Biphasic development of the mammalian ventricular conduction system.

Rationale: The ventricular conduction system controls the propagation of electric activity through the heart to coordinate cardiac contraction. This system is composed of specialized cardiomyocytes organized in defined structures including central components and a peripheral Purkinje fiber network. How the mammalian ventricular conduction system is established during development remains controversial.

To sweat or not to sweat? A hypothesis on the effects of venlafaxine and SSRIs.

The hypothesis put forward here attempts to explain how the efficacy of venlafaxine against climacteric symptoms, including sweating, can be reconciled with the fact that this medication is known to cause sweating as an adverse side-effect. Peripherally, the sweating function is regulated noradrenergically by the sympathetic nervous system, central noradrenergic signal transmission being subject partly to inhibitory, partly to excitatory influences by serotonin (5-HT). Theoretically, sweating can be both initiated and inhibited by the activity of selective 5-HT reuptake inhibitors (SSRIs), so that the noradrenergic "tone" resulting from the interaction of noradrenergic and serotonergic neurons in the various regions of the brain probably determines the degree of sweating.

Interferon-beta modulates protein synthesis in the central nervous system.

Interferon-beta (IFN-beta), acting canonically via the modulation of transcription, affects neocortical pyramidal neurons. By use of 2-D differential gel electrophoresis and subsequent mass spectrometry we identified IFN-beta regulated proteins in the central nervous system. These proteins are involved in cytoskeleton assembly, protein transport and nucleotide metabolism and, as such, serve regenerative and protective functions.

Assistive technology, telecare and people with intellectual disabilities: ethical considerations.

Increasingly, commissioners and providers of services for people with intellectual disabilities are turning to assistive technology and telecare as a potential solution to the problem of the increased demand for services, brought about by an expanding population of people with intellectual disabilities in the context of relatively static or diminishing resources. While there are numerous potential benefits of assistive technology and telecare, both for service providers and service users, there are also a number of ethical issues. The aim of this paper is to raise these issues and to set them within the ethical framework proposed by Beauchamp and Childress.

The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF.

Posttranslational histone modifications serve to store epigenetic information and control both nucleosome assembly and recruitment of non-histone proteins. Histone methylation occurs on arginine and lysine residues and is involved in the regulation of gene transcription. A dynamic control of these modifications is exerted by histone methyltransferases and the recently discovered histone demethylases.

Transcription of genes coding for metabolic key functions in Nitrosomonas europaea during aerobic and anaerobic growth.

Nitrosomonas europaea can grow under conditions of chemolithoautotrophic aerobic (oxygen as oxidant) as well as anaerobic [nitrogen dioxide (NO(2)) as oxidant] nitrification or chemoorganotrophic anaerobic pyruvate-dependent denitrification. In this study, the adaptation of the transcription (mRNA synthesis/concentration) of N. europaea to aerobic and anaerobic growth conditions was evaluated and the transcription of genes coding for metabolic key functions was analyzed: nitrogen and energy metabolism (amoA, hao, rh1, nirK, norB, nsc, aceE, ldhA, ppc, gltA, odhA, coxA), carbon dioxide fixation (cbbL), gluconeogenesis (ppsA), cell growth (ftsZ), and oxidative stress (sodB).

Do cell surface trafficking impairments account for variable cell surface sodium iodide symporter levels in breast cancer?

The Na(+)/I(-) symporter (NIS) is a transmembrane glycoprotein that mediates iodide uptake into thyroid follicular cells and serves as the molecular basis of radioiodine imaging and therapy for thyroid cancer patients. The finding that NIS protein is present in 80-90% of breast tumors suggests that breast cancer patients may also benefit from NIS-mediated radionuclide imaging and targeted therapy. However, only 17-25% of NIS-positive breast tumors have detectable radionuclide uptake activity.

Neuroproteomics in stem cell differentiation.

The term "proteome" is used to describe the entire complement of proteins in a given organism or in a system at a given time. Proteome analysis in neuroscience, also called "neuroproteomics" or "neuromics" is in its initial stage, and shows a deficit of studies in the context of brain development. It is the main objective of this review to illustrate the potential of neuroproteomics as a tool to unravel the differentiation of neural stem or progenitor cells to terminally differentiated neurons.

Complete genome sequence of the myxobacterium Sorangium cellulosum.

The genus Sorangium synthesizes approximately half of the secondary metabolites isolated from myxobacteria, including the anti-cancer metabolite epothilone. We report the complete genome sequence of the model Sorangium strain S. cellulosum So ce56, which produces several natural products and has morphological and physiological properties typical of the genus.

Reverse-phase LbL-encapsulation of highly water soluble materials by layer-by-layer polyelectrolyte self-assembly.

We report on a novel method for the encapsulation of highly water soluble materials by using layer-by-layer (LbL) polyelectrolyte self-assembly. State of the art polyelectrolyte self-assembly LbL coating and encapsulation methods are only applicable to insoluble or poorly water soluble template materials, because the process is performed in water causing dissolution of the solid template. Our method extends the material spectrum to highly water soluble template materials by using non-ionized polyelectrolytes in an organic phase (reverse-phase) instead of polyelectrolyte salts in an aqueous environment.

SECM characterization of immobilised enzymes by self-assembled monolayers on titanium dioxide surfaces.

SECM in generator-collector mode was used to detect the presence of immobilised enzymes on titanium dioxide layers which were chemically or electrochemically generated with possible application as chemical sensors and biosensors. Glucose oxidase (GOx) and horseradish peroxidase (HRP) were immobilised by SAM generation using aminopropyltriethoxysilane (APTES) and ascorbic acid. The enzymes were successfully immobilised on two different TiO(2) surfaces.

Spiroketal polyketide formation in Sorangium: identification and analysis of the biosynthetic gene cluster for the highly cytotoxic spirangienes.

Natural products constitute important lead structures in drug discovery. In bacteria, they are often synthesized by large, modular multienzyme complexes. Detailed analysis of the biosynthetic machinery should enable its directed engineering and production of desirable analogs.

Depressive symptoms may explain elevated plasma levels of homocysteine in females with eating disorders.

Elevated plasma homocysteine levels have been found in different psychiatric disorders, including major depression and eating disorders. The aim of the present study was to evaluate whether presence of depression or depressive symptoms is associated with elevated homocysteine levels in patients with eating disorders. Total plasma homocysteine levels were assessed in 44 females with anorexia nervosa (n = 21) or bulimia nervosa (n = 23).

2-DE profiling of GDNF overexpression-related proteome changes in differentiating ST14A rat progenitor cells.

Targeted differentiation of neural progenitor cells (NPCs) is a challenge for treatment of neurodegenerative diseases by cell replacement therapy and cell signalling manipulation. Here, we applied a proteome profiling approach to the rat striatal progenitor model cell line ST14A in order to elucidate cellular differentiation processes. Native cells and cells transfected with the glial cell line-derived neurotrophic factor (GDNF) gene were investigated at the proliferative state and at seven time points up to 72 h after induction of differentiation.

2-DE proteomic profiling of neuronal stem cells.

Proteomics has become a powerful tool in neuroscience studies. Although numerous human neural stem cells are available for research purposes since many years, there exists only limited information on proteomic data from stable neural stem cell lines. Profiling and functional proteome studies of neuronal stem cells will help to describe the protein inventory as well as protein activity and interactions, subcellular localization and posttranslational modifications.

A mutation in the GABA(A) receptor alpha(1)-subunit is associated with absence epilepsy.

Objective: To detect mutations in GABRA1 in idiopathic generalized epilepsy.

Methods: GABRA1 was sequenced in 98 unrelated idiopathic generalized epilepsy patients. Patch clamping and confocal imaging was performed in transfected mammalian cells.

Long-term experience with oral or inhaled vasodilator combination therapy in patients with pulmonary hypertension.

Background: Disease progression in pulmonary hypertension (PH) is common despite standard vasodilator monotherapy with iloprost, bosentan or sildenafil.

Objective: To investigate if the combination of these non-invasively applicable treatments is an effective option to address the multiple pathophysiological mechanisms present in PH.

Methods: We analysed the clinical course of 23 patients with PH, diagnosed as idiopathic (n = 15), chronic thromboembolic (n = 4), and associated with collagen vascular disease (n = 4), receiving combination vasodilator therapy at our institution.

A modular DNA signal translator for the controlled release of a protein by an aptamer.

Owing to the intimate linkage of sequence and structure in nucleic acids, DNA is an extremely attractive molecule for the development of molecular devices, in particular when a combination of information processing and chemomechanical tasks is desired. Many of the previously demonstrated devices are driven by hybridization between DNA 'effector' strands and specific recognition sequences on the device. For applications it is of great interest to link several of such molecular devices together within artificial reaction cascades.

2-DE proteome analysis of a proliferating and differentiating human neuronal stem cell line (ReNcell VM).

The proteome of a proliferating human stem cell line was analyzed and then utilized to detect stem cell differentiation-associated changes in the protein profile. The analysis was conducted with a stable human fetal midbrain stem cell line (ReNcell VM) that displays the properties of a neural stem cell. Therefore, acquisition of proteomic data should be representative of cultured human neural stem cells (hNSCs) in general.

Comparison of software tools to improve the detection of carcinogen induced changes in the rat liver proteome by analyzing SELDI-TOF-MS spectra.

A common animal model of chemical hepatocarcinogenesis was used to demonstrate the potential identification of carcinogenicity related protein signatures/biomarkers. Therefore, an animal study in which rats were treated with the known liver carcinogen N-nitrosomorpholine (NNM) or the corresponding vehicle was evaluated. Histopathological investigation as well as SELDI-TOF-MS analysis was performed.

Dietary constituents are able to play a beneficial role in canine epidermal barrier function.

Epidermal barrier function is a critical attribute of mammalian skin. The barrier is responsible for preventing skin-associated pathologies through controlling egress of water and preventing ingress of environmental agents. Maintaining the quality and integrity of the epidermal barrier is therefore of considerable importance.

Identification of StiR, the first regulator of secondary metabolite formation in the myxobacterium Cystobacter fuscus Cb f17.1.

Myxobacteria are well established as proficient producers of natural products with numerous biological activities. Although some knowledge has been gained regarding the biosynthesis of secondary metabolites in this class of bacteria, almost nothing is known about the underlying regulatory mechanisms. In order to identify regulatory elements, we submitted the argyrin and stigmatellin producer Cystobacter fuscus to a random transposon mutagenesis strategy and screened 1,000 mutants for the occurrence of strains showing remarkably increased or decreased production of these compounds.