Decisions about testing and termination of pregnancy for different fetal conditions: a qualitative study of European White and Pakistani mothers of affected children.

The aim of this study is to explore reasons for and against prenatal testing and termination for a range of conditions in women from two different ethnic backgrounds. A total of 19 Pakistani and European women in West Yorkshire, UK, who either had a child with a genetic condition or had terminated a pregnancy for one, completed a questionnaire about their attitudes regarding prenatal testing and termination for 30 different fetal conditions and were interviewed about their reasons for their responses. There were more similarities than differences between the Pakistani and European white women.

The production of reactive oxygen species by complex I.

ROS (reactive oxygen species) are considered to be a major cause of cellular oxidative stress, linked to neuromuscular diseases and aging. Complex I (NADH:ubiquinone oxidoreductase) is one of the main contributors to superoxide production by mitochondria, and knowledge of its mechanism of O2 reduction is required for the formulation of causative connections between complex I defects and pathological effects. There is evidence for two distinct (but not mutually exclusive) sites of O2 reduction by complex I.

Reversible interconversion of carbon dioxide and formate by an electroactive enzyme.

Carbon dioxide (CO(2)) is a kinetically and thermodynamically stable molecule. It is easily formed by the oxidation of organic molecules, during combustion or respiration, but is difficult to reduce. The production of reduced carbon compounds from CO(2) is an attractive proposition, because carbon-neutral energy sources could be used to generate fuel resources and sequester CO(2) from the atmosphere.

Reduction of the iron-sulfur clusters in mitochondrial NADH:ubiquinone oxidoreductase (complex I) by EuII-DTPA, a very low potential reductant.

NADH:ubiquinone oxidoreductase (complex I) is the first enzyme of the mitochondrial electron transport chain. It contains a flavin mononucleotide to oxidize NADH, and eight iron-sulfur clusters. Seven of them transfer electrons between the flavin and the quinone-binding site, and one is on the opposite side of the flavin.

Brain allopregnanolone in the fetal and postnatal rat in response to uteroplacental insufficiency.

Background/aims: Allopregnanolone suppresses central nervous system activity and has neuroprotective actions in hypoxia-induced brain injury. In pregnant sheep allopregnanolone concentrations are high during fetal life and decline rapidly after birth. We investigated brain allopregnanolone concentrations of fetal and postnatal rats derived from normal and growth restricted pregnancies.

Search strategies in structural bioinformatics.

Optimisation problems pervade structural bioinformatics. In this review, we describe recent work addressing a selection of bioinformatics challenges. We begin with a discussion of research into protein structure comparison, and highlight the utility of Kolmogorov complexity as a measure of structural similarity.

Effects of chronic celecoxib on testicular function in normal and lipopolysaccharide-treated rats.

Celecoxib (Celebrex), an inhibitor of cyclooxygenase-2 (COX-2; prostaglandin-endoperoxide synthase 2; EC 1.14.99.

Modular construction of oxide structures--compositional control of transition metal coordination environments.

The effects of reaction temperature and pO2 were investigated on a series of (Ba,Ca,Nd)FeO3-delta perovskite systems in order to isolate phases containing ordered arrangements of the distinct vacancy and cation ordering patterns identified in less compositionally complex iron oxide systems. Initial synthesis in air at high temperature yields cubic perovskite phases (I) with average iron oxidation states higher than 3; selected area electron diffraction together with diffuse features observed in the synchrotron X-ray diffraction (SXRD) patterns of these materials show evidence of small domains of short-range cation and vacancy order. Annealing these materials in nitrogen or in a sealed tube in the presence of an NiO/Ni buffer yielded the Fe(3+) phase Ca2Ba2Nd2Fe6O16 (II), closely related to Sr2LaFe3O8 but with partial cation order as well as anion order present the larger Ba cations are largely present in the 12-coordinate site between the octahedral iron layers, and Ca is largely present in 10-coordinate sites between octahedral and tetrahedral sites.

Auxilin depletion causes self-assembly of clathrin into membraneless cages in vivo.

Auxilin is a cofactor for Hsc70-mediated uncoating of clathrin-coated vesicles (CCVs). However, small interfering RNA (siRNA) knockdown of the ubiquitous auxilin 2 in HeLa cells only moderately impairs clathrin-dependent trafficking. In this study, we show that HeLa cells also express auxilin 1, previously thought to be neuron specific, and that both auxilins need to be depleted for inhibition of clathrin-mediated endocytosis and intracellular sorting.

Production of reactive oxygen species by complex I (NADH:ubiquinone oxidoreductase) from Escherichia coli and comparison to the enzyme from mitochondria.

The generation of reactive oxygen species by mitochondrial complex I (NADH:ubiquinone oxidoreductase) is considered a significant cause of cellular oxidative stress, linked to neuromuscular diseases and aging. Defining its mechanism is important for the formulation of causative connections between complex I defects and pathological effects. Oxygen is probably reduced at two sites in complex I, one associated with NADH oxidation in the mitochondrial matrix and the other associated with ubiquinone reduction in the membrane.

Prediction of recursive convex hull class assignments for protein residues.

Motivation: We introduce a new method for designating the location of residues in folded protein structures based on the recursive convex hull (RCH) of a point set of atomic coordinates. The RCH can be calculated with an efficient and parameterless algorithm.

Results: We show that residue RCH class contains information complementary to widely studied measures such as solvent accessibility (SA), residue depth (RD) and to the distance of residues from the centroid of the chain, the residues' exposure (Exp).

Charge-transfer transitions in the vacuum-ultraviolet of protein circular dichroism spectra.

Circular dichroism (CD) is widely used in the structural characterization and secondary structure determination of proteins. The vacuum UV region (below 190 nm), where charge-transfer transitions have an influence on the CD spectra, can be accessed using synchrotron radiation circular dichroism (SRCD) spectroscopy. Recently, charge-transfer transitions in a conformationally diverse set of dipeptides have been characterized ab initio using complete active space self-consistent field calculations, and the relevant charge distributions have been parametrized for use in the matrix method for calculations of protein CD.

Off-pathway, oxygen-dependent thiamine radical in the Krebs cycle.

The catalytic cofactor thiamine diphosphate is found in many enzymes of central metabolism and is essential in all extant forms of life. We demonstrate the presence of an oxygen-dependent free radical in the thiamine diphosphate-dependent Escherichia coli 2-oxoglutarate dehydrogenase, which is a key component of the tricarboxylic acid (Krebs) cycle. The radical was sufficiently long-lived to be trapped by freezing in liquid nitrogen, and its electronic structure was investigated by electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR).

Episodic hypersomnia and unusual behaviors in a 14-year old adolescent.

John, a 14-year old white male of European Jewish descent without a prior history of medical or psychiatric problems, presented following several days of increased need for sleep (16-20 hours per day), disorientation, difficulty maintaining attention and concentration, bizarre behaviors. He was sexually inappropriate toward his mother, sister, and housekeeper, masturbated in public, and sang nonsense lyrics. In addition, he had brief periods of agitation, paranoia (including fear that he was being followed and that he would be hurt by the physicians), and periods of distraction by auditory and visual hallucinations.

Transhydrogenation reactions catalyzed by mitochondrial NADH-ubiquinone oxidoreductase (Complex I).

NADH-ubiquinone oxidoreductase (complex I) is the first enzyme of the respiratory electron transport chain in mitochondria. It conserves the energy from NADH oxidation, coupled to ubiquinone reduction, as a proton motive force across the inner membrane. Complex I catalyzes NADPH oxidation, NAD+ reduction, and hydride transfers from reduced to oxidized nicotinamide nucleotides also.

Pathological interactions with the timing of birth and uterine activation.

The physiological processes that regulate the onset of parturition and birth are slowly being elucidated, and the points at which pathology can intervene are becoming more apparent. The data support the view that multiple pathways lead to myometrial activation. The clinical corollary is that combinations of tocolytics that operate via different mechanisms may be more effective than single agents.

ProCKSI: a decision support system for Protein (structure) Comparison, Knowledge, Similarity and Information.

Background: We introduce the decision support system for Protein (Structure) Comparison, Knowledge, Similarity and Information (ProCKSI). ProCKSI integrates various protein similarity measures through an easy to use interface that allows the comparison of multiple proteins simultaneously. It employs the Universal Similarity Metric (USM), the Maximum Contact Map Overlap (MaxCMO) of protein structures and other external methods such as the DaliLite and the TM-align methods, the Combinatorial Extension (CE) of the optimal path, and the FAST Align and Search Tool (FAST).

Conformation and dynamics of the three-helix bundle UBA domain of p62 from experiment and simulation.

The ubiquitin associated domain of p62 is a small three-helix bundle of approximately 50 residues that mediates the recognition of polyubiquitin chains and ubiquitylated substrates. The solution structure of a 52 residue construct containing this domain has been characterized using heteronuclear nuclear magnetic resonance (NMR) methods. The resulting ensemble of NMR-derived structures was used in molecular dynamics (MD) simulations to investigate the equilibrium conformation and dynamics of this domain.

Neurosteroids in the fetus and neonate: potential protective role in compromised pregnancies.

Complications during pregnancy and birth asphyxia lead to brain injury, with devastating consequences for the neonate. In this paper we present evidence that the steroid environment during pregnancy and at birth aids in protecting the fetus and neonate from asphyxia-induced injury. Earlier studies show that the placental progesterone production has a role in the synthesis and release of neuroactive steroids or their precursors into the fetal circulation.

An iron-sulfur domain of the eukaryotic primase is essential for RNA primer synthesis.

Primases synthesize the RNA primers that are necessary for replication of the parental DNA strands. Here we report that the heterodimeric archaeal/eukaryotic primase is an iron-sulfur (Fe-S) protein. Binding of the Fe-S cluster is mediated by an evolutionarily conserved domain at the C terminus of the large subunit.

Reevaluating the relationship between EPR spectra and enzyme structure for the iron sulfur clusters in NADH:quinone oxidoreductase.

NADH:quinone oxidoreductase (complex I) plays a pivotal role in cellular energy production. It employs a series of redox cofactors to couple electron transfer to the generation of a proton-motive force across the inner mitochondrial or bacterial cytoplasmic membrane. Complex I contains a noncovalently bound flavin mononucleotide at the active site for NADH oxidation and eight or nine iron-sulfur clusters to transfer electrons between the flavin and a quinone-binding site.

Modulation of heme redox potential in the cytochrome c6 family.

Cytochrome c6A is a unique dithio-cytochrome of green algae and plants. It has a very similar core structure to that of bacterial and algal cytochromes c6 but is unable to fulfill the same function of transferring electrons from cytochrome f to photosystem I. A key feature is that its heme midpoint potential is more than 200 mV below that of cytochrome c6 despite having His and Met as axial heme-iron ligands.

Circular and linear dichroism of proteins.

Circular dichroism (CD) is an important technique in the structural characterisation of proteins, and especially for secondary structure determination. The CD of proteins can be calculated from first principles using the so-called matrix method, with an accuracy which is almost quantitative for helical proteins. Thus, for proteins of unknown structure, CD calculations and experimental data can be used in conjunction to aid structure analysis.

The role of cargo proteins in GGA recruitment.

Coat proteins are recruited onto membranes to form vesicles that transport cargo from one compartment to another, but the extent to which the cargo helps to recruit the coat proteins is still unclear. Here we have examined the role of cargo in the recruitment of Golgi-localized, gamma-ear-containing, ADP ribosylation factor (ARF)-binding proteins (GGAs) onto membranes in HeLa cells. Moderate overexpression of CD8 chimeras with cytoplasmic tails containing DXXLL-sorting signals, which bind to GGAs, increased the localization of all three GGAs to perinuclear membranes, as observed by immunofluorescence.