Comprehensively Surveying Structure and Function of RING Domains from Drosophila melanogaster

Using a complete set of RING domains from Drosophila melanogaster, all the solved RING domains and cocrystal structures of RING-containing ubiquitin-ligases (RING-E3) and ubiquitin-conjugating enzyme (E2) pairs, we analyzed RING domains structures from their primary to quarternary structures. The results showed that: i) putative orthologs of RING domains between Drosophila melanogaster and the human largely occur (118/139, 84.9%); ii) of the 118 orthologous pairs from Drosophila melanogaster and the human, 117 pairs (117/118, 99.2%) were found to retain entirely uniform domain architectures, only Iap2/Diap2 experienced evolutionary expansion of domain architecture; iii) 4 evolutionary structurally conserved regions (SCRs) are responsible for homologous folding of RING domains at the superfamily level; iv) besides the conserved Cys/His chelating zinc ions, 6 equivalent residues (4 hydrophobic and 2 polar residues) in the SCRs possess good-consensus and conservation- these 4 SCRs function in the structural positioning of 6 equivalent residues as determinants for RING-E3 catalysis; v) members of these RING proteins located nucleus, multiple subcellular compartments, membrane protein and mitochondrion are respectively 42 (42/139, 30.2%), 71 (71/139, 51.1%), 22 (22/139, 15.8%) and 4 (4/139, 2.9%); vi) CG15104 (Topors) and CG1134 (Mul1) in C3HC4, and CG3929 (Deltex) in C3H2C3 seem to display broader E2s binding profiles than other RING-E3s; vii) analyzing intermolecular interfaces of E2/RING-E3 complexes indicate that residues directly interacting with E2s are all from the SCRs in RING domains. Of the 6 residues, 2 hydrophobic ones contribute to constructing the conserved hydrophobic core, while the 2 hydrophobic and 2 polar residues directly participate in E2/RING-E3 interactions. Based on sequence and structural data, SCRs, conserved equivalent residues and features of intermolecular interfaces were extracted, highlighting the presence of a nucleus for RING domain fold and formation of catalytic core in which related residues and regions exhibit preferential evolutionary conservation

Balanced truncation with relative/multiplicative error bounds in L∞ norm

We study a class of balanced truncation algorithms applicable to relative/multiplicative model reduction. These algorithms seek to balance the controllability Gramian of a given transfer function and the observability Gramian of its right inverse. For this reason, the algorithms are referred to as inverse-weighted balanced truncation (IWBT) algorithms. It is shown that by using IWBT algorithms one can derive relative and multiplicative L∞ error bounds that are known to hold for other reduction algorithms. It is also shown that the balanced stochastic truncation (BST) method is actually one special, but an \u27optimal\u27 version of the IWBT algorithms. As such, our result also serves to establish the fact that the available error bounds pertaining to BST algorithms actually hold for IWBT algorithms

A Light-Responsive Reversible Molecule-Gated System Using Thymine-Modified Mesoporous Silica Nanoparticles

In this paper, a reversible light-responsive molecule-gated system based on mesoporous silica nanoparticles (MSN) functionalized with thymine derivatives is designed and demonstrated. The closing/opening protocol and release of the entrapped guest molecules is related by a photodimerization–cleavage cycle of thymine upon different irradiation. In the system, thymine derivatives with hydrophilicity and biocompatibility were grafted on the pore outlets of MSN. The irradiation with 365 nm wavelength UV light to thymine-functionalized MSN led to the formation of cyclobutane dimer in the pore outlet, subsequently resulting in blockage of pores and strongly inhibiting the diffusion of guest molecules from pores. With 240 nm wavelength UV light irradiation, the photocleavage of cyclobutane dimer opened the pore and allowed the release of the entrapped guest molecules. As a proof-of-the-concept, Ru­(bipy)₃²⁺ was selected as the guest molecule. Then the light-responsive loading and release of Ru­(bipy)₃²⁺ were investigated. The results indicated that the system had an excellent loading amount (53 μmol g^–1 MSN) and controlled release behavior (82% release after irradiation for 24 h), and the light-responsive loading and release procedure exhibited a good reversibility. Besides, the light-responsive system loaded with Ru­(bipy)₃²⁺ molecule could also be used as a light-switchable oxygen sensor

Synbiotic Combination between <i>Lactobacillus paracasei</i> VL8 and Mannan-Oligosaccharide Repairs the Intestinal Barrier in the Dextran Sulfate Sodium-Induced Colitis Model by Regulating the Intestinal Stem Cell Niche

Previously, Lactobacillus paracasei VL8, a lactobacillus strain isolated from the traditional Finnish fermented dairy product Viili, demonstrated immunomodulatory and antibacterial effects. The prebiotic mannan-oligosaccharide (MOS) further promoted its antibacterial activity and growth performance, holding promise for maintaining intestinal health. However, this has not been verified in vivo. In this study, we elucidated the process by which L. paracasei VL8 and its synbiotc combination (SYN) with MOS repair the intestinal barrier function in dextran sodium sulfate (DSS)-induced colitis mice. SYN surpasses VL8 or MOS alone in restoring goblet cells and improving the tight junction structure. Omics analysis on gut microbiota reveals SYN’s ability to restore Lactobacillus spp. abundance and promote tryptophan metabolism. SYN intervention also inhibits the DSS-induced hyperactivation of the Wnt/β-catenin pathway. Tryptophan metabolites from Lactobacillus induce intestinal organoid differentiation. Co-housing experiments confirm microbiota transferability, replicating intestinal barrier repair. In conclusion, our study highlights the potential therapeutic efficacy of the synbiotic combination of Lactobacillus paracasei VL8 and MOS in restoring the damaged intestinal barrier and offers new insights into the complex crosstalk between the gut microbiota and intestinal stem cells

Synbiotic Combination between <i>Lactobacillus paracasei</i> VL8 and Mannan-Oligosaccharide Repairs the Intestinal Barrier in the Dextran Sulfate Sodium-Induced Colitis Model by Regulating the Intestinal Stem Cell Niche

Previously, Lactobacillus paracasei VL8, a lactobacillus strain isolated from the traditional Finnish fermented dairy product Viili, demonstrated immunomodulatory and antibacterial effects. The prebiotic mannan-oligosaccharide (MOS) further promoted its antibacterial activity and growth performance, holding promise for maintaining intestinal health. However, this has not been verified in vivo. In this study, we elucidated the process by which L. paracasei VL8 and its synbiotc combination (SYN) with MOS repair the intestinal barrier function in dextran sodium sulfate (DSS)-induced colitis mice. SYN surpasses VL8 or MOS alone in restoring goblet cells and improving the tight junction structure. Omics analysis on gut microbiota reveals SYN’s ability to restore Lactobacillus spp. abundance and promote tryptophan metabolism. SYN intervention also inhibits the DSS-induced hyperactivation of the Wnt/β-catenin pathway. Tryptophan metabolites from Lactobacillus induce intestinal organoid differentiation. Co-housing experiments confirm microbiota transferability, replicating intestinal barrier repair. In conclusion, our study highlights the potential therapeutic efficacy of the synbiotic combination of Lactobacillus paracasei VL8 and MOS in restoring the damaged intestinal barrier and offers new insights into the complex crosstalk between the gut microbiota and intestinal stem cells

Synbiotic Combination between <i>Lactobacillus paracasei</i> VL8 and Mannan-Oligosaccharide Repairs the Intestinal Barrier in the Dextran Sulfate Sodium-Induced Colitis Model by Regulating the Intestinal Stem Cell Niche

Previously, Lactobacillus paracasei VL8, a lactobacillus strain isolated from the traditional Finnish fermented dairy product Viili, demonstrated immunomodulatory and antibacterial effects. The prebiotic mannan-oligosaccharide (MOS) further promoted its antibacterial activity and growth performance, holding promise for maintaining intestinal health. However, this has not been verified in vivo. In this study, we elucidated the process by which L. paracasei VL8 and its synbiotc combination (SYN) with MOS repair the intestinal barrier function in dextran sodium sulfate (DSS)-induced colitis mice. SYN surpasses VL8 or MOS alone in restoring goblet cells and improving the tight junction structure. Omics analysis on gut microbiota reveals SYN’s ability to restore Lactobacillus spp. abundance and promote tryptophan metabolism. SYN intervention also inhibits the DSS-induced hyperactivation of the Wnt/β-catenin pathway. Tryptophan metabolites from Lactobacillus induce intestinal organoid differentiation. Co-housing experiments confirm microbiota transferability, replicating intestinal barrier repair. In conclusion, our study highlights the potential therapeutic efficacy of the synbiotic combination of Lactobacillus paracasei VL8 and MOS in restoring the damaged intestinal barrier and offers new insights into the complex crosstalk between the gut microbiota and intestinal stem cells