Ubiquilin and p97/VCP bind erasin, forming a complex involved in ERAD

Loss of ubiquilin or erasin activates ER stress, increases accumulation of polyubiquitinated proteins, and shortens lifespan in worms

Ubiquilin at a crossroads in protein degradation pathways

Ubiquilin proteins are conserved across all eukaryotes and function in the regulation of protein degradation. We found that ubiquilin functions to regulate macroautophagy and that the protein is also a substrate of chaperone-mediated autophagy

Enhanced Heterogeneous Catalytic Conversion of Furfuryl Alcohol into Butyl Levulinate

We study the catalytic condensation of furfuryl alcohol with 1‐butanol to butyl levulinate. A screening of several commercial and as‐synthesized solid acid catalysts shows that propylsulfonic acid‐functionalized mesoporous silica outperforms the state‐of‐the‐art phosphotungstate acid catalysts. The catalyst is prepared via template‐assisted sol‐gel polycondensation of TEOS and MPTMS. It gives 96 % yield (and 100 % selectivity) of butyl levulinate in 4 h at 110 °C. Reaction profiles before and after a hot filtration test confirm that the active catalytic species do not leach into the solution. The catalyst synthesis, characterization, and mode of operation are presented and discussed

Mechanisms underlying the inhibitory effects of tachykinin receptor antagonists on eosinophil recruitment in an allergic pleurisy model in mice

1. The activation of tachykinin NK receptors by neuropeptides may induce the recruitment of eosinophils in vivo. The aim of the present study was to investigate the effects and underlying mechanism(s) of the action of tachykinin receptor antagonists on eosinophil recruitment in a model of allergic pleurisy in mice. 2. Pretreatment of immunized mice with capsaicin partially prevented the recruitment of eosinophils after antigen challenge, suggesting the potential contribution of sensory nerves for the recruitment of eosinophils. 3. Local (10–50 nmol per pleural cavity) or systemic (100–300 nmol per animal) pretreatment with the tachykinin NK(1) receptor antagonist SR140333 prevented the recruitment of eosinophils induced by antigen challenge of immunized mice. Neither tachykinin NK(2) nor NK(3) receptor antagonists suppressed eosinophil recruitment. 4. Pretreatment with SR140333 failed to prevent the antigen-induced increase of interleukin-5 concentrations in the pleural cavity. Similarly, SR140333 failed to affect the bone marrow eosinophilia observed at 48 h after antigen challenge of immunized mice. 5. SR140333 induced a significant increase in the concentrations of antigen-induced eotaxin at 6 h after challenge. 6. Antigen challenge of immunized mice induced a significant increase of Leucotriene B(4) (LTB(4)) concentrations at 6 h after challenge. Pretreatment with SR140333 prevented the antigen-induced increase of LTB(4) concentrations. 7. Our data suggest an important role for NK(1) receptor activation with consequent LTB(4) release and eosinophil recruitment in a model of allergic pleurisy in the mouse. Tachykinins appear to be released mainly from peripheral endings of capsaicin-sensitive sensory neurons and may act on mast cells to facilitate antigen-driven release of LTB(4)

Treatment with a Novel Chemokine-Binding Protein or Eosinophil Lineage-Ablation Protects Mice from Experimental Colitis

Eosinophils are multifunctional leukocytes implicated in numerous inflammatory diseases. The present study was conducted to clarify the precise role of eosinophils in the development of colitis by using eosinophil-depleted mice and a novel chemokine-binding protein that neutralizes CCL11 action. Colitis was induced by administration of dextran sodium sulfate (DSS) to wild-type and eosinophil-deficient ΔdblGATA-1 mice. Accumulation of eosinophils in the gut of mice given DSS paralleled worsening of clinical score and weight loss. In response to DSS, ΔdblGATA-1 mice showed virtual absence of eosinophil recruitment, amelioration of clinical score, weight loss, and tissue destruction, and no lethality. There was a decrease in CXCL1 and CCL3 production and decreased neutrophil influx in the intestine of ΔdblGATA-1 mice. Transfer of bone marrow cells from wild-type mice reconstituted disease manifestation in DSS-treated ΔdblGATA-1 mice, and levels of CCL11 were increased after DSS treatment and localized to inflammatory cells. Treatment with the chemokine-binding protein evasin-4 at a dose that prevented the function of CCL11 greatly ameliorated clinical score, weight loss, overall tissue destruction, and death rates. In conclusion, the influx of eosinophils is critical for the induction of colitis by DSS. Treatment with a novel chemokine-binding protein decreased eosinophil influx and greatly ameliorated colitis, suggesting that strategies that interfere with the recruitment of eosinophils may be useful as therapy for colitis

Catalytic routes towards acrylic acid, adipic acid and ε-caprolactam starting from biorenewables

The majority of bulk chemicals are derived from crude oil, but the move to biorenewable resources is gaining both societal and commercial interest. Reviewing this transition, we first summarise the types of today's biomass sources and their economical relevance. Then, we assess the biobased productions of three important bulk chemicals: acrylic acid, adipic acid and epsilon-caprolactam. These are the key monomers for high-end polymers (polyacrylates, nylon 6.6 and nylon 6, respectively) and are all produced globally in excess of two million metric tons per year. The biobased routes for each target molecule are analysed separately, comparing the conventional processes with their sustainable alternatives. Some processes have already received extensive scientific attention. Other, more novel routes are also being considered. We find several common trends: For all three compounds, there are no commercial methods for direct conversion of biobased feedstocks. However, combinations of biotechnologically produced platform chemicals with subsequent chemical modifications are emerging and showing promising results. We then discuss several distinct strategies for implementing biorenewable processes. For each biotechnological and chemocatalytic route, current efficiencies and limitations are presented, but we urge that these routes should be assessed mainly on their potential and prospects for future application. Today, biorenewable routes cannot yet compete with their petrochemical equivalents. However, given that most of them are still in the early stages of development, we foresee their commercial implementation in the next two decades