Structure elecidation of mammalian TCDD-metabolites

Summary Thin layer and gas chromatographic examination of the bile of dogs which were given tritium-labelled TCDD revealed the presence of several polar biotransformation products. The structure of 5 phenolic metabolites was elecidated by combined gas chromatography-mass spectrometry. A metabolic breakdown scheme for TCDD in the dog is proposed.     

Similar pattern of fine structure in the basement lamella of the skin and the external sheath of the notochord inXenopus larvae

Zusammenfassung Auf Grund von elektronenmikroskopischen Beobachtungen wird nachgewiesen, dass die Basalmembran der Epidermis und die äussere Chordascheide im Schwanz vonXenopuslarven eine übereinstimmende Feinstruktur besitzen; sie ist gekennzeichnet durch orthogonal angeordnete Kollagenfibrillen.

---

---

Supported by the Swiss National Science Foundation for the Promotion of Scientific Research.     

Application de l'analyse discriminante à l'étude des différences anthropométriques selon les groupes sanguins du système ABO

Summary Anthropological measurements on 193 Swiss recruits have been studied using discriminatory analysis. Out of the 9 characters measured on each individual, 3 were chosen to ascertain whether differences between the ABO blood groups exist. Discriminatory analysis gives a simultaneous evaluation of the differences of the 3 measurements. They are found not to be significant.     

Nachweis der Selbst-Erregung der circadianen Periodizität bei Carabiden (Coleoptera Ins.)

Summary Most of the active individuals ofCarabus cancellatus (Coleoptera) investigated were synchronized by zeitgeber-lengths of 8/8 10/10 or 16/16 h. On the other hand, a smaller number of beetles lost the periodicities of these Zeitgebers and showed a circadian activity rhythm. According to these experiments, the existence of a self-sustained circadian oscillation in carabid beetles is demonstrated. As we believe, a special numerical method of computing the length of activity periodicities was used for the first time.     

Untersuchungen zur Neurosekretion beiAcheta domesticus L

Summary PAF-positive material, which is found in the brain and stomatogastric system of adultAcheta domesticus, can in addition be demonstrated in the Nervus corporis allati II. In the suboesophageal ganglion and the ventral nerve cord 3 different types of neurosecretory cells are described.     

Crystallographic studies on the activity of glycogen phosphorylase b

High resolution studies on the crystal structure of glycogen phosphorylase b have identified the catalytic site to which the substrate glucose-1-phosphate binds strongly with some local conformational changes. The site is situated 8 A (phosphate-to-phosphate distance) from pyridoxal phosphate, an essential cofactor of all glycogen phosphorylases. The catalytic site is 33 A from the site in the N-terminal portion of the molecule to which adenine nucleotides bind. In contrast to phosphorylase a (the active form of the enzyme which is phosphorylated at Ser 14), the positions of the first 19 residues of phosphorylase b are not well defined.     

Requirements for leukocyte transmigration via the transmembrane chemokine CX3CL1

The surface-expressed transmembrane CX3C chemokine ligand 1 (CX3CL1/fractalkine) induces firm adhesion of leukocytes expressing its receptor CX3CR1. After shedding by the disintegrins and metalloproteinases (ADAM) 10 and 17, CX3CL1 also acts as soluble leukocyte chemoattractant. Here, we demonstrate that transmembrane CX3CL1 expressed on both endothelial and epithelial cells induces leukocyte transmigration. To investigate the underlying mechanism, we generated CX3CR1 variants lacking the intracellular aspartate-arginine-tyrosine (DRY) motif or the intracellular C-terminus which led to a defect in intracellular calcium response and impaired ligand uptake, respectively. While both variants effectively mediated firm cell adhesion, they failed to induce transmigration and rather mediated retention of leukocytes on the CX3CL1-expressing cell layer. Targeting of ADAM10 led to increased adhesion but reduced transmigration in response to transmembrane CX3CL1, while transmigration towards soluble CX3CL1 was not affected. Thus, transmembrane CX3CL1 mediates leukocyte transmigration via the DRY motif and C-terminus of CX3CR1 and the activity of ADAM10.     

Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10

A disintegrin and metalloproteinase10 (ADAM10) has been implicated as a major sheddase responsible for the ectodomain shedding of a number of important surface molecules including the amyloid precursor protein and cadherins. Despite a well-documented role of ADAM10 in health and disease, little is known about the regulation of this protease. To address this issue we conducted a split-ubiquitin yeast two-hybrid screen to identify membrane proteins that interact with ADAM10. The yeast experiments and co-immunoprecipitation studies in mammalian cell lines revealed tetraspanin15 (TSPAN15) to specifically associate with ADAM10. Overexpression of TSPAN15 or RNAi-mediated knockdown of TSPAN15 led to significant changes in the maturation process and surface expression of ADAM10. Expression of an endoplasmic reticulum (ER) retention mutant of TSPAN15 demonstrated an interaction with ADAM10 already in the ER. Pulse-chase experiments confirmed that TSPAN15 accelerates the ER-exit of the ADAM10-TSPAN15 complex and stabilizes the active form of ADAM10 at the cell surface. Importantly, TSPAN15 also showed the ability to mediate the regulation of ADAM10 protease activity exemplified by an increased shedding of N-cadherin and the amyloid precursor protein. In conclusion, our data show that TSPAN15 is a central modulator of ADAM10-mediated ectodomain shedding. Therapeutic manipulation of its expression levels may be an additional approach to specifically regulate the activity of the amyloid precursor protein alpha-secretase ADAM10.