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

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

The Functional Diversity of the High-Affinity Nitrate Transporter Gene Family in Hexaploid Wheat: Insights from Distinct Expression Profiles

High-affinity nitrate transporters (NRT) are key components for nitrogen (N) acquisition and distribution within plants. However, insights on these transporters in wheat are scarce. This study presents a comprehensive analysis of the NRT2 and NRT3 gene families, where the aim is to shed light on their functionality and to evaluate their responses to N availability. A total of 53 NRT2s and 11 NRT3s were identified in the bread wheat genome, and these were grouped into different clades and homoeologous subgroups. The transcriptional dynamics of the identified NRT2 and NRT3 genes, in response to N starvation and nitrate resupply, were examined by RT-qPCR in the roots and shoots of hydroponically grown wheat plants through a time course experiment. Additionally, the spatial expression patterns of these genes were explored within the plant. The NRT2s of clade 1, TaNRT2.1-2.6, showed a root-specific expression and significant upregulation in response to N starvation, thus emphasizing a role in N acquisition. However, most of the clade 2 NRT2s displayed reduced expression under N-starved conditions. Nitrate resupply after N starvation revealed rapid responsiveness in TaNRT2.1-2.6, while clade 2 genes exhibited gradual induction, primarily in the roots. TaNRT2.18 was highly expressed in above-ground tissues and exhibited distinct nitrate-related response patterns for roots and shoots. The TaNRT3 gene expression closely paralleled the profiles of TaNRT2.1-2.6 in response to nitrate induction. These findings enhance the understanding of NRT2 and NRT3 involvement in nitrogen uptake and utilization, and they could have practical implications for improving nitrogen use efficiency. The study also recommends a standardized nomenclature for wheat NRT2 genes, thereby addressing prior naming inconsistencies

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

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

Charge and nematic orders in AFe2As2 (A = Rb, Cs) superconductors

We discuss the results of 75As nuclear quadrupole resonance (NQR) and muon spin relaxation measurements in AFe2As2 (A = Cs, Rb) iron-based superconductors. We point out that the crossover detected in the nuclear spin-lattice relaxation rate 1/T1 (around 150 K in RbFe2As2 and around 75 K in CsFe2As2), from a high temperature nearly localized to a low temperature delocalized behavior, is associated with the onset of an inhomogeneous local charge distribution causing the broadening or even the splitting of the NQR spectra as well as an increase in the muon spin relaxation rate. We argue that this crossover, occurring at temperatures well above the phase transition to the nematic long-range order, is due to a charge disproportionation at the Fe sites induced by competing Hund’s and Coulomb couplings. In RbFe2As2 around 35 K, far below that crossover temperature, we observe a peak in the NQR 1/T1 which is possibly associated with the critical slowing down of electronic nematic fluctuations on approaching the transition to the nematic long-range order

Nutrient dynamics in wheat

Nutrients are taken up by plant roots in a regulated manner and are then distributed around the plant according to demand. As the plant develops and matures, requirements will change and new sinks for nutrients will replace old. In the case of wheat, the developing grain replaces the canopy as the major sink. Hence, nutrient allocation is a dynamic phenomenon, achieved by nutrient recycling and linked to processes of development including senescence. The effectiveness of these processes strongly influences performance and quality, particularly grain protein and mineral nutrient content, which are important health and quality attributes of the seeds. The effective reuse of nutrients is an essential contributor to nutrient use efficiency, an important sustainability trait. Movement of nutrients is achieved by multiple large gene families encoding for transporters, each family usually specific for transporting individual substrates, but often with family members showing varied distribution and regulatory patterns. There are observed interactions between nutrients resulting in coordinated accumulation within the plant. Cycling of nutrients refers to the process of internal movements of nutrients between cells, compartments, and organs or their reuse in metabolic processes. It may also refer to processes occurring within the ecosystem including cycling in the soil and between soil and crop. In this article, emphasis is placed on initial uptake and use of nutrients by the wheat plant and the recycling and partitioning of these nutrients to grain tissues