bluuebunny/crossref_metadata_2025 huggingface dataset:
GRACE observations of M2 and S2 ocean tides underneath the Filchner‐Ronne and Larsen ice shelves, Antarctica
Authors: Han Shin‐Chan , Shum C. K. , Matsumoto Koji
Published: October 2005

By processing the GRACE satellite‐to‐satellite tracking data and estimating the temporal gravity fields regionally over the southern polar region with a 5‐day interval, we observed M2 and S2 ocean tides underneath the Filchner‐Ronne and Larsen ice shelves, Antarctica. Based on the predicted aliased periods, we extracted the M2 and S2 signals from the time‐series of 5‐daily mean GRACE regional gravity estimates. The GRACE observations agreed well with the predicted tides from the FES2004 and CATS02.01 models after smoothing the models to the commensurate spatial resolution as GRACE. Overall, the GRACE and the models agreed within 10∼20% difference in the tidal amplitude and 20° in phase for both M2 and S2. Our results suggest that GRACE provides valuable observations of ocean tides, with a spatial resolution as short as 300 km, over the remote area lacking of quality observations, such as the Antarctica ice shelves.
Acute denervation alters the epithelial response to adrenoceptor activation through an increase in α1‐adrenoceptor expression on villus enterocytes
Authors: Baglole Carolyn J , Sigalet David L , Martin Gary R , Yao Shengtao , Meddings Jon B
Published: October 2005

Loss of sympathetic input due to intestinal denervation results in hypersensitivity and increased intestinal secretion. It is unknown whether denervation‐induced alterations in intestinal epithelial physiology are the result of changes in adrenoceptors on enterocytes (ENTs).

The purpose of this study was to examine adrenoceptor distribution and pharmacology on small intestinal ENTs following acute intestinal denervation.

Lewis rats underwent small bowel transplantation (SBT) or sham operation and proximal small intestinal segments were harvested 1, 2 and 4 weeks postoperatively. Intestinal electrolyte movement was assessed using short‐circuit current (Isc) measurements of stripped epithelial sheets following stimulation with phenylephrine (PE), an α1‐adrenoceptor agonist. The presence of adrenoceptor subtypes on separated villus and crypt ENTs was assessed using flow cytometry.

α1‐Adrenoceptors were found on approximately 27% of jejunal villus ENTs, but not crypt ENTs, following acute extrinsic denervation. ENTs from the Lewis rat have few β‐adrenoceptors.

α1‐Adrenoceptor stimulation of acutely denervated intestinal epithelial sheets decreased Isc by −13.45%. This effect was mediated by a reduction in chloride (Cl−) secretion; the absence of Cl− reversed the Isc to +13.79%.

In conclusion, loss of sympathetic innervation to the gastrointestinal epithelium causes acute upregulation of α1‐adrenoceptors on villus ENTs, leading to inhibition of Cl− secretion at the villus tip. The increase in adrenoceptors may reflect a compensatory mechanism to combat the increased secretory state of the bowel due to the loss of the sympathetic innervation and tonic control over intestinal secretion.

British Journal of Pharmacology (2006) 147, 101–108. doi:10.1038/sj.bjp.0706424
A delayed ATP‐elicited K+current in freshly isolated smooth muscle cells from mouse aorta
Authors: Serir Karima , Hayoz Sebastien , Fanchaouy Mohammed , Bény Jean‐Louis , Bychkov Rostislav
Published: October 2005

Adenosine 5′‐triphosphate (ATP) activated two sequential responses in freshly isolated mouse aortic smooth muscle cells. In the first phase, ATP activated Ca2+‐dependent K+or Cl−currents and the second phase was the activation of a delayed outward current with a reversal potential of −75.9±1.4 mV.

A high concentration of extracellular K+(130 mM) shifted the reversal potential of the delayed ATP‐elicited current to −3.5±1.3 mV. The known K+‐channel blockers, iberiotoxin, charybdotoxin, glibenclamide, apamin, 4‐aminopyridine, Ba2+and tetraethylammonium chloride all failed to inhibit the delayed ATP‐elicited K+current. Removal of ATP did not decrease the amplitude of the ATP‐elicited current back to the control values.

The simultaneous recording of cytosolic free Ca2+and membrane currents revealed that the first phase of the ATP‐elicited response is associated with an increase in intracellular Ca2+, while the second delayed phase develops after the return of cytosolic free Ca2+to control levels.

ATP did not activate Ca2+‐dependent K+currents, but did elicit Ca2+‐independent K+currents, in cells dialyzed with ethylene glycol‐bis (2‐aminoethylether)‐N,N,N′,N′‐tetraacetic acid (EGTA). The delay of activation of Ca2+‐independent currents decreased from 10.5+3.4 to 1.27±0.33 min in the cells dialyzed with 2 mMEGTA.

Adenosine alone failed to elicit a Ca2+‐independent K+current but simultaneous application of ATP and adenosine activated the delayed K+current. Intracellular dialysis of cells with guanosine 5′‐O‐(2‐thiodiphosphate) transformed the Ca2+‐independent ATP‐elicited response from a sustained to a transient one. A phospholipase C inhibitor, U73122 (1 μM), was shown to abolish the delayed ATP‐elicited response.

These results indicate that the second phase of the ATP‐elicited response was a delayed Ca2+‐independent K+current activated by exogenous ATP. This phase might represent a new vasoregulatory pathway in vascular smooth muscle cells.

British Journal of Pharmacology(2006)147, 45–54. doi:10.1038/sj.bjp.0706432
AM 251 produces sustained reductions in food intake and body weight that are resistant to tolerance and conditioned taste aversion
Authors: Chambers Adam P , Koopmans Henry S , Pittman Quentin J , Sharkey Keith A
Published: October 2005

The cannabinoid 1 (CB1) receptor has been implicated in the regulation of food intake. Here, we examine the effect of the CB1 receptor antagonist AM 251 on food intake and body weight over a prolonged period. Further, we examine whether AM 251 produces conditioned taste aversion (CTA) and if sustained antagonism at central receptors contributes to its anorectic effect.

The effect of AM 251 of food intake and body weight was examined in daily (1 mg kg−1) and 5‐day (5 mg kg−1) dosing schedules. Matching reductions in food intake and body weight were observed in both paradigms. A single administration of AM 251 (5 mg kg−1) significantly reduced food intake for 4 days. Tolerance to the anorectic effects of AM 251 did not develop in either dosing strategy.

Active avoidance of AM 251 (3; 5 mg kg−1, i.p.) was examined using a CTA assay. Rats showed no evidence of CTA associated with AM 251.

We investigated the sustained effect of AM 251 (5 mg kg−1, i.p.) on CB1 receptors in the hypothalamus using Δ9‐tetrahydrocannabinol (8 mg kg−1, i.p.) induced hypothermia. AM 251 initially blocked hypothermia, but this effect was not seen 2 or 4 days later.

The results demonstrate that smaller, or infrequent, administrations of AM 251 can produce sustained reductions in food intake and body weight in rat. Reductions in food intake were sustained longer than AM 251 antagonized the effects of a CB1 receptor agonist in the hypothalamus, and occurred independently of CTA.

British Journal of Pharmacology (2006) 147, 109–116. doi:10.1038/sj.bjp.0706439
Microstructural study of epitaxial Zn1−xMgxO composition spreads
Authors: Bendersky L. A. , Takeuchi I. , Chang K.-S. , Yang W. , Hullavarad S. , Vispute R. D.
Published: October 2005

We have fabricated Zn1−xMgxO epitaxial thin-film composition spreads by layer-by-layer pulsed laser deposition (PLD) method where the composition across the chip is linearly varied from ZnO to MgO. In this paper we discuss the cross-sectional transmission electron microscopy study of the combinatorial spreads. The full orientation relationships between substrate and the ZnO and MgO phases were established. Formation of twin-related domain structure was found for the [111]-oriented MgO. Formation of the [100]-oriented cubic MgO in [0001]-oriented ZnO was observed in the mixed region in the middle of the spread. This relationship can potentially be used to grow [100]-oriented cubic structures epitaxially on c-axis-oriented hexagonal substrates. For the extended solid solution of ZnO, a high density of defects was found. Analysis of the defects established that they are translational domains formed by three-dimensional island growth of PLD and specific to the crystallography of ZnO. The ZnO phase appears without precipitation of the MgO phase, which supports the idea of extended substitutional solid solution.
Osmium impurity-related deep levels in n-type GaAs
Authors: Majid A. , Zafar Iqbal M. , Dadgar A. , Bimberg D.
Published: October 2005

The 5d transition-metal impurity, osmium, has been incorporated during the growth of n-type GaAs epitaxial layers using low-pressure metal-organic chemical-vapor deposition to characterize defect states associated with this heavy and, therefore, thermally stable dopant impurity. Deep-level transient spectroscopy has been employed to investigate the electrical characteristics of Os-related deep levels. Two prominent deep levels have been identified with Os at Ec−0.28eV (Os1) and Ec−0.41eV (Os2) in the upper half-band-gap of GaAs, while no Os-related level has been clearly detected in the lower half-band-gap. The detailed characteristics determined for the two levels include thermal emission rate signatures, leading to the above cited thermal activation energies, electron-capture cross sections, and their temperature dependence, measured by direct pulse-filling technique and deep-level concentrations. Further, both levels are found to exhibit a significant dependence of thermal emission rates on the junction electric field. While Os1 does not allow accurate quantitative investigations of this field dependence due to its relatively low concentration, detailed quantitative data on the field dependence of the level Os2 are reported. Analysis of these data in light of the available theoretical models allows us to conclude that Os2 is probably a substitutional donor-type defect in GaAs.
Orbital-free embedding applied to the calculation of induced dipole moments in CO2⋯X (X=He, Ne, Ar, Kr, Xe, Hg) van der Waals complexes
Authors: Jacob Christoph R. , Wesolowski Tomasz A. , Visscher Lucas
Published: October 2005

The orbital-free frozen-density embedding scheme within density-functional theory [T. A. Wesolowski and A. Warshel, J. Phys. Chem. 97, 8050 (1993)] is applied to the calculation of induced dipole moments of the van der Waals complexes CO2⋯X (X=He, Ne, Ar, Kr, Xe, Hg). The accuracy of the embedding scheme is investigated by comparing to the results of supermolecule Kohn-Sham density-functional theory calculations. The influence of the basis set and the consequences of using orbital-dependent approximations to the exchange-correlation potential in embedding calculations are examined. It is found that in supermolecular Kohn-Sham density-functional calculations, different common approximations to the exchange-correlation potential are not able to describe the induced dipole moments correctly and the reasons for this failure are analyzed. It is shown that the orbital-free embedding scheme is a useful tool for applying different approximations to the exchange-correlation potential in different subsystems and that a physically guided choice of approximations for the different subsystems improves the calculated dipole moments significantly.
Experimental study of substrate roughness and surfactant effects on the Landau-Levich law
Authors: Krechetnikov R. , Homsy G. M.
Published: October 2005

In this work we present an experimental study of deviations from the classical Landau-Levich law in the problem of dip coating. Among the examined causes leading to deviations are the nature of the liquid-gas and liquid-solid interfaces. The thickness of the coating film created by withdrawal of a plate from a bath was measured gravimetrically over a wide range of capillary numbers for both smooth and well-characterized rough substrates, and for clean and surfactant interface cases. In view of the dependence of the lifetime of a film on the type of liquid and substrate, and liquid-gas and liquid-solid interfaces, we characterized the range of measurability of the film thickness in the parameter space defined by the withdrawal capillary number, the surfactant concentration, and substrate roughness size. We then study experimentally the effect of a film thickening due to the presence of surfactants. Our recent theory based on a purely hydrodynamic role of the surface active substance suggests that there is a sorption-controlled coating regime in which Marangoni effects should lead to film thinning. However, our experiments conducted in this regime demonstrate film thickening, calling into question the conventional wisdom, which is that Marangoni stresses (as accounted by the conventional interfacial boundary conditions) lead to film thickening. Next we examine the effect of well-characterized substrate roughness on the coated film thickness, which also reveals its influence on wetting-related processes and an effective boundary condition at the wall. In particular, it is found that roughness results in a significant thickening of the film relative to that on a smooth substrate and a different power of capillary number than the classical Landau-Levich law.
Enhancement of iridium-based organic light-emitting diodes by spatial doping of the hole transport layer
Authors: Wang Ying , Gao Weiying , Braun Slawomir , Salaneck William R. , Amy Fabrice , Chan Calvin , Kahn Antoine
Published: October 2005

The electroluminescence efficiency of Ir-based green emitter devices is very sensitive to the nature of the hole transport layer used. We show that by inserting a 1 nm layer of bis[4-(N,N-diethylamino)-2-methylphenyl](4-methylphenyl)methane (MPMP) in a 4,4′-bis-(carbazol-9-yl)biphenyl (CBP) hole transport layer, a device that combines the positive attributes of both MPMP (high efficiency) and CBP (low injection voltage) is obtained. These results can be understood based on a combined ultraviolet photoemission spectroscopy/inverse photoemission spectroscopy study, which reveals the very low electron affinity and superior electron blocking capability of MPMP.
Electronic properties of potassium-doped CuPc
Authors: Molodtsova O. V. , Zhilin V. M. , Vyalikh D. V. , Aristov V. Yu. , Knupfer M.
Published: October 2005

We have studied the electronic structure of potassium-doped copper phthalocyanine (CuPc) using photoemission spectroscopy. A detailed analysis of the core-level spectra allows us to propose possible lattice sites for the potassium ions. None of the films prepared in our studies showed a finite electronic density of states at the Fermi level (EF), which is in contrast to reports in the literature. Possible reasons for this discrepancy are discussed.
Transient-current measurement of the trap charge density at interfaces of a thin-film metal∕ferroelectric∕metal structure
Authors: Delimova L. A. , Grekhov I. V. , Mashovets D. V. , Tyaginov S. E. , Shin Sangmin , Koo June-Moo , Kim Suk-Pil , Park Youngsoo
Published: October 2005

A method providing estimation of the trap density at metal∕ferroelectric interfaces of a depleted ferroelectric film located between back-to-back Schottky barriers has been developed. The method is based on the recharge of interface traps induced by external bias pulse applied to the metal∕ferroelectric∕metal structure. It is shown that the transient current under bias pulse can be controlled by the trap recharge on the reverse-biased interface. Using the method, the trap charge density on interfaces of the Pt∕PZT∕Ir(Ti∕SiO2∕Si) capacitor was found from transient-current measurements to be two orders of magnitude less than the remnant polarization of PbZrxTi1−xO3 film.
Compressive strain dependence of hole mobility in strained Ge channels
Authors: Sawano K. , Abe Y. , Satoh H. , Shiraki Y. , Nakagawa K.
Published: October 2005

The strain dependence of the hole mobility was systematically investigated in the compressively strained Ge channel modulation-doped structure. It was clearly observed that the mobility increases with increasing compressive strain until the strain as high as 1.9%. The highest mobility of 20 800 and 2000cm2∕Vs at 8 K and room temperature, respectively, was obtained for the Ge channel structure grown on the relaxed SiGe buffer layers with Ge composition of 53%. The origins of this mobility increase are speculated to be the reduction of effective mass, suppression of interband phonon scattering, and the increased confinement of the holes in the channel layer.
Dielectric and ferroelectric properties of (Na0.8K0.2)0.5Bi0.5TiO3 thin films prepared by metalorganic solution deposition
Authors: Yang Changhong , Han Jianru , Cheng Xiufeng , Yin Xin , Wang Zhuo , Zhao Minglei , Wang Chunlei
Published: October 2005

( Na 0.8 K 0.2 ) 0.5 Bi 0.5 TiO 3 thin films have been prepared on Pt∕TiO2∕SiO2∕Si and p-type Si substrates using a metalorganic solution deposition method. The films annealed at 700 °C crystallize well and present perovskite phase. The films exhibit a well-defined hysteresis loop at an applied voltage of 4 V, with a remanent polarization of 4.7μC∕cm2 and a coercive field of 38kV∕cm. The films also show fatigue-free response up to 1.5×1010 switching cycles. The relaxor behavior of the films is confirmed by the frequency-dependence of capacitance-temperature relation. The capacitance-voltage curves show that the films are polarization-type switching and the memory window is about 2.5 V at ±4V applied dc bias voltages. The changes of dielectric constant and dissipation factor with frequency are also investigated briefly.
Ring and axis mode switching in multielectrode strained InGaAsP multiple-quantum-well quasistadium laser diodes
Authors: Fukushima Takehiro , Tanaka Tomoko , Harayama Takahisa
Published: October 2005

We describe the mode switching operation of multielectrode strained InGaAsP multiple-quantum-well quasistadium laser diodes. Far-field patterns exhibit highly directional emission along the laser cavity axis for current injection at the axis electrode and highly directional emission at angles ±19° from the cavity axis for current injection at the ring electrode. These directions correspond to the axis mode and the ring trajectory mode of the laser cavity. We also succeeded in obtaining single peak output beams using narrow curved end mirrors of 40μm width.
Increased capacity for sucrose uptake leads to earlier onset of protein accumulation in developing pea seeds
Authors: Rosche Elke G. , Blackmore Daniel , Offler Christina E. , Patrick John W.
Published: October 2005

Pea (Pisum sativum L.) cotyledons, overexpressing a potato sucrose transporter (StSUT1), were used to explore the hypothesis that sucrose stimulates the onset of storage protein biosynthesis. The study focused on the transition between pre-storage and storage phases of seed development. During this period supply of sucrose and hexose to transgenic cotyledons was unaffected by StSUT1 expression. However, protoplasmic levels of sucrose but not hexoses were elevated in transgenic cotyledons. Total protein levels in cotyledons followed the same temporal trend as observed for sucrose and this was reflected in an earlier appearance of protein bodies. Protein levels in wild type and StSUT1 cotyledons were found to lie on the same sucrose dose-response curve and this could be reproduced in vitro when wild type cotyledons were cultured on media containing various sucrose concentrations. Rates of [14C]sucrose uptake and incorporation into polymeric forms were consistent with protoplasmic sucrose supplying a proportion of the carbon skeletons required for storage protein accumulation. In addition, vicilin gene expression was up-regulated earlier in StSUT1 cotyledons. We conclude that sucrose functions both as a signal and fuel to stimulate storage protein accumulation and assembly into protein bodies. An earlier stimulation of storage protein synthesis is considered to largely account for the 14% increase in protein levels of StSUT1 seeds at harvest.
Helicobacter pylori
CagA induces a transition from polarized to invasive phenotypes in MDCK cells
Authors: Bagnoli Fabio , Buti Ludovico , Tompkins Lucy , Covacci Antonello , Amieva Manuel R.
Published: October 2005

CagA is a bacterial effector protein of
Helicobacter pylori
that is translocated via a type IV secretion system into gastric epithelial cells. We previously described that
H. pylori
require CagA to disrupt the organization and assembly of apical junctions in polarized epithelial cells. In this study, we provide evidence that CagA expression is not only sufficient to disrupt the apical junctions but also perturbs epithelial differentiation. CagA-expressing cells lose apicobasal polarity and cell–cell adhesion, extend migratory pseudopodia, and degrade basement membranes, acquiring an invasive phenotype. Expression of the CagA C-terminal domain, which contains the tyrosine phosphorylated EPIYA motifs, induces pseudopodial activity but is not sufficient to induce cell migration. Conversely, the N terminus targets CagA to the cell–cell junctions. Neither domain is sufficient to disrupt cell adhesion or cell polarity, but coexpressed
in trans
, the N terminus determines the localization of both polypeptides. We show that CagA induces a morphogenetic program in polarized Madin–Darby canine kidney cells resembling an epithelial-to-mesenchymal transition. We propose that altered cell–cell and cell matrix interactions may serve as an early event in
H. pylori
-induced carcinogenesis.
Interplay among coactivator-associated arginine methyltransferase 1, CBP, and CIITA in IFN-γ-inducible MHC-II gene expression
Authors: Zika Eleni , Fauquier Lucas , Vandel Laurence , Ting Jenny P.-Y.
Published: October 2005

Class II major histocompatibility(MHC-II) genes are prototype targets of IFN-γ. IFN-γ activates the expression of the non-DNA-binding master regulator ofMHC-II, class II transactivator (CIITA), which is crucial for enhanceosome formation and gene activation. This report shows the importance of the histone methyltransferase, coactivator-associated arginine methyltransferase (CARM1/PRMT4), during IFN-γ-inducedMHC-IIgene activation. It also demonstrates the coordinated regulation of CIITA, CARM1, and the acetyltransferase cyclic-AMP response element binding (CREB)-binding protein (CBP) during this process. CARM1 synergizes with CIITA in activating MHC-II transcription and synergy is abrogated when an arginine methyltransferase-defective CARM1 mutant is used. Protein-arginine methyltransferase 1 has much less effect on MHC-II transcription. Specific RNA interference reduced CARM1 expression as well as MHC-II expression. The recruitment of CARM1 to the promoter requires endogenous CIITA and results in methylation of histone H3-R17; hence, CIITA is an upstream regulator of histone methylation. Previous work has shown that CARM1 can methylate CBP at three arginine residues. Using wild-type CBP and a mutant of CBP lacking the CARM1-targeted arginine residues (R3A), we show that arginine methylation of CBP is required for IFN-γ induction of MHC-II. A kinetic analysis shows that CIITA, CARM1, and H3-R17 methylation all precede CBP loading on theMHC-IIpromoter during IFN-γ treatment. These results suggest functional and temporal relationships among CIITA, CARM1, and CBP for IFN-γ induction ofMHC-II.
Concurrent working memory load can reduce distraction
Authors: Kim So-Yeon , Kim Min-Shik , Chun Marvin M.
Published: October 2005

People have difficulty performing two tasks at once. For example, maintaining items in working memory (WM) makes people more distractible. However, different types of WM load may have different effects on attentional selection depending on whether WM load overlaps with mechanisms involved in target or distractor processing. Three experiments examined the effect of concurrent WM load on Stroop tasks, a widely used measure of executive control and inhibition. Stroop interference increased when the type of WM load overlapped with the type of information required for the target task (experiment 1). In striking contrast, Stroop interference decreased when the type of WM load overlapped with distractor processing (experiment 2). Experiment 3 replicated these results in a different Stroop task. Thus, concurrent WM load does not always impair executive control; performance depends on how contents of WM and task-relevant information overlap. The results highlight how dissociable components of WM interact with perception and executive control.
Probing helix propensity of monomers within a helical oligomer
Authors: Dolain Christel , Léger Jean-Michel , Delsuc Nicolas , Gornitzka Heinz , Huc Ivan
Published: October 2005

A simple strategy is proposed to assess the propensity of a given monomer to follow or not follow a particular helical scheme and to study helix reversal phenomena within helical oligomers. It consists of placing a monomer having a low helix propensity between two conformationally stable helical segments. Helix reversion then occurs preferentially at the site of this monomer, leading to the formation of isomers having P (right-handed) or M (left-handed) helicities at each of the two helical segments. The proportion between the P-P/M-M and P-M isomers is indicative of the stereochemical relations between the inserted monomer and the helical frame. Thus, xylylene or carboxylic acid anhydride spacers have been introduced between two helical oligoamides of 8-amino-2-quinolinecarboxylic acid. Both these spacers presumably lack some of the structural features that confer quinoline units with a high helix propensity. Only one species is observed in solution in the case of an anhydride spacer. This species was shown by x-ray crystallography to be a racemic mixture of P-P and M-M helices. Unexpectedly, the anhydride is consistently incorporated within helical oligoamides. For the xylylene spacer, the P-P/M-M racemate and P-M
meso
compound are in equal proportions in chloroform, showing that this spacer does not have a propensity to adopt any helical conformation in this solvent. However, the equilibria between the various isomers are shifted in toluene, where one species largely prevails. This species was shown by x-ray crystallography to be the P-P/M-M racemate. Molecular dynamics simulations are consistent with these solution data.
Detection and quantification of mutations in the plasma of patients with colorectal tumors
Authors: Diehl Frank , Li Meng , Dressman Devin , He Yiping , Shen Dong , Szabo Steve , Diaz Luis A. , Goodman Steven N. , David Kerstin A. , Juhl Hartmut , Kinzler Kenneth W. , Vogelstein Bert
Published: October 2005

The early detection of cancers through analysis of circulating DNA could have a substantial impact on morbidity and mortality. To achieve this goal, it is essential to determine the number of mutant molecules present in the circulation of cancer patients and to develop methods that are sufficiently sensitive to detect these mutations. Using a modified version of a recently developed assay for this purpose, we found that patients with advanced colorectal cancers consistently contained mutant adenomatous polyposis coli (
APC
) DNA molecules in their plasma. The median number of
APC
DNA fragments in such patients was 47,800 per ml of plasma, of which 8% were mutant. Mutant
APC
molecules were also detected in >60% of patients with early, presumably curable colorectal cancers, at levels ranging from 0.01% to 1.7% of the total
APC
molecules. These results have implications for the mechanisms through which tumor DNA is released into the circulation and for diagnostic tests based on this phenomenon.
Genetic reduction of embryonic leukemia-inhibitory factor production rescues placentation in SOCS3-null embryos but does not prevent inflammatory disease
Authors: Robb Lorraine , Boyle Kristy , Rakar Steven , Hartley Lynne , Lochland Janelle , Roberts Andrew W. , Alexander Warren S. , Metcalf Donald
Published: October 2005

The suppressor of cytokine-signaling (SOCS) proteins act as negative-feedback inhibitors of cytokine and growth-factor-induced signal transduction.
In vivo
studies have implicated SOCS3 as a negative regulator of signaling downstream of gp130, the receptor subunit shared by IL-6-like cytokines. Mice lacking SOCS3 die at midgestation because of placental failure, and SOCS3 ablation in a cell-type-specific manner results in changes in the functional outcome of gp130 signaling in response to IL-6. In this study, we show that genetic reduction of leukemia-inhibitory factor (LIF) production by embryo-derived tissues is sufficient to prevent the placental defect. This establishes LIF signaling as a major physiological regulator of trophoblast differentiation
in vivo
. Mice deficient in both SOCS3 and LIF are born in predicted numbers and appear normal at birth but exhibit failure to thrive and high neonatal mortality. Adult SOCS3-null mice on a LIF-null background succumb to a spontaneous fatal inflammatory disease characterized by neutrophilia and inflammatory-cell tissue infiltrates. The disease spectrum mimics that seen in mice with a conditional deletion of SOCS3 in hematopoietic and endothelial cells, extending the evidence for a major role for SOCS3 in the homeostatic regulation of the inflammatory response and indicates that LIF is not required for this process.
Nucleoid remodeling by an altered HU protein: Reorganization of the transcription program
Authors: Kar Sudeshna , Edgar Rotem , Adhya Sankar
Published: October 2005

Bacterial nucleoid organization is believed to have minimal influence on the global transcription program. Using an altered bacterial histone-like protein, HUα, we show that reorganization of the nucleoid configuration can dynamically modulate the cellular transcription pattern. The mutant protein transformed the loosely packed nucleoid into a densely condensed structure. The nucleoid compaction, coupled with increased global DNA supercoiling, generated radical changes in the morphology, physiology, and metabolism of wild-type K-12
Escherichia coli
. Many constitutive housekeeping genes involved in nutrient utilization were repressed, whereas many quiescent genes associated with virulence were activated in the mutant. We propose that, as in eukaryotes, the nucleoid architecture dictates the global transcription profile and, consequently, the behavior pattern in bacteria.
Intronic regulation of
matrix metalloproteinase-2
revealed by
in vivo
transcriptional analysis in ischemia
Authors: Lee Jackie G. , Dahi Sia , Mahimkar Rajeev , Tulloch Nathaniel L. , Alfonso-Jaume Maria A. , Lovett David H. , Sarkar Rajabrata
Published: October 2005

Matrix metalloproteinase-2 (MMP-2) plays an essential role in angiogenesis and arteriogenesis, two processes critical to restoration of tissue perfusion after ischemia.
MMP-2
expression is increased in tissue ischemia, but the responsible mechanisms remain unknown. We studied the transcriptional activation of the MMP-2 gene in a model of hindlimb ischemia by using various MMP-2-lacZ reporter mice and chromatin immunoprecipitation. MMP-2 activity and mRNA were increased after hindlimb ischemia. Mice with targeted deletion of
MMP-2
had impaired restoration of perfusion and a high incidence of limb gangrene, indicating that MMP-2 plays a critical role in ischemia-induced revascularization. Ischemia induced the expression and binding of c-Fos, c-Jun, JunB, FosB, and Fra2 to a noncanonical activating protein-1 (AP-1) site present in the
MMP-2
promoter and decreased binding of the transcriptional repressor JunD. Ischemia also activated the expression and binding of p53 to an adjacent enhancer site (RE-1) and increased expression and binding of nuclear factor of activated T-cells-c2 to consensus sequences within the first intron. Deletion of either the 5′ AP-1/RE-1 region of the promoter or substitution of the first intron abolished ischemia-induced
MMP-2
transcription
in vivo
. Thus, AP-1 transcription factors and intronic activation by nuclear factor of activated T-cells-c2 act in concert to drive ischemia-induced MMP-2 transcription. These findings define a critical role for MMP-2 in ischemia-induced revascularization and identify both previously uncharacterized regulatory elements within the
MMP-2
gene and the cognate transcription factors required for
MMP-2
activation
in vivo
after tissue ischemia.
Isolating gene-corrected stem cells without drug selection
Authors: Hatada Seigo , Arnold Larry W. , Hatada Tomoko , Cowhig John E. , Ciavatta Dominic , Smithies Oliver
Published: October 2005

Progress in isolating stem cells from tissues, or generating them from adult cells by nuclear transfer, encourages attempts to use stem cells from affected individuals for gene correction and autologous therapy. Current viral vectors are efficient at introducing transgenic sequences but result in random integrations. Gene targeting, in contrast, can directly correct an affected gene, or incorporate corrective sequences into a site free from undesirable side effects, but efficiency is low. Most current targeting procedures, consequently, use positive-negative selection with drugs, often requiring ≥10 days. This drug selection causes problems with stem cells that differentiate in this time or require feeder cells, because the feeders must be drug resistant and so are not eliminated by the selection. To overcome these problems, we have developed a procedure for isolating gene-corrected stem cells free from feeder cells after 3-5 days culture without drugs. The method is still positive-negative, but the positive and negative drug-resistance genes are replaced with differently colored fluorescence genes. Gene-corrected cells are isolated by FACS. We tested the method with mouse ES cells having a mutant hypoxanthine phosphoribosyltransferase (
Hprt
) gene and grown on feeder cells. After 5 days in culture, gene-corrected cells were obtained free from feeder cells at a “purity” of >30%, enriched >2,000-fold and with a recovery of ≈20%. Corrected cells were also isolated singly for clonal expansion. Our FACS-based procedure should be applicable at small or large scale to stem cells that can be cultured (with feeder cells, if necessary) for ≥3 days.
Use of national food balance data to estimate the adequacy of zinc in national food supplies: methodology and regional estimates
Authors: Wuehler Sara E , Peerson Janet M , Brown Kenneth H
Published: October 2005

Objectives

Adequate zinc nutriture is critically important for human health, but the development of programmes to control zinc deficiency is limited by the lack of reliable information on population zinc status. The present analyses were conducted to: (1) estimate the absorbable zinc content of national food supplies; (2) compare this information with theoretical population requirements for zinc; and (3) use these results to predict national risks of inadequate zinc intake.

Setting and design: National food balance data were obtained for 176 countries from the Food and Agriculture Organization of the United Nations. The amount of absorbable zinc in these foods was estimated from food composition data, and zinc absorption was predicted using a model developed by the International Zinc Nutrition Consultative Group (IZiNCG). Demographic data were obtained from United Nations estimates, and age- and sex-specific physiological requirements for absorbable zinc were estimated using IZiNCG recommendations.

Results and conclusions: The mean per capita absorbable zinc content of national food supplies ranged from 2.98–3.01 mg day−1 in Western Europe and USA & Canada to 2.09 mg day−1 in Southeast Asia. The estimated percentage of individuals at risk of inadequate zinc intake ranged from 9.3–9.5% in the regions of North Africa & Eastern Mediterranean and USA & Canada to 33.1% in Southeast Asia. Overall, approximately 20.5% of the world's population is estimated to be at risk of inadequate zinc intake. Data on the absorbable zinc content of national food supplies can be used to determine whether further assessments of population zinc status and development of intervention programmes are warranted.
Beneficial effects of short-term nutritional counselling at the primary health-care level among Brazilian adults
Authors: Sartorelli Daniela Saes , Sciarra Elaine Cristina , Franco Laércio Joel , Cardoso Marly Augusto
Published: October 2005

Objective

To evaluate the impact of a low-cost nutritional intervention in changing the lifestyle of adults.

Design

Randomised clinical trial.

Setting

Primary health-care centre in São José do Rio Preto, São Paulo State, Brazil.

Subjects

We randomly assigned 104 adults (83 women and 21 men aged 30–65 years, body mass index 24–35 kg m−2, non-diabetic) into two groups: nutrition counselling and control. Each subject in the intervention group received three individualised nutritional counselling sessions during the first 6 months aimed at increasing intakes of fruits, vegetables and olive oil, reducing saturated fat and improving physical activity. Body composition, biochemical indicators and lifestyle were assessed at baseline and at 6 months and 1 year in both groups.

Results

After 6 months of follow-up, body weight, waist circumference, diastolic blood pressure, fasting blood glucose, total and low-density lipoprotein cholesterol, total and saturated fat, and dietary energy and cholesterol levels showed a more significant decrease among subjects in the intervention group than in the control group (P<05). Moreover, the intervention group showed significantly greater improvement in each intervention goal, such as reduced intake of saturated fat and increased intakes of fruits, vegetables, fibre and olive oil (P<0.05). After 12 months of follow-up, most of the outcomes were maintained.

Conclusions

The low-cost nutritional intervention programme improved serum lipids profile and weight control, and appeared to be feasible for use at a primary health-care centre in a developing country.
Physical activity levels in 10- to 11-year-olds: clustering of psychosocial correlates
Authors: Cardon Greet , Philippaerts Renaat , Lefevre Johan , Matton Lynn , Wijndaele Katrien , Balduck Anne-Line , Bourdeaudhuij Ilse De
Published: October 2005

Objectives

To evaluate gender differences for levels of physical activity, for sedentary behaviour and for psychosocial correlates in children, to evaluate whether psychosocial correlates cluster in meaningful ways and to examine whether physical activity and sedentary behaviour differ between children of clusters, differentiated by the level of perceived barriers and benefits, attitudes, social support and self-efficacy.

Design

Cross-sectional study using the Flemish Physical Activity Questionnaire.

Setting

Questionnaires to be filled out by the children and one of their parents, contacted through the school system.

Subjects

A sample of 1124 10- to 11-year-olds (579 boys and 545 girls).

Results

Girls were found to be less active than boys, with boys scoring better for social support, perceived benefits and self-efficacy compared with girls. The way of clustering differed between boys and girls. Boys were allocated to three clusters: one cluster with positive correlates towards physical activity, labelled ‘positives’; one with negative correlates, labelled ‘negatives’; and one characterised mainly by high perceived barriers, labelled ‘hindered’;. In both genders the highest levels of physical activity were found in the ‘positives’;, the lowest in the ‘negatives’;. In girls a fourth cluster was identified, characterised mainly by low perceived barriers and low social support. Physical activity levels in the girls of this cluster, labelled ‘indifferents’;, were the second highest.

Conclusions

More research is needed to further characterise these clusters. To prevent the physical activity decline during the transition from childhood to adulthood, novel interventions need to be explored that focus on children of the clusters with the most negative correlates.
Evaluation of the Carcinogenic Potential of Clofibrate in FVB/Tg.AC Mouse After Oral Administration—Part I
Authors: Torrey Carla E. , Wall Henry G. , Campbell James A. , Kwanyuen Puntipa , Hoivik Debie J. , Miller Richard T. , Allen Jane S. , Jayo Manuel J. , Selinger Krzysztof , Savina Paul M. , Santostefano Michael J.
Published: October 2005

This study was conducted as part of the International Life Sciences Institute (ILSI) program to evaluate the carcinogenic potential of clofibrate, a nongenotoxic, peroxisome proliferator-activated receptor (PPAR) α agonist following oral administration to Tg.AC (transgenic) and wild-type FVB (nontransgenic) mice for a minimum for 6 months. Clofibrate was well tolerated at doses up to 500 (males) and 650 (females) mg/kg/day. Oral administration of clofibrate to Tg.AC or FVB (wild-type) male and female mice for 6 months did not result in the increased formation of neoplastic lesions. Epithelial hyperplasia in the urinary bladder (Tg.AC and FVB) and prostate gland (Tg.AC only), and interstitial-cell hyperplasia in the testes (Tg.AC) were noted at 500 mg/kg/day. Non-neoplastic nonproliferative findings included hepatic hypertrophy and hematopoietic changes (myeloid hyperplasia, myelodysplasia, lymphoid depletion, and erythropoiesis) in Tg.AC and FVB mice of both sexes; reproductive (cystic degeneration and dilatation, hypospermia, spermatocele, dilated inspissated protein) and urogenital (tubular-cell hypertrophy, degenerative/regenerative nephropathy, necrosis/fibrosis) changes in Tg.AC and FVB male mice; congestion in the lung in male Tg.AC mice; gall bladder dilatation in female Tg.AC mice; and adrenal (intracellular lipofuscinosis and atrophy) and heart (eosinophillic myofibers) findings in Tg.AC mice of both sexes and in female FVB mice. The results of this study indicate that the clofibrate is not carcinogenic when administered to Tg.AC mice by oral gavage for 6 months at doses up to 500 (males) and 650 (females) mg/kg/day, which did produce liver hypertrophy.
Classification using functional data analysis for temporal gene expression data
Authors: Leng Xiaoyan , Müller Hans-Georg
Published: October 2005

Motivation: Temporal gene expression profiles provide an important characterization of gene function, as biological systems are predominantly developmental and dynamic. We propose a method of classifying collections of temporal gene expression curves in which individual expression profiles are modeled as independent realizations of a stochastic process. The method uses a recently developed functional logistic regression tool based on functional principal components, aimed at classifying gene expression curves into known gene groups. The number of eigenfunctions in the classifier can be chosen by leave-one-out cross-validation with the aim of minimizing the classification error.

Results: We demonstrate that this methodology provides low-error-rate classification for both yeast cell-cycle gene expression profiles and Dictyostelium cell-type specific gene expression patterns. It also works well in simulations. We compare our functional principal components approach with a B-spline implementation of functional discriminant analysis for the yeast cell-cycle data and simulations. This indicates comparative advantages of our approach which uses fewer eigenfunctions/base functions. The proposed methodology is promising for the analysis of temporal gene expression data and beyond.

Availability: MATLAB programs are available upon request.

Contact:  ileng@wfubmc.edu

Supplementary information: Supplementary materials are available on the journal's website.
A generic motif discovery algorithm for sequential data
Authors: Jensen Kyle L. , Styczynski Mark P. , Rigoutsos Isidore , Stephanopoulos Gregory N.
Published: October 2005

Motivation: Motif discovery in sequential data is a problem of great interest and with many applications. However, previous methods have been unable to combine exhaustive search with complex motif representations and are each typically only applicable to a certain class of problems.

Results: Here we present a generic motif discovery algorithm (Gemoda) for sequential data. Gemoda can be applied to any dataset with a sequential character, including both categorical and real-valued data. As we show, Gemoda deterministically discovers motifs that are maximal in composition and length. As well, the algorithm allows any choice of similarity metric for finding motifs. Finally, Gemoda's output motifs are representation-agnostic: they can be represented using regular expressions, position weight matrices or any number of other models for any type of sequential data. We demonstrate a number of applications of the algorithm, including the discovery of motifs in amino acids sequences, a new solution to the (l,d)-motif problem in DNA sequences and the discovery of conserved protein substructures.

Availability: Gemoda is freely available at

Contact:  gregstep@mit.edu

Supplementary Information: Available at
Robust multi-scale clustering of large DNA microarray datasets with the consensus algorithm
Authors: Grotkjær Thomas , Winther Ole , Regenberg Birgitte , Nielsen Jens , Hansen Lars Kai
Published: October 2005

Motivation: Hierarchical and relocation clustering (e.g. K-means and self-organizing maps) have been successful tools in the display and analysis of whole genome DNA microarray expression data. However, the results of hierarchical clustering are sensitive to outliers, and most relocation methods give results which are dependent on the initialization of the algorithm. Therefore, it is difficult to assess the significance of the results. We have developed a consensus clustering algorithm, where the final result is averaged over multiple clustering runs, giving a robust and reproducible clustering, capable of capturing small signal variations. The algorithm preserves valuable properties of hierarchical clustering, which is useful for visualization and interpretation of the results.

Results: We show for the first time that one can take advantage of multiple clustering runs in DNA microarray analysis by collecting re-occurring clustering patterns in a co-occurrence matrix. The results show that consensus clustering obtained from clustering multiple times with Variational Bayes Mixtures of Gaussians or K-means significantly reduces the classification error rate for a simulated dataset. The method is flexible and it is possible to find consensus clusters from different clustering algorithms. Thus, the algorithm can be used as a framework to test in a quantitative manner the homogeneity of different clustering algorithms. We compare the method with a number of state-of-the-art clustering methods. It is shown that the method is robust and gives low classification error rates for a realistic, simulated dataset. The algorithm is also demonstrated for real datasets. It is shown that more biological meaningful transcriptional patterns can be found without conservative statistical or fold-change exclusion of data.

Availability:  Matlab source code for the clustering algorithm ClusterLustre, and the simulated dataset for testing are available upon request from T.G. and O.W.

Contact:  tg@biocentrum.dtu.dk and owi@imm.dtu.dk

Supplementary information: