bluuebunny/crossref_metadata_2025 huggingface dataset:
Eclipsing binaries as a test for synthetic photometry
Authors: Heiter U. , Smalley B. , Stütz Ch. , Kupka F. , Kochukhov O.
Published: May 2007

Narrow band photometry is a useful tool to characterize large numbers of stars, but observed colors and indices must be connected to astrophysical parameters by synthetic photometry. We present synthetic Hβ indices calculated from 1D model atmospheres implementing different convection treatments. The calculated indices are transformed to the standard system using observed medium-resolution spectra. We test the synthetic photometry with observed indices of eclipsing binary systems. The computed indices agree with the observed ones up to an amount expected from the observational errors, the accuracy of the atmospheric parameters, and computational uncertainties.
Convection-driven planetary dynamos
Authors: Christensen Ulrich R. , Aubert Julien , Olson Peter
Published: May 2007

Numerical simulations of convection-driven dynamos in rotating spherical shells are employed to better understand the observed strength and geometry of planetary magnetic fields. The model computations cannot be performed for realistic values of several of the control parameters. By varying parameters within the accessible range, it is possible to derive scaling laws for the magnetic field strength and the flow velocity in the dynamo region and for the dipole moment. Our scaling laws suggest that, even though diffusivities are far too large in the models, diffusive processes do not play an important role, just as in planetary cores. Extrapolating the scaling laws to planetary values of the control parameters leads to reasonable predictions for the field strength in the dynamo region and fits the observed dipole moments decently, in particular in the cases of Earth and Jupiter. For Mercury, which does not fit well when applying the scaling laws in a straightforward way, a model is proposed in which the upper part of the fluid core is stably stratified and the dynamo operates only in its deep regions. The time-varying dynamo field must diffuse through the stable region and is attenuated by the skin effect. The model explains why Mercury has a very weak but probably dipole-dominated magnetic field.
Prospects of using simulations to study the photospheres of brown dwarfs
Authors: Ludwig Hans-Günter
Published: May 2007

We discuss prospects of using multi-dimensional time-dependent simulations to study the atmospheres of brown dwarfs and extrasolar giant planets, including the processes of convection, radiation, dust formation, and rotation. We argue that reasonably realistic simulations are feasible, however, separated into two classes of local and global models. Numerical challenges are related to potentially large dynamic ranges, and the treatment of scattering of radiation in multi-D geometries.
Heat transport in 3D anelastic simulations of the internal dynamics of giant planets without cores
Authors: Evonuk Martha , Glatzmaier Gary A.
Published: May 2007

Differential rotation, similar to that seen on our gas giants, is manifested at the surface of three-dimensional (3D) computer simulations of thermal convection in density-stratified rotating planets without solid cores. Below the surface, the flow forms short axially-aligned vortices, generated by fluid expanding as it rises and contracting as it sinks. The convergence of the nonlinear Reynolds stresses resulting from the vorticity generated by fluid flowing through the density stratification maintains the surface banded zonal flow without the classical vortex stretching of Taylor columns. These preliminary simulations demonstrate that large non-convecting cores are not required to obtain multiple zonal jets at the surface, and show greater convective heat flux towards the poles relative to that seen at the equator. This result could help explain the nearly uniform with latitude thermal emission observed at the surface of Jupiter.
Toward three-dimensional simulations of stellar core collapse with magnetic fields
Authors: Liebendörfer M. , Whitehouse S. , Fischer T.
Published: May 2007

In spherical symmetry, very reliable models of stellar core collapse, bounce, and the postbounce phase can be constructed based on general relativistic Boltzmann neutrino transport. However, even if the time-integrated neutrino luminosity in the region between the surface of the protoneutron star and the stalled accretion shock is one or two orders of magnitude larger than the energy of a supernova explosion, it is generally accepted that the net energy transfer is not efficient enough to drive an explosion, unless the fluid instabilities in this regime are taken into account. Complementary to other groups, who are elaborating an extension of the accurate neutrino physics to axisymmetric simulations, we construct efficient parameterizations of the neutrino physics that enable three-dimensional magneto-hydrodynamics simulations that do not constrain the fluid instabilities by artificially imposed symmetries. We evaluate our approximations with respect to spherically symmetric Boltzmann neutrino transport, present preliminary MHD simulations with a resolution of 600 zones cubed, and illustrate the questions that can be addressed by this approach.
Comparing convection in the Sun with Procyon A
Authors: Robinson Frank , Demarque Pierre
Published: May 2007

As well as reproducing observable features like solar granulation, 3D simulations can provide useful information for local or non-local stellar modeling. Examples include testing out the mixing length theory in the surface layers, providing the turbulent correction for stellar models ofp-mode frequencies, testing eddy viscocity prescriptions used in tidal dissipation models and comparing different closures of higher order moments. Having validated the 3D code with the sun we applied it to other stars. For Procyon A the turbulence is about twice as strong as it is in the Sun (estimated by the peak root mean square vertical velocity which is about 6.5 km/s) and the granules are nearly an order of magnitude larger, with plumes regularly extending down 2-3 pressure scale heights below the surface of Procyon A. An interesting feature of the Procyon simulation is that the horizontal layers in the vicinity of the granules appear to radially pulsate in a quasi-periodic manner. This makes the superadiabatic layer move in and out over a distance of about half a pressure scale height in a time of about 20-30 minutes. This motion appears to be tied to the granulation but there may be other phenomena involved such as some kind of local kappa-mechanism confined to the granulation surface layers. We find similar behaviour in a simulation of an 11 Gyr subgiant sun. As the velocities are more like the sun (about 3km/s), the time period of the pulsation in the subgiant is 2-3 times longer than in Procyon A.
Small amplitude variable red giants
Authors: Xiong D. R. , Deng L.
Published: May 2007

Small amplitude variable red giants were discovered long time ago (Eggen 1969, Henry et al. 2000, Jorison et al. 1997). The revolutionary turning point for the study of this type of variable was due to the work of Wood (2000) and Soszyński et al. (2004) based on the very large stellar sample of the Magellanic clouds MACHO project and OGLE photometric data. By using our non-local time-dependent theory of convection (Xiong 1989), we carried out a linear stability survey for red giants with initial mass of M = 1 − 3M⊙. Explanations for the observed variabilities and analysis of mode identifications in red giant stars are presented in this work.
Turbulent compressible convection with rotation
Authors: Brummell Nicholas H.
Published: May 2007

We examine the effect of rotation on turbulent compressible penetrating convection, motivated by the dynamics of the solar interior. We find that rotation can influence large-scale coherent structures in the turbulent flow whilst leaving the small-scales isotropic. The dynamics in this case are very different from more laminar situations where all scales are rotationally-influenced. This may hint as to why full models of the global solar differential rotation are difficult.
Large-scale flows and convection at the base of solar convection zone
Authors: Tikhomolov Evgeniy
Published: May 2007

Development of convection in sun's outer shell is caused by reduction of effectiveness of energy transfer by radiation. Traditionally, models of solar convection are considered to be axisymmetric on the scale of solar radius. Such models provide basic understanding of convection under solar conditions. However, interpretation of a number of observable large-scale long-lived solar phenomena requires developing a non-axisymmetric approach. We present such a model in which large-scale non-axisymmetry is caused by large-scale flows such as Rossby waves and vortices. We model flows near the base of the solar convection zone. Anelastic approximation is used, which is valid for flow velocities much smaller than local sound speed. Our three-dimensional numerical simulations show that interaction of convection with large-scale flows leads to the establishment of non-axisymmetric large-scale temperature distribution. The interaction also gives rise to large-scale variations of penetration depth of convective plumes. Generation of the magnetic field by large-scale non-axisymmetric flows can explain such solar phenomena as complexes of activity, active longitudes, drifts of large-scale magnetic fields from equator to the poles, and appearance of distinct rotation periods of magnetic fields at some latitudes. We discuss a possibility of detection of large-scale non-axisymmetric flows and temperature distributions associated with them by the methods of helioseismology.
On the interactions of turbulent convection and rotation in RGB stars
Authors: Palacios Ana , Brun Allan S.
Published: May 2007

We have performed the first three-dimensional non-linear simulation of the turbulent convective envelope of a rotating 0.8 M⊙ RGB star using the ASH code. Adopting a global typical rotation rate of a tenth of the solar rate, we have analyzed the dynamical properties of the convection and the transport of angular momentum within the inner 50% in radius of the convective envelope. The convective patterns consist of a small number of large cell, associated with fast flows (∼3000m/s) and large temperature fluctuations (∼300K) in order to carry outward the large luminosity (L ∼ 400L⊙) of the star. The interactions between convection and rotation give rise to a large radial differential rotation and a meridional circulation possessing one cell per hemisphere, the flow being poleward in both hemisphere. By analysing the redistribution of angular momentum, we find that the meridional circulation transports the angular momentum outward in the radial direction, and poleward in the latitudinal direction, and that the transport by Reynolds stresses acts in the opposite direction. From this 3-D simulation, we have derived an average radial rotation profile, that we will ultimately introduce back into 1-D stellar evolution code.
Simulations of solar magnetic dynamo action in the convection zone and tachocline
Authors: Browning Matthew K. , Miesch Mark S. , Brun Allan Sacha , Toomre Juri
Published: May 2007

We present results from a global 3-D nonlinear simulation of magnetic dynamo action achieved by solar convection in a penetrative geometry. We include within the spherical computational domain both the bulk of the convection zone and a portion of the underlying stable layer. A tachocline of rotational shear is realized below the convection zone, where we have imposed both a hydrodynamic drag term and small thermal perturbations consistent with thermal wind balance. Thus we are capturing many of the dynamical elements thought to be essential in the operation of the global solar dynamo, including differential rotation arising from convection, magnetic pumping, and the stretching and amplification of toroidal fields within the tachocline. In the stable region, the simulation reveals that strong axisymmetric toroidal magnetic fields (about 3000 G in strength) are realized, in contrast to the mostly fluctuating fields that predominate in the convection zone. The toroidal fields in the stable region exhibit a striking antisymmetric parity akin to that observed in sunspots, with fields in the northern hemisphere largely of the opposite sign to those in the southern hemisphere. These deep toroidal fields are accompanied by mostly dipolar mean poloidal fields, whose polarity has retained the same sense over multiple years of simulated evolution.
SLAM and its role in T cell activation and Th cell responses
Authors: Aversa Gregorio , Carballido Jose , Punnonen Juha , Chang Chia‐Chun J , Hauser Thomas , Cocks Benjamin G , De Vries Jan E
Published: May 2007

Following the initial events of T cell activation, triggered by binding of specific peptide‐MHC complex to the TCR for antigen and engagement of costimulatory molecules, a number of activation molecules are expressed on the cell surface. Many of these molecules regulate T cell function. T‐T cell interactions and the interaction of T cells with other cells. One such molecule is SLAM, a multifunctional 70 kDa glycoprotein member of the Ig superfamily with multiple isoforms. SLAM is rapidly induced on natve T cells and B cells following activation. Engagement of SLAM by a specific antibody (mAb A12) results in IL‐2‐independent T cell expansion and induction/up‐regulation of IFN‐γ by activated T cells, including Th2 cells. SLAM was found to be a high‐affinity self‐ligand mediating molecular and cellular homophilic interactions. In this review we discuss SLAM as a receptor involved in T cell expansion and in directing immune responses to a Th0‐Th 1 pathway.
Comparison of strategies for the construction of libraries of artificial antibodies
Authors: Iba Yoshitaka , Kurosawa Yoshikazu
Published: May 2007

Construction of libraries of artificial antibodies has been reported by several groups of investigators. Various forms of antibody fused to a surface protein, cpIII, are expressed on the surface of filamentous phage. Since phages that encode desired antibodies can be easily grown in Escherichia coli after selection with target antigens, the phage‐display antibody system appears to be very useful for various biological purposes. In this brief review, recent progress in research into the production of artificial antibodies is summarized and the strategies used for the construction of libraries of artificial antibodies are compared.
Tumour eradication with high‐dose idarubicin‐anti‐Ly‐2.1 with murine tumour necrosis factor‐α in mice
Authors: Pietersz Geoffrey A , Bogdanovski Mary , Wenjun Li
Published: May 2007

The antitumour efficacy of Ida‐anti‐Ly‐2.1 immunoconjugate in combination with murine TNF‐α (mTNF‐α) has been evaluated in a disseminated murine thymic lymphoma model E3. This tumour model shows characteristics similar to lymphoma in humans with widely disseminated tumour in major organs. In vitro both idarubicin (Ida) and Ida‐anti‐Ly‐2.1 showed additive and synergistic cytotoxic effects, respectively, with mTNF‐α when tested using the isobolagram method. Similar synergistic effects were also seen in vivo. Tumour‐bearing mice were treated with various doses of mTNF‐α and Ida alone, however, neither showed a therapeutic response in mice. When mice were treated with Ida‐anti‐Ly‐2.1 ‘early’ the median survival time (MST) was increased by 8 days, however, ‘late’ treatment was ineffective. Combination therapy of mTNF‐α and Ida‐anti‐Ly‐2.1 conjugate (42 μg) given ‘early’ was capable of curing 50% of mice. However, when tumour‐bearing mice were given a high dose (234 μg) of Ida‐anti‐Ly‐2.1 together with mTNF‐α 100% of mice survived disease free. Such an effect was not observed when free mTNF‐α. Ida‐anti‐Ly‐2.1. anti‐Ly‐2.1 or a mixture of anti‐Ly‐2.1 + mTNF‐α was given at the same dose. These results show that a combination of very toxic drug immunoconjugates and TNF could lead to the eradication of disseminated tumour m mice and may be relevant for the treatment of minimal residual disease in cancer patients.
DNA immunization
Authors: Ramsay Alistair J , Ramshaw Ian A , Ada Gordon L
Published: May 2007

DNA immunization has recently emerged as a highly promising approach for the prevention and therapy of a wide range of infectious and non‐infectious diseases. Here, we review the rapid development of this field and recent advances in our understanding of some of the mechanisms by which DNA vaccines stimulate the immune system.
DNA vaccines for bacterial infections
Authors: Strugnell RA , Drew D , Mercieca J , Dinatale S , Firez N , Dunstan SJ , Simmons CP , Vadolas J
Published: May 2007

DNA vaccines are an exciting development in vaccine technology which may have a special role in preventing viral infections and as ‘theracines’ for cancer. Their use in preventing bacterial infections has, by comparison, been less well documented. While it is unlikely that traditional, highly successful and cheap vaccines for diseases such as diphtheria will be replaced by DNA vaccines, naked DNA may be particularly appropriate for preventing bacterial infections where cytotoxic T cells confer protection, or where a Thl type T cell response mediates resistance. For example, DNA vaccines containing different mycobacterial antigens have been shown to inhibit overt infections by Mycobacterium tuberculosis in rodent models. The use of DNA vaccines in bacterial infections may be complicated by fundamental differences between prokaryotic and eukaryotic genes and gene products, including mRNA stability, codon bias, secondary structures surrounding native start sequences and glycosylation. These problems can be solved by re‐synthesis of bacterial genes to produce ‘new’ sequences which are more highly expressed by eukaryotic cells.
Use of degenerate primers and heat‐soaked polymerase chain reaction (PCR) to clone a serine protease antigen from Dermatophilus congolensis
Authors: Mine Ontiretse M , Carnegie Patrick R
Published: May 2007

Serine proteases are thought to he involved in the initial attack on sheep skin by Dermatophilus congolensis and are obvious antigens for inclusion in a vaccine to prevent lumpy wool disease (dermato‐philosis). Degenerate primers were designed after alignment of seven bacterial serine proteases. Inosine was incorporated into the primers at positions of three‐ and four‐base redundancy, and this reduced the complexity of the primer mixtures from several thousand to sixteen different sequences for each primer. The primers were validated by production and sequencing of amplicons from serine protease genes in Bacillus suhtilis and Serratia marcescens. The primers were used with heat‐soaked polymerase chain reaction (PCR) to produce amplicons from two D. congolensis strains, AG and MB. In the amplicon codons for arginine, rather than the expected serine, were found where inosine was used for both the first and third positions for a codon in the primer. A search with the deduced amino acid sequences of the amplicons showed significant similarity to a keratinase and other serine proteases from various organisms. Similarity was most apparent around the active site residues and other essential secondary structural elements.
Production of B cell differentiation factors by mouse parenchymal liver cells
Authors: Takahashi Megumi , Watari Eiji , Mabuchi Ayako , Yokomuro Kozo
Published: May 2007

Previously we reported that most antibody secreting cells secreted IgA in the liver. Here we assessed the possibility that parenchymal liver cells (PLC) produced factors, transforming growth factor (TGF)‐p and IL‐5, which participate in the differentiation of B cells to IgA‐secreting cells. We showed that TGF‐p activity was present in the culture supernatant of PLC. and IL‐5 activity was in the lysate of PLC. Moreover, it was confirmed that IL‐5 protein produced by PLC was mainly localized in the cell membrane by histochemical staining. The findings that both TGF‐P and IL‐5 were produced by PLC should provide useful information concerning the fact that IgA‐secreting cells were dominant in the liver.
Interaction of Mechanisms Involving Epoxyeicosatrienoic Acids, Adenosine Receptors, and Metabotropic Glutamate Receptors in Neurovascular Coupling in Rat Whisker Barrel Cortex
Authors: Shi Yanrong , Liu Xiaoguang , Gebremedhin Debebe , Falck John R , Harder David R , Koehler Raymond C
Published: May 2007

Adenosine, astrocyte metabotropic glutamate receptors (mGluRs), and epoxyeicosatrienoic acids (EETs) have been implicated in neurovascular coupling. Although A2A and A2B receptors mediate cerebral vasodilation to adenosine, the role of each receptor in the cerebral blood flow (CBF) response to neural activation remains to be fully elucidated. In addition, adenosine can amplify astrocyte calcium, which may increase arachidonic acid metabolites such as EETs. The interaction of these pathways was investigated by determining if combined treatment with antagonists exerted an additive inhibitory effect on the CBF response. During whisker stimulation of anesthetized rats, the increase in cortical CBF was reduced by approximately half after individual administration of A2B, mGluR and EET antagonists and EET synthesis inhibitors. Combining treatment of either a mGluR antagonist, an EET antagonist, or an EET synthesis inhibitor with an A2B receptor antagonist did not produce an additional decrement in the CBF response. Likewise, the CBF response also remained reduced by ∼50% when an EET antagonist was combined with an mGluR antagonist or an mGluR antagonist plus an A2B receptor antagonist. In contrast, A2A and A3 receptor antagonists had no effect on the CBF response to whisker stimulation. We conclude that (1) adenosine A2B receptors, rather than A2A or A3 receptors, play a significant role in coupling cortical CBF to neuronal activity, and (2) the adenosine A2B receptor, mGluR, and EETs signaling pathways are not functionally additive, consistent with the possibility of astrocytic mGluR and adenosine A2B receptor linkage to the synthesis and release of vasodilatory EETs.
Comparison of the effects of dietary saturated, mono-unsaturated and polyunsaturated fatty acids on very-low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnant-like particles
Authors: Lopez-Soldado I. , Avella M. , Botham K.M.
Published: May 2007

The effect of chylomicron remnant-like particles (CRLPs) enriched in saturated, mono-unsaturated or n−6 polyunsaturated fatty acids (derived from palm, olive or corn oil, respectively) on the secretion of VLDL (very-low-density lipoprotein) by rat hepatocytes in culture was investigated. CRLPs were incubated with cultured hepatocytes for 5 h. The medium was then removed and the secretion of cholesterol and triacylglycerol (TAG) into the whole medium during the following 16 h was determined. After exposure of the cells to olive oil as compared with corn and palm oil CRLPs, secretion of TAG into the medium was decreased. The TAG content of the cells was also lower in experiments with olive oil as compared with corn oil CRLPs. The levels of apoB48 (apolipoprotein B48) found in the medium remained unchanged after the exposure of the cells to the different types of remnants. These findings indicate that the type of fat in the diet directly affects VLDL lipid secretion on delivery to the liver in chylomicron remnants.
Modulation of the effects of chylomicron remnants on endothelial function by minor dietary lipid components
Authors: Perona J.S. , Cabello-Moruno R. , Ruiz-Gutierrez V.
Published: May 2007

There is emerging evidence that minor components from dietary oils can modulate or even improve events occurring in the development of atherosclerosis. One of the earliest events of the atherosclerotic process is endothelial dysfunction, which is an activation of the endothelium manifested by an increase in pro-inflammatory molecules, such as cytokines and adhesion molecules. Chylomicron remnants, such as LDL (low-density lipoprotein), are considered to be pro-atherogenic lipoproteins because they interact with endothelial cells and macrophages, increasing endothelial dysfunction mainly by the disturbance of the redox state in the cell. However, chylomicrons are, at the same time, the natural carriers of dietary lipids in plasma, which gives minor lipid components the opportunity to interact with the cells implicated in endothelial dysfunction and atherogenesis. Some of these components are known to exhibit antioxidant, anti-inflammatory and anti-atherogenic effects in vitro, even forming part of triacylglycerol-rich lipoproteins, such as chylomicrons.
Dietary fats induce human monocyte activation in vitro
Authors: Bentley C. , Bejta F. , De Pascale C. , Avella M. , Wheeler-Jones C.P.D. , Botham K.M. , Lawson C.
Published: May 2007

In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is amplified, and migration of monocytes into the walls of the aorta and large arteries is increased, due partly to de novo expression or activation of monocyte adhesion molecules. Although there is increasing evidence that CMRs (chylomicron remnants) are strongly atherogenic, the outcomes of interactions between blood monocytes and circulating CMRs are not known. Here, we have studied the effects of CRLPs (CMR-like particles) on THP-1 human monocyte oxidative burst. The particles induced a significant increase in reactive oxygen species within 1 h, which persisted for 24 h. We suggest that monocyte–CMR interactions may be important in early atherosclerosis when many activated monocytes are found in susceptible areas of the artery wall.
Chylomicron and apoB48 metabolism in the JCR:LA corpulent rat, a model for the metabolic syndrome
Authors: Mangat R. , Su J. , Scott P.G. , Russell J.C. , Vine D.F. , Proctor S.D.
Published: May 2007

Postprandial (PP) lipaemia is a significant contributor to the development of dyslipidaemia and cardiovascular disease (CVD). It is also evident that PP lipaemia is prevalent during conditions of obesity and insulin resistance (IR) and may contribute to increased progression of CVD. Our group has assessed the potential of the obese JCR:LA-cp rat as a model of PP lipaemia in order to explore CM (chylomicron) metabolism during the onset and development of IR in the metabolic syndrome. Studies confirm that both fasting plasma and PP apoB48 (apolipoprotein B48) area under the curve are significantly elevated in the obese JCR:LA-cp phenotype as compared with lean controls. Mechanistic studies have also shown that the concentration of lymphatic CM apoB48 and CM size are significantly increased in this model. Furthermore, PP dyslipidaemia in the obese rat can be improved acutely with supplementation of n−3 polyunsaturated fatty acids. Using a different approach, we have subsequently hypothesized that the vascular remodelling that accompanies IR may explain accelerated entrapment of apoB48-containing particles. Small leucine-rich proteoglycans (including biglycan and decorin) have been observed to co-localize with apoB in human tissue. However, the potential impact of IR on vascular remodelling, particularly in the presence of obesity, remains unclear. Preliminary observations from the JCR:LA-cp model indicate that biglycan protein core content increases with age and is exacerbated by IR, suggestive of pro-atherogenic remodelling. The focus of this review is to contribute to the perspective of PP lipaemia in CVD risk associated with the metabolic syndrome through the use of animal models.
Apolipoprotein B48: a novel marker of metabolic risk in overweight children?
Authors: Nzekwu M.M.U. , Ball G.D.C. , Jetha M.M. , Beaulieu C. , Proctor S.D.
Published: May 2007

Clinical studies in adults indicate there is a positive and significant association between insulin resistance, dyslipidaemia, fasting intestinally derived lipoproteins [via apoB48 (apolipoprotein B48)] and visceral fat. All of these factors contribute to increased risk of CVD (cardiovascular disease). Since little is known about postprandial dyslipidaemia in overweight children, we sought to compare fasting levels of apoB48 with the HOMA-IR (homoeostasis model assessment of insulin resistance) score, classic lipid profile and VAT (visceral adipose tissue). Pre-pubertal, overweight boys and girls were recruited from the wider-Edmonton area (Alberta). Body composition was determined using both dual-energy X-ray absorptiometry and MRI (magnetic resonance imaging). Fasting apoB48 was quantified in plasma using an adapted SDS/PAGE immunoblotting technique, and insulin, glucose, TC (total cholesterol), TAG (triacylglycerol), LDL (low-density lipoprotein) and HDL (high-density lipoprotein) were determined by calorimetric assay. In this overweight sample, we observed elevated fasting apoB48 concentrations, greater than the normal adult range. In addition, apoB48 was significantly related to HOMA-IR and TAG levels. Although apoB48 was positively correlated with TC and LDL and negatively associated with HDL, these relationships did not achieve significance. Our ongoing MRI analysis reveals a positive relationship between apoB48 and VAT volume. To our knowledge, this is the first study to report apoB48 concentrations in overweight pre-pubertal children. Thus this article will provide a brief rationale for our study and its methodology.
PDNA as building blocks for membrane-guided self-assemblies
Authors: Pompon D. , Laisné A.
Published: May 2007

Different semi-synthetic PDNAs (protein–DNA complexes), which encompass a protein core engineered from the cytochrome b5 scaffold, an embedded tuneable redox cofactor, a synthetic linker and a large oligonucleotide, were designed, synthesized and purified to homogeneity. These building blocks can be reversibly attached to Ni-DOGS {1,2-dioleoyl-sn-glycero-3-[N(5-amino-1-carboxypentyl)iminodiacetic acid]succinyl}-doped supported membranes through a metal chelate bridge with the protein part and be polymerized in a fully controllable manner using a solid-phase synthesis strategy and a stepwise addition of suitable complementary oligonucleotides. The resulting structures could recreate a large range of regular distribution of patterned redox and absorbing centres separated by fully tuneable distances and geometry. Kinetic parameters for the self-assembly of building blocks were determined using SPRI (surface plasmon resonance imagery). Structures of resulting nano-objects were characterized using gel electrophoresis and single molecule approaches following decoration of assemblies with quantum dots.
The delivery of PEBBLE nanosensors to measure the intracellular environment
Authors: Webster A. , Coupland P. , Houghton F.D. , Leese H.J. , Aylott J.W.
Published: May 2007

Cellular introduction of PEBBLEs (photonic explorers for bioanalysis with biologically localized embedding) has been investigated by a wide variety of methods in a range of cell types. These methods include surface functionalization with CPPs (cell-penetrating peptides), pinocytosis, commercial lipid transfection agents, cytochalasin D, picoinjection, and Gene gun bombardment. This paper will overview several of the most popular methods used for the introduction of PEBBLE nanosensors to the cellular environment and discuss the efficacy of the techniques.
Raman microspectroscopy for non-invasive biochemical analysis of single cells
Authors: Swain R.J. , Stevens M.M.
Published: May 2007

Recent developments in biomedical vibrational spectroscopy now permit the non-invasive imaging of cells and tissues within both the laboratory and clinical settings. The rapid nature and diagnostic potential of both Raman and FTIR (Fourier-transform IR) spectroscopy have resulted in their widespread application to a number of biological fields including fundamental cell biology, medical imaging, tissue engineering and pharmacology. In particular, Raman microspectroscopy shows tremendous promise for the analysis of biological processes within living cells, such as cell cycle dynamics, cell differentiation and cell death. Unlike conventional biological assays, laser-based Raman spectroscopy enables rapid and non-invasive biochemical analysis of cells in the absence of fixatives or labels. The low Raman signal of cell culture buffer/media permits the rapid monitoring of living cells growing under standard cell culture conditions. The Raman spectrum of a cell is a biochemical ‘fingerprint’, containing molecular-level information about all biopolymers contained within the cell. The high information content of Raman spectra can be used to characterize the distribution of multiple cellular components, and to study the dynamics of subcellular reactions, with excellent spatial resolution. This review highlights recent developments in Raman microspectroscopy, with a focus on non-invasive biochemical analysis of single living cells.
The quest for Factor VIIa exosite inhibitors
Authors: Amour A. , Hutchinson J. , Ruiz Avendaño A.M. , Ratcliffe S. , Alvarez E. , Martin J. , Toomey J.R. , Senger S. , Wolfendale M. , Mooney C.
Published: May 2007

Coagulation proteases are involved in a highly orchestrated proteolytic cascade which is essential for haemostasis and blood clotting. In particular, the initiator of the coagulation cascade, Factor VIIa, binds to its cofactor, tissue factor, and its substrate, Factor X, via exosite interactions to form a ternary catalytic complex named extrinsic Xase. These exosite interactions have also been shown to allosterically induce the active conformation of the catalytic site of Factor VIIa. We have developed a direct continuous fluorescence polarization-based extrinsic Xase assay, which has been used to screen in excess of 1 million structurally diverse low-molecular-mass compounds as a potential starting point for the development of anticoagulants. The primary screen hits were categorized with deconvolution assays into either active-site or exosite inhibitors. The latter category of hits displayed both competitive and uncompetitive modalities of inhibition with respect to Factor X activation. An uncompetitive mechanism of action is of particular interest as it offers a hypothetical inhibitory advantage in the context of inhibiting a proteolytic cascade such as the blood coagulation pathway.
13C- and 1H-NMR studies of oxyanion and tetrahedral intermediate stabilization by the serine proteinases: optimizing inhibitor warhead specificity and potency by studying the inhibition of the serine proteinases by peptide-derived chloromethane and glyoxal inhibitors
Authors: Malthouse J.P.G.
Published: May 2007

Catalysis by the serine proteinases proceeds via a tetrahedral intermediate whose oxyanion is stabilized by hydrogen-bonding in the oxyanion hole. There have been extensive 13C-NMR studies of oxyanion and tetrahedral intermediate stabilization in trypsin, subtilisin and chymotrypsin using substrate-derived chloromethane inhibitors. One of the limitations of these inhibitors is that they irreversibly alkylate the active-site histidine residue which results in the oxyanion not being in the optimal position in the oxyanion hole. Substrate-derived glyoxal inhibitors are reversible inhibitors which, if they form tetrahedral adducts in the same way as substrates form tetrahedral intermediates, will overcome this limitation. Therefore we have synthesized 13C-enriched substrate-derived glyoxal inhibitors which have allowed us to use 13C-NMR and 1H-NMR to determine how they interact with proteinases. It is hoped that these studies will help in the design of specific and highly potent warheads for serine proteinase inhibitors.
A copper-binding site in the cytoplasmic domain of BACE1 identifies a possible link to metal homoeostasis and oxidative stress in Alzheimer's disease
Authors: Dingwall C.
Published: May 2007

The amyloidogenic processing pathway of the APP (amyloid precursor protein) generates Aβ (amyloid β-peptide), the major constituent in Alzheimer's disease senile plaques. This processing is catalysed by two unusual membrane-localized aspartic proteinases, β-secretase [BACE1 (β-site APP-cleaving enzyme 1)] and the γ-secretase complex. There is a clear link between APP processing and copper homoeostasis in the brain. APP binds copper and zinc in the extracellular domain and Aβ also binds copper, zinc and iron. We have found that a 24-residue peptide corresponding to the C-terminal domain of BACE1 binds a single copper(I) atom with high affinity through cysteine residues. We also observed that the cytoplasmic domain of BACE1 interacts with CCS, the dedicated copper chaperone for SOD1 (superoxide dismutase 1). Overproduction of BACE1 reduces SOD1 activity in cells. Consequently, SOD1 activity, cytosolic copper and ectodomain cleavage of APP are linked through BACE1.
Regulation of the lipidation of β-secretase by statins
Authors: Parsons R.B. , Farrant J.K. , Price G.C. , Subramaniam D. , Austen B.M.
Published: May 2007

Statins inhibit the dimerization of β-secretase [BACE (β-site amyloid precursor protein-cleaving enzyme)] by inhibiting the lipidation of BACE and associated proteins. Our studies have demonstrated a clearly defined temporal sequence for these reactions in the assembly of the BACE complex, which may provide targets for the treatment of Alzheimer's disease.
Roles and regulation of membrane-associated serine proteases
Authors: Qiu D. , Owen K. , Gray K. , Bass R. , Ellis V.
Published: May 2007

Pericellular proteolytic activity affects many aspects of cellular behaviour, via mechanisms involving processing of the extracellular matrix, growth factors and receptors. The serine proteases have exquisitely sensitive regulatory mechanisms in this setting, involving both receptor-bound and transmembrane proteases. Receptor-bound proteases are exemplified by the uPA (urokinase plasminogen activator)/uPAR (uPAR receptor) plasminogen activation system. The mechanisms initiating the activity of this proteolytic system on the cell surface, a critical regulatory point, are poorly understood. We have found that the expression of the TTSP (type II transmembrane serine protease) matriptase is highly regulated in leucocytes, and correlates with the presence of active uPA on their surface. Using siRNA (small interfering RNA), we have demonstrated that matriptase specifically activates uPAR-associated pro-uPA. The uPA/uPAR system has been implicated in the activation of the plasminogen-related growth factor HGF (hepatocyte growth factor). However, we find no evidence for this, but instead that HGF can be activated by both matriptase and the related TTSP hepsin in purified systems. Hepsin is of particular interest, as the proteolytic cleavage sequence of HGF is an ‘ideal substrate’ for hepsin and membrane-associated hepsin activates HGF with high efficiency. Both of these TTSPs can be activated autocatalytically at the cell surface, an unusual mechanism among the serine proteases. Therefore these TTSPs have the capacity to be true upstream initiators of proteolytic activity with subsequent downstream effects on cell behaviour.
The Testis as a Conduit for Genomic Plasticity: an advanced interdisciplinary workshop
Authors: Miller D. , Brinkworth M. , Iles D.
Published: May 2007

The premise for this unusual amalgamation of reproductive biologists, molecular geneticists and evolutionary biologists rested on the evidence-based assumption that reproductive tissues could be ideal environments for the expression and transmission of transposable elements that can move into new locations in the genome. These elements include DNA transposons and retrotransposons that, together, make up over 40% of the human genome. The testis may be a particularly good niche for their expression because of the unique dynamic of spermatogenesis, where the methylation–demethylation status of germ cell DNA is at its most plastic. Hence windows of opportunity can arise that may release transposable elements from the tight regulatory control of expression imposed on them by bulk DNA methylation. As the testis is where most mutations become embedded in the germline, the meeting included a number of keynote presentations that aimed to examine the potential for transposable elements to heritably alter the genome and effect variation independently of the usual Mendelian mechanisms. In essence, could the testis be one of the favoured sites where genomic plasticity makes its mark?
Genomewide identification of nuclear matrix attachment regions: an analysis of methods
Authors: Linnemann A.K. , Platts A.E. , Doggett N. , Gluch A. , Bode J. , Krawetz S.A.
Published: May 2007

High-throughput technologies now afford the opportunity to directly determine the distribution of MARs (matrix attachment regions) throughout a genome. The utility of cosmid and oligonucleotide platforms to identify human chromosome 16 MARs from preparations that employed LIS (lithium di-iodosalicylic acid) and NaCl extraction protocols was examined. The effectiveness of the platforms was then evaluated by Q-PCR (quantitative real-time PCR). Analysis revealed that caution must be exercised, since the representation of non-coding regions varies among platforms. Nevertheless, several interesting trends were revealed. We expect that these technologies will prove useful in systems approaches directed towards defining the role of MARs in various cell types and cellular processes.
APOBEC3 proteins: major players in intracellular defence against LINE-1-mediated retrotransposition
Authors: Schumann G.G.
Published: May 2007

Mammalian genomes are littered with enormous numbers of transposable elements interspersed within and between single-copy endogenous genes. The only presently spreading class of human transposable elements comprises non-LTR (long terminal repeat) retrotransposons, which cover approx. 34% of the human genome. Non-LTR retrotransposons include the widespread autonomous LINEs (long interspersed nuclear elements) and non-autonomous elements such as processed pseudogenes, SVAs [named after SINE (short interspersed nuclear element), VNTR (variable number of tandem repeats) and Alu] and SINEs. Mobilization of these elements affects the host genome, can be deleterious to the host cell, and cause genetic disorders and cancer. In order to limit negative effects of retrotransposition, host genomes have adopted several strategies to curb the proliferation of transposable elements. Recent studies have demonstrated that members of the human APOBEC3 (apolipoprotein B mRNA editing enzyme catalytic polypeptide 3) protein family inhibit the mobilization of the non-LTR retrotransposons LINE-1 and Alu significantly and participate in the intracellular defence against retrotransposition by mechanisms unknown to date. The striking coincidence between the expansion of the APOBEC3 gene cluster and the abrupt decline in retrotransposon activity in primates raises the possibility that these genes may have been expanded to prevent genomic instability caused by endogenous retroelements.
Quantum fluctuations in antiferromagnets of the BX2 family (abstract)
Authors: Rastelli E. , Tassi A.
Published: May 2007

The hexagonal antiferromagnets of the BX2 family, where B is a magnetic ion, and X a halogen, are characterized by an in plane exchange interaction J much stronger than the exchange interaction J′ along the c axis, so that some features of the triangular antiferromagnet (TA) could survive in these real compounds. In particular we are interested to investigate a possible ‘‘planar’’ phase with the spins lying in the c plane supported by quantum fluctuations when an external magnetic field H is applied perpendicular to the c axis. We find that such a phase is stable for sufficiently small interplane coupling owing to the zero point motion energy, whereas an ‘‘umbrella’’ phase would be expected on the basis of the classical approximation for any nonzero interplane coupling. Notice that for the TA model the planar and umbrella configurations are degenerate in classical approximation for any H and infinite isoenergetic planar configurations exist. Quantum fluctuations select a planar configuration with a spin over three opposite to the field. We find that the classical scenario itself is substantially different for any j=J′/J≠0, because only a planar configuration with a spin over three nearly perpendicular to the field and the umbrella configuration minimize the energy of the model and the umbrella is stable. However, quantum fluctuations stabilize the planar configuration for any H below a critical interplane coupling j*. For intermediate j the planar configuration is stable for low and high fields, whereas only the umbrella phase is stable of j large enough.
Vaccinating young adults against human papillomavirus: the importance of understanding health decision-making and behaviour
Authors: Skinner S. Rachel , Kang Melissa , Rosenthal Susan L.
Published: May 2007

Vaccination of young teenage females against human papillomavirus (HPV) with a newly licenced quadrivalent vaccine designed to prevent cervical cancer and genital warts has recently been recommended by the Australian government and will be implemented through schools from April 2007. In addition, a fully funded ‘catch-up’ vaccination program for young women up to age 26 years has been approved for a 2-year period, from July 2007. As general practitioners (GPs) will be the main immunisation providers for this age group, in order to achieve high vaccination coverage and maximal impact on disease, it will be critical for GPs to be opportunistic in recommending this vaccine. An initial study of young Australians’ attitudes towards HPV vaccination and hypothetical acceptance of the vaccine was published in this journal. We draw on this study and data published elsewhere to discuss issues of HPV vaccine acceptability, and the likely challenges of a mass vaccination initiative in this age group in Australia. We suggest specific strategies to support GPs, and highlight areas for further research in HPV vaccine acceptability.
Geometry-induced asymmetric diffusion
Authors: Shaw Robert S. , Packard Norman , Schröter Matthias , Swinney Harry L.
Published: May 2007

Past work has shown that ions can pass through a membrane more readily in one direction than the other. We demonstrate here in a model and an experiment that for a mixture of small and large particles such asymmetric diffusion can arise solely from an asymmetry in the geometry of the pores of the membrane. Our deterministic simulation considers a two-dimensional gas of elastic disks of two sizes diffusing through a membrane, and our laboratory experiment examines the diffusion of glass beads of two sizes through a metal membrane. In both experiment and simulation, the membrane is permeable only to the smaller particles, and the asymmetric pores lead to an asymmetry in the diffusion rates of these particles. The presence of even a small percentage of large particles can clog a membrane, preventing passage of the small particles in one direction while permitting free flow of the small particles in the other direction. The purely geometric kinetic constraints may play a role in common biological contexts such as membrane ion channels.