Zonaroic acid from the brown seaweedDictyopteris undulata (=zonarioides)

Summary A sesquiterpene-substituted 4-hydroxybenzoic acid, zonaroic acid (5), is described from the brown seaweedDictyopteris undulata (=zonarioides). The absolute stereochemistry in the zonarol (1)-chromazonarol (2) and zonaroic acid (5) series has also been defined. The occurrence of5 along with zonarol (1), the corresponding sesquiterpene-substituted hydroquinone, suggests that 4-hydroxybenzoic acid is the ring precursor as in ubiquinone biogenesis.     

基于 PARAFAC 分析的西藏昌都大骨节病地区水体腐殖质性质研究

基于荧光平行因子分析法(PARAFAC), 对西藏昌都大骨节病病区与非病区饮水及沉积物中腐殖质进行研究。腐殖质总有机碳含量在病区和非病区样本间未表现显著差异。PARAFAC识别出5个荧光成分:成分1为类氧化醌, 成分2为类色氨酸, 成分3为陆地源类腐殖质, 成分4为类还原醌, 成分5为类酪氨酸。病区水中富里酸(FA)的成分1 (p<0.10)、成分4 (p<0.05)以及水中胡敏酸(HA)的成分4 (p<0.10)等类醌成分含量高于非病区, 并且存在显著差异。对比水中腐殖质醌氧化还原系统在病区和非病区之间的差异, 发现还原醌形态的差异大于氧化醌形态, FA醌系统的差异大于HA醌系统。虽然HA中还原醌含量较高, 但HA在水中的碳含量很低, 对大骨节病影响较弱, 在病区与非病区之间差异较小。沉积物中腐殖质还原醌含量较高, 且与水中腐殖质存在一定的相互转化关系, 但在病区和非病区之间未表现显著差异。深入了解腐殖质不同组分以及醌的不同氧化还原形态在病区与非病区之间的差异, 对病区改水工程有重要意义。     

MicroRNA control of Nodal signalling

MicroRNAs are crucial modulators of gene expression, yet their involvement as effectors of growth factor signalling is largely unknown. Ligands of the transforming growth factor-beta superfamily are essential for development and adult tissue homeostasis. In early Xenopus embryos, signalling by the transforming growth factor-beta ligand Nodal is crucial for the dorsal induction of the Spemann's organizer. Here we report that Xenopus laevis microRNAs miR-15 and miR-16 restrict the size of the organizer by targeting the Nodal type II receptor Acvr2a. Endogenous miR-15 and miR-16 are ventrally enriched as they are negatively regulated by the dorsal Wnt/beta-catenin pathway. These findings exemplify the relevance of microRNAs as regulators of early embryonic patterning acting at the crossroads of fundamental signalling cascades.     

Asymptotic normal and bootstrap inference in structural VAR analysis

The aim of the paper is to examine the performance of bootstrap and asymptotic parametric inference methods in structural VAR analysis. The results obtained through a Monte Carlo experiment suggest that the two approaches are largely equivalent in most, but not all, cases. While the asymptotic method turns out to be surprisingly robust with respect to the distribution of the errors, the bootstrap does deliver results superior in terms of both length of the confidence interval and coverage when highly non-linear statistics (such as the components of the variance of the forecast error) are considered.     

The insulin-degrading enzyme is an allosteric modulator of the 20S proteasome and a potential competitor of the 19S

The interaction of insulin-degrading enzyme (IDE) with the main intracellular proteasome assemblies (i.e, 30S, 26S and 20S) was analyzed by enzymatic activity, mass spectrometry and native gel electrophoresis. IDE was mainly detected in association with assemblies with at least one free 20S end and biochemical investigations suggest that IDE competes with the 19S in vitro. IDE directly binds the 20S and affects its proteolytic activities in a bimodal fashion, very similar in human and yeast 20S, inhibiting at (IDE)?≤?30 nM and activating at (IDE)?≥?30 nM. Only an activating effect is observed in a yeast mutant locked in the “open” conformation (i.e., the α-3ΔN 20S), envisaging a possible role of IDE as modulator of the 20S “open”–”closed” allosteric equilibrium. Protein–protein docking in silico proposes that the interaction between IDE and the 20S could involve the C-term helix of the 20S α-3 subunit which regulates the gate opening of the 20S.     

FRET studies of various conformational states adopted by transthyretin

Transthyretin (TTR) is an extracellular protein able to deposit into well-defined protein aggregates called amyloid, in pathological conditions known as senile systemic amyloidosis, familial amyloid polyneuropathy, familial amyloid cardiomyopathy and leptomeningeal amyloidosis. At least three distinct partially folded states have been described for TTR, including the widely studied amyloidogenic state at mildly acidic pH. Here, we have used fluorescence resonance energy transfer (FRET) experiments in a monomeric variant of TTR (M-TTR) and in its W41F and W79F mutants, taking advantage of the presence of a unique, solvent-exposed, cysteine residue at position 10, that we have labelled with a coumarin derivative (DACM, acceptor), and of the two natural tryptophan residues at positions 41 and 79 (donors). Trp41 is located in an ideal position as it is one of the residues of β-strand C, whose degree of unfolding is debated. We found that the amyloidogenic state at low pH has the same FRET efficiency as the folded state at neutral pH in both M-TTR and W79F-M-TTR, indicating an unmodified Cys10–Trp41 distance. The partially folded state populated at low denaturant concentrations also has a similar FRET efficiency, but other spectroscopic probes indicate that it is distinct from the amyloidogenic state at acidic pH. By contrast, the off-pathway state accumulating transiently during refolding has a higher FRET efficiency, indicating non-native interactions that reduce the Cys10–Trp41 spatial distance, revealing a third distinct conformational state. Overall, our results clarify a negligible degree of unfolding of β-strand C in the formation of the amyloidogenic state and establish the concept that TTR is a highly plastic protein able to populate at least three distinct conformational states.