Macroeconomic policy interaction: State dependency and implications for financial stability in UK: A systemic review

The association between economic and financial stabilities and influence of macroeconomic policies on the financial sector creates scope of active policy role in financial stability. As a contribution to the existing body of knowledge, this study has analysed the implications of macroeconomic policy interaction/coordination for financial stability, proxied by financial assets, i.e. equity and bonds price oscillation. The critical review and analysis of the existing literature on the subject suggests that there is also ample evidence of interdependence between monetary and fiscal policies and this interrelation necessitates coordination between them for the sake of financial stability. There is also a case for analysing the symmetry of financial markets responses to macroeconomic policy interaction. On methodological and empirical grounds, it is vital to test the robustness of policy recommendations to overcome the limitation of a single empirical approach (Jeffrey–Lindley’s paradox). Hence, the Frequentist and Bayesian approaches should be used in commentary manner. The policy interaction and optimal policy combination should also be analysed in the context of institutional design and major financial events to gain insight into the implications of policy interaction in the periods of stable economic and financial environments as well as period of financial and economic distress

Chaperones convert the energy from ATP into the nonequilibrium stabilization of native proteins.

During and after protein translation, molecular chaperones require ATP hydrolysis to favor the native folding of their substrates and, under stress, to avoid aggregation and revert misfolding. Why do some chaperones need ATP, and what are the consequences of the energy contributed by the ATPase cycle? Here, we used biochemical assays and physical modeling to show that the bacterial chaperones GroEL (Hsp60) and DnaK (Hsp70) both use part of the energy from ATP hydrolysis to restore the native state of their substrates, even under denaturing conditions in which the native state is thermodynamically unstable. Consistently with thermodynamics, upon exhaustion of ATP, the metastable native chaperone products spontaneously revert to their equilibrium non-native states. In the presence of ATPase chaperones, some proteins may thus behave as open ATP-driven, nonequilibrium systems whose fate is only partially determined by equilibrium thermodynamics

Solution NMR structure of an immunodominant epitope of myelin basic protein

Using solution NMR spectroscopy, three-dimensional structures have been obtained for an 18-residue synthetic polypeptide fragment of 18.5 kDa myelin basic protein (MBP, human residues Q81–T98) under three conditions emulating the protein's natural environment in the myelin membrane to varying degrees: (a) an aqueous solution (100 mm KCl pH 6.5), (b) a mixture of trifluoroethanol (TFE-d2) and water (30 : 70% v/v), and (c) a dispersion of 100 mm dodecylphosphocholine (DPC-d38, 1 : 100 protein/lipid molar ratio) micelles. This polypeptide sequence is highly conserved in MBP from mammals, amphibians, and birds, and comprises a major immunodominant epitope (human residues N83–T92) in the autoimmune disease multiple sclerosis. In the polypeptide fragment, this epitope forms a stable, amphipathic, α helix under organic and membrane-mimetic conditions, but has only a partially helical conformation in aqueous solution. These results are consistent with recent molecular dynamics simulations that showed this segment to have a propensity to form a transient α helix in aqueous solution, and with electron paramagnetic resonance (EPR) experiments that suggested a α-helical structure when bound to a membrane [I. R. Bates, J. B. Feix, J. M. Boggs & G. Harauz (2004) J Biol Chem, 279, 5757–5764]. The high sensitivity of the epitope structure to its environment is characteristic of intrinsically unstructured proteins, like MBP, and reflects its association with diverse ligands such as lipids and other proteins

The classic basic protein of myelin-conserved structural motifs and the dynamic molecular barcode involved in membrane adhesion, protein–protein interactions, and pathogenesis in multiple sclerosis

The myelin basic protein (MBP) family comprises a variety of developmentally-regulated members arising from different transcription start sites, differential splicing, and post-translational modifications. The “classic” isoforms of MBP include the 18.5-kDa form, which predominates in adult human myelin and facilitates compaction of the mature myelin sheath in the central nervous system, thereby maintaining its structural integrity. In addition to membrane-association, the 18.5-kDa and all other classic isoforms are able to interact with a multitude of proteins, including Ca2+-calmodulin, actin, tubulin, and SH3-domain-containing proteins, and thus may be signalling linkers during myelin development and remodelling. All proteins in this family are intrinsically disordered, creating a large effective surface to facilitate multiple protein associations, and are post-translationally modified to various degrees by methylation, phosphorylation, and deimination. We have used spectroscopic (fluorescence, circular dichroism, electron paramagnetic resonance, and nuclear magnetic resonance) and computational (molecular dynamics) approaches to study MBP’s conformational adaptability. A highly-conserved central domain consists of an amphipathic α-helix that associates with a phospholipid membrane. In multiple sclerosis, this segment represents a primary immunodominant epitope. This α-helical structure is adjacent to a proline-rich region that contains a classic SH3-ligand along with two threonyl MAP-kinase phosphorylation sites, and forms a poly-proline type II (PPII) structure. This α-helical segment of the protein is thus essential to proper positioning of the PPII protein-interaction motif, with the local conformation and accessibility being modulated by MAP-kinases, and may represent an important molecular switch. Aberrant post-translational or other modifications in this segment of the protein may participate in the onset and pathogenesis of the human demyelinating disease multiple sclerosis

Binding of the proline-rich segment of Myelin Basic Protein to SH3-domains – spectroscopic, microarray and modelling studies of ligand conformation and effects of post-translational modifications

Myelin basic protein (MBP) is a multifunctional protein involved in maintaining the stability and integrity of the myelin sheath by a variety of interactions with membranes and with cytoskeletal and other proteins. A central segment of MBP is highly conserved in mammals and consists of a membrane surface-associated amphipathic -helix, immediately followed by a proline-rich segment that we hypothesize is an SH3 ligand. We show by circular dichroic spectroscopy that this proline-rich segment forms a polyproline type II helix in vitro under physiological conditions and that phosphorylation at a constituent threonyl residue has a stabilizing effect on its conformation. Using SH3 domain microarrays, we observe that the unmodified recombinant murine 18.5 kDa MBP isoform (rmC1 component) binds the following SH3 domains: Yes1 > PSD95 > cortactin = PexD = Abl = Fyn = c-Src = Itk in order of decreasing affinity. A quasi-deiminated form of the protein (rmC8) binds the SH3 domains Yes1 > Fyn > cortactin = c-Src > PexD = Abl. Phosphorylation of rmC1 at 1-2 threonines within the proline-rich segment by mitogen-activated protein kinase in vitro has no effect on the binding specificity to the SH3 domains on the array. An SH3 domain of chicken Fyn is also demonstrated to bind to lipid membrane-associated C1, phosphorylated C1, and rmC8. Molecular docking simulations of the interaction of the putative SH3 ligand of classic MBP with the human Fyn SH3 domain indicate that the strength of the interaction is of the same order of magnitude as with calmodulin and that the molecular recognition and association is mediated by some weak CH··· interactions between the ligand prolyl residues and the aromatic ones of the SH3 binding site. One such interaction is well-conserved and involves the stacking of an MBP-peptide prolyl and an SH3 domain tryptophanyl residue, as in most other SH3-ligand complexes. Lysyl and arginyl residues in the peptide canonically interact via salt bridges and cation- interactions with negatively charged and aromatic residues in the SH3 domain binding site. Posttranslational modifications (phosphorylation or methylation) of the ligand cause noticeable shifts in the conformation of the flexible peptide and its side chains but do not predict any major inhibition of the binding beyond somewhat less favorable interactions for peptides with phosphorylated seryl or threonyl residues

Les phytosterols (intérêt nutritionnel pour la prise en charge des hypercholestérolemies)

Il est clairement établi qu'une cholestérolémie élevée et un LDL-cholestérol élevé sont des facteurs de risque majeur de maladie cardiovasculaire avec une probabilité élevée de maladie coronarienne. Les phytostérols composés retrouvés uniquement dans le monde végétal, apparaissent aujourd'hui comme un moyen diététique complémentaire pour la prise en charge des hypercholestérolémies. En effet ne dose de 1,5 g/jour d'équivalent en phytostérol libre permet de diminuer le LDL-cholestérol de 10%. Le mécanisme principal de cette diminution semble être lié à l'inhibition compétitive de l'absorption du cholestérol au niveau de sa phase de solubilisation micellaire intestinal. Si leur tolérance à court terme est bonne, aucune étude à long terme n'a été réalisée à ce jour permettant de conclure à l'absence de risque lié à leur consommation à des doses de 1 à 2 g/jour. Le principal effet indésirable décrit est la diminution du b-carotène mais le risque le plus préoccupant semble être la possibilité de formation de dérivés oxydés des phytostérols. Le rapport bénéfice risque va dans le sens de l'utilisation de ces produits pour réduire le LDL-cholestérol sérique et les risques de maladie coronarienne.GRENOBLE1-BU Médecine pharm. (385162101) / SudocSudocFranceF

Unpleasant monetarist arithmetic: Macroprudential edition

This paper shows that the recent trend of separating macroprudential and monetary policies (M&Ms) into two autonomous institutions is undesirable. A strategic (game of chicken type) conflict is likely to occur, whereby each M&M ignores exuberant credit booms, trying to induce the other institution to tighten conditions. This has been observed, for example, in Sweden and Norway after 2010. We postulate a generalised concept of stochastic leadership and argue that greater rigidities give the prudential authority the upper hand strategically on the central bank. We show how this leads to a second type of unpleasant monetarist arithmetic and costly economic fluctuations.Web of Science96312391