Applying New Research Criteria for Diagnosis of Early Alzheimer's Disease: Sex and Intelligence Matter

Alzheimer's disease (AD) can be diagnosed according to new research criteria proposed recently (Dubois et al., 2007). Diagnosis is made on grounds of episodic memory deficits and one pathological biomarker: cerebrospinal fluid (CSF) or structural/functional imaging. Goal was to investigate the dependence of episodic memory function on material (verbal, visuospatial), gender and premorbid intellectual ability (IQ). The new research criteria of AD were applied retrospectively using data of 68 patients (Mini-Mental-Status Examination, MMSE ≥ 22) from a university memory clinic. Women with lower IQ performed worse on visuospatial episodic memory than women with higher IQ and men with the same IQ. Thus, women with lower IQ appear to be particularly vulnerable to visuospatial episodic memory deficits despite similar CSF tau values indicating a similar activity of the neurodegenerative process. Gender, premorbid IQ, and visuospatial material need to be considered in the assessment of episodic memory breakdown applying the newly proposed research criteria for the diagnosis of AD

Molekulare und funktionelle Charakterisierung von potenziell pathogenitatsrelevanten Genen aus <i>Verticillium longisporum</i>

Die Gattung Verticillium gehört zu einer der am weitest verbreiteten Gruppen von pflanzenpathogenen Pilzen auf der Welt und beheimatet eine Vielzahl von Arten, die durch die Infektion der Wirtspflanzen schwere wirtschaftliche Verluste verursachen. Molekulare Studien der an der Infektion von Brassica napus mit Verticillium longisporum beteiligten Gene bieten die Möglichkeit auf ein besseres Verständnis der durch den Pilz hervorgerufenen Krankheitssymptome. Ergebnisse dieser Studien können Hilfestellung bei der Entwicklung neuer Strategien zur Vorbeugung oder der Kontrolle der Infektion geben. Die hier vorliegende Arbeit konzentriert sich auf die Ergebnisse der Analyse von zwei vermeintlich pathogenitätsrelevanten Genen, die im Genom von V. longisporum detektiert wurden. Zahlreiche Kandidatengene von V. longisporum wurden während der Forschung für diese Dissertation effizient durch RNA-Interferenz (RNAi) herunterreguliert. Durch die intrazelluläre Expression von den zu den Kandidatengenen gehörenden, spezifischen Hairpin (HP)-Konstrukten, wird RNAi ausgelöst. Dazu testeten wir verschiedene, in den letzten Jahren publizierte, auf PCR basierende Ansätze, um HP-Fragmente zu generieren. Alle diese Methoden nutzen die Overlap Extension-PCR (OE-PCR), um Sense- und Antisense-Fragmente eines Kandidatengens mit einem dazwischenliegenden Spacer zu verbinden und sind daher nicht abhängig von zeitraubenden Restriktionsenzym-basierenden Klonierungsschritten. Die bei der Etablierung dieser Methoden aufgetretenen Probleme geben tiefe Einblicke in die Anwendbarkeit der OE-PCR für die Konstruktion von HP-Fragmenten. Alle generierten Silencing-Mutanten wiesen eine Reduktion der spezifischen Genexpression von mindestens 90% auf, so dass wir ein zuverlässiges Werkzeug für die Charakterisierung von vermeintlich pathogenitätsrelevanten Genen erhielten, um deren Rolle im Lebenszyklus von V. longisporum zu bewerten. Während unserer Forschung konnten wir zeigen, dass die Herunterregulation eines Gens aus der Familie der Nekrose- und Ethylen-induzierenden Peptide (NEP) eine Reduktion der Symptome an B. napus hervorruft. Es konnte gezeigt werden, dass die abgeschwächten Symptome an der Wirtspflanze durch eine verminderte Fähigkeit der Silencing-Mutanten, sich in der Pflanze zu verbreiten, ausgelöst werden. Insgesamt wurden fünf NEP Gene im Genom von V. longisporum detektiert. Von diesen, als Vl-NEP-1 bis 5 bezeichneten Genen, wiesen drei Gene (Vl-NEP-1, -2, -5 ) eine starke, durch qRT-PCR gemessene in planta-Expression auf. Unsere Ergebnisse für Vl-NEP-1 zeigen, dass das synthetisierte Genprodukt in das Xylem der Wirtspflanze sekretiert wird und dabei höchstwahrscheinlich die umliegenden Zellmembranen des Xylemzylinders permeabilisiert. Diese Ergebnisse weisen darauf hin, dass Vl-NEP-1 ein Virulenzfaktor von V. longisporum während der Infektion von B. napus ist. Das zweite in der vorliegenden Arbeit behandelte Kandidatengen zeigt hohe Homologie zu Genen der Typ I Polyketid-Synthasen (PKS) des wA-Types und wurde daher als Vl-PKS-1 bezeichnet. PKS katalysieren die Aneinanderlagerung von kurzen Carbonsäureketten zu Polyketiden (PK), welche zu einer großen Gruppe von pilzlichen Sekundärmetaboliten gehören. PK von phytopathogenen Pilzen sind in der Literatur dadurch beschrieben, dass sie eine essentielle Rolle während der Interaktion mit anderen Pilzen oder als Pathogenitäts- bzw. Virulenzfaktoren in der Interaktion mit Wirtspflanzen spielen. Silencing-Mutanten von Vl-PKS-1 zeigen im Vergleich zum Wildtyp von V. longisporum eine signifikant erhöhte Wachstumsrate, einen teilweisen Verlust der Wettbewerbsfähigkeit zu anderen phytopathogenen Pilzen sowie eine verzögerte Pigmentierung des Pilzmyzels. Trotz der durch qRT-PCR gemessenen erhöhten in planta-Genexpression, konnten wir nach der Infektion von B. napus mit den Silencing-Mutanten keinen veränderten Phänotyp der Pflanzen beobachten. Daher ist es wahrscheinlich, dass Vl-PKS-1 kein Virulenz- bzw. Pathogenitätsfaktor von V. longisporum für die Infektion von B. napus ist

The Common European Framework of Reference for Languages: A European framework for foreign language speech development?

This paper explores the representation of speech development and particularly perceptive skills in the CEFR level descriptions. The speech-related CEFR sections and related level descriptions are vague and none of the assumptions made therein (such as the supposed linear progression between levels) have been sufficiently tested yet. This paper presents an exploratory study on speech perception in language learners at different levels of proficiency and from different first language (L1) backgrounds (Spanish and German). The study is based on transcriptions in response to short narratives, and investigates what kind of influence listeners’ levels of proficiency in the second language (in this case English) and their L1 backgrounds have on how intelligibility is perceived. The results suggest that proficiency levels and L1 background do indeed influence intelligibility (though not always as anticipated) and partially confirm the idea of a linear progression as proposed in the CEFR

Metal/organic/metal bistable memory devices

We report a bistable organic memory made of a single organic layer embedded between two electrodes, we compare to the organic/metal nanoparticle/organic tri-layers device [L.P. Ma, J. Liu, and Y. Yang, Appl. Phys. Lett. 80, 2997 (2002)]. We demonstrate that the two devices exhibit similar temperature-dependent behaviors, a thermally-activated behavior in their low conductive state (off-state) and a slightly "metallic" behavior in their high conductive state (on-state). This feature emphasizes a similar origin for the memory effect. Owing to their similar behavior, the one layer memory is advantageous in terms of fabrication cost and simplicity

Credibility of native and non-native speakers of English revisited: Do non-native listeners feel the same?

This study reports on research stimulated by Lev-Ari and Keysar (2010) who showed that native listeners find statements delivered by foreign-accented speakers to be less true than those read by native speakers. Our objective was to replicate the study with non-native listeners to see whether this effect is also relevant in international communication contexts. The same set of statements from the original study was recorded by 6 native and 6 nonnative speakers of English. 121 non-native listeners rated the truthfulness of the statements on a 7-point scale. The results of our study tentatively do confirm a negative bias against non-native speakers as perceived by non-native listeners, showing that subconscious attitudes to language varieties are also relevant in communication among non-native speakers

The International Bathymetric Chart of the Arctic Ocean (IBCAO) Version 3.0

[1] The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999. The IBCAO bathymetric portrayals have since supported a wide range of Arctic science activities, for example, by providing constraint for ocean circulation models and the means to define and formulate hypotheses about the geologic origin of Arctic undersea features. IBCAO Version 3.0 represents the largest improvement since 1999 taking advantage of new data sets collected by the circum-Arctic nations, opportunistic data collected from fishing vessels, data acquired from US Navy submarines and from research ships of various nations. Built using an improved gridding algorithm, this new grid is on a 500 meter spacing, revealing much greater details of the Arctic seafloor than IBCAO Version 1.0 (2.5 km) and Version 2.0 (2.0 km). The area covered by multibeam surveys has increased from ∼6% in Version 2.0 to ∼11% in Version 3.0

Impacts of mercury contaminated mining waste on soil quality, crops, bivalves, and fish in the Naboc River area,

Abstract Rice paddy fields in the Naboc area, near Monkayo on the island of Mindanao, Philippines, have been irrigated four times a year over the last decade using Naboc River water contaminated with mercury (Hg) by artisanal gold mining in the Diwalwal area. Silt containing up to at least 90 mg Hg/kg (d.w.) has been deposited in rice paddy fields during the 1990s and this has been repeatedly mixed into the rice root zone through ploughing. Hg in the rice paddy field soils averages 24 mg Hg/kg and generally exceeds the UK and Canadian soil quality thresholds for agricultural soils as well as the proposed Dutch Intervention value and the USEPA soil ingestion Soil Screening Level (SSL) for inorganic Hg. Much lower Hg concentrations (0.05-0.99 mg/kg) within the range expected for uncontaminated soils, characterise soils on which corn and bananas are cultivated, largely because these are not irrigated with Hg-contaminated water from the Naboc River. The estimated total weekly MeHg intake for a person living in the Naboc area related to the weekly consumption of 2.1 kg of rice grown on Hg-contaminated soils (15 Ag MeHg) in conjunction with 1 kg of fish (220 Ag MeHg) and 100 g of mussels (50 Ag MeHg) from the Naboc River, would total 285 Ag MeHg (equivalent to 4.75 Ag/kg bw for a 60 kg adult), which is nearly three times the JECFA PTWI of 1.6 Ag/kg bw. This will significantly contribute to the population mercury exposure and might explain why 38% of the local inhabitants were classified as Hg intoxicated during a mercury toxicity assessmen

Dopamine Agonists and their risk to induce psychotic episodes in Parkinson's disease: a case-control study

<p>Abstract</p> <p>Background</p> <p>Psychosis is rare in untreated patients with Parkinson's disease (PD) but the prevalence rises to 40% during dopaminergic treatment. So far, no systematic comparison of the psychogenic potential of different dopaminergic drugs had been performed.</p> <p>Methods</p> <p>Eighty PD patients with psychotic episodes were compared to an age-matched control group of PD patients without psychotic episodes (n = 120) in a cross-sectional retrospective study.</p> <p>Results</p> <p>We found a positive correlation between psychotic episodes and dementia, number of concomitant medication, and pergolide intake. Odds ratio calculation confirmed the association with dementia. With respect to dopaminergic treatment, pergolide showed the highest odds ratio, levodopa the lowest. An adjusted logistic regression model confirmed the strong association with psychotic episodes and pergolide and no association with levodopa (adjusted odds ratio 2.01 and 0.11, respectively).</p> <p>Conclusion</p> <p>The analysis indicates that dementia and concomitant medication are factors in PD associated with psychotic symptoms. Furthermore, different dopaminergic drugs showed markedly different associations with psychotic symptoms</p

Dissymmetrical U-Shaped π-Stacked Supramolecular Assemblies by Using a Dinuclear CuI Clip with Organophosphorus Ligands and Monotopic Fully π-Conjugated Ligands

International audienceReactions between the U-shape binuclear CuI complex A bearing short metal-metal distances and the cyano-capped monotopic π-conjugated ligands 1-5 carrying gradually bulkier polyaromatic terminal fragments lead to the formation of π-stacked supramolecular assemblies 6-10 respectively in 50-80 % yields. These derivatives have been characterized by multinuclear NMR spectroscopy and X-ray diffraction studies. Their solid state structures show the selective formation of U-shaped supramolecular assemblies in which two monotopic π-conjugated systems present large (6,7,9) or medium (8,10) intramolecular π-overlap revealing π-π interactions. These assemblies self-organize into head-to-tail π-stacked dimers that in turn self-assemble affording infinite columnar π-stacks. The nature, the extentand the complexity of the intermolecular contacts within the head-to-tail π-stacked dimer depends on the nature of the terminal polyaromatic fragment carried by the cyano-capped monotopic ligand but it does not alter the result of the self-assembling process. These results demonstrate that the dinuclear molecular clip A bearing short metal-metal distance allows selective supramolecular assembling processes driven by the formation of intra- and intermolecular short π-π interactions in the resulting self-assembled structures demonstrating that their shape is not only dictated by the symmetry of the building blocks. This approach opens perspectives toward the formation of extented π-stacked columns based on dissymmetrical and functionnal π-conjugated systems

Accelerometer-based physical activity in a large observational cohort - study protocol and design of the activity and function of the elderly in Ulm (ActiFE Ulm) study

<p>Abstract</p> <p>Background</p> <p>A large number of studies have demonstrated a positive effect of increased physical activity (PA) on various health outcomes. In all large geriatric studies, however, PA has only been assessed by interview-based instruments which are all subject to substantial bias. This may represent one reason why associations of PA with geriatric syndromes such as falls show controversial results. The general aim of the Active-Ulm study was to determine the association of accelerometer-based physical activity with different health-related parameters, and to study the influence of this standardized objective measure of physical activity on health- and disability-related parameters in a longitudinal setting.</p> <p>Methods</p> <p>We have set up an observational cohort study in 1500 community dwelling older persons (65 to 90 years) stratified by age and sex. Addresses have been obtained from the local residents registration offices. The study is carried out jointly with the IMCA - Respiratory Health Survey in the Elderly implemented in the context of the European project IMCA II. The study has a cross-sectional part (1) which focuses on PA and disability and two longitudinal parts (2) and (3). The primary information for part (2) is a prospective 1 year falls calendar including assessment of medication change. Part (3) will be performed about 36 months following baseline. Primary variables of interest include disability, PA, falls and cognitive function. Baseline recruitment has started in March 2009 and will be finished in April 2010.</p> <p>All participants are visited three times within one week, either at home or in the study center. Assessments included interviews on quality of life, diagnosed diseases, common risk factors as well as novel cognitive tests and established tests of physical functioning. PA is measured using an accelerometer-based sensor device, carried continuously over a one week period and accompanied by a prospective activity diary.</p> <p>Discussion</p> <p>The assessment of PA using a high standard accelerometer-based device is feasible in a large population-based study. The results obtained from cross-sectional and longitudinal analyses will shed light on important associations between PA and various outcomes and may provide information for specific interventions in older people.</p