bluuebunny/crossref_metadata_2025 huggingface dataset:
Fixation of transposable elements in the Drosophila melanogaster genome
Authors: MASIDE XULIO , ASSIMACOPOULOS STAVROULA , CHARLESWORTH BRIAN
Published: August 2005

We have investigated at the molecular level four cases in which D. melanogaster middle repetitive DNA probes consistently hybridized to a particular band on chromosomes sampled from a D. melanogaster natural population. Two corresponded to true fixations of a roo and a Stalker element, and the others were artefacts of the in situ hybridization technique caused by the presence of genomic DNA flanking the transposable elements (TEs) in the probes. The two fixed elements are located in the β-heterochromatin (20A and 80B, respectively) and are embedded in large clusters of other elements, many of which may also be fixed. We also found evidence that this accumulation is an ongoing process. These results support the hypothesis that TEs accumulate in the non-recombining part of the genome. Their implications for the effects of TEs on determining the chromatin structure of the host genomes are discussed in the light of recent evidence for the role of TE-derived small interfering-RNAs as cis-acting determinants of heterochromatin formation.
Combined line-cross and half-sib QTL analysis of crosses between outbred lines
Authors: KIM JONG-JOO , ZHAO HONGHUA , THOMSEN HAUKE , ROTHSCHILD MAX F. , DEKKERS JACK C. M.
Published: August 2005

Data from an F2 cross between breeds of livestock are typically analysed by least squares line-cross or half-sib models to detect quantitative trait loci (QTL) that differ between or segregate within breeds. These models can also be combined to increase power to detect QTL, while maintaining the computational efficiency of least squares. Tests between models allow QTL to be characterized into those that are fixed (LC QTL), or segregating at similar (HS QTL) or different (CB QTL) frequencies in parental breeds. To evaluate power of the combined model, data wih various differences in QTL allele frequencies (FD) between parental breeds were simulated. Use of all models increased power to detect QTL. The line-cross model was the most powerful model to detect QTL for FD>0·6. The combined and half-sib models had similar power for FD<0·4. The proportion of detected QTL declared as LC QTL decreased with FD. The opposite was observed for HS QTL. The proportion of CB QTL decreased as FD deviated from 0·5. Accuracy of map position tended to be greatest for CB QTL. Models were applied to a cross of Berkshire and Yorkshire pig breeds and revealed 160 (40) QTL at the 5% chromosome (genome)-wise level for the 39 growth, carcass composition and quality traits, of which 72, 54, and 34 were declared as LC, HS and CB QTL. Fourteen CB QTL were detected only by the combined model. Thus, the combined model can increase power to detect QTL and mapping accuracy and enable characterization of QTL that segregate within breeds.
Genetic variation and correlation of dietary response in an advanced intercross mouse line produced from two divergent growth lines
Authors: EHRICH THOMAS H. , KENNEY-HUNT JANE P. , PLETSCHER L. SUSAN , CHEVERUD JAMES M.
Published: August 2005

Levels of human obesity have increased over the past 20 years worldwide, primarily due to changes in diet and activity levels. Although environmental changes are clearly responsible for the increasing prevalence of obesity, individuals may show genetic variation in their response to an obesogenic environment. Here, we measure genetic variation in response to a high-fat diet in a mouse model, an F16 Advanced Intercross Line derived from the cross of SM/J and LG/J inbred mouse strains. The experimental population was separated by sex and fed either a high-fat (42% of energy from fat) or low-fat (15% of energy from fat) diet. A number of phenotypic traits related to obesity and diabetes such as growth rate, glucose tolerance traits, organ weights and fat pad weights were collected and analysed in addition to serum levels of insulin, free fatty acids, cholesterol and triglycerides. Most traits are different between the sexes and between dietary treatments and for a few traits, including adult growth, fat pad weights, insulin and glucose tolerance, the dietary effect is stronger in one sex than the other. We find that fat pad weights, liver weight, serum insulin levels and adult growth rates are all phenotypically and genetically correlated with one another in both dietary treatments. Critically, these traits have relatively low genetic correlations across environments (average r=0·38). Dietary responses are also genetically correlated across these traits. We found substantial genetic variation in dietary response and low cross environment genetic correlations for traits aligned with adiposity. Therefore, genetic effects for these traits are different depending on the environment an animal is exposed to.
Further mapping of quantitative trait loci for postnatal growth in an intersubspecific backcross of wild Mus musculus castaneus and C57BL/6J mice
Authors: ISHIKAWA AKIRA , HATADA SAYURI , NAGAMINE YOSHITAKA , NAMIKAWA TAKAO
Published: August 2005

We regret that in the article by Akira Ishikawa et al. in Genetical Research (2005) Vol. 85, No. 2, pp. 127–137, Fig. 1 on page 131 should have been reproduced in colour, not in black and white. Please find the correct version below.
Does Nurse-Led Pre-operative Assessment Reduce the Cancellation Rate of Elective Surgical In-Patient Procedures?: A Systematic Review of the Research Literature
Authors: Craig Sarah E.
Published: August 2005

Pre-operative assessment (POA) has been advocated for use to achieve a number of goals including reducing cancelled operations on the day of surgery, and therefore waiting lists. POA has historically been provided by junior doctors, but the change in focus of their role in addition to the new roles being taken on by nurses has led to nurse-led POA. The aim of this review was to determine whether nurse-led POA reduces the cancellation rate of elective surgical in-patient procedures. The Cochrane Library, Medline, Cinahl and Embase databases were searched for systematic reviews, randomised control trials and cohort studies examining nurse-led POA. After applying inclusion criteria only four cohort studies were deemed to be suitable to be critically appraised. One study had no cancellations in either the doctor or nurse-led POA groups. Another study had low cancellation rates in the nurse-led POA group, but the control group was not suitably defined for adequate verification as to whether the cancellation rates were lower because they had been pre-assessed. The final two studies revealed similar absolute risk reductions, number needed to treat and odds ratios. In summary nurse-led POA appears to reduce cancellation rates on admission, but the evidence for this is relatively weak, primarily because study samples have been small. Further trials are needed which have samples that are sufficient to detect a true difference between the intervention and control group if one exists.
Audit of Anaesthetic Chart Documentation in Major Orthopaedic Surgery
Authors: Davis S.
Published: August 2005

Objective: To investigate the completeness of documentation of anaesthetic charts in elective orthopaedic anaesthesia.

Design: Data collection from medical records.

Setting: Orthopaedic department, teaching hospital.

Participants: Anonymous anaesthetic consultants participating in orthopaedic surgery.

Intervention: E-mail and verbal message regarding 2nd data collection to anaesthetic colleagues.

Main outcome measures: Documentation of data of variables on anaesthetic chart.

Results: Good documentation of most variables. An average improvement of 5.7% in data documentation, range of −2.7% to 24.7%. Poor documentation of blood loss and urinary output.

Conclusions: The importance of the anaesthetic chart cannot be underestimated. A close working relationship with ones colleagues in anaesthesia promotes a fuller use of the chart and contributes to its continued development as a source of information.
Paleomagnetism of Ar‐Ar dated lava flows from the Ceboruco‐San Pedro volcanic field (western Mexico): Evidence for the Matuyama‐Brunhes transition precursor and a fully reversed geomagnetic event in the Brunhes chron
Authors: Petronille Marie , Goguitchaichvili Avto , Henry Bernard , Alva‐Valdivia Luis M. , Rosas‐Elguera José , Urrutia‐Fucugauchi Jaime , Rodriguez Cejá Maria , Calvo‐Rathert Manuel
Published: August 2005

We report a detailed paleomagnetic and rock magnetic study of 17 independent lava flows belonging to the Trans‐Mexican Volcanic Belt; 175 oriented samples were collected in the Ceboruco‐San Pedro volcanic field. These sites were previously dated by means of a state‐of‐the‐art 40Ar‐39Ar geochronological method and span from 819 to 2 ka. Rock magnetic experiments, which included continuous susceptibility and hysteresis measurements, point to simple magnetic mineralogy. In most cases, the remanence is carried by Ti‐poor titanomagnetite of pseudosingle‐domain magnetic structure. Fourteen flows give normal magnetic polarities, while two are reversely magnetized; only one cooling unit yields intermediate paleodirections. The paleodirections of the flow dated at 819 ± 25 ka correspond to a VGP latitude of 18°N. This anomalous field behavior apparently recorded prior to the Matuyama‐Brunhes (M‐B) reversal may coincide with the transitionally magnetized lavas on La Palma, Canary Islands (40Ar‐39Ar age of 822.2 ± 8.7 ka), and with an event featured in several marine sediment records. Thus this geomagnetic event, defined as M‐B precursor, is probably global in extent. Two independent lava flows, dated at 623 ± 91 and 614 ± 16 ka, yield reverse paleodirections. Age uncertainties make it difficult to claim the discovery of a new geomagnetic event. It is possible that these lavas erupted during the worldwide observable Big Lost event (40Ar‐39Ar age of 580.2 ± 7.8 ka), which has probably been longer and more complex than it is generally believed for geomagnetic excursions.
Waveform tomography of crustal structure in the south San Francisco Bay region
Authors: Pollitz Fred F. , Fletcher Jon P.
Published: August 2005

We utilize a scattering‐based seismic tomography technique to constrain crustal structure around the southern San Francisco Bay region (SFBR). This technique is based on coupled traveling wave scattering theory, which has usually been applied to the interpretation of surface waves in large regional‐scale studies. Using fully three‐dimensional kernels, this technique is here applied to observed P, S, and surface waves of intermediate period (3–4 s dominant period) observed following eight selected regional events. We use a total of 73 seismograms recorded by a U.S. Geological Survey short‐period seismic array in the western Santa Clara Valley, the Berkeley Digital Seismic Network, and the Northern California Seismic Network. Modifications of observed waveforms due to scattering from crustal structure include (positive or negative) amplification, delay, and generation of coda waves. The derived crustal structure explains many of the observed signals which cannot be explained with a simple layered structure. There is sufficient sensitivity to both deep and shallow crustal structure that even with the few sources employed in the present study, we obtain shallow velocity structure which is reasonably consistent with previous P wave tomography results. We find a depth‐dependent lateral velocity contrast across the San Andreas fault (SAF), with higher velocities southwest of the SAF in the shallow crust and higher velocities northeast of the SAF in the midcrust. The method does not have the resolution to identify very slow sediment velocities in the upper approximately 3 km since the tomographic models are smooth at a vertical scale of about 5 km.
Spatial sensitivity of the Gravity Recovery and Climate Experiment (GRACE) time‐variable gravity observations
Authors: Chen J. L. , Wilson C. R. , Famiglietti J. S. , Rodell M.
Published: August 2005

We analyze the spatial sensitivities of terrestrial water storage and geoid height changes determined from the time‐variable gravity observed by the Gravity Recovery and Climate Experiment (GRACE) twin satellite mission. On the basis of 15 GRACE monthly gravity solutions, covering the period April 2002 to December 2003, we examine the effects of spatial smoothing at radii varying from 400 to 2000 km and conclude that a 800 km Gaussian smoothing radius is effective for GRACE‐derived terrestrial water storage and produces the minimum RMS residuals over the land of the differences between GRACE results and estimated water storage change from a global land data assimilation system. For GRACE estimated geoid height change, the effective smoothing radius can go down to 600 km. When the annual (e.g., the sine and cosine) components are the primary concern, the effective spatial resolution can reach 600 and 400 km for GRACE estimated terrestrial water storage or geoid height change, respectively.
Grain boundary wetness of texturally equilibrated rocks, with implications for seismic properties of the upper mantle
Authors: Yoshino Takashi , Takei Yasuko , Wark David A. , Watson E. Bruce
Published: August 2005

Melt‐ or fluid‐filled pore geometry in texturally equilibrated aggregates characterized by various dihedral angles and degrees of faceting was investigated quantitatively by measuring the grain boundary wetness, which is defined as the ratio of solid‐liquid boundary area over the total area of interphase boundaries. The wetness (ψ) increases monotonically with increasing liquid volume fraction (ϕ). For systems showing no faceting and low dihedral angle, the relation between ϕ and ψ agrees well with the theoretical prediction for an ideal isotropic model assuming tetrakaidecahedral packing. This is true for the olivine‐basalt system, whereas partially molten lherzolite shows systematically lower wetness. For systems showing strong faceting, the wetness is systematically lower than the theoretical prediction. For all systems, the obtained ψ‐ϕ relationship can be fitted well to the formulae ψ = Aϕ1/2 with fitting parameter A, indicating that the three‐dimensional pore shape is a tubular one. Seismic wave velocities are calculated for the model systems in terms of the equivalent aspect ratio (EAR) of the oblate spheroid model based on the above ψ‐ϕ relation. Calculated EARs can be used to predict ϕ in texturally equilibrated rocks using VP or VS data and also to interpret the seismologically observed variation of dlnVS/dlnVP in terms of the variation of pore geometry. Our results show that seismic wave velocities of partially molten peridotites are not significantly affected by faceting and that values of dlnVS/dlnVP larger than 1.5 cannot be explained by texturally equilibrated partially molten rocks.
Calcareous nannofossil evidence for the existence of the Gulf Stream during the late Maastrichtian
Authors: Watkins David K. , Self‐Trail Jean M.
Published: August 2005

Upper Maastrichtian calcareous nannofossil assemblages, from eight cores on the South Carolina Coastal Plain (onshore set) and three deep sea drilling sites from the continental slope and abyssal hills (offshore set), were analyzed by correlation and principal component analysis to examine the ancient surface water thermal structure. In addition, a temperature index derived from independently published paleobiogeographic information was applied to the sample data. All three methods indicate a strong separation of the samples into onshore and offshore sets, with the offshore data set exhibiting significantly warmer paleotemperatures. The great disparity between these two sample sets indicates that there was a strong thermal contrast between the onshore and offshore surface water masses that persisted throughout the late Maastrichtian despite evident short‐term changes in fertility, productivity, and community structure. This suggests the Gulf Stream was present as a major oceanographic feature during the late Maastrichtian.
Three‐dimensional displacement‐length scaling and maximum dimension of normal faults in layered rocks
Authors: Soliva Roger , Schultz Richard A. , Benedicto Antonio
Published: August 2005

We analyze the magnitudes and distributions of displacements on normal faults that are contained within a five layer marly‐limestone/silty‐clay sedimentary sequence. Observations of bedding plane exposures of the well‐exposed mechanically isolated faults reveal a systematic strong decrease in the displacement gradient related to the horizontal lengthening of faults growing at constant height. Because mechanically heterogeneous sequences produce populations of vertically restricted faults having a large range of aspect ratios (length/downdip height), much of the scatter on a displacement‐length diagram can be attributed to nonlinear growth paths. Our results demonstrate the significant influence of layering on fault scaling relations, growth, and maximum dimensions.
The trochoid‐like track in Typhoon Dujuan (2003)
Authors: Hong Jing‐Shan , Chang Pao‐Liang
Published: August 2005

The present study examines a prominent double eyewall case, namely, Typhoon Dujuan (2003) as it neared the island of Taiwan. This typhoon was unusual in that its double eye was not concentric. It has been suggested that vertical wind shear caused the inner eye to drift away from the typhoon circulation center. Thus, the inner eye tended to circulate due to the steering of the rotational flow in the moat with a period of 3.5 ∼ 4 h. The orbited inner eye motion superimposed on the typhoon motion as a whole resulted in a substantial oscillation, or wobble, and eventually manifested itself as a trochoid‐like track. The orbiting inner eye also periodically produced additional abrupt wind increase up to 15 m s−1 for 1 ∼ 2 hour, and has been noted to be an important issue for nowcasting and hazard mitigations.
On laboratory simulation and the evaporation rate of water on Mars
Authors: Sears Derek W. G. , Moore Shauntae R.
Published: August 2005

In order to better understand the stability of water on Mars, and factors likely to affect that stability, we have measured the evaporation rate of water in a CO2 atmosphere at 7 mbar and ∼0°C in a large environmental chamber that minimizes fluctuation in conditions. The average evaporation rate we measured was 1.01 ± 0.19 mm/h. This includes correction for water vapor build‐up in the chamber, but not the effect of Mars' lower gravity. When corrections for this are applied, our predicted evaporation rate for water on Mars at 0°C and 7 mbar is 0.73 ± 0.14 mm/h. This is in very good agreement with the value calculated by assuming that evaporation depends on diffusion and buoyancy. The consistency of these results suggests that – at least for these conditions – our approaches to the calculations and the laboratory simulations are reasonable.
Spectral reconstruction of teleseismic P Green's functions
Authors: Baig A. M. , Bostock M. G. , Mercier J.‐P.
Published: August 2005

Accurate, full‐band estimates of teleseismic P Green's functions are recovered using constraints from the autospectra and cross spectra of seismograms generally representing multiple sources and receivers. This advance represents a higher‐order refinement of traditional “receiver functions” that sacrifice structural signals finishing as P energy on a three‐component seismogram to approximate the source signature. We estimate the autospectrum of a source signature from the cross correlogram of two seismogram channels that record this same source. Imposing a well‐founded assumption on the phase spectrum of the P component of the teleseismic P Green's function, namely, that it is minimum phase, allows the total vector impulse response to be retrieved. We assess the accuracy of this spectral reconstruction approach to the deconvolution problem through synthetic and real data examples.
Transient rheology of the upper mantle beneath central Alaska inferred from the crustal velocity field following the 2002 Denali earthquake
Authors: Pollitz Fred F.
Published: August 2005

The M7.9 2002 Denali earthquake, Alaska, is one of the largest strike‐slip earthquakes ever recorded. The postseismic GPS velocity field around the 300‐km‐long rupture is characterized by very rapid horizontal velocity up to ∼300 mm/yr for the first 0.1 years and slower but still elevated horizontal velocity up to ∼100 mm/yr for the succeeding 1.5 years. I find that the spatial and temporal pattern of the displacement field may be explained by a transient mantle rheology. Representing the regional upper mantle as a Burghers body, I infer steady state and transient viscosities of η1 = 2.8 × 1018 Pa s and η2 = 1.0 × 1017 Pa s, respectively, corresponding to material relaxation times of 1.3 and 0.05 years. The lower crustal viscosity is poorly constrained by the considered horizontal velocity field, and the quoted mantle viscosities assume a steady state lower crust viscosity that is 7η1. Systematic bias in predicted versus observed velocity vectors with respect to a fixed North America during the first 3–6 months following the earthquake is reduced when all velocity vectors are referred to a fixed site. This suggests that the post‐Denali GPS time series for the first 1.63 years are shaped by a combination of a common mode noise source during the first 3–6 months plus viscoelastic relaxation controlled by a transient mantle rheology.
Compound clathrate hydrate on Titan's surface
Authors: Osegovic John P. , Max Michael D.
Published: August 2005

Large‐scale multicomponent (compound) clathrate hydrate formation is stable relative to water ice on the surface of Titan. Compound clathrate hydrates are nonstoichiometric crystal of guest molecules trapped inside cages of varying sizes formed by latticeworks of water molecules. They have shorter induction periods and faster reaction rates than pure clathrate hydrates. Compound hydrate is a likely sink for many chemicals occurring on Titan's surface, including ethane, xenon, and other preferred clathrate formers. Water, whose availability is the main control to hydrate formation on Titan, moderates hydrate formation given its relatively small abundance compared to the other hydrate‐forming components.
Inhibitors of fatty acid amide hydrolase reduce carrageenan‐induced hind paw inflammation in pentobarbital‐treated mice: comparison with indomethacin and possible involvement of cannabinoid receptors
Authors: Holt Sandra , Comelli Francesca , Costa Barbara , Fowler Christopher J
Published: August 2005

The in vivo effect of inhibitors of fatty acid amide hydrolase (FAAH) upon oedema volume and FAAH activity was evaluated in the carrageenan induced hind paw inflammation model in the mouse. Oedema was measured at two time points, 2 and 4 h, after intraplantar injection of carrageenan to anaesthetised mice.

Intraperitoneal (i.p.) injections of the FAAH inhibitor URB597 (0.1, 0.3, 1 and 3 mg kg−1) 30 min prior to carrageenan administration, dose‐dependently reduced oedema formation. At the 4 h time point, the ED50 for URB597 was ∼0.3 mg kg−1. Indomethacin (5 mg kg−1 i.p.) completely prevented the oedema response to carrageenan.

The antioedema effects of indomethacin and URB597 were blocked by 3 mg kg−1 i.p. of the CB2 receptor antagonist SR144528. The effect of URB597 was not affected by pretreatment with the peroxisome proliferator‐activated receptor γ antagonist bisphenol A diglycidyl ether (30 mg kg−1 i.p.) or the TRPV1 antagonist capsazepine (10 mg kg−1 i.p.), when oedema was assessed 4 h after carrageenan administration. The CB1 receptor antagonists AM251 (3 mg kg−1 i.p.) and rimonabant (0.5 mg kg−1 i.p.) gave inconsistent effects upon the antioedema effect of URB597.

FAAH measurements were conducted ex vivo in the paws, spinal cords and brains of the mice. The activities of FAAH in the paws and spinal cords of the inflamed vehicle‐treated mice were significantly lower than the corresponding activities in the noninflamed mice. PMSF treatment almost completely inhibited the FAAH activity in all three tissues, as did the highest dose of URB597 (3 mg kg−1) in spinal cord samples, whereas no obvious changes were seen ex vivo for the other treatments.

In conclusion, the results show that in mice, treatment with indomethacin and URB597 produce SR144528‐sensitive anti‐inflammatory effects in the carrageenan model of acute inflammation.

British Journal of Pharmacology (2005) 146, 467–476. doi:10.1038/sj.bjp.0706348
Functional characterisation of the S512Y mutant vanilloid human TRPV1 receptor
Authors: Sutton Kathy G , Garrett Elizabeth M , Rutter A Richard , Bonnert Timothy P , Jarolimek Wolfgang , Seabrook Guy R
Published: August 2005

Mammalian transient receptor potential (TRP) channels include the nonselective cation channel TRPV1, which is activated by a range of stimuli including low pH, vanilloids and heat. Previously, selective mutagenesis experiments identified an intracellular residue (S512Y) critical to discriminating between pH and vanilloid (capsaicin) gating of the rat TRPV1 receptor.

In this study, switching the equivalent residue in the human TRPV1 (which has some significant differences with the rat TRPV1) also rendered this channel relatively insensitive to activation by capsaicin and proved critical in determining the receptor's sensitivity to the putative endovanilloid N‐arachidonoyl‐dopamine (NADA), suggesting a similar mode of activation for these two agonists.

Potency of pH gating was reduced; however, voltage‐dependent outward rectification properties of the pH‐dependent current and gating by heat and pH sensitisation of the S512Y heat response remained unaffected.

Surprisingly, residual capsaicin gating was detected and could be sensitised by pH even in the presence of a competitive antagonist. Taken together, these findings indicate that effective functional interaction of capsaicin with the S512Y channel still occurred, although the vanilloid‐dependent gating per se was severely compromised.

This observation provides additional evidence for capsaicin interacting at multiple sites, distinct from the S512 residue located close to the intracellular face of the pore.

British Journal of Pharmacology (2005) 146, 702–711. doi:10.1038/sj.bjp.0706356
Inhibition of endogenous hydrogen sulfide formation reduces the organ injury caused by endotoxemia
Authors: Collin Marika , Anuar Farhana B M , Murch Oliver , Bhatia Madhav , Moore Philip K , Thiemermann Christoph
Published: August 2005

Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter, which may play important roles in normal physiology and disease. Here, we investigated the role of H2S in the organ injury caused by severe endotoxemia in the rat.

Male Wistar rats were subjected to acute endotoxemia (Escherichia coli lipopolysaccharide (LPS) 6 mg kg−1 intravenously (i.v.) for 6 h) and treated with vehicle (saline, 1 ml kg−1 i.v.) or DL‐propargylglycine (PAG, 10–100 mg kg−1 i.v.), an inhibitor of the H2S‐synthesizing enzyme cystathionine‐γ‐lyase (CSE). PAG was administered either 30 min prior to or 60 min after the induction of endotoxemia.

Endotoxemia resulted in circulatory failure (hypotension and tachycardia) and an increase in serum levels of alanine aminotransferase and aspartate aminotransferase (markers for hepatic injury), lipase (indicator of pancreatic injury) and creatine kinase (indicator of neuromuscular injury). In the liver, endotoxemia induced a significant increase in the myeloperoxidase (MPO) activity, and in the expression and activity of the H2S‐synthesizing enzymes CSE and cystathionine‐β‐synthase.

Administration of PAG either prior to or after the injection of LPS dose‐dependently reduced the hepatocellular, pancreatic and neuromuscular injury caused by endotoxemia, but not the circulatory failure. Pretreatment of rats with PAG abolished the LPS‐induced increase in the MPO activity and in the formation of H2S and in the liver.

These findings support the view that an enhanced formation of H2S contributes to the pathophysiology of the organ injury in endotoxemia. We propose that inhibition of H2S synthesis may be a useful therapeutic strategy against the organ injury associated with sepsis and shock.

British Journal of Pharmacology (2005) 146, 498–505. doi:10.1038/sj.bjp.0706367
The regulation of veratridine‐stimulated electrogenic ion transport in mouse colon by neuropeptide Y (NPY), Y1 and Y2 receptors
Authors: Hyland Niall P , Cox Helen M
Published: August 2005

Neuropeptide Y (NPY) is a prominent enteric neuropeptide with prolonged antisecretory effects in mammalian intestine. Veratridine depolarises neurons consequently causing epithelial anion secretion across mouse colon mucosa. Our aim was to characterise functionally, veratridine‐stimulated mucosal responses and to determine the roles for NPY, Y1, and Y2 receptors in modulating these neurogenic effects.

Colon mucosae (with intact submucous innervation) from wild‐type mice (+/+) and knockouts lacking either NPY (NPY−/−), Y1−/− or Y2−/− were placed in Ussing chambers and voltage clamped at 0 mV. Veratridine‐stimulated short‐circuit current (Isc) responses in +/+, Y1 or Y2 antagonist pretreated +/+ colon, Y1−/− and NPY−/− colon were insensitive to cholinergic blockade by atropine (At; 1 μM) and hexamethonium (Hex; 10 μM). Tetrodotoxin (TTX, 100 nM) abolished veratridine responses, but had no effect upon carbachol (CCh) or vasoactive intestinal polypeptide (VIP)‐induced secretory responses.

To establish the functional roles for Y1 and Y2 receptors, +/+ tissues were pretreated with either the Y1 or Y2 receptor antagonist (BIBO3304 (300 nM) or BIIE0246 (1 μM), respectively) and veratridine responses were compared with those from Y1−/− or Y2−/− colon. Neither BIBO3304 nor Y1−/− altered veratridine‐induced secretion, but Y1 agonist responses were abolished in both preparations. In contrast, the Y2 antagonist BIIE0246 significantly amplified veratridine responses in +/+ mucosa. Unexpectedly, NPY−/− colon exhibited significantly attenuated veratridine responses (between 1 and 5 min).

We demonstrate that electrogenic veratridine responses in mouse colon are noncholinergic and that NPY can act directly upon epithelia, a Y1 receptor effect. The enhanced veratridine response observed in +/+ tissue following BIIE0246, indicates that Y2 receptors are located on submucosal neurons and that their activation by NPY will inhibit enteric noncholinergic secretory neurotransmission.

We also demonstrate Y1 and Y2 receptor‐mediated antisecretory tone in +/+ colon and show selective loss of each in Y1 and Y2 null colon respectively. In NPY−/− tissue, only Y1‐mediated tone was present, this presumably being mediated by endogenous endocrine peptide YY. Y2 tone was absent from NPY−/− (and Y2−/−) colon and we conclude that NPY activation of neuronal Y2 receptors attenuates secretory neurotransmission thereby providing an absorptive electrolyte tone in isolated colon.

British Journal of Pharmacology (2005) 146, 712–722. doi:10.1038/sj.bjp.0706368
Volume regulation in cortical collecting duct cells: role of AQP2
Authors: Ford Paula , Rivarola Valeria , Chara Osvaldo , Blot‐Chabaud Marcel , Cluzeaud Françoise , Farman Nicolette , Parisi Mario , Capurro Claudia
Published: August 2005

Background information. The renal CCD (cortical collecting duct) plays a role in final volume and concentration of urine by a process that is regulated by the antidiuretic hormone, [arginine]vasopressin. This hormone induces an increase in water permeability due to the translocation of AQP2 (aquaporin 2) from the intracellular vesicles to the apical membrane of principal cells. During the transition from antidiuresis to diuresis, CCD cells are exposed to changes in environmental osmolality, and cell‐volume regulation may be especially important for the maintenance of intracellular homoeostasis. Despite its importance, cell‐volume regulation in CCD cells has not been widely investigated. Moreover, no studies have been carried out till date to evaluate the putative role of AQPs during this process in renal cells.

Results. In the present study, we have studied the regulatory cell‐volume responses to hypo‐osmotic or hyperosmotic challenges in two CCD cell lines: one not expressing AQPs and the other stably transfected with AQP2. We have used a fluorescent probe technique in which the acquisition of single‐cell kinetic data can be simultaneously recorded with the intracellular pH. Experiments with hyperosmotic mannitol media demonstrated that, independent of AQP2 expression, CCD cells shrink but fail to show regulatory volume increase, at least under the studied conditions. In contrast, under hypo‐osmotic shocks, regulatory volume decrease occurs and the activation of these mechanisms is more rapid in AQP2 transfected cells. This regulatory response takes place in parallel with intracellular acidification, which is faster in cells expressing AQP2. The acidification and the initial regulatory volume decrease response were inhibited by glibenclamide and BaCl2 only in AQP2 cells.

Conclusions. These results suggest that increases in the osmotic water permeability due to the expression of AQP2 are critical for a rapid activation of regulatory volume decrease mechanisms, which would be linked to cystic fibrosis transmembrane conductance regulator and to barium‐sensitive potassium channels.
Dynamics of the Ins(1,4,5)P3 receptor during polarization of MDCK cells
Authors: Cruttwell Caroline , Bernard Jérôme , Hilly Mauricette , Nicolas Valérie , Tunwell Richard E.A. , Mauger Jean‐Pierre
Published: August 2005

Background information. The uneven distribution of the Ins(1,4,5)P3R [Ins(1,4,5)P3 receptor] within the ER (endoplasmic reticulum) membrane generates spatially complex Ca2+ signals. The ER is a dynamic network, which allows the rapid diffusion of membrane proteins from one part of the cell to another. However, little is known about the localization and the dynamics of the Ins(1,4,5)P3R in the ER of living cells. We have used a MDCK (Madin—Darby canine kidney) clone stably expressing the Ins(1,4,5)P3R1‐GFP (where GFP stands for green fluorescent protein) to investigate the effect of cell polarity on the lateral mobility of the Ins(1,4,5)P3R.

Results. In non‐confluent MDCK cells, the chimaera is homogeneously distributed throughout the ER and the nuclear envelope. FRAP (fluorescence recovery after photobleaching) experiments showed that the receptor can move freely in the ER with a diffusion constant (D=0.01 μm2/s) approx. ten times lower than other ER membrane proteins. In confluent polarized cells, two populations of receptor can be defined: one population is distributed in the cytoplasm and is mobile but with a slower diffusion constant (D=0.004 μm2/s) compared with non‐confluent cells, whereas the other population is concentrated at the periphery of the cells and is apparently immobile.

Conclusions. The observed differences in the mobility of the Ins(1,4,5)P3R are most probably due to its interactions with stable protein complexes that form at the periphery of the polarized cells.
Triptan-induced contractile (5-HT1B receptor) responses in human cerebral and coronary arteries: relationship to clinical effect
Authors: Edvinsson Lars , Uddman Erik , Wackenfors Angelica , Davenport Anthony , Longmore Jenny , Malmsjö Malin
Published: August 2005

Triptans are agonists at 5-HT1B and 5-HT1D (where 5-HT is 5-hydroxytryptamine; serotonin) receptors and cause vasoconstriction of isolated blood vessels. The aim of the present study was to determine vasoconstrictor potency (EC50) of triptans in human coronary and cerebral arteries and to examine whether there was any relationship with the maximal plasma concentrations (Cmax; nM) of the drugs achieved following oral administration of clinically relevant doses to man using values reported in the literature. We also examined the expression of 5-HT1B receptors in atherosclerotic and normal coronary arteries. The vasocontractile responses to sumatriptan, rizatriptan or eletriptan were characterized by in vitro pharmacology. The ratio of Cmax/EC50 was calculated. 5-HT1B and 5-HT1D receptors were visualized by immunohistochemical techniques in coronary arteries. Sumatriptan, rizatriptan and eletriptan were powerful vasoconstrictors in cerebral artery. The rank order of agonist potency was eletriptan=rizatriptan=sumatriptan. In the coronary artery, the triptans were weaker vasoconstrictors. The rank order of potency was similar. In cerebral artery the ratio of Cmax/EC50 was not significantly different from unity, indicating a relationship between these two parameters. In general for the coronary artery, the ratios were significantly less than unity, indicating no direct relationship. Immunohistochemistry showed expression of 5-HT1B receptors in the medial layer, but did not reveal any obvious difference in 5-HT1B receptor expression between normal and atherosclerotic coronary arteries. The results support the notion that triptans are selective vasoconstrictors of cerebral arteries over coronary arteries and that there is a relationship between vasoconstrictor potency in cerebral arteries and clinically relevant plasma levels.
Modulation of lipid metabolism by n−3 polyunsaturated fatty acids in gestational diabetic rats and their macrosomic offspring
Authors: Soulimane-Mokhtari Nassima A. , Guermouche Baya , Yessoufou Akadiri , Saker Myrieum , Moutairou Kebirou , Hichami Aziz , Merzouk Hafida , Khan Naim A.
Published: August 2005

The time course of changes in lipid metabolism by dietary n−3 PUFAs (polyunsaturated fatty acids) in streptozotocin-induced diabetic rats during pregnancy (days 12 and 21) and their macrosomic offspring at birth (day 0) and through adulthood (days 60 and 90) was studied with respect to adipose tissue, liver and serum lipid concentrations, and fatty acid composition. Glucose and insulin levels were also assessed in order to characterize the diabetic state of macrosomic offspring. Pregnant diabetic and control rats were fed either an Isio-4 or EPAX diet (enriched with n−3 PUFA). The same diets were also consumed by pups at weaning. Compared with control rats, during pregnancy diabetic rats had a significant elevation in liver and serum triacylglycerol (triglyceride) and cholesterol concentrations. At birth, macrosomic pups had higher serum insulin and glucose levels than control pups. The macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight and lipid content through the first 12 weeks of age. The macrosomic pups from diabetic rats fed the Isio-4 diet also showed a significant enhancement in liver and serum triacylglycerol and cholesterol levels at birth and during adulthood. Feeding the EPAX diet to diabetic mothers as well as their macrosomic pups increased serum and liver levels of EPA (eicospentaenoic acid) and DHA (docosahexaenoic acid) with a reduction in arachidonic acid. The EPAX diet induced a significant decrease in liver and serum triacylglycerol and cholesterol concentrations in mothers during pregnancy and in their macrosomic pups during adulthood. Since the EPAX diet improves lipid anomalies considerably in diabetic mothers and their macrosomic offspring, it may prevent long-term metabolic abnormalities associated with macrosomia.
Prescription for the design and selection of density functional approximations: More constraint satisfaction with fewer fits
Authors: Perdew John P. , Ruzsinszky Adrienn , Tao Jianmin , Staroverov Viktor N. , Scuseria Gustavo E. , Csonka Gábor I.
Published: August 2005

We present the case for the nonempirical construction of density functional approximations for the exchange-correlation energy by the traditional method of “constraint satisfaction” without fitting to data sets, and present evidence that this approach has been successful on the first three rungs of “Jacob’s ladder” of density functional approximations [local spin-density approximation (LSD), generalized gradient approximation (GGA), and meta-GGA]. We expect that this approach will also prove successful on the fourth and fifth rungs (hyper-GGA or hybrid and generalized random-phase approximation). In particular, we argue for the theoretical and practical importance of recovering the correct uniform density limit, which many semiempirical functionals fail to do. Among the beyond-LSD functionals now available to users, we recommend the nonempirical Perdew–Burke–Ernzerhof (PBE) GGA and the nonempirical Tao–Perdew–Staroverov–Scuseria (TPSS) meta-GGA, and their one-parameter hybrids with exact exchange. TPSS improvement over PBE is dramatic for atomization energies of molecules and surface energies of solids, and small or moderate for other properties. TPSS is now or soon will be available in standard codes such as GAUSSIAN, TURBOMOLE, NWCHEM, ADF, WIEN, VASP, etc. We also discuss old and new ideas to eliminate the self-interaction error that plagues the functionals on the first three rungs of the ladder, bring up other related issues, and close with a list of “do’s and don’t’s” for software developers and users.
Orbital-dependent correlation energy in density-functional theory based on a second-order perturbation approach: Success and failure
Authors: Mori-Sánchez Paula , Wu Qin , Yang Weitao
Published: August 2005

We have developed a second-order perturbation theory (PT) energy functional within density-functional theory (DFT). Based on PT with the Kohn–Sham (KS) determinant as a reference, this new ab initio exchange-correlation functional includes an exact exchange (EXX) energy in the first order and a correlation energy including all single and double excitations from the KS reference in the second order. The explicit dependence of the exchange and correlation energy on the KS orbitals in the functional fits well into our direct minimization approach for the optimized effective potential, which is a very efficient method to perform fully self-consistent calculations for any orbital-dependent functionals. To investigate the quality of the correlation functional, we have applied the method to selected atoms and molecules. For two-electron atoms and small molecules described with small basis sets, this new method provides excellent results, improving both second-order Møller–Plesset expression and any conventional DFT results significantly. For larger systems, however, it performs poorly, converging to very low unphysical total energies. The failure of PT based energy functionals is analyzed, and its origin is traced back to near degeneracy problems due to the orbital- and eigenvalue-dependent algebraic structure of the correlation functional. The failure emerges in the self-consistent approach but not in perturbative post-EXX calculations, emphasizing the crucial importance of self-consistency in testing new orbital-dependent energy functionals.
Recent development of self-interaction-free time-dependent density-functional theory for nonperturbative treatment of atomic and molecular multiphoton processes in intense laser fields
Authors: Chu Shih-I
Published: August 2005

In this paper, we present a short account of some recent developments of self-interaction-free density-functional theory (DFT) and time-dependent density-functional theory (TDDFT) for accurate and efficient treatment of the electronic structure, and time-dependent quantum dynamics of many-electron atomic and molecular systems. The conventional DFT calculations using approximate and explicit exchange-correlation energy functional contain spurious self-interaction energy and improper long-range asymptotic potential, preventing reliable treatment of the excited, resonance, and continuum states. We survey some recent developments of DFT/TDDFT with optimized effective potential (OEP) and self-interaction correction (SIC) for both atomic and molecular systems for overcoming some of the above mentioned difficulties. These DFT (TDDFT)/OEP-SIC approaches allow the use of orbital-independent single-particle local potential which is self-interaction free. In addition we discuss several numerical techniques recently developed for efficient and high-precision treatment of the self-interaction-free DFT/TDDFT equations. The usefulness of these procedures is illustrated by a few case studies of atomic, molecular, and condensed matter processes of current interests, including (a) autoionizing resonances, (b) relativistic OEP-SIC treatment of atomic structure (Z=2–106), (c) shell-filling electronic structure in quantum dots, (d) atomic and molecular processes in intense laser fields, including multiphoton ionization, and very-high-order harmonic generation, etc. For the time-dependent processes, an alternative Floquet formulation of TDDFT is introduced for time-independent treatment of multiphoton processes in intense periodic or quasiperiodic fields. We conclude this paper with some open questions and perspectives of TDDFT.
Normal incidence intersubband photoresponse from phosphorus δ-doped Ge dots
Authors: Tong S. , Kim Hyung-Jun , Wang Kang L.
Published: August 2005

Normal incidence mid- and far-infrared photodetectors based on phosphorus δ-doped Ge dots were achieved on Si (100) substrates. Ge dots embedded in Si spacer layers were grown by molecular-beam epitaxy in the Stranski–Krastanov mode. The heavily doped (5×1019cm−3) Ge dot in the intrinsic Si matrix forms self-consistent potential wells in the conduction band for the ionized electrons. Photoresponse was demonstrated for an n-i-n structure in both the mid- and far-infrared wavelength ranges. The nonvanishing normal incidence response was due to the presence of nonzero off-diagonal terms for the electron mass tensor in Ge.
Turbulent fluxes and entropy production rate
Authors: Garbet X. , Dubuit N. , Asp E. , Sarazin Y. , Bourdelle C. , Ghendrih P. , Hoang G. T.
Published: August 2005

The entropy production rate is calculated for an interchange driven turbulence both in fluid and kinetic regimes. This calculation provides a rigorous way to define thermodynamical forces and fluxes. It is found that the forces are the gradients of density and temperature normalized to their “canonical” values, which are Lagrangian invariants of the flow. This formulation is equivalent to expressing the fluxes in terms of “curvature pinches,” where the curvature pinches are proportional to the logarithmic gradient of canonical profiles. Off diagonal terms in the transport matrix are found, which correspond to thermodiffusion and its Onsager symmetrical contribution to the heat flux. Hence, if thermodiffusion is significant, a heat pinch due to the density gradient also exists. The entropy production rate is found to be minimum when the profiles are equal to their canonical values. This property yields a generalized form of profile stiffness. However, a state where all profiles match their canonical values is not attainable because it is linearly stable.
A self-consistent transport model for molecular conduction based on extended Hückel theory with full three-dimensional electrostatics
Authors: Zahid F. , Paulsson M. , Polizzi E. , Ghosh A. W. , Siddiqui L. , Datta S.
Published: August 2005

We present a transport model for molecular conduction involving an extended Hückel theoretical treatment of the molecular chemistry combined with a nonequilibrium Green’s function treatment of quantum transport. The self-consistent potential is approximated by CNDO (complete neglect of differential overlap) method and the electrostatic effects of metallic leads (bias and image charges) are included through a three-dimensional finite element method. This allows us to capture spatial details of the electrostatic potential profile, including effects of charging, screening, and complicated electrode configurations employing only a single adjustable parameter to locate the Fermi energy. As this model is based on semiempirical methods it is computationally inexpensive and flexible compared to ab initio models, yet at the same time it is able to capture salient qualitative features as well as several relevant quantitative details of transport. We apply our model to investigate recent experimental data on alkane dithiol molecules obtained in a nanopore setup. We also present a comparison study of single molecule transistors and identify electronic properties that control their performance.