Optically powered fiber networks.

Optically powered networks are demonstrated. Heterogeneous subscribers having widely varying needs with respect to power and band-width can be effectively controlled and optically supplied by a central of-fice. The success of the scheme relies both on power-efficient innovative hardware and on a novel low-energy medium access control protocol. We demonstrate a sensor network with subscribers consuming less than 1 microW average power, and an optically powered high-speed video link transmitting data at a bitrate of 100 Mbit/s.

Recognition of peroxisomal targeting signal type 1 by the import receptor Pex5p.

We have studied how Pex5p recognizes peroxisomal targeting signal type 1 (PTS1)-containing proteins. A randomly mutagenized pex5 library was screened in a two-hybrid setup for mutations that disrupted the interaction with the PTS1 protein Mdh3p or for suppressor mutations that could restore the interaction with Mdh3p containing a mutation in its PTS1. All mutations localized in the tetratricopeptide repeat (TPR) domain of Pex5p. The Pex5p TPR domain was modeled based on the crystal structure of a related TPR protein. Mapping of the mutations on this structural model revealed that some of the loss-of-interaction mutations consisted of substitutions in alpha-helices of TPRs with bulky amino acids, probably resulting in local misfolding and thereby indirectly preventing binding of PTS1 proteins. The other loss-of-interaction mutations and most suppressor mutations localized in short, exposed, intra-repeat loops of TPR2, TPR3, and TPR6, which are predicted to mediate direct interaction with PTS1 amino acids. Additional site-directed mutants at conserved positions in intra-repeat loops underscored the importance of the loops of TPR2 and TPR3 for PTS1 interaction. Based on the mutational analysis and the structural model, we put forward a model as to how PTS1 proteins are selected by Pex5p.

The peroxisomal membrane protein Pex13p shows a novel mode of SH3 interaction.

Src homology 3 (SH3) domains are small non-catalytic protein modules capable of mediating protein-protein interactions by binding to proline-X-X-proline (P-X-X-P) motifs. Here we demonstrate that the SH3 domain of the integral peroxisomal membrane protein Pex13p is able to bind two proteins, one of which, Pex5p, represents a novel non-P-X-X-P ligand. Using alanine scanning, two-hybrid and in vitro interaction analysis, we show that an alpha-helical element in Pex5p is necessary and sufficient for SH3 interaction. Sup pressor analysis using Pex5p mutants located in this alpha-helical element allowed the identification of a unique site of interaction for Pex5p on the Pex13p-SH3 domain that is distinct from the classical P-X-X-P binding pocket. On the basis of a structural model of the Pex13p-SH3 domain we show that this interaction probably takes place between the RT- and distal loops. Thus, the Pex13p-SH3-Pex5p interaction establishes a novel mode of SH3 interaction.

Saccharomyces cerevisiae PTS1 receptor Pex5p interacts with the SH3 domain of the peroxisomal membrane protein Pex13p in an unconventional, non-PXXP-related manner.

A number of peroxisome-associated proteins have been described that are involved in the import of proteins into peroxisomes, among which is the receptor for peroxisomal targeting signal 1 (PTS1) proteins Pex5p, the integral membrane protein Pex13p, which contains an Src homology 3 (SH3) domain, and the peripheral membrane protein Pex14p. In the yeast Saccharomyces cerevisiae, both Pex5p and Pex14p are able to bind Pex13p via its SH3 domain. Pex14p contains the classical SH3 binding motif PXXP, whereas this sequence is absent in Pex5p. Mutation of the conserved tryptophan in the PXXP binding pocket of Pex13-SH3 abolished interaction with Pex14p, but did not affect interaction with Pex5p, suggesting that Pex14p is the classical SH3 domain ligand and that Pex5p binds the SH3 domain in an alternative way. To identify the SH3 binding site in Pex5p, we screened a randomly mutagenized PEX5 library for loss of interaction with Pex13-SH3. Such mutations were all located in a small region in the N-terminal half of Pex5p. One of the altered residues (F208) was part of the sequence W(204)XXQF(208), that is conserved between Pex5 proteins of different species. Site-directed mutagenesis of Trp204 confirmed the essential role of this motif in recognition of the SH3 domain. The Pex5p mutants could only partially restore PTS1-protein import in pex5Delta cells in vivo. In vitro binding studies showed that these Pex5p mutants failed to interact with Pex13-SH3 in the absence of Pex14p, but regained their ability to bind in the presence of Pex14p, suggesting the formation of a heterotrimeric complex consisting of Pex5p, Pex14p, and Pex13-SH3. In vivo, these Pex5p mutants, like wild-type Pex5p, were still found to be associated with peroxisomes. Taken together, this indicates that in the absence of Pex13-SH3 interaction, other protein(s) is able to bind Pex5p at the peroxisome; Pex14p is a likely candidate for this function.

Rab4 and Rab7 define distinct nonoverlapping endosomal compartments.

Several Rab GTPases have been localized to distinct compartments of the endocytic pathway. Rab4 is associated with early endosomes and recycling vesicles and regulates membrane recycling from early endosomes. Rab7 is localized to late endosomes and is involved in the regulation of membrane transport between late endosomes and lysosomes. Although Rab4 and Rab7 appear to regulate distinct transport events in endocytosis, it is not clear whether they perform their activities in related or entirely distinct intracellular compartments. To address this question, we generated stable cell lines expressing Rab4 tagged with a novel X31 influenza hemagglutinin (NH) epitope tag. These antibodies are characterized in this paper and were used to immunoisolate endocytic vesicles with cytoplasmically exposed NHRab4. Immunoisolated membranes contain internalized 125I-transferrin, but are devoid of Rab7. Confocal immunofluorescence microscopy showed that the early endosomal GTPases Rab4 and Rab5 both do not codistribute with Rab7 within the same cell. These observations suggest that each of the three Rab GTPases operationally defines a distinct station of the endocytic pathway.

[Loss of neurons in the granular layer of the cerebellum in epilepsy]. / Zellverluste im Stratum granulosum cerebelli bei Epilepsie.

Morphometric examination of the neurons in the cerebellar granular layer in epilepsy showed a significant mean decrease in their number. There is no correlation between this reduction and the duration of epilepsy or frequency of seizures, respectively. The pattern of lesions reach from slight patchy cell loss to severe diffuse reduction of neurons. The diameters of the granular neuronal nuclei showed a great variability. There is no correlation between age and the distribution of these diameters.

[Liver rupture after prolonged use of contraceptive]. / Leberruptur nach mehrjähriger hormonaler Kontrazeption.

Since several years benign liver tumours have been observed as complication of a long-term intake of hormonal contraceptives. Apart from a clinical unconspicuousness uncharacteristic complaints of the epigastrium up to the picture of the acute abdomen due to rupture of the tumour rich in vessels may be appear. A preoperative diagnosis is only rarely successful, and only the laparotomy brings the final diagnostic clarification.

[Benign hepatomata while taking oral contraceptives (author's transl)]. / Gutartige Lebertumoren bei Einnahme von hormonellen Antikonzeptiva.

In recent years an increase in benign hepatomata during administration of oral contraceptives has been reported many times. A case is reported here of a 38-year-old woman who took such contraceptives for 8 years. The cardinal symptom was a tumor in the right upper quadrant of the abdomen. Laparotomy revealed several nodules in both lobes of the liver which could be almost completely removed by a wedge-shaped incision. Histologically a multicentric, focal nodular hyperplasia was present. Follow-up examinations after 24 months show no enlargement of the remaining tumor residues.

[Effects of striatum stimulation and micro-iontophoretically applied dopamine and acetylcholine on the neuronal activity of the globus pallidus]. / Der Einfluss von Striatumreizung und mikroiontophoretisch appliziertem Dopamin und Azetylcholin auf die neuronale Aktivität im Globus pallidus.

Alert, myorelaxed rats were used to study the influence of electrical stimulation of the stiatum and micro-iontophoretic application of dopamine and acetylcholine upon the discharge activity of neurons of the Globus pallidus. Out of 55 pallidal neurons, 25 responded to striatum stimulation with an initial inhibition and subsequent irritation, and 21 with an irritation-inhibition sequence. 40% of the neurons were dopamine-sensitive (23% irritation, 77% inhibition) and 38% choline-sensitive (63% inhibition, 37% irritation). 25% of the dopamine-sensitive neurons were at the same time choline-sensitive. There was no direct relation demonstrable between the effects of striatum stimulation and micro-iontophoretic application of acetylcholine or dopamine.

[Therapy with synthetic ACTH]. / Therapie mit synthetischem ACTH.

With the development of the fully-synthetic preparation (tetracosactide) the therapy with ACTH has again obtained importance. The application in internal medicine above all takes place in rheumatoid arthritis and in bronchial asthma. Advantages and disadvantages are described and the possibility of withdrawal of cortisone is especially emphasized.

[Total substitution of the esophagus after resection or as a temporary measure (author's transl)]. / Zum totalen Ersatz der Speiseröhre nach Resektion oder als Uberbrückung

In recent years, communications have been made repeatedly on methods for substitution of the esophagus after total extirpation or as a temporary measure. However, under the impression of disappointments and resignation, the statistical material has remained small and so far it has not been possible to develop a skilled standard procedure. On the other hand, a partial substitution of the lower third of the esophagus by stomach has become a much-practised and usually successful surgical procedure. Total resection of the esophagus with surgical transposition is a big intervention, especially when perfomred as a single operation. But it is our opinion that when the patient's condition is satisfactory in respect of the indication for operation, one should certainly be critical but on the whole less restrained.

[A method for the objective determination of tremors in the rat]. / Verfahren zur objektiven Tremorerfassung an der Ratte

Two methods for determining tremors in the rat, acceleration pick-up and electromyogram, including electronic evaluation by impluse rate and frequency are described technically, and the results obtained with either method are compared. Both methods allow quantitative analysis of the drug induced (arecoline) tremor. Electromyographically, the tremor effect can be recorded already after lower doses compared with the electro-mechanical method. Besides, the EMG can be employed on immobilized animals.