Protein Kinase A and Protein Kinase C Modulators Have Reciprocal Effects on Mesenchymal Condensation during Skin Appendage Morphogenesis

AbstractThe molecular signaling of secondary induction is a fundamental process in organogenesis during embryonic development. To study the signal transduction pathways involved, we used developing chicken skin as a model and focused on the roles of intracellular signaling during feather morphogenesis. Protein kinase C (PKC) immunoreactivity increases in the whole layer of forming dermis around H and H stage 30. This is followed by a gradual and highly localized decrease of PKC expression immediately beneath each forming feather germ. In contrast, cAMP response element binding protein (CREB) is ubiquitously expressed in both epithelium and mesenchyme. From stage 29 on, phosphorylated CREB (P-CREB), reflecting the activity of protein kinase A (PKA), begins to be seen in placode but not in interplacode epithelia. P-CREB is also expressed in bud mesenchyme transiently between stages 33 and 36, but not in the interbud mesenchyme. The presence and activity of PKC, PKA, and P-CREB in developing chicken skin are further characterized by immunoblot, kinase activity, and gel shift assays. To explore their physiological significance, embryonic chicken dorsal skin explants were treated with different modulators in medium or in beads for localized effects. The results showed that PKA activators and PKC inhibitors can expand a feather bud domain by enhancing dermal condensation, while PKC activators and PKA inhibitors can expand interbud domains. Neural cell adhesion molecule (N-CAM) is involved in dermal condensation. We observed that activation of PKA causes diffused expression of N-CAM in mesenchyme while activation of PKC causes the disappearance of N-CAM in precondensed mesenchymal regions. A model of how the well-concerted PKA and PKC signaling may be involved in the formation and size regulation of dermal condensation is presented

Aluminum with dispersed nanoparticles by laser additive manufacturing.

While laser-printed metals do not tend to match the mechanical properties and thermal stability of conventionally-processed metals, incorporating and dispersing nanoparticles in them should enhance their performance. However, this remains difficult to do during laser additive manufacturing. Here, we show that aluminum reinforced by nanoparticles can be deposited layer-by-layer via laser melting of nanocomposite powders, which enhance the laser absorption by almost one order of magnitude compared to pure aluminum powders. The laser printed nanocomposite delivers a yield strength of up to 1000 MPa, plasticity over 10%, and Young's modulus of approximately 200 GPa, offering one of the highest specific Young's modulus and specific yield strengths among structural metals, as well as an improved specific strength and thermal stability up to 400 °C compared to other aluminum-based materials. The improved performance is attributed to a high density of well-dispersed nanoparticles, strong interfacial bonding between nanoparticles and Al matrix, and ultrafine grain sizes

Wilcoxon Rank-Based Tests for Clustered Data with R Package clusrank

Wilcoxon rank-based tests are distribution-free alternatives to the popular two-sample and paired t tests. For independent data, they are available in several R packages such as stats and coin. For clustered data, in spite of the recent methodological developments, there did not exist an R package that makes them available at one place. We present a package clusrank where the latest developments are implemented and wrapped under a unified user-friendly interface. With different methods dispatched based on the inputs, this package offers great flexibility in rank-based tests for various clustered data. Exact tests based on permutations are also provided for some methods. Details of the major schools of different methods are briefly reviewed. Usages of the package clusrank are illustrated with simulated data as well as a real dataset from an ophthalmological study. The package also enables convenient comparison between selected methods under settings that have not been studied before and the results are discussed

Federated Reinforcement Learning for Electric Vehicles Charging Control on Distribution Networks

With the growing popularity of electric vehicles (EVs), maintaining power grid stability has become a significant challenge. To address this issue, EV charging control strategies have been developed to manage the switch between vehicle-to-grid (V2G) and grid-to-vehicle (G2V) modes for EVs. In this context, multi-agent deep reinforcement learning (MADRL) has proven its effectiveness in EV charging control. However, existing MADRL-based approaches fail to consider the natural power flow of EV charging/discharging in the distribution network and ignore driver privacy. To deal with these problems, this paper proposes a novel approach that combines multi-EV charging/discharging with a radial distribution network (RDN) operating under optimal power flow (OPF) to distribute power flow in real time. A mathematical model is developed to describe the RDN load. The EV charging control problem is formulated as a Markov Decision Process (MDP) to find an optimal charging control strategy that balances V2G profits, RDN load, and driver anxiety. To effectively learn the optimal EV charging control strategy, a federated deep reinforcement learning algorithm named FedSAC is further proposed. Comprehensive simulation results demonstrate the effectiveness and superiority of our proposed algorithm in terms of the diversity of the charging control strategy, the power fluctuations on RDN, the convergence efficiency, and the generalization ability

FGF Induces New Feather Buds From Developing Avian Skin

Induction of skin appendages involves a cascade of molecular events. The fibroblast growth factor (FGF) family of peptide growth factors is involved in cell proliferation and morphogenesis. We explored the role of the FGFs during skin appendage induction using developing chicken feather buds as a model. FGF-1, FGF-2, or FGF-4 was added directly to the culture medium or was released from pre-soaked Affigel blue beads. Near the midline, FGFs led to fusion of developing feather buds, representing FGFs' ability to expand feather bud domains in developing skin. In lateral regions of the explant where feather placodes have not formed, FGF treatment produces a zone of condensation and a region with an increased number of feather buds. In ventral epidermis that is normally apteric (without feathers), FGFs can also induce new feather buds. Like normal feather buds, the newly induced buds express Shh. The expression of Grb, Ras, Raf, and Erk, intracellular signaling molecules known to be downstream to tyrosine kinase receptors such as the FGF receptor, was enriched in feather bud domains. Genistein, an inhibitor of tyrosine kinase, suppressed feather bud formation and the effect of FGF. These results indicate that there are varied responses to FGFs depending on epithelial competence. All the phenotypic responses, however, show that FGFs facilitate the formation of skin appendage domains

Optimization of a pretreatment and hydrolysis process for the efficient recovery of recycled sugars and unknown compounds from agricultural sweet sorghum bagasse stem pith solid waste

Background Sweet sorghum bagasse (SSB), comprising both a dermal layer and pith, is a solid waste generated by agricultural activities. Open burning was previously used to treat agricultural solid waste but is harmful to the environment and human health. Recent reports showed that certain techniques can convert this agricultural waste into valuable products. While SSB has been considered an attractive raw material for sugar extraction and the production of value-added products, the pith root in the SSB can be difficult to process. Therefore, it is necessary to pretreat bagasse before conventional hydrolysis. Methods A thorough analysis and comparison of various pretreatment methods were conducted based on physicochemical and microscopic approaches. The responses of agricultural SSB stem pith with different particle sizes to pretreatment temperature, acid and alkali concentration and enzyme dosage were investigated to determine the optimal pretreatment. The integrated methods are beneficial to the utilization of carbohydrate-based and unknown compounds in agricultural solid waste. Results Acid (1.5−4.5%, v/v) and alkali (5−8%, w/v) reagents were used to collect cellulose from different meshes of pith at 25–100 °C. The results showed that the use of 100 mesh pith soaked in 8% (w/v) NaOH solution at 100 °C resulted in 32.47% ± 0.01% solid recovery. Follow-up fermentation with 3% (v/v) acid and 6.5% (w/v) alkali at 50 °C for enzymolysis was performed with the optimal enzyme ratio. An analysis of the surface topography and porosity before and after pretreatment showed that both the pore size of the pith and the amount of exposed cellulose increased as the mesh size increased. Interestingly, various compounds, including 42 compounds previously known to be present and 13 compounds not previously known to be present, were detected in the pretreatment liquid, while 10 types of monosaccharides, including D-glucose, D-xylose and D-arabinose, were found in the enzymatic solution. The total monosaccharide content of the pith was 149.48 ± 0.3 mg/g dry matter. Discussion An integrated technique for obtaining value-added products from sweet sorghum pith is presented in this work. Based on this technique, lignin and hemicellulose were effectively broken down, amorphous cellulose was obtained and all sugars in the sweet sorghum pith were hydrolysed into monosaccharides. A total of 42 compounds previously found in these materials, including alcohol, ester, acid, alkene, aldehyde ketone, alkene, phenolic and benzene ring compounds, were detected in the pretreatment pith. In addition, several compounds that had not been previously observed in these materials were found in the pretreatment solution. These findings will improve the transformation of lignocellulosic biomass into sugar to create a high-value-added coproduct during the integrated process and to maximize the potential utilization of agricultural waste in current biorefinery processing