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David Atkinson

Publications and source records attributed to David Atkinson.

At least 19 recordsLinked to original sources
PubMed2006

Structure and stability of apolipoprotein a-I in solution and in discoidal high-density lipoprotein probed by double charge ablation and deletion mutation.

To identify residues and segments in the central region of apolipoprotein A-I (apoA-I) that are important for the protein structure and stability, we studied the effects of four double charge ablations, D102A/D103A, E110A/E111A, R116V/K118A, and R160V/H162A, and two deletion mutations, Delta(61-78) and Delta(121-142), on the conformation and stability of apoA-I in the lipid-free state and in reconstituted discoidal phospholipid-cholesterol-apoA-I particles (rHDL). The findings suggest that D102/D103 and E110/E111 located in helix 4 and segment(s) between residues 61 and 78 are involved in maintenance of the conformation and stability of apoA-I in both the lipid-free state and in rHDL. R116/K118 located in helix 4 are essential for the conformation and stabilization of apoA-I in rHDL but not vital for the lipid-free state of the protein. The R160V/H162A substitutions in helix 6 lead to a less compact tertiary structure of lipid-free apoA-I without notable effects on the lipid-free or lipid-bound secondary conformation, suggesting involvement of R160/H162 in important interhelical interactions. The results on the Delta(121-142) mutant, together with our earlier findings, suggest disordered structure of a major segment between residues 121 and 143, likely including residues 131-143, in lipid-free apoA-I. Our findings provide the first experimental evidence for stabilization of rHDL by specific electrostatic interhelical interactions, in agreement with the double belt model. The effects of alterations in the conformation and stability of the apoA-I mutants on in vitro and in vivo functions of apoA-I and lipid homeostasis are discussed.

Anilino Naphthalenesulfonates↗
PubMed2006

Beyond the g-factor limit in sensitivity encoding using joint histogram entropy.

The maximum practical speed-up that can be achieved using parallel imaging methods is widely accepted to be limited by g-factor noise. An approximate expression for the g-factor noise as a function of the principal eigenvector of the inverse sensitivity matrix is derived. This formulation allows g-factor enhanced noise to be reduced by a constrained optimization procedure with joint image histogram entropy between a reference image and a SENSE image as an image quality metric. The reference image does not need to have identical resolution or contrast. The reference image may also be used for coil calibration. The limits of the method are explored using simulated and real array coil data with high g-factor using a variety of contrast and resolution combinations. The method preserves image structure, contrast, and lesions even when these were not observable in the reference data. In all cases g-factor was dramatically reduced.

Brain Mapping↗
PubMed2006

Incoherent artefact correction using PPI.

Multiple coils provide extra information about a patient which is frequently used to shorten exam times. This review looks at how the extra information might be used to reduce incoherent artefacts arising from physiological processes such as motion or pulsatile flow.

Algorithms↗
PubMed2005

Measurement of total pulmonary arterial compliance using invasive pressure monitoring and MR flow quantification during MR-guided cardiac catheterization.

Pulmonary hypertensive disease is assessed by quantification of pulmonary vascular resistance. Pulmonary total arterial compliance is also an indicator of pulmonary hypertensive disease. However, because of difficulties in measuring compliance, it is rarely used. We describe a method of measuring pulmonary arterial compliance utilizing magnetic resonance (MR) flow data and invasive pressure measurements. Seventeen patients with suspected pulmonary hypertension or congenital heart disease requiring preoperative assessment underwent MR-guided cardiac catheterization. Invasive manometry was used to measure pulmonary arterial pressure, and phase-contrast MR was used to measure flow at baseline and at 20 ppm nitric oxide (NO). Total arterial compliance was calculated using the pulse pressure method (parameter optimization of the 2-element windkessel model) and the ratio of stroke volume to pulse pressure. There was good agreement between the two estimates of compliance (r = 0.98, P < 0.001). However, there was a systematic bias between the ratio of stroke volume to pulse pressure and the pulse pressure method (bias = 61%, upper level of agreement = 84%, lower level of agreement = 38%). In response to 20 ppm NO, there was a statistically significant fall in resistance, systolic pressure, and pulse pressure. In seven patients, total arterial compliance increased >10% in response to 20 ppm NO. As a population, the increase did not reach statistical significance. There was an inverse relation between compliance and resistance (r = 0.89, P < 0.001) and between compliance and mean pulmonary arterial pressure (r = 0.72, P < 0.001). We have demonstrated the feasibility of quantifying total arterial compliance using an MR method.

Adolescent↗
PubMed2005

The interfacial properties of ApoA-I and an amphipathic alpha-helix consensus peptide of exchangeable apolipoproteins at the triolein/water interface.

Apolipoprotein A-I (apoA-I) is the major protein in high density lipoprotein (HDL). During lipid metabolism, apoA-I moves among HDL and triacylglycerol-rich lipoproteins. The main structure and the major lipid binding motif of apoA-I is the amphipathic alpha-helix. To understand how apoA-I behaves at hydrophobic lipoprotein interfaces, the interfacial properties of apoA-I and an amphipathic alpha-helical consensus sequence peptide (CSP) were studied at the triolein/water (TO/W) interface. CSP ((PLAEELRARLRAQLEELRERLG)2-NH2) contains two 22-residue tandem repeat sequences that form amphipathic alpha-helices modeling the central part of apoA-I. ApoA-I or CSP added into the aqueous phase surrounding a triolein drop lowered the interfacial tension (gamma) of TO/W in a concentration- and time-dependent fashion. The gamma(TO/W) was lowered approximately 16 millinewtons (mN)/m by apoA-I at 1.4 x 10(-6) m and approximately 15 mN/m by CSP at 2.6 x 10(-6) m. At equilibrium gamma, both apoA-I and CSP desorbed from the interface when compressed and readsorbed when expanded. The maximum surface pressure CSP could withstand without being ejected (PiMAX) was 16 mN/m. The PiMAX) of apoA-I was only 14.8 mN/m, but re-adsorption kinetics suggested that only part of the apoA-I desorbed at Pi between 14.8 and 19 mN/m. However, above approximately 19 mN/m (PiOFF) the entire apoA-I molecule desorbed into the water. ApoA-I was more flexible at the TO/W interface than CSP and showed more elasticity at oscillation periods 4-128 s even at high compression, whereas CSP was elastic only at faster periods (4 and 8 s) and moderate compression. Flexibility and surface pressure-mediated desorption and re-adsorption of apoA-I probably provides lipoprotein stability during metabolic-remodeling reactions in plasma.

Apolipoprotein A-I↗
PubMed2004

Conformation and lipid binding of the N-terminal (1-44) domain of human apolipoprotein A-I.

Because of its role in reverse cholesterol transport, human apolipoprotein A-I is the most widely studied exchangeable apolipoprotein. Residues 1-43 of human apoA-I, encoded by exon 3 of the gene, are highly conserved and less well understood than residues 44-243, encoded by exon 4. In contrast to residues 44-243, residues 1-43 do not contain the 22 amino acid tandem repeats thought to form lipid binding amphipathic helices. To understand the structural and functional roles of the N-terminal region, we studied a synthetic peptide representing the first 44 residues of human apoA-I ([1-44]apoA-I). Far-ultraviolet circular dichroism spectra showed that [1-44]apoA-I is unfolded in aqueous solution. However, in the presence of n-octyl beta-d-glucopyranoside, a nonionic lipid mimicking detergent, above its critical micelle concentration ( approximately 0.7% at 25 degrees C), sodium dodecyl sulfate, an ionic detergent, above its CMC ( approximately 0.2%), trimethylamine N-oxide, a folding inducing organic osmolyte, or trifluoroethanol, an alpha-helix inducer, alpha-helical structure was formed in [1-44]apoA-I up to approximately 45%. Characterization by density gradient ultracentrifugation and visualization by negative staining electron microscopy demonstrated that [1-44]apoA-I interacts with dimyristoylphosphatidylcholine (DMPC) over a wide range of lipid:peptide ratios from 1:1 to 12:1 (w/w). At 1:1 DMPC:[1-44]apoA-I (w/w) ratio, discoidal complexes with composition approximately 4:1 (w/w) and approximately 100 A diameter were formed in equilibrium with free peptide. At higher ratios, discoidal complexes were shown to exist together with a heterogeneous population of lipid vesicles with peptide bound also in equilibrium with free peptide. When bound to DMPC, [1-44]apoA-I has approximately 60% helical structure, independent of whether it forms discoidal or vesicular complexes. This helical content is consistent with that of the predicted G helix (residues 8-33). Our data provide the first strong and direct evidence that the N-terminal region of apoA-I binds lipid and can form discoidal structures and a heterogeneous population of vesicles. In doing so, approximately 60% of this region folds into alpha-helix from random coil. The composition of the 100 A discoidal complex is approximately 5 [1-44]apoA-I and approximately 150 DMPC molecules per disk. The helix length of 5 [1-44]apoA-I molecules in lipid-bound form is just long enough to wrap around the DMPC bilayer disk once.

Apolipoprotein A-I↗
PubMed2004

Coil-based artifact reduction.

Multiple MRI receiver coils provide extra information and can enable the reconstruction of multiple images using data from different combinations of coils. Comparison of these images shows that artifacts due to motion or flowing blood appear with different intensities due to the differing coil sensitivities. Typically, the artifact appears amplified in regions of low coil sensitivity. An optimization routine was developed to correct for the artifact by comparing reconstructions from various coil combinations and favoring a self-consistent solution. It is demonstrated that images artifacted by blood flowing in the aorta, or translational motion of the head, can be improved.

Algorithms↗
PubMed2004

Crop protection--what will shape the future picture?

The drivers which influence the types of crop protection most needed by agriculture are changing. A polarisation of approaches has resulted in the needs of organic agriculture and biotechnological agriculture, which can be identified as the current extremes of the spectrum, becoming very different. The main requirements of these two sectors are identified here and used as the basis for questioning future EU research requirements in crop protection. Factors affecting/influencing organic farming and the use of genetically modified crops are discussed in some detail.

Crops, Agricultural↗
PubMed2004

Retrospective respiratory motion correction for navigated cine velocity mapping.

In general, high spatial and temporal resolutions in cine cardiac imaging require long scan times, making breath-hold acquisition impossible in many cases. To enable free-breathing cardiac imaging, methods such as navigator gating were developed to reduce image artifacts due to respiratory motion. Nevertheless, residual image blurring is seen in images acquired late in the cardiac cycle. Image blurring itself hampers accurate blood flow quantification, especially in vessels exhibiting high flows during diastole. In the present work, the navigator gating and slice tracking method was extended by using navigator information to correct for in-slice motion components throughout the cardiac cycle. For this purpose, a standard two-dimensional (2D) cine phase contrast sequence with navigator gating and slice position correction was used, and navigator information was recorded along with the raw k-space data. In postprocessing, in-plane motion components arising from respiration during the actual data acquisition were estimated and corrected according to the Fourier shift theorem. In phantom experiments, the performance of the correction algorithm for different slice angulations with respect to the navigator orientation was validated. In vivo, coronary flow measurements were performed in 9 healthy volunteers. The correction algorithm led to considerably improved vessel sharpness throughout the cardiac cycle in all measured subjects [increase in vessel sharpness: 16+/-11% (mean+/-SD)]. Furthermore, these improvements resulted in increased volume flow rates [16+/-13% (mean+/-SD)] after retrospective correction indicating the impact of the method. It is concluded that retrospective respiratory motion corrections for navigated cine two-dimensional (2D) velocity mapping can correct for in-plane motion components, providing better image quality for phases acquired late in the cardiac cycle. Therefore, this method holds promise in particular for free-breathing coronary flow quantification.

Blood Flow Velocity↗
PubMed2004

Artifact reduction using parallel imaging methods.

Multiple receiver coils produce images with different but complementary views of a patient. This can be used to shorten scans times but there often remain image artifacts caused by patient motion or physiological processes such as flowing blood. This paper reviews how the extra information from the multiple coils can be used to reduce image artifacts. In one method, affected portions of data can be identified and discarded but enough information is still available to reconstruct an improved image. In other methods, the motion itself is determined and the corrupted data is then corrected, leading to an image with reduced artifacts. Results are presented from images corrupted by motion or by flowing blood.

Aortic Diseases↗
PubMed2003

Protists decrease in size linearly with temperature: ca. 2.5% degrees C(-1).

An inverse relationship between organism size and rearing temperature is widely observed in ectotherms ('the temperature-size rule', TSR). This has rarely been quantified for related taxa, and its applicability to protists also required testing. Here, we quantify the relationship between temperature and mean cell volume within the protists by a meta-analysis of published data covering marine, brackish water and freshwater autotrophs and heterotrophs. In each of 44 datasets, a linear relationship between temperature and size could not be rejected, and a negative trend was found in 32 cases (20 gave significant negative regressions, p < 0.05). By combining 65 datasets, we revealed, for each 1 degrees C increase, a cell-size reduction of 2.5% (95% CI of 1.7-3.3%) of the volume observed at 15 degrees C. The value did not differ across taxa (amoebae, ciliates, diatoms, dinoflagellates, flagellates), habitats, modes of nutrition or combinations of these. The data are consistent with two hypotheses that are capable of explaining the TSR in ectotherms generally: (i) resource, especially respiratory gas, limitation; and (ii) fitness gains from dividing earlier as population growth increases. Using the above relationship we show how changes in cell numbers with temperature can be estimated from changes in biomass and vice versa; ignoring this relationship would produce a systematic error.

Animals↗
PubMed2003

Lipid-binding studies of human apolipoprotein A-I and its terminally truncated mutants.

Apolipoprotein A-I (apoA-I, 243 amino acids) is the major protein of high-density lipoproteins (HDL) that plays an important structural and functional role in lipid transport and metabolism. The central region of apoA-I (residues 60-183) is predicted to contain exclusively amphipathic alpha-helices formed from tandem 22-mer sequence repeats. To analyze the lipid-binding properties of this core domain, four terminally truncated mutants of apoA-I, Delta(1-41), Delta(1-59), Delta(1-41,185-243), and Delta(1-59,185-243), were expressed in baculovirus infected Sf-9 cells. The effects of mutations on the ability of apoA-I to form bilayer disk complexes with dimyristoyl phosphatidylcholine (DMPC) that resemble nascent HDL were analyzed by density gradient ultracentrifugation and electron microscopy (EM). The N-terminal deletion mutants, Delta(1-41) and Delta(1-59), showed altered lipid-binding ability as compared to plasma and wild-type apoA-I, and in the double deletion mutants, Delta(1-41, 185-243) and Delta(1-59, 185-243), the lipid binding was abolished. Thermal unfolding of variant apoA-I/DMPC complexes monitored by circular dichroism (CD) showed hysteresis and a shift in the melting curves by about -12 degrees C upon reduction in the heating rate from 1.0 to 0.067 K/min. This indicates an irreversible kinetically controlled transition with a high activation energy E(a) = 60 +/- 5 kcal/mol. CD and EM studies of the apoA-I/DMPC complexes at different pH demonstrated that changes in the net charge or in the charge distribution on the apoA-I molecule have critical effects on the conformation and lipid-binding ability of the protein.

Apolipoprotein A-I↗
PubMed2003

Interfacial properties of an amphipathic alpha-helix consensus peptide of exchangeable apolipoproteins at air/water and oil/water interfaces.

Amphipathic alpha-helices are the main structure and the major lipid binding motif of exchangeable apolipoproteins. To understand how these apolipoproteins behave at an hydrophobic lipoprotein interface, the interfacial properties of a consensus sequence peptide (CSP) derived from three exchangeable apolipoproteins (A-I, A-IV, and E) were studied using an oil drop tensiometer at air/water (A/W) and dodecane/water (DD/W) interfaces. CSP ((PLAEELRARLRAQLEELRERLG)2-NH2) contains two 22-amino acid tandem repeat sequences that form amphipathic alpha-helices. CSP, when added into the aqueous phase, lowered the interfacial tension (gamma) of A/W and DD/W in a concentration-dependent fashion. The gammaA/W was lowered approximately 24 mn/m, and gammaDD/W approximately 31 mn/m, indicating a greater affinity of CSP for DD/W. Using the Gibbs equation for surface, the surface area per CSP molecule was estimated at approximately 702 A2 ( approximately 16 A2/amino acid) on A/W and approximately 622 A2 on DD/W ( approximately 14 A2/amino acid) suggesting that adsorbed CSP lies flat with alpha-helices in the plane of both interfaces. At equilibrium gamma, CSP desorbed from the interface when compressed and re-adsorbed when expanded. The adsorption rate was concentration-dependent, but the desorption rate was not. Less CSP desorbed from DD/W than A/W indicating that CSP has higher affinity for DD/W. Dynamic analysis of elasticity shows that the faster the oscillation period (4, 8 s) and the lower the oscillation amplitude the more elastic the surfaces. CSP can be compressed 6-12% while remaining on the surface, but large increases in pressure eject it from the surface. We suggest that surface pressure-mediated desorption and readsorption of amphipathic alpha-helices provide lipoprotein stability during remodeling reactions in plasma.

Amino Acid Sequence↗
PubMed2003

Structural studies of N- and C-terminally truncated human apolipoprotein A-I.

Apolipoprotein A-I (apoA-I) plays an important structural and functional role in lipid transport and metabolism. This work is focused on the central region of apoA-I (residues 60-183) that is predicted to contain exclusively amphipathic alpha-helices. Six N- and/or C-terminally truncated mutants, delta(1-41), delta(1-59), delta(198-243), delta(209-243), delta(1-41,185-243), and delta(1-59,185-243), were analyzed in their lipid-free state in solution at pH 4.7-7.8 by far- and near-UV CD spectroscopy. At pH 7.8, all mutants show well-defined secondary structures consisting of 40-52% alpha-helix. Comparison of the alpha-helix content in the wild type and mutants suggests that deletion of either the N- or C-terminal region induces helical unfolding elsewhere in the structure, indicating that the terminal regions are important for the integrity of the solution conformation of apoA-I. Near-UV CD spectra indicate significant tertiary and/or quaternary structural changes resulting from deletion of the N-terminal 41 residues. Reduction in pH from 7.8 to 4.7 leads to an increase in the mutant helical content by 5-20% and to a large increase in thermal unfolding cooperativity. Van't Hoff analysis of the mutants at pH 4.7 indicates melting temperatures T(m) ranging from 51 to 59 degrees C and effective enthalpies deltaH(v)(T(m)) = 35 +/- 5 kcal/mol, similar to the values for plasma apoA-I at pH 7.8 (T(m) = 57 degrees C, deltaH(v) = 32 kcal/mol). Our results provide the first report of the pH effects on the secondary, tertiary, and/or quaternary structure of apoA-I variants and indicate the importance of the electrostatic interactions for the solution conformation of apoA-I.

Animals↗
PubMed2003

Diversity of arbuscular mycorrhizal fungi colonising roots of the grass species Agrostis capillaris and Lolium perenne in a field experiment.

Analysis of arbuscular mycorrhizal (AM) fungal diversity through morphological characters of spores and intraradicular hyphae has suggested previously that preferential associations occur between plants and AM fungi. A field experiment was established to investigate whether AM fungal diversity is affected by different host plants in upland grasslands. Indigenous vegetation from plots in an unimproved pasture was replaced with monocultures of either Agrostis capillaris or Lolium perenne. Modification of the diversity of AM fungi in these plots was evaluated by analysis of partial sequences in the large subunit (LSU) ribosomal RNA (rDNA) genes. General primers for AM fungi were designed for the PCR amplification of partial sequences using DNA extracted from root tissues of A. capillaris and L. perenne. PCR products were used to construct LSU rDNA libraries. Sequencing of randomly selected clones indicated that plant roots were colonised by AM fungi belonging to the genera Glomus, Acaulospora and Scutellospora. There was a difference in the diversity of AM fungi colonising roots of A. capillaris and L. perenne that was confirmed by PCR using primers specific for each sequence group. These molecular data suggest the existence of a selection pressure of plants on AM fungal communities.

Agrostis↗
PubMed2003

Reconstruction after rotational motion.

Patient rotational motion during a scan causes the k-space sampling to be both irregular and undersampled. Conventional regridding requires an estimate of the sampling density at each measured point and is not strictly consistent with sampling theory. Here, a 2D problem is converted to a series of 1D regriddings by exact interpolation along the measured readouts. Each 1D regridding, expressed in matrix form, requires a matrix inversion to gain an exact solution. Undersampled regions make the matrix ill-conditioned but summing the matrix columns (without inversion) indicates the undersampled regions. The missing data could be reacquired, but in this study it is estimated using a Delaunay triangle-based linear interpolation on the original 2D data. The matrix conditioning is improved, leading to images with reduced artifacts compared to other regridding schemes. Furthermore, there is no requirement to estimate a density compensation function at each of the measured points.

Head↗
PubMed2002

Lipid-free structure and stability of apolipoprotein A-I: probing the central region by mutation.

To probe the structure and stability of the central region of lipid-free apolipoprotein (apo) A-I (residues 123-165), we studied the effects of four mutations made in this region on the conformation, stability, dimyristoylphosphatidylcholine (DMPC) binding kinetics, and size of discoidal reconstituted high-density lipoprotein (rHDL) particles. The apoA-I deletion delta(144-165) leads to a red shift in the wavelength of maximum fluorescence and a reduction in the alpha-helical content, the stability, the initial rate of association with DMPC liposomes, and the size of the discoidal particles. The data are consistent with the helical structure of residues 144-165, and the deletion appears to perturb the tertiary organization of the N-terminal half of apoA-I. In contrast, the deletion of the adjacent region, delta(136-143), leads to stabilization without altering the number of residues in the helical conformation or the initial rate of association with DMPC liposomes. The quadruple substitution E125K/E128K/K133E/E139K leads to approximately 17 additional residues in the helical conformation and an increase in the stability, the initial rate of association with DMPC liposomes, and the size of the rHDL particles. The findings are consistent with the disordered structure of the segment of residues 123-142, which becomes helical as a result of the quadruple mutation or upon lipid binding. The naturally occurring mutation L141R (also associated with coronary heart disease) that is located in this segment does not change the protein conformation but leads to a reduced stability and a decreased rate of association with DMPC liposomes that may relate to the observed altered functions of this mutant.

Amino Acid Substitution↗