Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of ascaris reveals a novel fold and two discrete lipid-binding sites

Parasitic nematode worms cause serious health problems in humans and other animals. They can induce allergic-type immune responses, which can be harmful but may at the same time protect against the infections. Allergens are proteins that trigger allergic reactions and these parasites produce a type that is confined to nematodes, the nematode polyprotein allergens (NPAs). These are synthesized as large precursor proteins comprising repeating units of similar amino acid sequence that are subsequently cleaved into multiple copies of the allergen protein. NPAs bind small lipids such as fatty acids and retinol (Vitamin A) and probably transport these sensitive and insoluble compounds between the tissues of the worms. Nematodes cannot synthesize these lipids, so NPAs may also be crucial for extracting nutrients from their hosts. They may also be involved in altering immune responses by controlling the lipids by which the immune and inflammatory cells communicate. We describe the molecular structure of one unit of an NPA, the well-known ABA-1 allergen of Ascaris and find its structure to be of a type not previously found for lipid-binding proteins, and we describe the unusual sites where lipids bind within this structur

Increased dynamics in the 40-57 Ω-loop of the G41S variant of human cytochrome c promote its pro-apoptotic conformation

Thrombocytopenia 4 is an inherited autosomal dominant thrombocytopenia, which occurs due to mutations in the human gene for cytochrome c that results in enhanced mitochondrial apoptotic activity. The Gly41Ser mutation was the first to be reported. Here we report stopped-flow kinetic studies of azide binding to human ferricytochrome c and its Gly41Ser variant, together with backbone amide H/D exchange and 15N-relaxation dynamics using NMR spectroscopy, to show that alternative conformations are kinetically and thermodynamically more readily accessible for the Gly41Ser variant than for the wild-type protein. Our work reveals a direct conformational link between the 40-57 Ω-loop in which residue 41 resides and the dynamical properties of the axial ligand to the heme iron, Met80, such that the replacement of glycine by serine promotes the dissociation of the Met80 ligand, thereby increasing the population of a peroxidase active state, which is a key non-native conformational state in apoptosis

Cost savings for elective laparoscopic resection compared with open resection for colorectal cancer in a region of high uptake

Previous cost analyses of laparoscopic resection for colorectal cancer (CRC) reported slightly higher or similar costs to those of open resection. These analyses were based on randomised controlled trials when the laparoscopic approach was newly adopted. This study compared costs for laparoscopic versus open resection in a region of high uptake where adoption is mature.Hospital cost data were obtained for elective resections for CRC that occurred between June 2009 and June 2011 in public hospitals in Queensland, Australia. The primary outcome was total cost and secondary outcomes were length-of-stay, operating time, and ICU admission. Multivariate least-squares regression was used to adjust for potential confounders: age, sex, comorbidities, procedure, and hospital volume.The crude mean cost for laparoscopic resection was euro 20,036 compared with that for open resection of euro 22,780 (difference = euro 2,744). Patients who underwent laparoscopic resection (744/1,397; 53 %) were slightly younger and had fewer comorbidities (decreasing costs) but more had rectal surgery (increasing costs). The adjusted mean cost for laparoscopic resection was euro 20,396 compared with euro 22,442 for open resection (difference = euro 2,054). Compared with open resection, when adjusted for potential confounders, laparoscopic resection resulted in similar operating time (216 vs. 214 min), shorter length-of-stay (difference = -1.1 days, 95 % CI -1.9, -0.3), and shorter admission to ICU (difference = -7.3 h, 95 % CI -11.9, -2.7).This non-randomised study in a region of high uptake found a similar operating time and lower cost for laparoscopic resection for CRC compared with those of open resection due to a shorter length-of-stay and shorter time in ICU. Laparoscopic resection for CRC saves money when the procedure is widely adopted and surgeons are experienced in the technique