bluuebunny/crossref_metadata_2025 huggingface dataset:
31P NMR and ESI-MS studies of metal ion-phosphorus pesticide residue complexes
Authors: Koo In Sun , Ali Dildar , Yang Kiyull , Park Yong , Esbata Abdelhamid , vanLoon Gary W. , Buncel Erwin
Published: February 2009

31P NMR and ESI-MS structural studies have been carried out for O,O-dimethylphosphorothioate anion (PA–) interacting with Ag+, Hg2+, and Na+ cations. Evidence is presented for the formation of PA–···Ag+ and PA–···Hg2+ metal complexes and for ionic PA–Na+, with 31P chemical shift values of 43, 40, and 65 ppm, respectively. The 31P chemical shifts for PA–···Ag+ and PA–···Hg2+ complexes exhibit an initial sharp rise as the [Ag+]/[PA] and [Hg2+]/[PA] ratio increases from 0 to 1.0 and 0 to 0.5, respectively, and remain almost constant beyond these ratios. These results indicate the formation of 1:1 PA–···Ag+ and 2:1 (PA–)2···Hg2+ complexes. Electrospray ionization mass spectroscopy (ESI-MS) revealed peaks corresponding to [O-P(=S)(OCH3)2 + Ag + H]+ and {2[O-P(=S)(OCH3)2] + Hg + H}+ for PAH interacting with Ag+ and Hg2+, supporting the 1:1 PA–···Ag+ and 2:1 (PA–)2···Hg2+ stoichiometry. The experimental results support the predominance of species with greater P=O double bond and P–S single bond character, relative to P-O/P=S. Our results on 31P NMR chemical shifts have a bearing on the use of 31P chemical shifts as a tool for organophosphorus pesticide identification.
Investigations of the supramolecular host properties of a fluorescent bistren cage compound
Authors: Boland Patricia G. , Accardi Sara J. , Snow Carrie A. , Wagner Brian D.
Published: February 2009

The host properties of a bistren cage compound, previously reported to be an efficient anion sensor, are shown to include encapsulation of small aromatic guest molecules. It is also shown that the intrinsic fluorescence of this cage compound, arising from the anthracenyl moiety in its structure, is sensitive to the encapsulation of aromatic guests in aqueous solution and can be used to measure the binding constants for any such guest. This makes this bistren cage a rare example of a fluorescent host for aromatic guests, and suggests potential applications of this compound as a versatile fluorescent sensor for a variety of guests of interest. The binding of a number of benzene derivatives was studied; these were all found to form 1:2 host–guest inclusion complexes with a wide range in total binding constants (K1K2), from 6.4 × 103 to 3.5 × 107 (mol/L)–2, indicating a significant degree of selectivity for different benzene derivatives. The binding strength was found to depend on both the guest polarity and aqueous solubility.
Comparing the fragmentation chemistry of gas-phase adducts of poly(dimethylsiloxane) oligomers with metal and organic ions
Authors: Renaud Justin , Alhazmi Abdulhrahman M. , Mayer Paul M.
Published: February 2009

Gas-phase ions of poly(dimethylsiloxane) oligomers were formed by electrospray ionization either by protonating them in solution with formic acid or by generating adducts of the oligomers with the metal ions Li+, Na+, K+, and Ag+ as well as with the organic cations NH4+, CH3CH2NH3+, and protonated glycine, aspartic acid, and 1,2-diphenylethylamine. The collision-induced fragmentation of the oligomeric ions was strongly dependent on the nature of the charging species. Ag+ adducts dissociated in a manner previously observed in secondary ion mass spectrometry experiments generating a series of linear and cyclic fragment ions, while Li+ adducts fragmented to form two ions: an adduct of the metal ion with the oligomer end-group and one with the remaining oligomer. Na+ and K+ adducts simply dissociate to form the bare metal ion. The organic species, to varying extents, transfer the proton to the oligomer to form a protonated poly(siloxane) ion. These protonated oligomers then dissociate at very low laboratory-frame collision energy along the siloxane backbone by loss of a silanol. These backbone fragments can then lose a methyl group to form a second series of fragment ions. Suggestions for probable mechanistic pathways for these processes are presented.
ABSOLUTE NEUTRINO MASS FROM HELICITY MEASUREMENTS
Authors: NISHI C. C.
Published: February 2009

The possibility to access the absolute neutrino mass scale through the measurement of the wrong helicity contribution of charged leptons is investigated in pion decay. Through this method, one may have access to the same effective mass [Formula: see text] extractable from the tritium beta decay experiments for electron neutrinos as well as the analogous effective mass [Formula: see text] for muon neutrinos. In the channel [Formula: see text], the relative probability of producing an antineutrino with left helicity is enhanced if compared with the naive expectation (mν/2Eν)2. The possibility to constrain new interactions in the context of two-Higgs-Doublet models is also investigated.
DAMA/LIBRA FINDINGS URGE REPLACEMENT OF THE WIMP HYPOTHESES BY THE DAEMON PARADIGM AS A BASIS FOR EXPERIMENTAL STUDIES OF DM OBJECTS
Authors: DROBYSHEVSKI E. M.
Published: February 2009

The simplest version of the daemon paradigm suggests the modulated 2–6-keV range events in DAMA/NaI and DAMA/LIBRA detectors are caused by the iodine ions knocked out elastically by the electrically neutral c-daemons moving with V = 30–50 km/s (c-daemon is a complex of negative daemon located in a remainder of formerly captured nucleus where the daemon decomposes nucleons one by one with ~ 10-6 s mean interval). Furthermore, after the 2–6 keV event occurred, in subsequent ~ 10-6 s, the c-daemon (which becomes negative during this time) recaptures new nucleus with resulting scintillations in ~ 10 MeV range! The last possibility was so far overlooked in the experiments as it did not stem from WIMP hypotheses. A modification of the NaI(Tl) experiments is suggested for revealing the effect described. Independently of the outcome, any obtained result will be important for refining the daemon paradigm further on.
The Functions and Roles of the Extracellular Ca2+–Sensing Receptor along the Gastrointestinal Tract
Authors: Geibel John P. , Hebert Steven C.
Published: February 2009

Digestion of food and normal salt and water homeostasis in the body require a functional digestive tract. Recently an increasing number of studies have demonstrated a role for the calcium-sensing receptor along the entire gastrointestinal tract and its role in normal gut physiology. Detailed studies have been performed on colonic fluid transport and gastric acid secretion. We have now demonstrated that the receptor can modulate fluid secretion and absorption along the intestine and can thereby be a potent target to prevent secretory diarrhea. Recent studies have demonstrated that organic nutrients such as polyamines and l-amino acids can act as agonists by allosterically modifying the receptor. Thus, the receptor may detect nutrient availability to epithelial cells along the gastrointestinal tract and may be involved in the coordinated rapid turnover of the intestinal epithelium. Furthermore, the receptor has been suggested as a link for the mechanisms leading to calcium uptake by the colon and may thus reduce the risk for colon cancer.
Sensing Odorants and Pheromones with Chemosensory Receptors
Authors: Touhara Kazushige , Vosshall Leslie B.
Published: February 2009

Olfaction is a critical sensory modality that allows living things to acquire chemical information from the external world. The olfactory system processes two major classes of stimuli: (a) general odorants, small molecules derived from food or the environment that signal the presence of food, fire, or predators, and (b) pheromones, molecules released from individuals of the same species that convey social or sexual cues. Chemosensory receptors are broadly classified, by the ligands that activate them, into odorant or pheromone receptors. Peripheral sensory neurons expressing either odorant or pheromone receptors send signals to separate odor- and pheromone-processing centers in the brain to elicit distinct behavioral and neuroendocrinological outputs. General odorants activate receptors in a combinatorial fashion, whereas pheromones activate narrowly tuned receptors that activate sexually dimorphic neural circuits in the brain. We review recent progress on chemosensory receptor structure, function, and circuitry in vertebrates and invertebrates from the point of view of the molecular biology and physiology of these sensory systems.
Activation of guanylate cyclase C signaling pathway protects intestinal epithelial cells from acute radiation-induced apoptosis
Authors: Garin-Laflam M. P. , Steinbrecher K. A. , Rudolph J. A. , Mao J. , Cohen M. B.
Published: February 2009

Uroguanylin (UGN) is a peptide hormone that binds to and activates the intestinal epithelial cell (IEC) transmembrane receptor guanylate cyclase C (GC-C), which in turn increases intracellular cGMP. Gene targeting of murine UGN or GC-C results in significantly lower levels of cGMP in IECs. On the basis of effects of cGMP in nonintestinal systems, we hypothesized that loss of GC-C activation would increase intestinal epithelial apoptosis following radiation-induced injury. We first compared apoptosis from the proximal jejunum of C57BL/6 wild-type (WT) and GC-C knockout (KO) mice 3 h after they received 5 Gy of γ-irradiation. We then investigated whether supplementation via intraperitoneal injection of 1 mM 8BrcGMP would mitigate radiation-induced apoptosis in these experimental animals. Identical experiments were performed in BALB/c UGN WT and KO mice. Apoptosis was assessed by quantitating morphological indications of cell death, terminal dUTP nick-end labeling, and cleaved caspase 3 immunohistochemistry. Both UGN KO and GC-C KO mice were more susceptible than their WT littermates in this in vivo model of apoptotic injury. Furthermore, cGMP supplementation in both GC-C and UGN KO animals ameliorated radiation-induced apoptosis. Neither WT strain demonstrated significant alteration in apoptotic susceptibility as a result of cGMP supplementation before radiation injury. These in vivo findings demonstrate increased radiosensitivity of IECs in UGN and GC-C KO mice and a role for cGMP as a primary downstream mediator of GC-C activation in the protection of these IECs from radiation-induced apoptosis.
Acetylcholine-induced activation of M3 muscarinic receptors stimulates robust matrix metalloproteinase gene expression in human colon cancer cells
Authors: Xie Guofeng , Cheng Kunrong , Shant Jasleen , Raufman Jean-Pierre
Published: February 2009

Previously, we showed that ACh-induced proliferation of human colon cancer cells is mediated by transactivation of epidermal growth factor (EGF) receptors (EGFRs). In the present study, we elucidate the molecular mechanism underlying this action. ACh-induced proliferation of H508 colon cancer cells, which express exclusively M3 muscarinic receptors (M3Rs), was attenuated by anti-EGFR ligand binding domain antibody, a broad-spectrum matrix metalloproteinase (MMP) inhibitor, anti-MMP7 antibody, a diphtheria toxin analog that blocks release of an EGFR ligand [heparin-binding EGF-like growth factor (HBEGF)], and anti-HBEGF antibody. Conditioned media from ACh-treated H508 cells induced proliferation of SNU-C4 colon cancer cells that express EGFR but not M3R. These actions were attenuated by an EGFR inhibitor and by anti-EGFR and anti-HBEGF antibodies. In H508, but not SNU-C4, colon cancer cells, ACh caused a striking dose- and time-dependent increase in levels of MMP7 mRNA and MMP7 protein. Similarly, ACh induced robust MMP1 and MMP10 gene transcription. ACh-induced MMP1, MMP7, and MMP10 gene transcription was attenuated by atropine, anti-EGFR antibody, and chemical inhibitors of EGFR and ERK activation. In contrast, inhibitors of phosphatidylinositol 3-kinase and NF-κB activation did not alter MMP gene transcription. Collectively, these findings indicate that MMP7-catalyzed release of HBEGF mediates ACh-induced transactivation of EGFR and consequent proliferation of colon cancer cells. ACh-induced activation of EGFR and downstream ERK signaling also regulates transcriptional activation of MMP7, thereby identifying a novel feed-forward mechanism for neoplastic cell proliferation.
Intramuscular metabolism during low-intensity resistance exercise with blood flow restriction
Authors: Suga Tadashi , Okita Koichi , Morita Noriteru , Yokota Takashi , Hirabayashi Kagami , Horiuchi Masahiro , Takada Shingo , Takahashi Tomohiro , Omokawa Masashi , Kinugawa Shintaro , Tsutsui Hiroyuki
Published: February 2009

Although recent studies have reported that low-intensity resistance training with blood flow restriction could stress the muscle effectively and provide rapid muscle hypertrophy and strength gain equivalent to those of high-intensity resistance training, the exact mechanism and its generality have not yet been clarified. We investigated the intramuscular metabolism during low-intensity resistance exercise with blood flow restriction and compared it with that of high-intensity and low-intensity resistance exercises without blood flow restriction using 31P-magnetic resonance spectroscopy. Twenty-six healthy subjects (22 ± 4 yr) participated and performed unilateral plantar flexion (30 repetitions/min) for 2 min. Protocols were as follows: low-intensity exercise (L) using a load of 20% of one-repetition maximum (1 RM), L with blood flow restriction (LR), and high-intensity exercise using 65% 1 RM (H). Intramuscular phosphocreatine (PCr) and diprotonated phosphate (H2PO4−) levels and intramuscular pH at rest and during exercise were obtained. We found that the PCr depletion, the H2PO4− increase, and the intramuscular pH decrease during LR were significantly greater than those in L ( P < 0.001); however, those in LR were significantly lower than those in H ( P < 0.001). The recruitment of fast-twitch fiber evaluated by inorganic phosphate splitting occurred in only 31% of the subjects in LR, compared with 70% in H. In conclusion, the metabolic stress in skeletal muscle during low-intensity resistance exercise was significantly increased by applying blood flow restriction, but did not generally reach that during high-intensity resistance exercise. This new method of resistance training needs to be examined for optimization of the protocol to reach equivalence with high-intensity resistance training.
The GABAAagonist muscimol attenuates induced airway constriction in guinea pigs in vivo
Authors: Gleason Neil R. , Gallos George , Zhang Yi , Emala Charles W.
Published: February 2009

GABAAchannels are ubiquitously expressed on neuronal cells and act via an inward chloride current to hyperpolarize the cell membrane of mature neurons. Expression and function of GABAAchannels on airway smooth muscle cells has been demonstrated in vitro. Airway smooth muscle cell membrane hyperpolarization contributes to relaxation. We hypothesized that muscimol, a selective GABAAagonist, could act on endogenous GABAAchannels expressed on airway smooth muscle to attenuate induced increases in airway pressures in anesthetized guinea pigs in vivo. In an effort to localize muscimol's effect to GABAAchannels expressed on airway smooth muscle, we pretreated guinea pigs with a selective GABAAantagonist (gabazine) or eliminated lung neural control from central parasympathetic, sympathetic, and nonadrenergic, noncholinergic (NANC) nerves before muscimol treatment. Pretreatment with intravenous muscimol alone attenuated intravenous histamine-, intravenous acetylcholine-, or vagal nerve-stimulated increases in peak pulmonary inflation pressure. Pretreatment with the GABAAantagonist gabazine blocked muscimol's effect. After the elimination of neural input to airway tone by central parasympathetic nerves, peripheral sympathetic nerves, and NANC nerves, intravenous muscimol retained its ability to block intravenous acetylcholine-induced increases in peak pulmonary inflation pressures. These findings demonstrate that the GABAAagonist muscimol acting specifically via GABAAchannel activation attenuates airway constriction independently of neural contributions. These findings suggest that therapeutics directed at the airway smooth muscle GABAAchannel may be a novel therapy for airway constriction following airway irritation and possibly more broadly in diseases such as asthma and chronic obstructive pulmonary disease.
Probing airway conditions governing ventilation defects in asthma via hyperpolarized MRI image functional modeling
Authors: Campana Lisa , Kenyon Jennifer , Zhalehdoust-Sani Sanaz , Tzeng Yang-Sheng , Sun Yanping , Albert Mitchell , Lutchen Kenneth R.
Published: February 2009

Image functional modeling (IFM) has been introduced as a method to simultaneously synthesize imaging and mechanical data with computational models to determine the degree and location of airway constriction in asthma. Using lung imaging provided by hyperpolarized 3He MRI, we advanced our IFM method to require matching not only to ventilation defect location but to specific ventilation throughout the lung. Imaging and mechanical data were acquired for four healthy and four asthmatic subjects pre- and postbronchial challenge. After provocation, we first identified maximum-size airways leading exclusively to ventilation defects and highly constricted them. Constriction patterns were then found for the remaining airways to match mechanical data. Ventilation images were predicted for each pattern, and visual and statistical comparisons were done with measured data. Results showed that matching of ventilation defects requires severe constriction of small airways. The mean constriction of such airways leading to the ventilation defects needed to be 70–80% rather than fully closed. Also, central airway constriction alone could not account for dysfunction seen in asthma, so small airways must be involved.
Ciclosporin Does Not Influence Bone Marrow-Derived Cell Differentiation to Myofibroblasts Early after Renal Ischemia/Reperfusion
Authors: Broekema Martine , Harmsen Martin C. , Koerts Jasper A. , van Kooten Theo G. , Uges Donald R.A. , Petersen Arjen H. , van Luyn Marja J.A. , Navis Gerjan , Popa Eliane R.
Published: February 2009

Background: Ischemia/reperfusion injury (IRI) is a risk factor for the development of interstitial fibrosis. Previously we had shown that after renal IRI, bone marrow-derived cells (BMDC) can differentiate to interstitial myofibroblasts. Here we hypothesized that the immunosuppressant ciclosporin A (CsA), known for its profibrotic side effect, promotes myofibroblast differentiation of BMDC in the postischemic kidney. Methods: Using a model of unilateral renal IRI in rats reconstituted with R26-human placental alkaline phosphatase transgenic bone marrow, CsA was administered in a previously defined critical window for differentiation of BMDC to myofibroblasts. We evaluated fibrotic changes in the kidney and myofibroblast differentiation of BMDC on day 14 after CsA treatment. Results: CsA treatment for 14 days led to increased transforming growth factor-β transcript levels and collagen III deposition in the postischemic kidney. However, neither the total number of α-smooth-muscle-actin-positive interstitial myofibroblasts, nor the bone marrow-derived fraction thereof was affected by CsA administration, irrespective of dosage and duration of treatment. Conclusions: In the critical postischemic window of BMDC differentiation to myofibroblasts, CsA did not promote BMDC differentiation to myofibroblasts, suggesting that, in the clinical setting, CsA is not involved in myofibroblastic differentiation of BMDC.
Molecular Imaging in Atherosclerosis, Thrombosis, and Vascular Inflammation
Authors: Choudhury Robin P. , Fisher Edward A.
Published: February 2009

Appreciation of the molecular and cellular processes of atherosclerosis, thrombosis, and vascular inflammation has identified new targets for imaging. The common goals of molecular imaging approaches are to accelerate and refine diagnosis, provide insights that reveal disease diversity, guide specific therapies, and monitor the effects of those therapies. Here we undertake a comparative analysis of imaging modalities that have been used in this disease area. We consider the elements of contrast agents, emphasizing how an understanding of the biology of atherosclerosis and its complications can inform optimal design. We address the potential and limitations of current contrast approaches in respect of translation to clinically usable agents and speculate on future applications.
Bradykinin-Induced Dilation of Human Coronary Arterioles Requires NADPH Oxidase–Derived Reactive Oxygen Species
Authors: Larsen Brandon T. , Bubolz Aaron H. , Mendoza Suelhem A. , Pritchard Kirkwood A. , Gutterman David D.
Published: February 2009

Objective—Hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor in human coronary arterioles (HCAs). H2O2mediates bradykinin (BK)-induced vasodilation and reduces bioavailability of epoxyeicosatrienoic acids (EETs); however, the cellular and enzymatic source of H2O2is unknown.

Methods and Results—NADPH oxidase expression was determined by immunohistochemistry. Superoxide and H2O2production was assayed in HCAs and human coronary artery endothelial cells (HCAECs) using dihydroethidium and dichlorodihydrofluorescein histofluorescence, respectively. Superoxide was quantified by HPLC separation of dihydroethidium products. Diameter changes of HCAs were measured by videomicroscopy. NADPH oxidase subunits Nox1, Nox2, Nox4, p22, p47, and p67 were each expressed in HCA endothelium. In HCAs or HCAECs incubated with dihydroethidium and dichlorodihydrofluorescein, BK induced superoxide and H2O2formation, which was inhibited by gp91ds-tat or apocynin but not by gp91scram-tat or rotenone. HPLC analysis confirmed that BK specifically induced superoxide production. Gp91ds-tat reduced vasodilation to BK but not to papaverine. 14,15-EEZE (an EET antagonist) further reduced the residual dilation to BK in the presence of gp91ds-tat, but had no effect in the presence of gp91scram-tat, suggesting that NADPH oxidase–derived ROS modulate EET bioavailability.

Conclusion—We conclude that endothelial NADPH oxidase is a functionally relevant source of H2O2that mediates agonist-induced dilation in the human heart.
Comprehensive Whole-Genome and Candidate Gene Analysis for Response to Statin Therapy in the Treating to New Targets (TNT) Cohort
Authors: Thompson John F. , Hyde Craig L. , Wood Linda S. , Paciga Sara A. , Hinds David A. , Cox David R. , Hovingh G. Kees , Kastelein John J.P.
Published: February 2009

Background—

Statins are effective at lowering low-density lipoprotein cholesterol and reducing risk of cardiovascular disease, but variability in response is not well understood. To address this, 5745 individuals from the Treating to New Targets (TNT) trial were genotyped in a combination of a whole-genome and candidate gene approach to identify associations with response to atorvastatin treatment.

Methods and Results—

A total of 291 988 single-nucleotide polymorphisms (SNPs) from 1984 individuals were analyzed for association with statin response, followed by genotyping top hits in 3761 additional individuals. None was significant at the whole-genome level in either the initial or follow-up test sets for association with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglyceride response. In addition to the whole-genome platform, 23 candidate genes previously associated with statin response were analyzed in these 5745 individuals. Three SNPs in
apoE
were most highly associated with low-density lipoprotein cholesterol response, followed by 1 in
PCSK9
with a similar effect size. At the candidate gene level, SNPs in
HMGCR
were also significant though the effect was less than with those in
apoE
and
PCSK9
. rs7412/
apoE
had the most significant association (
P
=6�10
−30
), and its high significance in the whole-genome study (
P
=4�10
−9
) confirmed the suitability of this population for detecting effects. Age and gender were found to influence low-density lipoprotein cholesterol response to a similar extent as the most pronounced genetic effects.

Conclusions—

Among SNPs tested with an allele frequency of at least 5%, only SNPs in
apoE
are found to influence statin response significantly. Less frequent variants in
PCSK9
and smaller effect sizes in SNPs in
HMGCR
were also revealed.
Kv4 Potassium Channels Form a Tripartite Complex With the Anchoring Protein SAP97 and CaMKII in Cardiac Myocytes
Authors: El-Haou Saïd , Balse Elise , Neyroud Nathalie , Dilanian Gilles , Gavillet Bruno , Abriel Hugues , Coulombe Alain , Jeromin Andreas , Hatem Stéphane N.
Published: February 2009

Membrane-associated guanylate kinase (MAGUK) proteins are major determinants of the organization of ion channels in the plasma membrane in various cell types. Here, we investigated the interaction between the MAGUK protein SAP97 and cardiac Kv4.2/3 channels, which account for a large part of the outward potassium current,
I
to
, in heart. We found that the Kv4.2 and Kv4.3 channels C termini interacted with SAP97 via a SAL amino acid sequence. SAP97 and Kv4.3 channels were colocalized in the sarcolemma of cardiomyocytes. In CHO cells, SAP97 clustered Kv4.3 channels in the plasma membrane and increased the current independently of the presence of KChIP and dipeptidyl peptidase-like protein-6. Suppression of SAP97 by using short hairpin RNA inhibited
I
to
in cardiac myocytes, whereas its overexpression by using an adenovirus increased
I
to
. Kv4.3 channels without the SAL sequence were no longer regulated by Ca
2+
/calmodulin kinase (CaMK)II inhibitors. In cardiac myocytes, pull-down and coimmunoprecipitation assays showed that the Kv4 channel C terminus, SAP97, and CaMKII interact together, an interaction suppressed by SAP97 silencing and enhanced by SAP97 overexpression. In HEK293 cells, SAP97 silencing reproduced the effects of CaMKII inhibition on current kinetics and suppressed Kv4/CaMKII interactions. In conclusion, SAP97 is a major partner for surface expression and CaMKII-dependent regulation of cardiac Kv4 channels.
Bosentan Enhances Viral Load via Endothelin-1 Receptor Type-A–Mediated p38 Mitogen-Activated Protein Kinase Activation While Improving Cardiac Function During Coxsackievirus-Induced Myocarditis
Authors: Marchant David , Dou Ying , Luo Honglin , Garmaroudi Farshid S. , McDonough John E. , Si Xiaoning , Walker Elizabeth , Luo Zongshu , Arner Anders , Hegele Richard G. , Laher Ismail , McManus Bruce M.
Published: February 2009

Reduced cardiac output is one of the consequences of myocarditis. Bosentan, an endothelin-1 receptor (ET1R) antagonist, could be useful to reduce cardiac afterload, preserving cardiac output. In this study, we investigated the potential therapeutic use of bosentan in an animal model of viral myocarditis. Using a mouse model of coxsackievirus B3 (CVB3)-induced myocarditis, we demonstrated preserved ejection fraction (EF) and fractional shortening (FS) by treatment with bosentan (68±5.8% EF and 40±3.7% FS for treated versus 48±2.2% EF and 25±2.6% FS for controls;P=0.028). However, bosentan enhanced cardiac viral load (10.4±6.7% in the bosentan group versus 5.0±5.5% in control group;P=0.02), likely through enhancement of p38 mitogen-activated protein kinase (MAPK) phosphorylation (0.77±0.40% ATF2 activation in the bosentan group versus 0.03±0.02% in controls;P=0.0002), mediated by endothelin receptor type-A. We further demonstrate that a water soluble inhibitor of p38 MAPK, SB203580 HCl, is a potent inhibitor of virus replication in the heart (0.28% antisense viral genome stained area for 3 mg/kg dose versus 2.9% stained area for controls;P=0.01), attenuates CVB3-induced myocardial damage (blinded cardiac histopathologic scores of 1.8±1.6 and 2.05±1.2 for the 3 mg/kg and 10 mg/kg doses, respectively, versus 3.25±1.2 for the controls), and preserves cardiac function (69±3.5% EF for 3 mg/kg dose and 71±6.7% EF for 10 mg/kg dose versus 60±1.5% EF control;P=0.038 andP=0.045, as compared to control, respectively). Bosentan, a prescribed vasodilator, improves cardiac function but enhances viral load and myocarditis severity through ETRA mediated p38 MAPK activation; p38 MAPK is a desirable antiviral target. Caution must be exercised during treatment of suspected infectious myocarditis with supportive vasoactive remedies.
A Novel Role of MicroRNA in Late Preconditioning
Authors: Yin Chang , Salloum Fadi N. , Kukreja Rakesh C.
Published: February 2009

MicroRNAs (miRNAs) are noncoding RNAs of 18 to 24 nucleotides that are involved in posttranscriptional regulation of protein expression. Their role in ischemic preconditioning (IPC) is currently unknown. We hypothesized that miRNAs induced after IPC in the heart may create a preconditioned phenotype through upregulating proteins including endothelial nitric oxide synthase (eNOS)/inducible nitric oxide synthase (iNOS) and heat shock protein (HSP)70, which are implicated in the late-phase protection of IPC. miRNAs were extracted from hearts of ICR mice following IPC. The purified miRNAs were injected in vivo into the left ventricular wall of mice, and, 48 hours later, the hearts were subjected to regional ischemia/reperfusion injury by left anterior descending artery ligation for 30 minutes followed by reperfusion for 24 hour. IPC caused no changes in miRNA-23b and miRNA-483 whereas miRNA-1, miRNA-21and miRNA-24 were significantly increased. The IPC-miRNA treatment caused an increase in eNOS mRNA and protein, whereas iNOS was not changed. HSF-1 (heat shock transcription factor 1) and HSP70 were also increased with IPC-miRNA treatment versus control. Moreover, injection of IPC-miRNA protected the hearts against ischemia/reperfusion injury, as shown by a reduction of infarct size as compared with saline or non-IPC miRNA-treated control. We conclude that IPC-induced miRNAs trigger cardioprotection similar to the delayed phase of IPC, possibly through upregulating eNOS, HSP70, and the HSP70 transcription factor HSF-1.
Rainfall Variability over Mountainous and Adjacent Lake Areas: The Case of Lake Tana Basin at the Source of the Blue Nile River
Authors: Haile Alemseged T. , Rientjes Tom , Gieske Ambro , Gebremichael Mekonnen
Published: February 2009

The water resource of the Blue Nile River is of key regional importance to the northeastern African countries. However, little is known about the characteristics of the rainfall in the basin. In this paper, the authors presented the space–time variability of the rainfall in the vicinity of Lake Tana, which is the source of the Blue Nile River. The analysis was based on hourly rainfall data from a network of newly installed rain gauges, and cloud temperature indices from the Meteosat Second Generation (MSG–2) Spinning Enhanced Visible and Infrared Imager (SEVIRI) satellite sensor. The spatial and temporal patterns of rainfall were examined using not only statistical techniques such as exceedance probabilities, spatial correlation structure, harmonic analysis, and fractal analysis but also marginal statistics such as mean and standard deviation. In addition, a convective index was calculated from remote sensing images to infer the spatial and temporal patterns of rainfall. Heavy rainfall is frequent at stations that are relatively close to the lake. The correlation distances for the hourly and the daily rainfall are found at about 8 and 18 km, respectively. The rainfall shows a strong spatially varying diurnal cycle. The nocturnal rainfall was found to be higher over the southern shore of Lake Tana than over the mountainous area farther to the south. The maximum convection occurs between 1600 and 1700 local standard time (LST) over the Gilgel Abbay, Ribb, and Gumara catchments, and between 2200 and 2300 LST over Lake Tana and the Megech catchments. In addition, the hourly rainfall of the station with the highest elevation is relatively closely clustered as compared to those stations at lower elevation. The study provides relevant information for understanding rainfall variation with elevation and distance from a lake. This understanding benefits climate and hydrological studies, water resources management, and energy development in the region.
Understanding Land–Sea Warming Contrast in Response to Increasing Greenhouse Gases. Part I: Transient Adjustment
Authors: Dong Buwen , Gregory Jonathan M. , Sutton Rowan T.
Published: February 2009

Climate model simulations consistently show that surface temperature over land increases more rapidly than over sea in response to greenhouse gas forcing. The enhanced warming over land is not simply a transient effect caused by the land–sea contrast in heat capacities, since it is also present in equilibrium conditions. This paper elucidates the transient adjustment processes over time scales of days to weeks of the surface and tropospheric climate in response to a doubling of CO2 and to changes in sea surface temperature (SST), imposed separately and together, using ensembles of experiments with an atmospheric general circulation model. These adjustment processes can be grouped into three stages: immediate response of the troposphere and surface processes (day 1), fast adjustment of surface processes (days 2–5), and adjustment of the whole troposphere (days 6–20).

Some land surface warming in response to doubled CO2 (with unchanged SSTs) occurs immediately because of increased downward longwave radiation. Increased CO2 also leads to reduced plant stomatal resistance and hence restricted evaporation, which increases land surface warming in the first day. Rapid reductions in cloud amount lead in the next few days to increased downward shortwave radiation and further warming, which spreads upward from the surface, and by day 5 the surface and tropospheric response is statistically consistent with the equilibrium value. Land surface warming in response to imposed SST change (with unchanged CO2) is slower. Tropospheric warming is advected inland from the sea, and over land it occurs at all levels together rather than spreading upward from the surface. The atmospheric response to prescribed SST change in about 20 days is statistically consistent with the equilibrium value, and the warming is largest in the upper troposphere over both land and sea. The land surface warming involves reduction of cloud cover and increased downward shortwave radiation, as in the experiment with CO2 change, but in this case it is due to the restriction of moisture supply to the land (indicated by reduced soil moisture), whereas in the CO2 forcing experiment it is due to restricted evaporation despite increased moisture supply (indicated by increased soil moisture). The warming over land in response to SST change is greater than over the sea and is the dominant contribution to the land–sea warming contrast under enhanced CO2 forcing.
A New Method for Exploring Coupled Land–Atmosphere Dynamics
Authors: DelSole Timothy , Zhao Mei , Dirmeyer Paul
Published: February 2009

This paper proposes a new method for investigating coupled land–atmosphere interactions. The method is to apply an empirical correction technique to distinct components of a model and then examine differences between forecasts of the empirically corrected models. The correction technique is based on adding a time-dependent term to the tendency equations that subtracts the estimated tendency error at every time step. This methodology can be interpreted more generally as a series of data assimilation experiments in which only certain components of a coupled model are assimilated at a time. The correction is applied to a state-of-the-art coupled land–atmosphere model in three different ways, namely, to the atmosphere only, to the land only, and to the land and atmosphere simultaneously. The land–atmosphere interactions are inferred from monthly-mean differences between experiments. The results suggest that the land–atmosphere coupling in midlatitudes can be understood from straightforward water balance considerations, whereas the coupling in the deep tropics involves a more complicated change in regional circulation. Specifically, in midlatitudes, moisture injected into the soil is transferred to the atmosphere directly above, which in turn advects downstream and subsequently moistens the atmosphere in the downwind regions to produce positive precipitation anomalies. In the deep tropics, the regional circulation, including precipitation, is sensitive to perturbations and has no obvious relation to corrections in the atmosphere or land. The similarity of biases among different models suggests that the conclusions and methodology may be relevant to other models.
Effects of Rain Gauge Temporal Resolution on the Specification of a Z–R Relationship
Authors: Mapiam Punpim Puttaraksa , Sriwongsitanon Nutchanart , Chumchean Siriluk , Sharma Ashish
Published: February 2009

The weather radar is an efficient alternative for measuring spatially varying rainfall covering a large area at a high temporal resolution. This paper studies the impact of rainfall gauge temporal resolution on optimal relationships between radar reflectivity (Z) and rainfall rate (R). Four datasets of radar reflectivity and corresponding rain gauge rainfall data from Sydney and Brisbane, Australia, and one dataset from Bangkok, Thailand, were used in the analysis. Climatological Z–R relationships were calibrated using rainfall aggregated over 1–24 h to investigate the evidence of temporal scaling in the Z–R calibrated parameters. This analysis points to an increase in the multiplicative term (the A parameter) of the Z–R relationship as temporal resolutions become finer. This pattern is repeated in all the datasets analyzed. Thereafter, a simple scaling hypothesis was proposed to develop transformations that could scale the A parameter in the Z–R relation across a range of temporal resolutions. This scaling relationship was found to be suitable, with the scaling exponent attaining values close to 0.055 across all the datasets analyzed. The proposed relationship has a significant role in radar rainfall estimation studies, especially in regions where subdaily gauge rainfall measurements are not readily available to ascertain optimal Z–R parameters.
`An Institution is Born'
Authors: Karlsson Michael
Published: February 2009

Lithuania's formation of a counter-terrorism institution after 9/11 sheds new light on three premises often associated with the study of institutional formation. First, while the distinction between the creation phase and the operation phase is logical, the appearance of extra-institutional guidance suggests that established institutions within other domains (e.g. military security) can temporarily fill an institutional vacuum (counter-terrorism). Second, the dynamic between agency and structure is readily seen, but in this case it was quite clear that agency was strongly dependent upon changes in some of the structural contexts (threat of terrorism, international institutions, age of the security state). Third, the role of sequencing and timing turned out to be more important than expected. There was a strong temporal order between the sequences of the formation phase and a significant spillover from two contemporary security processes (preparations for NATO membership, reforms of the security state).
What are New Zealand children eating at school? A content analysis of `consumed versus unconsumed' food groups in a lunch-box survey
Authors: Dresler-Hawke Emma , Whitehead Dean , Coad Jane
Published: February 2009

Eating patterns among school-aged children continue to be highly reliant on frequent consumption of food items that are perceived to have low or poor nutritional value. This has become a serious public health concern. In this New Zealand-based study, primary school children's food consumption behaviour was investigated via two sources: a cross-sectional survey of school foods from 927 lunch-boxes, and the content analysis of unconsumed foods deposited in provided food waste disposal bins. The results indicated that most lunch-boxes contained an over-representation of the food groups high in fat, sodium and sugar, and an under-representation of fruit and vegetables. In this study, the measured high proportions of unconsumed healthy foods (mainly fruit and vegetables), in comparison to unhealthy foods, being thrown away by school-children were of concern. The results indicate that schools and parents should pursue initiatives that support healthy diets for children as best practice.
Exploring the reality of applied partnerships: The case of the Greek school health education curriculum
Authors: Soultatou Pelagia , Duncan Peter
Published: February 2009

Objective To explore the barriers and facilitators of building partnerships in terms of the national school health education (SHE) curriculum in Greek secondary education.

Setting One large urban public secondary school, local authorities and external partners.

Methods A single case study, adopting an ethnographic approach, sought to record and explore the reality of partnerships at school level. Multilevel sampling was employed to extract one secondary school as a site for `good practice'. Individual interviews, focus groups, observation and document analysis were used to build this case study of applied partnerships. Grounded theory coding and thematic analysis identified themes associated with the idea of partnerships through the corpus of textual data (verbal and written).

Results (a) The key professional in the coordinating mechanism (local authorities) lacked sufficient support. (b) Voluntary collaborations alleviate the gaps in human resources. (c) Parents' engagement was marginal. (d) Top-down imposed partnerships did not work effectively. (e) `Social' health promoters were dismissed in favour of `biomedical' partners.

Conclusions Overall an explicit trend of failure in the process of building partnerships was shown in terms of this case of SHE curriculum implementation. To explain this trend, it is necessary to engage in attempts to understand the culture and context of the case.
High fidelity? How should we consider variations in the delivery of school-based health promotion interventions?
Authors: Holliday Jo , Audrey Suzanne , Moore Laurence , Parry-Langdon Nina , Campbell Rona
Published: February 2009

Objective The complexity and scale of health promotion interventions present challenges for the standardization of delivery. Furthermore, health promotion practice favours adapting interventions according to perceived client need. This paper examines the fidelity of intervention delivery within A Stop Smoking in Schools Trial (ASSIST), identifying if and why variations occurred, the consequences of these variations for the integrity of the intervention, and the broader implications for the delivery of evidence-based health promotion in schools.

Design The ASSIST intervention involved influential Year 8 students being trained to encourage their peers, through informal conversations, to be smoke-free. Its effectiveness was evaluated by a pragmatic randomized controlled trial with an integral process evaluation to examine the context, implementation and receipt of the intervention.

Setting Thirty secondary schools in South Wales and the west of England.

Method A variety of methods, including interviews, questionnaires and observation, were used to obtain data from key participants. Qualitative data were analysed using the constant comparative method.

Results Whilst overall fidelity was high, some variations were observed. Despite this variation, the intervention was largely delivered successfully and appropriately across a range of schools. Lessons learned from ASSIST enabled us to develop a model to categorize variations in intervention delivery.

Conclusion The model developed can inform the design of health promotion interventions and identify the level of fidelity which should be expected outside of a trial. We believe that this model can contribute to good practice in the implementation of evidence-based health promotion in schools.
Does Indiscriminate Violence Incite Insurgent Attacks?
Authors: Lyall Jason
Published: February 2009

Does a state's use of indiscriminate violence incite insurgent attacks? To date, most existing theories and empirical studies have concluded that such violence is highly counterproductive because it creates new grievances while forcing victims to seek security, if not safety, in rebel arms. This proposition is tested using Russian artillery fire in Chechnya (2000 to 2005) to estimate indiscriminate violence's effect on subsequent patterns of insurgent attacks across matched pairs of similar shelled and nonshelled villages. The findings are counterintuitive. Shelled villages experience a 24 percent reduction in posttreatment mean insurgent attacks relative to control villages. In addition, commonly cited “triggers” for insurgent retaliation, including the lethality and destructiveness of indiscriminate violence, are either negatively correlated with insurgent attacks or statistically insignificant.
When Is the Father Really There?
Authors: Krampe Edythe M.
Published: February 2009

The article reconceptualizes father presence as the psychological presence of the father in the child. The article explicates the components of father presence as comprised of the following: (a) an inner sense of father in the child that orients him or her to the father; (b) the child's relationship with the personal father; (c) other family influences on father presence in the child; and (d) cultural and religious beliefs about the father found in the larger societal context, which are transmitted to the child in the family and other primary groups. The article postulates a conceptual model of father presence that consists of concentric spheres of influence that affect the development of the psychological presence of the father and also discusses the importance of studying father presence from the child's perspective.
Depression and anxiety symptoms after lower limb amputation: the rise and fall
Authors: Singh Rajiv , Ripley David , Pentland Brian , Todd Iain , Hunter John , Hutton Lynne , Philip Alistair
Published: February 2009

Objective: To examine the time course of anxiety and depressive symptoms over a three year period after amputation.

Design and settings: A prospective study in inpatients admitted to a rehabilitation ward after lower limb amputation.

Subjects: Successive admissions over a one-year period of whom 68 were alive at follow-up, 2—3 years later.

Interventions: Nil.

Main measures: Hospital Anxiety and Depression Scale (HADS) on admission and discharge from inpatient rehabilitation and at a 2.7(SD=0.4) year mean follow-up period with correlation to demographic and patient features.

Results: Of the 68 responding patients, 12 (17.6%) and 13 (19.1%) had symptoms of depression and anxiety respectively. This compared to an original incidence of 16 (23.5%) for both on admission and 2 (2.9%) on discharge. This rise in incidence from time of discharge was highly significant for both depression (P<0.001) and anxiety (P<0.001). Depression at follow-up was correlated to depressive symptoms at admission (P=0.03) and to having other significant comorbidities (P=0.02). Anxiety symptoms were commoner in younger patients (P=0.03). There was no association with age, gender, living in isolation, vascular cause for amputation, wearing a limb prosthesis or length of original inpatient stay.

Conclusions: Depression and anxiety are common after lower limb amputation but resolve during inpatient rehabilitation. The incidence then rises again after discharge.