bluuebunny/crossref_metadata_2025_split huggingface dataset:
The human paraoxonase‐1 phenotype modifies the effect of statins on paraoxonase activity and lipid parameters
Authors: Mirdamadi Hossein Z. , Sztanek Ferenc , Derdak Zoltan , Seres Ildiko , Harangi Mariann , Paragh György 
Published: April 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • It has been suggested that the human paraoxonase‐1 (PON1) genotype is an important determinant of the therapeutic response given to statin treatment.• It is also known that the PON1 activity status is a better predictor of coronary heart disease risk than any of the known PON1 genotypes.• Our goal was to answer this previously uninvestigated, still clinically relevant question: does the PON1 phenotype have an impact on the paraoxonase‐activating and lipid‐lowering effect of different types of statins. WHAT THIS STUDY ADDS • All the statins (atorvastatin, simvastatin and fluvastatin) included in this study were able to increase serum paraoxonase activity and decrease triglyceride levels effectively; however, this response seemed to be more significant in patients with AB+BB PON1 phenotype than in those bearing AA PON1 phenotype.• Furthermore, the apolipoprotein B‐lowering effect of atorvastatin was also found to be PON1 phenotype‐dependent.• Our results indicate that the PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.AimsHuman serum paraoxonase‐1 (PON1) protects lipoproteins against oxidation by hydrolysing lipid peroxides in oxidized low‐density lipoprotein, therefore it may protect against atherosclerosis. One of the two common PON1 gene polymorphisms within the PON1 gene is the Q192R, whose prevalence can be estimated by phenotype distribution analysis. The goal of this study was to clarify the role of PON1 phenotypes on the effect of three different statins on paraoxonase activity and lipid parameters.MethodsOne hundred and sixty‐four patients with type IIb hypercholesterolaemia were involved in the study. We examined the effect of 10 mg day−1 atorvastatin, 10/20 mg day−1 simvastatin and 80 mg day−1 extended‐release fluvastatin treatment on lipid levels and paraoxonase activity in patients with different PON1 phenotypes. The phenotype distribution of PON1 was determined by the dual substrate method.ResultsThree months of statin treatment significantly increased paraoxonase activity in every statin‐treated group. In patients with AB+BB phenotype, statin treatment was significantly more effective on paraoxonase activity than in the AA group. Statin treatment more effectively decreased triglyceride levels in the AB+BB group compared with the AA group in the whole study population and in the simvastatin‐treated group. Atorvastatin treatment was significantly more effective on apolipoprotein B levels in patients with AB+BB phenotype than in the AA phenotype group.ConclusionsThe PON1 phenotype may be a novel predictive factor for the effectiveness of statin treatment on PON1 activity and serum lipid levels; however, different types of statins may exert different effects on these parameters.
A pharmacokinetic study of etravirine (TMC125) co‐administered with ranitidine and omeprazole in HIV–negative volunteers
Authors: Schöller‐Gyüre Monika , Kakuda Thomas N. , De Smedt Goedele , Vanaken Hilde , Bouche Marie‐Paule , Peeters Monika , Woodfall Brian , Hoetelmans Richard M. W. 
Published: April 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Drug–drug interactions with acid‐suppressing agents were previously described with several other antiretroviral drugs.• Etravirine (TMC125) is a next‐generation non‐nucleoside reverse transcriptase inhibitor, metabolized by CYP3A and CYP2C enzymes with demonstrated efficacy in treatment‐experienced HIV‐infected patients.• The effect of acid‐suppressing agents on the pharmacokinetics of etravirine was unknown. WHAT THIS STUDY ADDS • No clinically relevant effect was shown on the pharmacokinetics of etravirine when co‐administered with ranitidine or omeprazole, drugs that increase gastric pH.• A drug–drug interaction due to CYP2C19 inhibition by omeprazole has been identified.• Etravirine can be co‐administered with proton pump inhibitors and H2 antagonists without dose adjustments.AimsEtravirine is a next‐generation non‐nucleoside reverse transcriptase inhibitor (NNRTI) with activity against wild‐type and NNRTI‐resistant HIV. Proton pump inhibitors and H2‐antagonists are frequently used in the HIV‐negative‐infected population, and drug–drug interactions have been described with other antiretrovirals. This study evaluated the effect of steady‐state omeprazole and ranitidine on the pharmacokinetics of a single dose of etravirine.MethodsIn an open‐label, randomized, one‐way, three‐period crossover trial, HIV‐negative volunteers randomly received a single dose of 100 mg etravirine alone (treatment A); 11 days of 150 mg ranitidine b.i.d. (treatment B); and 11 days of 40 mg omeprazole q.d. (treatment C). A single dose of 100 mg etravirine was co‐administered on day 8 of sessions 2 and 3. Each session was separated by a 14‐day wash‐out.ResultsNineteen volunteers (seven female) participated. When a single dose of etravirine was administered in the presence of steady‐state ranitidine, etravirine least squares means ratios (90% confidence interval) for AUClast and Cmax were 0.86 (0.76, 0.97) and 0.94 (0.75, 1.17), respectively, compared with administration of etravirine alone. When administered with steady‐state omeprazole, these values were 1.41 (1.22, 1.62) and 1.17 (0.96, 1.43), respectively. Co‐administration of a single dose of etravirine and ranitidine or omeprazole was generally safe and well tolerated.ConclusionsRanitidine slightly decreased etravirine exposure, whereas omeprazole increased it by approximately 41%. The increased exposure of etravirine when co‐administered with omeprazole is attributed to CYP2C19 inhibition. Considering the favourable safety profile of etravirine, these changes are not clinically relevant. Etravirine can be co‐administered with proton pump inhibitors and H2 antagonists without dose adjustments.
Refugia in the Cordilleran ice sheet of western North America: chloroplast DNA diversity in the Arctic–alpine plant Oxyria digyna
Authors: Marr Kendrick L. , Allen Geraldine A. , Hebda Richard J. 
Published: April 2008

AbstractAim  Late Pleistocene ice sheets are thought to have covered most of western Canada, including all of British Columbia (BC). We examine patterns of genetic variation in an Arctic–alpine plant to evaluate the possibility of full glacial refugia within the area covered by the Cordilleran ice sheet (CIS) and to uncover post‐glacial migration routes.Location  Western North America.Methods  We sampled 1030 individuals of the Arctic–alpine plant Oxyria digyna from 117 populations distributed over much of its range in western and northern North America. DNA haplotypes were identified using restriction site analysis of two chloroplast DNA intergene spacer regions, psbA‐trnH and trnT‐L. We examined the geographical distribution of haplotype diversity in relation to latitude, and also compared various indices of diversity in putatively glaciated and unglaciated regions. Patterns of migration were inferred using nested clade analysis.Results  We detected a total of 20 haplotypes. High haplotype diversity was found in Beringia, in unglaciated western USA, and in northern BC at 57–59° N, well within the accepted limits of the CIS. Ancestral haplotypes were also centred in northern BC.Main conclusions  High genetic diversity of Oxyria digyna is expected in unglaciated regions, but unexpected in northern BC if British Columbia was entirely covered by ice during the late Pleistocene. Our observations suggest the presence of unglaciated areas providing late Pleistocene refugia in northern BC. Such refugia would have important implications for the origins and migrations of many plant and animal species in north‐western North America.
ORIGINAL ARTICLE: Colonization and diversification in the African ‘sky islands’ by Eurasian Lychnis L. (Caryophyllaceae)
Authors: Popp Magnus , Gizaw Abel , Nemomissa Sileshi , Suda Jan , Brochmann Christian 
Published: April 2008

AbstractAim  Many plants occurring on the isolated mountain peaks of Africa have their closest relatives in very remote areas, even in temperate Europe and Asia. Their biogeographical history is poorly understood. The Afro‐montane element of the primarily Eurasian genus Lychnis is a typical example of such a disjunction. Here, we aim to reconstruct the phylogeny of the Afro‐montane endemics of Lychnis and to infer the history of immigration into Africa and of the subsequent dispersal and speciation.Location  The Afro‐montane representatives of Lychnis occur in Ethiopia, Kenya, Tanzania, Uganda, Rwanda, Burundi, the Democratic Republic of Congo, Cameroon, and Nigeria.Methods  Silica‐dried plant materials collected in Ethiopia in 2004 as well as herbarium material were used for DNA extractions. We used parsimony analysis of nucleotide data from the rps16 intron and psbE‐petL region in plastids, and the internal transcribed spacer (ITS) and a region spanning exon 18–24 in the second largest subunit of RNA polymerase II (RPB2) from the nucleus. DAPI‐flow cytometry was used to determine relative genome size and to infer polyploidization events.Results  Monophyly of the Afro‐montane Lychnis with the Eurasian diploid L. flos‐cuculi resolved as sister was strongly supported by the phylogenetic analyses. The Afro‐montane group was further divided into two strongly supported groups correlated with DNA ploidy levels. The relative genome size was species‐specific except for L. abyssinica, which had two genome‐size variants.Main conclusions  Our results demonstrate that the biogeographical history of the Afro‐montane Lychnis has been highly dynamic, including polyploidization and both old and recent long‐distance dispersal events, even between Eastern and West Africa. The ancestor is inferred to have immigrated once from Eurasia via the Arabian Peninsula to the Ethiopian highlands. Divergence in the lineage containing diploid taxa was followed by several dispersals from Ethiopia to the Eastern and Western Rift Mountains, and recently to West Africa. Divergence of the lineage including the tetraploid L. crassifolia may have taken place in Ethiopia, from where it dispersed to the Eastern and Western Rift Mountains; alternatively, it may have taken place in the Eastern Rift Mountains, followed by dispersal from there to the Western Rift Mountains and then to Ethiopia.
Climate‐driven range dynamics of the freshwater limpet, Ancylus fluviatilis (Pulmonata, Basommatophora)
Authors: Cordellier Mathilde , Pfenninger Markus 
Published: April 2008

AbstractAim  Our aim was to understand the processes that have shaped the present‐day distribution of the freshwater limpet Ancylus fluviatilis sensu stricto in order to predict the consequences of global climate change for the geographical range of this species.Location  North‐western Europe.Methods  We sampled populations of A. fluviatilis sensu stricto over the entire range of the species (north‐western Europe) and sequenced 16S ribosomal RNA (16S) and cytochrome oxidase subunit I (COI) mitochondrial fragments to perform phylogenetic and phylogeographical analyses. Climatic niche modelling allowed us to infer the climatic preferences of the species. A principal components analysis identified the most important climatic factors explaining the actual range of A. fluviatilis. We also identified which climatic factor was the most limiting at range margins, and predicted the species’ geographical range under a climate change scenario [Community Climate Model 3 (CCM3)].Results  By means of the phylogeographical analysis, we infer that A. fluviatilis sensu stricto occupied northern refuges during the Last Glacial Maximum. We show that the climatic preferences of Baltic populations are significantly different from those of Central European populations. The projection of the occupied area under the CCM3 climate model predicts a moderate poleward shift of the northern range limits, but a dramatic loss of areas currently occupied, for instance in northern Germany and in southern Great Britain.Main conclusions  The post‐glacial range dynamics of A. fluviatilis are not governed by niche conservatism. Therefore, we must be cautious about bioclimatic model predictions: the expected impact of climate change could be tempered by the adaptive potential this species has already shown in its evolutionary history. Thus, modelling approaches should rather be seen as conservative forecasts of altered species ranges as long as the adaptive potential of the organisms in question cannot be predicted.
Vegetation, climate and palaeoaltitude reconstructions of the Eastern Alps during the Miocene based on pollen records from Austria, Central Europe
Authors: Jiménez‐Moreno Gonzalo , Fauquette Séverine , Suc Jean‐Pierre 
Published: April 2008

AbstractAim To reconstruct the flora, vegetation, climate and palaeoaltitude during the Miocene (23.03–5.33 Ma) in Central Europe.Location Six outcrop sections located in different basins of the Central Paratethys in Austria.Methods Pollen analysis was used for the reconstruction of the vegetation and climate. The altitude of the Eastern Alps that are adjacent to the Alpine Foreland and Vienna basins has been estimated using a new quantification method based on pollen data. This method uses biogeographical and climatological criteria such as the composition of the modern vegetation belts in the European mountains and Miocene annual temperature estimates obtained from fossil pollen data.Results Pollen changes from Early to Late Miocene have been observed. The vegetation during the Burdigalian and Langhian (20.43–13.65 Ma) was dominated by thermophilous elements such as evergreen trees, typical of a present‐day evergreen rain forest at low altitudes (i.e. south‐eastern China). During the Serravallian and Tortonian (13.65–7.25 Ma) several thermophilous elements strongly decreased, and some disappeared from the Central European region. This kind of vegetation was progressively substituted by one enriched in deciduous and mesothermic plants. Middle‐altitude (Cathaya,CedrusandTsuga) and high‐altitude (AbiesandPicea) conifers increased considerably during the Langhian and later on during the Serravallian and Tortonian.Main conclusions Pollen changes are related to climatic changes and to the uplift of the Alpine massifs. The vegetation during the Burdigalian and Langhian reflects the Miocene climatic optimum. The decrease in thermophilous plants during the Serravallian and Tortonian can be interpreted as a climatic cooling and can be correlated with global and regional climatic changes. This study shows that the palaeoaltitude of the eastern part of the Eastern Alps during the Burdigalian was not high enough forAbiesandPiceato form a forest. Therefore, we inferred that the summits of most of the mountains would have been less than 1800 m. The substantial increase of middle‐ and high‐altitude conifers in the pollen spectra suggests that the uplift rate increased during the Langhian in this region. Based on higher palaeoaltitude estimations for the pollen floras from the studied sections of Austria, we infer that the uplift of the easternmost part of the Alpine chain continued during the Serravallian and Tortonian.
Compression and crevasses in vitreous sections under different cutting conditions
Authors: HAN H.‐M. , ZUBER B. , DUBOCHET J. 
Published: April 2008

SummaryCompression and crevasses are common cutting artefacts in cryo‐ultramicrotomy of vitreous sections. They can be reduced or suppressed under optimal cutting conditions. In the present study, compression and thickness were measured for different cutting speeds and knife angles. It was found that compression decreased with feed and that crevasses appeared only above a certain thickness. The optimal feed for vitreous sections was between 50 and 80 nm. The thickness, calculated by two independent methods, was quantitatively related to feed and compression.
Selective detection of luminescence from semiconductor quantum dots by nanosecond time‐gated imaging with a colour‐masked CCD detector
Authors: MITCHELL A. C. , DAD S. , MORGAN C. G. 
Published: April 2008

SummaryQuantum dots are of considerable interest as highly detectable labels with broad absorption, narrow spectral emission and good quantum yields. The luminescence emission has a longer decay time than that of the most common fluorophores, leading to facile rejection of much background emission (such as autofluorescence from biological samples) by means of gated detection. Here, it is shown that a new technique, true‐colour nanosecond time‐gated luminescence imaging, can be used for selective detection of quantum dot luminescence and should prove valuable for multiplexed detection on the basis of both spectral emission profile and luminescence decay time.
Single wavelength micro‐endoscopy in non‐surgical vascular lesion diagnosis & characterization
Authors: PAPAGATSIA Z. , TAPPUNI A. , WATSON T. F. , COOK R. J. 
Published: April 2008

SummaryMalignant and dysplastic epithelial lesions have often been reported to excite vascular responses by histopathological characterization. Little is reported concerning in vivo real‐time imaging of vascular patterns and flow in health or disease but the development of miniature imaging instrumentation has now allowed such developments.We describe the application of a selective wavelength (540 nm) epi‐illumination Hopkins pattern endoscopic imaging system to image vascular tissues and capillary blood flow in vivo. The contrast mechanism in such imaging was characterized, haemoglobin acting as a chromatic transmission filter despite endoscopy being a non‐invasive and therefore principally reflection mode imaging system. In vivo adrenergic vascular responses, capillary flow rate variations over time and variations in normal capillary architecture around the oral cavity were recorded; demonstrating that simple imaging systems can be used for non‐surgical diagnosis and characterization of vascular lesions, tumours and treatment responses.
AFM for diagnosis of nanocrystallization of steels in hardening processes
Authors: POMPEO G. , GIRASOLE M. , LONGO G. , CRICENTI A. , BAILO D. , RONCI F. , MARAS A. , SERRACINO M. , MORETTI P. F. 
Published: April 2008

SummaryIntroduction: The aim of this study is to investigate the nanocrystallization of steels caused by the transformation from the austenitic to the martensitic phase induced by a severe plastic deformation (SPD) treatment. In this framework, we applied an air blast shot peening treatment, which is a simple protocol widely used for industrial purposes.Methods: AISI 286 and AISI 316 specimens were peened for different times and polished using diamond pastes in order to remove corrugations higher than 1 μm. The characterization of the steel surfaces was performed by atomic force microscopy (AFM) operating in contact mode. Additional EDXD measurements were performed to confirm the phase transition.Results and Discussion: An AFM‐based characterization at nanometric level of the steel surfaces is provided. When the peening exceeds a threshold time that, as expected, depends on the steel composition, a uniform nanostructuration is detected. It is well known that such rearrangement is associated to the growth of a martensitic phase. To date, AFM has been employed in this field only for few applications and to solve specific problems. On the other hand, our results demonstrate that this is a useful technique for the characterization of hardened surfaces, especially when non‐destructive sample preparation treatments are required. Moreover, we show that AFM can be a useful tool also for in situ industrial diagnostics of metallic parts.
Comparative study using scanning electron techniques for imaging of micro‐architecture and antigen appearance
Authors: SOCHER R. , BENAYAHU D. 
Published: April 2008

SummaryWe have used various scanning electron microscopy technologies for the analysis of structures and the appearance of antigen on eukaryotic cells. Various scanning electron microscopy including conventional scanning electron microscopy, high‐resolution scanning electron microscopy and environmental scanning electron microscopy applied for cell surface analysis allow obtaining sub‐micrometre surface features on cell membranes. We used cell systems for imaging along with molecular localization of a cell surface antigen, SVEP1 protein. SVEP1 was studied using the immuno‐gold technique for the identification of cell surface features and protein localization. We used an antibody to SVEP1 molecule that was labelled with secondary antibody conjugated with gold particles. The comparison between scanning electron methods enabled the visualization of surface structures and the molecular imaging for the distribution of SVEP1.
Silver enhancement of Nanogold particles during freeze substitution for electron microscopy
Authors: MORPHEW M. , HE W. , BJORKMAN P. J. , McINTOSH J. RICHARD 
Published: April 2008

SummaryRecent advances in rapid freezing and fixation by freeze substitution have allowed structural cell biologists to apply these reliable modes of sample preparation to a wide range of specimens and scientific problems. Progress in electron tomography has produced cellular images with resolution approaching 4 nm in 3D, but our ability to localize macromolecules in these well‐fixed, well‐resolved samples has remained limited. When light fixation and low temperature embedding are employed with appropriate resins, immuno‐localizations can recognize antigens at a section's surface, but labelling is therefore confined, not throughout the section's depth. Small, electron‐dense markers, like Nanogold®, will often enter a living cell, serving as reliable tracers for endocytic activity, but these markers are usually too small to be visible in the context of a cell. We have developed a method for the silver enhancement of Nanogold particles that works during freeze substitution in organic solvents at low temperature. Here, we describe the development of this method, based on in vitro tests of reagents and conditions. We then show results from application of the method to an in vivo system, using Nanogold to track the internalization of immunoglobulin by neonatal murine intestinal epithelium, a specific example of receptor‐mediated membrane traffic.
Golgi apparatus studied in vitreous sections
Authors: BOUCHET‐MARQUIS C. , STARKUVIENE V. , GRABENBAUER M. 
Published: April 2008

SummaryCryo‐electron microscopy of vitrified specimen is the method of choice to explore cellular ultrastructure at high resolution as close as possible to the native state and environment. In this study, we investigated the Golgi apparatus – the main organelle of the secretory pathway. Cultured mammalian cells were fixed by high‐pressure freezing, sectioned in vitreous ice and subjected to cryo‐electron microscopy and cryo‐electron tomography. Although the overall morphology of Golgi stacks was comparable to well prepared and plastic‐embedded samples, in detail we reached much higher resolution in terms of distinction between biological structures based on their native density. On cisternal buds and peri‐Golgi vesicles – some associated with microtubules – we detected two different subtypes of COPI coats: (1) a homogenous coat and (2) an inhomogeneous spiky coat, providing an 8–9 nm regularity, clearly distinct from clathrin coat. Next, we monitored the secretion of cargo, namely, procollagen I, through the Golgi complex. Temporally correlated with fluorescence microscopy, we performed three‐dimensional cryo‐electron tomography analysis and detected Golgi cisternae enlarged to saccules, containing cargo and showing inter‐cisternal connections. Our work provides a first step towards the high‐resolution description of the secretory pathway in native vitrified samples and describes the challenges associated with this attempt.