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Showing papers by "University of Graz published in 2004"


Journal ArticleDOI
TL;DR: This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.
Abstract: Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.

3,044 citations


Journal ArticleDOI
19 Nov 2004-Science
TL;DR: It is reported that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis, and it is interesting that ATGL contains a “patatin domain” common to plant acyl-hydrolases.
Abstract: Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.

1,859 citations


Journal ArticleDOI
TL;DR: Adapt nonlinear model predictive control is promising for the control of glucose concentration during fasting conditions in subjects with type 1 diabetes.
Abstract: A nonlinear model predictive controller has been developed to maintain normoglycemia in subjects with type 1 diabetes during fasting conditions such as during overnight fast. The controller employs a compartment model, which represents the glucoregulatory system and includes submodels representing absorption of subcutaneously administered short-acting insulin Lispro and gut absorption. The controller uses Bayesian parameter estimation to determine time-varying model parameters. Moving target trajectory facilitates slow, controlled normalization of elevated glucose levels and faster normalization of low glucose values. The predictive capabilities of the model have been evaluated using data from 15 clinical experiments in subjects with type 1 diabetes. The experiments employed intravenous glucose sampling (every 15 min) and subcutaneous infusion of insulin Lispro by insulin pump (modified also every 15 min). The model gave glucose predictions with a mean square error proportionally related to the prediction horizon with the value of 0.2 mmol L(-1) per 15 min. The assessment of clinical utility of model-based glucose predictions using Clarke error grid analysis gave 95% of values in zone A and the remaining 5% of values in zone B for glucose predictions up to 60 min (n = 1674). In conclusion, adaptive nonlinear model predictive control is promising for the control of glucose concentration during fasting conditions in subjects with type 1 diabetes.

1,164 citations


Journal ArticleDOI
TL;DR: In this article, a taxonomy of both bias and equivalence is presented, and the most frequently encountered sources of bias and their remedies are described. But the taxonomy is limited to cross-cultural studies.
Abstract: In every cross-cultural study, the question as to whether test scores obtained in different cultural populations can be interpreted in the same way across these populations has to be dealt with. Bias and equivalence have become the common terms to refer to the issue. Taxonomy of both bias and equivalence is presented. Bias can be engendered by the theoretical construct (construct bias), the method such as the form of test administration (method bias), and the item content (item bias). Equivalence refers to the measurement level at which scores can be compared across cultures. Three levels of equivalence are possible: the same construct is measured in each cultural group but the functional form of the relationship between scores obtained in various groups is unknown (structural equivalence), scores have the same measurement unit across populations but have different origins (measurement unit equivalence), and scores have the same measurement unit and origin in all populations (full scale equivalence). The most frequently encountered sources of bias and their remedies are described.

877 citations


Journal ArticleDOI
TL;DR: Observations of ALS4 suggest that mutations in SETX may cause neuronal degeneration through dysfunction of the helicase activity or other steps in RNA processing.
Abstract: Juvenile amyotrophic lateral sclerosis (ALS4) is a rare autosomal dominant form of juvenile amyotrophic lateral sclerosis (ALS) characterized by distal muscle weakness and atrophy, normal sensation, and pyramidal signs. Individuals affected with ALS4 usually have an onset of symptoms at age Senataxin gene ( SETX ). The SETX gene encodes a novel 302.8-kD protein. Although its function remains unknown, SETX contains a DNA/RNA helicase domain with strong homology to human RENT1 and IGHMBP2, two genes encoding proteins known to have roles in RNA processing. These observations of ALS4 suggest that mutations in SETX may cause neuronal degeneration through dysfunction of the helicase activity or other steps in RNA processing.

783 citations


Journal ArticleDOI
TL;DR: This study provides a phylogenetic synthesis for the Fungi and a framework for future phylogenetic studies on fungi and the impact of this newly discovered phylogenetic structure on supraordinal classifications is discussed.
Abstract: Based on an overview of progress in molecular systematics of the true fungi (Fungi/Eumycota) since 1990, little overlap was found among single-locus data matrices, which explains why no large-scale multilocus phylogenetic analysis had been undertaken to reveal deep relationships among fungi. As part of the project ‘‘Assembling the Fungal Tree of Life’’ (AFTOL), results of four Bayesian analyses are reported with complementary bootstrap assessment of phylogenetic confidence based on (1) a combined two-locus data set (nucSSU and nucLSU rDNA) with 558 species representing all traditionally recognized fungal phyla (Ascomycota, Basidiomycota, Chytridiomycota, Zygomycota) and the Glomeromycota, (2) a combined three-locus data set (nucSSU, nucLSU, and mitSSU rDNA) with 236 species, (3) a combined three-locus data set (nucSSU, nucLSU rDNA, and RPB2) with 157 species, and (4) a combined four-locus data set (nucSSU, nucLSU, mitSSU rDNA, and RPB2) with 103 species. Because of the lack of complementarity among single-locus data sets, the last three analyses included only members of the Ascomycota and Basidiomycota. The four-locus analysis resolved multiple deep relationships within the Ascomycota and Basidiomycota that were not revealed previously or that received only weak support in previous studies. The impact of this newly discovered phylogenetic structure on supraordinal classifications is discussed. Based on these results and reanalysis of subcellular data, current knowledge of the evolution of septal features of fungal hyphae is synthesized, and a preliminary reassessment of ascomal evolution is presented. Based on previously unpublished data and sequences from GenBank, this study provides a phylogenetic synthesis for the Fungi and a framework for future phylogenetic studies on fungi.

754 citations


Journal ArticleDOI
TL;DR: A missense mutation in the gene encoding 27-kDa small heat-shock protein B1 (HSPB1, also called HSP27) that segregates in the family with CMT2F is reported and four additional missense mutations are identified.
Abstract: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuromuscular disease and is characterized by considerable clinical and genetic heterogeneity. We previously reported a Russian family with autosomal dominant axonal CMT and assigned the locus underlying the disease (CMT2F; OMIM 606595) to chromosome 7q11-q21 (ref. 2). Here we report a missense mutation in the gene encoding 27-kDa small heat-shock protein B1 (HSPB1, also called HSP27) that segregates in the family with CMT2F. Screening for mutations in HSPB1 in 301 individuals with CMT and 115 individuals with distal hereditary motor neuropathies (distal HMNs) confirmed the previously observed mutation and identified four additional missense mutations. We observed the additional HSPB1 mutations in four families with distal HMN and in one individual with CMT neuropathy. Four mutations are located in the Hsp20-alpha-crystallin domain, and one mutation is in the C-terminal part of the HSP27 protein. Neuronal cells transfected with mutated HSPB1 were less viable than cells expressing the wild-type protein. Cotransfection of neurofilament light chain (NEFL) and mutant HSPB1 resulted in altered neurofilament assembly in cells devoid of cytoplasmic intermediate filaments.

570 citations


Journal ArticleDOI
TL;DR: It is suggested that apoptosis in yeast confers a selective advantage for this unicellular organism, and that old yeast cells release substances into the medium that stimulate survival of the clone.
Abstract: During the past years, yeast has been successfully established as a model to study mechanisms of apoptotic regulation. However, the beneficial effects of such a cell suicide program for a unicellular organism remained obscure. Here, we demonstrate that chronologically aged yeast cultures die exhibiting typical markers of apoptosis, accumulate oxygen radicals, and show caspase activation. Age-induced cell death is strongly delayed by overexpressing YAP1, a key transcriptional regulator in oxygen stress response. Disruption of apoptosis through deletion of yeast caspase YCA1 initially results in better survival of aged cultures. However, surviving cells lose the ability of regrowth, indicating that predamaged cells accumulate in the absence of apoptotic cell removal. Moreover, wild-type cells outlast yca1 disruptants in direct competition assays during long-term aging. We suggest that apoptosis in yeast confers a selective advantage for this unicellular organism, and demonstrate that old yeast cells release substances into the medium that stimulate survival of the clone.

530 citations


Journal ArticleDOI
Ante Pulic1
TL;DR: In this paper, the authors define a new index, namely the value creation efficiency of intellectual capital, which is defined as the difference between revenue, profit, and GDP to indicate successful performance, while value is being destroyed and not created.
Abstract: Taking into account the transformation in economic reality towards a knowledge economy it seems logical that we treat IC as a resource, equal to that land, physical assets, and financial capital. This means that it is not anymore treated as a cost but as an investment. In order for the new system to be consistent we have to define a new index, namely the value creation efficiency of intellectual capital. Its empirical applications shows that while revenue, profit and GDP may indicate successful performance, IC efficiency may indicate the opposite, that value is being destroyed and not created.

512 citations


Journal ArticleDOI
TL;DR: Sclerosing cholangitis in Mdr2(-/-) mice is a multistep process with regurgitation of bile from leaky ducts into the portal tracts, leading to induction of periductal inflammation, followed by activation of peroductal fibrogenesis, finally causing obliterative cholangsitis owing to atrophy and death of biles duct epithelial cells.

420 citations


Journal ArticleDOI
TL;DR: Experimental data of individual samples indicated anisotropic and highly nonlinear tissue properties as well as considerable interspecimen differences in the atherosclerotic lesions.
Abstract: Knowledge of the biomechanical properties of human atherosclerotic plaques is of essential importance for developing more insights in the pathophysiology of the cardiovascular system and for better predicting the outcome of interventional treatments such as balloon angioplasty. Available data are mainly based on uniaxial tests, and most of the studies investigate the mechanical response of fibrous plaque caps only. However, stress distributions during, for example, balloon angioplasty are strongly influenced by all components of atherosclerotic lesions. A total number of 107 samples from nine human high-grade stenotic iliac arteries were tested; associated anamnesis of donors reported. Magnetic resonance imaging was employed to test the usability of the harvested arteries. Histological analyses has served to characterize the different tissue types. Prepared strips of 7 different tissue types underwent cyclic quasistatic uniaxial tension tests in axial and circumferential directions; ultimate tensile stresses and stretches were documented. Experimental data of individual samples indicated anisotropic and highly nonlinear tissue properties as well as considerable interspecimen differences. The calcification showed, however a linear property, with about the same stiffness as observed for the adventitia in high stress regions. The stress and stretch values at calcification fracture are smaller (179 +/- 56 kPa and 1.02 +/- 0.005) than for each of the other tissue components. Of all intimal tissues investigated, the lowest fracture stress occurred in the circumferential direction of the fibrous cap (254.8 +/- 79.8 kPa at stretch 1.182 +/- 0.1). The adventitia demonstrated the highest and the nondiseased media the lowest mechanical strength on average.

Journal ArticleDOI
TL;DR: It is shown that the yeast AIF homologue Ynr074cp controls yeast apoptosis and is renamed AIF-1 (Aif1p, gene AIF1), a cell death effector in yeast, which is essential for normal mammalian development and participates in pathological apoptosis.
Abstract: Apoptosis-inducing factor (AIF), a key regulator of cell death, is essential for normal mammalian development and participates in pathological apoptosis. The proapoptotic nature of AIF and its mode of action are controversial. Here, we show that the yeast AIF homologue Ynr074cp controls yeast apoptosis. Similar to mammalian AIF, Ynr074cp is located in mitochondria and translocates to the nucleus of yeast cells in response to apoptotic stimuli. Purified Ynr074cp degrades yeast nuclei and plasmid DNA. YNR074C disruption rescues yeast cells from oxygen stress and delays age-induced apoptosis. Conversely, overexpression of Ynr074cp strongly stimulates apoptotic cell death induced by hydrogen peroxide and this effect is attenuated by disruption of cyclophilin A or the yeast caspase YCA1. We conclude that Ynr074cp is a cell death effector in yeast and rename it AIF-1 (Aif1p, gene AIF1).

Journal ArticleDOI
TL;DR: To improve the efficiency and applicability of biocatalytic redox-reactions for asymmetric ketone-reduction and enantioselective alcohol-oxidation catalyzed by nicotinamide-dependent dehydrogenases/reductases, several achievements for cofactor-recycling have been made during the last two years.

Journal ArticleDOI
TL;DR: Kp-10, a dekapeptide derived from the primary translation product of KiSS-1, was identified as a novel paracrine/endocrine regulator in fine-tuning trophoblast invasion generated by the trophoblasts itself.
Abstract: Trophoblast invasion of the uterine extracellular matrix, a critical process of human implantation and essential for fetal development, is a striking example of controlled invasiveness. To identify molecules that regulate trophoblast invasion, mRNA signatures of trophoblast cells isolated from first trimester (high invasiveness) and term placentae (no/low invasiveness) were compared using U95A GeneChip microarrays yielding 220 invasion/migration-related genes. In this `invasion cluster9, KiSS-1 and its G-protein-coupled receptor KiSS-1R were expressed at higher levels in first trimester trophoblasts than at term of gestation. Receptor and ligand mRNA and protein were localized to the trophoblast compartment. In contrast to KiSS-1, which is only expressed in the villous trophoblast, KiSS-1R was also found in the extravillous trophoblast, suggesting endocrine/paracrine activation mechanisms. The primary translation product of KiSS-1 is a 145 amino acid polypeptide (Kp-145), but shorter kisspeptins (Kp) with 10, 13, 14 or 54 amino acid residues may be produced. We identified Kp-10, a dekapeptide derived from the primary translation product, in conditioned medium of first trimester human trophoblast. Kp-10, but not other kisspeptins, increased intracellular Ca2+ levels in isolated first trimester trophoblasts. Kp-10 inhibited trophoblast migration in an explant as well as transwell assay without affecting proliferation. Suppressed motility was paralleled with suppressed gelatinolytic activity of isolated trophoblasts. These results identifed Kp-10 as a novel paracrine/endocrine regulator in fine-tuning trophoblast invasion generated by the trophoblast itself.

Journal ArticleDOI
TL;DR: Seipin is an integral membrane protein of the endoplasmic reticulum (ER) and affected glycosylation of seipin and result in aggregate formation leading to neurodegeneration.
Abstract: Distal hereditary motor neuropathy (dHMN) or distal spinal muscular atrophy (OMIM #182960) is a heterogeneous group of disorders characterized by an almost exclusive degeneration of motor nerve fibers, predominantly in the distal part of the limbs(1). Silver syndrome (OMIM #270685) is a rare form of hereditary spastic paraparesis mapped to chromosome 11q12q14 (SPG17) in which spasticity of the legs is accompanied by amyotrophy of the hands and occasionally also the lower limbs(2,3). Silver syndrome and most forms of dHMN are autosomal dominantly inherited with incomplete penetrance and a broad variability in clinical expression. A genome-wide scan in an Austrian family with dHMN-V (ref. 4) showed linkage to the locus SPG17, which was confirmed in 16 additional families with a phenotype characteristic of dHMN or Silver syndrome. After refining the critical region to 1 Mb, we sequenced the gene Berardinelli-Seip congenital lipodystrophy (BSCL2) and identified two heterozygous missense mutations resulting in the amino acid substitutions N88S and S90L. Null mutations in BSCL2, which encodes the protein seipin, were previously shown to be associated with autosomal recessive Berardinelli-Seip congenital lipodystrophy 5 (OMIM #269700). We show that seipin is an integral membrane protein of the endoplasmic reticulum (ER). The amino acid substitutions N88S and S90L affect glycosylation of seipin and result in aggregate formation leading to neurodegeneration.

Journal ArticleDOI
TL;DR: In this paper, the authors investigated the use of topological derivatives in combination with the standard level set method for shape reconstruction and optimization problems and proposed a new approach generalizing the standard speed method, which is obtained by using a source term in the level set equation that depends on the topological derivative of the objective functional.

Journal ArticleDOI
TL;DR: Long-term survivors of acute respiratory distress syndrome seem to face a major risk of PTSD and major impairments in health-related quality of life in the long term.
Abstract: Objective Intensive care often means exposure to physical and psychological stress, with long-lasting emotional sequelae for most patients. Psychiatric morbidity and negative effects on health-related quality of life were assessed in long-term survivors of acute respiratory distress syndrome. Method Forty-six long-term survivors were enrolled in a psychiatric follow-up study. All patients had received standard, protocol-driven treatment during intensive care. The median follow-up time was 8 years after treatment. DSM-IV was used for psychiatric diagnosis. Psychological tests were performed to measure posttraumatic stress symptoms; depression; state anxiety; somatization; symptoms regarding concentration, attention, and short-term memory; social support; and health-related quality of life. Results At time of discharge, 20 of the patients suffered from posttraumatic stress disorder (PTSD) and four from sub-PTSD. At follow-up, 11 patients continued to suffer from PTSD and eight from sub-PTSD. The patients with PTSD demonstrated a pronounced tendency for somatization and state anxiety. Among the groups with PTSD, sub-PTSD, and no PTSD, there were no statistically significant differences regarding social support and symptoms of cognitive dysfunction. Those with PTSD showed major impairments in some dimensions of health-related quality of life, whereas those without PTSD had scores that were in the range of the general population. Except for duration of stay on the intensive care unit, neither age, gender, sociodemographic variables, premorbid psychopathology, nor initial severity of illness discriminated between the groups. Conclusions Long-term survivors of acute respiratory distress syndrome seem to face a major risk of PTSD and major impairments in health-related quality of life in the long term.

Journal ArticleDOI
TL;DR: The elevated expression and release of AVP within the PVN of HAB rats together with the behavioral effects of the AVP V1-receptor antagonist suggest a critical involvement of this neuropeptide in neuroendocrine and behavioral phenomena associated with trait anxiety/depression.

Journal ArticleDOI
TL;DR: Pumpkin seed oil is a common salad oil in Austria and it is not only of interest because of its typical taste but also because of the potential in curing prostate disease as discussed by the authors.

Journal ArticleDOI
01 Mar 2004-Diabetes
TL;DR: There was a strong interaction of diabetes and hypertension, such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants.
Abstract: Diabetic patients are at increased risk for stroke, but little is known about the presence of other brain lesions. We studied the association of magnetic resonance imaging-detected brain lesions to diabetes in 1,252 individuals aged 65-75 years who were randomly selected from eight European population registries or defined working populations. All scans were centrally read for brain abnormalities, including infarcts, white matter lesions, and atrophy. We used a three-point scale to rate periventricular white matter lesions, and the volume of subcortical lesions was calculated according to their number and size. Subjective grading of cortical atrophy by lobe and summation of the lobar grades resulted in a total cortical atrophy score. The mean of three linear measurements of the ventricular diameter relative to the intracranial cavity defined the severity of subcortical atrophy. After adjustment for possible confounders, diabetes was associated with cortical brain atrophy but not with any focal brain lesions or subcortical atrophy. There was a strong interaction of diabetes and hypertension, such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants. Cognitive and pathological data are needed to determine the clinical significance of these findings as well as to understand the mechanisms underlying these associations.

Journal ArticleDOI
TL;DR: In this article, the interaction between the planetary magnetosphere and atmosphere of the close-in extrasolar planets HD 209458b and OGLE-TR-56b with the stellar wind during the evolution of their host stars was studied.
Abstract: We study the interaction between the planetary magnetosphere and atmosphere of the close-in extrasolar planets HD 209458b and OGLE-TR-56b with the stellar wind during the evolution of their host stars. Recent astrophysical observations of solar-like stars indicate that the radiation and particle environments of young stars are orders of magnitudes larger than for stars with ages comparable to the sun (∼4.6 Gyr). We model the interaction for the present and for early evolutionary stages, showing that it is possible that Hot Jupiters have an ionosphere-stellar wind interaction like Venus, Our study suggests that the internal magnetic field of exoplanets orbiting close to their host stars may be very weak due to tidal locking. The magnetic moments can be less than one tenth of the value presently observed for the rapidly rotating planet Jupiter. We find that the stronger stellar wind of younger solar-type stars compresses the magnetosphere to a standoff distance at which the ionized part of the upper atmosphere, hydrodynamically expanded by the XUV-flux, builds an obstacle. Because of a much larger stellar wind particle flux during the first ∼0.5 Gyr after the host stars arrived on the Zero-Age-Main-Sequence, Hot Jupiters may have not been protected by their intrinsic magnetic fields, even if one neglects the effect of tidal locking. In such a case, the unshielded upper atmosphere will be affected by different ionization and non-thermal ion loss processes. This contributes to the estimated neutral hydrogen loss rates of about ≥10 10 g/s of the observed expanded exosphere of HD 209458b (Vidal-Madjar et al. 2003) and will be an ionized part of the estimated upper energy-limited neutral hydrogen loss rates of about 10 12 g/s (Lammer et al. 2003a).

Journal ArticleDOI
TL;DR: In den vergangenen Jahren ist das Erhitzen and Beschleunigen chemischer Reaktionen durch Mikrowellenenergie popular geworden as discussed by the authors.
Abstract: Die offene Flamme konnte erst gezielt als Heizquelle fur Reaktionsgefase in der Synthesechemie verwendet werden, nachdem Robert Bunsen 1855 den nach ihm benannten Brenner erfunden hatte. Der Bunsen-Brenner wurde spater durch den Heizpilz, das Olbad und die Heizplatte als Warmequellen fur chemische Reaktionen abgelost. In den vergangenen Jahren ist das Erhitzen und Beschleunigen chemischer Reaktionen durch Mikrowellenenergie popular geworden. Diese Heiztechnik hat sich von einer Laborkuriositat zu einer etablierten Methode entwickelt, die an Universitaten und in der Industrie stark genutzt wird. Die effiziente Verringerung der Reaktionszeiten (von Tagen und Stunden auf Minuten und Sekunden) ist nur einer der vielen Vorteile des schnellen Erhitzens mit Mikrowellen (“microwave flash heating”). Dieser Aufsatz gibt einen Uberblick uber neuere Anwendungen des kontrollierten Mikrowellenerhitzens in der modernen organischen Synthese und diskutiert einige grundlegende Vorgange.

Journal ArticleDOI
28 May 2004-Langmuir
TL;DR: Aqueous submicron-sized dispersions of the binary monolinolein/water system, which are stabilized by means of a polymer, internally possess a distinct nanostructure, and it is demonstrated for the first time that the internal structure of the dispersed particles can be tuned by temperature in a reversible way.
Abstract: Aqueous submicron-sized dispersions of the binary monolinolein/water system, which are stabilized by means of a polymer, internally possess a distinct nanostructure. Taking this as our starting point, we were able to demonstrate for the first time that the internal structure of the dispersed particles can be tuned by temperature in a reversible way. Upon increasing the temperature, the internal structure undergoes a transition from cubic via hexagonal to fluid isotropic, the so-called L2 phase, and vice versa. Intriguingly, in addition to the structural changes in topology, the particles expel (take up) water to (from) the aqueous continuous phase when increasing (decreasing) the temperature in a reversible way. At each temperature, the internal structure of the dispersed particles corresponds very well to the structure observed in nondispersed binary monolinolein with excess water. This agreement is independent of any thermal history (including phase transitions), which proves that the structures in the ...

Journal ArticleDOI
TL;DR: Results from the present study suggest that part of cerebral apolipoprotein A‐I and αTocH originates from plasma HDL transcytosed across the blood–brain barrier and that caveolae‐located SR‐BI facilitates selective uptake of HDL‐associated αTOCH at the BBB.
Abstract: The present study aimed to investigate pathways that contribute to uptake and transcytosis of high-density lipoproteins (HDLs) and HDL-associated α-tocopherol (αTocH) across an in vitro model of the blood–brain barrier (BBB). In primary porcine brain capillary endothelial cells HDL-associated αTocH was taken up in 10-fold excess of HDL holoparticles, indicating efficient selective uptake, a pathway mediated by scavenger receptor class B, type I (SR-BI). SR-BI was present in caveolae of brain capillary endothelial cells and expressed almost exclusively at the apical membrane. Disruption of caveolae with methyl-β-cyclodextrin (CDX) resulted in (mis)sorting of SR-BI to the basolateral membrane. Immunohistochemistry of porcine brain cryosections revealed SR-BI expression on brain capillary endothelial cells and presumably astrocytic endfeet. HDL-associated [14C]αTocH taken up by brain capillary endothelial cells was recovered in sucrose gradient fractions containing the majority of cellular caveolin-1, the major caveolae-associated protein. During mass transfer studies using αTocH-enriched HDL, approximately 50% of cellular αTocH was recovered with the bulk of cellular caveolin-1 and SR-BI. Efflux experiments revealed that a substantial amount of cell-associated [14C]αTocH could be mobilized into the culture medium. In addition, apical-to-basolateral transport of HDL holoparticles and HDL-associated αTocH was saturable. Results from the present study suggest that part of cerebral apolipoprotein A-I and αTocH originates from plasma HDL transcytosed across the BBB and that caveolae-located SR-BI facilitates selective uptake of HDL-associated αTocH at the BBB.

Journal ArticleDOI
TL;DR: In this article, the authors identified the GAG binding epitopes of MCP-1/CCL2 by characterizing a panel of surface alanine mutants in a series of heparin-binding assays.

Journal ArticleDOI
TL;DR: The data provide evidence that the PARK8 locus is responsible for the disease in a subset of families of white ancestry with autosomal dominant parkinsonism, suggesting that it could be a more common locus.
Abstract: Recently, a new locus (PARK8) for autosomal dominant parkinsonism has been identified in one large Japanese family. Linkage has been shown to a 16-cM centromeric region of chromosome 12, between markers D12S1631 and D12S339. We tested 21 white families with Parkinson disease and an inheritance pattern compatible with autosomal dominant transmission for linkage in this region. Criteria for inclusion were at least three affected individuals in more than one generation. A total of 29 markers were used to saturate the candidate region. One hundred sixty-seven family members were tested (84 affected and 83 unaffected). Under the assumption of heterogeneity and through use of an affecteds-only model, a maximum multipoint LOD score of 2.01 was achieved in the total sample, with an estimated proportion of families with linkage of 0.32. This LOD score is significant for linkage in a replication study and corresponds to a P value of .0047. Two families (family A [German Canadian] and family D [from western Nebraska]) reached significant linkage on their own, with a combined maximum multipoint LOD score of 3.33, calculated with an affecteds-only model (family A: LOD score 1.67, P =.0028; family D: LOD score 1.67, P =.0028). When a penetrance-dependent model was calculated, the combined multipoint LOD score achieved was 3.92 (family A: LOD score 1.68, P =.0027; family D: LOD score 2.24, P =.0007). On the basis of the multipoint analysis for the combined families A and D, the 1-LOD support interval suggests that the most likely disease location is between a CA repeat polymorphism on genomic clone AC025253 (44.5 Mb) and marker D12S1701 (47.7 Mb). Our data provide evidence that the PARK8 locus is responsible for the disease in a subset of families of white ancestry with autosomal dominant parkinsonism, suggesting that it could be a more common locus.

Journal ArticleDOI
TL;DR: Dermoscopy improves the diagnostic accuracy in pigmented skin lesions, but it is also useful in the evaluation of nonpigmented skin tumours as it allows the recognition of vascular structures that are not visible to the naked eye.
Abstract: Background Dermoscopy improves the diagnostic accuracy in pigmented skin lesions, but it is also useful in the evaluation of nonpigmented skin tumours as it allows the recognition of vascular structures that are not visible to the naked eye. Bowen's disease (BD) or squamous cell carcinoma in situ is usually nonpigmented, but may also rarely be pigmented.

Journal ArticleDOI
TL;DR: With the exception of SPTCL, analysis of follow-up data from patients with subcutaneous, blastic natural killer (NK), NK/T-cell, or other non–mycosis fungoides cytotoxic T-cell lymphomas of the skin showed that these groups of lymphomas are characterized by an aggressive course, regardless of the diagnostic category.
Abstract: A new group of subcutaneous, natural killer (NK), NK/T-cell, and other cytotoxic T-cell lymphomas of the skin has been recently described, and some have been included as distinct clinicopathologic entities in the classification of hematologic malignancies recently proposed by the World Health Organization. In the European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas, they would be classified either as CD30- large T-cell lymphoma, small/medium pleomorphic T-cell lymphoma, or subcutaneous T-cell lymphoma. Precise clinicopathologic and prognostic features of all of them have not yet been well characterized. We studied retrospectively 81 biopsies from 50 patients with subcutaneous, blastic natural killer (NK), NK/T-cell, or other non-mycosis fungoides cytotoxic T-cell lymphomas of the skin. Clinical, morphologic, phenotypical, and genetic features and data on Epstein-Barr virus association allowed us to classify our cases according to the following 7 categories: a) subcutaneous "panniculitis-like" T-cell lymphoma (SPTCL): 10 cases (estimated 5-year survival: 80%); b) blastic NK-cell lymphoma: 12 cases (estimated 5-year survival: 0%); c) nasal-type extranodal NK/T-cell lymphoma: 5 patients (estimated 5-year survival: 0%); d) epidermotropic CD8+ T-cell lymphoma: 5 cases (estimated 5-year survival: 0%); e) cutaneous gamma/delta T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); f) cutaneous alpha/beta pleomorphic T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); and g) cutaneous medium/large pleomorphic T-cell lymphoma, not otherwise specified: 2 cases. Our study shows that these cutaneous lymphomas can be classified according to precise diagnostic categories. With the exception of SPTCL, analysis of follow-up data from our patients showed that these groups of lymphomas are characterized by an aggressive course, regardless of the diagnostic category.

Journal ArticleDOI
TL;DR: In this paper, the potential of 11 different synthetic phenolic antioxidants to improve the oxidation stability of biodiesel prepared from different feedstocks was investigated, and the results showed that the efficiency of the antioxidants varied depending on the different types of different biodiesel.
Abstract: The potential of 11 different synthetic phenolic antioxidants to improve the oxidation stability of biodiesel prepared from different feedstocks was investigated. Measurements of oxidation stability were carried out according to the European biodiesel specifications with a Rancimat instrument at 110 °C. At antioxidant concentrations of 1000 mg/kg, an improvement in oxidation stability could be achieved with all antioxidants tested. Especially the antioxidants DTBHQ, IONOX 220, Vulkanox ZKF, Vulkanox BKF, and Baynox were able to significantly improve the oxidation stability, leading to stabilization factors between 1.89 and 13.07. Variation of antioxidant concentrations between 100 and 1000 mg/kg showed that the efficiency of the antioxidants varied depending on the different types of biodiesel. When used as additives, Baynox showed good effects on rapeseed oil methyl ester (RME) stability, DBHQ on recycled cooking oil methyl ester (RCOME) stability, Vulkanox BKF on distilled RCOME (DRCOME) stability, and IONOX 220 on tallow methyl ester (TME) stability. Evaluation of the influence of the antioxidants on critical biodiesel fuel parameters showed no negative impacts on viscosities, densities, carbon residues, CFPP, and sulphated ash contents of the different biodiesel samples. However, in terms of acid values, a noticeable increase could be observed at antioxidant levels of 1000 mg/kg. At lower antioxidant concentrations, this increase was much lower and the values remained within the required limits.

Journal ArticleDOI
TL;DR: There are now a total of nine patients diagnosed with ICOS deficiency most likely due to a common founder, and ICOS-L deficiency could not be identified in families with AR-CVID.