Bryanholm1117

In planta, we show, via temporal additions of DOZ, that SL receptors are required at a specific time during seed conditioning. This conditioning is essential to prime seed germination at the right time; thus, this SL-sensitive stage appears to be critical for adequate receptor signaling. Aside from uncovering a function for ShHTL during seed conditioning, these results suggest that future Ag-Biotech Solutions to Striga infestations will need to carefully time the application of antagonists to exploit receptor availability and outcompete natural SLs, critical elements for successful parasitic plant invasions.Dihydroceramide is a lipid molecule generated via the action of (dihydro)ceramide synthases (CerSs), which use two substrates, namely sphinganine and fatty acyl-CoAs. Sphinganine is generated via the sequential activity of two integral membrane proteins located in the endoplasmic reticulum. Less is known about the source of the fatty acyl-CoAs, although a number of cytosolic proteins in the pathways of acyl-CoA generation modulate ceramide synthesis via direct or indirect interaction with the CerSs. In this study, we demonstrate, by proteomic analysis of immunoprecipitated proteins, that fatty acid transporter protein 2 (FATP2) (also known as very long-chain acyl-CoA synthetase) directly interacts with CerS2 in mouse liver. Studies in cultured cells demonstrated that other members of the FATP family can also interact with CerS2, with the interaction dependent on both proteins being catalytically active. In addition, transfection of cells with FATP1, FATP2, or FATP4 increased ceramide levels although only FATP2 and 4 increased dihydroceramide levels, consistent with their known intracellular locations. Finally, we show that lipofermata, an FATP2 inhibitor which is believed to directly impact tumor cell growth via modulation of FATP2, decreased de novo dihydroceramide synthesis, suggesting that some of the proposed therapeutic effects of lipofermata may be mediated via (dihydro)ceramide rather than directly via acyl-CoA generation. In summary, our study reinforces the idea that manipulating the pathway of fatty acyl-CoA generation will impact a wide variety of down-stream lipids, not least the sphingolipids, which utilize two acyl-CoA moieties in the initial steps of their synthesis.Recent discoveries have implicated the potential of Cannabidiol (CBD) in the prevention of Alzheimer's disease (AD). Danirixin antagonist However, how CBD affects such neurodegenerative disorders remains unclear. Herein, Caenorhabditis elegans (C. elegans) was used as the model organism to elucidate the mechanism by which CBD ameliorates AD in vivo. CBD was found to alleviate the progression of Aβ-induced AD but not tau protein-induced AD or α-syn-induced Parkinson's disease. CBD inhibited the aggregation of Aβ in C. elegans. However, CBD failed to prevent the formation of β-sheet aggregation in vitro. Moreover, CBD was found to scavenge reactive oxygen species (ROS) in vivo without inducing the overexpression of antioxidative genes. In addition, CBD treatment enhanced the worm resistance to oxidative stress, which was independent of the classical transcription factors DAF-16 and SKN-1. These results supported that the in vivo antioxidative activity of CBD was most likely due to its intrinsic antioxidative property. Furthermore, the phenolic hydroxyl groups of CBD were found to be critical for scavenging ROS in vitro and in vivo, alleviating the aggregation of Aβ in vivo, and ameliorating Aβ-associated neurotoxicity. These studies show that CBD protects against AD in C. elegans via the ROS scavenging activity of its phenolic hydroxyl groups, which provides insight for further structure-activity relationship studies of CBD as an AD therapeutic.Kidney organoids derived from pluripotent stem cells and epithelial organoids derived from adult tissue (tubuloids) have been used to study various kidney disorders with a strong genetic component, such as polycystic kidney disease, Wilms tumor, and congenital nephrotic syndrome. However, complex disorders without clear genetic associations, such as acute kidney injury and many forms of chronic kidney disease, are only just beginning to be investigated using these in vitro approaches. Although organoids are a reductionist model, they contain clinically relevant cell populations that may help to elucidate human-specific pathogenic mechanisms. Thus, organoids may complement animal disease models to accelerate the translation of laboratory proof-of-concept research into clinical practice. This review discusses whether kidney organoids and tubuloids are suitable models for the study of complex human kidney disease and highlights their advantages and limitations compared with monolayer cell culture and animal models.Collapsin response mediator protein 1 (CRMP1), also known as dihydropyrimidinase-related protein 1, participates in cytoskeleton remodeling during axonal guidance and neuronal migration. In cochlear hair cells, the assembly and maintenance of the cytoskeleton is of great interest because it is crucial for the morphogenesis and maintenance of hair cells. Previous RNA sequencing analysis found that Crmp1 is highly expressed in cochlear hair cells. However, the expression profile and functions of CRMP1 in the inner ear remain unknown. In this study, the expression and localization of CRMP1 in hair cells was investigated using immunostaining, and was shown to be highly expressed in both outer and inner hair cells. Next, the stereocilia morphology of Crmp1-deficient mice was characterized. Abolishing CRMP1 did not affect the morphogenesis of hair cells. Interestingly, scanning electron microscopy detected hair cell loss at the basal cochlear region, an area responsible for high-frequency auditory perception, in Crmp1-deficient mice. Correspondingly, an auditory brainstem response test showed that mice lacking CRMP1 had progressive hearing loss at high frequencies. In summary, these data suggest that CRMP1 is required for high-frequency auditory perception.Progression of prostate cancer (PCa) is characterized by metastasis and castration resistance after response to androgen deprivation. Therapeutic options are limited, causing high morbidity and lethality. Recent work reported pro-oncogenic implications of the Mediator subunits cyclin-dependent kinase (CDK) 8 and 19 for the progression of PCa. The current study explored the underlying molecular mechanisms of CDK8/CDK19 and tested effects of novel CDK8/CDK19 inhibitors. PC3, DU145, LNCaP, and androgen-independent LNCaP Abl were used for in vitro experiments. Two inhibitors and CDK19 overexpression were used to modify CDK8/CDK19 activity. MTT assay, propidium iodide staining, wound healing assay, Boyden chamber assay, and adhesion assay were used to investigate cell viability, cell cycle, migration, and adhesion, respectively. Peptide-kinase screen using the PamGene platform was conducted to identify phosphorylated targets. Combining CDK8/CDK19 inhibitors with anti-androgens led to synergistic antiproliferative effects and sensitized androgen-independent cells to bicalutamide. CDK8/CDK19 inhibition resulted in reduced migration and increased collagen I-dependent adhesion. Phosphorylation of multiple peptides linked to cancer progression was identified to be dependent on CDK8/CDK19. In summary, this study substantially supports recent findings on CDK8/CDK19 in PCa progression. These findings contribute to a better understanding of underlying pro-oncogenic effects, which is needed to develop CDK8/CDK19 as a therapeutic target in PCa.In this study, a three-dimensional composite scaffold is proposed consisting of polylactic acid and spray dried glass-ceramic microparticles (SGCMs). The compositional and structural characterization showed that the obtained spray dried powder formed as glass-ceramic (GC) with a completely interconnected porosity structure. Before direct printing of scaffolds, the rheological behavior of polylactic acid (PLA) and PLA-GC (PLA matrix containing SGCMs) inks were investigated. The PLA-GC composite ink represents sharper shear-thinning behavior and higher loss and storage modulus comparable to that of pure PLA. Microscopic observations and elemental mapping elements showed that 3D scaffolds had well-defined interconnected porosity and uniform distribution of the glass-ceramic particles. Mechanical tests indicated that compression strength is dependent on the scaffold porosity and the presence of SGCMs. Apatite formation evaluation besides ion release study showed better biomineralization capacity of PLA-GC scaffolds, as larger and denser sediments formed on the PLA-GC scaffolds after 7- and 14-day soaking. The preliminary cell response was studied with primary human mesenchymal stem cells (hMSCs) and revealed that SGCMs improved cell adhesion and viability and ALP activity. The appropriate combination of the biomaterials/methods to fabricate 3D porous constructs and their available bioactivity and biocompatibility, both being important characteristics for bone tissue engineering applications.Improving the performance of wood adhesive is important for the development of the veneer industry. This work investigated the effects of various durations of enzymatic hydrolysis to improve and enhance the properties of starch-based wood adhesive (SWA). The results showed that moderate enzymatic hydrolysis for 2 h of starch molecule could improve the properties of SWA. The bonding strength of SWA was increased from 2.72 MPa (0 h) to 6.87 MPa (2 h) in the dry state and from 0.87 MPa (0 h) to 2.69 MPa (2 h) in the wet state. A significant decrease in the viscosity of SWA was also observed after 2 h hydrolysis of starch molecules, which allowed smooth spreading and penetration of adhesive through the wood surface. Meanwhile, the dynamic mechanical analysis and scanning electron microscopy showed that SWA with 2 h enzymatic hydrolysis exhibited better elastic deformation and smooth surfaces compared with SWA with un-hydrolysis starch. This study provides important information regarding the possible applications of SWA in the wood industry and presents a potential alternative to less environmentally friendly formaldehyde-based wood adhesives.In this work, a sustainable flame retardant and superhydrophobic cotton fabric was prepared by a two-step process the cotton fabric was firstly treated with a chitosan/sodium polyborate polyelectrolyte complex water solution to obtain a flame retardant layer, and then treated with a polydimethylsiloxane (PDMS) tetrahydrofuran solution to construct a superhydrophobic layer. The phase-separated chitosan with a micro-nano roughness structure was covered by PDMS, which synergistically improved the hydrophobicity of the cotton fabric. The flammability evaluation indicated that the limiting oxygen index value of the treated fabric was increased to 40.0% from 18.2%, the peak of heat release rate was reduced by 63.8%, and the total heat release was reduced by 57.6% compared with that of the control sample. The enhanced flame retardancy was attributed to the excellent charring ability in the condensed phase. The treated fabric also showed anti-sticking, self-cleaning, and oil/water-separating properties. This coating treatment without any F, Cl, Br, P elements involved is regarded as a clean methodology for producing flame retardant and superhydrophobic cotton fabrics.