bluuebunny/crossref_metadata_2025 huggingface dataset:
Vitamin C protects against ethanol and PTZ‐induced apoptotic neurodegeneration in prenatal rat hippocampal neurons
Authors: Naseer M.I. , Ullah N. , Ullah I. , Koh P.O. , Lee H.Y. , Park M.S. , Kim M.O.
Published: October 2010

Exposure to alcohol during brain development may cause a neurological syndrome called fetal alcohol syndrome, characterized by pre‐ and postnatal growth deficiencies, craniofacial anomalies, and evidence of CNS dysfunction. The objective of this study was to evaluate pentylenetetrazol (PTZ) and ethanol effects on Bax, Bcl‐2 expression, which further induced activation of caspase‐3, release of cytochrome‐c from mitochondria, and to observe the protective effects of vitamin C (vit‐C) against PTZ and ethanol‐induced apoptotic neurodegeneration in primary‐cultured neuronal cells at gestational day 17.5. Apoptotic neurodegeneration and neuroprotective effect of vit‐C were measured by using 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenly tetrazolium bromide assay, Western blot analysis, which further conformed by the measurement of mitochondrial membrane potential using JC‐1 detection kit and immunofluorescence analysis. The results showed that PTZ and ethanol produced extensive Bax‐dependent caspase‐9 and caspase‐3 activation and caused neuronal apoptosis. Furthermore, the cotreatment of vit‐C along with ethanol and PTZ showed significantly decreased expression of Bax, caspase‐9, caspase‐3, cytochrome‐c, and significantly increased expression of antiapoptotic Bcl‐2 protein when compared with control group. Our findings indicate that PTZ and ethanol activate an intrinsic apoptotic death program in neurons that is likely to contribute to the neuropathologic effects in fetal alcohol exposure, and vit‐C can prevent some of the deleterious effects of PTZ and ethanol on the developing brain. The available experimental evidence and the safety of vit‐C in pregnancy suggest the experimental use of ascorbic acid as a new and effective protective agent ethanol and PTZ‐induced apoptotic neurodegeneration. Synapse, 2011. © 2010 Wiley‐Liss, Inc.
Discrimination of n‐3 Rich Oils by Gas Chromatography
Authors: Araujo Pedro , Zeng Yingxu , Du Zhen‐Yu , Nguyen Thu‐Thao , Frøyland Livar , Grung Bjørn
Published: October 2010

Exploring the capabilities of instrumental techniques for discriminating n‐3 rich oils derived from animals is a very important though much neglected area that was emphasized more than 100 years ago. In this study the potential of gas chromatography (GC) for discriminating full fatty acid methyl ester (FAME) profiles from fish (cod liver and salmon) and marine mammal (seal and whale) oils is evaluated by means of principal component analysis (PCA). The FAME profiles from plant oils such as rapeseed, linseed and soy oils and seven different brands of n‐3 supplements are also used in the discrimination process. The results from the PCA plots can reliably distinguish between plant, n‐3 supplements, fish and marine mammal oils. By removing the contribution of the n‐3 supplements and plant oils it is possible to discriminate between types of fish and marine animal oils. GC offers a rapid, simple and convenient means of discriminating oils from different species, brands and grades.
Lipid Classes and Fatty Acid Patterns are Altered in the Brain of γ‐Synuclein Null Mutant Mice
Authors: Guschina Irina , Millership Steve , O’Donnell Valerie , Ninkina Natalia , Harwood John , Buchman Vladimir
Published: October 2010

The well‐documented link between α‐synuclein and the pathology of common human neurodegenerative diseases has increased attention to the synuclein protein family. The involvement of α‐synuclein in lipid metabolism in both normal and diseased nervous system has been shown by many research groups. However, the possible involvement of γ‐synuclein, a closely‐related member of the synuclein family, in these processes has hardly been addressed. In this study, the effect of γ‐synuclein deficiency on the lipid composition and fatty acid patterns of individual lipids from two brain regions has been studied using a mouse model. The level of phosphatidylserine (PtdSer) was increased in the midbrain whereas no changes in the relative proportions of membrane polar lipids were observed in the cortex of γ‐synuclein‐deficient compared to wild‐type (WT) mice. In addition, higher levels of docosahexaenoic acid were found in PtdSer and phosphatidylethanolamine (PtdEtn) from the cerebral cortex of γ‐synuclein null mutant mice. These findings show that γ‐synuclein deficiency leads to alterations in the lipid profile in brain tissues and suggest that this protein, like α‐synuclein, might affect neuronal function via modulation of lipid metabolism.
Rice planting systems, global warming and outbreaks of Nilaparvata lugens (Stål)
Authors: Hu G. , Cheng X.N. , Qi G.J. , Wang F.Y. , Lu F. , Zhang X.X. , Zhai B.P.
Published: October 2010

Brown Planthopper (BPH, Nilaparvata lugens (Stål)) is one of the most serious pests of rice in both temperate and tropical regions of East and South Asia and has become especially problematic over the past few years. In order to analyze the effect of the change of rice cropping system on the population dynamics of BPH, field surveys of the occurrence and distribution of BPH were performed and other relevant data, including light trap data and ovary dissection data were collected in nearly 40 Chinese counties encompassing six provinces (or municipalities), including Hainan, Guangxi, Anhui, Shanghai, Fujian and Guangdong from April to October in 2007.

The mixed planting areas of single- and double-cropping rice in China include Hubei, South and Central Anhui, North Hunan, and North Jiangxi. In these areas, double-cropping rice has now been greatly reduced and single-cropping rice has been rapidly increasing since 1997. The surveys revealed that when the immigration peak of BPH occurred in June and July, the single-cropping rice was at the tillering to booting stage and fit for BPH, but early rice had already matured and most of late rice had not yet been transplanted. BPH immigrants from southern rice areas prefer to inhabit and breed in single-cropping rice paddies. Moreover, farming activities between early rice and late rice interrupted the continuous growth of BPH populations in double-cropping rice paddies. As a result, in comparison with data collected 30 years ago, the spatiotemporal dynamics and migration patterns of BPH have dramatically changed in the lower-middle reaches of the Yangtze River. In the mixed planting areas, due to their high suitability, the BPH population in single-cropping rice grew so quickly that it caused serious local damage and there was mass emigration of macropterous progeny to the Yangtze River Delta in late August and early September.

Global warming may also affect BPH populations, where results suggest steadily warmer autumns have occurred from the 1990s on, with such conditions gradually the norm. The combination of ‘cooler summer’ and ‘warmer autumn’ are conditions known to promote outbreaks of BPH in the lower-middle reaches of the Yangtze River. Immigrant BPH arrivals in late August and September now cause serious damage to late-maturing mid-season rice and late rice in the lower-middle reaches of the Yangtze River.
A comparative assessment of the response of three fruit fly species (Diptera: Tephritidae) to a spinosad-based bait: effect of ammonium acetate, female age, and protein hunger
Authors: Piñero J.C. , Mau R.F.L. , Vargas R.I.
Published: October 2010

Ammonia-releasing substances are known to play an important role in fruit fly (Diptera: Tephritidae) attraction to food sources, and this information has been exploited for the development of effective synthetic food-based lures and insecticidal baits. In field studies conducted in Hawaii, we examined the behavioural response of wild female oriental fruit fly (Bactrocera dorsalis(Hendel)), melon fly (B. cucurbitae(Coquillett)), and Mediterranean fruit fly (Ceratitis capitata(Wiedemann)) to spinosad-based GF-120 NF Naturalyte Fruit Fly Bait©formulated to contain either 0, 1 or 2% ammonium acetate. Use of visually-attractive yellow bait stations for bait application in the field allowed for proper comparisons among bait formulations. Field cage tests were also conducted to investigate, using a comparative behavioural approach, the effects of female age and protein starvation on the subsequent response of F1generationB. cucurbitaeandB. dorsalisto the same three bait formulations that were evaluated in the field. Our field results indicate a significant positive effect of the presence, regardless of amount, of AA in GF-120 forB. dorsalisandB. cucurbitae. ForC. capitata, there was a significant positive linear relationship between the relative amounts of AA in bait and female response. GF-120 with no AA was significantly more attractive to femaleC. capitata, but not to femaleB. dorsalisorB. cucurbitae,than the control treatment. Our field cage results indicate that the effects of varying amounts of AA present in GF-120 can be modulated by the physiological stage of the female flies and that the response of femaleB. cucurbitaeto GF-120 was consistently greater than that ofB. dorsalisover the various ages and levels of protein starvation regimes evaluated. Results are discussed in light of their applications for effective fruit fly suppression.
P300 deficits in adults with attention deficit hyperactivity disorder: a meta-analysis
Authors: Szuromi B. , Czobor P. , Komlósi S. , Bitter I.
Published: October 2010

Background

The P300 (P3) event-related potential (ERP) component, a possible endophenotype for attention deficit hyperactivity disorder (ADHD), has been widely examined in children, but received little attention in adults. Our objective was to conduct a meta-analysis of P3 studies in adults with ADHD.

Method

We searched the Medline and PsycINFO databases for controlled studies examining both adult ADHD and matched healthy controls. Six relevant publications were identified for the meta-analysis, which had comparable data across studies with regard to the amplitude of ERP components related to target detection (P3, P3b). Pooled effect size (ES) for P3 amplitude as well as the association of the ES with age and gender were investigated using meta-regression.

Results

Comparing the ADHD group versus controls, the pooled effect size for a decrease in P3 amplitude was in the medium range (Cohen's d=−0.55, p=0.0006). Additionally, meta-regression revealed that decrease in P3 amplitude significantly varied with the mean age of ADHD patients (p=0.0087), with a gradual increasing of the difference at higher ages. Results also showed a significant association between the ES and gender, indicating a more pronounced reduction of P3 amplitude in the ADHD group versus controls when females were predominantly represented in the sample.

Conclusions

To our knowledge, this is the first meta-analysis of P3 characteristics in adults with ADHD. It reveals a significantly decreased P3 amplitude during target detection. Our result that the reduction in P3 amplitude increases with age is interpreted in a neurodevelopmental context.
Spontaneous confabulation, temporal context confusion and reality monitoring: A study of three patients with anterior communicating artery aneurysms
Authors: TURNER MARTHA S. , CIPOLOTTI LISA , SHALLICE TIM
Published: October 2010

Spontaneous confabulation involves the production of false or distorted memories, and is commonly associated with ventromedial prefrontal damage. One influential theory proposes that the critical deficit is a failure to suppress currently irrelevant memory traces that intrude into ongoing thinking (Schnider & Ptak, 1999). In this study, we report experimental investigations with three spontaneously confabulating patients aimed at exploring this account. Using Schnider and Ptak’s (1999) continuous recognition paradigm, we replicated their experimental results with our patients. However, our data suggest that the critical impairment might be more generalized than a failure to suppress currently irrelevant memories. First, a temporal source monitoring task failed to show that previous memory traces intrude into the present. Second, a reality monitoring task revealed that confabulating patients had a tendency to misidentify imagined events as real, a result that cannot be explained in terms of temporal confusion. This error was specific to confabulating patients and was not shared by non-confabulating ACoA patients. Our data therefore suggest a more generalized impairment in source monitoring, not only on the basis of temporality or current relevance, but across a range of contextual domains, including information used to distinguish real memories from imaginings. (JINS, 2010, 16, 984–994.)
Development of a New Quantitative X-Ray Microanalysis Method for Electron Microscopy
Authors: Horny Paula , Lifshin Eric , Campbell Helen , Gauvin Raynald
Published: October 2010

Quantitative X-ray microanalysis of thick samples is usually performed by measuring the characteristic X-ray intensities of each element in a sample and in corresponding standards. The ratio of the measured intensities from the unknown material to that from the standard is related to the concentration using the ZAF or ϕ(ρz) equations. Under optimal conditions, accuracies approaching 1% are possible. However, all the experimental conditions must remain the same during the sample and standard measurements. This is not possible with cold field emission scanning electron microscopes (FE-SEMs) where beam current can fluctuate around 5% in its stable regime. Very little work has been done on variable beam current conditions (Griffin, B.J. & Nockolds, C.E.,Scanning13, 307–312, 1991), and none relating to cold FE-SEM applications. To address this issue, a new method was developed using a single spectral measurement. It is similar in approach to the Cliff-Lorimer method developed for the analytical transmission electron microscope. However, corrections are made for X rays generated from thick specimens using the ratio of the characteristic X-ray intensities of two elements in the same material. The proposed method utilizes the ratio of the intensity of a characteristic X-ray normalized by the sum of X-ray intensities of all the elements measured for the sample, which should also reduce the amplitude of error propagation. Uncertainties in the physical parameters of X-ray generation are corrected using a calibration factor that must be previously acquired or calculated. As an example, when this method was applied to the calculation of the composition of Au-Cu National Institute of Standards and Technology standards measured with a cold field emission source SEM, relative accuracies better than 5% were obtained.
Streamlined Embedding of Cell Monolayers on Gridded Glass-Bottom Imaging Dishes for Correlative Light and Electron Microscopy
Authors: Hanson Hugo H. , Reilly James E. , Lee Rebecca , Janssen William G. , Phillips Greg R.
Published: October 2010

Correlative light and electron microscopy (CLEM) has facilitated study of intracellular trafficking. Routine application of CLEM would be advantageous for many laboratories but previously described techniques are particularly demanding, even for those with access to laser scanning confocal microscopy (LSCM) and transmission electron microscopy (TEM). We describe streamlined methods for TEM of green fluorescent protein (GFP)-labeled organelles after imaging by LSCM using gridded glass bottom imaging dishes. GFP-MAP 1A/1B LC3 (GFP-LC3) transfected cells were treated with rapamycin, fixed and imaged by LSCM. Confocal image stacks were acquired enabling full visualization of each GFP-LC3 labeled organelle. After LSCM, cells were embedded for TEM using a simplified two step method that stabilizes the glass bottom such that the block can be separated from the glass by mild heating. All imaging and TEM processing are performed in the same dish. The LSCM imaged cells were relocated on the block and serial sectioned. Correlation of LSCM, DIC, and TEM images was facilitated by cellular landmarks. All GFP labeled structures were successfully reidentified and imaged by serial section TEM. This method could make CLEM more accessible to nonspecialized laboratories with basic electron microscopy expertise and could be used routinely to confirm organelle localization of fluorescent puncta.
Oxidation and age-related macular degeneration: insights from molecular biology
Authors: Khandhadia Sam , Lotery Andrew
Published: October 2010

Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. It is a multifactorial disease, and current therapy predominantly limits damage only when it has already occurred. The macula is a source of high metabolic activity, and is therefore exposed to correspondingly high levels of reactive oxygen species (ROS). With age, the balance between production of ROS and local antioxidant levels is shifted, and damage ensues. Systemic ROS and antioxidant levels in AMD reflect these local processes. Genetic studies investigating mutations in antioxidant genes in AMD are inconclusive and further studies are indicated, especially to determine the role of mitochondria. Oral antioxidant supplements could be beneficial, and diet modification may help. Future treatments might either increase antioxidant capacity or reduce the production of ROS, using methods such as genetic manipulation. This article reviews the role of oxidative stress in AMD and the potential therapies that might have a role in preventing the blindness resulting from this disease.
Chronisches Subduralhämatom – Beurteilung und Management
Authors: Kress  , Gallay  , Korte  , Hildebrandt
Published: October 2010

Subduralhämatome (SDH) sind mit einer erhöhten Morbidität und Mortalität vergesellschaftet und treten in der Regel als chronische SDH bei älteren Patienten auf. Die häufigsten Zeichen und Symptome eines chronischen SDH – Kopfschmerzen, Vigilanzänderungen, Gangunsicherheit und Hemiparese – kommen auch bei anderen Krankheitsbildern vor, was in der Differentialdiagnose berücksichtigt werden muss. Bei symptomatischen Patienten mit fokalen neurologischen Ausfällen sollte eine chirurgische Intervention in Erwägung gezogen werden, während bei asymptomatischen Patienten oder solchen, die lediglich an Kopfschmerzen leiden, auch eine konservative Behandlung mit klinisch-radiologischer Nachkontrolle in Frage kommt. Auch nach chirurgischer Intervention kommt es leider in 5–33% zu einem Rezidiv des chronischen SDH, weshalb Patienten mit einem chronischen SDH, ungeachtet der Indikation für eine orale Antikoagulation, eine Herausforderung für die behandelnden Ärzte darstellen.
Leberschaden unter oraler Antikoagulation, Statin- und ACE-Hemmertherapie
Authors: Bruggisser  , Terraciano  , Rätz Bravo  , Haschke
Published: October 2010

Ein 71-jähriger Patient stellt sich mit Epistaxis und ikterischen Skleren auf der Notfallstation vor. Der Patient steht unter einer Therapie mit Phenprocoumon, Atorvastatin und Perindopril. Anamnestisch besteht ein langjähriger Alkoholabusus. Laborchemisch werden massiv erhöhte Leberwerte (ALAT, Bilirubin) gesehen. Der INR ist unter oraler Antikoagulation und bei akuter Leberinsuffizienz >12. Die weiterführenden Abklärungen schliessen eine Virushepatitis und eine Autoimmunhepatitis aus. Nachdem eine Leberbiopsie durchgeführt werden kann, wird eine medikamentös-toxische Hepatitis, ausgelöst durch die Komedikation von Atorvastatin, Phenprocoumon und Perindopril bei durch Alkohol bereits vorgeschädigter Leber diagnostiziert. Epidemiologie, Pathophysiologie und Klink der medikamentös induzierten Leberschäden (drug induced liver injury, DILI), speziell von Coumarinen, Statinen und ACE-Hemmern werden im Anschluss an den Fallbericht diskutiert.
Characterization of GPS time series at the Neapolitan volcanic area by statistical analysis
Authors: Bottiglieri M. , Falanga M. , Tammaro U. , De Martino P. , Obrizzo F. , Godano C. , Pingue F.
Published: October 2010

The GPS time series recorded at the Neapolitan volcanic area reveals a very peculiar behavior. When a clear deformation is observed, the amplitude distribution evolves from a super‐Gaussian to a broader distribution. This behavior can be characterized by evaluating the kurtosis. Spurious periodic components were evidenced by independent component analysis and then removed by filtering the original signal. The time series for all stations was modeled with a fifth‐order polynomial fit, which represents the deformation history at that place. Indeed, when this polynomial is subtracted from the time series, the distributions again become super‐Gaussian. A simulation of the deformation time evolution was performed by superposing a Laplacian noise and a synthetic deformation history. The kurtosis of the obtained signals decreases as the superposition increases, enlightening the insurgence of the deformation. The presented approach represents a contribution aimed at adding further information to the studies about the deformation at the Neapolitan volcanic area by revealing geologically relevant data.
Kinetics of water adsorption on minerals and the breathing of the Martian regolith
Authors: Beck P. , Pommerol A. , Schmitt B. , Brissaud O.
Published: October 2010

Several observations of the total amount of water vapor in Mars atmosphere display diurnal variations. A possible explanation is an atmosphere/surface coupling that occurs through H2O exchange with the regolith, where adsorbed water molecules have been proposed as a consequent water reservoir. In order to test this hypothesis, experimental laboratory measurements of adsorption isotherms are needed together with adsorption kinetics measurements. Following our previous measurements of the adsorption isotherms of a series of Mars surface analog materials, we report here on kinetics measurements on the same samples at a temperature of 243 K (volcanic tuff, dunite, ferrihydrite, smectite, JSC‐Mars1). We observed that even for thin samples (1 mm), diffusion through the sample might influence the adsorption process and significant caution is required to infer kinetics parameters of strongly adsorbing samples. The kinetics parameters kd and dka/dP were extracted following the Langmuir theory. Results show that adsorption is fast but not instantaneous with regard to the diurnal time scale (kd = 10−2–10−3 s−1, dka/dP = 10−3–10−4 Pa−1 s−1). Large variations are found between the different samples, which suggest a possible geological control on the amount of exchangeable water between the regolith and the atmosphere. We estimate the impact of a noninstantaneous kinetics on the diurnal water vapor cycle by calculating the maximum amount of exchangeable water. We found that a significant amount of H2O can be trapped within the regolith, even in weakly adsorbing analog materials. The similarity in adsorption properties between the JSC‐Mars1 and ferrihydrite samples suggests that the adsorption properties of the latter are controlled by the presence of iron oxyhydroxide. These materials have strong adsorption capacities, and their presence on the Martian surface might explain the observed spatial correlation between the average surface humidity and the abundance of surface dust.
Upper mantle anisotropy and transition zone thickness beneath southeastern North America and implications for mantle dynamics
Authors: Long Maureen D. , Benoit Margaret H. , Chapman Martin C. , King Scott D.
Published: October 2010

A variety of models for mantle flow beneath southeastern North America have been proposed, including those that invoke westward driven return flow from the sinking Farallon slab, small‐scale convective downwelling at the edge of the continental root, or the upward advective transport of volatiles from the deep slab through the upper mantle. We use shear wave splitting observations and receiver function analysis at broadband seismic stations in the southeastern United States to test several of these proposed mantle flow geometries. Near the coast, stations exhibit well‐resolved null (no splitting) behavior for SKS phases over a range of back azimuths, consistent with either isotropic upper mantle or with a vertical axis of anisotropic symmetry. Farther inland we identify splitting with mainly NE–SW fast directions, consistent with asthenospheric shear due to absolute plate motion (APM), lithospheric anisotropy aligned with Appalachian tectonic structure, or a combination of these. Phase‐weighted stacking of individual receiver functions allows us to place constraints on the timing of arrivals from the 410 and 660 km discontinuities and on average transition zone thickness beneath individual stations. At most stations we find transition zone thicknesses that are consistent with the global average (∼240 km), with two stations showing evidence for a slightly thickened transition zone (∼250 km). Our results are relevant for testing different models for mantle dynamics beneath the southeastern United States, but due to the sparse station coverage, we are unable to uniquely constrain the pattern of mantle flow beneath the region. Our SKS splitting observations support a model in which mantle flow is primarily vertical (either upwelling or downwelling) beneath the southeastern edge of the North American continent, in contrast to the likely horizontal, APM‐driven flow beneath the continental interior. However, our receiver function analysis does not provide unequivocal support either for widespread hydration of the transition zone or for widespread thickening due to the downwelling of relatively cold mantle material. We expect that the necessary data to constrain such models more tightly can be obtained from the operation of denser seismic networks, including the Transportable Array and Flexible Array components of USArray.
Electric field statistics and modulation characteristics of bursty Langmuir waves observed in the cusp
Authors: LaBelle J. , Cairns Iver H. , Kletzing C. A.
Published: October 2010

HF wave receivers on the Twin Rockets to Investigate Cusp Electrodynamics (TRICE) detect numerous 20–250 ms duration Langmuir wave bursts. Investigation of 41 bursts at 967–984 km, where the gyrofrequency exceeds the plasma frequency, reveals a characteristic signature whereby the Langmuir wave bandwidth and highest frequency maximize at the center of the bursts, suggesting that bursts coincide with density enhancements. The Langmuir waveforms are modulated at frequencies up to 50 kHz, with significant modulation at frequencies <1 kHz about 10% of the time. Where amplitudes of the modulated waves pass through zero, the phase of the carrier wave shifts by 180°, consistent with a superposition of interfering waves. The corresponding wave spectrum has multiple <1 kHz bandwidth peaks separated by <1–50 kHz. For no averaging, the wave E field statistics, dominated by the carrier Langmuir wave, show an E+1 dependence at small E fields as expected for rectified sine waves. For moderate averaging, the statistics, dominated by the envelope field, show a spectral index of ≈ +2 at small E fields, consistent with numerical simulations of independent stochastically driven waves. The wave statistics, absence of VLF waves, lack of transition in the modulation occurrence as a function of frequency, and tendency of the spread spectrum to cut off at the ambient plasma frequency outside the density enhancement associated with the wave burst suggest that linear growth and mixing of Langmuir modes provides a more natural explanation of modulated Langmuir waves than do wave‐wave processes previously proposed, at least for cusp waves encountered by TRICE.
Genetic polymorphism and clinical outcome: identification of individuals at risk of a poor clinical outcome
Authors: Strange R. C. , Matthias C. , Jahnke V. , Jones P. W. , Alldersea J. , Hoban P. R. , Fryer A. A.
Published: October 2010

Susceptibility and outcome in complex disorders such as asthma and cancer appear to be determined, at least in part, by genetic polymorphism. However, while our ability to identify new allelic variants and study them in case and control populations has greatly improved, considerable difficulties remain in elucidating how many genes determine particular clinical phenotypes. This is because most studies have concentrated on study of single genes in relatively small study groups. The important issues of gene–gene interactions (epistasis) and high‐risk subgroups have not yet been adequately addressed. We now describe a general approach, using patients with head and neck cancers as an example. Our purpose is to demonstrate candidate gene selection, statistical approaches, and identification of patient subgroups.
How to make foods safer – genetically modified foods
Authors: Moseley Bevan E. B.
Published: October 2010

It is the responsibility of companies developing genetically modified foods, and of regulatory authorities that approve their marketing, to ensure that they are at least as safe as the traditional foods they are intended to replace in the diet. This requires that any novel material introduced into the food material should not be allergenic. If the novel gene has come from an allergenic source, e.g. nuts, it is necessary to demonstrate using immunological procedures applied to the IgE fractions of pooled sera from individuals with confirmed allergies that the novel protein is non‐allergenic. When the novel gene is from a non‐allergenic source then it is necessary to demonstrate lack of significant amino acid sequence homology to known allergens together with sensitivity to food manufacturing and digestive processes. Consumer confidence in genetically modified foods would be significantly improved if hypoallergenic varieties of crops and food products that are currently allergenic could be developed. Techniques such as antisense technology and single site amino acid substitution have been shown to have such potential.
Platelet Mitochondrial Complex I and I+III Activities Do Not Correlate with Cerebral Mitochondrial Oxidative Metabolism
Authors: Powers William J , Haas Richard H , Le Thuy , Videen Tom O , Markham Joanne , Perlmutter Joel S
Published: October 2010

Assays of mitochondrial electron transport system (ETS) activity in circulating blood platelets have been used to investigate the cause of neurodegenerative diseases. However, the correspondence between platelet ETS function and cerebral mitochondrial metabolism is not well characterized. To assess the validity of using platelet ETS activity to infer cerebral mitochondrial metabolism, we measured platelet ETS activity (complex I and complex I+III), cerebral metabolic rate of oxygen (CMRO2), and the CMRO2/cerebral metabolic rate for glucose ratio in 40 subjects: 7 with never-medicated Parkinson's disease, 13 with genetically proved Huntington's disease, and 20 normal controls. We found no correlation between in vivo measures of cerebral mitochondrial oxidative metabolism and ex vivo assays of platelet complex I and complex I+III activity performed on blood collected immediately before cerebral metabolism studies. We saw no evidence of a threshold effect when comparing platelet complex I and complex I+III activity with cerebral oxidative metabolism across a 4- to 10-fold range of platelet ETS activity. On the basis of these data, we conclude that measures of mitochondrial complex I and I+III activity in platelets within the ranges we have studied do not correlate with oxidative function of cerebral mitochondria.
Bio2RDF: Convert, Provide And Reuse.
Authors: Nolin Marc-Alexandre , Corbeil Jacques , Lamontagne Luc , Dumontier Michel
Published: October 2010

The Bio2RDF project uses open-source Semantic Web technologies to provide interlinked life science data in order to maximize productivity and facilitate biological knowledge discovery. Using both syntactic and semantic data integration techniques, Bio2RDF puts into practice a simple methodology to generate and seamlessly integrate machine-interpretable data that can be powerfully interrogated with SPARQL-based queries to answer sophisticated questions.At its core, database records are converted into a set of statements or so-called triples that are captured together as a named graph annotated with provenance. The records and the entities they are about are provided with a Uniform Resource Identifier (URI) of the form http://bio2rdf.org/prefix:identifier, where the prefix indicates a reserved name for the dataset, record or terminological resource. The application of this simple method allows resources from over 40 datasets to integrate seamlessly at the syntactic level irrespective of whether the original data contains non-Bio2RDF URIs.However, when original data providers such as Uniprot provide their own RDF they will rightfully use URIs that resolve to their servers, but what should they do for externally defined entities? If they follow in Bio2RDF’s footsteps then every data provider will use a different URI. However, should original data providers present and implement a URI scheme, then it becomes possible for others to establish stable links to their resources. As such, we will witness the birth of a more stable linked data network, ensuring that data providers need not provide third party data in a redundant manner.
Antigen‐presenting cells and tolerance induction
Authors: Von Bubnoff D. , De La Salle H. , Weßendorf J. , Koch S. , Hanau D. , Bieber T.
Published: October 2010

T cell tolerance induction to foreign and self‐antigens has occupied research since the beginning of the understanding of the immune system. Much controversy still exists on this question even though new methods became available to investigate immunoregulatory mechanisms. Antigen‐presenting cells play a pivotal role in transferring information from the periphery of the organism to lymphoid organs. There, they initiate not only the activation of naive T cells but seem to deliver important signals which result in T cell unresponsiveness with antigen‐specific tolerance induction.
Monoclonal antibodies to recombinant Der f 2 and development of a two‐site ELISA sensitive to major Der f 2 isoallergen in Korea
Authors: Jeong K.Y. , Jin H.S. , Oh S.H. , Hong C.‐S. , Lee I.‐Y. , Ree H.‐I. , Yong T.‐S.
Published: October 2010

Background: Der f 2 is a major sensitizing allergen in patients allergic to house dust mites worldwide. Isoforms of Der f 2 have been reported and are known to have different antigenicities. The aim of this study was to facilitate antigenic analysis and to develop an improved method for the detection of Der f 2 isoallergen, which is prevalent in Korea.

Methods: A two‐site ELISA was developed with monoclonal antibodies (mAbs) which were produced against recombinant Der f 2 (rDer f 2) and applied to assess Der f 2 in bedding samples.

Results: A major isoform of Der f 2, found in Korea, was found to have amino acid variations especially at position 100 from lysine to glutamic acid, which is known to reduce significantly the binding affinity of mAbs when used to assess group 2 allergens. The detection limit of the developed two‐site ELISA was determined to be about 8 ng/ml with rDer f 2 and 1 µg/ml with Dermatophagoides farinae crude extract. The average amount of Der f 2 in dust obtained from bedding samples from 89 homes in Seoul was estimated to be 25.61 ± 10.70 µg/g dust.

Conclusions:  Assays using mAbs for rDer f 2 could be useful for the assessment of environmental allergen exposure and mAbs could be used to further characterize the isoallergens of Der f 2.
Siberian hamster: a new indoor source of allergic sensitization and respiratory disease
Authors: Bertó J. M. , Peláez A. , Fernández E. , Lombardero M. , Ferrer M.
Published: October 2010

Background: The identification of ‘unknown’ allergic sensitizations may determine the prognosis and treatment of patients with respiratory airway disease. Currently, the presence in homes of ‘exotic’ animals as pets is increasing. In this article the Siberian hamster or dwarf hamster (Phodopus sungorus) was identified as a new indoor source of aeroallergens and respiratory disease.

Methods: The subjects were six outpatients who were treated for asthma and rhinitis. Siberian hamster hair extract was prepared with a standard wt/vol method, and patients were skin‐prick tested with the extract. Serum‐specific immunoglobulin (Ig)E against the Siberian hamster, common hamster (Cricetus cricetus) and golden hamster (Mesocricetus auratus) was determined. IgE‐immunoblotting was also performed for all six sera. Specific bronchial challenge was carried out with the Siberian hamster extract.

Results:  Skin prick tests (SPT) with the Siberian hamster extract, and specific IgE‐antibodies against Siberian hamster, were strongly positive in all six patients. Determinations of specific IgE‐antibodies against C. cricetus and M. auratus were negative in all patients. IgE‐immunoblotting of the sera revealed two IgE‐binding fractions (MW 18 and 32 kDa) in five of the six sera. Specific bronchial provocation tests resulted in early asthmatic responses in the two patients who were challenged.

Conclusions: The present study reveals the Siberian hamster to be able to induce both sensitization and disease, and this species of hamster should be taken into consideration as a cause of respiratory disease in exposed subjects. A noteworthy finding was the lack of sensitization in our patients to common hamster allergens (M. auratus and C. cricetus) that are usually tested when hamster allergy is suspected.
The Earth’s inner core
Authors: Jacobs J. A.
Published: October 2010

The Earth’s inner core has been the focus of much attention in recent years — its evolution, when it began to form and how quickly it grew, and what role it plays in the generation and reversals of the Earth’s magnetic field. It has also been found that it is elastically anisotropic and, even more surprisingly, that it is rotating faster than the rest of the Earth.
Apatite fission track analysis in the Argentera massif: evidence of contrasting denudation rates in the External Crystalline Massifs of the Western Alps
Authors: Bogdanoff S. , Michard A. , Mansour M. , Poupeau G.
Published: October 2010

Apatite fission track dating from a central transect in the Argentera massif (southernmost External Crystalline Massif = ECM) yielded ages between 8.05 ± 0.6 and 2.4 ± 0.2 Myr, with a positive age/altitude correlation above 3 Ma, 1200 m. Recognising a thermal peak at c. 250°C, 33 Ma, based on stratigraphic, metamorphic and 39Ar/40Ar data, the present results suggest a slow cooling rate (8–5°C) for the Argentera massif during the Oligocene–early Pliocene. This rate compares with that from the Pelvoux massif, but contrasts with those observed in the northern ECM (Mont‐Blanc and Aar: up to 14°C Myr−1) for the same time interval. This can be related to the different location of the ECM within the collided European margin. At about 3–4 Ma, the denudation rate would have increased up to c. 1 mm yr−1 in the Argentera massif, reaching the same value as in the Belledonne and northern ECM, likely a consequence of Penninic thrust inversion.
The legacy of the NE German Basin — reactivation by compressional buckling
Authors: Marotta A.M. , Bayer U. , Thybo H.
Published: October 2010

In contrast to previously published models for the area, the seismic reflection Moho is essentially flat beneath the NE German Basin along the DEKORP deep seismic profile Basin’96. This raises the question, whether the present structure of the crust and flat Moho reflect the initial formation of the basin or modification by more recent processes. A 2D flexural model, developed for a thin elastic plate, is presented together with lithospheric strength profiles calculated along the BASIN 9601 reflection seismic line. The analysis shows a southward decrease of lithospheric strength below the Basin, with a lithospheric decoupling between the crust and the mantle. The modelling supports the hypothesis that the present Moho topography is caused by flexural buckling which caused subsidence of the NE German Basin during the Upper Cretaceous–Early Cenozoic inversion event. This suggests that the basin is in isostatic disequilibrium, and that compressive stresses are required to keep the present basin geometry.
The level of the tissue‐specific factor GATA‐1 affects the cell‐cycle machinery
Authors: Whyatt David , Karis Alar , Harkes Inge , Verkerk Anton , Gillemans Nynke , Elefanty Andrew , Vairo Gino , Ploemacher Rob , Grosveld Frank , Philipsen Sjaak
Published: October 2010

GATA‐1 is a tissue‐specific DNA‐binding protein containing two zinc‐finger‐like domains. It is expressed predominantly in erythrocytes. Consensus binding sites for GATA‐1 have been found in the regulatory elements of all erythroid‐specific genes examined. GATA‐1 protein is required for erythroid differentiation beyond the proerythroblast stage. In this paper, we demonstrate that the overexpression of GATA‐1 in murine erythroleukaemia (MEL) cells alleviates DMSO‐induced terminal erythroid differentiation. Hence, there is no induction of globin gene transcription and the cells do not arrest in the G1 phase of the cell cycle. Furthermore, we demonstrate that expression of GATA‐1 in non‐transformed erythroid precursors also affects their proliferative capacity and terminal differentiation, as assayed by adult globin gene transcription. To gain insight into the mechanism of this effect, we studied the levels and activities of regulators of cell‐cycle progression during DMSO‐induced differentiation. A decrease in cyclin D‐dependent kinase activity was observed during the induction of both control and GATA‐1‐overexpressing MEL cells. However, cyclin E‐dependent kinase activity decreased more than 20‐fold in control but less than 2‐fold in GATA‐1‐overexpressing MEL cells upon induction. Thus GATA‐1 may exert its effects by regulating cyclin E‐dependent kinase activity. We also show that GATA‐1 binds to the retinoblastoma protein in vitro, but not to the related protein p107, which may indicate that GATA‐1 interacts directly with specific members of the cell‐cycle machinery in vivo. We conclude that GATA‐1 regulates cell fate, in terms of differentiation or proliferation, by affecting the cell‐cycle apparatus.
Human presenilin‐1, but not familial Alzheimer’s disease (FAD) mutants, facilitate Caenorhabditis elegans Notch signalling independently of proteolytic processing
Authors: Baumeister Ralf , Leimer Uwe , Zweckbronner Inge , Jakubek Constanze , Grünberg Jürgen , Haass Christian
Published: October 2010

The majority of cases with familial Alzheimer’s disease (FAD) are linked to mutations of the presenilin (PS) genes. These genes show considerable sequence similarity to the sel‐12 gene of Caenorhabditis elegans, which has been postulated to function in the facilitated signalling by lin‐12 and glp‐1. In order to analyse the functional conservation of the presenilins, we introduced the human PS‐1 cDNA, as well as clinical and deletion mutant proteins, into sel‐12 mutant animals and tested their potential to rescue the egg‐laying defect. Human PS‐1 expressed from the sel‐12 promoter fully rescued the sel‐12 phenotype, whereas two missense mutations, C410Y and A246E, identified in pedigrees with FAD, exhibited a strongly decreased rescuing activity. The large hydrophilic loop and transmembrane domain 7 are required for the biological activity of PS‐1. PS‐1 protein was proteolytically cleaved in C. elegans as it is in human cells. A PS‐1 splice variant (FAD mutation Δexon9) that does not undergo proteolytic cleavage also substituted for sel‐12. The conservation of function of human PS‐1 and C. elegans sel‐12 suggests that presenilin proteins are required, directly or indirectly, for the proper operation of the Notch signalling pathway. FAD‐associated mutant proteins tested showed different rescuing activities, indicating that they might affect different functional or regulatory aspects of PS‐1. Proteolytic processing is not a prerequisite for PS‐1 function in C. elegans.
An auxiliary peptide required for the function of two activation domains in upstream stimulatory factor 2 (USF2) transcription factor
Authors: Gourdon Laurence , Lefrançois‐Martinez Anne‐Marie , Viollet Benoît , Martinez Antoine , Kahn Axel , Raymondjean Michel
Published: October 2010

Ubiquitous upstream stimulatory factors (USF1, USF2a and USF2b) are members of the basic‐helix–loop–helix‐leucine‐zipper family of transcription factors that have been shown to be involved in the transcriptional response of the L‐type pyruvate kinase (L‐PK) gene to glucose. To understand the mechanisms of action of the USF2 isoforms, we initiated a series of co‐transfection assays with deletion mutants and Gal4–USF2 fusions. The transactivating efficiency of the different native and mutant factors was determined at similar DNA binding activity. We found that: (i) exons 3‐ and 5‐encoded regions are activation domains, (ii) a modulator domain encoded by exon 4 could be necessary to their additive action, (iii) a hexapeptide encoded by the first 5′ codons of exon 6 is indispensable for transmitting activation due to both exon 3‐ and exon 5‐encoded domains to the transcriptional machinery. Therefore, USF2 presents a modular structure and mediates transcriptional activation thanks to two non‐autonomous activation domains dependent on an auxiliary peptide for expressing their activating potential.
Gain adaptation and phase dynamics of compensatory eye movements in mice
Authors: Koekkoek Sebastiaan , V. Alphen Arjan , V.d. Burg Johannes , Grosveld Frank , Galjart Niels , De Zeeuw Chris
Published: October 2010

The vestibulocerebellum is involved in the control of compensatory eye movements. To investigate its role in the learning and timing of motor behaviour, eye movements in normal and mutant mice were investigated for the first time with the use of search coils. Wild‐type mice showed the ability to increase the gain of their vestibulo‐ocular reflex by visuo‐vestibular training. This adaptation did not occur in lurcher mice, a natural mouse mutant that completely lacks Purkinje cells. During the optokinetic reflex the phase (timing) of the eye movements of lurchers lagged behind that of wild‐type littermates, whereas during the vestibulo‐ocular reflex it led that of the wild types. Ablations of different parts of the vestibulocerebellum indicated that the flocculus is necessary for the adaptation and the phase‐leading effects of the cerebellum, whereas the nodulus might contribute to its phase‐lagging effects. We conclude that Purkinje cells in the vestibulocerebellum are necessary for both learning and timing of compensatory eye movements in mice, and that the flocculus and nodulus may play antagonistic roles in these processes. The present description of the basic principles of cerebellar eye‐movement control opens up the possibility to investigate the mechanisms of this motor behaviour at the molecular level in genetically manipulated mutant mice.