bluuebunny/crossref_metadata_2025 huggingface dataset:
Anomalous Criticality in the Electrical Resistivity of La

2–
x

Sr

x

CuO
4
Authors: Cooper R. A. , Wang Y. , Vignolle B. , Lipscombe O. J. , Hayden S. M. , Tanabe Y. , Adachi T. , Koike Y. , Nohara M. , Takagi H. , Proust Cyril , Hussey N. E.
Published: December 2008

The presence or absence of a quantum critical point and its location in the phase diagram of high-temperature superconductors have been subjects of intense scrutiny. Clear evidence for quantum criticality, particularly in the transport properties, has proved elusive because the important low-temperature region is masked by the onset of superconductivity. We present measurements of the low-temperature in-plane resistivity of several highly doped La

2–
x

Sr

x

CuO
4
single crystals in which the superconductivity had been stripped away by using high magnetic fields. In contrast to other quantum critical systems, the resistivity varies linearly with temperature over a wide doping range with a gradient that scales monotonically with the superconducting transition temperature. It is maximal at a critical doping level (
p
c
) ∼ 0.19 at which superconductivity is most robust. Moreover, its value at
p
c
corresponds to the onset of quasi-particle incoherence along specific momentum directions, implying that the interaction that first promotes high-temperature superconductivity may ultimately destroy the very quasi-particle states involved in the superconducting pairing.
Femtosecond XANES Study of the Light-Induced Spin Crossover Dynamics in an Iron(II) Complex
Authors: Bressler Ch. , Milne C. , Pham V.-T. , ElNahhas A. , van der Veen R. M. , Gawelda W. , Johnson S. , Beaud P. , Grolimund D. , Kaiser M. , Borca C. N. , Ingold G. , Abela R. , Chergui M.
Published: December 2008

X-ray absorption spectroscopy is a powerful probe of molecular structure, but it has previously been too slow to track the earliest dynamics after photoexcitation. We investigated the ultrafast formation of the lowest quintet state of aqueous iron(II) tris(bipyridine) upon excitation of the singlet metal-to-ligand-charge-transfer (
1
MLCT) state by femtosecond optical pump/x-ray probe techniques based on x-ray absorption near-edge structure (XANES). By recording the intensity of a characteristic XANES feature as a function of laser pump/x-ray probe time delay, we find that the quintet state is populated in about 150 femtoseconds. The quintet state is further evidenced by its full XANES spectrum recorded at a 300-femtosecond time delay. These results resolve a long-standing issue about the population mechanism of quintet states in iron(II)-based complexes, which we identify as a simple
1
MLCT→
3
MLCT→
5
T cascade from the initially excited state. The time scale of the
3
MLCT→
5
T relaxation corresponds to the period of the iron-nitrogen stretch vibration.
Fumarole-Supported Islands of Biodiversity within a Hyperarid, High-Elevation Landscape on Socompa Volcano, Puna de Atacama, Andes
Authors: Costello Elizabeth K. , Halloy Stephan R. P. , Reed Sasha C. , Sowell Preston , Schmidt Steven K.
Published: December 2008

Fumarolic activity supports the growth of mat-like photoautotrophic communities near the summit (at 6,051 m) of Socompa Volcano in the arid core of the Andes mountains. These communities are isolated within a barren, high-elevation landscape where sparse vascular plants extend to only 4,600 m. Here, we combine biogeochemical and molecular-phylogenetic approaches to characterize the bacterial and eucaryotic assemblages associated with fumarolic and nonfumarolic grounds on Socompa. Small-subunit rRNA genes were PCR amplified, cloned, and sequenced from two fumarolic soil samples and two reference soil samples, including the volcanic debris that covers most of the mountain. The nonfumarolic, dry, volcanic soil was similar in nutrient status to the most extreme Antarctic Dry Valley or Atacama Desert soils, hosted relatively limited microbial communities dominated by
Actinobacteria
and
Fungi
, and contained no photoautotrophs. In contrast, modest fumarolic inputs were associated with elevated soil moisture and nutrient levels, the presence of chlorophyll
a
, and
13
C-rich soil organic carbon. Moreover, this soil hosted diverse photoautotroph-dominated assemblages that contained novel lineages and exhibited structure and composition comparable to those of a wetland near the base of Socompa (3,661-m elevation). Fumarole-associated eucaryotes were particularly diverse, with an abundance of green algal lineages and a novel clade of microarthropods. Our data suggest that volcanic degassing of water and
13
C-rich CO
2
sustains fumarole-associated primary producers, leading to a complex microbial ecosystem within this otherwise barren landscape. Finally, we found that human activities have likely impacted the fumarolic soils and that fumarole-supported photoautotrophic communities may be exceptionally sensitive to anthropogenic disturbance.
Application of Recognition of Individual Genes-Fluorescence In Situ Hybridization (RING-FISH) To Detect Nitrite Reductase Genes (nirK) of Denitrifiers in Pure Cultures and Environmental Samples
Authors: Pratscher Jennifer , Stichternoth Catrin , Fichtl Katrin , Schleifer Karl-Heinz , Braker Gesche
Published: December 2008

Denitrification is an alternative type of anaerobic respiration in which nitrate is reduced to gaseous products via nitrite. The key step in this process is the reduction of nitrite to nitric oxide, which is catalyzed by two structurally different but functionally equivalent forms of nitrite reductase encoded by thenirKandnirSgenes. Cultivation-independent studies based on these functional marker genes showed that in the environment there was a dominance of organisms withnirKandnirSgenes presumably derived from organisms that have not been cultured yet. However, the phylogenetic affiliation of these organisms has not been resolved since the ability to denitrify is widespread in phylogenetically unrelated organisms. To unravel the phylogeny of the organisms from which the nitrite reductase (nirK) genes originated, one option is to use a special variant of whole-cell hybridization termed recognition of individual genes-fluorescence in situ hybridization (RING-FISH). In RING-FISH a multiply labeled transcript polynucleotide probe is used to detect a single gene on the bacterial chromosome during FISH. Here, RING-FISH was used with laboratory cultures and environmental samples, such as activated sludge. Furthermore, probe-based cell sorting using magnetic beads could also be carried out with mixtures of pure cultures, which led to effective depletion of thenirK-negative organism but capture of thenirK-positive organism, which was demonstrated by terminal restriction fragment length polymorphism analysis based on 16S rRNA genes. The results indicate that RING-FISH coupled with probe-based cell sorting could be used with environmental samples, which could provide a means for phylogenetic classification ofnirK-type denitrifiers. Thus, the results of RING-FISH could increase our understanding of the phylogeny and function of denitrifying microorganisms in the environment.
Functional Differentiation of
tbf1
Orthologues in Fission and Budding Yeasts
Authors: Cockell Moira M. , Lo Presti Libera , Cerutti Lorenzo , Cano Del Rosario Elena , Hauser Philippe M. , Simanis Viesturs
Published: December 2008

In
Saccharomyces cerevisiae
,
TBF1
, an essential gene, influences telomere function but also has other roles in the global regulation of transcription. We have identified a new member of the
tbf1
gene family in the mammalian pathogen
Pneumocystis carinii
. We demonstrate by transspecies complementation that its ectopic expression can provide the essential functions of
Schizosaccharomyces pombe tbf1
but that there is no rescue between fission and budding yeast orthologues. Our findings indicate that an essential function of this family of proteins has diverged in the budding and fission yeasts and suggest that effects on telomere length or structure are not the primary cause of inviability in
S. pombe tbf1
null strains.
The White Cell Response to Pheromone Is a General Characteristic of
Candida albicans
Strains
Authors: Sahni Nidhi , Yi Song , Pujol Claude , Soll David R.
Published: December 2008

For
Candida albicans
, evidence has suggested that the mating pheromones activate not only the mating response in mating-competent opaque cells but also a unique response in mating-incompetent white cells that includes increased cohesion and adhesion, enhanced biofilm formation, and expression of select mating-related and white cell-specific genes. On the basis of a recent microarray analysis comparing changes in the global expression patterns of white cells in two strains in response to α-pheromone, however, skepticism concerning the validity and generality of the white cell response has been voiced. Here, we present evidence that the response occurs in all tested media (Lee's, RPMI, SpiderM, yeast extract-peptone-dextrose, and a synthetic medium) and in all of the 27 tested strains, including
a
/
a
and α/α strains, derivatives of the common laboratory strain SC5314, and representatives from all of the five major clades. The white cell response to pheromone is therefore a general characteristic of
MTL
-homozygous strains of
C. albicans
.
Crystal Structures of Cytochrome P450 105P1 fromStreptomyces avermitilis: Conformational Flexibility and Histidine Ligation State
Authors: Xu Lian-Hua , Fushinobu Shinya , Ikeda Haruo , Wakagi Takayoshi , Shoun Hirofumi
Published: December 2008

The polyene macrolide antibiotic filipin is widely used as a probe for cholesterol in biological membranes. The filipin biosynthetic pathway ofStreptomyces avermitiliscontains two position-specific hydroxylases, C26-specific CYP105P1 and C1′-specific CYP105D6. In this study, we describe the three X-ray crystal structures of CYP105P1: the ligand-free wild-type (WT-free), 4-phenylimidazole-bound wild-type (WT-4PI), and ligand-free H72A mutant (H72A-free) forms. The BC loop region in the WT-free structure has a unique feature; the side chain of His72 within this region is ligated to the heme iron. On the other hand, this region is highly disordered and widely open in WT-4PI and H72A-free structures, respectively. Histidine ligation of wild-type CYP105P1 was not detectable in solution, and a type II spectral change was clearly observed when 4-phenylimidazole was titrated. The H72A mutant showed spectroscopic characteristics that were almost identical to those of the wild-type protein. In the H72A-free structure, there is a large pocket that is of the same size as the filipin molecule. The highly flexible feature of the BC loop region of CYP105P1 may be required to accept a large hydrophobic substrate.
Roles of ExoI and SbcCD Nucleases in “Reckless” DNA Degradation inrecAMutants ofEscherichia coli
Authors: Zahradka Ksenija , Buljubašić Maja , Petranović Mirjana , Zahradka Davor
Published: December 2008

Exponentially growingrecAmutant cells ofEscherichia colidisplay pronounced DNA degradation that starts at the sites of DNA damage and depends on RecBCD nuclease (ExoV) activity. As a consequence of this “reckless” DNA degradation, populations ofrecAmutants contain a large proportion of anucleate cells. We have found that both DNA degradation and anucleate-cell production are efficiently suppressed by mutations in thexonA(sbcB) andsbcDgenes. The suppressive effects of these mutations were observed in normally grown, as well as in UV-irradiated,recAcells. The products of thexonAandsbcDgenes are known to code for the ExoI and SbcCD nucleases, respectively. Since bothxonAandsbcDmutations are required for strong suppression of DNA degradation while individual mutations have only a weak suppressive effect, we infer that ExoI and SbcCD play partially redundant roles in regulating DNA degradation inrecAcells. We suggest that their roles might be in processing (blunting) DNA ends, thereby producing suitable substrates for RecBCD binding.
P2Y receptors mediate Ca2+signaling in duodenocytes and contribute to duodenal mucosal bicarbonate secretion
Authors: Dong Xiao , Smoll Eric James , Ko Kwang Hyun , Lee Jonathan , Chow Jimmy Yip , Kim Ho Dong , Insel Paul A. , Dong Hui
Published: December 2008

Since little is known about the role of P2Y receptors (purinoceptors) in duodenal mucosal bicarbonate secretion (DMBS), we sought to investigate the expression and function of these receptors in duodenal epithelium. Expression of P2Y2receptors was detected by RT-PCR in mouse duodenal epithelium and SCBN cells, a duodenal epithelial cell line. UTP, a P2Y2-receptor agonist, but not ADP (10 μM), significantly induced murine duodenal short-circuit current and DMBS in vitro; these responses were abolished by suramin (300 μM), a P2Y-receptor antagonist, or 2-aminoethoxydiphenyl borate (2-APB; 100 μM), a store-operated channel blocker. Mucosal or serosal addition of UTP induced a comparable DMBS in wild-type mice, but markedly impaired response occurred in P2Y2knockout mice. Acid-stimulated DMBS in vivo was significantly inhibited by suramin (1 mM) or PPADS (30 μM). Both ATP and UTP, but not ADP (1 μM), raised cytoplasmic-free Ca2+concentrations ([Ca2+]cyt) with similar potencies in SCBN cells. ATP-induced [Ca2+]cytwas attenuated by U-73122 (10 μM), La3+(30 μM), or 2-APB (10 μM), but was not significantly affected by nifedipine (10 μM). UTP (1 μM) induced a [Ca2+]cyttransient in Ca2+-free solutions, and restoration of external Ca2+(2 mM) raised [Ca2+]cytdue to capacitative Ca2+entry. La3+(30 μM), SK&F96365 (30 μM), and 2-APB (10 μM) inhibited UTP-induced Ca2+entry by 92, 87, and 94%, respectively. Taken together, our results imply that activation of P2Y2receptors enhances DMBS via elevation of [Ca2+]cytthat likely results from an initial increase in intracellular Ca2+release followed by extracellular Ca2+entry via store-operated channel.
Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat
Authors: Casey David B. , Badejo Adeleke M. , Dhaliwal Jasdeep S. , Murthy Subramanyam N. , Hyman Albert L. , Nossaman Bobby D. , Kadowitz Philip J.
Published: December 2008

Recent studies show that pulmonary vasodilator responses to nitrite are enhanced by hypoxia. However, the mechanism by which nitrite is converted to vasoactive nitric oxide (NO) is uncertain. In the present study, intravenous injections of sodium nitrite decreased pulmonary and systemic arterial pressures and increased cardiac output. The decreases in pulmonary arterial pressure were enhanced when tone in the pulmonary vascular bed was increased with U-46619. Under elevated tone conditions, decreases in pulmonary and systemic arterial pressures in response to nitrite were attenuated by allopurinol in a dose that did not alter responses to the NO donors, sodium nitroprusside and diethylamine/NO, suggesting that xanthine oxidoreductase is the major enzyme-reducing nitrite to NO. Ventilation with a 10% O2gas mixture increased pulmonary arterial pressure, and the response to hypoxia was enhanced by NG-nitro-l-arginine methyl ester and not altered by allopurinol. This suggests that NO formed by the endothelium and not from the reduction of plasma nitrite modulates the hypoxic pulmonary vasoconstrictor response. Although intravenous injections of sodium nitrite reversed pulmonary hypertensive responses to U-46619, hypoxia, and NG-nitro-l-arginine methyl ester, the pulmonary vasodilator response to nitrite was not altered by ventilation with 10% O2when baseline pulmonary arterial pressure was increased to similar values in animals breathing room air or the hypoxic gas. These data provide evidence that xanthine oxidoreductase is the major enzyme-reducing nitrite to vasoactive NO, and that this mechanism is not modified by hypoxia.
Control of cardiac rate, contractility, and atrioventricular conduction by medullary raphé neurons in anesthetized rats
Authors: Salo Lauren M. , Nalivaiko Eugene , Anderson Colin R. , McAllen Robin M.
Published: December 2008

The sympathetic actions of medullary raphé neurons on heart rate (HR), atrioventricular conduction, ventricular contractility, and rate of relaxation were examined in nine urethane-anesthetized (1–1.5 g/kg iv), artificially ventilated rats that had been adrenalectomized and given atropine methylnitrate (1 mg/kg iv). Mean arterial pressure (MAP), ECG, and left ventricular pressure were recorded. The peak rates of rise and fall in the first derivative of left ventricular (LV) pressure (dP/d tmaxand dP/d tmin, respectively) and the stimulus-R ($-R) interval were measured during brief periods of atrial pacing at 8.5 Hz before and after ventral medullary raphé neurons were activated by dl-homocysteic acid (DLH, 0.1 M) or inhibited by GABA (0.3 M) in local microinjections (90 nl). LV dP/d tmaxvalues were corrected for the confounding effect of MAP, determined at the end of the experiments after giving propranolol (1 mg/kg iv) to block sympathetic actions on the heart. DLH microinjections into the ventral medullary raphé region increased HR by 44 ± 2 beats/min, LV dP/d tmaxby 1,055 ± 156 mmHg/s, and the negative value of LV dP/d tminby 729 ± 204 mmHg/s (all, P < 0.001) while shortening the $-R interval by 2.8 ± 0.8 ms ( P < 0.01). GABA microinjections caused no significant change in HR, LV dP/d tmax, or $-R interval but reduced LV dP/d tminfrom −5,974 ± 93 to −5,548 ± 171 mmHg/s and MAP from 115 ± 4 to 105 ± 5 mmHg (both, P < 0.01). Rises in tail skin temperature confirmed that GABA injections effectively inhibited raphé neurons. When activated, the neurons in the ventral medullary raphé region thus enhance atrioventricular conduction, ventricular contractility, and relaxation in parallel with HR, but they provide little or no tonic sympathetic drive to the heart.
Novel soluble guanylyl cyclase stimulator BAY 41-2272 attenuates ischemia-reperfusion-induced lung injury
Authors: Egemnazarov Bakytbek , Sydykov Akylbek , Schermuly Ralph T. , Weissmann Norbert , Stasch Johannes-Peter , Sarybaev Akpai S. , Seeger Werner , Grimminger Friedrich , Ghofrani Hossein A.
Published: December 2008

The protective effects of nitric oxide (NO), a physiological activator of soluble guanylyl cyclase (sGC), have been reported in ischemia-reperfusion (I/R) syndrome of the lung. Therefore, we studied the effects of BAY 41-2272, a novel sGC stimulator, on I/R injury of the lung in an isolated intact organ model. Lung injury was assessed by measuring weight gain and microvascular permeability (capillary filtration coefficient, Kfc). Release of reactive oxygen species (ROS) into the perfusate was measured during early reperfusion by electron spin resonance (ESR) spectroscopy. Rabbit lungs were treated with BAY 41-2272, NG-monomethyl-l-arginine (l-NMMA), or NO to evaluate the effects on I/R-induced lung injury. In untreated lungs, a dramatic rise in Kfcvalues and weight gain during reperfusion were observed, and these results were associated with increased ROS production. Both, BAY 41-2272 and l-NMMA significantly attenuated vascular leakage and suppressed ROS release. Additional experiments showed that BAY 41-2272 diminished PMA-induced ROS production by NADPH oxidase. A pharmacological inhibition of the enzyme with consequent reduction in ROS levels decreased I/R injury. NO had only marginal effect on I/R injury. Thus BAY 41-2272 protects against I/R-induced lung injury by interfering with the activation of NADPH oxidases.
Contribution of glycosaminoglycans to viscoelastic tensile behavior of human ligament
Authors: Lujan Trevor J. , Underwood Clayton J. , Jacobs Nathan T. , Weiss Jeffrey A.
Published: December 2008

The viscoelastic properties of human ligament potentially guard against structural failure, yet the microstructural origins of these transient behaviors are unknown. Glycosaminoglycans (GAGs) are widely suspected to affect ligament viscoelasticity by forming molecular bridges between neighboring collagen fibrils. This study investigated whether GAGs directly affect viscoelastic material behavior in human medial collateral ligament (MCL) by using nondestructive tensile tests before and after degradation of GAGs with chondroitinase ABC (ChABC). Control and ChABC treatment (83% GAG removal) produced similar alterations to ligament viscoelasticity. This finding was consistent at different levels of collagen fiber stretch and tissue hydration. On average, stress relaxation increased after incubation by 2.2% (control) and 2.1% (ChABC), dynamic modulus increased after incubation by 3.6% (control) and 3.8% (ChABC), and phase shift increased after incubation by 8.5% (control) and 8.4% (ChABC). The changes in viscoelastic behavior after treatment were significantly more pronounced at lower clamp-to-clamp strain levels. A 10% difference in the water content of tested specimens had minor influence on ligament viscoelastic properties. The major finding of this study is that mechanical interactions between collagen fibrils and GAGs are unrelated to tissue-level viscoelastic mechanics in mature human MCL. These findings narrow the possible number of extracellular matrix molecules that have a direct contribution to ligament viscoelasticity.
Long-loop pathways in cardiovascular electroacupuncture responses
Authors: Li Peng , Tjen-A-Looi Stephanie C. , Guo Zhi-Ling , Fu Liang-Wu , Longhurst John C.
Published: December 2008

We have shown that electroacupuncture (EA) at P 5–6 (overlying median nerves) activates arcuate (ARC) neurons, which excite the ventrolateral periaqueductal gray (vlPAG) and inhibit cardiovascular sympathoexcitatory neurons in the rostral ventrolateral medulla (rVLM). To investigate whether the ARC inhibits rVLM activity directly or indirectly, we stimulated the splanchnic nerve to activate rVLM neurons. Micropipettes were inserted in the rVLM, vlPAG, and ARC for neural recording or injection. Microinjection of kainic acid (KA; 1 mM, 50 nl) in the ARC blocked EA inhibition of the splanchnic nerve stimulation-induced reflex increases in rVLM neuronal activity. Microinjection of d,l-homocysteic acid (4 nM, 50 nl) in the ARC, like EA, inhibited reflex increases in the rVLM neuronal discharge. The vlPAG neurons receive convergent input from the ARC, splanchnic nerve, P 5–6, and other acupoints. Microinjection of KA bilaterally into the rostral vlPAG partially reversed rVLM neuronal responses and cardiovascular inhibition during d,l-homocysteic acid stimulation of the ARC. On the other hand, injection of KA into the caudal vlPAG completely reversed these responses. We also observed that ARC neurons could be antidromically activated by stimulating the rVLM, and that ARC perikarya was labeled with retrograde tracer that had been microinjected into the rVLM. These neurons frequently contained β-endorphin and c-Fos, activated by EA stimulation. Therefore, the vlPAG, particularly, the caudal vlPAG, is required for ARC inhibition of rVLM neuronal activation and subsequent EA-related cardiovascular activation. Direct projections from the ARC to the rVLM, which serve as an important source of β-endorphin, appear also to exist.
mTOR Regulates Vascular Smooth Muscle Cell Differentiation From Human Bone Marrow–Derived Mesenchymal Progenitors
Authors: Hegner Björn , Lange Maria , Kusch Angelika , Essin Kirill , Sezer Orhan , Schulze-Lohoff Eckhard , Luft Friedrich C. , Gollasch Maik , Dragun Duska
Published: December 2008

Objective—

Vascular smooth muscle cells (VSMCs) and circulating mesenchymal progenitor cells (MSCs) with a VSMC phenotype contribute to neointima formation and lumen loss after angioplasty and during allograft arteriosclerosis. We hypothesized that phosphoinositol-Akt-mammalian target of rapamycin-p70S6 kinase (PI3K/Akt/mTOR/p70S6K) pathway activation regulates VSMC differentiation from MSCs.

Methods and Results—

We studied effects of PI3K/Akt/mTOR signaling on phenotypic modulation of MSC and VSMC marker expression, including L-type Ca(2+) channels. Phosphorylation of Akt and p70S6K featured downregulation of VSMC markers in dedifferentiated MSCs. mTOR inhibition with rapamycin at below pharmacological concentrations blocked p70S6K phosphorylation and induced a differentiated contractile phenotype with smooth muscle (sm)-calponin, sm-α-actin, and SM protein 22-alpha (SM22α) expression. The PI3K inhibitor Ly294002 abolished Akt and p70S6K phosphorylation and reversed the dedifferentiated phenotype via induction of sm-calponin, sm-α-actin, SM22α, and myosin light chain kinase. Rapamycin acted antiproliferative without impairing MSC viability. In VSMCs, rapamycin increased a homing chemokine for MSCs, stromal cell–derived factor-1–alpha, at mRNA and protein levels. The CXCR4-mediated MSC migration toward conditioned medium of rapamycin-treated VSMCs was enhanced.

Conclusions—

We describe novel pleiotropic effects of rapamycin at very low concentrations that stabilized differentiated contractile VSMCs from MSCs in addition to exerting antiproliferative and enhanced homing effects.
Estrogen Attenuates Left Ventricular and Cardiomyocyte Hypertrophy by an Estrogen Receptor–Dependent Pathway That Increases Calcineurin Degradation
Authors: Donaldson Cameron , Eder Sarah , Baker Corey , Aronovitz Mark J. , Weiss Alexandra Dabreo , Hall-Porter Monica , Wang Feng , Ackerman Adam , Karas Richard H. , Molkentin Jeffery D. , Patten Richard D.
Published: December 2008

Left ventricular (LV) hypertrophy commonly develops in response to chronic hypertension and is a significant risk factor for heart failure and death. The serine-threonine phosphatase calcineurin (Cn)A plays a critical role in the development of pathological hypertrophy. Previous experimental studies in murine models show that estrogen limits pressure overload–induced hypertrophy; our purpose was to explore further the mechanisms underlying this estrogen effect. Wild-type, ovariectomized female mice were treated with placebo or 17β-estradiol (E2), followed by transverse aortic constriction (TAC), to induce pressure overload. At 2 weeks, mice underwent physiological evaluation, immediate tissue harvest, or dispersion of cardiomyocytes. E2 replacement limited TAC-induced LV and cardiomyocyte hypertrophy while attenuating deterioration in LV systolic function and contractility. These E2 effects were associated with reduced abundance of CnA. The primary downstream targets of CnA are the nuclear factor of activated T-cell (NFAT) family of transcription factors. In transgenic mice expressing a NFAT-activated promoter/luciferase reporter gene, E2 limited TAC-induced activation of NFAT. Moreover, the inhibitory effects of E2 on LV hypertrophy were absent in CnA knockout mice, supporting the notion that CnA is an important target of E2-mediated inhibition. In cultured rat cardiac myocytes, E2 inhibited agonist-induced hypertrophy while also decreasing CnA abundance and NFAT activation. Agonist stimulation also reduced CnA ubiquitination and degradation that was prevented by E2; all in vitro effects of estrogen were reversed by an estrogen receptor (ER) antagonist. These data support that E2 reduces pressure overload induced hypertrophy by an ER-dependent mechanism that increases CnA degradation, unveiling a novel mechanism by which E2 and ERs regulate pathological LV and cardiomyocyte growth.
Postoperative Cortical Neural Loss Associated With Cerebral Hyperperfusion and Cognitive Impairment After Carotid Endarterectomy
Authors: Chida Kohei , Ogasawara Kuniaki , Suga Yasunori , Saito Hideo , Kobayashi Masakazu , Yoshida Kenji , Otawara Yasunari , Ogawa Akira
Published: December 2008

Background and Purpose—

Although cerebral hyperperfusion after carotid endarterectomy (CEA) often impairs cognitive function, MRI does not always demonstrate structural brain damage associated with postoperative cognitive impairment. The purpose of the present study was to determine whether postoperative cortical neural loss, which can be detected by
123
I-iomazenil single-photon emission CT, is associated with cerebral hyperperfusion after CEA and whether it correlates with postoperative cognitive impairment.

Methods—

In 60 patients undergoing CEA for ipsilateral internal carotid artery stenosis (>70%), cerebral blood flow was measured using
N
-isopropyl-
p
-[
123
I]-iodoamphetamine single-photon emission CT before and immediately after CEA and on the third postoperative day. The distribution of benzodiazepine receptor binding potential in the cerebral cortex was assessed using
123
I-iomazenil single-photon emission CT before and 1 month after surgery and was analyzed using 3-dimensional stereotactic surface projection. Neuropsychological testing was also performed preoperatively and at the first postoperative month.

Results—

Post-CEA hyperperfusion and postoperative cognitive impairment were observed in 9 patients (15%) and 8 patients (13%), respectively. Post-CEA hyperperfusion was significantly associated with postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 2.765 to 148.804;
P
=0.0031). Post-CEA hyperperfusion (95% CIs, 1.183 to 229.447;
P
=0.0370) and postoperative hemispheric reduction of benzodiazepine receptor binding potential (95% CIs, 1.003 to 77.381;
P
=0.0496) were also significantly associated with postoperative cognitive impairment.

Conclusions—

Cerebral hyperperfusion after CEA results in postoperative cortical neural loss that correlates with postoperative cognitive impairment.
U.S. Public Diplomacy in the Arab World
Authors: Cherribi Sam
Published: December 2008

This article explores the ways in which the debut of Undersecretary for State and Public Diplomacy Karen Hughes was covered in the Arab media. Her outreach efforts to market and rebrand the image of America in the Arab world were announced proudly on the Arab satellite television network Al-Jazeera before the news spread to other Arab media outlets. In making Al-Jazeera the preeminent choice for her first appearance to launch the campaign to win the hearts and minds of Arab publics, Karen Hughes implicitly and explicitly endorses or at the very least subscribes to part of Al-Jazeera's agenda. Through the choice of Al-Jazeera as gateway to the Arab public, Karen Hughes waters down her own opinions and in this case made concessions regarding vital policy issues of the U.S. administration.
Public Diplomacy
Authors: Crane Melinda
Published: December 2008

This article discusses public diplomacy as practiced via the medium of television current affairs programs. Examples from recent years show how effective this format can be for U.S. politicians to communicate with the German public. The article stems from the remarks made by the author at a panel session in Dresden, Germany, on “Media and Transatlantic Relations,” sponsored by The Claus M. Halle Institute for Global Learning.
Interactive Visualization of Assessment Data
Authors: Ünlü Ali , Sargin Anatol
Published: December 2008

Mondrian is state-of-the-art statistical data visualization software featuring modern interactive visualization techniques for a wide range of data types. This article reviews the capabilities, functionality, and interactive properties of this software package. Key features of Mondrian are illustrated with data from the Programme for International Student Assessment (PISA) and for item analysis applications.
Paroxetine-induced increase in LDL cholesterol levels
Authors: Le Melledo JM , Mailo K , Lara N , Abadia MC , Gil L , Van Ameringen M , Baker G , Perez-Parada J
Published: December 2008

Abstract

Paroxetine is widely prescribed because it has the indication for multiple psychiatric disorders. Our objective was to assess the effect of short-term administration of paroxetine on low-density lipoprotein cholesterol (LDL-C) levels in both healthy controls (HCs) and in patients with panic disorder (PD). Blood samples for measurement of LDL-C were collected atbaseline, after 8 weeks of paroxetine administration and post-discontinuation in 24 male HCs and nine male patients suffering from PD, for a total of 33 subjects. Paroxetine treatment, both in HCs and PD patients, induced a mean 9% increase per subject in LDL-C that normalized post-discontinuation, suggesting causality. The National Cholesterol Education Program (NCEP) guidelines suggest that this paroxetine-induced increase in LDL-C is clinically significant but would not warrant therapeutic intervention in this population selected to be at low cardiovascular risk. However, the increase in LDL-C levels raised above the threshold of 2.7 mmol/L (100 mg/dL) in 36% of our low-risk subjects. The LDL-C increase in this subgroup would be associated with a minor increase in coronary heart disease (CHD) risk. A similar 9% paroxetine-induced increase in LDL-C observed in the large number of psychiatric patients suffering from comorbid established CHD would be detrimental from a cardiovascular perspective and would oppose the new NCEP therapeutic goals of decreasing LDL-C levels by 30–40% in high and moderately high-risk patients. It is possible that longer treatment duration and use of higher doses of paroxetine would lead to a greater increase in LDL-C.
Plasma free tryptophan revisited: what you need to know and do before measuring it
Authors: Badawy AA-B
Published: December 2008

Plasma free tryptophan (Trp) is an important peripheral parameter widely used by psychopharmacologists to assess Trp entry into the brain for cerebral serotonin synthesis, although, along with total Trp, it can give much more information on Trp metabolism and disposition. Plasma free Trp is, however, a labile parameter easily influenced by a great many modulators, including fasting, food intake, many prescribed and over the counter medications, consumption of alcoholic and of common hot beverages, illicit drug use, some hormones, exercise and mild stressors. Interpretation of changes in plasma free Trp requires appropriate preparation of ultrafiltrates from freshly isolated plasma or serum, accurate analytical methodology and awareness of the multitude of physiological and pharmacological modulators of its concentration. This article highlights these points and makes recommendations aimed at avoiding pitfalls in studies involving this parameter.
Lamotrigine augmentation in schizophrenia and schizoaffective patients with obsessive-compulsive symptoms
Authors: Poyurovsky M. , Glick I. , Koran LM
Published: December 2008

Obsessive-compulsive symptoms (OCS) are clinically important phenomena in schizophrenia patients. Lamotrigine has a modulating effect on glutamatergic neurotransmission relevant to pathophysiology of both schizophrenia and OCD. Efficacy and tolerability of lamotrigine in schizophrenia and schizoaffective patients with comorbid OCS were evaluated. In an 8-week, open-label trial, lamotrigine (25 mg/day for 1 week, 50 mg for 2 weeks, 100 mg for 2 weeks, 200 mg for 3 weeks) was added to ongoing psychotropic drug regimens in schizophrenia (N = 5) and schizoaffective disorder (N = 6) patients with clinically significant OCS [Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) score > 16]. The Y-BOCS score for nine completers decreased significantly from baseline to week 8 (22.9 ± 6.1 vs 17.4 ± 3.6; t = 2.33, df = 1, P = 0.033). Five patients, all with schizoaffective disorder, were responders (≥35% decrease in Y-BOCS score). No significant changes were detected in schizophrenia symptom severity. Depressive symptoms, assessed with the Calgary Depression Rating Scale, improved significantly (6.4 ± 1.5 vs 4.0 ± 2.5; t = 3.19, df = 1, P = 0.013); this change positively correlated with OCS improvement (r = 0.69, P = 0.04). Lamotrigine was safe and well tolerated. Explicit evaluation of therapeutic efficacy of adjunctive lamotrigine in schizoaffective disorder patients with comorbid OCS merits further investigation.
Ziprasidone in the treatment of acute mania: a 12-week, placebo-controlled, haloperidol-referenced study
Authors: Vieta E. , Ramey T. , Keller D. , English PA , Loebel AD , Miceli J.
Published: December 2008

This 12-week, double-blind, two-part study in 438 adults with bipolar-associated acute mania began with a 3-week period comparing ziprasidone (80—160 mg/day) and placebo with haloperidol (8—30 mg/day) as active reference. Changes from baseline Mania Rating Scale (MRS) scores for ziprasidone and haloperidol were superior to placebo from day 2 (P = 0.001) to week 3 (P < 0.001); change from baseline at week 3 was greater for haloperidol than ziprasidone (P ≤ 0.001). At week 3, the response rate (≥50% decrease from baseline MRS score) was 36.9, 54.7 and 20.5% for ziprasidone, haloperidol and placebo, respectively (P ≤ 0.05, active treatments versus placebo and ziprasidone versus haloperidol). In the 9-week extension phase, ziprasidone replaced placebo to examine tolerability. Maintenance of improvement was evaluated for ziprasidone (40—160 mg/day) or haloperidol (4—30 mg/day). Responses were maintained through the last visit for 88.1% receiving ziprasidone and 96.3% receiving haloperidol. More patients receiving haloperidol than ziprasidone discontinued treatment during weeks 4—12 (21.1% versus 9.6%) and had significantly higher rates of movement disorders. Mean doses of ziprasidone and haloperidol for the first 3-week and 9-week extension were 116.2 mg/day and 121.4 mg/day and 16.0 mg/day and 16.1 mg/day, respectively. Ziprasidone was shown to be effective monotherapy for acute treatment of bipolar mania. Although haloperidol showed greater efficacy, ziprasidone showed a superior tolerability profile.
The effects of acute tryptophan depletion on affective behaviour and cognition in Brown Norway and Sprague Dawley rats
Authors: Jans LAW , Korte-Bouws GAH , Korte SM , Blokland A.
Published: December 2008

Previous studies in rats and humans have shown that the essential amino acid tryptophan (TRP) is depleted after consumption of a gelatin-based protein-carbohydrate mixture, which is lacking L-tryptophan (TRP−). In rats, TRP depletion caused impaired object recognition but only had a modest effect on affective behaviour. Because these studies were preformed with Wistar rats, the aim of the present experiment was to evaluate strain differences in behavioural responses to acute TRP depletion between Brown Norway (BN) and Sprague Dawley (SD) rats. The rats were repeatedly treated with TRP− or a balanced control (TRP+) and were tested in tests of anxiety- and depression-related behaviour (open-field test, home cage emergence test, social interaction test, forced swim test) and memory. SD rats, but not BNs, showed more anxiety- and depression-related behaviour and impaired object recognition after TRP− treatment. There was a dissociation between plasma TRP levels, central 5-HT concentrations and 5-HIAA/5-HT turnover. Both strains showed about 60% decrease in plasma TRP/ΣLNAA levels, whereas hippocampal 5-HT levels were lower after TRP− in BN but not SD rats. Conversely, 5-HIAA/5-HT turnover was lower after TRP− in SD but not BN rats, suggesting a dissociation between 5-HT storage and release in SDs. The present study suggests that acute tryptophan depletion effects are strain dependent on the behavioural and the neurochemical level.
Housekeeping gene expression is affected by antidepressant treatment in a mouse fibroblast cell line
Authors: Sugden K. , Pariante CM , McGuffin P. , Aitchison KJ , D'Souza UM
Published: December 2008

Quantitative real-time polymerase chain reaction (PCR) is an effective approach in investigating the effects of exogenous compounds on gene expression. This is often achieved by exploiting so-called ‘housekeeping’ genes as baseline controls to normalise expression levels, which have historically been assumed to have a relatively stable expression pattern. Recent non-in-vitro studies have questioned the validity of this, but previous in-vitro data were lacking following antidepressant treatment. We here investigated the stability of 12 housekeeping genes during treatment of the mouse L929 fibroblast cell line with escitalopram and nortriptyline. Cells were cultured in the presence of antidepressant at 1 μM or 10 μM for 30 min, 24 h or 48 h, and RNA subjected to quantitative PCR (qPCR). Stability of relative transcript expression values was assessed via gene-gene expression ratios and intra- and inter-group variation (using geNorm and NormFinder programs). The three most stable transcripts were adenosine triphosphate (ATP) synthase, H+ transporting mitochondrial F1 complex, β subunit, β-2 microglobulin and cytochrome c-1. The least stable were Gapdh, eukaryotic translation initiation factor 4A2 and Calnexin (Canx). In conclusion, care must be taken when choosing reference transcripts for analysis in qPCR. For in-vitro pharmacological studies, it should not be assumed that ‘housekeeping’ genes are stable.
``A More Definite System''
Authors: Boothman Barry E. C.
Published: December 2008

Examinations of the rise of modern retail activities traditionally have emphasized developments in the United States, where firms could exploit strong economies of scale and scope and could service transcontinental markets. In middle-sized economies such as Canada, the opportunities for expansion were more limited and firms often were slower to adopt new modes of marketing organization. This study reappraises the rise of large retailers in the Canadian grocery industry during the interwar era. It provides an overview of the issues that propelled the formation of the firms, their organizational traits, and the factors that slowed the ability of the firms to achieve market dominance.
Mutation Analysis in a Population-Based Cohort of Boys With Duchenne or Becker Muscular Dystrophy
Authors: Cunniff Christopher , Andrews Jennifer , Meaney F. John , Mathews Katherine D. , Matthews Dennis , Ciafaloni Emma , Miller Timothy M. , Bodensteiner John B. , Miller Lisa A. , James Katherine A. , Druschel Charlotte M. , Romitti Paul A. , Pandya Shree
Published: December 2008

The type and frequency of diagnostic testing was analyzed in a population-based cohort of boys with Duchenne muscular dystrophy or Becker muscular dystrophy. Use of muscle biopsy declined from 66.0% of boys born between January 1982 and September 1987 to 32.6% born between April 1999 and September 2004. DMD mutation was documented for 345 (73.4%) boys. Deletions were more common and point mutations were less common than that has been reported in specialty clinic or laboratory-based cohorts. Deletion of one or more exons was detected in 270 individuals (57.4% of all patients and 78.3% with a DMD mutation). Duplication was identified in 39 individuals (8.3% of all patients and 11.3% with a DMD mutation). Point mutation, small insertion, or small deletion was found in 36 individuals (7.7% of all patients and 10.4% with a DMD mutation). Point mutation analysis was performed in only 37 of 130 (28.5%) individuals with negative deletion and/or duplication testing.
Review Paper: A Review of the Cellular Response on Electrospun Nanofibers for Tissue Engineering
Authors: Nisbet D.R. , Forsythe J.S. , Shen W. , Finkelstein D.I. , Horne M.K.
Published: December 2008

Electrospinning has been employed extensively in tissue engineering to generate nanofibrous scaffolds from either natural or synthetic biodegradable polymers to simulate the cellular microenvironment. Electrospinning rapidly produces fibers of the nanolength scale and the process offers many opportunities to tailor the physical, chemical, and biological properties of a material for specific applications and cellular environments. There is growing evidence that nanofibers amplify certain biological responses such as contact guidance and differentiation, however this has not been fully exploited in tissue engineering. This review addresses the cellular interactions with electrospun scaffolds, with particular focus on neural, bone, cartilage, and vascular tissue regeneration. Some aspects of scaffold design, including architectural properties, surface functionalization and materials selection are also addressed.
The Narcotics Initiative
Authors: McCabe James E.
Published: December 2008

In the mid-1990s, the New York City Police Department (NYPD) developed a new approach to address drug conditions called the narcotics initiative. Centered on a three-prong enforcement strategy, the initiatives were concentrated in specific clusters of precincts and successively deployed over a period of several years throughout New York City. This study examines the impact of two initiatives deployed in Queens County, NY, and examines the effectiveness of the initiatives based on the decrease in crime and increase in enforcement associated with their deployment. Hierarchical linear modeling (HLM) is used to examine the data, and the results showed limited impact in community conditions after the initiatives were deployed.
Making Meaningful Connections
Authors: Kobayashi Karen M. , Cloutier-Fisher Denise , Roth Marilyn
Published: December 2008

Objective: The objectives of the study are: (a) to develop a profile of socially isolated older adults (SIOA) in British Columbia (BC) based on sociodemographic and health characteristics and (b) to examine whether SIOA under-or overutilize health care services. Method: This study uses telephone interview data collected from a random sample of 1,064 older adults (65+) in BC. The sample was identified using established criteria from the six-item Lubben Social Network Scale. Results: The results indicate that 17% of the sample is socially isolated. To summarize, the strongest predictors of social isolation are income, gender, marital status, self-rated health, length of residence, and home ownership. Further analysis indicates that SIOA were not more inclined to overuse health services. Discussion: The findings underscore the importance of understanding differential profiles of need and service use for SIOA within broader social contexts, and are discussed in terms of their implications for health care policy and program planning for this vulnerable population.
Deepening Learning and Inspiring Rigor
Authors: Orpett Long Susan , Akande Yemi Susan , Purdy R.W. , Nakano Keiko
Published: December 2008

American students are increasingly incorporating study in a foreign country into their college educations, but many participate in short-term programs that limit their engagement with any more than the superficial aspects of the host culture. This article describes a short-term study abroad course for American students to Japan in which the authors drew on an “emic” host country model of group travel in an effort to combine high academic standards, personal growth, and deepened engagement with Japanese culture. The authors first consider the history of study tours in U.S. study abroad and then look at an alternative model provided by Japanese school trips. The authors explain the process by which their American students read, research, and work in groups to plan the itinerary for their study tour. The final section reports on their preliminary evaluations of the program and their plans for future excursions sponsored by the East Asian Studies program.
Massage Therapy for Children With Cancer
Authors: Post-White Janice , Fitzgerald Maura , Savik Kay , Hooke Mary C. , Hannahan Anne B. , Sencer Susan F.
Published: December 2008

This pilot study aimed to determine the feasibility of providing massage to children with cancer to reduce symptoms in children and anxiety in parents. Twenty-three children/parent dyads were enrolled; 17 completed all data points. Children with cancer, ages 1 to 18 years, received at least 2 identical cycles of chemotherapy, and one parent, participated in the 2-period crossover design in which 4 weekly massage sessions alternated with 4 weekly quiet-time control sessions. Changes in relaxation (heart and respiratory rates, blood pressure, and salivary cortisol level) and symptoms (pain, nausea, anxiety, and fatigue) were assessed in children; anxiety and fatigue were measured in parents. Massage was more effective than quiet time at reducing heart rate in children, anxiety in children less than age 14 years, and parent anxiety. There were no significant changes in blood pressure, cortisol, pain, nausea, or fatigue. Children reported that massage helped them feel better, lessened their anxiety and worries, and had longer lasting effects than quiet time. Massage in children with cancer is feasible and appears to decrease anxiety in parents and younger children.