Synthesis of human amyloid restricted to liver results in an Alzheimer disease–like neurodegenerative phenotype

Several lines of study suggest that peripheral metabolism of amyloid beta (Aß) is associated with risk for Alzheimer disease (AD). In blood, greater than 90% of Aß is complexed as an apolipoprotein, raising the possibility of a lipoprotein-mediated axis for AD risk. In this study, we report that genetic modification of C57BL/6J mice engineered to synthesise human Aß only in liver (hepatocyte-specific human amyloid (HSHA) strain) has marked neurodegeneration concomitant with capillary dysfunction, parenchymal extravasation of lipoprotein-Aß, and neurovascular inflammation. Moreover, the HSHA mice showed impaired performance in the passive avoidance test, suggesting impairment in hippocampal-dependent learning. Transmission electron microscopy shows marked neurovascular disruption in HSHA mice. This study provides causal evidence of a lipoprotein-Aß /capillary axis for onset and progression of a neurodegenerative process.

It has been suggested that peripheral metabolism of amyloid-beta is associated with risk for Alzheimer’s disease. This study reveals that the expression of human amyloid exclusively in the liver induces Alzheimer’s disease-like pathologies in mice, potentially indicating a completely novel pathway of Alzheimer’s disease aetiology and therapies.     

A DEF/GLO-like MADS-box gene from a gymnosperm: Pinus radiata contains an ortholog of angiosperm B class floral homeotic genes.

The specification of floral organ identity during development depends on the function of a limited number of homeotic genes grouped into three classes: A, B, and C. Pairs of paralogous B class genes, such as DEF and GLO in Antirrhinum, and AP3 and PI in Arabidopsis, are required for establishing petal and stamen identity. To gain a better understanding of the evolutionary origin of petals and stamens, we have looked for orthologs of B class genes in conifers. Here we report cDNA cloning of PrDGL (Pinus radiata DEF/GLO-like gene) from radiata pine. We provide phylogenetic evidence that PrDGL is closely related to both DEF- and GLO-like genes of angiosperms, and is thus among the first putative orthologs of floral homeotic B function genes ever reported from a gymnosperm. Expression of PrDGL is restricted to the pollen strobili (male cones) and was not detected in female cones. PrDGL expression was first detected in emergent male cone primordia and persisted through the early stages of pollen cone bud differentiation. Based on the results of our phylogeny reconstructions and expression studies, we suggest that PrDGL could play a role in distinguishing between male (where expression is on) and female reproductive structures (where expression is off) in radiata pine. We speculate that this could be the general function of DEF/GLO-like genes in gymnosperms that may have been recruited for the distinction between stamens and carpels, the male and female reproductive organs of flowering plants, during the evolution of angiosperms out of gymnosperm-like ancestors.     

Bactericidal Efficacy of Oxidized Silver against Biofilms Formed by Curtobacterium flaccumfaciens pv. flaccumfaciens

Bacterial wilt is a re-emerging disease on dry bean and can affect many other crop species within the Fabaceae. The causal agent, Curtobacterium flaccumfaciens pv. flaccumfaciens (CFF), is a small, Gram-positive, rod-shaped bacterium that is seed-transmitted. Infections in the host become systemic, leading to wilting and economic loss. Clean seed programs and bactericidal seed treatments are two critical management tools. This study characterizes the efficacies of five bactericidal chemicals against CFF. It was hypothesized that this bacterium was capable of forming biofilms, and that the cells within biofilms would be more tolerant to bactericidal treatments. The minimum biocide eradication concentration assay protocol was used to grow CFF biofilms, expose the biofilms to bactericides, and enumerate survivors compared to a non-treated control (water). Streptomycin and oxysilver bisulfate had EC₉₅ values at the lowest concentrations and are likely the best candidates for seed treatment products for controlling seed-borne bacterial wilt of bean. The results showed that CFF formed biofilms during at least two phases of the bacterial wilt disease cycle, and the biofilms were much more difficult to eradicate than their planktonic counterparts. Overall, biofilm formation by CFF is an important part of the bacterial wilt disease cycle in dry edible bean and antibiofilm bactericides such as streptomycin and oxysilver bisulfate may be best suited for use in disease management.     

Does a homogeneous population of elementary movement detectors activate the landing response of blowflies,Calliphora erythrocephala?

The landing response of tethered flying blowflies, Calliphora erythrocephala, was elicited by moving periodic gratings, and by stripes moving apart. The influence of binocular interactions on the landing response was investigated by comparing the responses of intact (“binocular”) animals to the response of flies which had one eye covered with black paint (“monocular” flies) effectively eliminating the input from this eye. Directions of motion eliciting a maximal response (preference direction) were determined in intact animals, and in “molecular” flies for different regions of the visual field. Preference directions determined in “monocular” flies follow the orientation of Z-axes (Fig. 4). Preference directions determined in intact animals and in “monocular” flies differ in the binocular eye region: in intact animals, the preference directions corresponds to vertical directions of motion; whereas the preference direction determined for the same area in “monocular” flies are inclined obliquely against the vertical plane. Sex-specific differences were found for the ventral binocular eye region in which the shift of preference directions is more pronounced in male than in female flies. The experimental data support the hypothesis that elementary movement detectors are aligned along the Z-axes of the eye, and that preference directions deviating from the orientation of elementary movement detectors are caused by binocular interactions.     

Genetically Modified Ruminal Bacteria Protect Sheep from Fluoroacetate Poisoning

Four strains of Butyrivibrio fibrisolvens, transformed with a gene encoding fluoroacetate dehalogenase, maintained a combined population of 10⁶ to 10⁷ cells ml⁻¹ in the rumens of test sheep. Five inoculated sheep showed markedly reduced toxicological symptoms after fluoroacetate poisoning when behavioral, physiological, and histological effects were compared with those of five uninoculated control sheep.     

Die Dauer der Dunkeladaptation beim Fliegenauge nach Belichtung mit heterochromatischen Blitzen

Zusammenfassung Versuche mit heterochromatischen Lichtblitzen von 2 msec Dauer zeigen, daß die Dauer der Dunkeladaptation beim Calliphora-ERG von der Reihenfolge der Farbblitze abhängt. Versuche mit 2 diskreten Blitzabständen von 40 msec und 2 sec ergaben unterschiedliche Wirkungsspektren. Bei 40 msec Blitzabstand wirkt UV-Strahlung verlängernd auf die Adaptationszeit, bei 2 sec Abstand verkürzend. Die aufgenommenen Wirkungsspektren sprechen für das Auftreten eines kurzlebigen, bei 490 nm absorbierenden Intermediärfarbstoffes während der Potentialbildung und für das Auftreten eines stark im UV-Bereich absorbierenden Folgefarbstoffes sofort nach der Potentialbildung.

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Dark-adaptation after heterochromatic flash-illumination in the compound eye of the blow-fly

Summary The time course of dark adaptation (increase in amplitude of the electroretinogram) in the fly Calliphora was tested by light flashes (2 msec) of various wavelengths. The results showed that the time course depends on the wavelength of the test flashes, and on the interval between them. Using white test light the time for completion of dark adaptation increases with the interval between flashes, up to an interval of 20 sec. With longer intervals dark adaptation proceeds slightly faster. In contrast, using ultra-violet (UV) test light, a short (40 msec) interval increases the duration of the dark adaptation, and a longer (2 sec) interval reduces the duration. The results suggest that an intermediate photopigment is formed during the generation of the receptor potential. The pigment, which absorbs maximally at 490 nm, exists for a short period only. Immediately after the receptor potential is set up, an UV absorbing secondary pigment is formed.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft, SFB Bionach.     

Small molecule control of pre-mRNA splicing

SR proteins regulate alternative splicing by binding to exonic sequences where, via an arginine/serine-rich splicing activation domain, they enhance the binding of the spliceosome to the adjacent splice sites. Here, a system is described in which a nontoxic derivative of the small molecule rapamycin is used to control pre-mRNA splicing in vitro. This involves the rapamycin-dependent recruitment of a splicing activation domain located on one protein to a second protein bound to the pre-mRNA. These results provide a new approach to explore for regulating gene expression in vivo with small molecules by controlling pre-mRNA splicing.     

Mutually exclusive splicing of the insect Dscam pre-mRNA directed by competing intronic RNA secondary structures

Drosophila Dscam encodes 38,016 distinct axon guidance receptors through the mutually exclusive alternative splicing of 95 variable exons. Importantly, known mechanisms that ensure the mutually exclusive splicing of pairs of exons cannot explain this phenomenon in Dscam. I have identified two classes of conserved elements in the Dscam exon 6 cluster, which contains 48 alternative exons--the docking site, located in the intron downstream of constitutive exon 5, and the selector sequences, which are located upstream of each exon 6 variant. Strikingly, each selector sequence is complementary to a portion of the docking site, and this pairing juxtaposes one, and only one, alternative exon to the upstream constitutive exon. The mutually exclusive nature of the docking site:selector sequence interactions suggests that the formation of these competing RNA structures is a central component of the mechanism guaranteeing that only one exon 6 variant is included in each Dscam mRNA.