Construction of histidine-tagged yeast mitochondrial cytochrome c oxidase for facile purification of mutant forms.

Yeast CcO (cytochrome c oxidase) has been developed as a facile system for the production and analysis of mutants of a mitochondrial form of CcO for mechanistic studies. First, a 6H tag (His6 tag) was fused to the C-terminus of a nuclear-encoded subunit of CcO from yeast Saccharomyces cerevisiae. This allowed efficient purification of a WT (wild-type) mitochondrial CcO, 6H-WT (yeast CcO with a 6H tag on the nuclear-encoded Cox13 subunit), with a recovery yield of 45%.

Antischistosomal activity of trioxaquines: in vivo efficacy and mechanism of action on Schistosoma mansoni.

Schistosomiasis is among the most neglected tropical diseases, since its mode of spreading tends to limit the contamination to people who are in contact with contaminated waters in endemic countries. Here we report the in vitro and in vivo anti-schistosomal activities of trioxaquines. These hybrid molecules are highly active on the larval forms of the worms and exhibit different modes of action, not only the alkylation of heme.

Enteral nutrition reduces delayed gastric emptying after standard pancreaticoduodenectomy with child reconstruction.

Background: Delayed gastric emptying (DGE) is a common complication following pancreaticoduodenectomy (PD). Our retrospective study aimed to evaluate the influence of enteral nutrition (EN) on DGE incidence after standard PD with antrectomy and Child reconstruction.

Methods: We retrospectively analyzed 275 consecutive patients who underwent standard PD between January 2000 and September 2009.

An in silico approach combined with in vivo experiments enables the identification of a new protein whose overexpression can compensate for specific respiratory defects in Saccharomyces cerevisiae.

Background: The mitochondrial inner membrane contains five large complexes that are essential for oxidative phosphorylation. Although the structure and the catalytic mechanisms of the respiratory complexes have been progressively established, their biogenesis is far from being fully understood. Very few complex III assembly factors have been identified so far.

Questioning the functional relevance of mitochondrial supercomplexes by time-resolved analysis of the respiratory chain.

Mitochondria are the powerhouses of eukaryotic cells as they feed metabolism with its major substrate. Oxidative-phosphorylation relies on the generation, by an electron/proton transfer chain, of an electrochemical transmembrane potential utilized to synthesize ATP. Although these fundamental principles are not a matter of debate, the emerging picture of the respiratory chain diverges from the linear and fluid scheme.

[Imaging in ankle traumas with special attention to fractures and their mechanisms].

The ankle is the most frequently injured joint. The most common causes include sports injuries, highway accidents and household or workplace accidents. The therapeutic decision is based on radiological and clinical interpretation.

Yeast cytochrome c oxidase: a model system to study mitochondrial forms of the haem-copper oxidase superfamily.

The known subunits of yeast mitochondrial cytochrome c oxidase are reviewed. The structures of all eleven of its subunits are explored by building homology models based on the published structures of the homologous bovine subunits and similarities and differences are highlighted, particularly of the core functional subunit I. Yeast genetic techniques to enable introduction of mutations into the three core mitochondrially-encoded subunits are reviewed.

Open versus laparoscopically-assisted oesophagectomy for cancer: a multicentre randomised controlled phase III trial - the MIRO trial.

Background: Open transthoracic oesophagectomy is the standard treatment for infracarinal resectable oesophageal carcinomas, although it is associated with high mortality and morbidity rates of 2 to 10% and 30 to 50%, respectively, for both the abdominal and thoracic approaches. The worldwide popularity of laparoscopic techniques is based on promising results, including lower postoperative morbidity rates, which are related to the reduced postoperative trauma. We hypothesise that the laparoscopic abdominal approach (laparoscopic gastric mobilisation) in oesophageal cancer surgery will decrease the major postoperative complication rate due to the reduced surgical trauma.

Cellular and molecular large-scale features of fetal adipose tissue: is bovine perirenal adipose tissue brown?

Epidemiological and fetal programming studies point to the role of fetal growth in adult adipose tissue (AT) mass in large mammals. Despite the incidence of fetal AT growth for human health and animal production outcomes, there is still a lack of relevant studies. We determined the cellular and large-scale-molecular features of bovine fetal perirenal AT sampled at 110, 180, 210, and 260 days post-conception (dpc) with the aim of identifying key cellular and molecular events in AT growth.

Trioxaquine PA1259 alkylates heme in the blood-feeding parasite Schistosoma mansoni.

Trioxaquine PA1259 is an efficient drug on larval- and adult-stage schistosomes, able to alkylate heme inside worms treated with it, leading to the formation of covalent heme-drug adducts. Such a mechanism, similar to one reported for other trioxaquines in Plasmodium, indicates that heme may be a common target of these trioxane-based drugs in different blood-feeding parasites.

Deleterious effect of the Qo inhibitor compound resistance-conferring mutation G143A in the intron-containing cytochrome b gene and mechanisms for bypassing it.

The mutation G143A in the inhibitor binding site of cytochrome b confers a high level of resistance to fungicides targeting the bc(1) complex. The mutation, reported in many plant-pathogenic fungi, has not evolved in fungi that harbor an intron immediately after the codon for G143 in the cytochrome b gene, intron bi2. Using Saccharomyces cerevisiae as a model organism, we show here that a codon change from GGT to GCT, which replaces glycine 143 with alanine, hinders the splicing of bi2 by altering the exon/intron structure needed for efficient intron excision.

Pre-duodenal portal vein in polysplenia syndrome: clinical effects and surgical application.

Unlabelled: STATING BACKGROUND: Pre-duodenal portal vein (PPV) is a rare congenital anomaly, usually asymptomatic and thus detected only incidentally in adults. It is often associated with other anomalies which can be included into polysplenic syndrome.

Methods: In this case, a 56-year-old-female was admitted for a degenerative ampullome.

Heme as trigger and target for trioxane-containing antimalarial drugs.

Heme is not only just the binding site responsible for oxygen transport by hemoglobin, but it is also the prosthetic group of many different heme-containing enzymes, such as cytochromes P450, peroxidases, catalase, and several proteins involved in electron transfer. Heme plays a key role in the mechanism of action of many different antimalarial drugs. In degrading the host's hemoglobin, the malaria parasite Plasmodium and several other heme-eating parasites are faced with this redox-active metal complex.

Photolysis and thermolysis of platinum(IV) 2,2'-bipyridine complexes lead to identical platinum(II)-DNA adducts.

Two Pt(IV) and two Pt(II) complexes containing a 2,2'-bipyridine ligand were treated with a short DNA oligonucleotide under light irradiation at 37°C or in the dark at 37 and 50°C. Photolysis and thermolysis of the Pt(IV) complexes led to spontaneous reduction of the Pt(IV) to the corresponding Pt(II) complexes and to binding of Pt(II) 2,2'-bipyridine complexes to N7 of guanine. When the reduction product was [Pt(bpy)Cl(2)], formation of bis-oligonucleotide adducts was observed, whereas [Pt(bpy)(MeNH(2))Cl](+) gave monoadducts, with chloride ligands substituted in both cases.

Development of image analysis tool for the classification of muscle fibre type using immunohistochemical staining.

An accurate characterisation of muscle fibres is essential for studying muscle plasticity. During some transient events such as ageing, myogenesis, physical activity or conversion of muscle to meat, the morphological parameters and/or the fibre type distribution may change. Nowadays, this information is generally obtained using immunohistology techniques, but these analyses are acknowledged to be laborious and time-consuming.

Development of isoniazid-NAD truncated adducts embedding a lipophilic fragment as potential bi-substrate InhA inhibitors and antimycobacterial agents.

Isoniazid-NAD truncated adducts embedding a lipophilic fragment were designed, synthesized and evaluated as inhibitors of the enoyl-acyl carrier protein (ACP) reductase (InhA) of Mycobacterium tuberculosis and as antimycobacterial agents. These compounds, planned as bi-substrate inhibitors and inspired from the active metabolite of isoniazid, combine both the nicotinamide moiety of the cofactor NAD and a lipophilic hydrocarbon chain mimic of the InhA substrate. The lipophilic fragment was introduced using either Suzuki-Miyaura cross-coupling or a classical nucleophilic substitution reaction.

Ultraviolet-absorbing compounds in milk are related to forage polyphenols.

The aim of this work was to characterize UV-absorbing compounds (UAC) in milk in relation to diet. In winter, 4 groups of cows each received a different diet: concentrate rich containing 35% cocksfoot hay (CCH), maize silage (MS), rye grass silage (RS), or rye grass hay (RH). In summer, 2 additional diets were given: mountain grassland hay (GH) and mountain grassland pasture (GP).

Role of preoperative optimization of the liver for resection in patients with hilar cholangiocarcinoma type III.

Background: Long-term survival after complete resection of hilar cholangiocarcinoma remains disappointing. The aim of this retrospective study was to assess the impact of liver optimization on postoperative outcome of hilar cholangiocarcinoma type III.

Materials And Methods: In a retrospective, single-center analysis, outcomes in patients with hilar cholangiocarcinoma type III who underwent resection after preoperative liver optimization (preoperative transhepatic biliary drainage [PTBD], bile replacement, and/or portal vein embolization [PVE]) were compared with nonoptimized controls.

Removal of transanastomotic pancreatic stent tubes after pancreaticoduodenectomy: a new role for double-balloon enteroscopy.

Background: Endoscopic interventions are usually very challenging in patients with anatomic changes caused by earlier GI surgery. The recent development of the double-balloon enteroscopy (DBE) system creates an opportunity to reach the biliary tract and the pancreatic duct in postsurgical conditions.

Objective: To report a further application of DBE in surgical patients; namely, extraction of pancreatic stents placed in pancreaticojejunal anastomosis during pancreaticoduodenectomy.

Trioxaferroquines as new hybrid antimalarial drugs.

The synthesis, characterization, and antimalarial evaluation of a new series of potential antimalarial molecules, named trioxaferroquines, are reported. Trioxaferroquines are hybrid antimalarial drugs containing a 1,2,4-trioxane covalently linked to ferroquine (Fq), a synthetic ferrocenylquinoline derivative currently under clinical development. The aim was to combine, within a single structure, an iron(II) species, a 1,2,4-trioxane, as in artemisinin, and a substituted quinoline, as in chloroquine.

Validation of a Dot-Blot quantitative technique for large scale analysis of beef tenderness biomarkers.

Beef tenderness is a very complex and multifactorial sensorial meat quality trait, which depends partly on muscle characteristics. This tissue is very variable according to animal type (age, breed and sex) and rearing conditions. Consequently, beef tenderness exhibits a great variability.

Formation of the redox cofactor centers during Cox1 maturation in yeast cytochrome oxidase.

The biogenesis of cytochrome c oxidase initiates with synthesis and maturation of the mitochondrion-encoded Cox1 subunit prior to the addition of other subunits. Cox1 contains redox cofactors, including the low-spin heme a center and the heterobimetallic heme a(3):Cu(B) center. We sought to identify the step in the maturation of Cox1 in which the redox cofactor centers are assembled.

[Liver transplantation for subcapsular haematoma during HELLP Syndrome].

The hepatic rupture of a subcapsular haematoma during HELLP syndrome is a rare complication carrying a high mortality. There is no clear guideline management in the literature. We report here a case of a subcapsular haematoma which required liver transplantation.