Lacroixwheeler1882

cis-Prenyltransferases (cis-PTs) catalyze consecutive condensations of isopentenyl diphosphate to an allylic diphosphate acceptor to produce a linear polyprenyl diphosphate of designated length. Dimer formation is a prerequisite for cis-PTs to catalyze all cis-prenyl condensation reactions. The structure-function relationship of a conserved C-terminal RXG motif in cis-PTs that forms inter-subunit interactions and has a role in catalytic activity has attracted much attention. Here, we solved the crystal structure of a medium-chain cis-PT from Thermobifida fusca that produces dodecaprenyl diphosphate as a polyprenoid glycan carrier for cell wall synthesis. The structure revealed a characteristic dimeric architecture of cis-PTs in which a rigidified RXG motif of one monomer formed inter-subunit hydrogen bonds with the catalytic site of the other monomer, while the RXG motif of the latter remained flexible. Careful analyses suggested the existence of a possible long-range negative cooperativity between the two catalytic sites on the two monomeric subunits that allowed the binding of one subunit to stabilize the formation of the enzyme-substrate ternary complex and facilitated the release of Mg-PPi and subsequent intra-molecular translocation at the counter subunit so that the condensation reaction could occur in consecutive cycles. The current structure reveals the dynamic nature of the RXG motif and provides a rationale for pursuing further investigations to elucidate the inter-subunit cooperativity of cis-PTs.Dimethyl fumarate (DMF) has emerged as a first-line treatment for the relapsing-remitting multiple sclerosis (RRMS) subtype. It is hypothesized that DMF has anti-inflammatory and antioxidant effects although mechanisms are not fully understood. This study used RNA-seq to profile gene expression responses to DMF in cultured astrocytes. DMOG Responses were compared with those of isosorbide di-(methyl fumarate) (IDMF), a newly designed fumarate that may partially replicate DMF activity with fewer adverse effects. Both compounds altered the expression of MS-associated genes, including those near MS susceptibility loci and genes dysregulated in MS patient astrocytes. The shared DMF/IDMF transcriptome response involved altered expression of antioxidant genes (e.g., HMOX1) and genes linked to extracellular matrix integrity (TIMP3, MMP9) and migration of pro-inflammatory cells into CNS (CCL2). IDMF-specific transcriptome responses included down-regulation of mitotic genes associated with a proliferative reactive astrocyte phenotype (ICAM1) and repression of genes encoding NF-kappaB subunits (NFKB2, RELA, RELB) and NF-kappaB targets (NCAPG, CXCL1, OAS3). Overall, these results identify astrocyte-centered mechanisms that may contribute to the established efficacy of DMF as an RRMS treatment. Furthermore, our findings support a rationale for further studies of IDMF as a novel fumarate, which may have unique suppressive effects on astrocyte reactivity and glial scar formation. [200 words].A polyacrylamide-based hydrophilic microsphere with a lot of hydroxyl groups on surface (PAM-OH HMS) was prepared in one step. The synthetic process was simple reverse suspension polymerization without any chemical derivation or grafting steps. The properties of obtained HMS were characterized by scanning electron microscopy (SEM), static water contact angle measurement, and FT-IR. The abundant hydroxyl groups on the surface make the material highly good hydrophilic and thus it was utilized for N-glycopeptides enrichment. The enrichment efficiency of PAM-OH HMSs was demonstrated by capturing N-linked glycopeptides from tryptic digest of human immunoglobulin G (IgG). The detection sensitivity for N-glycopeptides identification by MALDI-TOF MS was as low as 10 fmol for tryptic digest of standard human IgG. The selectivity of the HMS towards N-glycopeptides had almost no decrease when the molar ratio of BSA tryptic digest to IgG tryptic digest was increased from 101 to 1001. Moreover, in the LC-MS/MS analysis of real biological sample, a total of 344 unique N-glycosites in 598 unique N-glycopeptides from 172 N-glycoproteins were identified from 2 μL human serum after deglycosylated by PNGase F, and 825 intact N-glycopeptides with different types of glycoform were detected when directly analyzed the N-glycopeptides enriched by PAM-OH HMS. To show the potential of our material in solving real biological issues, N-glycopeptides in the serum from hepatocelluar carcinoma (HCC) patient and health control were enriched and quantified. All the experiments demonstrated that this polyacrylamide-based hydrophilic microsphere shows a great potential to enrich the low-abundance N-glycopeptides for glycoproteome analysis of real complicated biological samples.Recently, there has been growing interests in the development of composite materials as the new alternative gas sensing materials for replacing metal oxide based sensors which require the elevated operating temperature. Herein, we reported the fabrication and testing of new sensing composite materials based on the conductive poly(p-phenylene) (PPP) nanoparticle and zeolites for sulfur dioxide (SO2) detection at room temperature under the effects of doping, zeolite type, zeolite content, SO2 concentration as well as interferences and humidity. The relative electrical conductivity response depended critically on the doping agent type, doping ratio, and doping temperature. The addition of porous zeolites into the doped-PPP (dPPP) matrix induced the improvement in selectivity and sensing performances towards SO2 as it promoted more surface area for SO2 adsorption and its new synergistic effect with the conductive dPPP, related to the additional conductive polymer doping from the dissolution of the SO2 in intrazeolitic water as identified and reported here. Among all materials, the dPPP/ZSM-5 composite with perchloric acid (HClO4) as the doping agent, the doping ratio of 501, the doping temperature of 70 °C, and the zeolite content of 30% exhibited the highest relative response of 25.42 towards 500 mg L-1 SO2 with good repeatability. This composite provided the SO2 sensitivity of 0.0483 L mg-1 with R2 of 0.9927 and the limit of detection (LOD) of 5 mg L-1 as determined from the electrical conductivity signal to noise ratio. The present sensing material is a potential candidate in the practical detection of SO2 at room temperature.