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Showing papers by "University of Antwerp published in 2005"


Journal ArticleDOI
TL;DR: Outpatient antibiotic use in 26 countries in Europe between Jan 1, 1997, and Dec 31, 2002 was investigated by calculating the number of defined daily doses (DDD) per 1000 inhabitants per day according to WHO anatomic therapeutic chemical classification and DDD measurement methodology, and the ecological association between antibiotic use and antibiotic resistance rates was assessed using Spearman's correlation coefficients.

2,894 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the regionalization phase and associated hinterland concepts demand new approaches to port governance and a functional focus that goes beyond the traditional port perimeter.
Abstract: Logistics integration and network orientation in the port and maritime industry have redefined the functional role of ports in value chains and have generated new patterns of freight distribution and new approaches to port hierarchy. Existing models on the spatial and functional evolution of ports and port systems only partially fit into the new freight distribution paradigm. This paper aims to add to existing literature by introducing a port regionalization phase in port and port system development. It is demonstrated that the regionalization phase and associated hinterland concepts demand new approaches to port governance and a functional focus that goes beyond the traditional port perimeter.

1,002 citations


Journal ArticleDOI
TL;DR: The surprising consistency of response across diverse sites provides a benchmark to evaluate predictions of ecosystem and global models and allows us to focus on unresolved questions about carbon partitioning and retention, and spatial variation in NPP response caused by availability of other growth limiting resources.
Abstract: Climate change predictions derived from coupled carbon-climate models are highly dependent on assumptions about feedbacks between the biosphere and atmosphere. One critical feedback occurs if C uptake by the biosphere increases in response to the fossil-fuel driven increase in atmospheric [CO2] (“CO2 fertilization”), thereby slowing the rate of increase in atmospheric [CO2]. Carbon exchanges between the terrestrial biosphere and atmosphere are often first represented in models as net primary productivity (NPP). However, the contribution of CO2 fertilization to the future global C cycle has been uncertain, especially in forest ecosystems that dominate global NPP, and models that include a feedback between terrestrial biosphere metabolism and atmospheric [CO2] are poorly constrained by experimental evidence. We analyzed the response of NPP to elevated CO2 (≈550 ppm) in four free-air CO2 enrichment experiments in forest stands. We show that the response of forest NPP to elevated [CO2] is highly conserved across a broad range of productivity, with a stimulation at the median of 23 ± 2%. At low leaf area indices, a large portion of the response was attributable to increased light absorption, but as leaf area indices increased, the response to elevated [CO2] was wholly caused by increased light-use efficiency. The surprising consistency of response across diverse sites provides a benchmark to evaluate predictions of ecosystem and global models and allows us now to focus on unresolved questions about carbon partitioning and retention, and spatial variation in NPP response caused by availability of other growth limiting resources.

988 citations


Journal ArticleDOI
TL;DR: The ROBPCA approach, which combines projection pursuit ideas with robust scatter matrix estimation, yields more accurate estimates at noncontaminated datasets and more robust estimates at contaminated data.
Abstract: We introduce a new method for robust principal component analysis (PCA). Classical PCA is based on the empirical covariance matrix of the data and hence is highly sensitive to outlying observations. Two robust approaches have been developed to date. The first approach is based on the eigenvectors of a robust scatter matrix such as the minimum covariance determinant or an S-estimator and is limited to relatively low-dimensional data. The second approach is based on projection pursuit and can handle high-dimensional data. Here we propose the ROBPCA approach, which combines projection pursuit ideas with robust scatter matrix estimation. ROBPCA yields more accurate estimates at noncontaminated datasets and more robust estimates at contaminated data. ROBPCA can be computed rapidly, and is able to detect exact-fit situations. As a by-product, ROBPCA produces a diagnostic plot that displays and classifies the outliers. We apply the algorithm to several datasets from chemometrics and engineering.

935 citations


Journal ArticleDOI
TL;DR: In this paper, the authors identify determinants of corporate environmental disclosure using multi-theoretical lenses that rely on economic incentives, public pressures and institutional theory, focusing on large firms from a continental Europe country, Germany, with a distinct legal and regulatory context and where environmental concerns are especially acute.
Abstract: Investors and stakeholders in continental Europe are becoming increasingly concerned about corporate environmental policies. As a result, many firms are voluntarily increasing the extent of their environmental disclosure in their annual report. While mostly unregulated, corporate environmental disclosure does have potential economic significance considering the scarcity of alternative information sources. The purpose of this study is to identify determinants of corporate environmental disclosure using multi-theoretical lenses that rely on economic incentives, public pressures and institutional theory. The study focuses on large firms from a continental Europe country, Germany, with a distinct legal and regulatory context and where environmental concerns are especially acute. Results show that Risk, Ownership, Fixed Assets Age, Firm Size as well as routine determine the level of environmental disclosure by German firms in a given year. Moreover, consistent with institutional theory, results sugge...

887 citations


Journal ArticleDOI
TL;DR: In the present update on mucoadhesive ocular dosage forms, the tremendous advances in the biochemistry of mucins, the development of new polymers, the use of drug complexes and other technological advances are discussed.

844 citations


Journal ArticleDOI
TL;DR: In this paper, a meta-analysis investigated the influence of assessment on the reported effects of problem-based learning by applying Sugrue's (1995) model of cognitive components of problem solving.
Abstract: This meta-analysis investigated the influence of assessment on the reported effects of problem-based learning (PBL) by applying Sugrue’s (1995) model of cognitive components of problem solving. Three levels of the knowledge structure that can be targeted by assessment of problem solving are used as the main independent variables: (a) understanding of concepts, (b) understanding of the principles that link concepts, and (c) linking of concepts and principles to conditions and procedures for application. PBL had the most positive effects when the focal constructs being assessed were at the level of understanding principles that link concepts. The results suggest that the implications of assessment must be considered in examining the effects of problem-based learning and probably in all comparative education research.

693 citations


Journal ArticleDOI
TL;DR: In this paper, the authors provided an overall picture of the bone-specific actions of TGF-β1 and reconciled experimental discrepancies that have been reported for this multifunctional cytokine.
Abstract: TGF-β1 is a ubiquitous growth factor that is implicated in the control of proliferation, migration, differentiation, and survival of many different cell types. It influences such diverse processes as embryogenesis, angiogenesis, inflammation, and wound healing. In skeletal tissue, TGF-β1 plays a major role in development and maintenance, affecting both cartilage and bone metabolism, the latter being the subject of this review. Because it affects both cells of the osteoblast and osteoclast lineage, TGF-β1 is one of the most important factors in the bone environment, helping to retain the balance between the dynamic processes of bone resorption and bone formation. Many seemingly contradictory reports have been published on the exact functioning of TGF-β1 in the bone milieu. This review provides an overall picture of the bone-specific actions of TGF-β1 and reconciles experimental discrepancies that have been reported for this multifunctional cytokine.

645 citations


Journal ArticleDOI
TL;DR: Both correlational and experimental studies support the existence of positive, rather than negative, density-dependent dispersal in birds and mammals.
Abstract: Density-dependent dispersal can be caused by various mechanisms, from competition inducing individuals to emigrate (positive density-dependence) to social crowding effects impeding free movement (negative density-dependence). Various spatial population models have incorporated positively density-dependent dispersal algorithms, and recent theoretical models have explored the conditions for density-dependent dispersal (DD) to evolve. However, while the existence of DD is well documented in some taxa such as insects, there is no clear picture on its generality in vertebrates. Here I review the available empirical data on DD in birds and mammals, focusing mainly on variation in dispersal between years and on experimental density manipulations. Surprisingly few studies have explicitly focused on DD, and interpretation of the available data is often hampered by differences in approach, small sample sizes and/or statistical shortcomings. Positive DD was reported in 50 and 33% of the selected mammal and bird studies, respectively, while two studies on mammals (out of eight) reported negative DD. Among bird studies, DD was more often reported for emigration rates or long-distance recoveries than for average distances within finite study areas. Experimental studies manipulating densities (mainly on mammals) have consistently generated positive DD, typically showing reduced emigration in response to partial population removal. Studies that examined dispersal in relation to seasonal changes in density (small mammals only) have more often reported negative DD. Studies that compared dispersal between sites differing in density, also show a mixture of positive and negative DD. This suggests that dispersal changes in a more complex way with seasonal and spatial density variation than with annual densities, and/or that these results are confounded by other factors differing between seasons and sites, such as habitat quality. I conclude that both correlational and experimental studies support the existence of positive, rather than negative, density-dependent dispersal in birds and mammals.

577 citations


Journal ArticleDOI
TL;DR: The phenol extraction protocol was optimized for banana and was subsequently applied to two other plant species: apple and potato, and is useful for guiding the experimental setup of many other nonmodel species, containing various interfering elements.
Abstract: This study focuses on the specific problems of protein extraction from recalcitrant plant tissues and evaluates several methods to bypass them. Sample preparation is a critical step in a two-dimensional gel electrophoresis proteome approach and is absolutely essential for good results. We evaluated four methods: the classical trichloroacetic acid (TCA)/acetone precipitation, TCA/acetone precipitation and fractionation, an alternative based on fractionation and without precipitation, and phenol extraction methanol/ammonium acetate precipitation. We optimized the phenol extraction protocol for small amounts of tissue, which is essential when the study material is limited. The protocol was optimized for banana (Musa spp.) and was subsequently applied to two other plant species: apple (Malus domestica L.) and potato (Solanum tuberosum L.). Banana (Musa spp.) is a good representative of a "difficult" plant species since it contains many interfering metabolites. Only classical TCA/acetone precipitation and phenol extraction methods proved useful as standard methods. Both methods are associated with a minor but reproducible loss of proteins. Every extraction method and the subsequent analytical procedure have their physicochemical limitations; both methods should be investigated before selecting an appropriate protocol. The study, which is presented in this paper, is useful for guiding the experimental setup of many other nonmodel species, containing various interfering elements.

487 citations


Journal ArticleDOI
TL;DR: In this paper, the authors investigate whether voluntary adoption of International Financial Reporting Standards (IFRS) is associated with lower earnings management in German listed companies and find that companies that adopt IFRS engage significantly less in earnings management compared to German companies reporting under German generally accepted accounting principles (GAAP).
Abstract: This paper addresses the question whether voluntary adoption of International Financial Reporting Standards (IFRS) is associated with lower earnings management. Ball et al. (Journal of Accounting and Economics, 36(1–3), pp. 235–270, 2003) argue that adopting high quality standards might be a necessary condition for high quality information, but not necessarily a sufficient one. In Germany, a code-law country with low investor protection rights, a relatively large number of companies have chosen to voluntarily adopt IFRS prior to 2005. We investigate whether German companies that have adopted IFRS engage significantly less in earnings management compared to German companies reporting under German generally accepted accounting principles (GAAP), while controlling for other differences in earnings management incentives. Our sample, consisting of German listed companies, contains 636 firm-year observations relating to the period 1999–2001. Our results suggest that IFRS-adopters do not present differe...

Journal ArticleDOI
TL;DR: The association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations was assessed and two genotypes had significantly more-severe HI than that of 35delG homozygotes.
Abstract: Hearing impairment (HI) affects 1 in 650 newborns, which makes it the most common congenital sensory impairment. Despite extraordinary genetic heterogeneity, mutations in one gene, GJB2, which encodes the connexin 26 protein and is involved in inner ear homeostasis, are found in up to 50% of patients with autosomal recessive nonsyndromic hearing loss. Because of the high frequency of GJB2 mutations, mutation analysis of this gene is widely available as a diagnostic test. In this study, we assessed the association between genotype and degree of hearing loss in persons with HI and biallelic GJB2 mutations. We performed cross-sectional analyses of GJB2 genotype and audiometric data from 1,531 persons, from 16 different countries, with autosomal recessive, mild-to-profound nonsyndromic HI. The median age of all participants was 8 years; 90% of persons were within the age range of 0-26 years. Of the 83 different mutations identified, 47 were classified as nontruncating, and 36 as truncating. A total of 153 different genotypes were found, of which 56 were homozygous truncating (T/T), 30 were homozygous nontruncating (NT/NT), and 67 were compound heterozygous truncating/nontruncating (T/NT). The degree of HI associated with biallelic truncating mutations was significantly more severe than the HI associated with biallelic nontruncating mutations (P<.0001). The HI of 48 different genotypes was less severe than that of 35delG homozygotes. Several common mutations (M34T, V37I, and L90P) were associated with mild-to-moderate HI (median 25-40 dB). Two genotypes--35delG/R143W (median 105 dB) and 35delG/dela(GJB6-D13S1830) (median 108 dB)--had significantly more-severe HI than that of 35delG homozygotes.

Journal ArticleDOI
TL;DR: It is demonstrated that phagocytosis of ACs is impaired in atherosclerotic plaques, which is at least partly attributed to oxidative stress and cytoplasmic saturation with indigestible material.
Abstract: Objective— Apoptotic cell death has been demonstrated in advanced human atherosclerotic plaques. Apoptotic cells (ACs) should be rapidly removed by macrophages, otherwise secondary necrosis occurs, which in turn elicits inflammatory responses and plaque progression. Therefore, we investigated the efficiency of phagocytosis of ACs by macrophages in atherosclerosis. Methods and Results— Human endarterectomy specimens and human tonsils were costained for CD68 (macrophages) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) (apoptosis). Free and phagocytized ACs were counted in both tissues. The ratio of free versus phagocytized AC was 19-times higher in human atherosclerotic plaques as compared with human tonsils, indicating a severe defect in clearance of AC. Impaired phagocytosis of AC was also detected in plaques from cholesterol-fed rabbits and did not further change with plaque progression. In vitro experiments with J774 or peritoneal mouse macrophages showed that several factors caused impaired phagocytosis of AC including cytoplasmic overload of macrophages with indigestible material (beads), free radical attack, and competitive inhibition among oxidized red blood cells, oxidized low-density lipoprotein and ACs for the same receptor(s) on the macrophage. Conclusion— Our data demonstrate that phagocytosis of ACs is impaired in atherosclerotic plaques, which is at least partly attributed to oxidative stress and cytoplasmic saturation with indigestible material.

Journal ArticleDOI
TL;DR: A role for IDO activity in the pathophysiology of IFN-α-induced depressive symptoms is supported, through its induction of neurotoxic KYN metabolites.
Abstract: Studies show that administration of interferon (IFN)-α causes a significant increase in depressive symptoms. The enzyme indoleamine 2,3-dioxygenase (IDO), which converts tryptophan (TRP) into kynurenine (KYN) and which is stimulated by proinflammatory cytokines, may be implicated in the development of IFN-α-induced depressive symptoms, first by decreasing the TRP availability to the brain and second by the induction of the KYN pathway resulting in the production of neurotoxic metabolites. Sixteen patients with chronic hepatitis C, free of psychiatric disorders and eligible for IFN-α treatment, were recruited. Depressive symptoms were measured using the Montgomery Asberg Depression Rating Scale (MADRS). Measurements of TRP, amino acids competing with TRP for entrance through the blood–brain barrier, KYN and kynurenic acid (KA), a neuroprotective metabolite, were performed using high-performance liquid chromatography. All assessments were carried out at baseline and 1, 2, 4, 8, 12 and 24 weeks after treatment was initiated. The MADRS score significantly increased during IFN-α treatment as did the KYN/TRP ratio, reflecting IDO activity, and the KYN/KA ratio, reflecting the neurotoxic challenge. The TRP/CAA (competing amino acids) ratio, reflecting TRP availability to the brain, did not significantly change during treatment. Total MADRS score was significantly associated over time with the KYN/KA ratio, but not with the TRP/CAA ratio. Although no support was found that IDO decreases TRP availability to the brain, this study does support a role for IDO activity in the pathophysiology of IFN-α-induced depressive symptoms, through its induction of neurotoxic KYN metabolites.

Journal ArticleDOI
TL;DR: An overview of the recent insights concerning pathogenesis and therapeutic possibilities to prevent ischemia/reperfusion injury is given.

Journal ArticleDOI
TL;DR: A MATLAB library of robust statistical methods used by chemometricians, statisticians, chemists, and engineers is introduced and many graphical tools to detect and classify the outliers are provided.

Journal ArticleDOI
04 Aug 2005-Neuron
TL;DR: It is demonstrated that both global and Purkinje cell-specific knockouts of Fmr1 show deficits in classical delay eye-blink conditioning in that the percentage of conditioned responses as well as their peak amplitude and peak velocity are reduced.

Journal ArticleDOI
TL;DR: In this article, an isoprene/NO X /air mixture was irradiated in a flow reactor smog chamber in both the absence and presence of SO 2 to measure the SOA yield and to establish whether the two 2-methyl tetrols and 2methyl glyceric acid are present in isoprane SOA and could serve as SOA indicator compounds.

Journal ArticleDOI
TL;DR: In this article, the authors describe screening practices by European business incubators and compare these results with the American incubators in the eighties, finding that the tenant survival rate is positively related to a more balanced screening profile.
Abstract: Business incubators guide starting enterprises through their growth process and as such constitute a strong instrument to promote innovation and entrepreneurship. In this article we sketch the European business incubator landscape. Then we describe screening practices by European business incubators in 2003 and compare these results with the American incubators in the eighties. In the last phase a cautious link between screening practices and performance, measured in terms of tenant failure, is established. Most incubators do not screen potential tenants on a balanced set of factors, but concentrate either on the characteristics of the tenant's market or on the characteristics of the tenant's management team. However, we found that the tenant survival rate is positively related to a more balanced screening profile. Based on our study results, we propose some recommendations for the main stakeholders in the field: authorities, incubators and innovative entrepreneurs.

Journal ArticleDOI
31 Mar 2005-Vaccine
TL;DR: The genotypes show a distinct geographical distribution between and even within regions, and are proving to be an invaluable tool in tracing the molecular evolution and patterns and modes of spread of hepatitis B virus.

Journal ArticleDOI
TL;DR: A more careful treatment of behavioural components of mobility within observational and experimental studies of animal dispersal is needed to model dispersal with more biological realism and better understand evolutionary consequences.

Journal ArticleDOI
TL;DR: In this article, the authors identified unique mutations in dynamin 2 (DNM2) in all the families associated with CMT neuropathies in three unrelated families originating from Australia, Belgium and North America.
Abstract: Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of peripheral neuropathies. Different chromosomal loci have been linked with three autosomal dominant, 'intermediate' types of CMT: DI-CMTA, DI-CMTB and DI-CMTC. We refined the locus associated with DI-CMTB on chromosome 19p12-13.2 to 4.2 Mb in three unrelated families with CMT originating from Australia, Belgium and North America. After screening candidate genes, we identified unique mutations in dynamin 2 (DNM2) in all families. DNM2 belongs to the family of large GTPases and is part of the cellular fusion-fission apparatus. In transiently transfected cell lines, mutations of DNM2 substantially diminish binding of DNM2 to membranes by altering the conformation of the beta3/beta4 loop of the pleckstrin homology domain. Additionally, in the Australian and Belgian pedigrees, which carry two different mutations affecting the same amino acid, Lys558, CMT cosegregated with neutropenia, which has not previously been associated with CMT neuropathies.

Journal ArticleDOI
TL;DR: Dysregulation of apoptosis contributes to many diseases, including cancer, on the other hand, apoptosis-regulating proteins also provide targets for drug discovery and new approaches to the treatment of cancer.
Abstract: Apoptosis or programmed cell death is a process with typical morphological characteristics including plasma membrane blebbing, cell shrinkage, chromatin condensation and fragmentation. A family of cystein-dependent aspartate-directed proteases, called caspases, is responsible for the proteolytic cleavage of cellular proteins leading to the characteristic apoptotic features, e.g. cleavage of caspase-activated DNase resulting in internucleosomal DNA fragmentation. Currently, two pathways for activating caspases have been studied in detail. One starts with ligation of a death ligand to its transmembrane death receptor, followed by recruitment and activation of caspases in the death-inducing signalling complex. The second pathway involves the participation of mitochondria, which release caspase-activating proteins into the cytosol, thereby forming the apoptosome where caspases will bind and become activated. In addition, two other apoptotic pathways are emerging: endoplasmic reticulum stress-induced apoptosis and caspase-independent apoptosis. Naturally occurring cell death plays a critical role in many normal processes like foetal development and tissue homeostasis. Dysregulation of apoptosis contributes to many diseases, including cancer. On the other hand, apoptosis-regulating proteins also provide targets for drug discovery and new approaches to the treatment of cancer.

Journal ArticleDOI
TL;DR: In this paper, the authors explored the importance of the borrower's gender and the lending technology for intra-household decision-making processes, and found that direct bank-borrower credit delivery does not challenge the existing decisionmaking patterns, regardless of whether men or women receive the credit.
Abstract: Evaluations of the effects of microfinance programmes on women's empowerment generate mixed results. While some are supportive of microfinance's ability to induce a process of economic, social and political empowerment, others are more sceptical and even point to a deterioration of women's overall well-being. Against this background, development scholars and practitioners have sought to distil some of the ingredients that might increase the likelihood of empowerment or at least reduce adverse effects. This article formally tests the impact of some of the suggested changes in programme features on one particular dimension of empowerment: decision-making agency. Using household survey data from South India, the author explores the importance of the borrower's gender and the lending technology for intra-household decision-making processes. It is shown that direct bank–borrower credit delivery does not challenge the existing decision-making patterns, regardless of whether men or women receive the credit. These findings change when credit is combined with financial and social group intermediation. Women's group membership seriously shifts overall decision-making patterns from norm-guided behaviour and male decision-making to more joint and female decision-making. Longer-term group membership and more intensive training and group meetings strengthen these patterns.

Journal ArticleDOI
TL;DR: The findings suggest that BDNF may be a susceptibility gene for MDD and schizophrenia-in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.

Journal ArticleDOI
TL;DR: Current efforts to improve or to facilitate adherence of people with type 2 diabetes to treatment recommendations do not show significant effects nor harms, and the question whether any intervention enhances adherence to treatment recommendation effectively remains unanswered.
Abstract: Background Research suggests adherence to treatment recommendations is low. In type 2 diabetes, which is a chronic condition slowly leading to serious vascular, nephrologic, neurologic and ophthalmological complications, it can be assumed that enhancing adherence to treatment recommendations may lead to a reduction of complications. Treatment regimens in type 2 diabetes are complicated, encompassing life-style adaptations and medication intake. Objectives To assess the effects of interventions for improving adherence to treatment recommendations in people with type 2 diabetes mellitus. Search strategy Studies were obtained from searches of multiple electronic bibliographic databases supplemented with hand searches of references. Date of last search: November 2002. Selection criteria Randomised controlled and controlled clinical trials, before-after studies and epidemiological studies, assessing changes in adherence to treatment recommendations, as defined in the objectives section, were included. Data collection and analysis Two teams of reviewers independently assessed the trials identified for inclusion. Three teams of two reviewers assessed trial quality and extracted data. The analysis for the narrative part was performed by one reviewer (EV), the meta-analysis by two reviewers (EV, JW). Main results Twentyone studies assessing interventions aiming at improving adherence to treatment recommendations, not to diet or exercise recommendations, in people living with type 2 diabetes in primary care, outpatient settings, community and hospital settings, were included. Outcomes evaluated in these studies were heterogeneous, there was a variety of adherence measurement instruments. Nurse led interventions, home aids, diabetes education, pharmacy led interventions, adaptation of dosing and frequency of medication taking showed a small effect on a variety of outcomes including HbA1c. No data on mortality and morbidity, nor on quality of life could be found. Authors' conclusions Current efforts to improve or to facilitate adherence of people with type 2 diabetes to treatment recommendations do not show significant effects nor harms. The question whether any intervention enhances adherence to treatment recommendations in type 2 diabetes effectively, thus still remains unanswered.

Journal ArticleDOI
TL;DR: The high carrier frequency in Finland, the high number of patients in Norway, and the ancient European founder chromosome indicate that this newly identified ataxia should be considered in the first-line differential diagnosis of progressive atAXia syndromes.
Abstract: Mutations in the catalytic subunit of the mitochondrial DNA polymerase γ (POLG) have been found to be an important cause of neurological disease. Recently, we and collaborators reported a new neurodegenerative disorder with autosomal recessive ataxia in four patients homozygous for two amino acid changes in POLG: W748S in cis with E1143G. Here, we studied the frequency of this allele and found it to be among the most common genetic causes of inherited ataxia in Finland. We identified 27 patients with mitochondrial recessive ataxia syndrome (MIRAS) from 15 Finnish families, with a carrier frequency in the general population of 1:125. Since the mutation pair W748S+E1143G has also been described in European patients, we examined the haplotypes of 13 non-Finnish, European patients with the W748S mutation. Haplotype analysis revealed that all the chromosomes carrying these two changes, in patients from Finland, Norway, the United Kingdom, and Belgium, originate from a common ancient founder. In Finland and Norway, long, common, northern haplotypes, outside the core haplotype, could be identified. Despite having identical homozygous mutations, the Finnish patients with this adult- or juvenile-onset disease had surprisingly heterogeneous phenotypes, albeit with a characteristic set of features, including ataxia, peripheral neuropathy, dysarthria, mild cognitive impairment, involuntary movements, psychiatric symptoms, and epileptic seizures. The high carrier frequency in Finland, the high number of patients in Norway, and the ancient European founder chromosome indicate that this newly identified ataxia should be considered in the first-line differential diagnosis of progressive ataxia syndromes.

Journal ArticleDOI
TL;DR: The finding of a large number of affected subjects with only one GJB2 mutant allele complicates the molecular diagnosis of DFNB1 deafness, which has become the standard of care for the diagnosis of patients with non-syndromic hearing impairment of unknown cause.
Abstract: Hearing impairment is a common and highly heterogeneous sensory disorder. Genetic causes are thought to be responsible for more than 60% of the cases in developed countries.1 In the majority of cases, non-syndromic hearing impairment is inherited in an autosomal recessive pattern.2 Thirty eight different loci and 20 genes for autosomal recessive non-syndromic hearing impairment (ARNSHI) have been identified to date.3 In many populations, up to 50% of all cases of ARNSHI are caused by mutations in the DFNB1 locus (MIM 220290) on 13q12.4 This locus contains the GJB2 gene (MIM 121011), encoding connexin-26 (Cx26),5 which belongs to a family of transmembrane proteins with about 20 members in humans. Hexamers of connexins (connexons) are displayed in the plasma membrane. Docking of connexons on the surfaces of two adjacent cells results in the formation of intercellular gap junction channels.6 Several different connexins, including Cx26, have been shown to participate in the complex gap junction networks of the cochlea.7,8 It has been postulated that these networks play a key role in potassium homeostasis, which is essential for the sound transduction mechanism.9 Given the high prevalence of DFNB1 deafness, molecular testing for GJB2 mutations has become the standard of care for the diagnosis of patients with non-syndromic hearing impairment of unknown cause.10 However, the finding of a large number of affected subjects with only one GJB2 mutant allele complicates the molecular diagnosis of DFNB1 deafness. In different studies, these have accounted for 10–50% of deaf subjects with GJB2 mutations.4 It was hypothesised that there could be other mutations in the DFNB1 locus but outside the GJB2 gene. This hypothesis gained support by the finding of a deletion in the DFNB1 locus outside GJB2 but truncating the neighbouring GJB6 gene (MIM 604418), which …

Journal ArticleDOI
TL;DR: In this article, the authors report the first direct imaging of the giant pores distribution in the MIL-101 compound, which represents the largest porous MOF discovered up to now, with cage volumes up to ca. 20'600 A3.
Abstract: Here we report the first direct imaging of the giant pores distribution in the MIL-101 compound, which represents the largest porous MOF discovered up to now, with cage volumes up to ca. 20 600 A3 ...

Journal ArticleDOI
TL;DR: The broad influence of CO2 on the E. huxleyi bloom suggests that changes in CO2 concentration directly affect cell physiology with likely effects on the marine biogeochemistry.
Abstract: We studied the direct effects of CO2 and related changes in seawater carbonate chemistry on marine planktonic organisms in a mesocosm experiment. In nine outdoor enclosures (~11 m3 each), the partial pressure of CO2 (pCO2) in the seawater was modified by an aeration system. The triplicate mesocosm treatments represented low (~190 parts per million by volume (ppmV) CO2), present (~410 ppmV CO2), and high (~710 ppmV CO2) pCO2 conditions. After initial fertilization with nitrate and phosphate a bloom dominated by the coccolithophorid Emiliania huxleyi occurred simultaneously in all of the nine mesocosms; it was monitored over a 19-day period. The three CO2 treatments assimilated nitrate and phosphate similarly. The concentration of particulate constituents was highly variable among the replicate mesocosms, disguising direct CO2-related effects. Normalization of production rates within each treatment, however, indicated that the net specific growth rate of E. huxleyi, the rate of calcification per cell, and the elemental stoichiometry of uptake and production processes were sensitive to changes in pCO2. This broad influence of CO2 on the E. huxleyi bloom suggests that changes in CO2 concentration directly affect cell physiology with likely effects on the marine biogeochemistry.