Mißbildungen bei Nachkommen von Besamungsbullen

Inhalt: Auf Grand fünfjähriger systematischer Registrierung der angeborenen Anomalien bei allen Rinderrassen des Landes Hessen wird festgestellt, daß unter den Nachkommen von Besamungsbullen prozentual nicht mehr mißgebildete Kälber auftreten als bei den Nachkommen von Bullen, die im Natursprung eingesetzt waren. Das breitgestreute Spektrum der Organdefekte umfaßt etwa 43 Mißbildungskategorien und Mißbildungssyndrome; das Zentralnervensystem ist mit ca. 25% am häufigsten beteiligt. Die Aufstellung von "Teratograrnnaen" der Nachkommengruppen ermöglicht die verhältnismäßig frühzeitige Testung von Jungbullen, die für den Einsatz in der KB vorgesehen sind. Da zwischen Nachkommenzahl (Einsatzdauer) der einzelnen Bullen und Mißbildungshäufigkeit bei ihren Nachkommen positive Beziehungen bestehen, bedeuten signifikante Abweichungen von diesen "Normalwerten" der Mißbildungsfrequenzen innerhalb der Nachkommengrößenklassen besondere genetische Situationen der Väter. Diese können in der Anlage für besondere pathologische Merkmale bestehen oder sich in zufallsbedingten embryonalen Entwicklungs-storungen mannigfacher Art als Folge einer individuellen Genomlabilität der Embryonen äußern .     

Amplification of ribosomal DNA of Anoplocephalidae: Anoplocephala perfoliata diagnosis by PCR as a possible alternative to coprological methods

The diagnosis of tapeworm infections in horses relies on copro-diagnostic methods, which are time-consuming and of limited sensitivity for determination of the exact prevalence. The development of serological tests has slightly improved the detection of tapeworm infections, but more sensitive methods are still required. A polymerase chain reaction (PCR)-based approach may constitute a valuable tool to improve tapeworm diagnosis. Nuclear ribosomal DNA (rDNA) is a useful target for species and/or strain markers. Partial 18S, the internal transcribed spacer 1 (ITS-1), the 5.8S, the internal transcribed spacer 2 (ITS-2), and partial 28S rDNA of the equine tapeworms Anoplocephala perfoliata and Anoplocephaloides mamillana were amplified and sequenced. The lengths and GC contents of the regions sequenced were 2087-2091bp and 49.35-49.69% for A. perfoliata, and 2110-2119bp and 49.15-49.32% for A. mamillana, respectively. Sequence alignment and comparison of both taxa showed 79.3-80.2% identity. The lowest identities were found in the ITS regions with 39.9-43.5% for the ITS-1 and 59.5-61.2% for the ITS-2. No matches of the ITS-2 of A. perfoliata and A. mamillana were found with other species by BLAST search. For this reason, ITS-2 sequences seemed appropriate as accurate species markers and A. perfoliata ITS-2 primers were developed. The ITS-2 PCR enabled the detection of genomic DNA as low as 0.5 pgs. First efforts on the practical application of the PCR-based approach were made. A 6-mg fragment of a tapeworm proglottid was detected in 0.5 and 1g of faeces.     

Hereditary early-onset Parkinson's disease caused by mutations in PINK1

Parkinson's disease (PD) is a neurodegenerative disorder characterized by degeneration of dopaminergic neurons in the substantia nigra. We previously mapped a locus for a rare familial form of PD to chromosome 1p36 (PARK6). Here we show that mutations in PINK1 (PTEN-induced kinase 1) are associated with PARK6. We have identified two homozygous mutations affecting the PINK1 kinase domain in three consanguineous PARK6 families: a truncating nonsense mutation and a missense mutation at a highly conserved amino acid. Cell culture studies suggest that PINK1 is mitochondrially located and may exert a protective effect on the cell that is abrogated by the mutations, resulting in increased susceptibility to cellular stress. These data provide a direct molecular link between mitochondria and the pathogenesis of PD.     

The structure of a mycobacterial outer-membrane channel

Mycobacteria have low-permeability outer membranes that render them resistant to most antibiotics. Hydrophilic nutrients can enter by way of transmembrane-channel proteins called porins. An x-ray analysis of the main porin from Mycobacterium smegmatis, MspA, revealed a homooctameric goblet-like conformation with a single central channel. This is the first structure of a mycobacterial outer-membrane protein. No structure-related protein was found in the Protein Data Bank. MspA contains two consecutive beta barrels with nonpolar outer surfaces that form a ribbon around the porin, which is too narrow to fit the thickness of the mycobacterial outer membrane in contemporary models.     

Oncogenic CARD11 mutations in human diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. In the least curable (ABC) subtype of DLBCL, survival of the malignant cells is dependent on constitutive activation of the nuclear factor-kappaB (NF-kappaB) signaling pathway. In normal B cells, antigen receptor-induced NF-kappaB activation requires CARD11, a cytoplasmic scaffolding protein. To determine whether CARD11 contributes to tumorigenesis, we sequenced the CARD11 gene in human DLBCL tumors. We detected missense mutations in 7 of 73 ABC DLBCL biopsies (9.6%), all within exons encoding the coiled-coil domain. Experimental introduction of CARD11 coiled-coil domain mutants into lymphoma cell lines resulted in constitutive NF-kappaB activation and enhanced NF-kappaB activity upon antigen receptor stimulation. These results demonstrate that CARD11 is a bona fide oncogenein DLBCL, providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy.     

Self-assembly of proteins into designed networks

A C4-symmetric tetrameric aldolase was used to produce a quadratic network consisting of the enzyme as a rigid four-way connector and stiff streptavidin rods as spacers. Each aldolase subunit was furnished with a His6 tag for oriented binding to a planar surface and two tethered biotins for binding streptavidin in an oriented manner. The networks were improved by starting with composite units and also by binding to nickel-nitrilotriacetic acid-lipid monolayers. The mesh was adjustable in 5-nanometer increments. The production of a net with switchable mesh was initiated with the use of a calcium ion-containing beta-helix spacer that denatured on calcium ion depletion.     

Efficient inhibition of the Alzheimer's disease beta-secretase by membrane targeting

beta-Secretase plays a critical role in beta-amyloid formation and thus provides a therapeutic target for Alzheimer's disease. Inhibitor design has usually focused on active-site binding, neglecting the subcellular localization of active enzyme. We have addressed this issue by synthesizing a membrane-anchored version of a beta-secretase transition-state inhibitor by linking it to a sterol moiety. Thus, we targeted the inhibitor to active beta-secretase found in endosomes and also reduced the dimensionality of the inhibitor, increasing its local membrane concentration. This inhibitor reduced enzyme activity much more efficiently than did the free inhibitor in cultured cells and in vivo. In addition to effectively targeting beta-secretase, this strategy could also be used in designing potent drugs against other membrane protein targets.     

Soils of the Main Ethiopian Rift Valley escarpment: A transect study

The mountainous environment of the Ethiopian highlands has a great variety of ecotopes and thus demands great flexibility in land management. Different climatic conditions and landscape positions induce different soil forming processes, leading to various soil types with specific risks and potentials. The present study portrays a soil sequence of the central section of the Main Ethiopian Rift Valley, from the footslopes of the eastern escarpment to the marginal volcano structures. Six profiles under natural vegetation are described for classification according to the USDA Soil Taxonomy and World Reference Base for Soil Resources classification systems, and special site characteristics are discussed. The Acacia savannah of the footslopes (1900 m a. s. l.) is characterized by Vertisols (Mazic Vertisols/Aridic Haplusterts), with often pronounced effects of seasonal waterlogging. All other soils are well-drained and reflect the general increase in rainfall with elevation and slope, causing a decline in topsoil pH and a change from cation-rich clay soils of the Podocarpus-dominated forest at 2300 m a. s. l. (Mollic Nitisols/Typic Palehumults) to strongly-leached Humic Umbrisols/Humic Dystrudepts of the Hagenia-dominated forest around 2600 m a. s. l. The highland savannah plain (2700 m a. s. l.) with a drier and cooler environment has typically Mollic Cambisols/Dystric Haplustepts, which are less leached and have a rather brownish colour. At 2900 m a. s. l., Niti-umbric Alisols/Andic Hapludalfs are found in the Hypericum forest at the midslopes of the marginal volcanoes receiving high rainfall, whereas soil development is at a more initial state in the Erica-dominated forest at 3200 m a. s. l. (Umbric Andosols/Alic Hapludands). Clay mineral composition is kaolinite-dominated for the upper five profiles, with a high proportion of poorly crystalline components in the upper savannah and the volcano upslopes. The lowermost profile probably has a polygenetic origin indicated by an abrupt change from a smectitic to a kaolinitic composition in the subsoil. Soil development on quite homogeneous bedrock appears essentially controlled by relief and climate, underlining the suitability of the region as a model area for in-depth gradient studies on ecosystem processes and land use.