Investigating the Role of Pellin03 in TNF Signalling

Tumor necrosis factor (TNF) is an important modulator of the innate immune system, responsible for the activation of immune cells as well as the removal of damaged cells. Aberrant TNF signalling can cause a number of pathologic conditions. TNF binding to TNF receptor 1 triggers the activation of nuclear factor kappa B (NF-κB) leading to pro-inflammatory gene expression as well as the activation of the caspase cascade leading to death. In this study we observed that knockdown or knockout of the ubiquitin E3 ligase, Pellino3, sensitizes cells to TNF-induced apoptosis. Suppressed expression of Pellino3 leads to the activation of NF-κB, thereby inducing the expression of a series of antiapoptotic proteins, indicating that the increased apoptosis that is observed in Pellino3-knockdown or –deficient cells is not due to the regulation of the NF-κB pathway. We found that Pellino3 deficiency enhanced formation of the death-induced signalling complex in response to TNF. Pellino3 directly interacts with DISC components, RIP1 and caspase-8, but not FADD. Furthermore we show that Pellino3 regulates the formation of DISC and apoptosis in a manner that is dependent on the FHA domain but independent of the RING-like domain of Pellino3. The physiological importance of Pellino3 as a regulator of TNF signalling is confirmed by Pellino3-deficient mice showing increased sensitivity to TNF-induced apoptosis and greatly increased lethality in response to TNF administration. These findings define Pellino3 as a novel regulator of TNF signalling and a critical determining factor in dictating whether TNF induces cell survival or death

Investigating the Role of Pellin03 in TNF Signalling

Tumor necrosis factor (TNF) is an important modulator of the innate immune system, responsible for the activation of immune cells as well as the removal of damaged cells. Aberrant TNF signalling can cause a number of pathologic conditions. TNF binding to TNF receptor 1 triggers the activation of nuclear factor kappa B (NF-κB) leading to pro-inflammatory gene expression as well as the activation of the caspase cascade leading to death. In this study we observed that knockdown or knockout of the ubiquitin E3 ligase, Pellino3, sensitizes cells to TNF-induced apoptosis. Suppressed expression of Pellino3 leads to the activation of NF-κB, thereby inducing the expression of a series of antiapoptotic proteins, indicating that the increased apoptosis that is observed in Pellino3-knockdown or –deficient cells is not due to the regulation of the NF-κB pathway. We found that Pellino3 deficiency enhanced formation of the death-induced signalling complex in response to TNF. Pellino3 directly interacts with DISC components, RIP1 and caspase-8, but not FADD. Furthermore we show that Pellino3 regulates the formation of DISC and apoptosis in a manner that is dependent on the FHA domain but independent of the RING-like domain of Pellino3. The physiological importance of Pellino3 as a regulator of TNF signalling is confirmed by Pellino3-deficient mice showing increased sensitivity to TNF-induced apoptosis and greatly increased lethality in response to TNF administration. These findings define Pellino3 as a novel regulator of TNF signalling and a critical determining factor in dictating whether TNF induces cell survival or death

Role of peptide–cell surface interactions in cosmetic peptide application

Cosmetic peptides have gained popularity in a wide range of skincare products due to their good biocompatibility, effective anti-oxidative properties, and anti-aging effects. However, low binding between peptides and the cell surface limits the efficacy of functional peptides. In this study, we designed two novel targeting peptide motifs to enhance the interaction between cosmetic peptides and the cell surface, thereby improving their performance for skin health. To achieve this, we optimized the well-known peptide tripeptide-1 (GHK) by separately grafting the integrin αvβ3-binding motif RGD and the chondroitin sulfate (CS)-binding motif sOtx2 onto it, forming two chimeric targeting peptides, RGD-GHK and sOtx2-GHK. Comparative analysis showed that both RGD-GHK and sOtx2-GHK exhibited superior anti-oxidative and anti-apoptotic effects compared to the non-targeting peptide, GHK. Furthermore, RGD-GHK demonstrated exceptional anti-aging activity, and its potential for promoting wound healing and repairing the skin barrier was evaluated in vitro using cells and skin models. In vitro permeation and in vivo adsorption testing confirmed that RGD-GHK achieved a high local concentration in the skin layer, initiating peptide effects and facilitating in vivo wound healing, while maintaining excellent biocompatibility. The enhancement of signaling cosmetic peptides can be attributed to the specific interaction between the binding motif and cell surface components. Consequently, this targeting peptide holds promising potential as a novel functional peptide for application in cosmetics

The impacts of precipitation increase and nitrogen addition on soil respiration in a semiarid temperate steppe

Soil respiration, Rs, is strongly controlled by water availability in semiarid grasslands. However, how Rs is affected by precipitation change (either as rainfall or as snowfall) especially under increasing nitrogen (N) deposition has been uncertain. A manipulative experiment to investigate the responses of growing season Rs to changes in spring snowfall or summer rainfall with or without N addition was conducted in the semiarid temperate steppe of China during three hydrologically contrasting years. Our results showed that both spring snow addition and summer water addition significantly increased Rs by increasing soil moisture. The effect of spring snow addition only occurred in years with both relatively lower natural snowfall and later snowmelt time. Summer water addition showed a much stronger effect on Rs by increasing plant root growth and microbial activities, but the magnitude also largely depended on the possible legacy effect of previous year precipitation. Our results indicated that precipitation increase in the form of snowfall had weaker effects than that in the form of rainfall as the former only accounted for less than 30% of total precipitation. Compared with other ecosystem processes, Rs was less responsible for increase in N deposition as it did not increase root productivity and microbial activities in the soils. Our results provided field data constraints for modeling the ecosystem carbon balance under the future global change scenarios in semiarid grasslands

PAR-1 Kinase Phosphorylates Dlg and Regulates Its Postsynaptic Targeting at the Drosophila Neuromuscular Junction

SummaryTargeting of synaptic molecules to their proper location is essential for synaptic differentiation and plasticity. PSD-95/Dlg proteins have been established as key components of the postsynapse. However, the molecular mechanisms regulating the synaptic targeting, assembly, and disassembly of PSD-95/Dlg are not well understood. Here we show that PAR-1 kinase, a conserved cell polarity regulator, is critically involved in controlling the postsynaptic localization of Dlg. PAR-1 is prominently localized at the Drosophila neuromuscular junction (NMJ). Loss of PAR-1 function leads to increased synapse formation and synaptic transmission, whereas overexpression of PAR-1 has the opposite effects. PAR-1 directly phosphorylates Dlg at a conserved site and negatively regulates its mobility and targeting to the postsynapse. The ability of a nonphosphorylatable Dlg to largely rescue PAR-1-induced synaptic defects supports the idea that Dlg is a major synaptic substrate of PAR-1. Control of Dlg synaptic targeting by PAR-1-mediated phosphorylation thus constitutes a critical event in synaptogenesis

Synergistic photovoltaic-thermoelectric effect in a nanostructured CdTe/Bi2Te3 heterojunction for hybrid energy harvesting

Recent advances in the photovoltaic and thermoelectric material synthesis and characterization have engendered significant interest in their solar energy harvesting. However, examples of energy harvesting by the two effects in one single cell are relatively rare, and at present there are no known examples to solve the heat problem in a conventional solar cell. Here we show that a synergistic photovoltaic and thermoelectric effect takes place in a single heterojunction solar cell that consists a p-type CdTe nanorod array and n-type Bi2Te3 nanostructures. This novel cell is capable of converting light and heat into electricity via combined photovoltaic and thermoelectric processes, providing a simple and elegant material structure for development of high efficiency solar cells which can harvest solar energy over a wider solar spectrum. In addition, this discovery may provide a viable solution to the heat problems in conventional solar cells. Based on the synergistic photovoltaic and thermoelectric effect, the cell of FTO/CdS/CdTe/Bi2Te3 has been prepared and an efficiency (η) increase of 23.3% is achieved after 1 min illuminatio

A poxviral homolog of the Pellino protein inhibits Toll and Toll-like receptor signalling

Toll-like receptor (TLR) signalling pathways constitute an evolutionarily conserved component of the host immune response to pathogenic infection. Here, we describe the ability of a virally encoded form of the Pellino protein to inhibit Toll- and TLR-mediated activation of downstream Rel family transcription factors. In addition to inhibiting drosomycin promoter activation by Spa¨ tzle in Drosophila melanogaster cells, viral Pellino attenuates the activation of NF-jB by TLR signalling components and by the TLR4 ligand, LPS, in human cells. We propose that viral Pellino, like mammalian Pellinos, contains a forkhead-associated domain but differs from the mammalian forms in that it lacks a complete and functional RING-like domain. We produce a homology model and present experimental data to support this model by demonstrating that, like mammalian Pellinos, viral Pellino can interact with IRAK-1 via its forkhead-associated domain, whereas unlike its mammalian counterparts, it fails to post-translationally modify IRAK-1. Furthermore, we demonstrate that viral Pellino can functionally antagonise the activity of human Pellino3S. Thus, our findings identify potential immunoevasive capabilities possessed by a poxviral homolog of the Pellino protein and add growing evidence for a likely role for Pellino proteins in Toll and TLR signalling

Endothelial Cells Promote Calcification in Aortic Smooth Muscle Cells from Spontaneously Hypertensive Rats

Background/Aims: Vascular calcification and hypertension are intimately linked, and the progression of hypertension is closely correlated with endothelial dysfunction. However, the role of endothelial cells (ECs) in vascular calcification of hypertension remains unclear. Therefore, the present study explored the effects of ECs on calcification of smooth muscle cells (SMCs) from aortas of spontaneously hypertensive rats (SHR). Methods: Aortic ECs and SMCs were isolated from SHR and Wistar rats, respectively. The roles of ECs in the regulation of SMCs calcification were investigated by co-culture and conditioned culture model. Calcium deposition of SMCs was detected by von Kossa staining. Quantization of calcium content in SMCs was determined colorimetrically by the o-cresolphthalein complexone method. Alkaline phosphatase (ALP) activity was measured colorimetrically by p-nitrophenol. The expression levels of MMP-2, MMP-9 and the calcification-promoting proteins were analyzed by Western blot. Results: Calcium deposition, ALP activity and the expression levels of calcification-promoting proteins in SMCs of SHR were significantly higher than that cultured without ECs after 6 days of co-culture with ECs or conditioned culture with the medium of ECs, however, there were no statistical differences between SMCs of Wistar rats. MMP-2 and MMP-9 in co-cultured ECs from SHR were dramatically higher than that cultured without SMCs, nevertheless, there were no statistical differences between ECs from Wistar rats and between SMCs from SHR or Wistar rats. Moreover, SB-3CT, a specific inhibitor of gelatinases, decreased calcium content and the expression levels of calcification-promoting proteins in both co-cultured and conditionally cultured SMCs from SHR. Conclusion: ECs have the ability to promote calcification of aortic SMCs of SHR, and elevated expressions of MMP-2 and MMP-9 in ECs of SHR might facilitate the calcification of SMCs