Inhibition of APP trafficking by tau protein does not increase the generation of amyloid-beta peptides

Amyloid-beta, a peptide derived from the precursor protein APP, accumulates in the brain and contributes to the neuropathology of Alzheimer's disease. Increased generation of amyloid-beta might be caused by axonal transport inhibition, via increased dwell time of APP vesicles and thereby higher probability of APP cleavage by secretase enzymes residing on the same vesicles. We tested this hypothesis using a neuronal cell culture model of inhibited axonal transport and by imaging vesicular transport of fluorescently tagged APP and beta-secretase (BACE1). Microtubule-associated tau protein blocks vesicle traffic by inhibiting the access of motor proteins to the microtubule tracks. In neurons co-transfected with CFP-tau, APP-YFP traffic into distal neurites was strongly reduced. However, this did not increase amyloid-beta levels. In singly transfected axons, APP-YFP was transported in large tubules and vesicles moving very fast (on average 3 microm/s) and with high fluxes in the anterograde direction (on average 8.4 vesicles/min). By contrast, BACE1-CFP movement was in smaller tubules and vesicles that were almost 2x slower (on average 1.6 microm/s) with approximately 18x lower fluxes (on average 0.5 vesicles/min). Two-colour microscopy of co-transfected axons confirmed that the two proteins were sorted into distinct carriers. The results do not support the above hypothesis. Instead, they indicate that APP is transported on vesicles distinct from the secretase components and that amyloid-beta is not generated in transit when transport is blocked by tau.     

Top-down and bottom-up effects on the spatiotemporal dynamics of cereal aphids: testing scaling theory for local density

The relationship between density and area depends on local growth rates and the area-dependence of migration rates. These rates vary among taxa due to dispersal behaviour, plot productivity and natural enemy impact. Previous studies in aphids suggest that aphid densities are highest in patches of intermediate sizes, and lower in small and large patches. The suggested mechanism causing these patterns is that the dispersal behaviour in aphids creates a mixture of area- and perimeter-dependent migration rates. In this paper, we used these predictions to examine the additional consequences of nutrient availability and natural enemies on the density-area relationship. The derived predictions were compared to data from a system with three aphid species, a set of aphid parasitoids and generalist natural enemies, and at two levels of plant nutrient availability. We find that predictions from the model based only on dispersal and local growth agree with the temporal dynamics of density-area relationships for aphids in high nutrient patches. In patches with low nutrients, high parasitism rates appeared to cause a negative density-area relationship for aphids, thereby deviating from predictions driven by the aphids' dispersal behavior. Hence, the dispersal model with scale-dependent migration rates can provide a useful tool for understanding insect distribution in patch size gradients, but the relative importance of top-down effects can completely change with plot productivity.     

Differences between human and mouse embryonic stem cells

We compared gene expression profiles of mouse and human ES cells by immunocytochemistry, RT-PCR, and membrane-based focused cDNA array analysis. Several markers that in concert could distinguish undifferentiated ES cells from their differentiated progeny were identified. These included known markers such as SSEA antigens, OCT3/4, SOX-2, REX-1 and TERT, as well as additional markers such as UTF-1, TRF1, TRF2, connexin43, and connexin45, FGFR-4, ABCG-2, and Glut-1. A set of negative markers that confirm the absence of differentiation was also developed. These include genes characteristic of trophoectoderm, markers of germ layers, and of more specialized progenitor cells. While the expression of many of the markers was similar in mouse and human cells, significant differences were found in the expression of vimentin, beta-III tubulin, alpha-fetoprotein, eomesodermin, HEB, ARNT, and FoxD3 as well as in the expression of the LIF receptor complex LIFR/IL6ST (gp130). Profound differences in cell cycle regulation, control of apoptosis, and cytokine expression were uncovered using focused microarrays. The profile of gene expression observed in H1 cells was similar to that of two other human ES cell lines tested (line I-6 and clonal line-H9.2) and to feeder-free subclones of H1, H7, and H9, indicating that the observed differences between human and mouse ES cells were species-specific rather than arising from differences in culture conditions.     

Rootstock genotype and orchard replant position rather than soil fumigation or compost amendment determine tree growth and rhizosphere bacterial community composition in an apple replant soil

Apple replant disease (ARD) is a complex soilborne disease syndrome that often causes problems when renovating old orchard sites. Soil fumigants sometimes control ARD, but biological and cultural alternatives are needed. In this study the growth of two widely used clonal apple (Malus domestica) rootstocks (M7 and M26) were compared to three new rootstocks from the Cornell-Geneva series (CG16, CG30 and CG210 (a.k.a. CG6210)) in an orchard site with a history of ARD, in Ithaca, NY. Trees were planted in two distinguishable positions – the previous tree rows versus the old inter-row grass lanes. Additionally, we compared the effects of compost amendment and fumigation with dichloropropene plus chloropicrin on tree growth on each replant rootstock. Rhizosphere bacteria and actinobacteria were assessed using PCR-DGGE for the rootstocks M7, M26, CG30 and CG210. Tree growth on the rootstocks M7, M26 and CG16 was suppressed in the old tree rows relative to grass lanes, while trees on CG30 and CG210 rootstocks grew equally well in both positions. The species composition of rhizosphere bacteria and actinobacteria differed significantly between the planting positions and between the rootstocks M7 and M26 compared to CG30 and CG210. In contrast, the preplant compost or fumigation soil treatments had no effect on tree growth and little impact on rhizosphere bacterial community composition. Abbreviations: ARD – apple replant disease; DGGE – denaturing gradient gel electrophoresis; PCR – polymerase chain reaction.     

The multifunctional sensory complex in the antennae ofAllacma fusca (Insecta)

Summary The antennal-tip sensory complex inAllacma fusca (Collembola) was reconstructed from serial ultrathin sections. The complex contains 16 sensory cells which belong to three spatially separated subunits: (1) a sensory hair; (2) a cuticular protrusion, containing two highly-specialized dendritic outer segments from a single sensory cell encapsulated by an enveloping cell and a gland cell (Figs. 4 and 5); and (3) two sensory cells with partly lamellated, double dendritic outer segments located well away from the cuticular surface (Fig. 3). A phylogenetic evaluation reveals a mosaic of apparently primitive characters, and trends toward higher structural complexity as well as toward reduction (Table 1). There is support for a hypothesis that the receptors of the sensory hair are chemosensitive. The functional interpretation of the other components of the complex is problematic due to their unusual structural properties. The sensory cell beneath the cuticular protrusion is considered to be proprioceptive.Supported by the Deutsche Forschungsgemeinschaft (Al 56/6)     

Methanococcus thermolithotrophicus,a novel thermophilic lithotrophic methanogen

An autotrophic thermophilic motile coccoid methanogen was isolated from geothermally heated sea sediments close to Naples, Italy. Growth occurs on H₂/CO₂ and on formate between 30 and 70°C with an optimum at 65°C. The optimal doubling time is only 55 min. The NaCl-concentration ranges from 1.3% to 8.3% with an optimum around 4%. By its G+C-content of 31.3 mol%, its subunit envelope, and by DNA-RNA hybridization the new isolate is clearly defined to be a member of the genusMethanococcus. We name itMethanococcus thermolithotrophicus.Abbreviations G+C Guanine + Cytosine - SDS Sodium dodecylsulfate (Sodium lauryl sulfate)     

Benzothieno and benzofurano annelated estranes

The preparation of estrone derived benzothieno- and benzofurano fused steroids is described. Keystep is an intramolecular thienyl(/furyl)-ene-yne cyclization of 16-ethynyl-17-heterarylestra-1,3,5(10),16-tetraenes. The cyclization was carried out under Pt as well as under Ru catalysis.     

The alternatively folded state of the antibody C(H)3 domain

The C(H)3 domain of antibodies is characterized by two antiparallel beta-sheets forming a disulfide-linked sandwich-like structure. At acidic pH values and low ionic strength, C(H)3 becomes completely unfolded. The addition of salt transforms the acid-unfolded protein into an alternatively folded state exhibiting a characteristic secondary structure. The transition from native to alternatively folded C(H)3 is a fast reaction. Interestingly, this reaction involves the formation of a defined oligomer consisting of 12-14 subunits. Association is completely reversible and the native dimer is quantitatively reformed at neutral pH. This alternatively folded protein is remarkably stable against thermal and chemical denaturation and the unfolding transitions are highly cooperative. With a t(m) of 80 degrees C, the stability of the alternatively folded state is comparable to that of the native state of C(H)3. The defined oligomeric structure of C(H)3 at pH 2 seems to be a prerequisite for the cooperative unfolding transitions.