Lens differentiation is controlled by the balance between PDGF and FGF signaling

How multiple receptor tyrosine kinases coordinate cell fate determination is yet to be elucidated. We show here that the receptor for platelet-derived growth factor (PDGF) signaling recruits the p85 subunit of Phosphoinositide 3-kinase (PI3K) to regulate mammalian lens development. Activation of PI3K signaling not only prevents B-cell lymphoma 2 (BCL2)-Associated X (Bax)- and BCL2 Antagonist/Killer (Bak)-mediated apoptosis but also promotes Notch signaling to prevent premature cell differentiation. Reducing PI3K activity destabilizes the Notch intracellular domain, while the constitutive activation of Notch reverses the PI3K deficiency phenotype. In contrast, fibroblast growth factor receptors (FGFRs) recruit Fibroblast Growth Factor Receptor Substrate 2 (Frs2) and Rous sarcoma oncogene (Src) Homology Phosphatase 2 (Shp2) to activate Mitogen-Activated Protein Kinase (MAPK) signaling, which induces the Notch ligand Jagged 1 (Jag1) and promotes cell differentiation. Inactivation of Shp2 restored the proper timing of differentiation in the p85 mutant lens, demonstrating the antagonistic interaction between FGF-induced MAPK and PDGF-induced PI3K signaling. By selective activation of PI3K and MAPK, PDGF and FGF cooperate with and oppose each other to balance progenitor cell maintenance and differentiation

Crk proteins transduce FGF signaling to promote lens fiber cell elongation

Specific cell shapes are fundamental to the organization and function of multicellular organisms. Fibroblast Growth Factor (FGF) signaling induces the elongation of lens fiber cells during vertebrate lens development. Nonetheless, exactly how this extracellular FGF signal is transmitted to the cytoskeletal network has previously not been determined. Here, we show that the Crk family of adaptor proteins, Crk and Crkl, are required for mouse lens morphogenesis but not differentiation. Genetic ablation and epistasis experiments demonstrated that Crk and Crkl play overlapping roles downstream of FGF signaling in order to regulate lens fiber cell elongation. Upon FGF stimulation, Crk proteins were found to interact with Frs2, Shp2 and Grb2. The loss of Crk proteins was partially compensated for by the activation of Ras and Rac signaling. These results reveal that Crk proteins are important partners of the Frs2/Shp2/Grb2 complex in mediating FGF signaling, specifically promoting cell shape changes

The water lily genome and the early evolution of flowering plants

Water lilies belong to the angiosperm order Nymphaeales. Amborellales, Nymphaeales and Austrobaileyales together form the so-called ANA-grade of angiosperms, which are extant representatives of lineages that diverged the earliest from the lineage leading to the extant mesangiosperms1–3. Here we report the 409-megabase genome sequence of the blue-petal water lily (Nymphaea colorata). Our phylogenomic analyses support Amborellales and Nymphaeales as successive sister lineages to all other extant angiosperms. The N. colorata genome and 19 other water lily transcriptomes reveal a Nymphaealean whole-genome duplication event, which is shared by Nymphaeaceae and possibly Cabombaceae. Among the genes retained from this whole-genome duplication are homologues of genes that regulate flowering transition and flower development. The broad expression of homologues of floral ABCE genes in N. colorata might support a similarly broadly active ancestral ABCE model of floral organ determination in early angiosperms. Water lilies have evolved attractive floral scents and colours, which are features shared with mesangiosperms, and we identified their putative biosynthetic genes in N. colorata. The chemical compounds and biosynthetic genes behind floral scents suggest that they have evolved in parallel to those in mesangiosperms. Because of its unique phylogenetic position, the N. colorata genome sheds light on the early evolution of angiosperms.Supplementary Tables: This file contains Supplementary Tables 1-21.National Natural Science Foundation of China, the open funds of the State Key Laboratory of Crop Genetics and Germplasm Enhancement (ZW201909) and State Key Laboratory of Tree Genetics and Breeding, the Fujian provincial government in China, the European Union Seventh Framework Programme (FP7/2007-2013) under European Research Council Advanced Grant Agreement and the Special Research Fund of Ghent University.http://www.nature.com/naturecommunicationsam2021BiochemistryGeneticsMicrobiology and Plant Patholog

Waveform dissimilarity factor-based protection for main transformers in wind farms

Current differential protection (CDP) is widely used as main protection for transformers due to its high reliability and selectivity. Owing to non-fundamental frequency current, magnetizing inrush and current transformer (CT) saturation, CDP may undergo slow operating speed when the internal fault occurs. When the external fault occurs, CDP may false operate. Furthermore, given the disadvantage of Hausdorff distance being extremely sensitive to abnormal data, a new metric that reveals the dissimilarity degree of two waveforms is presented, namely waveform dissimilarity factor (WDF). WDF has inherent immunity to abnormal data. Subsequently, WDF-based protection for main transformer is proposed herein. In order to reduce the adverse effects of magnetizing inrush and CT saturation and accurately identify internal faults, the reward and punishment mechanism is designed. The protection principle is elaborated and its operating characteristics are analyzed under various conditions. Finally, by constructing the DFIG-based wind farm, PSCAD is used to verify the advantages of the novel protection algorithm based on WDF. Its performance is widely assessed in various scenarios in detail, including magnetizing inrushes, minor and server internal faults, inter-turn fault, turn-to-ground fault, internal fault with CT saturation and external fault with CT saturation, data loss, abnormal data, and CT error. The results show that the novel protection scheme has the characteristics of fast, secure, and robust

Evaluating the Effects of Mulch and Irrigation Amount on Soil Water Distribution and Root Zone Water Balance Using HYDRUS-2D

Water scarcity is the most critical constraint for sustainable cotton production in Xinjiang Province, northwest China. Drip irrigation under mulch is a major water-saving irrigation method that has been widely practiced for cotton production in Xinjiang. The performance of such an irrigation system should be evaluated for proper design and management. Therefore, a field experiment and a simulation study were conducted to (1) determine a modeling approach that can be applied to manage drip irrigation under mulch for cotton production in this region; and (2) examine the effects of irrigation amount and mulch on soil water distribution and root zone water balance components. In the experiment, four irrigation treatments were used: T1, 166.5 m3; T2, 140.4 m3; T3, 115.4 m3; and T4: 102.3 m3. The HYDRUS-2D model was calibrated, validated, and applied with the data obtained in this experiment. Soil water balance in the 0–70 cm soil profile was simulated. Results indicate that the observed soil water content and the simulated results obtained with HYDRUS-2D are in good agreement. The radius of the wetting pattern, root water uptake, and evaporation decreased as the amount of irrigation was reduced from T1 to T4, while a lot of stored soil water in the root zone was utilized and a huge amount of water was recharged from the layer below 70 cm to compensate for the decrease in irrigation amount. Mulch significantly reduced evaporation by 11.7 mm and increased root water uptake by 11.2 mm. Our simulation study suggests that this model can be applied to provide assistance in designing drip irrigation systems and developing irrigation strategies

A Mathematical Morphological Network Fault Diagnosis Method for Rolling Bearings Based on Acoustic Array Signal

To extract valuable characteristic information from the acoustic radiation signal of rolling bearings, a novel mathematical morphological network (MMNet) is proposed. First, a mathematical morphological network layer is constructed by leveraging the advantages of a multi-scale enhanced top-hat morphological operator (MEAVGH) that can extract positive and negative pulses, which are then integrated into the deep learning network. Second, the input signal undergoes processing with different scale structural elements (SEs) to obtain multi-branch data. This is followed by channel attention and spatial attention mechanism-based weighting of the generated multi-branch data. Finally, the fused information is fed to the neural network to yield the final result. The experimental results demonstrate the efficacy of the proposed method in extracting fault feature information, achieving a fault classification accuracy of 98.56%. Furthermore, the algorithm exhibits robustness and high training efficiency. Comparative analysis reveals that the proposed method outperforms other approaches regarding cluster analysis, accuracy, recall rate, and computational efficiency. These findings further highlight the advantages of MMNet in acoustic signal-based fault diagnosis for rolling bearings

The N-terminal 26-residue fragment of human programmed cell death 5 protein can form a stable α-helix having unique electrostatic potential character

PDCD5-(1–26) is a N-terminal 26-residue fragment of human PDCD5 (programmed cell death 5) protein. PDCD5 is an important novel protein that regulates both apoptotic and non-apoptotic programmed cell death. The conformation of PDCD5 protein is a stable helical core consisting of a triple-helix bundle and two dissociated terminal regions. The N-terminal region is ordered and contains abundant secondary structure. Overexpression and purification of the N-terminal 26-residure fragment, PDCD5-(1–26), was performed in this study to better understand its tertiary structure. The spectroscopic studies using CD and hetero- and homo-nuclear NMR methods determine a stable α-helix formed by Asp(3)–Ala(19) of PDCD5-(1–26). The N-terminal residues Asp(3)–Ala(19) of PDCD5 were then affirmed to have the capacity to form a stable α-helix independently of the core of the protein. Analysis of the helical peptide of PDCD5-(1–26) indicates that the surface of this well-formed α-helix has a unique electrostatic potential character. This may provide an environment for the N-terminal α-helix of PDCD5 to serve as an independent functional entity of the protein. The apoptosis activity assay shows that the deletion of the N-terminal α-helix of PDCD5 significantly attenuates the apoptosis-promoting effects on HL-60 cells induced by serum withdrawal

A combination of ultrasound-targeted microbubble destruction with transplantation of bone marrow mesenchymal stem cells promotes recovery of acute liver injury

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) can provide an additional source of therapeutic stem cells for regeneration of liver cells during acute liver injury (ALI). However, the insufficient hepatic homing by the transplanted BMSCs limits their applications. Ultrasound-targeted microbubble destruction (UTMD) has been reported to promote the homing of transplanted stem cells into the ischemic myocardium. In this study, we investigated whether UTMD promotes the hepatic homing of BMSCs in ALI rats and evaluated the therapeutic effect. Methods BMSCs were isolated from the femurs and tibias of Sprague-Dawley (SD) rats. The isolated BMSCs were stably transfected with a lentivirus expressing enhanced green fluorescent protein (EGFP) that can be visualized and quantified in vivo after transplantation. Both tumor necrosis factor α (TNF-α) and stromal cell-derived factor 1 (SDF-1) were used to verify the appropriate ultrasound parameters. The ALI rats were divided into four groups: control, BMSCs, UTMD, and UTMD + BMSCs. The protein and mRNA expression levels of SDF-1, intercellular cell adhesion molecule (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), hepatocyte growth factor (HGF), and monocyte chemotactic protein 1 (MCP-1) in the exposed livers were analyzed at 48 h after treatment. ALI recovery was determined by serum biochemical parameters and histology. Results The isolated rat BMSCs demonstrated a good proliferation potential that was both osteogenic and adipogenic in differentiation and expressed cluster of differentiation (CD) 29 and CD90, but not CD45 or CD11b/c. After BMSC and/or UTMD treatment, the number of GFP-labeled BMSCs in the UTMD + BMSCs group was significantly higher than that of the BMSCs group (9.8 ± 2.3 vs. 5.2 ± 1.1/per high-power field). Furthermore, the expression of GFP mRNA was performed for evaluation of the homing rate of BMSCs in injury sites as well. In addition, the expression levels of SDF-1, ICAM-1, VCAM-1, HGF, and MCP-1 were higher (p < 0.01) in UTMD+BMSCs group. The serum levels of biomarkers were significantly lower in the UTMD + BMSCs group, and the apoptotic rate of hepatocytes in the UTMD + BMSCs group was markedly lower than that of the BMSCs group (all p < 0.05). The hepatic pathology was significantly alleviated in the UTMD + BMSCs group. Conclusions UTMD treatment efficiently induced a favorable microenvironment for cell engraftment, resulting in improvement of hepatic homing of BMSCs, which was probably mediated through upregulation of the expression of adhesion molecules and cytokines. UTMD treatment appeared to be an effective and noninvasive approach to achieve better efficacy of BMSC-based therapy for repairing a severely injured liver