Identification of ‘cystic fibrosis protein’ as a complex of two calcium-binding proteins present in human cells of myeloid origin

Cystic fibrosis protein is a serum protein characterized by a pI close to 8.4 and present with a higher concentration in serum and plasma of cystic fibrosis carriers than in controls. This protein was found immunologically indistinguishable from the cystic fibrosis antigen isolated from granulocytes and presenting a sequence analogous to that of MRP-8, a calcium-binding protein expressed in the myeloid cell lineage. Using antibodies directed against MRP-8 and its closely associated calcium-binding protein, MRP-14, we demonstrate here that cystic fibrosis protein purified from serum is a complex of the two proteins MRP-8 and MRP-14.     

Structure and Function of the Hypertension Variant A486V of G Protein-coupled Receptor Kinase 4

G-protein-coupled receptor (GPCR) kinases (GRKs) bind to and phosphorylate GPCRs, initiating the process of GPCR desensitization and internalization. GRK4 is implicated in the regulation of blood pressure, and three GRK4 polymorphisms (R65L, A142V, and A486V) are associated with hypertension. Here, we describe the 2.6 Å structure of human GRK4α A486V crystallized in the presence of 5′-adenylyl β,γ-imidodiphosphate. The structure of GRK4α is similar to other GRKs, although slight differences exist within the RGS homology (RH) bundle subdomain, substrate-binding site, and kinase C-tail. The RH bundle subdomain and kinase C-terminal lobe form a strikingly acidic surface, whereas the kinase N-terminal lobe and RH terminal subdomain surfaces are much more basic. In this respect, GRK4α is more similar to GRK2 than GRK6. A fully ordered kinase C-tail reveals interactions linking the C-tail with important determinants of kinase activity, including the αB helix, αD helix, and the P-loop. Autophosphorylation of wild-type GRK4α is required for full kinase activity, as indicated by a lag in phosphorylation of a peptide from the dopamine D₁ receptor without ATP preincubation. In contrast, this lag is not observed in GRK4α A486V. Phosphopeptide mapping by mass spectrometry indicates an increased rate of autophosphorylation of a number of residues in GRK4α A486V relative to wild-type GRK4α, including Ser-485 in the kinase C-tail.     

Synthesis and biological evaluation of platensimycin analogs

Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity.     

Pulsed magnetohydrodynamic blood flow in a rigid vessel under physiological pressure gradient

Blood flow in a steady magnetic field has been of great interest over recent years. Many researchers have examined the effects of magnetic fields on velocity profiles and arterial pressure, and major studies have focused on steady or sinusoidal flows. In this paper, we present a solution for pulsed magnetohydrodynamic blood flow with a somewhat realistic physiological pressure wave obtained using a Windkessel lumped model. A pressure gradient is derived along a rigid vessel placed at the output of a compliant module which receives the ventricle outflow. Then, velocity profile and flow rate expressions are derived in the rigid vessel in the presence of a steady transverse magnetic field. As expected, results showed flow retardation and flattening. The adaptability of our solution approach allowed a comparison with previously addressed flow cases and calculations presented a good coherence with those well established solutions.     

Lipotropha dorci n. sp. [Neogregarinida], parasite des larves deDorcus parallelipipedus L. [Coleopt. scarab.]

Résumé Des larves deDorcus parallelipipedus L. provenant de Saint-Hilaire-de-Brethmas (Gard) dans la région méditerranéenne de France et récoltées dans des troncs décomposés de chataigniers, se sont révélées intensément parasitées par des Grégarines appartenant à l'ordre desNeogregarinida. Nous étudions leur localisation dans le tissu adipeux, leur cycle, l'action pathogène sur l'h?te et discutons leur place systématique.

---

Summary Lipotropha dorci n. sp. (Neogregarinida) is a parasite developing inDorcus parallelepipedus. The parasite is situated only in the fat body which can be destroyed completely by its activity. The life cycle ofLipotropha includes only one type of schizogony with 3–4 μ long merozo?ts, the spherical uninucleate gametocytes are gathered in pairs and form 23 μ long gametokysts. These give rise to 11 to 12 μ long sporocysts with a thick, non ornamented envelope, gathered round rests of cytoplasma. The size of these different stages enables to distinguishLipotropha dorci from the already described species:Lipotropha macrospora Keilin andLipotropha microspora Keilin.

     

Inhibition of lycopene cyclization by Capsicum chromoplast membranes by 2-aza-2,3-dihydrosqualene

2-Aza-2,3-dihydrosqualene strongly inhibited lycopene cyclase from Capsicum chromoplast membranes.     

Use of [Cit312,314] filaggrin (306–324) analogue for the diagnosis of rheumatoid arthritis. Conformational study by circular dichroism and fourier transformed infrared spectroscopy

Antifilaggrin autoantibodies (AFA) have described to be the most specific markers of rheumatoid arthritis (RA) and epitopes containing citrulline within the sequence of filaggrin identified as major antigenic sites recognised by AFA. In this paper we confirm that citrulline is an essential constituent of filaggrin related antigenic determinants recognised by RA specific autoantibodies, thus having an important role for the development of filaggrin peptides based serological tests. Moreover, we describe our findings on the comparative conformational analysis of filaggrin (306–324) peptide sequence and an analogue in which two arginines were simultaneously substituted by citrulline carried out by Circular Dichroism (CD) and Fourier-Transform Infrared Spectroscopy (FTIR). Results might contribute to the understanding of the structural features that may be important to explain the enhanced binding characteristics of citrullinated peptides to the autoantibodies in rheumatoid arthritis.     

Stabilization of a tetrameric enzyme (α-amino acid ester hydrolase from Acetobacter turbidans) enables a very improved performance of ampicillin synthesis

The stabilized derivative of the enzyme α-amino acid ester hydrolase from Acetobacter turbidans has been found to be very adequate as biocatalyst of the synthesis of the very relevant antibiotic ampicillin. This enzyme resulted much more adequate than the Penicillin G Acylase (PGA) from Escherichia coli (the most used enzyme). The stabilization of the enzyme was required because under optimal conditions (absence of phosphate and 40% of MeOH), no-stabilized derivatives or soluble enzyme from A. turbidans become very rapidly inactivated. Under these conditions, this new stabilized derivative exhibited a very high selectivity for the transferase activity compared to the esterase one, as well as a very low hydrolytic activity towards the antibiotic. Moreover, this new biocatalyst did not recognize -phenylglycine as substrate in the synthetic process. By using the racemic mixture of / phenylglycine methyl ester, 85% of the -ester could be transformed to ampicillin. In contrast, the enzyme from E. coli exhibited a high hydrolytic activity for the ampicillin yielding low synthetic yields. This enzyme also resulted much less enantioselective producing both isomers of the antibiotic.