Showing papers by "University of Valencia published in 2004"

Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration

Abstract: The subventricular zone (SVZ) is a principal source of adult neural stem cells in the rodent brain, generating thousands of olfactory bulb neurons every day. If the adult human brain contains a comparable germinal region, this could have considerable implications for future neuroregenerative therapy. Stem cells have been isolated from the human brain, but the identity, organization and function of adult neural stem cells in the human SVZ are unknown. Here we describe a ribbon of SVZ astrocytes lining the lateral ventricles of the adult human brain that proliferate in vivo and behave as multipotent progenitor cells in vitro. This astrocytic ribbon has not been observed in other vertebrates studied. Unexpectedly, we find no evidence of chains of migrating neuroblasts in the SVZ or in the pathway to the olfactory bulb. Our work identifies SVZ astrocytes as neural stem cells in a niche of unique organization in the adult human brain.

Factors Explaining the Interest Margin in the Banking Sectors of the European Union

Abstract: This study analyses the interest margin in the principal European banking sectors (Germany, France, the United Kingdom, Italy and Spain) in the period 1993–2000 using a panel of 15,888 observations, identifying the fundamental elements affecting this margin. Our starting point is the methodology developed in the original study by Ho and Saunders [Journal of Financial and Quantitative Analysis XVI (1981) 581–600] and later extensions, but widened to take banks' operating costs explicitly into account. Also, unlike the usual practice in the literature, a direct measure of the degree of competition (Lerner index) in the different markets is used. The results show that the fall of margins in the European banking system is compatible with a relaxation of the competitive conditions (increase in market power and concentration), as this effect has been counteracted by a reduction of interest rate risk, credit risk, and operating costs.

Magnetic Molecular Conductors

Abstract: 2.2. BETS Salts with Halometalate Anions 5424 3. Magnetic Metals and Semiconductors 5426 3.1. Mononuclear Metal Complexes 5427 3.1.1. Tetrahalometalates 5427 3.1.2. Hexahalo Anions 5431 3.1.3. Pseudohalide-Containing Anions 5431 3.2. Polynuclear Metal Complexes 5433 3.2.1. Dimeric Anions 5433 3.2.2. Polyoxometalate Clusters 5434 3.3. Chain Anions: Maleonitriledithiolates 5439 4. Ferromagnetic Conductors 5441 5. Ferrimagnetic Insulators 5443 6. Conclusions 5445 7. Acknowledgment 5446 8. References 5446

The ROSAT-ESO Flux Limited X-ray (REFLEX) Galaxy cluster survey. V. The cluster catalogue

Abstract: We present the catalogue of the REFLEX Cluster Survey providing information on the X-ray properties, redshifts, and some identification details of the clusters in the REFLEX sample. The catalogue describes a statistically complete X-ray flux-limited sample of 447 galaxy clusters above an X-ray flux of 3 x 10 -12 erg s -1 cm -2 (0.1 to 2.4 keV) in an area of 4.24 ster in the southern sky. The cluster candidates were first selected by their X-ray emission in the ROSAT-A11 Sky Survey and subsequently spectroscopically identified in the frame of an ESO key programme. Previously described tests have shown that the sample is more than 90% complete and there is a conservative upper limit of 9% on the fraction of clusters with a dominant X-ray contamination from AGN. In addition to the cluster catalogue we also describe the complete selection criteria as a function of the sky position and the conversion functions used to analyse the X-ray data. These are essential for the precise statistical analysis of the large-scale cluster distribution. This data set is at present the largest, statistically complete X-ray galaxy cluster sample. Together with these data set we also provide for the first time the full three-dimensional selection function. The sample forms the basis of several cosmological studies, one of the most important applications being the assessment of the statistics of the large-scale structure of the universe and the test of cosmological models. Part of these cosmological results have already been published.

Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus

Abstract: New neurons continue to be born in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus of adult mammals, including humans. Previous work has shown that astrocytes function as the progenitors of these new neurons through immature intermediate D cells. In the first part of the present study, we determined the structure of each of these progenitors and how they are organized in three dimensions. Serial-section reconstructions of the SGZ, using confocal and electron microscopy demonstrate that SGZ astrocytes form baskets that hold clusters of D cells, largely insulating them from the hilus. Two types of glial fibrillary acidic protein-expressing astrocytes (radial and horizontal) and three classes of doublecortin and PSA-NCAM-positive D cells (D1, D2, D3) were observed. Radial astrocytes appear to interact closely with clusters of D cells forming radial proliferative units. In the second part of this study, we show that retrovirally labeled radial astrocytes give rise to granule neurons. We also used bromodeoxyuridine and [3H]thymidine labeling to study the sequence of appearance of the different D cells after a 7-day treatment with anti-mitotics. This analysis, together with retroviral labeling data, suggest that radial astrocytes divide to generate D1 cells, which in turn divide once to form postmitotic D2 cells. D2 cells mature through a D3 stage to form new granule neurons. These observations provide a model of how the germinal zone of the adult hippocampus is organized and suggest a sequence of cellular stages in the generation of new granule neurons.

The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus.

Abstract: Little is known about the mutational fitness effects associated with single-nucleotide substitutions on RNA viral genomes. Here, we used site-directed mutagenesis to create 91 single mutant clones of vesicular stomatitis virus derived from a common ancestral cDNA and performed competition experiments to measure the relative fitness of each mutant. The distribution of nonlethal deleterious effects was highly skewed and had a long, flat tail. As expected, fitness effects depended on whether mutations were chosen at random or reproduced previously described ones. The effect of random deleterious mutations was well described by a log-normal distribution, with -19% reduction of average fitness; the effects distribution of preobserved deleterious mutations was better explained by a β model. The fit of both models was improved when combined with a uniform distribution. Up to 40% of random mutations were lethal. The proportion of beneficial mutations was unexpectedly high. Beneficial effects followed a γ distribution, with expected fitness increases of 1% for random mutations and 5% for preobserved mutations.

Determination of the Core of a Minimal Bacterial Gene Set

Abstract: The availability of a large number of complete genome sequences raises the question of how many genes are essential for cellular life. Trying to reconstruct the core of the protein-coding gene set for a hypothetical minimal bacterial cell, we have performed a computational comparative analysis of eight bacterial genomes. Six of the analyzed genomes are very small due to a dramatic genome size reduction process, while the other two, corresponding to free-living relatives, are larger. The available data from several systematic experimental approaches to define all the essential genes in some completely sequenced bacterial genomes were also considered, and a reconstruction of a minimal metabolic machinery necessary to sustain life was carried out. The proposed minimal genome contains 206 protein-coding genes with all the genetic information necessary for self-maintenance and reproduction in the presence of a full complement of essential nutrients and in the absence of environmental stress. The main features of such a minimal gene set, as well as the metabolic functions that must be present in the hypothetical minimal cell, are discussed.

Immersion and emotion: their impact on the sense of presence.

Abstract: The present study is designed to test the role of immersion and media content in the sense of presence. Specifically, we are interested in the affective valence of the virtual environments. This paper describes an experiment that compares three immersive systems (a PC monitor, a rear projected video wall, and a head-mounted display) and two virtual environments, one involving emotional content and the other not. The purpose of the experiment was to test the interactive role of these two media characteristics (form and content). Scores on two self-report presence measurements were compared among six groups of 10 people each. The results suggest that both immersion and affective content have an impact on presence. However, immersion was more relevant for non-emotional environments than for emotional ones.

The population genetics and evolutionary epidemiology of RNA viruses

Abstract: RNA viruses are ubiquitous intracellular parasites that are responsible for many emerging diseases, including AIDS and SARS. Here, we discuss the principal mechanisms of RNA virus evolution and highlight areas where future research is required. The rapidity of sequence change in RNA viruses means that they are useful experimental models for the study of evolution in general and it enables us to watch them change in 'real time', and retrace the spread through populations with molecular phylogenies. An understanding of the mechanisms of RNA virus sequence change is also crucial to predicting important aspects of their emergence and long-term evolution.

Ribonucleotide Reductase Messenger RNA Expression and Survival in Gemcitabine/Cisplatin-Treated Advanced Non-Small Cell Lung Cancer Patients

Abstract: Purpose: No chemotherapy regimen, including the widely used combination of gemcitabine/cisplatin, confers significantly improved survival over any other in metastatic non-small cell lung cancer (NSCLC); however, the selection of patients according to key genetic characteristics can help to tailor chemotherapy. Ribonucleotide reductase subunit M1 (RRM1) is involved in DNA synthesis and repair and in gemcitabine metabolism, and the excision repair cross-complementing group 1 ( ERCC1 ) gene has been related to cisplatin activity. Experimental Design: Patients were part of a large randomized trial carried out from September 1998 to July 2000, comparing gemcitabine/cisplatin versus gemcitabine/cisplatin/vinorelbine versus gemcitabine/vinorelbine followed by vinorelbine/ifosfamide. We analyzed RRM1 and ERCC1 mRNA expression in paraffin-embedded samples obtained from bronchoscopy by real-time quantitative reverse transcription-PCR. Results were correlated with survival using the Kaplan-Meier method. Results: A total of 100 patients were assessed. There was a strong correlation between RRM1 and ERCC1 mRNA expression levels (Spearman r = 0.410; P versus 3.6 months; 95% confidence interval (CI), 9.6–17.8 months; P = 0.009]. Median survival was also significantly longer among patients with low mRNA expression levels of both RRM1 and ERCC1 (not reached), than among those with high levels of both genes (6.8 months; 95% CI, 2.6–11.1 months; P = 0.016). Conclusions: RRM1 mRNA expression is a crucial predictive marker of survival in gemcitabine/cisplatin-treated patients. Genetic testing of RRM1 mRNA expression levels can and should be used to personalize chemotherapy.

The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes

Abstract: Regulation of gene expression by mitogen-activated protein kinases (MAPKs) is essential for proper cell adaptation to extracellular stimuli. Exposure of yeast cells to high osmolarity results in rapid activation of the MAPK Hog1, which coordinates the transcriptional programme required for cell survival on osmostress. The mechanisms by which Hog1 and MAPKs in general regulate gene expression are not completely understood, although Hog1 can modify some transcription factors. Here we propose that Hog1 induces gene expression by a mechanism that involves recruiting a specific histone deacetylase complex to the promoters of genes regulated by osmostress. Cells lacking the Rpd3-Sin3 histone deacetylase complex are sensitive to high osmolarity and show compromised expression of osmostress genes. Hog1 interacts physically with Rpd3 in vivo and in vitro and, on stress, targets the deacetylase to specific osmostress-responsive genes. Binding of the Rpd3-Sin3 complex to specific promoters leads to histone deacetylation, entry of RNA polymerase II and induction of gene expression. Together, our data indicate that targeting of the Rpd3 histone deacetylase to osmoresponsive promoters by the MAPK Hog1 is required to induce gene expression on stress.

A classification scheme for mobilization regions of bacterial plasmids.

Abstract: Transmissible plasmids can be classified according to their mobilization ability, as being conjugative (self-transmissible) or mobilizable (transmissible only in the presence of additional conjugative functions). Naturally occurring mobilizable plasmids carry the genetic information necessary for relaxosome formation and processing, but lack the functions required for mating pair formation. Mobilizable plasmids have a tremendous impact in horizontal gene transfer in nature, including the spread of antibiotic resistance. However, analysis of their promiscuity and diversity has attracted less attention than that of conjugative plasmids. This review will focus on the analysis of the diversity of mobilizable plasmids. For this purpose, we primarily compared the amino acid sequences of their relaxases and, when pertinent, we compared these enzymes with conjugative plasmid relaxases. In this way, we established phylogenetic relationships among the members of each superfamily. We conducted a database and literature analysis that led us to propose a classification system for small mobilizable plasmids in families and superfamilies according to their mobilization regions. This review outlines the genetic organization of each family of mobilization regions, as well as the most relevant properties and relationships among their constituent encoded proteins. In this respect, the present review constitutes a first approach to the characterization of the global gene pool of mobilization regions of small mobilizable plasmids.

Determination of pesticides and their degradation products in soil: critical review and comparison of methods

Abstract: Pesticides are applied widely to protect plants from disease, weeds and insect damage, and usually come into contact with soil, where they undergo a variety of transformations that provide a complex pattern of metabolites. This article reviews the most relevant analytical methods for determining pesticides and their transformation products in soils. We address some recent advances in sampling and sample-preparation technologies for soil analysis. We discuss and critically evaluate procedures, such as liquid extraction methods (pressurized liquid extraction or microwave-assisted extraction) and solid-phase based methods (headspace solid-phase microextraction, solid-phase microextraction or matrix-solid-phase dispersion). Analysis of pesticides is generally carried out by gas chromatography (GC) or liquid chromatography (LC) coupled to different detectors, especially to mass spectrometers (MSs). However, alternative and/or complementary methods, using capillary electrophoresis (CE), biosensors and bioassays have emerged recently. We also consider the advantages and the disadvantages of the various methodologies.

2MOLCAS as a development platform for quantum chemistry software

Abstract: This work presents the quantum chemistry package MOLCAS, with emphasis on its usefulness as a platform for developing new quantum chemical codes, and the reader is assumed to be familiar with such a process. The development of new codes for quantum chemistry is a time-consuming job that can be dramatically simplified by using libraries for standard problems (such as calculation of integrals), and tools to surmount computer language and operating system limitations. The MOLCAS quantum chemistry software contains modules for a variety of quantum chemical methods, such as Hartree-Fock (HF), density functional theory (DFT), coupled-cluster (CC), and multiconfigurational (MCSCF) approaches, including second-order perturbation theory. It runs on almost all UNIX-like platforms and contains a single source code for 32- and 64-bit architecture, as well as for serial and parallel execution. The MOLCAS environment allows the user to include, in a simple way, new codes integrated with libraries and other MOLCAS modules. The key features of the MOLCAS environment include a modular structure, an easy-to-use environment, an application programming interface (API) library for solving common computational and system-oriented problems, a solid verification control system, and tools for a distributed development.

A universal definition of life: autonomy and open-ended evolution.

Abstract: Life is a complex phenomenon that not only requires individual self-producing and self- sustaining systems but also a historical-collective organization of those individual systems, which brings about characteristic evolutionary dynamics. On these lines, we propose to define univer- sally living beings as autonomous systems with open-ended evolution capacities, and we claim that all such systems must have a semi-permeable active boundary (membrane), an energy trans- duction apparatus (set of energy currencies) and, at least, two types of functionally interdependent macromolecular components (catalysts and records). The latter is required to articulate a 'phenotype- genotype' decoupling that leads to a scenario where the global network of autonomous systems allows for an open-ended increase in the complexity of the individual agents. Thus, the basic- individual organization of biological systems depends critically on being instructed by patterns (informational records) whose generation and reliable transmission cannot be explained but take into account the complete historical network of relationships among those systems. We conclude that a proper definition of life should consider both levels, individual and collective: living systems cannot be fully constituted without being part of the evolutionary process of a whole ecosystem. Finally, we also discuss a few practical implications of the definition for different programs of research.

Topiramate in migraine prophylaxis--results from a placebo-controlled trial with propranolol as an active control.

Abstract: Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large placebo-controlled, dose-ranging trials. We conducted a randomised, double-blind, multicentre trial to evaluate the efficacy and safety of two doses of topiramate vs placebo for migraine prophylaxis, with propranolol (PROP) as an active control. Subjects with episodic migraine with and without aura were randomised to TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The primary efficacy measure was the change in mean monthly migraine frequency from the baseline phase relative to the double-blind treatment phase. Five hundred and seventy-five subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d was superior to placebo as measured by reduction in monthly migraine frequency, overall 50% responder rate, reduction in monthly migraine days, and reduction in the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were similar with respect to reductions in migraine frequency, responder rate, migraine days, and daily rescue medication usage. TPM 100 mg/d was better tolerated than TPM 200 mg/d, and was generally comparable to PROP. No unusual or unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited similar efficacy profiles.

Acute exercise activates nuclear factor (NF)-κB signaling pathway in rat skeletal muscle

Abstract: Two studies were performed to investigate the effects of an acute bout of physical exercise on the nuclear protein kappaB (NF-kappaB) signaling pathway in rat skeletal muscle. In Study 1, a group of rats (n=6) was run on the treadmill at 25 m/min, 5% grade, for 1 h or until exhaustion (Ex), and compared with a second group (n=6) injected with two doses of pyrrolidine dithiocarbamate (PDTC, 100 mg/kg, i.p.) 24 and 1 h prior to the acute exercise bout. Three additional groups of rats (n=6) were injected with either 8 mg/kg (i.p.) of lipopolysaccharide (LPS), 1 mmol/kg (i.p.) t-butylhydroperoxide (tBHP), or saline (C) and killed at resting condition. Ex rats showed higher levels of NF-kappaB binding and P50 protein content in muscle nuclear extracts compared with C rats. Cytosolic IkappaBalpha and IkappaB kinase (IKK) contents were decreased, whereas phospho-IkappaBalpha and phospho-IKK contents were increased, comparing Ex vs. C. The exercise-induced activation of NF-kappaB signaling cascade was partially abolished by PDTC treatment. LPS, but not tBHP, treatment mimicked and exaggerated the effects observed in Ex rats. In Study 2, the time course of exercise-induced NF-kappaB activation was examined. Highest levels of NF-kappaB binding were observed at 2 h postexercise. Decreased cytosolic IkappaBalpha and increased phosphor-IkappaBalpha content were found 0-1 h postexercise whereas P65 reached peak levels at 2-4 h. These data suggest that the NF-kappaB signaling pathway can be activated in a redox-sensitive manner during muscular contraction, presumably due to increased oxidant production. The cascade of intracellular events may be the overture to elevated gene expression of manganese superoxide dismutase reported earlier (Pfluegers Arch. 442, 426-434, 2001).

Atrial activity extraction for atrial fibrillation analysis using blind source separation

Abstract: This contribution addresses the extraction of atrial activity (AA) from real electrocardiogram (ECG) recordings of atrial fibrillation (AF). We show the appropriateness of independent component analysis (ICA) to tackle this biomedical challenge when regarded as a blind source separation (BSS) problem. ICA is a statistical tool able to reconstruct the unobservable independent sources of bioelectric activity which generate, through instantaneous linear mixing, a measurable set of signals. The three key hypothesis that make ICA applicable in the present scenario are discussed and validated: 1) AA and ventricular activity (VA) are generated by sources of independent bioelectric activity; 2) AA and VA present non-Gaussian distributions; and 3) the generation of the surface ECG potentials from the cardioelectric sources can be regarded as a narrow-band linear propagation process. To empirically endorse these claims, an ICA algorithm is applied to recordings from seven patients with persistent AF. We demonstrate that the AA source can be identified using a kurtosis-based reordering of the separated signals followed by spectral analysis of the sub-Gaussian sources. In contrast to traditional methods, the proposed BSS-based approach is able to obtain a unified AA signal by exploiting the atrial information present in every ECG lead, which results in an increased robustness with respect to electrode selection and placement.

The Determinants of Survival of Spanish Manufacturing Firms

Abstract: This paper analyses the factors determining Spanish manufacturing firms’ survival–and exit. The data are drawn from the survey Encuesta sobre Estrategias Empresariales for the period 1990–1999. The methodology includes both non-parametric techniques and the estimation of a Cox proportional hazards model (CPHM). Our results suggest that the probability of exit is higher for small firms and also for young and mature firms. Furthermore, exporting firms and firms performing R&D activities enjoy better survival prospects.

Environmental and food applications of LC-tandem mass spectrometry in pesticide-residue analysis: an overview.

Abstract: An overview is given on pesticide-residue determination in environmental and food samples by liquid chromatography/mass spectrometry/mass spectrometry (LC/MS/MS). Pesticides comprise a large number of substances that belong to many completely different chemical groups, the only common characteristic is that they are effective against pests. They still constitute a challenge in MS because there is no collective pathway for fragmentation. A brief introduction to the theory of tandem MS permits a discussion of which parameters influence the ionization efficiency when the ions are subjected to different actions. Emphasis is placed on the different tandem MS instruments: triple and ion-trap quadrupoles, and hybrid quadrupole time-of-flight (Q-TOF), including advantages and drawbacks, typical detection limits, and ion signals at low concentrations. The instrumental setup, as well as LC and mass spectrometric experimental conditions, must be carefully selected to increase the performance of the analytical system. The capacity of each instrument to provide useful data for the identification of pesticides, and the possibility to obtain structural information for the identification of target and non-target compounds, are discussed. Finally, sample preparation techniques and examples of applications are debated to reveal the potential of the current state-of-the-art technology, and to further promote the usefulness of tandem MS.

Olive Oils High in Phenolic Compounds Modulate Oxidative/Antioxidative Status in Men

Abstract: The aim of the present study was to evaluate whether olive oils high in phenolic compounds influence the oxidative/antioxidative status in humans. Healthy men (n = 12) participated in a double-blind, randomized, crossover study in which 3 olive oils with low (LPC), moderate (MPC), and high (HPC) phenolic content were given as raw doses (25 mL/d) for 4 consecutive days preceded by 10-d washout periods. Volunteers followed a strict very low-antioxidant diet the 3 d before and during the intervention periods. Short-term consumption of olive oils decreased plasma oxidized LDL (oxLDL), 8-oxo-dG in mitochondrial DNA and urine, malondialdehyde in urine (P < 0.05 for linear trend), and increased HDL cholesterol and glutathione peroxidase activity (P < 0.05 for linear trend), in a dose-dependent manner with the phenolic content of the olive oil administered. At d 4, oxLDL after MPC and HPC, and 8-oxo-dG after HPC administration (25 mL, respectively), were reduced when the men were in the postprandial state (P < 0.05). Phenolic compounds in plasma increased dose dependently during this stage with the phenolic content of the olive oils at 1, 2, 4, and 6 h, respectively (P < 0.01). Their concentrations increased in plasma and urine samples in a dose-dependent manner after short-term consumption of the olive oils (P < 0.01). In conclusion, the olive oil phenolic content modulated the oxidative/antioxidative status of healthy men who consumed a very low-antioxidant diet.