The mutation p.D313Y is associated with organ manifestation in Fabry disease.

Fabry disease (FD) is a multisystem lysosomal storage disorder caused by mutations in the GLA gene. The clinical significance of the mutation p.D313Y is still under debate. Retrospective chart analysis of clinical (neurological, cardiac, renal, and ophthalmological), genetic, and biochemical (lyso-globotriaosylsphingosine, lyso-Gb3; enzyme activity) data was performed in all our patients carrying the p.D313Y mutation. Fourteen patients from 5 families (10 female, 4 male; age range 10-51) were included. Symptoms and organ manifestations compatible with FD could be identified in 10 patients. Cerebrovascular events occurred in 4 females. Seven patients reported pain or acroparaesthesia. Cornea verticillata was found in 1 patient, mild retinal vascular tortuosity in 5 patients. Lyso-Gb3 was elevated in 2 females with cerebrovascular involvement. Classical cardiac, renal or skin manifestations could not be identified. The mutation p.D313Y in the GLA gene may lead to organ manifestations and elevation of the Fabry-specific biomarker lyso-Gb3. Neurological symptoms (stroke and pain) and ocular manifestations seem to be the leading findings. Annual routine visits are recommended for patients carrying the p.D313Y mutation. Enzyme replacement therapy might be considered in symptomatic patients.

Amyloid formation: functional friend or fearful foe?

Amyloid formation has been most studied in the context of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, as well as in amyloidosis. However, it is becoming increasingly clear that amyloid is also present in the healthy setting; for example nontoxic amyloid formation is important for melanin synthesis and in innate immunity. Furthermore, bacteria have mechanisms to produce functional amyloid structures with important roles in bacterial physiology and interaction with host cells. Here, we will discuss some novel aspects of fibril-forming proteins in humans and bacteria. First, the amyloid-forming properties of the antimicrobial peptide human defensin 6 (HD6) will be considered. Intriguingly, unlike other antimicrobial peptides, HD6 does not kill bacteria. However, recent data show that HD6 can form amyloid structures at the gut mucosa with strong affinity for bacterial surfaces. These so-called nanonets block bacterial invasion by entangling the bacteria in net-like structures. Next, the role of functional amyloid fibrils in human semen will be discussed. These fibrils were discovered through their property to enhance HIV infection but they may also have other yet unknown functions. Finally, the role of amyloid formation in bacteria will be reviewed. The recent finding that bacteria can make amyloid in a controlled fashion without toxic effects is of particular interest and may have implications for human disease. The role of amyloid in health and disease is beginning to be unravelled, and here, we will review some of the most recent findings in this exciting area.

Targeting allergenic fungi in agricultural environments aids the identification of major sources and potential risks for human health.

Fungi are, after pollen, the second most important producers of outdoor airborne allergens. To identify sources of airborne fungal allergens, a workflow for qPCR quantification from environmental samples was developed, thoroughly tested, and finally applied. We concentrated on determining the levels of allergenic fungi belonging to Alternaria, Cladosporium, Fusarium, and Trichoderma in plant and soil samples from agricultural fields in which cereals were grown. Our aims were to identify the major sources of allergenic fungi and factors potentially influencing their occurrence. Plant materials were the main source of the tested fungi at and after harvest. Amounts of A. alternata and C. cladosporioides varied significantly in fields under different management conditions, but absolute levels were very high in all cases. This finding suggests that high numbers of allergenic fungi may be an inevitable side effect of farming in several crops. Applied in large-scale studies, the concept described here may help to explain the high number of sensitization to airborne fungal allergens.

Restricted diffusion of small probe particles in a laponite dispersion.

Evanescent wave microscopy is used to study the dynamics of probe particles inside a laponite suspension, when the size of the latex probes is of the order of the diameter of the laponite disks. A correlation procedure is introduced that allows us to study quantitatively the diffusion of small probes. For all studied sizes, the motion exhibits two modes: a fast relaxation mode and a slow relaxation mode. In the fast relaxation mode, the probes diffuse in a viscous medium, whose viscosity does not depend on the diameter of the probes and is slightly larger than the viscosity of water. Then, the diffusion of the particles is restricted over distances larger than their diameters, which increase when the particle diameter decreases. In this regime, the probe particles experience the elasticity of the solution and the apparent elastic modulus increases when the diameter of the probe particle increases, whereas for large enough particles, the macroscopic behavior is recovered, in which the diffusing particles experience a homogeneous medium, and the macroscopic elastic modulus is recovered.

Resonantly diode-pumped continuous-wave and Q-switched Er:YAG laser at 1645 nm.

We describe an efficient Er:YAG laser that is resonantly pumped using continuous-wave (CW) laser diodes at 1470 nm. For CW lasing, it emits 6.1 W at 1645 nm with a slope efficiency of 36%, the highest efficiency reported for an Er:YAG laser that is pumped in this manner. In Q-switched operation, the laser produces diffraction-limited pulses with an average power of 2.5 W at 2 kHz PRF. To our knowledge this is the first Q-switched Er:YAG laser resonantly pumped by CW laser diodes.

HIV-induced immune activation: pathogenesis and clinical relevance - summary of a workshop organized by the German AIDS Society (DAIG e.v.) and the ICH Hamburg, Hamburg, Germany, November 22, 2008.

This manuscript is communicated by the German AIDS Society (DAIG) (www.daignet.de). It summarizes a series of presentations and discussions during a workshop on immune activation due to HIV infection. The workshop was held on November 22nd 2008 in Hamburg, Germany. It was organized by the ICH Hamburg under the auspices of the German AIDS Society (DAIG e.V.).

Changes of diversity pattern of proteolytic bacteria over time and space in an agricultural soil.

The genetic heterogeneity of neutral metalloprotease (npr) gene fragments from soil proteolytic bacteria was investigated at a cultivated field site with four different soil types and at three different depths in April, July, and October. Terminal restriction fragment length polymorphism (T-RFLP) analyses of polymerase chain reaction-amplified npr gene fragments were applied to study the dynamic of the npr gene pool with regard to environmental conditions. The aim of this study was to relate differences in npr community structure and richness to the vertical, site, and seasonal variations naturally occurring at the field site under investigation. T-RFLP analysis revealed a noticeable seasonal variability in the community structure of npr-containing bacteria. The data suggest that the composition of the npr proteolytic bacterial population in July differed from those at the other dates. Additionally, the diversity of npr genes decreased with increasing soil depth revealing the highest values in upper layers. The reasons behind the observed patterns in the community structure might be mainly seasonal and vertical variation of the quantity and heterogeneity of available substrates as well as spatial isolation caused by a varying water amount and the connectivity of soil particles among the soil profile. Sequencing and phylogenetical analysis of 120 npr clones from the top soils collected in July revealed that most of the clones exhibit only poor homology to npr genes of isolates previously obtained from various environments, indicating the presence of until now uncharacterized npr coding proteolytic bacteria at the study site.

Feedback control of thermal lensing in a high optical power cavity.

This paper reports automatic compensation of strong thermal lensing in a suspended 80 m optical cavity with sapphire test mass mirrors. Variation of the transmitted beam spot size is used to obtain an error signal to control the heating power applied to the cylindrical surface of an intracavity compensation plate. The negative thermal lens created in the compensation plate compensates the positive thermal lens in the sapphire test mass, which was caused by the absorption of the high intracavity optical power. The results show that feedback control is feasible to compensate the strong thermal lensing expected to occur in advanced laser interferometric gravitational wave detectors. Compensation allows the cavity resonance to be maintained at the fundamental mode, but the long thermal time constant for thermal lensing control in fused silica could cause difficulties with the control of parametric instabilities.

Role of Nef in primate lentiviral immunopathogenesis.

More than a decade ago it was established that intact nef genes are critical for efficient viral persistence and greatly accelerate disease progression in SIVmac-infected rhesus macaques and in HIV-1-infected humans. Subsequent studies established a striking number of Nef functions that evidently contribute to the maintenance of high viral loads associated with the development of immunodeficiency in the 'evolutionary-recent' human and the experimental macaque hosts. Recent data show that many Nef activities are conserved across different lineages of HIV and SIV. However, some differences also exist. For example, Nef alleles from most SIVs that do not cause disease in their natural monkey hosts, but not those of HIV-1 and its simian precursors, down-modulate TCR-CD3 to suppress T cell activation and programmed death. This evolutionary loss of a specific Nef function may contribute to the high virulence of HIV-1 in humans.

[Identification of 1,2,4-trichlorobenzene-mineralizing bacteria and their function analysis].

Two strains, E3 and F2, capable to mineralize 1,2,4-trichlorobenzene (1,2,4-TCB) were isolated from a chlorinated benzenes contaminated soil using (14)C-1, 2,4-TCB as carbon source. They were identified by their 16S rDNA coding genes and fluoresence in situ hybridization (FISH) analysis as members of the genus Bordetella. A similarity of 100% were observed between strains E3 and F2 with their 16S rDNA sequences. They had the highest homology of 100% with Bordetella sp. QJ2-5 and the closest relation to described species, Bordetella petrii (GDH030510) with a similary of 99.4%. Strains E3 and F2 could degrade about 90% of 1,2,4-TCB and mineralize 58% and 46% of 1,2,4-TCB to CO2 within 30 days in mineral liquid cultures, respectively. Biomass was formed during the mineralization process.

Compensation of strong thermal lensing in high-optical-power cavities.

In an experiment to simulate the conditions in high optical power advanced gravitational wave detectors, we show for the first time that the time evolution of strong thermal lenses follows the predicted infinite sum of exponentials (approximated by a double exponential), and that such lenses can be compensated using an intracavity compensation plate heated on its cylindrical surface. We show that high finesse approximately 1400 can be achieved in cavities with internal compensation plates, and that mode matching can be maintained. The experiment achieves a wave front distortion similar to that expected for the input test mass substrate in the Advanced Laser Interferometer Gravitational Wave Observatory, and shows that thermal compensation schemes are viable. It is also shown that the measurements allow a direct measurement of substrate optical absorption in the test mass and the compensation plate.

Diagram of the aging dynamics in laponite suspensions at low ionic strength.

We measure the dynamic structure factor (DSF) of probe particles embedded in an aging laponite suspension quenched by cessation of shear and the associated relaxation time tau as a function of wave vector q and aging time t(w). The different q dependences measured in the successive exponential and full aging regimes, respectively, tau approximately q(-2) and tau approximately q(-1.25), yield a weak positive q dependence for the aging time t(wc) corresponding to the crossover between the two regimes. This implies that the full aging behavior is first seen when investigating large length scales in the aging suspension. We propose a qualitative diagram of the aging dynamics and discuss the features of the DSF of the probes and of the matrix in the two aging regimes. Consistently with the idea that the full aging regime is first observed when probing large length scales, t(wc) is markedly shorter when the motion of the probes is tracked instead of the collective fluctuations of concentration in the matrix. The exponential aging regime is most probably related to the liquid-glass transition induced by the cessation of shear rather than to the aging of a glass.

Successive exponential and full aging regimes evidenced by tracer diffusion in a colloidal glass.

We study the aging of a colloidal laponite glass by measuring the dynamic structure factor of dilute embedded tracer particles on micrometric length scales. We show that an initial aging regime, where the decay time grows exponentially with aging time t(w), tau approximately exp (gamma t(w)), is followed by a full aging regime, tau approximately t(v)(w) with v approximately 1. The dynamics of the tracers is diffusive in the exponential regime and hyperdiffusive in the full aging regime, up to micrometric length scales.

Characterization of bacterial community structure in rhizosphere soil of grain legumes.

Molecular techniques were used to characterize bacterial community structure, diversity (16S rDNA), and activity (16S rRNA) in rhizospheres of three grain legumes: faba beans (Vicia faba L., cv. Scirocco), peas (Pisum sativum L., cv. Duel) and white lupin (Lupinus albus L., cv. Amiga). All plants were grown in the same soil under controlled conditions in a greenhouse and sampled after fruiting. Amplified 16S rDNA and rRNA products (using universal bacterial primers) were resolved by denaturing gradient gel electrophoresis (DGGE). Distinct profiles were observed for the three legumes with most of the bands derived from RNA being a subset of those derived from DNA. Comparing the total bacterial profiles with actinomycete-specific ones (using actinomycete-specific primers) highlighted the dominance of this group in the three rhizospheres. 16S PCR and RT-PCR products were cloned to construct libraries and 100 clones from each library were sequenced. Actinomycetes and proteobacteria dominated the clone libraries with differences in the groups of proteobacteria. Absence of beta-subdivision members in pea and gamma-subdivision members of proteobacteria in faba bean rhizosphere was observed. Plant-dependent rhizosphere effects were evident from significant differences in the bacterial community structure of the legume rhizospheres under study. The study gives a detailed picture of both residing and "active" bacterial community in the three rhizospheres. The high abundance of actinomycetes in the rhizospheres of mature legumes indicates their possible role in soil enrichment after the legumes are plowed into the soil as biofertilizers.

Flocculation, deflocculation, and ions migration in latex suspensions.

We have studied the dynamics of the flocculation of poly(styrene-butadiene-acrylic acid) latex suspensions. These suspensions were flocculated by the addition of Ca2+ ions at high concentrations of latex particles. Using diffusing wave spectroscopy and dynamic single light scattering after dilution, we have observed--depending on the pH and on the Ca2+ concentration--several scenarios for flocculation including successive flocculation and deflocculation. This complex behavior reveals that the Ca2+ migration within the shell of the latex is slow in acidic solvent but fast in basic solvent.

[Malaria in the emergency room. Results of the emergency treatment of 137 patients with symptomatic malaria]. / Malaria in der Notaufnahme. Ergebnisse der Notfallbehandlung bei 137 Patienten mit symptomatischer Malaria.

OBJECTIVE: To assess characteristics and outcome of emergency patients with acute malaria. PATIENTS AND METHODS: We retrospectively assessed the clinical and laboratory parameters of 137 consecutive patients (87 males, 50 females; median age 37 years, range 17 - 67 years) presenting with acute malaria to our tertiary care center between 1992 and 2002. RESULTS: Falciparum malaria was diagnosed in 116/137 and tertian malaria in 19/137 patients; a single patient was infected with both parasites while in another case the type of parasite remained unclear. Infections were acquired in Africa (121), Asia , and in the Americas . One traveler visited multiple continents. Only 36 % (50/137) of patients had used malaria chemoprophylaxis. 128/137 patients were treated as in-patients; 22 of these had to be treated on an intensive care unit. According to the criteria of the German Society of Tropical Medicine, 44/137 (32 %; 95 % confidence interval (CI): 25 - 40 %) patients suffered from complicated malaria. The overall mortality rate was 2/137 (1.5 %; 95 % CI: 0,4 - 5.2 %); the mortality rate of complicated malaria tropica was 2/44 (4,5 %; 95 % CI 1,3 - 15 %). Patients with complicated malaria were significantly older than those with uncomplicated malaria. Median length of hospital stay was 4 days in uncomplicated and 9 days in complicated cases. Based on costs of EUR 2500 per case, an attack rate of > 3 % in East African travelers and a cost of EUR 55 for a chemoprophylaxis with mefloquine, chemoprophylaxis is cost-effective. CONCLUSION: In our retrospective analysis, complicated malaria tropica was associated with older age. Although malaria causes considerable morbidity, the overall mortality from severe malaria is low. Reinforcement of chemoprophylaxis especially in travelers to Africa could reduce malaria cases and is cost-effective.

The plant's capacity in regulating resource demand.

Regulation of resource allocation in plants is the key to integrate understanding of metabolism and resource flux across the whole plant. The challenge is to understand trade-offs as plants balance allocation between different and conflicting demands, e.g., for staying competitive with neighbours and ensuring defence against parasites. Related hypothesis evaluation can, however, produce equivocal results. Overcoming deficits in understanding underlying mechanisms is achieved through integrated experimentation and modelling the various spatio-temporal scaling levels, from genetic control and cell metabolism towards resource flux at the stand level. An integrated, interdisciplinary research concept on herbaceous and woody plants and its outcome to date are used, while drawing attention to currently available knowledge. This assessment is based on resource allocation as driven through plant-pathogen and plant-mycorrhizosphere interaction, as well as competition with neighbouring plants in stands, conceiving such biotic interactions as a "unity" in the control of allocation. Biotic interaction may diminish or foster effects of abiotic stress on allocation, as changes in allocation do not necessarily result from metabolic re-adjustment but may obey allometric rules during ontogeny. Focus is required on host-pathogen interaction under variable resource supply and disturbance, including effects of competition and mycorrhization. Cost/benefit relationships in balancing resource investments versus gains turned out to be fundamental in quantifying competitiveness when related to the space, which is subject to competitive resource exploitation. A space-related view of defence as a form of prevention of decline in competitiveness may promote conversion of resource turnover across the different kinds of biotic interaction, given their capacity in jointly controlling whole plant resource allocation.