Aseptic meningitis in Germany associated with echovirus type 13

BACKGROUND: Echoviruses are the commonest cause of aseptic meningitis. Echovirus type 13 which has not been isolated in Germany over a long period of time was the predominant enterovirus serotype associated with different local outbreaks of aseptic meningitis in Germany in 2000. METHODS: Virus isolation was performed from cerebrospinal fluid and stools. In order to study the genetic relationship of echovirus type 13 isolates, sequence analysis of a part of VP1 (~300 nt) was carried out. Isolates from different geographic regions were compared to each other as well as to elder viruses (prototype strain from 1953, four isolates from 1965–1986). RESULTS: Overall, 55 isolates of echovirus type 13 were obtained from different parts of Germany. It was shown that the new isolated strains have a very high degree of homology on the nucleotide level (> 98%)) but differ significantly from the old strains (76–85%). CONCLUSIONS: a) Rare enterovirus serotypes can cause serious illness. b) The molecular drift has also been shown for other enterovirus serotypes

Regulation of the dystrophin-associated glycoprotein complex composition by the metabolic properties of muscle fibres

The dystrophin-glycoprotein complex (DGC) links the muscle cytoskeleton to the extracellular matrix and is responsible for force transduction and protects the muscle fibres from contraction induced damage. Mutations in components of the DGC are responsible for muscular dystrophies and congenital myopathies. Expression of DGC components have been shown to be altered in many myopathies. In contrast we have very little evidence of whether adaptive changes in muscle impact on DGC expression. In this study we investigated connection between muscle fibre phenotype and the DGC. Our study reveals that the levels of DGC proteins at the sarcolemma differ in highly glycolytic muscle compared to wild-type and that these changes can be normalised by the super-imposition of an oxidative metabolic programme. Importantly we show that the metabolic properties of the muscle do not impact on the total amount of DGC components at the protein level. Our work shows that the metabolic property of a muscle fibre is a key factor in regulating the expression of DGC proteins at the sarcolemma

Chromosome assignment of two cloned DNA probes hybridizing predominantly to human sex chromosomes

In situ hybridization experiments were carried out with two clones, YACG 35 and 2.8, which had been selected from two genomic libraries strongly enriched for the human Y chromosome. Besides the human Y chromosome, both sequences strongly hybridized to the human X chromosome, with few minor binding sites on autosomes. In particular, on the X chromosome DNA from clone YACG 35 hybridized to the centromeric region and the distal part of the short arm (Xp2.2). On the Y chromosome, the sequence was assigned to one site situated in the border region between Yq1.1 and Yq1.2. DNA from clone 2.8 also hybridized to the centromeric region of the X and the distal part of the short arm (Xq2.2). On the Y, however, two binding sites were observed (Yp1.1 and Yq1.2). The findings indicate that sex chromosomal sequences may be localized in homologous regions (as suggested from meiotic pairing) but also at ectopic sites

A novel method to analyze leukocyte rolling behavior in vivo

Leukocyte endothelial cell interaction is a fundamentally important process in many disease states. Current methods to analyze such interactions include the parallel-plate flow chamber and intravital microscopy. Here, we present an improvement of the traditional intravital microscopy that allows leukocyte-endothelial cell interaction to be studied from the time the leukocyte makes its initial contact with the endothelium until it adheres to or detaches from the endothelium. The leukocyte is tracked throughout the venular tree with the aid of a motorized stage and the rolling and adhesive behavior is measured off-line. Because this method can involve human error, methods to automate the tracking procedure have been developed. This novel tracking method allows for a more detailed examination of leukocyte-endothelial cell interactions

Is bicarbonate in Photosystem II the equivalent of the glutamate ligand to the iron atom in bacterial reaction centers?

Photosystem II of oxygen-evolving organisms exhibits a bicarbonate-reversible formate effect on electron transfer between the primary and secondary acceptor quinones, QA and QB. This effect is absent in the otherwise similar electron acceptor complex of purple bacteria, e.g. Rhodobacter sphaeroides. This distinction has led to the suggestion that the iron atom of the acceptor quinone complex in PS II might lack the fifth and sixth ligands provided in the bacterial reaction center (RC) by a glutamate residue at position 234 of the M-subunit in Rb. sphaeroides,RCs (M232 in Rps. viridis). By site-directed mutagenesis we have altered GluM234 in RCs from Rb. sphaeroides, replacing it with valine, glutamine and glycine to form mutants M234EV, M234EQ and M234EG, respectively. These mutants grew competently under phototrophic conditions and were tested for the formate-bicarbonate effect. In chromatophores there were no detectable differences between wild type (Wt) and mutant M234EV with respect to cytochrome b-561 reduction following a flash, and no effect of bicarbonate depletion (by incubation with formate). In isolated RCs, several electron transfer activities were essentially unchanged in Wt and M234EV, M234EQ and M234EG mutants, and no formate-bicarbonate effect was observed on: (a) the fast or slow phases of recovery of the oxidized primary donor (P+) in the absence of exogenous donor, i.e., the recombination of P+QA− or P+QB−, respectively; (b) the kinetics of electron transfer from QA− to QB; or (c) the flash dependent oscillations of semiquinone formation in the presence of donor to P+ (QB turnover). The absence of a formate-bicarbonate effect in these mutants suggests that GluM234 is not responsible for the absence of the formate-bicarbonate effect in Wt bacterial RCs, or at least that other factors must be taken into account. The mutant RCs were also examined for the fast primary electron transfer along the active (A-)branch of the pigment chain, leading to reduction of QA. The kinetics were resolved to reveal the reduction of the monomer bacteriochlorophyll (τ = 3.5 ps), followed by reduction of the bacteriopheophytin (τ = 0.9 ps). Both steps were essentially unaltered from the wild type. However, the rate of reduction of QA was slowed by a factor of 2 (τ = 410 ± 30 and 47 ± 30 ps for M234EQ and M234EV, respectively, compared to 220 ps in the wild type). EPR studies of the isolated RCs showed a characteristic g = 1.82 signal for the QA semiquinone coupled to the iron atom, which was indistinguishable from the wild type. It is concluded that GluM234 is not essential to the normal functioning of the acceptor quinone complex in bacterial RCs and that the role of bicarbonate in PS II is distinct from the role of this residue in bacterial RCs

ISOPHOT far-infrared serendipity sky survey

The ISOPHOT Serendipity Survey utilizes the slew time between ISO's pointed observations with strip scanning measurements of the sky in the far-IR at 170 micrometers . The slews contain information about two fundamentally different types of objects, namely unresolved galactic and extragalactic far-IR sources as well as extended regions of galactic cirrus emission. Since the structure of the obtained data is almost unique, the development of dedicated software to extract astrophysically interesting parameters for the crossed sources is mandatory. Data analysis is currently in its early stages and concentrates on the detection of point sources. First results from an investigation of a high galactic latitude field near the North Galactic Pole indicate that the detection completeness with respect to previously known IRAS sources will be almost 100 percent for sources with f(subscript 100micrometers > 2 Jy, dropping below approximately equals 50 percent for f(subscript 100micrometers < 1.5 Jy. Nevertheless, even faint sources down to a level of f(subscript 170micrometers approximately equals 1 Jy can be detected. Since the majority of the detected point sources are galaxies, the Serendipity Survey will result in a large database of approximately equals 2000 galaxies

First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors

Agonistic 4-1BB monoclonal antibodies were preclinically validated as promising cancer immunotherapies, both as monotherapy and as potentiators of the activity of PD-(L) 1–blocking agents. However, toxicity and a narrow therapeutic window have hampered their clinical development. DuoBodyPD-L1×4-1BB, a first-in-class, bispecific, next-generation checkpoint immunotherapy, was designed to overcome these limitations by activating T cells through conditional 4-1BB costimulation, while simultaneously blocking the PD-L1 axis. We present preliminary data from the ongoing, first-in-human, open-label, phase I/IIa trial of DuoBody-PD-L1×4-1BB in advanced solid tumors (NCT03917381)

The PANDA GEM-based TPC Prototype

We report on the development of a GEM-based TPC prototype for the PANDA experiment. The design and requirements of this device will be illustrated, with particular emphasis on the properties of the recently tested GEM-detector, the characterization of the read-out electronics and the development of the tracking software that allows to evaluate the GEM-TPC data.Comment: submitted to NIMA 4 pages, 6 picture

Quality management: reduction of waiting time and efficiency enhancement in an ENT-university outpatients' department

Background Public health systems are confronted with constantly rising costs. Furthermore, diagnostic as well as treatment services become more and more specialized. These are the reasons for an interdisciplinary project on the one hand aiming at simplification of planning and scheduling patient appointments, on the other hand at fulfilling all requirements of efficiency and treatment quality. Methods As to understanding procedure and problem solving activities, the responsible project group strictly proceeded with four methodical steps: actual state analysis, analysis of causes, correcting measures, and examination of effectiveness. Various methods of quality management, as for instance opinion polls, data collections, and several procedures of problem identification as well as of solution proposals were applied. All activities were realized according to the requirements of the clinic's ISO 9001:2000 certified quality management system. The development of this project is described step by step from planning phase to inauguration into the daily routine of the clinic and subsequent control of effectiveness. Results Five significant problem fields could be identified. After an analysis of causes the major remedial measures were: installation of a patient telephone hotline, standardization of appointment arrangements for all patients, modification of the appointments book considering the reason for coming in planning defined working periods for certain symptoms and treatments, improvement of telephonic counselling, and transition to flexible time planning by daily updates of the appointments book. After implementation of these changes into the clinic's routine success could be demonstrated by significantly reduced waiting times and resulting increased patient satisfaction. Conclusion Systematic scrutiny of the existing organizational structures of the outpatients' department of our clinic by means of actual state analysis and analysis of causes revealed the necessity of improvement. According to rules of quality management correcting measures and subsequent examination of effectiveness were performed. These changes resulted in higher satisfaction of patients, referring colleagues and clinic staff the like. Additionally the clinic is able to cope with an increasing demand for appointments in outpatients' departments, and the clinic's human resources are employed more effectively