ICAM G241A polymorphism and soluble ICAM-1 serum levels: Evidence for an active immune process in schizophrenia

Objectives: We have previously reported reduced serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in schizophrenic patients. A single-nucleotide polymorphism ( SNP) of the ICAM-1 gene was described at position 241. The G --> A SNP results in a nonsynonymous amino acid exchange of the ICAM-1 protein, and the A allele was shown to be also associated with several immunological disorders like rheumatoid arthritis. Methods: We investigated 70 schizophrenic patients and 128 unrelated healthy control persons regarding the relationship between the serum levels of sICAM-1 and the ICAM-1 G214A polymorphism. Results: We were able to replicate our previous finding of reduced sICAM-1 levels in schizophrenia. Healthy control persons carrying the polymorphic A allele showed markedly lower sICAM-1 serum levels than carriers of the homozygous GG wild type ( p < 0.004). In contrast, no significant difference in the sICAM-1 serum levels were seen regarding the G241A genotype distribution in schizophrenic patients. Conclusion: We hypothesize that the biochemical effect of the G241A SNP is masked in schizophrenic patients, indicating a disease-related mechanism leading to reduced levels of sICAM-1 in schizophrenia. Copyright (C) 2005 S. Karger AG, Basel

SFTA2 - a novel secretory peptide highly expressed in the lung - is modulated by lipopolysaccharide but not hyperoxia

Tissue-specific transcripts are likely to be of importance for the corresponding organ. While attempting to define the specific transcriptome of the human lung, we identified the transcript of a yet uncharacterized protein, SFTA2. In silico analyses, biochemical methods, fluorescence imaging and animal challenge experiments were employed to characterize SFTA2. Human SFTA2 is located on Chr. 6p21.33, a disease-susceptibility locus for diffuse panbronchiolitis. RT-PCR verified the abundance of SFTA2-specific transcripts in human and mouse lung. SFTA2 is synthesized as a hydrophilic precursor releasing a 59 amino acid mature peptide after cleavage of an N-terminal secretory signal. SFTA2 has no recognizable homology to other proteins while orthologues are present in all mammals. SFTA2 is a glycosylated protein and specifically expressed in nonciliated bronchiolar epithelium and type II pneumocytes. In accordance with other hydrophilic surfactant proteins, SFTA2 did not colocalize with lamellar bodies but colocalized with golgin97 and clathrin-labelled vesicles, suggesting a classical secretory pathway for its expression and secretion. In the mouse lung, Sfta2 was significantly downregulated after induction of an inflammatory reaction by intratracheal lipopolysaccharides paralleling surfactant proteins B and C but not D. Hyperoxia, however, did not alter SFTA2 mRNA levels. We have characterized SFTA2 and present it as a novel unique secretory peptide highly expressed in the lung

[SADE] A Maple package for the Symmetry Analysis of Differential Equations

We present the package SADE (Symmetry Analysis of Differential Equations) for the determination of symmetries and related properties of systems of differential equations. The main methods implemented are: Lie, nonclassical, Lie-B\"acklund and potential symmetries, invariant solutions, first-integrals, N\"other theorem for both discrete and continuous systems, solution of ordinary differential equations, reduction of order or dimension using Lie symmetries, classification of differential equations, Casimir invariants, and the quasi-polynomial formalism for ODE's (previously implemented in the package QPSI by the authors) for the determination of quasi-polynomial first-integrals, Lie symmetries and invariant surfaces. Examples of use of the package are given

A spontaneous missense mutation in the chromodomain helicase DNA‐binding protein 8 (CHD8) gene: a novel association with congenital myasthenic syndrome

Aims: Congenital myasthenic syndromes (CMS) are characterized by muscle weakness, ptosis and episodic apnoea. Mutations affect integral protein components of the neuromuscular junction (NMJ). Here we searched for the genetic basis of CMS in female monozygotic twins. Methods: We employed whole-exome sequencing for mutation detection and Sanger sequencing for segregation analysis. Immunohistology was done with antibodies against CHD8, rapsyn, β-catenin (βCAT) and golgin on fi-bro-blasts, human and mouse muscle. We recorded superresolution images of the NMJ using 3D-structured illumination microscopy. Results: We discovered a spontaneous missense mutation in CHD8 [chr14:g.21,884,051G>A, GRCh37.p11 | c.1732C>T, NM_00117062 | p.(R578C)], the gene encoding chromodomain helicase DNA-binding protein 8. This is the first missense mutation affecting Duplin, the short 110 kDa isoform of CHD8. It is known that CHD8/Duplin negatively regulates βCAT signalling in the WNT pathway and plays a role in chromatin remodelling. Inactivating CHD8 mutations are associated with autism spectrum disorder and intellectual disability in combination with facial dysmorphism, overgrowth and macrocephalus. No muscle-specific phenotype has been reported to date. Co-immunostaining with rapsyn on human and mouse muscle revealed a strong presence of CHD8 at the NMJ being located towards the sarcoplasmic side of the rapsyn cluster, where it co-localizes with βCAT. Conclusion: We hypothesize CHD8 to have a role in the maintenance of the structural integrity and function of the NMJ. Both patients benefited from treatment with 3,4-diaminopyridine, a reversible blocker of voltage-gated potassium channels at the nerve terminal that prolongs the action potential and increases acetylcholine release

Analytic calculation of the electric field of a coherent THz pulse

Accelerators can serve as sources for intense THz radiation by producing sub-ps long electron bunches, which generate synchrotron radiation coherently in the THz regime. In this paper, we present an analytic method to calculate the electric field pulse emitted by an electron bunch with arbitrary bunch shape. Our method is applied to a Gaussian bunch as well as a complex bunch profile resulting from a nonlinear beam dynamics simulation

Injection Molding of Magnesium Aluminate Spinel Nanocomposites for High‐Throughput Manufacturing of Transparent Ceramics

Transparent ceramics like magnesium aluminate spinel (MAS) are considered the next step in material evolution showing unmatched mechanical, chemical and physical resistance combined with high optical transparency. Unfortunately, transparent ceramics are notoriously difficult to shape, especially on the microscale. Therefore, a thermoplastic MAS nanocomposite is developed that can be shaped by polymer injection molding at high speed and precision. The nanocomposite is converted to dense MAS by debinding, pre-sintering, and hot isostatic pressing yielding transparent ceramics with high optical transmission up to 84 % and high mechanical strength. A transparent macroscopic MAS components with wall thicknesses up to 4 mm as well as microstructured components with single micrometer resolution are shown. This work makes transparent MAS ceramics accessible to modern high-throughput polymer processing techniques for fast and cost-efficient manufacturing of macroscopic and microstructured components enabling a plethora of potential applications from optics and photonics, medicine to scratch and break-resistant transparent windows for consumer electronics

One year ago not business as usual: Wound management, infection and psychoemotional control during tertiary medical care following the 2004 Tsunami disaster in southeast Asia

INTRODUCTION: Following the 2004 tsunami disaster in southeast Asia severely injured tourists were repatriated via airlift to Germany. One cohort was triaged to the Cologne-Merheim Medical Center (Germany) for further medical care. We report on the tertiary medical care provided to this cohort of patients. METHODS: This study is an observational report on complex wound management, infection and psychoemotional control associated with the 2004 Tsunami disaster. The setting was an adult intensive care unit (ICU) of a level I trauma center and subjects included severely injured tsunami victims repatriated from the disaster area (19 to 68 years old; 10 females and 7 males with unknown co-morbidities). RESULTS: Multiple large flap lacerations (2 × 3 to 60 × 60 cm) at various body sites were characteristic. Lower extremities were mostly affected (88%), followed by upper extremities (29%), and head (18%). Two-thirds of patients presented with combined injuries to the thorax or fractures. Near-drowning involved the aspiration of immersion fluids, marine and soil debris into the respiratory tract and all patients displayed signs of pneumonitis and pneumonia upon arrival. Three patients presented with severe sinusitis. Microbiology identified a variety of common but also uncommon isolates that were often multi-resistant. Wound management included aggressive debridement together with vacuum-assisted closure in the interim between initial wound surgery and secondary closure. All patients received empiric anti-infective therapy using quinolones and clindamycin, later adapted to incoming results from microbiology and resistance patterns. This approach was effective in all but one patient who died due to severe fungal sepsis. All patients displayed severe signs of post-traumatic stress response. CONCLUSION: Individuals evacuated to our facility sustained traumatic injuries to head, chest, and limbs that were often contaminated with highly resistant bacteria. Transferred patients from disaster areas should be isolated until their microbial flora is identified as they may introduce new pathogens into an ICU. Successful wound management, including aggressive debridement combined with vacuum-assisted closure was effective. Initial anti-infective therapy using quinolones combined with clindamycin was a good first-line choice. Psychoemotional intervention alleviated severe post-traumatic stress response. For optimum treatment and care a multidisciplinary approach is mandatory

Systematic Comparison of Three Methods for Fragmentation of Long-Range PCR Products for Next Generation Sequencing

Next Generation Sequencing (NGS) technologies are gaining importance in the routine clinical diagnostic setting. It is thus desirable to simplify the workflow for high-throughput diagnostics. Fragmentation of DNA is a crucial step for preparation of template libraries and various methods are currently known. Here we evaluated the performance of nebulization, sonication and random enzymatic digestion of long-range PCR products on the results of NGS. All three methods produced high-quality sequencing libraries for the 454 platform. However, if long-range PCR products of different length were pooled equimolarly, sequence coverage drastically dropped for fragments below 3,000 bp. All three methods performed equally well with regard to overall sequence quality (PHRED) and read length. Enzymatic fragmentation showed highest consistency between three library preparations but performed slightly worse than sonication and nebulization with regard to insertions/deletions in the raw sequence reads. After filtering for homopolymer errors, enzymatic fragmentation performed best if compared to the results of classic Sanger sequencing. As the overall performance of all three methods was equal with only minor differences, a fragmentation method can be chosen solely according to lab facilities, feasibility and experimental design

Role of substrate quality on the performance of semipolar (11 2 - 2) InGaN light-emitting diodes

We compare the optical properties and device performance of unpackaged InGaN/GaN multiple-quantum-well light-emitting diodes (LEDs) emitting at ∼430 nm grown simultaneously on a high-cost small-size bulk semipolar (11 2 - 2) GaN substrate (Bulk-GaN) and a low-cost large-size (11 2 - 2) GaN template created on patterned (10 1 - 2) r-plane sapphire substrate (PSS-GaN). The Bulk-GaN substrate has the threading dislocation density (TDD) of ∼ and basal-plane stacking fault (BSF) density of 0 cm-1, while the PSS-GaN substrate has the TDD of ∼2 × 108cm-2 and BSF density of ∼1 × 103cm-1. Despite an enhanced light extraction efficiency, the LED grown on PSS-GaN has two-times lower internal quantum efficiency than the LED grown on Bulk-GaN as determined by photoluminescence measurements. The LED grown on PSS-GaN substrate also has about two-times lower output power compared to the LED grown on Bulk-GaN substrate. This lower output power was attributed to the higher TDD and BSF density