Exclusion of PINK1 as candidate gene for the late-onset form of Parkinson's disease in two European populations.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recently, mutations in the PINK1 (PARK6) gene were shown to rarely cause autosomal-recessively transmitted, early-onset parkinsonism. In order to evaluate whether PINK1 contributes to the risk of common late-onset PD we analysed PINK1 sequence variations.

An improved surrogate method for detecting the presence of chaos in gait.

It has been suggested that the intercycle variability present in the time series of biomechanical gait data is of chaotic nature. However, the proper methodology for the correct determination of whether intercycle fluctuations in the data are deterministic chaos or random noise has not been identified. Our goal was to evaluate the pseudoperiodic surrogation (PPS) [Small et al.

Helium solubility in olivine and implications for high 3He/4He in ocean island basalts.

High 3He/4He ratios found in ocean island basalts are the main evidence for the existence of an undegassed mantle reservoir. However, models of helium isotope evolution depend critically on the chemical behaviour of helium during mantle melting. It is generally assumed that helium is strongly enriched in mantle melts relative to uranium and thorium, yet estimates of helium partitioning in mantle minerals have produced conflicting results.

Tumor necrosis factor-alpha-converting enzyme is expressed in the inflamed peripheral nervous system.

Tumor necrosis factor-alpha (TNF-alpha) is considered to play a critical role in the pathogenesis of immune-mediated inflammatory demyelinating disorders of the peripheral nervous system (PNS). Processing of membrane-bound inactive pro-TNF-alpha into the active soluble cytokine is mediated by a sheddase, the so-called TNF-alpha-converting enzyme (TACE), a member of the A Disintegrin and Metalloproteinase (ADAM) family. We explored the expression of TACE (ADAM-17) in sciatic nerves from Lewis rats with experimental autoimmune neuritis (EAN), an animal model of the Guillain-Barré syndrome (GBS), an immune-mediated polyradiculoneuropathy.

Conjugation to polyethylene glycol polymer promotes aptamer biodistribution to healthy and inflamed tissues.

Here, we examine biodistribution of radiolabeled aptamers and assess the relative ability of different stabilized aptamer compositions (mixed 2'-F/2'-O-Me; fully 2'-O-Me modified) to access inflamed tissues in a murine inflammation model. Biodistribution of 3H-labeled aptamers, including pegylated and unpegylated compositions, was assessed 3 hours postadministration using quantitative whole body autoradiography (QWBA). Aptamer penetration of cells in kidney and liver was also examined at a qualitative level by microautoradiography.

Functional, biochemical, and pathological effects of repeated oral administration of ochratoxin A to rats.

Ochratoxin A (OTA), a mycotoxin produced by several fungi of Aspergillus and Penicillium species, may contaminate agricultural products, resulting in chronic human exposure. In rats, OTA is a potent nephrotoxin, and repeated administration of OTA for 2 years to rats in doses up to 0.21 mg/kg of body wt resulted in high incidences of renal tumors arising from the proximal tubular epithelial cells.

An artificial neural network that utilizes hip joint actuations to control bifurcations and chaos in a passive dynamic bipedal walking model.

Chaos is a central feature of human locomotion and has been suggested to be a window to the control mechanisms of locomotion. In this investigation, we explored how the principles of chaos can be used to control locomotion with a passive dynamic bipedal walking model that has a chaotic gait pattern. Our control scheme was based on the scientific evidence that slight perturbations to the unstable manifolds of points in a chaotic system will promote the transition to new stable behaviors embedded in the rich chaotic attractor.

Generation of an influenza A virus vector expressing biologically active human interleukin-2 from the NS gene segment.

Engineering of the influenza A virus NS1 protein became an attractive approach to the development of influenza vaccine vectors since it can tolerate large inserts of foreign proteins. However, influenza virus vectors expressing long foreign sequences from the NS1 open reading frame (ORF) are usually replication deficient in animals due to the abrogation of their NS1 protein function. In this study, we describe a bicistronic expression strategy based on the insertion of an overlapping UAAUG stop-start codon cassette into the NS gene, allowing the reinitiation of translation of a foreign sequence.

Trends in the pharmacological treatment of patients with schizophrenia over a 12 year observation period.

In this study we evaluated whether our efforts to promote evidence-based guidelines for the psychopharmacological treatment of patients with schizophrenia have led to measurable changes of treatment practice in our hospital by investigating three primary hypotheses: 1) Polypharmacy has become less common in recent years, 2) Conventional neuroleptics have been replaced by second generation antipsychotics; and 3) Dosing regimes have changed towards lower doses. We have therefore collected data from the clinical records of all in-patients with ICD-9/ICD-10 diagnoses of schizophrenia hospitalized at the Department of Psychiatry of the Medical University Innsbruck in the years 1989, 1995, 1998 and 2001. Data from 1989 to 1998 showed a significant decrease in the use of two or more antipsychotics given simultaneously.

Antibiotics GE23077, novel inhibitors of bacterial RNA polymerase. II. Structure elucidation.

During the screening program for new antibacterial agents produced by actinomycetes, GE23077 was isolated from fermentation broths of an Actinomadura sp. strain as a complex of factors A1, A2, B1, B2. NMR, MS and GC/MS analysis carried out on the isolated components led to the conclusion that GE23077 is a novel cyclic heptapeptide consisting of common and unusual amino acids.

Pilot studies on the parallel production of soluble mouse proteins in a bacterial expression system.

We investigated the parallel production in medium throughput of mouse proteins, using protocols that involved recombinatorial cloning, protein expression screening and batch purification. The methods were scaled up to allow the simultaneous processing of tens or hundreds of protein samples. Scale-up was achieved in two stages.

Biotransformation and nephrotoxicity of ochratoxin B in rats.

Ochratoxin B (OTB), a secondary metabolite of Aspergillus ochraceus, is the nonchlorinated analogue of the mycotoxin ochratoxin A (OTA), which is one of the most potent renal carcinogens in rodents. Despite the closely related structure, OTB is considered to be of much lower toxicity. OTA is poorly metabolized and slowly eliminated, and this may play an important role in OTA toxicity, carcinogenicity, and organ specificity.

Gender differences in health-related quality of life on admission to a maintenance treatment program.

We compared the gender differences in health-related quality of life (QOL) on admission to a maintenance program. 103 opioid users (65 men and 38 women) admitted to a maintenance treatment program during 2000-2002 were studied. During this period we assessed the QOL status using the German version ('Berlin Quality of Life Profile') of the Lancashire Quality of Life Profile.

The effect of anterior cruciate ligament reconstruction on lower extremity relative phase dynamics during walking and running.

The purpose of this investigation was to use relative phase dynamics to evaluate gait in individuals with a reconstructed anterior cruciate ligament (ACL) during walking and running. Relative phase dynamics can describe the coordination strategies between the interacting segments at the lower extremity. Ten subjects who had undergone ACL reconstruction using the central third of their patellar tendon and ten healthy controls walked and ran on a treadmill at a self-selected pace.

Pharmacokinetics and biodistribution of novel aptamer compositions.

Purpose: Aptamers are highly selective nucleic acid-based drugs that are currently being developed for numerous therapeutic indications. Here, we determine plasma pharmacokinetics and tissue distribution in rat of several novel aptamer compositions, including fully 2'-O-methylated oligonucleotides and conjugates bearing high-molecular weight polyethylene glycol (PEG) polymers, cell-permeating peptides, and cholesterol.

Methods: Levels of aptamer conjugates in biological samples were quantified radiometrically and by a hybridization-based dual probe capture assay with enzyme-linked fluorescent readout.

Olfactory functioning in patients with alcohol dependence: impairments in odor judgements.

Aims: Prior studies indicate that alcohol-dependent patients have impaired olfactory sensitivity, odor quality discrimination and identification ability. However, olfactory functioning with regard to the immediate, perception driven odor associations is unknown. Therefore, this study assessed olfactory judgements in nonamnesic and nondemented patients with alcohol dependence.

Cigarette smoking in Parkinson's disease: influence on disease progression.

Previous studies have shown an inverse association between smoking and the prevalence of Parkinson's disease (PD), suggesting that smoking may induce a biological protection against nigral neuronal damage. In 1993, we examined the frequency of cigarette smokers among 239 patients with PD and two control groups. In addition, the progression of parkinsonism and other clinical features were followed prospectively in smoking and nonsmoking PD patients over an 8-year period.

Antibiotics GE23077, novel inhibitors of bacterial RNA polymerase. I. Taxonomy, isolation and characterization.

GE 23077 factors A1, A2, B1 and B2 are novel antibiotics isolated from fermentation broths of an Actinomadura sp. strain. GE23077 antibiotics are cyclic peptides, which inhibit Escherichia coli RNA polymerase at nM concentrations.

Interaction of the sliding clamp beta-subunit and Hda, a DnaA-related protein.

In Escherichia coli, interactions between the replication initiation protein DnaA, the beta subunit of DNA polymerase III (the sliding clamp protein), and Hda, the recently identified DnaA-related protein, are required to convert the active ATP-bound form of DnaA to an inactive ADP-bound form through the accelerated hydrolysis of ATP. This rapid hydrolysis of ATP is proposed to be the main mechanism that blocks multiple initiations during cell cycle and acts as a molecular switch from initiation to replication. However, the biochemical mechanism for this crucial step in DNA synthesis has not been resolved.

ADP-specific sensors enable universal assay of protein kinase activity.

Two molecular sensors that specifically recognize ADP in a background of over 100-fold molar excess of ATP are described. These sensors are nucleic-acid based and comprise a general method for monitoring protein kinase activity. The ADP-aptamer scintillation proximity assay is configured in a single-step, homogeneous format while the allosteric ribozyme (RiboReporter) sensor generates a fluorescent signal upon ADP-dependent ribozyme self-cleavage.

[Current consumer conditions among opioid addicts--implications for maintenance-treatment programmes provided by ambulatory drug treatment centers and physicians].

Background: Anonymous evaluation of the current conditions of drug scene and drug consumption, entrance age, personal motives for drug consumption and satisfaction among opioid-dependent clients with treatments available within an ambulant maintenance treatment setting.

Methods: The questionnaire for the study was based on representative studies and covered 112 questions regarding drug consumption. In addition, an instrument of the "Hessische Landesstelle gegen die Suchtgefahren", which measures satisfaction of opioid clients regarding public drug-treatment centers, was used.

A novel strategy for selection of allosteric ribozymes yields RiboReporter sensors for caffeine and aspartame.

We have utilized in vitro selection technology to develop allosteric ribozyme sensors that are specific for the small molecule analytes caffeine or aspartame. Caffeine- or aspartame-responsive ribozymes were converted into fluorescence-based RiboReporter trade mark sensor systems that were able to detect caffeine or aspartame in solution over a concentration range from 0.5 to 5 mM.

Does footwear affect ankle coordination strategies?

The hypothesis of this study was that shoe hardness and footwear affect ankle coordinative strategies during the running stance period. Subjects ran at a self-selected pace under three conditions-barefoot, wearing a hard shoe, and wearing a soft shoe-while sagittal and frontal view kinematic data were collected. Dynamic systems theory tools were used to explore ankle coordinative strategies under the three conditions.

Subtalar and knee joint interaction during running at various stride lengths.

Aim: It has been suggested that during running proper coordination between subtalar pronation/supination and knee flexion/extension via tibial rotation is important to attenuate ground reaction impact forces (GRIF). Lack of coordination over time may produce a wide range of injuries. It was hypothesized that increasing stride length would result in higher GRIF.