Differential channelling of liver lipids in relation to susceptibility to hepatic steatosis in two species of ducks

In the human, hepatic steatosis can be associated with an imbalance between synthesis, secretion and storage of hepatic lipids, and exhibits a genetic susceptibility. The effect of overfeeding on hepatic lipid channelling was investigated in two genotypes of ducks that differ in their susceptibility to fatty liver, i.e. the common duck, Anas platyrhynchos, and the Muscovy duck, Cairina moschata. Before overfeeeding, the Muscovy duck exhibited a lower subcutaneous adiposity and a higher muscular development, whereas hepatic composition was similar in both genotypes (>5% lipids and triglycerides accounting for 6–10% lipids). In the plasma lipoprotein profile, HDL predominated (5.5–7.8 g/l) over VLDL (0.09–0.25 g/l) and LDL (0.65–1.06 g/l). All lipid and lipoprotein concentrations were lower in the Muscovy duck. In response to overfeeding, the Muscovy duck exhibited a higher degree of hepatic steatosis (62 vs. 50% lipids), and a lower increase in adiposity and in the concentration of plasma triglycerides (6-fold vs. 10-fold) and VLDL (23-fold vs. 34-fold). Thus, certain genotypes may be more responsive to the dietary induction of fatty liver because of a less efficient channelling of hepatic lipids towards secretion into plasma and adipose storage, and the duck may represent a suitable model in which to study the development of hepatic steatosis and its pathogenesis.     

Drosophila necrotic mutations mirror disease-associated variants of human serpins

Polymerization of members of the serpin superfamily underlies diseases as diverse as cirrhosis, angioedema, thrombosis and dementia. The Drosophila serpin Necrotic controls the innate immune response and is homologous to human alpha(1)-antitrypsin. We show that necrotic mutations that are identical to the Z-deficiency variant of alpha(1)-antitrypsin form urea-stable polymers in vivo. These necrotic mutations are temperature sensitive, which is in keeping with the temperature-dependent polymerization of serpins in vitro and the role of childhood fevers in exacerbating liver disease in Z alpha-antitrypsin deficiency. In addition, we identify two nec mutations homologous to an antithrombin point mutation that is responsible for neonatal thrombosis. Transgenic flies carrying an S>F amino-acid substitution equivalent to that found in Siiyama-variant antitrypsin (nec(S>F.UAS)) fail to complement nec-null mutations and demonstrate a dominant temperature-dependent inactivation of the wild-type nec allele. Taken together, these data establish Drosophila as a powerful system to study serpin polymerization in vivo.     

Periplasmic electron carriers and photo-induced electron transfer in the photosynthetic bacterium Ectothiorhodospira sp.

A detailed analysis of the periplasmic electron carriers of the photosynthetic bacterium Ectothiorhodospira sp. has been performed. Two low mid-point redox potential electron carriers, cytochrome c′ and cytochrome c, are detected. A high potential iron–sulfur protein is the only high mid-point redox potential electron transfer component present in the periplasm. Analysis of light-induced absorption changes shows that this high potential iron–sulfur protein acts in vivo as efficient electron donor to the photo-oxidized high potential heme of the Ectothiorhodospira sp. reaction center. This revised version was published online in June 2006 with corrections to the Cover Date.     

Solution structure of the recombinant human oncoprotein p13 MTCP1

The human oncoprotein p13 ^MTCP1 is coded by the MTCP1 gene, a gene involved in chromosomal translocations associated with T-cell prolymphocytic leukemia, a rare form of human leukemia with a mature T-cell phenotype. The primary sequence of p13 ^MTCP1 is highly and only homologous to that of p14 ^TCL1 , a product coded by the gene TCL1 which is also involved in T-cell prolymphocytic leukemia. These two proteins probably represent the first members of a new family of oncogenic proteins. We present the three-dimensional solution structure of the recombinant p13 ^MTCP1 determined by homonuclear proton two-dimensional NMR methods at 600 MHz. After proton resonance assignments, a total of 1253 distance restraints and 64 dihedral restraints were collected. The solution structure of p13 ^MTCP1 is presented as a set of 20 DYANA structures. The rmsd values with respect to the mean structure for the backbone and all heavy atoms for the conformer family are 1.07 ± 0.19 and 1.71 ± 0.17 Å, when the structured core of the protein (residues 11–103) is considered. The solution structure of p13 ^MTCP1 consists of an orthogonal -barrel, composed of eight antiparallel -strands which present an original arrangement. The two -pleated loops which emerge from this barrel might constitute the interaction surface with a potential molecular partner.     

Genetic advances for studying Mycobacterium tuberculosis pathogenicity

Tuberculosis remains the greatest cause of death worldwide because of a single pathogen. Despite its importance, the genetic basis of the pathogenicity of Mycobacterium tuberculosis remains poorly understood, mainly because the most productive investigative approach, molecular genetic analysis, has been severely hampered by a lack of efficient tools. However, significant advances, including the development of methods for inactivating genes and studying their expression with reporter genes, have been recently made. This progress may lead to opportunities for developing new vaccines and antituberculous drugs. The aim of this review is to examine the present state of the art in mycobacterial molecular genetics and pinpoint some expected or promising areas for future research.     

OntoGene in BioCreative II

Background:

Research scientists and companies working in the domains of biomedicine and genomics are increasingly faced with the problem of efficiently locating, within the vast body of published scientific findings, the critical pieces of information that are needed to direct current and future research investment.

Results:

In this report we describe approaches taken within the scope of the second BioCreative competition in order to solve two aspects of this problem: detection of novel protein interactions reported in scientific articles, and detection of the experimental method that was used to confirm the interaction. Our approach to the former problem is based on a high-recall protein annotation step, followed by two strict disambiguation steps. The remaining proteins are then combined according to a number of lexico-syntactic filters, which deliver high-precision results while maintaining reasonable recall. The detection of the experimental methods is tackled by a pattern matching approach, which has delivered the best results in the official BioCreative evaluation.

Conclusion:

Although the results of BioCreative clearly show that no tool is sufficiently reliable for fully automated annotations, a few of the proposed approaches (including our own) already perform at a competitive level. This makes them interesting either as standalone tools for preliminary document inspection, or as modules within an environment aimed at supporting the process of curation of biomedical literature.

     

Effects of oxidation on the hydrolysis by cholesterol esterase of sitosteryl esters as compared to a cholesteryl ester

Phytosteryl esters (PE) are used as ingredients in functional food to decrease plasma concentration of low density lipoprotein-cholesterol (LDL-C). Effective impairment of cholesterol absorption by PE suggests that these esters are hydrolyzed by the pancreatic cholesterol esterase (CEase, EC 3.1.1.13) and the liberated sterol may interfere with cholesterol reducing its intestinal absorption. PE-enriched foods are marketed for cooking purposes, and temperature is one of the most important factors leading to the formation of oxidation products. Very little is known about the outcome of PE oxides during the digestive process. A new analytical method based on mass spectrometric detection directly after enzymatic reaction was developed to determine in vitro the activity of CEase on PE and their oxides present in functional food. Using this method, we identified a new inhibitor of CEase: sitosteryl 9,10-dihydroxystearate, which behaves as a non-competitive inhibitor of the hydrolysis of cholesteryl oleate and sitosteryl oleate.