Dissection of the amyloid formation pathway in AL amyloidosis

In antibody light chain (AL) amyloidosis, overproduced light chain (LC) fragments accumulate as fibrils in organs and tissues of patients. In vitro, AL fibril formation is a slow process, characterized by a pronounced lag phase. The events occurring during this lag phase are largely unknown. We have dissected the lag phase of a patient-derived LC truncation and identified structural transitions that precede fibril formation. The process starts with partial unfolding of the V-L domain and the formation of small amounts of dimers. This is a prerequisite for the formation of an ensemble of oligomers, which are the precursors of fibrils. During oligomerization, the hydrophobic core of the LC domain rearranges which leads to changes in solvent accessibility and rigidity. Structural transitions from an anti-parallel to a parallel beta-sheet secondary structure occur in the oligomers prior to amyloid formation. Together, our results reveal a rate-limiting multi-step mechanism of structural transitions prior to fibril formation in AL amyloidosis, which offers, in the long run, opportunities for therapeutic intervention. AL amyloidosis is caused by the accumulation of overproduced light chain (LC) fragments as fibrils in patient organs and it is the most prevalent systemic amyloidosis. Here, the authors combine biochemical and biophysical experiments to characterise the lag phase of a patient-derived truncated LC and they identify structural transitions that precede fibril formation

Full spin switch effect for the superconducting current in a superconductor/ferromagnet thin film heterostructure

Superconductor/ferromagnet (S/F) proximity effect theory predicts that the superconducting critical temperature of the F1/F2/S or F1/S/F2 trilayers for the parallel orientation of the F1 and F2 magnetizations is smaller than for the antiparallel one. This suggests a possibility of a controlled switching between the superconducting and normal states in the S layer. Here, using the spin switch design F1/F2/S theoretically proposed by Oh et al. [Appl. Phys. Lett. 71, 2376 (1997)], that comprises a ferromagnetic bilayer separated by a non-magnetic metallic spacer layer as a ferromagnetic component, and an ordinary superconductor as the second interface component, we have successfully realized a full spin switch effect for the superconducting current.Comment: 5 pages, 4 figure

The relative abundance of wheat Rubisco activase isoforms is post‑transcriptionally regulated

Diurnal rhythms and light availability affect transcription–translation feedback loops that regulate the synthesis of photosynthetic proteins. The CO2-fixing enzyme Rubisco is the most abundant protein in the leaves of major crop species and its activity depends on interaction with the molecular chaperone Rubisco activase (Rca). In Triticum aestivum L. (wheat), three Rca isoforms are present that differ in their regulatory properties. Here, we tested the hypothesis that the relative abundance of the redox-sensitive and redox-insensitive Rca isoforms could be differentially regulated throughout light–dark diel cycle in wheat. While TaRca1-β expression was consistently negligible throughout the day, transcript levels of both TaRca2-β and TaRca2-α were higher and increased at the start of the day, with peak levels occurring at the middle of the photoperiod. Abundance of TaRca-β protein was maximal 1.5 h after the peak in TaRca2-β expression, but the abundance of TaRca-α remained constant during the entire photoperiod. The redox-sensitive TaRca-α isoform was less abundant, representing 85% of the redox-insensitive TaRca-β at the transcript level and 12.5% at the protein level. Expression of Rubisco large and small subunit genes did not show a consistent pattern throughout the diel cycle, but the abundance of Rubisco decreased by up to 20% during the dark period in fully expanded wheat leaves. These results, combined with a lack of correlation between transcript and protein abundance for both Rca isoforms and Rubisco throughout the entire diel cycle, suggest that the abundance of these photosynthetic enzymes is post-transcriptionally regulated

Phylogeny and gene expression of the complete NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY (NPF) in Triticum aestivum L.

NPF genes encode membrane transporters involved in the transport of a large variety of substrates including nitrate and peptides. The NPF gene family has been described for many plants, but the whole NPF gene family for wheat has not been completely identified. The release of the wheat reference genome has enabled the identification of the entire wheat NPF gene family. A systematic analysis of the whole wheat NPF gene family was performed, including responses of specific gene expression to development and nitrogen supply. A total of 331 NPF genes (113 homoeologous groups) have been identified in wheat. The chromosomal location of the NPF genes is unevenly distributed with predominant occurrence in the long arms of the chromosomes. The phylogenetic analysis indicated that wheat NPF genes are closely clustered with Arabidopsis, Brachypodium and rice orthologs, and subdivided into eight subfamilies. The expression profiles of wheat NPF genes were examined using RNA-seq data and identified a subset of 44 NPF genes (homoeologous groups) with contrasting expression responses to nitrogen and/or development in different tissues. The systematic identification of gene composition, chromosomal locations, evolutionary relationships and expression profiles contributes to a better understanding of the roles of the wheat NPF genes and lays the foundation for further functional analysis in wheat

The Effect of Coherent Structures on Stochastic Acceleration in MHD Turbulence

We investigate the influence of coherent structures on particle acceleration in the strongly turbulent solar corona. By randomizing the Fourier phases of a pseudo-spectral simulation of isotropic MHD turbulence (Re $\sim 300$), and tracing collisionless test protons in both the exact-MHD and phase-randomized fields, it is found that the phase correlations enhance the acceleration efficiency during the first adiabatic stage of the acceleration process. The underlying physical mechanism is identified as the dynamical MHD alignment of the magnetic field with the electric current, which favours parallel (resistive) electric fields responsible for initial injection. Conversely, the alignment of the magnetic field with the bulk velocity weakens the acceleration by convective electric fields - \bfu \times \bfb at a non-adiabatic stage of the acceleration process. We point out that non-physical parallel electric fields in random-phase turbulence proxies lead to artificial acceleration, and that the dynamical MHD alignment can be taken into account on the level of the joint two-point function of the magnetic and electric fields, and is therefore amenable to Fokker-Planck descriptions of stochastic acceleration.Comment: accepted for publication in Ap

Entwicklung eines Inkubationssystems für ein inverses Mikroskop zur Langzeitbeobachtung von Zellkulturen in gekammerten Objektträgern

Trifunctional bispecific antibodies open up new immunological possibilities in tumour treatment. Prior to clinical application, comprehensive investigations using animal models and in vitro examinations need to be done. To investigate long-term interactions between Various immunologically active blood cells and individual tumour cells in the presence of antibodies, we developed an incubation system for experimental cell cultures on an inverted microscope. The system consists of a perspex box with a central moisture chamber with integrated water reservoir, external air circulation heating, and a CO2 supply. The sterile cell cultures are located in the wells of a slide positioned within a depression in the water reservoir. The newly developed incubation system enables continuous observation over the long term of experiments under optimal cell cultures conditions in combination with modern video techniques

Sitzung vom 12. December 1904

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