Über DPNH-Diaphorase und alkalische Phosphatase bei Präimplantationsstadien des Goldhamsters (Mesocricetus auratus Waterh.)

Summary The activity of the DPNH-diaphorase and the alkaline phosphatase were examined in golden-hamster eggs prior to fixation. The reactions for DPNH-diaphorase as well as for alkaline phosphatase were found to be positive already in the undivided egg and in early cleavage stages. The reaction products of both enzyme determinations showed a histophotometrically measurable polar distribution in the cytoplasm, in the one-cell stage as well as in the individual blastomeres of the examined early cleavage stages.     

Über die Vermehrung der Polkörperchen während der Segmentation von Ratteneiern bei Vitamin-A-Mangel und -Überdosierung

Summary In the course of histochemical investigations on pre-implanted rat eggs it was found that eggs from animals with vitamin-A-deficiency or -overdosage show an increased number of polar bodies during the first 2 cleavages. Moreover, the polar bodies persist longer than normal.     

Zur Frage der Neubildung von Primordialfollikeln aus dem Keimepithel während der Geschlechtsreife im menschlichen Ovar

Summary Findings in the human ovary confirmed the fact already pointed out in animal ovaries that under the influence of oestrogens the germinal epithelium is capable of forming new oocytes. Whether the germinal epithelium of the mature woman can form new oocytes under normal conditions cannot be determined as yet, but the present findings allow the conclusion that neo-oogenesis during the reproductive period of women seems possible. Further investigations, now in progress, are required to determine this possibility.     

Zur Lokalisation der Östrogenproduktion in der menschlichen Plazenta

Summary The syncytial sprouts of the human placenta were found to give a distinctly stronger reaction for glucose-6-phosphat-dehydrogenase, DPNH-diaphorase and steroid-3--ol-dehydrogenase than other regions of the trophoblastic syncytium. Besides they show a more intensive basophilic reaction and higher contents of fat than other parts of the syncytium. Therefore the syncytial sprouts can be regarded as the areas of the trophoblastic syncytium that are specialized for estrogen production.

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Herrn Prof. Dr.K. Goerttler zu seinem 70. Geburtstag gewidmet. — Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Structural insight into function and regulation of carnitine palmitoyltransferase

The control of fatty acid translocation across the mitochondrial membrane is mediated by the carnitine palmitoyltransferase (CPT) system. Modulation of its functionality has simultaneous effects on fatty acid and glucose metabolism. This encourages use of the CPT system as drug target for reduction of gluconeogenesis and restoration of lipid homeostasis, which are beneficial in the treatment of type 2 diabetes mellitus and obesity. Recently, crystal structures of CPT-2 were determined in uninhibited forms and in complexes with inhibitory substrate-analogs with anti-diabetic properties in animal models and in clinical studies. The CPT-2 crystal structures have advanced understanding of CPT structure–function relationships and will facilitate discovery of novel inhibitors by structure-based drug design. However, a number of unresolved questions regarding the biochemistry and pharmacology of CPT enzymes remain and are addressed in this review.     

Molecular recognition of a single sphingolipid species by a protein's transmembrane domain

Functioning and processing of membrane proteins critically depend on the way their transmembrane segments are embedded in the membrane. Sphingolipids are structural components of membranes and can also act as intracellular second messengers. Not much is known of sphingolipids binding to transmembrane domains (TMDs) of proteins within the hydrophobic bilayer, and how this could affect protein function. Here we show a direct and highly specific interaction of exclusively one sphingomyelin species, SM 18, with the TMD of the COPI machinery protein p24 (ref. 2). Strikingly, the interaction depends on both the headgroup and the backbone of the sphingolipid, and on a signature sequence (VXXTLXXIY) within the TMD. Molecular dynamics simulations show a close interaction of SM 18 with the TMD. We suggest a role of SM 18 in regulating the equilibrium between an inactive monomeric and an active oligomeric state of the p24 protein, which in turn regulates COPI-dependent transport. Bioinformatic analyses predict that the signature sequence represents a conserved sphingolipid-binding cavity in a variety of mammalian membrane proteins. Thus, in addition to a function as second messengers, sphingolipids can act as cofactors to regulate the function of transmembrane proteins. Our discovery of an unprecedented specificity of interaction of a TMD with an individual sphingolipid species adds to our understanding of why biological membranes are assembled from such a large variety of different lipids.     

Strukturelle und funktionelle Veränderungen am menschlichen Ovar unter Einwirkung hormonaler Antikonzeptiva

Summary In two cases, a fresh corpus luteum was found during treatment with hormonal anticonceptiva (Lyndiol 2.5^®). The decreased excretion of all oestrogen fractions can be explained by the lack of proliferation of the theca interna. The striking proliferation of the follicle epithelium after the completed ovulation is as yet an unexplained phenomenon. The possible endocrine actions of such steroid combinations upon the pituitary are discussed. Further investigations are in progress.     

Determinants of woody cover in African savannas

Savannas are globally important ecosystems of great significance to human economies. In these biomes, which are characterized by the co-dominance of trees and grasses, woody cover is a chief determinant of ecosystem properties. The availability of resources (water, nutrients) and disturbance regimes (fire, herbivory) are thought to be important in regulating woody cover, but perceptions differ on which of these are the primary drivers of savanna structure. Here we show, using data from 854 sites across Africa, that maximum woody cover in savannas receiving a mean annual precipitation (MAP) of less than approximately 650 mm is constrained by, and increases linearly with, MAP. These arid and semi-arid savannas may be considered 'stable' systems in which water constrains woody cover and permits grasses to coexist, while fire, herbivory and soil properties interact to reduce woody cover below the MAP-controlled upper bound. Above a MAP of approximately 650 mm, savannas are 'unstable' systems in which MAP is sufficient for woody canopy closure, and disturbances (fire, herbivory) are required for the coexistence of trees and grass. These results provide insights into the nature of African savannas and suggest that future changes in precipitation may considerably affect their distribution and dynamics.     

Mutations in the endosomal ESCRTIII-complex subunit CHMP2B in frontotemporal dementia

We have previously reported a large Danish pedigree with autosomal dominant frontotemporal dementia (FTD) linked to chromosome 3 (FTD3). Here we identify a mutation in CHMP2B, encoding a component of the endosomal ESCRTIII complex, and show that it results in aberrant mRNA splicing in tissue samples from affected members of this family. We also describe an additional missense mutation in an unrelated individual with FTD. Aberration in the endosomal ESCRTIII complex may result in FTD and neurodegenerative disease.