The Influence of Climatic Factors on the Provocation of Epileptic Seizures.

Recent studies provide the first indications of the impact of climate factors on human health, especially with individuals already grappling with internal and neurological conditions being particularly vulnerable. In the face of escalating climate change, our research delves into the specific influence of a spectrum of climatic factors and seasonal variations on the hospital admissions of patients receiving treatment for epileptic seizures at our clinic in Kaiserslautern. Our study encompassed data from 9366 epilepsy patients who were admitted to hospital due to epileptic seizures.

EEG Synchronization-Parameters in Patients With Subcortical Arteriosclerotic Encephalopathy and Gait Disorder.

Purpose: Subcortical arteriosclerotic encephalopathy (SAE) is characterized by extensive white matter lesions in the MRI. Clinical symptoms are cognitive impairment, ranging from mild deficits to vascular dementia, impaired executive functioning, and gait disorders. In the EEG of SAE patients with vascular dementia, the lower frequencies are increased.

Acute Symptomatic Seizures in Geriatric Patients with Multiple Risk Factors - A Diagnostic Challenge.

Background: Acute symptomatic seizures and epileptic disorders are frequent health problems of elderly patients. An early and reliable distinction of the seizure etiology is important to ensure adequate treatment, and to prevent unwarranted diagnostic and therapeutic procedures.

Methods: We review the current literature based on a MEDLINE search, describe age-related problems in detail, with particular attention to clinical practice, discuss possible criteria and potential pitfalls for diagnostics, and provide a compilation of etiologic factors for acute symptomatic seizures.

A Recurrent Increase of Synchronization in the EEG Continues from Waking throughout NREM and REM Sleep.

Pointwise transinformation (PTI) provides a quantitative nonlinear approach to spatiotemporal synchronization patterns of the rhythms of coupled cortical oscillators. We applied PTI to the waking and sleep EEGs of 21 healthy sleepers; we calculated the mean levels and distances of synchronized episodes and estimated the dominant frequency shift from unsynchronized to synchronized EEG segments by spectral analysis. Recurrent EEG synchronization appeared and ceased abruptly in the anterior, central, and temporal derivations; in the posterior derivations it appeared more fluctuating.

Pointwise transinformation distinguishes a recurrent increase of synchronization in the rapid eye movement sleep electroencephalogram.

The analysis of electroencephalogram (EEG) coupling patterns is essential for understanding how interrelations between cortical sites change with the wake-sleep cycle. Waking and sleep EEGs of 12 normal sleepers were analyzed by pointwise transinformation (PTI). Stage-dependent differences of PTI were assessed, and a spectral analysis of synchronized events was performed.

Mutation analysis of the SLX4/FANCP gene in hereditary breast cancer.

SLX4 coordinates three structure-specific endonucleases in the DNA damage response. One subtype of Fanconi anaemia, FA-P, has recently been attributed to biallelic SLX4 gene mutations. To investigate whether monoallelic SLX4 gene defects play some role in the inherited component of breast cancer susceptibility, in this study we resequenced the whole SLX4 coding region and flanking untranslated sections in genomic DNA samples obtained from a total of 52 German or Byelorussian patients with familial breast cancer.

Blood glucose minimum predicts maximal lactate steady state on running.

This study analyzed if the running speed corresponding to glucose minimum (GM) could predict the maximal lactate steady state (MLSS). Thirteen physically active men (25.2+/-4.

Detection of activation phases and quantification of coupling in NREM sleep EEG by pointwise transinformation.

Background: The coupling dynamics of two time series can be assessed by pointwise transinformation (PTI). Due to its high temporal resolution, this algorithm is ideal for analysis of sleep microstructure. Different types of electroencephalographic (EEG) activation phases, like single K-complexes, K-complexes associated with spindle or alpha activity, K-complexes mixed with delta waves, and arousals, can be detected and changes in EEG coupling can be quantified.

Modulation of agrin function by alternative splicing and Ca2+ binding.

The aggregation of acetylcholine receptors on postsynaptic membranes is a key step in neuromuscular junction development. This process depends on alternatively spliced forms of the proteoglycan agrin with "B-inserts" of 8, 11, or 19 residues in the protein's globular C-terminal domain, G3. Structures of the neural B8 and B11 forms of agrin-G3 were determined by X-ray crystallography.

Collagen stabilization at atomic level: crystal structure of designed (GlyProPro)10foldon.

In a designed fusion protein the trimeric domain foldon from bacteriophage T4 fibritin was connected to the C terminus of the collagen model peptide (GlyProPro)(10) by a short Gly-Ser linker to facilitate formation of the three-stranded collagen triple helix. Crystal structure analysis at 2.6 A resolution revealed conformational changes within the interface of both domains compared with the structure of the isolated molecules.

Characterization of the matrilin coiled-coil domains reveals seven novel isoforms.

Matrilins constitute a family of four oligomeric extracellular proteins that are involved in the development and homeostasis of cartilage and bone. To reveal their homo- and heterotypic oligomerization propensities, we analyzed the four human matrilin coiled-coil domains by biochemical and biophysical methods. These studies not only confirmed the homo- and heterotypic oligomerization states reported for the full-length proteins but revealed seven novel matrilin isoforms.

The laminin-binding domain of agrin is structurally related to N-TIMP-1.

Agrin is the key organizer of postsynaptic differentiation at the neuromuscular junction. This organization activity requires the binding of agrin to the synaptic basal lamina. Binding is conferred by the N-terminal agrin (NtA) domain, which mediates a high-affinity interaction with the coiled coil domain of laminins.

Stabilization of short collagen-like triple helices by protein engineering.

Recombinant expression of collagens and fragments of collagens is often difficult, as their biosynthesis requires specific post-translational enzymes, in particular prolyl 4-hydroxylase. Although the use of hydroxyproline-deficient variants offers one possibility to overcome this difficulty, these proteins usually differ markedly in stability when compared with the hydroxyproline-containing analogs. Here, we report a method to stabilize collagen-like peptides by fusing them to the N terminus of the bacteriophage T4 fibritin foldon domain.

An intrahelical salt bridge within the trigger site stabilizes the GCN4 leucine zipper.

We previously reported that a helical trigger segment within the GCN4 leucine zipper monomer is indispensable for the formation of its parallel two-stranded coiled coil. Here, we demonstrate that the intrinsic secondary structure of the trigger site is largely stabilized by an intrahelical salt bridge. Removal of this surface salt bridge by a single amino acid mutation induced only minor changes in the backbone structure of the GCN4 leucine zipper dimer as verified by nuclear magnetic resonance.

Crystal structure of a naturally occurring parallel right-handed coiled coil tetramer.

The crystal structure of a polypeptide chain fragment from the surface layer protein tetrabrachion from Staphylothermus marinus has been determined at 1.8 A resolution. As proposed on the basis of the presence of 11-residue repeats, the polypeptide chain fragment forms a parallel right-handed coiled coil structure.

Interaction of agrin with laminin requires a coiled-coil conformation of the agrin-binding site within the laminin gamma1 chain.

Coiled-coil domains are found in a wide variety of proteins, where they typically specify subunit oligomerization. Recently, we have demonstrated that agrin, a multidomain heparan sulfate proteoglycan with a crucial role in the development of the nerve-muscle synapse, binds to the three-stranded coiled-coil domain of laminin-1. The interaction with laminin mediates the integration of agrin into basement membranes.

Heterodimerization of a functional GABAB receptor is mediated by parallel coiled-coil alpha-helices.

A detailed understanding of GABAB receptor assembly is an important issue in view of its role as attractive target for treatment of epilepsy, anxiety, depression, cognitive defects, and nociceptive disorders. Heteromerization of GABAB-R1 and GABAB-R2 subunits is a prerequisite for the formation of a functional GABAB receptor. Each individual subunit contains one stretch of approximately 30 amino acid residues within its intracellular C-terminal domain that mediates heteromer formation.

An autonomous folding unit mediates the assembly of two-stranded coiled coils.

Subunit oligomerization of many proteins is mediated by coiled-coil domains. Although the basic features contributing to the thermodynamic stability of coiled coils are well understood, the mechanistic details of their assembly have not yet been dissected. Here we report a 13-residue sequence pattern that occurs with limited sequence variations in many two-stranded coiled coils and that is absolutely required for the assembly of the Dictyostelium discoideum actin-bundling protein cortexillin I and the yeast transcriptional activator GCN4.

Crystallization and preliminary X-Ray diffraction analysis of the 190-A-long coiled-coil dimerization domain of the actin-bundling protein cortexillin I from dictyostelium discoideum.

We have crystallized the approximately 190-A-long parallel two-stranded coiled-coil oligomerization domain of the actin-bundling protein cortexillin I from Dictyostelium discoideum. The orthorhombic crystals belong to the space group C2221 with unit cell dimensions of a = 71.3 A, b = 127.

A distinct 14 residue site triggers coiled-coil formation in cortexillin I.

We have investigated the process of the assembly of the Dictyostelium discoideum cortexillin I oligomerization domain (Ir) into a tightly packed, two-stranded, parallel coiled-coil structure using a variety of recombinant polypeptide chain fragments. The structures of these Ir fragments were analyzed by circular dichroism spectroscopy, analytical ultracentrifugation and electron microscopy. Deletion mapping identified a distinct 14 residue site within the Ir coiled coil, Arg311-Asp324, which was absolutely necessary for dimer formation, indicating that heptad repeats alone are not sufficient for stable coiled-coil formation.

Tenascin-C hexabrachion assembly is a sequential two-step process initiated by coiled-coil alpha-helices.

We have investigated the oligomerization process of tenascin-C using a variety of recombinant wild-type and mutant polypeptide chain fragments produced by heterologous gene expression in Escherichia coli. Biochemical and biophysical analyses of the structures and assemblies of these fragments indicated a sequential two-step oligomerization mechanism of tenascin-C involving the concerted interaction of two distinct domains and cysteines 64, 111, and 113. First, the sequence between alanine 114 and glutamine 139 initiates hexabrachion formation via a parallel three-stranded coiled coil.

Homophilic adhesion of E-cadherin occurs by a co-operative two-step interaction of N-terminal domains.

Cluster formation of E-cadherin on the cell surface is believed to be of major importance for cell-cell adhesion. To mimic this process the extracellular part of mouse E-cadherin (ECAD) was recombinantly fused to the assembly domain of rat cartilage oligomeric matrix protein (COMP), resulting in the chimeric protein ECAD-COMP. The COMP domain formed a five-stranded alpha-helical coiled-coil.

Effect of high-dose tyrosine supplementation on brain function in adults with phenylketonuria.

Objectives: To characterize abnormalities of brain function in patients with phenylketonuria (PKU) who had relaxed or stopped the dietary regimen and to test whether oral high-dose tyrosine (Tyr) supplementation has a beneficial effect.

Design: Comparison with a control group; double-blind, placebo-controlled study comprising six test times; crossover treatment groups; oral high-dose Tyr therapy (100 mg/kg body weight per day) or placebo administration for 4 weeks.

Subjects: Twenty-four early-treated patients with PKU aged 20.

High-affinity and low-affinity calcium binding and stability of the multidomain extracellular 40-kDa basement membrane glycoprotein (BM-40/SPARC/osteonectin).

Reversible binding of calcium ions to a single high-affinity binding site in the 40-kDa basement membrane protein (BM-40) caused a 33% increase of alpha-helicity, an about 60% change in intrinsic fluorescence and a dramatic increase of the rate of cleavage by alpha-chymotrypsin. All these effects exhibited identical dependencies on calcium concentration from which a dissociation constant Kd = 0.6 microM was determined.