A new class of long-acting hormonal steroid preparation: synthesis of dimeric androgens coupled at C3-C3 and C-17-C3 and of an androgen-progestogen combination

3β-Hydroxy-4-androsten-17-one was prepared from 4-androsten-3, 17-dione according to the method of Klimstra and Colton (1) and dimerized by means of esterification with succinic acid. The reduction with lithium-tri-t-butoxyaluminium hydride gave a testosterone derivative coupled between C₃-C₃ which showed after a single Injection of 10 mg a protracted but relatively weak androgenic effect in castrated male rats. The direct esterification of testosterone hemisuccinate with 4-androsten-3β,17β-diol gave the testosterone derivative coupled between C₁₇-C₃ which showed a more even and more protracted time response curve than testosterone enanthate. The testosterone-ethynodiol succinate also coupled between C₁₇-C₃, showed an androgenic depot-effect similar to that of the dimeric C₁₇-C₃ testosterone derivative.     

Comparative genomic analyses in Asparagus.

Garden asparagus (Asparagus officinalis L.) belongs to the monocot family Asparagaceae in the order Asparagales. Onion (Allium cepa L.) and Asparagus officinalis are 2 of the most economically important plants of the core Asparagales, a well supported monophyletic group within the Asparagales. Coding regions in onion have lower GC contents than the grasses. We compared the GC content of 3374 unique expressed sequence tags (ESTs) from A. officinalis with Lycoris longituba and onion (both members of the core Asparagales), Acorus americanus (sister to all other monocots), the grasses, and Arabidopsis. Although ESTs in A. officinalis and Acorus had a higher average GC content than Arabidopsis, Lycoris, and onion, all were clearly lower than the grasses. The Asparagaceae have the smallest nuclear genomes among all plants in the core Asparagales, which typically have huge genomes. Within the Asparagaceae, European Asparagus species have approximately twice the nuclear DNA of that of southern African Asparagus species. We cloned and sequenced 20 genomic amplicons from European A. officinalis and the southern African species Asparagus plumosus and observed no clear evidence for a recent genome doubling in A. officinalis relative to A. plumosus. These results indicate that members of the genus Asparagus with smaller genomes may be useful genomic models for plants in the core Asparagales.     

Die Zellelemente in der Leibeshöhlenflüssigkeit des Seeigels Psammechinus miliaris (Gmel.) und ihr bewegungsphysiologisches Verhalten

Ohne Zusammenfassung     

Protease-catalysed coupling of N-protected amino acids and peptides with 4-aminoantipyrine

The enzymatic synthesis of N-protected l-aminoacyl- and l-peptidyl-antipyrine amides was accomplished by proteases from different classes. Serine and cysteine proteases proved to be suitable tools for the production of amino acids and peptides conjugated to 4-aminoantipyrine, whereas metalloproteases do not seem to be very qualified for accepting this nucleophile. The product yields were optimised by applying ample opportunities of medium engineering, e.g. aqueous-organic, biphasic, suspension and solid-to-solid reaction systems. Thus, yields up to 100% could be obtained. The products were purified and characterised by polarimetry and NMR spectroscopy. These results broaden the common knowledge of the catalytic potential of proteases, in particular with regard to the suitability of a special heterocyclic 1,2-amino ketone as a nucleophile for the biocatalytic amidation of amino acids and peptides.     

Regional stiffening of the mitral valve anterior leaflet in the beating ovine heart

Left atrial muscle extends into the proximal third of the mitral valve (MV) anterior leaflet and transient tensing of this muscle has been proposed as a mechanism aiding valve closure. If such tensing occurs, regional stiffness in the proximal anterior mitral leaflet will be greater during isovolumic contraction (IVC) than isovolumic relaxation (IVR) and this regional stiffness difference will be selectively abolished by β-receptor blockade. We tested this hypothesis in the beating ovine heart. Radiopaque markers were sewn around the MV annulus and on the anterior MV leaflet in 10 sheep hearts. Four-dimensional marker coordinates were obtained from biplane videofluoroscopy before (CRTL) and after administration of esmolol (ESML). Heterogeneous finite element models of each anterior leaflet were developed using marker coordinates over matched pressures during IVC and IVR for CRTL and ESML. Leaflet displacements were simulated using measured left ventricular and atrial pressures and a response function was computed as the difference between simulated and measured displacements. Circumferential and radial elastic moduli for ANNULAR, BELLY and EDGE leaflet regions were iteratively varied until the response function reached a minimum. The stiffness values at this minimum were interpreted as the in vivo regional material properties of the anterior leaflet. For all regions and all CTRL beats IVC stiffness was 40–58% greater than IVR stiffness. ESML reduced ANNULAR IVC stiffness to ANNULAR IVR stiffness values. These results strongly implicate transient tensing of leaflet atrial muscle during IVC as the basis of the ANNULAR IVC–IVR stiffness difference.     

Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family

Background

Protein translocation across the membrane of the Endoplasmic Reticulum (ER) is the first step in the biogenesis of secretory and membrane proteins. Proteins enter the ER by the Sec61 translocon, a proteinaceous channel composed of three subunits, α, β and γ. While it is known that Sec61α forms the actual channel, the function of the other two subunits remains to be characterized.

Results

In the present study we have investigated the function of Sec61β in Drosophila melanogaster. We describe its role in the plasma membrane traffic of Gurken, the ligand for the Epidermal Growth Factor (EGF) receptor in the oocyte. Germline clones of the mutant allele of Sec61β show normal translocation of Gurken into the ER and transport to the Golgi complex, but further traffic to the plasma membrane is impeded. The defect in plasma membrane traffic due to absence of Sec61β is specific for Gurken and is not due to a general trafficking defect.

Conclusion

Based on our study we conclude that Sec61β, which is part of the ER protein translocation channel affects a post-ER step during Gurken trafficking to the plasma membrane. We propose an additional role of Sec61β beyond protein translocation into the ER.