scispace - formally typeset
Search or ask a question

Showing papers by "Utrecht University published in 2004"


Journal ArticleDOI
Sara A. Burt1
TL;DR: In vitro studies have demonstrated antibacterial activity of essential oils (EOs) against Listeria monocytogenes, Salmonella typhimurium, Escherichia coli O157:H7, Shigella dysenteria, Bacillus cereus and Staphylococcus aureus at levels between 0.2 and 10 microl ml(-1).

9,091 citations


Journal ArticleDOI
TL;DR: In this paper, a model is tested in which burnout and engagement have different predictors and different possible consequences, showing that burnout is mainly predicted by job demands but also by lack of job resources, whereas engagement is exclusively predicted by available job resources.
Abstract: This study focuses on burnout and its positive antipode—engagement. A model is tested in which burnout and engagement have different predictors and different possible consequences. Structural equation modeling was used to simultaneously analyze data from four independent occupational samples (total N = 1698). Results confirm the hypothesized model indicating that: (1) burnout and engagement are negatively related, sharing between 10 per cent and 25 per cent of their variances; (2) burnout is mainly predicted by job demands but also by lack of job resources, whereas engagement is exclusively predicted by available job resources; (3) burnout is related to health problems as well as to turnover intention, whereas engagement is related only to the latter; (4) burnout mediates the relationship between job demands and health problems, whereas engagement mediates the relationship between job resources and turnover intention. The fact that burnout and engagement exhibit different patterns of possible causes and consequences implies that different intervention strategies should be used when burnout is to be reduced or engagement is to be enhanced. Copyright © 2004 John Wiley & Sons, Ltd.

7,068 citations


Journal ArticleDOI
22 Apr 2004-Nature
TL;DR: Reliable quantification of the leaf economics spectrum and its interaction with climate will prove valuable for modelling nutrient fluxes and vegetation boundaries under changing land-use and climate.
Abstract: Bringing together leaf trait data spanning 2,548 species and 175 sites we describe, for the first time at global scale, a universal spectrum of leaf economics consisting of key chemical, structural and physiological properties. The spectrum runs from quick to slow return on investments of nutrients and dry mass in leaves, and operates largely independently of growth form, plant functional type or biome. Categories along the spectrum would, in general, describe leaf economic variation at the global scale better than plant functional types, because functional types overlap substantially in their leaf traits. Overall, modulation of leaf traits and trait relationships by climate is surprisingly modest, although some striking and significant patterns can be seen. Reliable quantification of the leaf economics spectrum and its interaction with climate will prove valuable for modelling nutrient fluxes and vegetation boundaries under changing land-use and climate.

6,360 citations


Journal ArticleDOI
Edzer Pebesma1
TL;DR: The gstat S package is introduced, an extension package for the S environments (R, S-Plus) that provides multivariable geostatistical modelling, prediction and simulation, as well as several visualisation functions.

2,455 citations


Journal ArticleDOI
TL;DR: In this paper, the authors used the job demands-resources model to examine the relationship between job characteristics, burnout, and (other-ratings of) performance, and found that job demands (e.g., work pressure and emotional demands) would be the most important antecedents of the exhaustion component of burnout.
Abstract: The job demands-resources (JD-R) model was used to examine the relationship between job characteristics, burnout, and (other-ratings of) performance (N = 146). We hypothesized that job demands (e.g., work pressure and emotional demands) would be the most important antecedents of the exhaustion component of burnout, which, in turn, would predict in-role performance (hypothesis 1). In contrast, job resources (e.g., autonomy and social support) were hypothesized to be the most important predictors of extra-role performance, through their relationship with the disengagement component of burnout (hypothesis 2). In addition, we predicted that job resources would buffer the relationship between job demands and exhaustion (hypothesis 3), and that exhaustion would be positively related to disengagement (hypothesis 4). The results of structural equation modeling analyses provided strong support for hypotheses 1, 2, and 4, but rejected hypothesis 3. These findings support the JD-R model's claim that job demands and job resources initiate two psychological processes, which eventually affect organizational outcomes. © 2004 Wiley Periodicals, Inc.

2,103 citations


Journal ArticleDOI
TL;DR: Endovascular repair is preferable to open repair in patients who have an abdominal aortic aneurysm that is at least 5 cm in diameter and long-term follow-up is needed to determine whether this advantage is sustained.
Abstract: Background Although the initial results of endovascular repair of abdominal aortic aneurysms were promising, current evidence from controlled studies does not convincingly show a reduction in 30-day mortality relative to that achieved with open repair. Methods We conducted a multicenter, randomized trial comparing open repair with endovascular repair in 345 patients who had received a diagnosis of abdominal aortic aneurysm of at least 5 cm in diameter and who were considered suitable candidates for both techniques. The outcome events analyzed were operative (30-day) mortality and two composite end points of operative mortality and severe complications and operative mortality and moderate or severe complications. Results The operative mortality rate was 4.6 percent in the open-repair group (8 of 174 patients; 95 percent confidence interval, 2.0 to 8.9 percent) and 1.2 percent in the endovascular-repair group (2 of 171 patients; 95 percent confidence interval, 0.1 to 4.2 percent), resulting in a risk ratio ...

1,891 citations


Journal ArticleDOI
TL;DR: To describe the 12‐month and lifetime prevalence rates of mood, anxiety and alcohol disorders in six European countries, a large number of countries with high prevalence of these disorders have been surveyed.
Abstract: Objective: To describe the 12-month and lifetime prevalence rates of mood, anxiety and alcohol disorders in six European countries. Method: A representative random sample of non-institutionalized inhabitants from Belgium, France, Germany, Italy, the Netherlands and Spain aged 18 or older (n = 21425) were interviewed between January 2001 and August 2003. DSM-IV disorders were assessed by lay interviewers using a revised version of the Composite International Diagnostic Interview (WMH-CIDI). Results: Fourteen per cent reported a lifetime history of any mood disorder, 13.6% any anxiety disorder and 5.2% a lifetime history of any alcohol disorder. More than 6% reported any anxiety disorder, 4.2% any mood disorder, and 1.0% any alcohol disorder in the last year. Major depression and specific phobia were the most common single mental disorders. Women were twice as likely to suffer 12-month mood and anxiety disorders as men, while men were more likely to suffer alcohol abuse disorders. Conclusion: ESEMeD is the first study to highlight the magnitude of mental disorders in the six European countries studied. Mental disorders were frequent, more common in female, unemployed, disabled persons, or persons who were never married or previously married. Younger persons were also more likely to have mental disorders, indicating an early age of onset for mood, anxiety and alcohol disorders.

1,780 citations


Journal ArticleDOI
TL;DR: Ticks and tick-borne diseases affect animal and human health worldwide and are the cause of significant economic losses and although some estimates are given, there is a lack of reliable data.
Abstract: Ticks and tick-borne diseases affect animal and human health worldwide and are the cause of significant economic losses. Approximately 10% of the currently known 867 tick species act as vectors of a broad range of pathogens of domestic animals and humans and are also responsible for damage directly due to their feeding behaviour. The most important tick species and the effects they cause are listed. The impact on the global economy is considered to be high and although some estimates are given, there is a lack of reliable data. The impact of ticks and tick-borne diseases on animal production and public health and their control are discussed.

1,623 citations


Journal ArticleDOI
TL;DR: In this paper, the authors discuss an umbrella model of levels of change that could serve as a framework for reflection and development in teacher education, highlighting relatively new areas of research, viz. teachers' professional identity and mission.

1,458 citations


Journal ArticleDOI
14 May 2004-Science
TL;DR: X-ray absorption spectroscopy and x-ray Raman scattering were used to probe the molecular arrangement in the first coordination shell of liquid water and set a strong limit for possible local structure distributions in liquid water.
Abstract: X-ray absorption spectroscopy and x-ray Raman scattering were used to probe the molecular arrangement in the first coordination shell of liquid water. The local structure is characterized by comparison with bulk and surface of ordinary hexagonal ice Ih and with calculated spectra. Most molecules in liquid water are in two hydrogen– bonded configurations with one strong donor and one strong acceptor hydrogen bond in contrast to the four hydrogen– bonded tetrahedral structure in ice. Upon heating from 25°C to 90°C, 5 to 10% of the molecules change from tetrahedral environments to two hydrogen– bonded configurations. Our findings are consistent with neutron and x-ray diffraction data, and combining the results sets a strong limit for possible local structure distributions in liquid water. Serious discrepancies with structures based on current molecular dynamics simulations are observed.

1,278 citations


Journal ArticleDOI
TL;DR: A mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias.
Abstract: The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue.

Journal ArticleDOI
24 Sep 2004-Science
TL;DR: A review of recent studies on various ecosystems that link self-organized patchiness to catastrophic shifts between ecosystem states and the implications for management and recovery strategies for such ecosystems.
Abstract: Unexpected sudden catastrophic shifts may occur in ecosystems, with concomitant losses or gains of ecological and economic resources. Such shifts have been theoretically attributed to positive feedback and bistability of ecosystem states. However, verifications and predictive power with respect to catastrophic responses to a changing environment are lacking for spatially extensive ecosystems. This situation impedes management and recovery strategies for such ecosystems. Here, we review recent studies on various ecosystems that link self-organized patchiness to catastrophic shifts between ecosystem states.

Journal ArticleDOI
TL;DR: This review presents a synthesis between the dorsal-ventral distinction and the more mediolateral-oriented functional striatal gradient.

Journal ArticleDOI
TL;DR: In this article, the results from a second characterisation of the 91500 zircon, including data from electron probe microanalysis, laser ablation inductively coupled plasma-mass spectrometer (LA-ICP-MS), secondary ion mass spectrometry (SIMS), and laser fluorination analyses, were reported.
Abstract: This paper reports the results from a second characterisation of the 91500 zircon, including data from electron probe microanalysis, laser ablation inductively coupled plasma-mass spectrometry (LA-ICP-MS), secondary ion mass spectrometry (SIMS) and laser fluorination analyses. The focus of this initiative was to establish the suitability of this large single zircon crystal for calibrating in situ analyses of the rare earth elements and oxygen isotopes, as well as to provide working values for key geochemical systems. In addition to extensive testing of the chemical and structural homogeneity of this sample, the occurrence of banding in 91500 in both backscattered electron and cathodoluminescence images is described in detail. Blind intercomparison data reported by both LA-ICP-MS and SIMS laboratories indicate that only small systematic differences exist between the data sets provided by these two techniques. Furthermore, the use of NIST SRM 610 glass as the calibrant for SIMS analyses was found to introduce little or no systematic error into the results for zircon. Based on both laser fluorination and SIMS data, zircon 91500 seems to be very well suited for calibrating in situ oxygen isotopic analyses.

Journal ArticleDOI
05 Aug 2004-Nature
TL;DR: In this paper, the spectral distribution and time-dependent decay of light emitted from excitons confined in the quantum dots are controlled by the host photonic crystal, and both inhibited and enhanced decay rates are observed depending on the optical emission frequency.
Abstract: Control of spontaneously emitted light lies at the heart of quantum optics. It is essential for diverse applications ranging from miniature lasers and light-emitting diodes, to single-photon sources for quantum information, and to solar energy harvesting. To explore such new quantum optics applications, a suitably tailored dielectric environment is required in which the vacuum fluctuations that control spontaneous emission can be manipulated. Photonic crystals provide such an environment: they strongly modify the vacuum fluctuations, causing the decay of emitted light to be accelerated or slowed down, to reveal unusual statistics, or to be completely inhibited in the ideal case of a photonic bandgap. Here we study spontaneous emission from semiconductor quantum dots embedded in inverse opal photonic crystals. We show that the spectral distribution and time-dependent decay of light emitted from excitons confined in the quantum dots are controlled by the host photonic crystal. Modified emission is observed over large frequency bandwidths of 10%, orders of magnitude larger than reported for resonant optical microcavities. Both inhibited and enhanced decay rates are observed depending on the optical emission frequency, and they are controlled by the crystals’ lattice parameter. Our experimental results provide a basis for all-solid-state dynamic control of optical quantum systems.

Journal ArticleDOI
01 Oct 2004-Cell
TL;DR: The PLETHORA1 (PLT1) and PLT2 genes encoding AP2 class putative transcription factors, which are essential for QC specification and stem cell activity, are identified.

Journal ArticleDOI
TL;DR: The structure of the concentrated polymer phase seems to resemble a continuous polymer phase in which the protein can diffuse around, as well as the individual polysaccharide molecules, which resembles the behaviour of a (viscous) concentrated particle dispersion.
Abstract: Coacervation of proteins and anionic polysaccharides is both of practical and theoretical interest. From a large body of literature, it seems that the phase separation is mainly entropically driven, and may most probably be attributed to the delocalisation of the counter ions of the protein and the polysaccharide. The protein and polysaccharide appear to form complexes in solution, which can be viewed as new colloidal entities. These complex particles are neutral and exhibit an attractive interaction, which leads to a phase separation of the gas-liquid type in which a (very) dilute colloidal phase coexists with a very concentrated colloidal phase. In the case of strong poly-acids, usually, a precipitate is formed rather than a liquid coacervate phase. The structure of the concentrated polymer phase seems to resemble a continuous polymer phase in which the protein can diffuse around, as well as the individual polysaccharide molecules. Time scales of diffusion vary from milliseconds to days depending on the strength of the interaction. From a rheological point of view, the concentrated phase is much more viscous than elastic and the rheology resembles the behaviour of a (viscous) concentrated particle dispersion. Theoretical developments are limited probably due to the difficulty to describe the (correlated) charge distribution in the system. There is a strong interest in coacervates for the use of encapsulation. For the same reason, much attention is given to replacing the traditional gelatin by milk and plant proteins.

Journal ArticleDOI
TL;DR: Current models are reviewed to identify priority issues for future land use change modelling research and six concepts important to land use modelling are discussed, based on level of analysis, cross-scale dynamics, driving forces, spatial interaction and neighbourhood effects, temporal dynamics, and level of integration.
Abstract: Land use change models are tools to support the analysis of the causes and consequences of land use dynamics. Scenario analysis with land use models can support land use planning and policy. Numerous land use models are available, developed from different disciplinary backgrounds. This paper reviews current models to identify priority issues for future land use change modelling research. This discussion is based on six concepts important to land use modelling: (1) Level of analysis; (2) Cross-scale dynamics; (3) Driving forces; (4) Spatial interaction and neighbourhood effects; (5) Temporal dynamics; and (6) Level of integration. For each of these concepts an overview is given of the variety of methods used to implement these concepts in operational models. It is concluded that a lot of progress has been made in building land use change models. However, in order to incorporate more aspects important to land use modelling it is needed to develop a new generation of land use models that better address the multi-scale characteristics of the land use system, implement new techniques to quantify neighbourhood effects, explicitly deal with temporal dynamics and achieve a higher level of integration between disciplinary approaches and between models studying urban and rural land use changes. If these requirements are fulfilled models will better support the analysis of land use dynamics and land use policy formulation.

Journal ArticleDOI
TL;DR: This article examined the bases of opposition to immigrant minorities in Western Europe, focusing on The Netherlands, and found that considerations of national identity dominate those of economic advantage in evoking exclusionary reactions to immigrants.
Abstract: This paper examines the bases of opposition to immigrant minorities in Western Europe, focusing on The Netherlands. The specific aim of this study is to test the validity of predictions derived from two theories—realistic conflict, which emphasizes considerations of economic well-being, and social identity, which emphasizes considerations of identity based on group membership. The larger aim of this study is to investigate the interplay of predisposing factors and situational triggers in evoking political responses. The analysis is based on a series of three experiments embedded in a public opinion survey carried out in The Netherlands (n = 2007) in 1997‐98. The experiments, combined with parallel individual-level measures, allow measurement of the comparative impact of both dispositionally based and situationally triggered threats to economic well-being and to national identity at work. The results show, first, that considerations of national identity dominate those of economic advantage in evoking exclusionary reactions to immigrant minorities and, second, that the effect of situational triggers is to mobilize support for exclusionary policies above and beyond the core constituency already predisposed to support them.

Journal ArticleDOI
TL;DR: A novel automated method for the enrichment of phosphopeptides from complex mixtures shows that TiO(2) has strong affinity for phosphorylated peptides, and thus, this material has a high potential in the field of phosphoproteomics.
Abstract: Selective detection of phosphopeptides from proteolytic digests is a challenging and highly relevant task in many proteomics applications. Often phosphopeptides are present in small amounts and need selective isolation or enrichment before identification. Here we report a novel automated method for the enrichment of phosphopeptides from complex mixtures. The method employs a two-dimensional column setup, with titanium oxide-based solid-phase material (Titansphere) as the first dimension and reversed-phase material as the second dimension. Phosphopeptides are separated from nonphosphorylated peptides by trapping them under acidic conditions on a TiO2 precolumn. Nonphosphorylated peptides break through and are trapped on a reversed-phase precolumn after which they are analyzed by nanoflow LC-ESI-MS/MS. Subsequently, phosphopeptides are desorbed from the TiO2 column under alkaline conditions, reconcentrated onto the reversed-phase precolumn, and analyzed by nanoflow LC-ESI-MS/MS. The selectivity and practica...

Journal ArticleDOI
TL;DR: In recent decades, a number of changes in the forms and mechanisms of governance by which institutional and orga- nizational societal sectors and spheres are governed, as well as in the location of governance from where command, administration, management and control of societal institutions and spheres were conducted as mentioned in this paper.
Abstract: Modern societies have in recent decades seen a destabilization of the traditional governing mechanisms and the advancement of new arrangements of governance. Con- spicuously, this has occurred in the private, semi-private and public spheres, and has involved local, regional, national, transnational and global levels within these spheres. We have wit- nessed changes in the forms and mechanisms of governance by which institutional and orga- nizational societal sectors and spheres are governed, as well as in the location of governance from where command, administration, management and control of societal institutions and spheres are conducted. We have also seen changes in governing capabilities (i.e., the extent to which societal institutions and spheres can, in fact, be steered), as well as in styles of gov- ernance (i.e., the processes of decision making and implementation, including the manner in which the organizations involved relate to each other). These shifts tend to have signifi- cant consequences for the governability, accountability, responsiveness and legitimacy of governance institutions. These developments have been generating a new and important research object for political science (including international relations). One of the crucial features of these developments is that they concern a diversity of sectors. In order to get a thorough understanding of 'shifts in governance', political science needs, and is also likely to adopt, a much stronger multidisciplinary orientation embracing politics, law, public admin- istration, economics and business administration, as well as sociology, geography and history.

Journal ArticleDOI
01 Jan 2004-Diabetes
TL;DR: It is demonstrated that adverse metabolic stress factors in type 1 diabetes are associated with reduced EPC numbers and angiogenicity, and hypothesize that EPC dysfunction contributes to the pathogenesis of vascular complications intype 1 diabetes.
Abstract: Type 1 diabetes is associated with reduced vascular repair, as indicated by impaired wound healing and reduced collateral formation in ischemia. Recently, endothelial progenitor cells (EPCs) have been identified as important regulators of these processes. We therefore explored the concept that EPCs are dysfunctional in diabetes. The number of EPCs obtained from type 1 diabetic patients in culture was 44% lower compared with age- and sex-matched control subjects ( P < 0.001). This reduction was inversely related to levels of HbA1c ( R = −0.68, P = 0.01). In addition, we demonstrated that patient EPCs were also impaired in function using an in vitro angiogenesis assay. Conditioned media from patient EPCs were significantly reduced in their capacity to support endothelial tube formation in comparison to control EPCs. Therefore, despite culturing the EPCs under normoglycemic conditions, functional differences between patient and control EPCs were maintained. Our findings demonstrate that adverse metabolic stress factors in type 1 diabetes are associated with reduced EPC numbers and angiogenicity. We hypothesize that EPC dysfunction contributes to the pathogenesis of vascular complications in type 1 diabetes.

Proceedings ArticleDOI
12 May 2004
TL;DR: This work compares the performance of a number of vessel segmentation algorithms on a newly constructed retinal vessel image database and defines the segmentation accuracy with respect to the gold standard as the performance measure.
Abstract: In this work we compare the performance of a number of vessel segmentation algorithms on a newly constructed retinal vessel image database. Retinal vessel segmentation is important for the detection of numerous eye diseases and plays an important role in automatic retinal disease screening systems. A large number of methods for retinal vessel segmentation have been published, yet an evaluation of these methods on a common database of screening images has not been performed. To compare the performance of retinal vessel segmentation methods we have constructed a large database of retinal images. The database contains forty images in which the vessel trees have been manually segmented. For twenty of those forty images a second independent manual segmentation is available. This allows for a comparison between the performance of automatic methods and the performance of a human observer. The database is available to the research community. Interested researchers are encouraged to upload their segmentation results to our website (http://www.isi.uu.nl/Research/Databases). The performance of five different algorithms has been compared. Four of these methods have been implemented as described in the literature. The fifth pixel classification based method was developed specifically for the segmentation of retinal vessels and is the only supervised method in this test. We define the segmentation accuracy with respect to our gold standard as the performance measure. Results show that the pixel classification method performs best, but the second observer still performs significantly better.

Journal ArticleDOI
TL;DR: The production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response.
Abstract: During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation of l-arginine that is catalyzed by the enzyme NO synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) have been shown to be modulators of bronchomotor tone. On the other hand, NO derived from iNOS seems to be a proinflammatory mediator with immunomodulatory effects. The concentration of this molecule in exhaled air is abnormal in activated states of different inflammatory airway diseases, and its monitoring is potentially a major advance in the management of, e.g., asthma. Finally, the production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response. The fundamental mechanisms driving the altered NO bioactivity under pathological conditions still need to be fully clarified, because their regulation provides a novel target in the prevention and treatment of chronic inflammatory diseases of the airways.

Journal ArticleDOI
TL;DR: It is shown that the classical mouse mutant luxoid contains a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells, and this is the first gene shown to be required in germ cells for stem cell self-renewal in mammals.
Abstract: Adult germline stem cells are capable of self-renewal, tissue regeneration and production of large numbers of differentiated progeny. We show here that the classical mouse mutant luxoid affects adult germline stem cell self-renewal. Young homozygous luxoid mutant mice produce limited numbers of normal spermatozoa and then progressively lose their germ line after birth. Transplantation studies showed that germ cells from mutant mice did not colonize recipient testes, suggesting that the defect is intrinsic to the stem cells. We determined that the luxoid mutant contains a nonsense mutation in the gene encoding Plzf, a transcriptional repressor that regulates the epigenetic state of undifferentiated cells, and showed that Plzf is coexpressed with Oct4 in undifferentiated spermatogonia. This is the first gene shown to be required in germ cells for stem cell self-renewal in mammals.

Journal ArticleDOI
TL;DR: The biochemistry of lysosomal storage disorders is summarized and downstream cellular pathways that are potentially affected in these disorders are discussed and that might help to delineate their pathological mechanisms.
Abstract: Lysosomal storage disorders, of which more than 40 are known, are caused by the defective activity of lysosomal proteins, which results in the intra-lysosomal accumulation of undegraded metabolites. Despite years of study of the genetic and molecular bases of lysosomal storage disorders, little is known about the events that lead from this intra-lysosomal accumulation to pathology. Here, we summarize the biochemistry of lysosomal storage disorders. We then discuss downstream cellular pathways that are potentially affected in these disorders and that might help us to delineate their pathological mechanisms.

Journal ArticleDOI
TL;DR: In this article, the authors reviewed the key factors determining the fluxes of nitrogen (N) and phosphorus (P) associated with submarine groundwater discharge and presented a compilation of measured rates, in particular, the water residence time and the redox conditions in coastal aquifers and sediments determine fluxes and ratios of N and P in SGD.

Journal ArticleDOI
TL;DR: In this article, the authors show that a small sample size at level two (meaning a sample of 50 or less) leads to biased estimates of the second-level standard errors and that only the standard errors for the random effects at the second level are highly inaccurate if the distributional assumptions concerning the level-2 errors are not fulfilled.
Abstract: A multilevel problem concerns a population with a hierarchical structure. A sample from such a population can be described as a multistage sample. First, a sample of higher level units is drawn (e.g. schools or organizations), and next a sample of the sub-units from the available units (e.g. pupils in schools or employees in organizations). In such samples, the individual observations are in general not completely independent. Multilevel analysis software accounts for this dependence and in recent years these programs have been widely accepted. Two problems that occur in the practice of multilevel modeling will be discussed. The first problem is the choice of the sample sizes at the different levels. What are sufficient sample sizes for accurate estimation? The second problem is the normality assumption of the level-2 error distribution. When one wants to conduct tests of significance, the errors need to be normally distributed. What happens when this is not the case? In this paper, simulation studies are used to answer both questions. With respect to the first question, the results show that a small sample size at level two (meaning a sample of 50 or less) leads to biased estimates of the second-level standard errors. The answer to the second question is that only the standard errors for the random effects at the second level are highly inaccurate if the distributional assumptions concerning the level-2 errors are not fulfilled. Robust standard errors turn out to be more reliable than the asymptotic standard errors based on maximum likelihood.

Journal ArticleDOI
TL;DR: A homeostasis mechanism for sustaining cellular reactive oxygen species that is controlled by signalling pathways that can convey both negative (PI‐3K/PKB) and positive (Ras/Ral) inputs is outlined.
Abstract: Forkhead transcription factors of the FOXO class are negatively regulated by PKB/c-Akt in response to insulin/IGF signalling, and are involved in regulating cell cycle progression and cell death. Here we show that, in contrast to insulin signalling, low levels of oxidative stress generated by treatment with H2O2 induce the activation of FOXO4. Upon treatment of cells with H2O2, the small GTPase Ral is activated and this results in a JNK-dependent phosphorylation of FOXO4 on threonine 447 and threonine 451. This Ral-mediated, JNK-dependent phosphorylation is involved in the nuclear translocation and transcriptional activation of FOXO4 after H2O2 treatment. In addition, we show that this signalling pathway is also employed by tumor necrosis factor α to activate FOXO4 transcriptional activity. FOXO members have been implicated in cellular protection against oxidative stress via the transcriptional regulation of manganese superoxide dismutase and catalase gene expression. The results reported here, therefore, outline a homeostasis mechanism for sustaining cellular reactive oxygen species that is controlled by signalling pathways that can convey both negative (PI-3K/PKB) and positive (Ras/Ral) inputs.

Journal ArticleDOI
05 Aug 2004-Neuron
TL;DR: Low-affinity LRP/Aβ interaction and/or Aβ-induced LRP loss at the BBB mediate brain accumulation of neurotoxic Aβ in transgenic mice and patients with cerebrovascular β-amyloidosis.