Reduced levels of IgM autoantibodies against N-truncated pyroglutamate Aβ in plasma of patients with Alzheimer's disease.

In the present work, we investigated the level of IgM autoantibodies directed against different Aβ epitopes as potential diagnostic biomarker for Alzheimer's disease (AD). Anti-Aβ autoantibody levels were measured in 75 plasma samples from patients with AD, individuals with mild cognitive impairment (MCI), and healthy age- and sex-matched controls (HC). To validate the presence of anti-Aβ IgMs, pooled plasma samples were subjected to gel-filtration analysis.

Formic acid is essential for immunohistochemical detection of aggregated intraneuronal Abeta peptides in mouse models of Alzheimer's disease.

The staining protocols so far applied to study intracellular Abeta accumulation in human tissue have been inconsistent with varying use of heat and formic acid (FA) for antigen retrieval. Microwave heat treatment has been reported to enhance the staining of intraneuronal Abeta as compared to no or enzymatic pretreatment. FA is widely used to increase the staining of plaque pathology in AD, yet the effect of FA on intraneuronal Abeta staining has been reported to be low and similar to the effect of heat or even to counteract the enhancing effect of heat pretreatment on intraneuronal Abeta immunohistochemical detection.

The influence of concentric and eccentric loading on the finger pulley system.

In this study we investigated the influence of the loading condition (concentric vs. eccentric loading) on the pulley system of the finger. For this purpose 39 cadaver finger (14 hands, 10 donors) were fixed into an isokinetic loading device.

Intraneuronal pyroglutamate-Abeta 3-42 triggers neurodegeneration and lethal neurological deficits in a transgenic mouse model.

It is well established that only a fraction of Abeta peptides in the brain of Alzheimer's disease (AD) patients start with N-terminal aspartate (Abeta(1D)) which is generated by proteolytic processing of amyloid precursor protein (APP) by BACE. N-terminally truncated and pyroglutamate modified Abeta starting at position 3 and ending with amino acid 42 [Abeta(3(pE)-42)] have been previously shown to represent a major species in the brain of AD patients. When compared with Abeta(1-42), this peptide has stronger aggregation propensity and increased toxicity in vitro.

Circulating immune complexes of Abeta and IgM in plasma of patients with Alzheimer's disease.

It has previously been shown that immune complexes (IC) of a given biomarker with class M immunoglobulins (IgM) provide better performances compared to the unbound biomarker in a number of cancer entities. In the present work, we investigated IC of IgM-Abeta as a potential biomarker for Alzheimer's disease (AD). Abeta-IgM concentration has been measured in 75 plasma samples from patients with AD, individuals with mild cognitive impairment (MCI), and healthy age- and sex-matched controls (HC).

APP/PS1KI bigenic mice develop early synaptic deficits and hippocampus atrophy.

Abeta accumulation has an important function in the etiology of Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and changes in personality. However, the mode of this toxic activity is still a matter of scientific debate. We used the APP/PS1KI mouse model for AD, because it is the only model so far which develops 50% hippocampal CA1 neuron loss at the age of 1 year.

Synthesis of methyl halides from biomass using engineered microbes.

Methyl halides are used as agricultural fumigants and are precursor molecules that can be catalytically converted to chemicals and fuels. Plants and microorganisms naturally produce methyl halides, but these organisms produce very low yields or are not amenable to industrial production. A single methyl halide transferase (MHT) enzyme transfers the methyl group from the ubiquitous metabolite S-adenoyl methionine (SAM) to a halide ion.

Cellular copper import by nanocarrier systems, intracellular availability, and effects on amyloid beta peptide secretion.

Studies in animals have reported that normalized or elevated Cu levels can inhibit or even remove Alzheimer's disease-related pathological plaques and exert a desirable amyloid-modifying effect. We tested engineered nanocarriers composed of diverse core-shell architectures to modulate Cu levels under physiological conditions through bypassing the cellular Cu uptake systems. Two different nanocarrier systems were able to transport Cu across the plasma membrane of yeast or higher eukaryotic cells, CS-NPs (core-shell nanoparticles) and CMS-NPs (core-multishell nanoparticles).

Robust photon locking.

We experimentally demonstrate a strong-field coherent control mechanism that combines the advantages of photon locking (PL) and rapid adiabatic passage (RAP). Unlike earlier implementations of PL and RAP by pulse sequences or chirped pulses, we use shaped pulses generated by phase modulation of the spectrum of a femtosecond laser pulse with a generalized phase discontinuity. The novel control scenario is characterized by a high degree of robustness achieved via adiabatic preparation of a state of maximum coherence.

Synthetic control of a fitness tradeoff in yeast nitrogen metabolism.

Background: Microbial communities are involved in many processes relevant to industrial and medical biotechnology, such as the formation of biofilms, lignocellulosic degradation, and hydrogen production. The manipulation of synthetic and natural microbial communities and their underlying ecological parameters, such as fitness, evolvability, and variation, is an increasingly important area of research for synthetic biology.

Results: Here, we explored how synthetic control of an endogenous circuit can be used to regulate a tradeoff between fitness in resource abundant and resource limited environments in a population of Saccharomyces cerevisiae.

Preliminary evaluation of a novel side-fire diode laser emitting light at 940 nm, for the potential treatment of benign prostatic hyperplasia: ex-vivo and in-vivo investigations.

Objectives: To evaluate, ex vivo and in vivo, the tissue-removal capacity and coagulation properties of a diode laser emitting light at 940 nm, as in the search for potential therapeutic strategies for benign prostatic hyperplasia that cause less morbidity than transurethral resection of the prostate (TURP), various types of lasers have been tested.

Materials And Methods: A diode laser system (prototype; wavelength 940 nm, Dornier MedTech, Wessling, Germany) was evaluated in an isolated, blood-perfused ex-vivo porcine kidney model at 10-60 W (five kidneys). An in-vivo beagle model was used to investigate the effects on six prostate lobes at a generator output power level of 200 W.

Transient intraneuronal A beta rather than extracellular plaque pathology correlates with neuron loss in the frontal cortex of APP/PS1KI mice.

The accumulation of beta-amyloid (A beta) plaques and neurofibrillary tangles consisting of hyperphosphorylated tau protein are pathological features of Alzheimer's disease (AD) commonly modeled in mice using known human familial mutations; however, the loss of neurons also found to occur in AD is rarely observed in such models. The mechanism of neuron degeneration remains unclear but is of great interest as it is very likely an important factor for the onset of adverse memory deficits occurring in individuals with AD. The role of A beta in the neuronal degeneration is a matter of controversial debates.

Effect of copper intake on CSF parameters in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial.

A plethora of reports suggest that copper (Cu) homeostasis is disturbed in Alzheimer's disease (AD). In the present report we evaluated the efficacy of oral Cu supplementation on CSF biomarkers for AD. In a prospective, randomized, double-blind, placebo-controlled phase 2 clinical trial (12 months long) patients with mild AD received either Cu-(II)-orotate-dihydrate (verum group; 8 mg Cu daily) or placebo (placebo group).

Model-guided design of ligand-regulated RNAi for programmable control of gene expression.

Progress in constructing biological networks will rely on the development of more advanced components that can be predictably modified to yield optimal system performance. We have engineered an RNA-based platform, which we call an shRNA switch, that provides for integrated ligand control of RNA interference (RNAi) by modular coupling of an aptamer, competing strand, and small hairpin (sh)RNA stem into a single component that links ligand concentration and target gene expression levels. A combined experimental and mathematical modelling approach identified multiple tuning strategies and moves towards a predictable framework for the forward design of shRNA switches.

[Alzheimer's disease. Molecular pathology, animal models, and current treatment].

The currently approved but only mildly efficient drugs against Alzheimer's disease treat merely the symptoms. Genetic, neuropathological, and biochemical data support the importance of the amyloid hypothesis of Alzheimer's disease, at the moment the most influential hypothesis. Many treatment strategies have been performed based on this hypothesis and were markedly successful in preclinical animal models.

Intracellular Aß triggers neuron loss in the cholinergic system of the APP/PS1KI mouse model of Alzheimer's disease.

Loss of cholinergic neurons in the Nucleus Basalis of Meynert in Alzheimer's disease (AD) patients was one of the first discoveries of neuron loss in AD. Despite an intense focus on the cholinergic system in AD, the reason for this cholinergic neuron loss is yet unknown. In the present study we examined Abeta-induced pathology and neuron loss in the cholinergic system of the bigenic APP/PS1KI mouse model.

Ex vivo and in vivo investigations of the novel 1,470 nm diode laser for potential treatment of benign prostatic enlargement.

Perioperative haemorrhage is still the major complication of transurethral resection of the prostate (TURP) for benign enlargement of the prostate. Photoselective vaporisation of the prostate (PVP) with the potassium-titanyl-phosphate (KTP) laser has been shown to achieve instant tissue ablation with excellent haemostatic properties. Our aim was to determine the tissue removal capacity, coagulation and haemostatic property of the novel 1,470 nm diode laser, ex vivo and in vivo.

The role of the segmentation gene hairy in Tribolium.

Hairy stripes in Tribolium are generated during blastoderm and germ band extension, but a direct role for Tc-h in trunk segmentation was not found. We have studied here several aspects of hairy function and expression in Tribolium, to further elucidate its role. First, we show that there is no functional redundancy with other hairy paralogues in Tribolium.

Inflammatory changes are tightly associated with neurodegeneration in the brain and spinal cord of the APP/PS1KI mouse model of Alzheimer's disease.

Inflammatory processes are considered to play an important role in the progression of neurodegenerative changes in Alzheimer's disease (AD). In the present study, we performed a systematic expression analysis of various inflammatory and oxidative stress markers in pre-symptomatic and diseased APP/PS1KI mice. This mouse model has been previously shown to harbor severe pathological alterations, including behavioral deficits, axonal degeneration and hippocampal neuron loss starting at the age of 6 months.

Intake of copper has no effect on cognition in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial.

Disturbed copper (Cu) homeostasis may be associated with the pathological processes in Alzheimer's disease (AD). In the present report, we evaluated the efficacy of oral Cu supplementation in the treatment of AD in a prospective, randomized, double-blind, placebo-controlled phase 2 clinical trial in patients with mild AD for 12 months. Sixty-eight subjects were randomized.

Age-dependent loss of dentate gyrus granule cells in APP/PS1KI mice.

Loss of neurons in the hippocampus and other brain regions is, besides the occurrence of plaques and tangles, a neuropathological feature of Alzheimer's disease (AD). In recent years a plethora of transgenic mouse models overexpressing mutant amyloid precursor protein (APP) has been developed, which represent valuable research tools. Whereas extracellular plaque pathology is a common feature of these models, neuronal loss is a rather rare characteristic.

Engineering stochasticity in gene expression.

Stochastic fluctuations (noise) in gene expression can cause members of otherwise genetically identical populations to display drastically different phenotypes. An understanding of the sources of noise and the strategies cells employ to function reliably despite noise is proving to be increasingly important in describing the behavior of natural organisms and will be essential for the engineering of synthetic biological systems. Here we describe the design of synthetic constructs, termed ribosome competing RNAs (rcRNAs), as a means to rationally perturb noise in cellular gene expression.