bluuebunny/crossref_metadata_2025 huggingface dataset:
Long term risk of invasive cancer after treatment for cervical intraepithelial neoplasia grade 3: population based cohort study
Authors: Strander Björn , Andersson-Ellström Agneta , Milsom Ian , Sparén Pär
Published: October 2007

Objective
To study the long term risk of invasive cancer of the cervix or vagina after treatment for cervical intraepithelial neoplasia grade 3.

Design
Prospective cohort study.

Setting
Swedish cancer registry.

Participants
All women in Sweden with severe dysplasia or cervical carcinoma in situ (equivalent to cervical intraepithelial neoplasia grade 3) treated during 1958-2002 (n=132 493) contributing 2 315 724 woman years.

Main outcome measures
Standardised incidence ratios with risk of cancer in the Swedish general female population as reference, and relative risks in multivariable log-linear regression model, with internal references.

Results
Women with previous cervical intraepithelial neoplasia grade 3 had an increased risk of invasive cervical cancer compared with the general female population (standardised incidence ratio 2.34, 95% confidence interval 2.18 to 2.50). The increased risk showed a decreasing trend with time since diagnosis for women treated later than 1970 but the risk was still increased after 25 years. An effect of age was found, with an accentuated increase in risk for women aged more than 50. The excess risk for cervical cancer associated with previous cervical intraepithelial neoplasia grade 3 has steadily increased since 1958. For vaginal cancer the standardised incidence ratio was 6.82 (5.61 to 8.21) but this decreased to 2.65 after 25 years. Adjustments in the multivariable log-linear regression model did not substantially alter these results.

Conclusions
Women previously treated for cervical intraepithelial neoplasia grade 3 are at an increased risk of developing invasive cervical cancer and vaginal cancer. This risk has increased since the 1960s and is accentuated in women aged more than 50. The risk is still increased 25 years after treatment.
Allelopathic effects of goldenrod and aster on young sugar maple
Authors: Fisher R. F. , Woods R. A. , Glavicic M. R.
Published: October 2007

A series of field, greenhouse, and laboratory studies were undertaken to elucidate the role of allelopathy in old-field sugar maple stands. Old-field weed residue inhibited germination and growth of maple even in the absence of competing vegetation. Goldenrod and aster were important producers of water soluble compounds that inhibited germination, nutrient uptake, and growth. These allelopathic chemicals were most readily extracted from putrefied plant residues, but they appeared to be natural plant products rather than microbial breakdown products. The deleterious effects of goldenrod on nutrition and growth of maple were overcome by large additions of soluble phosphorus fertilizer.
Heatsum–emergence relationship in Douglas-fir seedlings
Authors: Bloomberg W. J.
Published: October 2007

Usefulness of classifying Douglas-fir seed lots using heatsum–emergence relationship parameters was examined by (1) comparing nursery emergence with that predicted by the relationship, (2) testing seed lots for conformity to the relationship, and (3) computer simulation of emergence under various temperature regimes. The emergence parameters used were threshold heatsum (degree-hours above 0 °C that must be accumulated before emergence starts), emergence coefficient (percentage emergence per thousand degree-hours above the threshold), slow emergence percentage (percentage emergence at which the emergence rate is reduced), and slow emergence factor (amount by which the emergence coefficient is reduced). Emergence of seed lots at two nurseries was accurately predicted by a computer model based on the heatsum–emergence relationship. Five seed lots sown in growth chambers under two temperature regimes showed good conformity to the relationship. Computation of emergence percentage and days to 50 or 100% emergence was carried out by a computer model using various emergence parameter values chosen from the observed range and simulated temperature regimes comprising daily heatsums at the 0.5-cm soil depth for 40 days after sowing. These heatsums were derived by regression equation from air temperatures at a forest nursery and were increased or decreased to represent warm or cool regimes or combinations of both. Generally, emergence percentage increased and number of days to 50 or 100% emergence decreased as emergence coefficient and slow emergence percentage increased and threshold heatsum decreased. Emergence percentage was affected by temperature regime only at low emergence coefficients. Number of days to 100% emergence was affected by temperature regime only at average or high emergence coefficients.
Effects of nursery seedbed density and topdressing fertilization on survival and growth of 3 + 0 red pine
Authors: Mullin R. E. , Bowdery L.
Published: October 2007

Two experiments with red pine (Pinusresinosa Ait.) were established on 1 + 0 beds at Midhurst Nursery in 1966 and 1967 to study the effects on planting stock of two seedbed densities (160 and 320 trees/m2) and three fertilization levels of topdressing (superficial application of dry fertilizer: control (none), normal, and double). Observations were made as trees were lifted at 3 + 0 and also in the field 5 years after outplanting.Lower seedbed density produced heavier trees, larger stem diameters, and in most cases lower top–root ratios for outplanting. It also resulted in higher survival and taller trees at 5 years after outplanting. The normal 'N' fertilization did not significantly affect tree size in the nursery but was related to decreased survival rate and performance after outplanting.Comparisons with white pine (P. strobas L.) and white spruce (Piceaglauca (Moench) Voss.) are given.
Discolouration and decay associated with paraformaldehyde-treated tapholes in sugar maple
Authors: Walters Russell S. , Shigo Alex L.
Published: October 2007

More decay (higher incidence and greater total length of column) was associated with tapholes in mature sugar maples (Acersaccharum Marsh.) treated with a 250-mg paraformaldehyde pill than with control tapholes. This was apparent 20 months after treatment and at each successive examination to the final measurement at 56 months. Discoloured columns associated with pill-treated tapholes were longer than those associated with control tapholes for the first 8 months. From that time until the final measurement there were no statistically significant differences between lengths of discoloured columns associated with pill-treated and control tapholes. Cambial dieback occurred adjacent to many tapholes but there was no significant difference in closure rates of treated and control tapholes. Results were obtained from dissections and studies of 180 mature trees over a 56-month period in six locations in Vermont in one experiment, and from 75 trees over a 20-month period in three locations each in Vermont, Maine, New York, Pennsylvania, and Michigan in another experiment. The results indicate that repeated use of paraformaldehyde will lead to rapid development of decay in sugar maple trees.
Electrical resistance measurements of water potential in avocado and white spruce
Authors: Dixon M. A. , Thompson R. G. , Fensom D. S.
Published: October 2007

Simultaneous measurements of electrical resistance (or impedance (Z)) and water potential have been made on avocado Perseaamericana Mill. in the laboratory and on white spruce Piceaglauca (Moench) Voss in the field.A significant correlation was found between electrical impedance (corrected to standard temperature of 20 °C) and water potential of nearby leaves as measured by either pressure bomb or thermocouple psychrometer. When the resistance measurements were expressed as a percent of the measured maximum resistance reading the correlation with water potential was very nearly linear (correlation coefficient: Perseaamericana Mill., 0.98; Piceaglauca (Moench) Voss, 0.94). This relationship also seems to hold in Helianthusannuus L.The application of electrical resistance measurement techniques to these two plant systems has been shown to be a simple, nondestructive method of monitoring the water potential of such systems. The linear correlation between water potential and electrical resistance held whether the technique was applied on a tree at a fixed position through daily cycles, at different positions vertically up a tree, or under various degrees of hydration in a pressure bomb.
Electrical resistance related to phloem width in red maple
Authors: Carter Jonathan K. , Blanchard Robert O.
Published: October 2007

Electrical resistances of combined bark and wood of 50 red maple (Acerrubrum L.) trees were strongly correlated with phloem width with an inverse correlation coefficient of −0.92. Diameter at 1.4 m aboveground was determined to be transitively correlated with electrical resistance through its strong correlation with phloem width. Little detectable relationship existed between electrical resistance and potassium concentration in phloem tissues. An electrical model is presented to illustrate the path of electrical current between electrodes in the tissues measured.
Allocating inventory resources for multiple-use planning
Authors: Burkhart Harold E. , Stuck R. Dean , Leuschner William A. , Reynolds Marion R.
Published: October 2007

A user-oriented approach to allocate inventory resources for multiple-use planning is presented. The sequence used in the approach is to determine (1) the decisions to be made with the aid of inventory data, (2) the data needed to soundly base the decisions, and (3) the impact of sampling error in the data on the decisions. Sample intensities that minimize the cost of obtaining data plus the expected losses from using the data to make decisions were determined. A cost plus loss minimization framework for multiple-use planning inventory was developed and applied to a case study on a U.S. Forest Service planning unit. Results indicated that the procedure should provide useful guides for allocating sampling resources.
An apparatus to measure the crosscut shearing strength of roots
Authors: Ziemer Robert R.
Published: October 2007

Loss of tree root strength after timber cutting is a principal mechanism leading to slope failure and landslides. Measurement of root shear strength changes can be useful in evaluating effects of logging on slope stability. The simple apparatus described measures shear strength directly on roots up to 50 mm diameter. Tests on live roots showed excellent correlation between measurements of shear strength and tensile strength.
PHASE DIAGRAMS OF THE FCC BLUME–EMERY–GRIFFITHS MODEL ON A CELLULAR AUTOMATON
Authors: ÖZKAN A. , KUTLU B.
Published: October 2007

The spin-1 Ising (BEG) model has been simulated on a cellular automaton improved from the Creutz cellular automaton (CCA) for a face-centered cubic lattice. The simulations have been made in the 0 ≤ d = D/J ≤ 7 and -1.25 < k = K/J ≤ 0 parameter region. In this region, the ground state diagram (k, d) has ferromagnetic and perfect zero ordering regions. The ferromagnetic ordering region separates into four regions which exhibit different phase transition types as the first order, the second order, the reentrant, the double-reentrant and the successive phase transitions. The simulation results show that the model has the tricritical points, the critical end points and the bicritical points on the (kTC/zJ, d) and (kTC/zJ, k) planes as indicated by the Mean Field approximation results.
EFFECTS OF LANGMUIR KINETICS ON TWO-LANE TOTALLY ASYMMETRIC EXCLUSION PROCESSES OF MOLECULAR MOTOR TRAFFIC
Authors: WANG RUILI , JIANG RUI , LIU MINGZHE , LIU JIMING , WU QING-SONG
Published: October 2007

In this paper, we study a two-lane totally asymmetric simple exclusion process (TASEP) coupled with random attachment and detachment of particles (Langmuir kinetics) in both lanes under open boundary conditions. Our model can describe the directed motion of molecular motors, attachment and detachment of motors, and free inter-lane transition of motors between filaments. In this paper, we focus on some finite-size effects of the system because normally the sizes of most real systems are finite and small (e.g., size ≤ 10 000). A special finite-size effect of the two-lane system has been observed, which is that the density wall moves left first and then move towards the right with the increase of the lane-changing rate. We called it the jumping effect. We find that increasing attachment and detachment rates will weaken the jumping effect. We also confirmed that when the size of the two-lane system is large enough, the jumping effect disappears, and the two-lane system has a similar density profile to a single-lane TASEP coupled with Langmuir kinetics. Increasing lane-changing rates has little effect on density profiles after the density reaches maximum. Also, lane-changing rate has no effect on density profiles of a two-lane TASEP coupled with Langmuir kinetics at a large attachment/detachment rate and/or a large system size. Mean-field approximation is presented and it agrees with our Monte Carlo simulations.
EPIDEMIC SPREADING IN A COMPLEX NETWORK
Authors: HE MINGFENG , WANG BIN , XIAO XINHUA , SUN LEI
Published: October 2007

In this paper, a complex network is constructed as comprising "clusters" which can be interpreted as a group of people with regular contacts. In each "cluster" individuals contact fully. A given individual contact individuals in other "clusters" by links. Then we study the dynamical behavior of the epidemiological model in this complex network, and discuss the influence of the intra-cluster infection probability, the extra-cluster infection probability, and infection time before being detected on epidemic dynamics. The results show that extra-cluster infection reduction, early detection and swift isolation are good infection control practices.
MODEL OF THE POTENTIAL BARRIER OUTSIDE THE SURFACE OF A CONDUCTOR WITH WALLS OF FINITE THICKNESS
Authors: LI L. X. , LIU R. P. , ZHANG D. T. , LI B. H. , CUI Y. L. , ZHANG P. F. , SONG H. W.
Published: October 2007

Tunneling effect of graphite is studied by atomic force microscopy. The tunneling current in the gap between a conductive tip and a newly cleaved graphite surface at a given voltage keeps almost constant when the gap-distance varies within 1 μm, which cannot be explained by the commonly accepted well model of the potential outside a conductor. Thus modification of the well model is made and a cup model, with a certain wall thickness of the cup, is proposed in the present work.
DISPERSIONS AND FRÖHLICH ELECTRON–PHONON INTERACTION HAMILTONIAN OF PROPAGATING OPTICAL PHONON MODES IN QUASI-ONE-DIMENSIONAL WURTZITEGaN-BASED QUANTUM WELL WIRES
Authors: ZHANG L. , XIE HONG-JING
Published: October 2007

Based on the dielectric continuum model and Loudon's uniaxial crystal model, the propagating (PR) optical phonon modes and the Fröhlich-like electron–PR phonon interaction Hamiltonian in a quasi-one-dimensional (Q1D) wurtzite quantum well wire (QWW) structure are deduced and analyzed. Numerical calculations on AlGaN / GaN / AlGaN wurtzite QWW are performed. Results reveal that the dispersive frequencies of PR modes are the continuous functions of free wavenumber kzin z-direction and discrete functions of azimuthal quantum number m. The reduced behavior of the PR modes in wurtzite quantum systems is obviously observed. From the discussion of the electron–PR phonon coupling functions, it is found that the low-order PR modes in the case of small kzand m play a more important role in the electron–PR phonon interactions. Moreover, a detailed comparison of the PR modes in Q1D QWW structures with those in quasi-two-dimensional quantum wells are also carried out. The physical reasons resulting in the relationship and distinction in the two types of systems are also analyzed deeply.
FORMATION OF HOLLOW CAVITIES ON {100} FACES OF LAP CRYSTALS INVESTIGATED BY AFM
Authors: GENG Y. L. , SUN ZH. H. , XU D.
Published: October 2007

Atomic force microscopy (AFM) has been used to study the hollow cavity formation mechanisms of the L-arginine phosphate monohydrate (LAP) crystals. Hollow cavities are formed through three modes. During 2D nucleation growth, initially formed 2D cavity prevents the growth around it layer-by-layer and causes the formation of 3D cavity with stepped-walls inside. Interaction of the steps advancing along different directions generated by different dislocation sources is also responsible for the appearance of hollow cavities. When the steps overrun impurities incorporated into the kinks, triangular pits among regular elementary steps come into being.
NONDESTRUCTIVE IMPEDANCE SPECTROSCOPY EVALUATION OF THE BOND COAT OXIDATION IN THERMAL BARRIER COATINGS
Authors: YANG L. , ZHOU Y. C. , MAO W. G. , LIU Q. X.
Published: October 2007

In this paper, the impedance spectroscopy technique was employed to examine nondestructively the isothermal oxidation of air plasma sprayed (APS) thermal barrier coatings (TBCs) in air at 800°C. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) were also used to characterize the microstructure evolution of TBCs. After oxidation, the thermally grown oxide (TGO), which was mainly composed of alumina as confirmed by EDX, formed at the upper ceramic coat/bond coat interface, the lower bond coat/substrate interface, and the bond coat. Impedance diagrams obtained from impedance measurements at room temperature were analyzed according to the equivalent circuit model proposed for the TBCs. Various observed electrical responses relating to the growth of oxides and the sintering of YSZ were explained by simulating the impedance spectra of the TBCs.
ANIONIC GEMINI SURFACTANTS: SYNTHESIS AND SURFACE ACTIVE PROPERTIES
Authors: SHUKLA DIPTI , TYAGI V. K.
Published: October 2007

New compounds bearing two phosphate groups and two long chain (dodecyl) were prepared by two-step reaction: (i) phosphorylation of dodecanol with pyrophosphoric acid, (ii) reaction of dodecyl phosphate with N ( CH 3)4 OH and 1,6-dibromo hexane. The effect of reaction variables like time and molar ratio of reactants on yield has also been reported. The 1:2:0.5 molar ratio of reactants (dodecyl phosphate, N ( CH 3)4 OH , and Br ( CH 2)6 Br , respectively) and 3 h duration resulted to give maximum yield of anionic gemini surfactants. The structure of synthesized surfactant was investigated by modern analytical techniques, viz. FT-IR, 1H NMR, 13C NMR.

Amphipathic disodium phosphates were obtained by neutralization of free acids with sodium hydroxide and their surface active properties in aqueous solution were measured. These disodium phosphates possessed 77.3% anionic content and showed good water solubility. Foaming properties and wetting ability were also evaluated.
SURVISMETER, 2-IN-1 FOR VISCOSITY AND SURFACE TENSION MEASUREMENT, AN EXCELLENT INVENTION FOR INDUSTRIAL PROLIFERATION OF SURFACE FORCES IN LIQUIDS
Authors: SINGH MAN
Published: October 2007

Viscosities (η, N s m-2) and surface tensions (γ, N m-1) of methanol, ethanol, glycerol, ethyl acetate, n-hexane, diethyl ether, chloroform, benzene, carbon tetrachloride ( CCl 4), tetrahydrofuran (THF), dimethylformamide (DMF), dimethylsulfoxide (DMSO), acetonitrile, and formic acid have been measured with survismeter and compared with the data obtained by Ubbehold viscometer and stalagmometer, respectively. The ±1.1 × 10-5 N s m -2 and ±1.3 × 10-6 N m -1 deviations are noted in the data, in fact literature data of surface tension and viscosity are available to 2nd and 3rd place of decimals, respectively, while the survismeter measures them to 3rd and 4th place of decimals, respectively. The survismeter is 2-in-1 for viscosity and surface tension measurements together with high accuracies several times better than those of the separately measured data. Viscosities and surface tensions of aqueous DMSO, THF, DMF, and acetonitrile from 0.01 to 0.20 mol kg-1 and mannitol from 0.005 to 0.02 mol kg-1 have been measured with survismeter with ±1.2 × 10-5 N s m -2 and ±1.3 × 10-6 N m -1 deviations, respectively. The data are used for friccohesity and dipole moment determination, the lower viscosities, surface tension, and friccohesity values are noted for mannitol as compared to DMSO, THF, DMF, and acetonitrile solutions. The weaker molecular interactions are noted for mannitol. As compared to viscometer and stalagmometer individually, it is inexpensive and minimizes 2/3rd of consumables, human efforts, and infrastructure with 10 times better accuracies.
Shear stress and 17β-estradiol modulate cerebral microvascular endothelial Na-K-Cl cotransporter and Na/H exchanger protein levels
Authors: Chang Elaine , O'Donnell Martha E. , Barakat Abdul I.
Published: October 2007

Ion transporters of blood-brain barrier (BBB) endothelial cells play an important role in regulating the movement of ions between the blood and brain. During ischemic stroke, reduction in cerebral blood flow is accompanied by transport of Na and Cl from the blood into the brain, with consequent brain edema formation. We have shown previously that a BBB Na-K-Cl cotransporter (NKCC) participates in ischemia-induced brain Na and water uptake and that a BBB Na/H exchanger (NHE) may also participate. While the abrupt reduction of blood flow is a prominent component of ischemia, the effects of flow on BBB NKCC and NHE are not known. In the present study, we examined the effects of changes in shear stress on NKCC and NHE protein levels in cerebral microvascular endothelial cells (CMECs). We have shown previously that estradiol attenuates both ischemia-induced cerebral edema and CMEC NKCC activity. Thus, in the present study, we also examined the effects of estradiol on NKCC and NHE protein levels in CMECs. Exposing CMECs to steady shear stress (19 dyn/cm2) increased the abundance of both NKCC and NHE. Estradiol abolished the shear stress-induced increase in NHE but not NKCC. Abrupt reduction of shear stress did not alter NKCC or NHE abundance in the absence of estradiol, but it decreased NKCC abundance in estradiol-treated cells. Our results indicate that changes in shear stress modulate BBB NKCC and NHE protein levels. They also support the hypothesis that estradiol attenuates edema formation in ischemic stroke in part by reducing the abundance of BBB NKCC protein.
Co-expression of skeletal and cardiac troponin T decreases mouse cardiac function
Authors: Huang Q.-Q. , Feng H. Z. , Liu J. , Du J. , Stull L. B. , Moravec C. S. , Huang X. , Jin J.-P.
Published: October 2007

In contrast to skeletal muscles that simultaneously express multiple troponin T (TnT) isoforms, normal adult human cardiac muscle contains a single isoform of cardiac TnT. To understand the significance of myocardial TnT homogeneity, we examined the effect of TnT heterogeneity on heart function. Transgenic mouse hearts overexpressing a fast skeletal muscle TnT together with the endogenous cardiac TnT was investigated in vivo and ex vivo as an experimental system of concurrent presence of two classes of TnT in the adult cardiac muscle.This model of myocardial TnT heterogeneity produced pathogenic phenotypes: echocardiograph imaging detected age-progressive reductions of cardiac function; in vivo left ventricular pressure analysis showed decreased myocardial contractility; ex vivo analysis of isolated working heart preparations confirmed an intrinsic decrease of cardiac function in the absence of neurohumoral influence. The transgenic mice also showed chronic myocardial hypertrophy and degeneration. The dominantly negative effects of introducing a fast TnT into the cardiac thin filaments to produce two classes of Ca2+ regulatory units in the adult myocardium suggest that TnT heterogeneity decreases contractile function by disrupting the synchronized action during ventricular contraction that is normally activated as an electrophysiological syncytium.
Comparison of the effects of inorganic phosphate on caffeine-induced Ca2+ release in fast- and slow-twitch mammalian skeletal muscle
Authors: Posterino Giuseppe S. , Dunn Stacey L.
Published: October 2007

We compared the effects of 50 mM Pi on caffeine-induced Ca2+ release in mechanically skinned fast-twitch (FT) and slow-twitch (ST) skeletal muscle fibers of the rat. The time integral (area) of the caffeine response was reduced by ∼57% (FT) and ∼27% (ST) after 30 s of exposure to 50 mM Pi in either the presence or absence of creatine phosphate (to buffer ADP). Differences in the sarcoplasmic reticulum (SR) Ca2+ content between FT and ST fibers [∼40% vs. 100% SR Ca2+ content (pCa 6.7), respectively] did not contribute to the different effects of Pi observed; underloading the SR of ST fibers so that the SR Ca2+ content approximated that of FT fibers resulted in an even smaller (∼21%), but not significant, reduction in caffeine-induced Ca2+ release by Pi. These observed differences between FT and ST fibers could arise from fiber-type differences in the ability of the SR to accumulate Ca2+-Pi precipitate. To test this, fibers were Ca2+ loaded in the presence of 50 mM Pi. In FT fibers, the maximum SR Ca2+ content (pCa 6.7) was subsequently increased by up to 13 times of that achieved when loading for 2 min in the absence of Pi. In ST fibers, the SR Ca2+ content was only doubled. These data show that Ca2+ release in ST fibers was less affected by Pi than FT fibers, and this may be due to a reduced capacity of ST SR to accumulate Ca2+-Pi precipitate. This may account, in part, for the fatigue-resistant nature of ST fibers.
Disruption of the Cox-1 gene slows repair of microscopic lesions in the mouse gastric epithelium
Authors: Starodub Olga T. , Demitrack Elise S. , Baumgartner Heidi K. , Montrose Marshall H.
Published: October 2007

Cyclooxygenase-1 (Cox-1) contributes to gastric defense of healthy tissue, but the role in the protection of the gastric epithelium after minor, acute damage has been difficult to study in vivo. Using 710-nm two-photon light absorption to create microscopic gastric damage in anesthetized mice with the gastric mucosal surface surgically exposed and perfused on the microscope stage, the acute response of surface cells to injury could be monitored using in vivo microscopy within seconds after injury. Using exogenous (Cl-NERF) and endogenous fluorophores, extracellular pH and cell death were monitored in real time during the entire damage and repair cycle. Two-photon damage was initiated by scanning ∼200 μm2 of gastric surface cells with high laser intensity, causing rapid bleaching of NAD(P)H fluorescence in optically targeted cells. In both Cox-1+/− and Cox-1−/− mice, a similar initial damage area expanded to include bystander epithelial cells over the next 2–5 min, with larger maximal damage noted in Cox-1−/− mice. The maximal damage size seen in Cox-1−/− mice could be reduced by exogenous dimethyl-PGE2. All damaged cells exfoliated, and the underlying epithelium was coincidently repaired over a time interval that was briefer in Cox-1+/− (12 ± 2 min, n = 12) than in Cox-1−/− (24 ± 4 min, n = 14) mice. Directly after damage, pH increased transiently in the juxtamucosal layer (maximal at 3–6 min). A smaller peak pH change was noted in Cox-1−/− mice (ΔpH = 0.3 ± 0.04) than in Cox-1+/− mice (ΔpH = 0.6 ± 0.2). Recovery to normal surface pH took longer in Cox-1−/− mice (27 ± 5 min) than in Cox-1+/− mice (12 ± 1 min). In conclusion, constitutive loss of Cox-1 leaves the gastric mucosa more prone to damage and slowed repair of microlesions.
Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse
Authors: Ivanova Elena A. , Bechtold David A. , Dupré Sandrine M. , Brennand John , Barrett Perry , Luckman Simon M. , Loudon Andrew S. I.
Published: October 2007

The X-linked orphan receptor GPR50 shares 45% homology with the melatonin receptors, yet its ligand and physiological function remain unknown. Here we report that mice lacking functional GPR50 through insertion of a lacZ gene into the coding sequence of GPR50 exhibit an altered metabolic phenotype. GPR50 knockout mice maintained on normal chow exhibit lower body weight than age-matched wild-type littermates by 10 wk of age. Furthermore, knockout mice were partially resistant to diet-induced obesity. When placed on a high-energy diet (HED) for 5 wk, knockout mice consumed significantly more food per unit body weight yet exhibited an attenuated weight gain and reduced body fat content compared with wild-type mice. Wheel-running activity records revealed that, although GPR50 knockout mice showed no alteration of circadian period, the overall levels of activity were significantly increased over wild types in both nocturnal and diurnal phases. In line with this, basal metabolic rate (O2 consumption, CO2 production, and respiratory quotient) was found to be elevated in knockout mice. Using in situ hybridization (wild-type mice) and β-galactosidase activity (from LacZ insertion element in knockout mice), brain expression of GPR50 was found to be restricted to the ependymal layer of the third ventricle and dorsomedial nucleus of the hypothalamus. GPR50 expression was highly responsive to energy status, showing a significantly reduced expression following both fasting and 5 wk of HED. These data implicate GPR50 as an important regulator of energy metabolism.
Does impaired mitochondrial function affect insulin signaling and action in cultured human skeletal muscle cells?
Authors: Brown Audrey E. , Elstner Matthias , Yeaman Stephen J. , Turnbull Douglass M. , Walker Mark
Published: October 2007

Insulin-resistant type 2 diabetic patients have been reported to have impaired skeletal muscle mitochondrial respiratory function. A key question is whether decreased mitochondrial respiration contributes directly to the decreased insulin action. To address this, a model of impaired cellular respiratory function was established by incubating human skeletal muscle cell cultures with the mitochondrial inhibitor sodium azide and examining the effects on insulin action. Incubation of human skeletal muscle cells with 50 and 75 μM azide resulted in 48 ± 3% and 56 ± 1% decreases, respectively, in respiration compared with untreated cells mimicking the level of impairment seen in type 2 diabetes. Under conditions of decreased respiratory chain function, insulin-independent (basal) glucose uptake was significantly increased. Basal glucose uptake was 325 ± 39 pmol/min/mg (mean ± SE) in untreated cells. This increased to 669 ± 69 and 823 ± 83 pmol/min/mg in cells treated with 50 and 75 μM azide, respectively (vs. untreated, both P < 0.0001). Azide treatment was also accompanied by an increase in basal glycogen synthesis and phosphorylation of AMP-activated protein kinase. However, there was no decrease in glucose uptake following insulin exposure, and insulin-stimulated phosphorylation of Akt was normal under these conditions. GLUT1 mRNA expression remained unchanged, whereas GLUT4 mRNA expression increased following azide treatment. In conclusion, under conditions of impaired mitochondrial respiration there was no evidence of impaired insulin signaling or glucose uptake following insulin exposure in this model system.
Regulation of PDH in human arm and leg muscles at rest and during intense exercise
Authors: Kiilerich Kristian , Birk Jesper B. , Damsgaard Rasmus , Wojtaszewski Jørgen F. P. , Pilegaard Henriette
Published: October 2007

To test the hypothesis that pyruvate dehydrogenase (PDH) is differentially regulated in specific human muscles, regulation of PDH was examined in triceps, deltoid, and vastus lateralis at rest and during intense exercise. To elicit considerable glycogen use, subjects performed 30 min of exhaustive arm cycling on two occasions and leg cycling exercise on a third day. Muscle biopsies were obtained from deltoid or triceps on the arm exercise days and from vastus lateralis on the leg cycling day. Resting PDH protein content and phosphorylation on PDH-E1α sites 1 and 2 were higher ( P ≤ 0.05) in vastus lateralis than in triceps and deltoid as was the activity of oxidative enzymes. Net muscle glycogen utilization was similar in vastus lateralis and triceps (≈50%) but less in deltoid (likely reflecting less recruitment of deltoid), while muscle lactate accumulation was ≈55% higher ( P ≤ 0.05) in triceps than vastus lateralis. Exercise induced ( P ≤ 0.05) dephosphorylation of both PDH-E1α site 1 and site 2 in all three muscles, but it was more pronounced at PDH-E1α site 1 in triceps than in vastus lateralis ( P ≤ 0.05). The increase in activity of the active form of PDH (PDHa) after 10 min of exercise was more marked in vastus lateralis (≈246%) than in triceps (≈160%), but when it was related to total PDH-E1α protein content, no difference was evident. In conclusion, PDH protein content seems to be related to metabolic enzyme profile, rather than myosin heavy chain composition, and less PDH capacity in triceps is a likely contributing factor to higher lactate accumulation in triceps than in vastus lateralis.
Postburn trauma insulin resistance and fat metabolism
Authors: Cree Melanie G. , Wolfe Robert R.
Published: October 2007

Hyperglycemia and insulin resistance have long been recognized in severe burn patients. More recently, it has been observed that controlling hyperglycemia, or alleviating insulin resistance, is associated with improved outcomes. This has led to a renewed interest in the etiology of insulin resistance in this population. The postinjury hyperglycemic response appears to be associated with multiple metabolic abnormalities, such as elevated basal energy expenditure, increased protein catabolism, and, notably, significant alterations in fat metabolism. The synergy of all of the responses is not understood, although many studies have been conducted. In this article we will review the present understanding of the relationship between fat metabolism and insulin resistance posttrauma, and discuss some of the recent discoveries and potential therapeutic measures. We propose that the insulin resistance is likely related to the development of “ectopic” fat stores, i.e., triglyceride (TG) storage in sites such as the liver and muscle cells. Deposition of TG in ectopic sites is due to an increase in free fatty acid delivery secondary to catecholamine-induced lipolysis, in conjunction with decreased β-oxidation within muscle and decreased hepatic secretion of fats. The resultant increases in intracellular TG or related lipid products may in turn contribute to alterations in insulin signaling.
Activation of 5-HT1A receptors attenuates tachycardia induced by restraint stress in rats
Authors: Ngampramuan Sukonthar , Baumert Mathias , Beig Mirza Irfan , Kotchabhakdi Naiphinich , Nalivaiko Eugene
Published: October 2007

To better understand the central mechanisms that mediate increases in heart rate (HR) during psychological stress, we examined the effects of systemic and intramedullary (raphe region) administration of the serotonin-1A (5-HT1A) receptor agonist 8-hydroxy-2-(di- n-propylamino)tetraline (8-OH-DPAT) on cardiac changes elicited by restraint in hooded Wistar rats with preimplanted ECG telemetric transmitters. 8-OH-DPAT reduced basal HR from 356 ± 12 to 284 ± 12 beats/min, predominantly via a nonadrenergic, noncholinergic mechanism. Restraint stress caused tachycardia (an initial transient increase from 318 ± 3 to 492 ± 21 beats/min with a sustained component of 379 ± 12 beats/min). β-Adrenoreceptor blockade with atenolol suppressed the sustained component, whereas muscarinic blockade with methylscopolamine (50 μg/kg) abolished the initial transient increase, indicating that sympathetic activation and vagal withdrawal were responsible for the tachycardia. Systemic administration of 8-OH-DPAT (10, 30, and 100 μg/kg) attenuated stress-induced tachycardia in a dose-dependent manner, and this effect was suppressed by the 5-HT1A antagonist WAY-100635 (100 μg/kg). Given alone, the antagonist had no effect. Systemically injected 8-OH-DPAT (100 μg/kg) attenuated the sympathetically mediated sustained component (from +85 ± 19 to +32 ± 9 beats/min) and the vagally mediated transient (from +62 ± 5 to +25 ± 3 beats/min). Activation of 5-HT1A receptors in the medullary raphe by microinjection of 8-OH-DPAT mimicked the antitachycardic effect of the systemically administered drug but did not affect basal HR. We conclude that tachycardia induced by restraint stress is due to a sustained increase in cardiac sympathetic activity associated with a transient vagal withdrawal. Activation of central 5-HT1A receptors attenuates this tachycardia by suppressing autonomic effects. At least some of the relevant receptors are located in the medullary raphe-parapyramidal area.
A neutral CB1 receptor antagonist reduces weight gain in rat
Authors: Chambers Adam P. , Vemuri V. Kiran , Peng Yan , Wood JodiAnne T. , Olszewska Teresa , Pittman Quentin J. , Makriyannis Alexandros , Sharkey Keith A.
Published: October 2007

Cannabinoid (CB)1 receptor inverse agonists inhibit food intake in animals and humans but also potentiate emesis. It is not clear whether these effects result from inverse agonist properties or from the blockade of endogenous cannabinoid signaling. Here, we examine the effect of a neutral CB1 antagonist, AM4113, on food intake, weight gain, and emesis. Neutral antagonist and binding properties were confirmed in HEK-293 cells transfected with human CB1 or CB2 receptors. AM4113 had no effect on forskolin-stimulated cAMP production at concentrations up to 630 nM. The Ki value of AM4113 (0.80 ± 0.44 nM) in competitive binding assays with the CB1/2 agonist [3H]CP55,940 was 100-fold more selective for CB1 over CB2 receptors. We determined that AM4113 antagonized CB1 receptors in brain by blocking hypothermia induced by CP55,940. AM4113 (0–20 mg/kg) significantly reduced food intake and weight gain in rat. Compared with AM251, higher doses of AM4113 were needed to produce similar effects on food intake and body weight. Unlike AM251 (5 mg/kg), a highly anorectic dose of AM4113 (10 mg/kg) did not significantly potentiate vomiting induced by the emetic morphine-6-glucoronide. We show that a centrally active neutral CB1 receptor antagonist shares the appetite suppressant and weight loss effects of inverse agonists. If these compounds display similar properties in humans, they could be developed into a new class of antiobesity agents.
Association of soluble adenylyl cyclase with the V-ATPase in renal epithelial cells
Authors: Păunescu Teodor G. , Da Silva Nicolas , Russo Leileata M. , McKee Mary , Lu Hua A. J. , Breton Sylvie , Brown Dennis
Published: October 2007

Activation of soluble adenylyl cyclase (sAC) by bicarbonate causes local cAMP generation, indicating that sAC might act as a pH and/or bicarbonate sensor in kidney cells involved in acid-base homeostasis. Therefore, we examined the expression of sAC in renal acid-base transporting intercalated cells (IC) and compared its distribution to that of the vacuolar proton pumping ATPase (V-ATPase) under different conditions. In all IC, sAC and V-ATPase showed considerable overlap under basal conditions, but sAC staining was also found in other cellular locations in the absence of V-ATPase. In type A-IC, both sAC and V-ATPase were apically and subapically located, whereas in type B-IC, significant basolateral colocalization of sAC and the V-ATPase was seen. When apical membrane insertion of the V-ATPase was stimulated by treatment of rats with acetazolamide, sAC was also concentrated in the apical membrane of A-IC. In mice that lack a functional B1 subunit of the V-ATPase, sAC was colocalized apically in A-IC along with V-ATPase containing the alternative B2 subunit isoform. The close association between these two enzymes was confirmed by coimmunoprecipitation of sAC from kidney homogenates using anti-V-ATPase antibodies. Our data show that sAC and the V-ATPase colocalize in IC, that they are concentrated in the IC plasma membrane under conditions that “activate” these proton secretory cells, and that they are both present in an immunoprecipitated complex. This suggests that these enzymes have a close association and could be part of a protein complex that is involved in regulating renal distal proton secretion.
Spatial Frequency Integration for Binocular Correspondence in Macaque Area V4
Authors: Kumano Hironori , Tanabe Seiji , Fujita Ichiro
Published: October 2007

Neurons in the primary visual cortex (V1) detect binocular disparity by computing the local disparity energy of stereo images. The representation of binocular disparity in V1 contradicts the global correspondence when the image is binocularly anticorrelated. To solve the stereo correspondence problem, this rudimentary representation of stereoscopic depth needs to be further processed in the extrastriate cortex. Integrating signals over multiple spatial frequency channels is one possible mechanism supported by theoretical and psychophysical studies. We examined selectivities of single V4 neurons for both binocular disparity and spatial frequency in two awake, fixating monkeys. Disparity tuning was examined with a binocularly correlated random-dot stereogram (RDS) as well as its anticorrelated counterpart, whereas spatial frequency tuning was examined with a sine wave grating or a narrowband noise. Neurons with broader spatial frequency tuning exhibited more attenuated disparity tuning for the anticorrelated RDS. Additional rectification at the output of the energy model does not likely account for this attenuation because the degree of attenuation does not differ among the various types of disparity-tuned neurons. The results suggest that disparity energy signals are integrated across spatial frequency channels for generating a representation of stereoscopic depth in V4.
Transient Activity Induces a Long-Lasting Increase in the Excitability of Olfactory Bulb Interneurons
Authors: Inoue Tsuyoshi , Strowbridge Ben W.
Published: October 2007

Little is known about the cellular mechanisms that underlie the processing and storage of sensory in the mammalian olfactory system. Here we show that persistent spiking, an activity pattern associated with working memory in other brain regions, can be evoked in the olfactory bulb by stimuli that mimic physiological patterns of synaptic input. We find that brief discharges trigger persistent activity in individual interneurons that receive slow, subthreshold oscillatory input in acute rat olfactory bulb slices. A 2- to 5-Hz oscillatory input, which resembles the synaptic drive that the olfactory bulb receives during sniffing, is required to maintain persistent firing. Persistent activity depends on muscarinic receptor activation and results from interactions between calcium-dependent afterdepolarizations and low-threshold Ca spikes in granule cells. Computer simulations suggest that intrinsically generated persistent activity in granule cells can evoke correlated spiking in reciprocally connected mitral cells. The interaction between the intrinsic currents present in reciprocally connected olfactory bulb neurons constitutes a novel mechanism for synchronized firing in subpopulations of neurons during olfactory processing.
A Rose by Any Other Name: Would it Smell as Sweet?
Authors: Djordjevic Jelena , Lundstrom Johan N. , Clément Francis , Boyle Julie A. , Pouliot Sandra , Jones-Gotman Marilyn
Published: October 2007

We examined whether presenting an odor with a positive, neutral, or negative name would influence how people perceive it. In experiment 1, 40 participants rated 15 odors for their pleasantness, intensity, and arousal. In experiment 2, 30 participants passively smelled 10 odors while their skin conductance (SC), heart rate (HR), and sniffing were recorded. We found significant overall effects of odor names on perceived pleasantness, intensity, and arousal. Pleasantness showed the most robust effect of odor names: the same odors were perceived as more pleasant when presented with positive than with neutral and negative names and when presented with neutral than with negative names. In addition, odorants were rated as more intense when presented with negative than with neutral and positive names and as more arousing when presented with positive than with neutral names. Furthermore, SC and sniff volumes, but not HR, were modified by odor names, and the SC changes could not be accounted for by sniffing changes. Importantly, odor names presented with odorless water did not produce any effect on skin conductance and sniff volumes, ruling out the possibility that the naming-related findings were triggered by an emotional reaction to odor names. Taken together, these experiments show that there is a lot to a name, at least when it comes to olfactory perception.
Global and targeted gene expression and protein content in skeletal muscle of young men following short-term creatine monohydrate supplementation
Authors: Safdar Adeel , Yardley Nicholas J. , Snow Rodney , Melov Simon , Tarnopolsky Mark A.
Published: October 2007

Creatine monohydrate (CrM) supplementation has been shown to increase fat-free mass and muscle power output possibly via cell swelling. Little is known about the cellular response to CrM. We investigated the effect of short-term CrM supplementation on global and targeted mRNA expression and protein content in human skeletal muscle. In a randomized, placebo-controlled, crossover, double-blind design, 12 young, healthy, nonobese men were supplemented with either a placebo (PL) or CrM (loading phase, 20 g/day × 3 days; maintenance phase, 5 g/day × 7 days) for 10 days. Following a 28-day washout period, subjects were put on the alternate supplementation for 10 days. Muscle biopsies of the vastus lateralis were obtained and were assessed for mRNA expression (cDNA microarrays + real-time PCR) and protein content (Kinetworks KPKS 1.0 Protein Kinase screen). CrM supplementation significantly increased fat-free mass, total body water, and body weight of the participants ( P < 0.05). Also, CrM supplementation significantly upregulated (1.3- to 5.0-fold) the mRNA content of genes and protein content of kinases involved in osmosensing and signal transduction, cytoskeleton remodeling, protein and glycogen synthesis regulation, satellite cell proliferation and differentiation, DNA replication and repair, RNA transcription control, and cell survival. We are the first to report this large-scale gene expression in the skeletal muscle with short-term CrM supplementation, a response that suggests changes in cellular osmolarity.
Characterization of Two Signal Transduction Systems Involved in Intracellular Macrophage Survival and Environmental Stress Response in Enterococcus faecalis
Authors: Muller Cécile , Sanguinetti Maurizio , Riboulet Eliette , Hébert Laurent , Posteraro Brunella , Fadda Giovanni , Auffray Yanick , Rincé Alain
Published: October 2007

The intracellular survival in mouse peritoneal macrophages of 8 Enterococcus faecalis response regulator mutants was tested to assess if the corresponding 2-component signal transduction systems (TCS) are involved in the ability of E. faecalis to survive in macrophages. Three mutants (err04, err05 and err06) are more susceptible than the wild-type JH2-2 strain and 1 is more resistant (err10). Then, characterization of the TCS Err04-Ehk04 and Err06-Ehk06 reveals that the first (homolog of PhoP-PhoR of Bacillus subtilis) is induced in phosphate deprivation conditions, regulates its own expression and plays a role in the expression of pstF encoding a phosphate-binding protein. The Err06-Ehk06 is involved in oxidative stress response. A mutation in the err06 gene increases sensitivity of the bacterium to H2O2. The err06-ehk06 operon is induced by H2O2 stress and controlled by 2 transcriptional start sites, of which 1 is specifically active in oxidative stress conditions. We also demonstrated that the expression of the catalase gene (kat) is partly dependant of the Err06-Ehk06 TCS.