A novel variation of TaGW2-6B increases grain weight without penalty in grain protein content in wheat (Triticum aestivum L.).

Yield and quality are two crucial breeding objects of wheat therein grain weight and grain protein content (GPC) are two key relevant factors correspondingly. Investigations of their genetic mechanisms represent special significance for breeding. In this study, 199 F2 plants and corresponding F2:3 families derived from Nongda3753 (ND3753) and its EMS-generated mutant 564 (M564) were used to investigate the genetic basis of larger grain and higher GPC of M564. QTL analysis identified a total of 33 environmentally stable QTLs related to thousand grain weight (TGW), grain area (GA), grain circle (GC), grain length (GL), grain width (GW), and GPC on chromosomes 1B, 2A, 2B, 4D, 6B, and 7D, respectively, among which QGw.cau-6B.1, QTgw.cau-6B.1, QGa.cau-6B.1, and QGc.cau-6B.1 shared overlap confidence interval on chromosome 6B. This interval contained the TaGW2 gene playing the same role as the QTLs, so TaGW2-6B was cloned and sequenced. Sequence alignment revealed two G/A SNPs between two parents, among which the SNP in the seventh exon led to a premature termination in M564. A KASP marker was developed based on the SNP, and single-marker analysis on biparental populations showed that the mutant allele could significantly increase GW and TGW, but had no effect on GPC. Distribution detection of the mutant allele through KASP marker genotyping and sequence alignment against databases ascertained that no materials harbored this allele within natural populations. This allele was subsequently introduced into three different varieties through molecular marker-assisted backcrossing, and it was revealed that the allele had a significant effect on simultaneously increasing GW, TGW, and even GPC in all of three backgrounds. Summing up the above, it could be concluded that a novel elite allele of TaGW2-6B was artificially created and might play an important role in wheat breeding for high yield and quality. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01455-y.

Development of low-energy X-ray detectors using LGAD sensors.

Recent advances in segmented low-gain avalanche detectors (LGADs) make them promising for the position-sensitive detection of low-energy X-ray photons thanks to their internal gain. LGAD microstrip sensors fabricated by Fondazione Bruno Kessler have been investigated using X-rays with both charge-integrating and single-photon-counting readout chips developed at the Paul Scherrer Institut. In this work it is shown that the charge multiplication occurring in the sensor allows the detection of X-rays with improved signal-to-noise ratio in comparison with standard silicon sensors. The application in the tender X-ray energy range is demonstrated by the detection of the sulfur Kα and Kß lines (2.3 and 2.46 keV) in an energy-dispersive fluorescence spectrometer at the Swiss Light Source. Although further improvements in the segmentation and in the quantum efficiency at low energy are still necessary, this work paves the way for the development of single-photon-counting detectors in the soft X-ray energy range.

The Adaptive Gain Integrating Pixel Detector at the European XFEL.

The Adaptive Gain Integrating Pixel Detector (AGIPD) is an X-ray imager, custom designed for the European X-ray Free-Electron Laser (XFEL). It is a fast, low-noise integrating detector, with an adaptive gain amplifier per pixel. This has an equivalent noise of less than 1 keV when detecting single photons and, when switched into another gain state, a dynamic range of more than 104 photons of 12 keV. In burst mode the system is able to store 352 images while running at up to 6.5 MHz, which is compatible with the 4.5 MHz frame rate at the European XFEL. The AGIPD system was installed and commissioned in August 2017, and successfully used for the first experiments at the Single Particles, Clusters and Biomolecules (SPB) experimental station at the European XFEL since September 2017. This paper describes the principal components and performance parameters of the system.

MiR-200a negatively regulates TGF-ß1-induced epithelial-mesenchymal transition of peritoneal mesothelial cells by targeting ZEB1/2 expression.

Although epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells was recognized as the key process of peritoneal fibrosis, which is a major cause of peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unknown. In this study, we found that miR-200a was significantly downregulated in peritoneal tissues with fibrosis in a rat model of PD. In vitro, transforming growth factor (TGF)-ß1-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in human peritoneal mesothelial cells (HPMCs), was associated with downregulation of miR-200a but upregulation of zinc finger E-box-binding homeobox 1/2 (ZEB1/2), suggesting a close link between miR-200a and ZEB1/2 in TGF-ß1-induced EMT. It was further demonstrated that miR-200a was able to bind to the 3'UTR of ZEB1/2, and overexpression of miR-200a blocked TGF-ß1-induced upregulation of ZEB1/2 and, therefore, inhibited EMT and collagen expression. In contrast, overexpression ZEB1/2 blocked miR-200a inhibition of EMT and collagen expression in HMPCs. In conclusion, miR-200a could negatively regulate TGF-ß1-induced EMT by targeting ZEB1/2 in peritoneal mesothelial cells. Blockade of EMT in HPMCS indicates the therapeutic potential of miR-200a as a treatment for peritoneal fibrosis associated with PD.

Micrometer-resolution imaging using MÖNCH: towards G2-less grating interferometry.

MÖNCH is a 25 µm-pitch charge-integrating detector aimed at exploring the limits of current hybrid silicon detector technology. The small pixel size makes it ideal for high-resolution imaging. With an electronic noise of about 110 eV r.m.s., it opens new perspectives for many synchrotron applications where currently the detector is the limiting factor, e.g. inelastic X-ray scattering, Laue diffraction and soft X-ray or high-resolution color imaging. Due to the small pixel pitch, the charge cloud generated by absorbed X-rays is shared between neighboring pixels for most of the photons. Therefore, at low photon fluxes, interpolation algorithms can be applied to determine the absorption position of each photon with a resolution of the order of 1 µm. In this work, the characterization results of one of the MÖNCH prototypes are presented under low-flux conditions. A custom interpolation algorithm is described and applied to the data to obtain high-resolution images. Images obtained in grating interferometry experiments without the use of the absorption grating G2 are shown and discussed. Perspectives for the future developments of the MÖNCH detector are also presented.

Detector developments at DESY.

With the increased brilliance of state-of-the-art synchrotron radiation sources and the advent of free-electron lasers (FELs) enabling revolutionary science with EUV to X-ray photons comes an urgent need for suitable photon imaging detectors. Requirements include high frame rates, very large dynamic range, single-photon sensitivity with low probability of false positives and (multi)-megapixels. At DESY, one ongoing development project - in collaboration with RAL/STFC, Elettra Sincrotrone Trieste, Diamond, and Pohang Accelerator Laboratory - is the CMOS-based soft X-ray imager PERCIVAL. PERCIVAL is a monolithic active-pixel sensor back-thinned to access its primary energy range of 250 eV to 1 keV with target efficiencies above 90%. According to preliminary specifications, the roughly 10 cm × 10 cm, 3.5k × 3.7k monolithic sensor will operate at frame rates up to 120 Hz (commensurate with most FELs) and use multiple gains within 27 µm pixels to measure 1 to ∼100000 (500 eV) simultaneously arriving photons. DESY is also leading the development of the AGIPD, a high-speed detector based on hybrid pixel technology intended for use at the European XFEL. This system is being developed in collaboration with PSI, University of Hamburg, and University of Bonn. The AGIPD allows single-pulse imaging at 4.5 MHz frame rate into a 352-frame buffer, with a dynamic range allowing single-photon detection and detection of more than 10000 photons at 12.4 keV in the same image. Modules of 65k pixels each are configured to make up (multi)megapixel cameras. This review describes the AGIPD and the PERCIVAL concepts and systems, including some recent results and a summary of their current status. It also gives a short overview over other FEL-relevant developments where the Photon Science Detector Group at DESY is involved.

Time-over-threshold readout to enhance the high flux capabilities of single-photon-counting detectors.

The MYTHEN single-photon-counting (SPC) detector has been characterized using the time-over-threshold (ToT) readout method, i.e. measuring the time that the signal produced by the detected X-rays remains above the comparator threshold. In the following it is shown that the ToT readout preserves the sensitivity, dynamic range and capability of background suppression of the SPC mode, while enhancing the count-rate capability, which is the main limitation of state-of-the-art SPC systems.

Identification and Validation of Stable Quantitative Trait Loci for SDS-Sedimentation Volume in Common Wheat (Triticum aestivum L.).

Sodium dodecyl sulfate-sedimentation volume is an important index to evaluate the gluten strength of common wheat and is closely related to baking quality. In this study, a total of 15 quantitative trait locus (QTL) for sodium dodecyl sulfate (SDS)-sedimentation volume (SSV) were identified by using a high-density genetic map including 2,474 single-nucleotide polymorphism (SNP) markers, which was constructed with a doubled haploid (DH) population derived from the cross between Non-gda3753 (ND3753) and Liangxing99 (LX99). Importantly, four environmentally stable QTLs were detected on chromosomes 1A, 2D, and 5D, respectively. Among them, the one with the largest effect was identified on chromosome 1A (designated as QSsv.cau-1A.1) explaining up to 39.67% of the phenotypic variance. Subsequently, QSsv.cau-1A.1 was dissected into two QTLs named as QSsv.cau-1A.1.1 and QSsv.cau-1A.1.2 by saturating the genetic linkage map of the chromosome 1A. Interestedly, favorable alleles of these two loci were from different parents. Due to the favorable allele of QSsv.cau-1A.1.1 was from the high-value parents ND3753 and revealed higher genetic effect, which explained 25.07% of the phenotypic variation, mapping of this locus was conducted by using BC3F1 and BC3F2 populations. By comparing the CS reference sequence, the physical interval of QSsv.cau-1A.1.1 was delimited into 14.9 Mb, with 89 putative high-confidence annotated genes. SSVs of different recombinants between QSsv.cau-1A.1.1 and QSsv.cau-1A.1 detected from DH and BC3F2 populations showed that these two loci had an obvious additive effect, of which the combination of two favorable loci had the high SSV, whereas recombinants with unfavorable loci had the lowest. These results provide further insight into the genetic basis of SSV and QSsv.cau-1A.1.1 will be an ideal target for positional cloning and wheat breeding programs.

A Major Quantitative Trait Loci Cluster Controlling Three Components of Yield and Plant Height Identified on Chromosome 4B of Common Wheat.

Wheat yield is not only affected by three components of yield, but also affected by plant height (PH). Identification and utilization of the quantitative trait loci (QTL) controlling these four traits is vitally important for breeding high-yielding wheat varieties. In this work, we conducted a QTL analysis using the recombinant inbred lines (RILs) derived from a cross between two winter wheat varieties of China, "Nongda981" (ND981) and "Nongda3097" (ND3097), exhibiting significant differences in spike number per unit area (SN), grain number per spike (GNS), thousand grain weight (TGW), and PH. A total of 11 environmentally stable QTL for these four traits were detected. Among them, four major and stable QTLs (QSn.cau-4B-1.1, QGns.cau-4B-1, QTgw.cau-4B-1.1, and QPh.cau-4B-1.2) explaining the highest phenotypic variance for SN, GNS, TGW, and PH, respectively, were mapped on the same genomic region of chromosome 4B and were considered a QTL cluster. The QTL cluster spanned a genetic distance of about 12.3 cM, corresponding to a physical distance of about 8.7 Mb. Then, the residual heterozygous line (RHL) was used for fine mapping of the QTL cluster. Finally, QSn.cau-4B-1.1, QGns.cau-4B-1, and QPh.cau-4B-1.2 were colocated to the physical interval of about 1.4 Mb containing 31 annotated high confidence genes. QTgw.cau-4B-1.1 was divided into two linked QTL with opposite effects. The elite NILs of the QTL cluster increased SN and PH by 55.71-74.82% and 14.73-23.54%, respectively, and increased GNS and TGW by 29.72-37.26% and 5.81-11.24% in two environments. Collectively, the QTL cluster for SN, GNS, TGW, and PH provides a theoretical basis for improving wheat yield, and the fine-mapping result will be beneficial for marker-assisted selection and candidate genes cloning.

The MYTHEN detector for X-ray powder diffraction experiments at the Swiss Light Source.

The MYTHEN single-photon-counting silicon microstrip detector has been developed at the Swiss Light Source for time-resolved powder diffraction experiments. An upgraded version of the detector has been installed at the SLS powder diffraction station allowing the acquisition of diffraction patterns over 120 degrees in 2theta in fractions of seconds. Thanks to the outstanding performance of the detector and to the calibration procedures developed, the quality of the data obtained is now comparable with that of traditional high-resolution point detectors in terms of FWHM resolution and peak profile shape, with the additional advantage of fast and simultaneous acquisition of the full diffraction pattern. MYTHEN is therefore optimal for time-resolved or dose-critical measurements. The characteristics of the MYTHEN detector together with the calibration procedures implemented for the optimization of the data are described in detail. The refinements of two known standard powders are discussed together with a remarkable application of MYTHEN to organic compounds in relation to the problem of radiation damage.

Erratum: Immunosuppressive agents versus steroids in the treatment of IgA nephropathy-induced proteinuria: A meta-analysis.

[This corrects the article DOI: 10.3892/etm.2015.2860.].

Immunosuppressive agents versus steroids in the treatment of IgA nephropathy-induced proteinuria: A meta-analysis.

Immunoglobulin A nephropathy (IgAN) is one of the most common types of primary glomerular disease. Immunosuppressive treatment for patients with IgAN remains controversial. The present meta-analysis aimed to assess the efficacy and safety of various immunosuppressive agents compared with steroids in patients with IgAN and moderate to severe proteinuria. PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Weipu, Chinese Biomedical Literature Database and Qinghuatongfang were searched for relevant randomized controlled trials (RCTs) published between 1990 and September 2013. All eligible studies (biopsy proven IgA nephropathy, use of immunosuppressive agents) measured urinary protein excretion and proteinuria remission. Data were analyzed with the random effects model using Review Manager. A total of 29 RCTs were included, involving 1,466 patients. Compared with steroids, immunosuppressive agents, including azathioprine [corrected] (AZA) [complete response (CR)/partial response (PR); relative risk (RR), 3.43; 95% confidence interval (CI) 1.92-6.12; P<0.0001], mycophenolate mofetil (MMF) (CR/PR; RR, 2.19; 95% CI, 1.25-3.85; P=0.006) and leflunomide (LET) (CR/PR; RR, 2.64; 95% CI, 1.80-3.86; P<0.00001) resulted in increased partial or complete proteinuria remission. Cyclophosphamide (CTX) resulted in a higher reduction of urinary protein excretion than steroids (SMD, 0.91; 95% CI, 0.41-1.41; P=0.0004)). Compared to CTX, LET showed higher effectiveness (CR/PR; RR, 2.01; 95% CI, 1.08-3.75; P=0.03) with a lower incidence of adverse events. The present meta-analysis, which is based on IgAN patients, suggested that AZA, MMF, LET and CTX are effective in reducing proteinuria levels, with acceptable side effects. Therefore, immunosuppressive agents may be considered promising therapeutic agents for the treatment of IgAN and should be investigated further in large sample size, high-quality studies.