling of potential peroxisome proliferator-activated receptor (PPAR) target genes in human hepatoblastoma cell lines inducibly expressing different PPAR isoforms
Authors: Tachibana Keisuke , Kobayashi Yumi , Tanaka Toshiya , Tagami Masayuki , Sugiyama Akira , Katayama Tatsuya , Ueda Chihiro , Yamasaki Daisuke , Ishimoto Kenji , Sumitomo Mikako , Uchiyama Yasutoshi , Kohro Takahide , Sakai Juro , Hamakubo Takao , Kodama Tatsuhiko , Doi Takefumi 
Published: October 2005

Abstract

Background
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors and commonly play an important role in the regulation of lipid homeostasis. To identify human PPARs-responsive genes, we established tetracycline-regulated human hepatoblastoma cell lines that can be induced to express each human PPAR and investigated the gene expression profiles of these cells.

Results
The expression of each introduced PPAR gene was investigated using the various concentrations of doxycycline in the culture media. We found that the expression of each PPAR subtype was tightly controlled by the concentration of doxycycline in these established cell lines. DNA microarray analyses using these cell lines were performed with or without adding each subtype ligand and provided much important information on the PPAR target genes involved in lipid metabolism, transport, storage and other activities. Interestingly, it was noted that while ligand-activated PPARδ induced target gene expression, unliganded PPARδ repressed these genes. The real-time RT-PCR was used to verify the altered expression of selected genes by PPARs and we found that these genes were induced to express in the same pattern as detected in the microarray analyses. Furthermore, we analysed the 5'-flanking region of the human adipose differentiation-related protein (adrp) gene that responded to all subtypes of PPARs. From the detailed analyses by reporter assays, the EMSAs, and ChIP assays, we determined the functional PPRE of the human adrp gene.

Conclusion
The results suggest that these cell lines are important tools used to identify the human PPARs-responsive genes.
Interleukin-1β induced vascular permeability is dependent on induction of endothelial Tissue Factor (TF) activity
Authors: Puhlmann Markus , Weinreich David M , Farma Jeffrey M , Carroll Nancy M , Turner Ewa M , Alexander H Richard 
Published: October 2005

AbstractIL-1β is a pleotropic cytokine that may mediate increased procoagulant activity and permeability in endothelial tissue during inflammatory conditions. The procoagulant effects of IL-1β are mediated through induction of tissue factor (TF) but its alterations on vascular permeability are not well characterized. We found that IL-1β induced a rapid and dose-dependent increase in TF activity in human umbilical vein endothelial cells (ECs) under routine culture conditions. However, IL-1β caused a rapid and marked increase in permeability across confluent EC monolayers using a two-compartmentin vitromodel only in the presence of factor VIII-deficient plasma that was completely abrogated by neutralizing anti-TF antibody pre-treatment.In vitropermeability was associated with loss of EC surface expression of VE-cadherin and contraction of F-actin cytoskeletal elements that resulted in EC intercellular gap formation. These data demonstrate that IL-1β induces marked changes in permeability across activated endothelium via a TF dependent mechanism and suggest that modulation of TF activity may represent a strategy to treat various acute and chronic inflammatory conditions mediated by this cytokine.
Uncertainty principle of genetic information in a living cell
Authors: Strippoli Pierluigi , Canaider Silvia , Noferini Francesco , D'Addabbo Pietro , Vitale Lorenza , Facchin Federica , Lenzi Luca , Casadei Raffaella , Carinci Paolo , Zannotti Maria , Frabetti Flavia 
Published: October 2005

Abstract

Background
Formal description of a cell's genetic information should provide the number of DNA molecules in that cell and their complete nucleotide sequences. We pose the formal problem: can the genome sequence forming the genotype of a given living cell be known with absolute certainty so that the cell's behaviour (phenotype) can be correlated to that genetic information? To answer this question, we propose a series of thought experiments.

Results
We show that the genome sequence of any actual living cell cannot physically be known with absolute certainty, independently of the method used. There is an associated uncertainty, in terms of base pairs, equal to or greater than μs (where μ is the mutation rate of the cell type and s is the cell's genome size).

Conclusion
This finding establishes an "uncertainty principle" in genetics for the first time, and its analogy with the Heisenberg uncertainty principle in physics is discussed. The genetic information that makes living cells work is thus better represented by a probabilistic model rather than as a completely defined object.
Volume of the effect compartment in simulations of neuromuscular block
Authors: Nigrovic Vladimir , Proost Johannes H , Amann Anton , Bhatt Shashi B 
Published: October 2005

Abstract

Background
The study examines the role of the volume of the effect compartment in simulations of neuromuscular block (NMB) produced by nondepolarizing muscle relaxants.

Methods
The molar amount of the postsynaptic receptors at the motor end plates in muscle was assumed constant; the apparent receptor concentration in the effect compartment is the ratio of this amount and the volume arbitrarily assigned to the effect compartment. The muscle relaxants were postulated to diffuse between the central and the effect compartment and to bind to the postsynaptic receptors. NMB was calculated from the free concentration of the muscle relaxant in the effect compartment.

Results
The simulations suggest that the time profiles of NMB and the derived pharmacokinetic and pharmacodynamic variables are dependent on the apparent receptor concentration in the effect compartment. For small, but not for large, volumes, times to peak submaximal NMB are projected to depend on the magnitude of NMB and on the binding affinities.

Conclusion
An experimental design to estimate the volume of the effect compartment is suggested.