bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the role of 5‐HT2receptor subtypes in the control of the bladder and the urethra in the anaesthetized female rat
Authors: Mbaki Y , Ramage A G 
Published: July 2008

Background and purpose:Micturition is controlled by central 5‐HT‐containing pathways. 5‐HT2receptors have been implicated in this system especially in control of the urethra, which is a drug target for treating urinary incontinence. This study investigates the role of each of the three subtypes of this receptor with emphasis on sphincter regulation.Experimental approach:Recordings of urethral and bladder pressure, external urethral sphincter (EUS) EMG, as well as the micturition reflex induced by bladder distension along with blood pressure and heart rate were made in anaesthetized rats. The effects of agonists and antagonists for 5‐HT2receptor subtypes were studied on these variables.Key results:The 5‐HT2Cagonists Ro 60‐0175, WAY 161503 and mCPP, i.v., activated the EUS, increased urethral pressure and inhibited the micturition reflex. The effects of Ro 60‐0175 on the EUS were blocked by the 5‐HT2Cantagonist SB 242084 and the 5‐HT2Aantagonists, ketanserin and MDL 100907. SB 242084 also blocked the inhibitory action on the reflex, while the 5‐HT2Bantagonist RS 127445 only blocked the increase in urethral pressure. The 5‐HT2Areceptor agonist DOI given i.v. or i.t. but not i.c.v. activated the EUS.Conclusions and implications:5‐HT2A/2Creceptors located in the sacral spinal cord activate the EUS, while central 5‐HT2Creceptors inhibit the micturition reflex and 5‐HT2Breceptors, probably at the level of the urethra, increase urethral smooth muscle tone. Furthermore, 5‐HT2Band 5‐HT2Creceptors do not seem to play an important role in the physiological regulation of micturition.British Journal of Pharmacology(2008)155, 343–356; doi:10.1038/bjp.2008.273; published online 7 July 2008
Literature‐based evaluation of four ‘hard endpoint’ models for assessing drug‐induced torsades de pointes liability
Authors: Vos M A 
Published: July 2008

In safety pharmacology, a number of preclinical models for detecting drug‐induced proarrhythmia liability have been recently introduced that utilize hard endpoints: early after depolarziations (EADs), torsades de pointes (TdP) or both as the principal biomarker. To explore the validity of four of the most common of these models, (the isolated canine/rabbit left ventricular wedge preparation, the isolated rabbit heart, the methoxamine‐pretreated anaesthetized rabbit and the complete, chronic AV‐blocked (CAVB) dog (conscious and anaesthetized), the present article reviews published data sets for three drugs with recognized and different human TdP liabilities (cisparide, terfenadine and moxifloxacinin). Finally, this review considers the value of inclusion of analysis of beat‐to‐beat variability of repolarization (BVR) in TdP liability testing to improve sensitivity and specificity.British Journal of Pharmacology(2008)154, 1523–1527; doi:fn1; published online 7 July 2008
α2‐Adrenoceptor action on cell proliferation and mammary tumour growth in mice
Authors: Bruzzone A , Piñero C Pérez , Castillo L F , Sarappa M G , Rojas P , Lanari C , Lüthy I A 
Published: July 2008

Background and purpose:Breast cancer, the most common cancer in women in most countries, is a highly stressful disease. Catecholamines released during stress bind to adrenoceptors and we have recently described α2‐adrenoceptors in human breast cell lines, linked to enhanced cell proliferation. The purpose was to assess thein vivoeffects of compounds acting on α2‐adrenoceptors in a reliable model of breast cancer.Experimental approach:The expression of α2‐adrenoceptors was confirmed by immunocytochemistry, immunofluorescence and reverse transcription‐PCR in the mouse mammary tumour cell line MC4‐L5. Proliferation was assessed by [3H]thymidine incorporation and tumours were measured daily. Apoptosis was assessed by terminal deoxynucleotidyl transferase‐mediated dUTP digoxigenin nick‐end labelling.Key results:Incubation for 2 days with α2‐adrenoceptor agonists (clonidine and dexmedetomidine) significantly enhanced proliferation of the mouse mammary tumour cell line MC4‐L5. These agonists also significantly stimulated tumour growth of the progestin‐dependent tumour C4‐HD even in the presence of medroxyprogesterone acetate (MPA). In every tumour tested (C4‐HD, CC4‐2‐HD and CC4‐3‐HI), regardless of MPA sensitivity, clonidine significantly enhanced tumour growth in the absence of MPA. The α2‐adrenoceptor antagonists, yohimbine and rauwolscine, completely reversed the effects of clonidine. However, the group receiving yohimbine alone showed a nonsignificant but constant increase in tumour growth, whereas rauwolscine alone diminished tumour growth significantly, behaving as a reverse agonist. In CC4‐3‐HI tumours, rauwolscine treatment enhanced apoptosis and diminished the mitotic index, whereas clonidine had the inverse effect.Conclusions and implications:α2‐Adrenoceptor agonists enhanced tumour growth and rauwolscine behavedin vivoas a reverse agonist, suggesting that it may be tested for adjuvant treatment.British Journal of Pharmacology(2008)155, 494–504; doi:10.1038/bjp.2008.278; published online 7 July 2008
Novel long‐acting bronchodilators for COPD and asthma
Authors: Cazzola M , Matera M G 
Published: July 2008

An important step in simplifying asthma and chronic obstructive pulmonary disease (COPD) management and improving adherence with prescribed therapy is to reduce the dose frequency to the minimum necessary to maintain disease control. Therefore, the incorporation of once‐daily dose administration is an important strategy to improve adherence and is a regimen preferred by most patients, which may also lead to enhancement of compliance, and may have advantages leading to improved overall clinical outcomes. Once‐daily β2‐agonists or ultra long‐acting β2‐agonists (LABAs) such as carmoterol, indacaterol, GSK‐159797, GSK‐597901, GSK‐159802, GSK‐642444 and GSK‐678007 are under development for the treatment of asthma and COPD. Also some new long‐acting antimuscarinic agents (LAMAs) such as aclidinium, LAS‐35201, GSK656398, GSK233705, NVA‐237 (glycopyrrolate) and OrM3 are under development. In any case, the current opinion is that it will be advantageous to develop inhalers containing combination of several classes of long‐acting bronchodilator drugs in an attempt to simplify treatment regimens as much as possible. Consequently, several options for once‐daily dual‐action ultra LABA+LAMA combination products are currently being evaluated. A different approach is to have a dimer molecule in which both pharmacologies are present (these molecules are known as M3 antagonist‐β2 agonist (MABA) bronchodilators). The advent of a successful MABA product will revolutionize the field and open the door for a new range of combination products.British Journal of Pharmacology (2008) 155, 291–299; doi:10.1038/bjp.2008.284; published online 7 July 2008
Bradykinin regulates human colonic ion transport in vitro
Authors: Baird A W , Skelly M M , O'Donoghue D P , Barrett K E , Keely S J 
Published: July 2008

Background and purpose:Kinins are acknowledged as important regulators of intestinal function during inflammation; however, their effects on human intestinal ion transport have not been reported. Here, we used muscle‐stripped human colonic tissue and cultured T84‐cell monolayers to study bradykinin (BK) actions on human intestinal ion transport.Experimental approach:Ion transport was measured as changes in short‐circuit current (Isc) across colonic epithelia mounted in Ussing chambers.Key results:In intact tissue, there was a distinct polarity to BK‐elicited Isc responses. Whereas basolateral BK stimulated sustained responses (EC50=0.5±0.1 μM), those to apical BK were more rapid and transient (EC50=4.1±1.2 nM). In T84 cells, responses to both apical and basolateral BK were similar to those seen upon apical addition to intact tissues. Cross‐desensitization between apical and basolateral domains was not observed. BK‐induced responses were largely due to Cl− secretion as shown by their sensitivity to bumetanide and removal of Cl− from the bathing solution. Studies using selective agonists and antagonists indicate responses to BK are mediated by B2 receptors. Finally, responses to basolateral BK in intact tissues were inhibited by tetrodotoxin (1 μM), atropine (1 μM), capsaicin (100 μM) and piroxicam (10 μM). BK‐stimulated prostaglandin (PG)E2 release from colonic tissue.Conclusions:BK stimulates human colonic Cl− secretion by activation of apical and basolateral B2 receptors. Responses to apical BK reflect a direct action on epithelial cells, whereas those to basolateral BK are amplified by stimulation of enteric nerves and PG synthesis.British Journal of Pharmacology (2008) 155, 558–566; doi:10.1038/bjp.2008.288; published online 7 July 2008
An exceptional salt-tolerant antimicrobial peptide derived from a novel gene family of haemocytes of the marine invertebrate Ciona intestinalis
Authors: Fedders Henning , Michalek Matthias , Grötzinger Joachim , Leippe Matthias 
Published: July 2008

A novel gene family coding for putative antimicrobial peptides was identified in the EST (expressed sequence tag) database of the sea squirt Ciona intestinalis, and one of these genes was molecularly cloned from the Northern European Ciona subspecies. In situ hybridization and immunocytochemical analysis revealed that the natural peptide is synthesized and stored in a distinct haemocyte type, the univacuolar non-refractile granulocytes. By semiquantitative RT–PCR (reverse transcription–PCR) analysis, it was shown that the expression of the gene is markedly up-regulated in haemocytes after immune challenge. To evaluate the antimicrobial potency of the putative defence protein, we synthesized a peptide corresponding to its cationic core region. The peptide was highly effective against Gram-negative and Gram-positive bacteria including several human and marine pathogens as well as the yeast Candida albicans. Notably, the antibacterial activity of the peptide was retained at salt concentrations of up to 450 mM NaCl. Using two different methods we demonstrated that the peptide kills Gram-negative and Gram-positive bacteria by permeabilizing their cytoplasmic membranes. CD spectroscopy revealed that, in the presence of liposomes composed of negatively charged phospholipids, the peptide undergoes a conformational change and adopts an α-helical structure. Moreover, the peptide was virtually non-cytolytic for mammalian erythrocytes. Hence, the designed salt-tolerant antimicrobial peptide may represent a valuable template for the development of novel antibiotics.
Immunoregulatory roles of eosinophils: a new look at a familiar cell
Authors: Akuthota P. , Wang H. B. , Spencer L. A. , Weller P. F. 
Published: July 2008

SummaryEosinophils are usually considered as end‐stage degranulating effector cells of innate immunity. However, accumulating evidence has revealed additional roles for eosinophils that are immunoregulatory in nature in both the adaptive and innate arms of immunity. Specifically, eosinophils have key immunoregulatory roles as professional antigen‐presenting cells and as modulators of CD4+ T cell, dendritic cell, B cell, mast cell, neutrophil, and basophil functions. This review addresses the emerging immunoregulatory roles of eosinophils with a focus on recent data that support this new paradigm. Recognizing both the effector and immunoregulatory functions of eosinophils will enable a fuller understanding of the roles of eosinophils in allergic airways inflammation and may be pertinent to therapies that target eosinophils both for their acute and ongoing immunomodulatory functions.
The impact of added sugar consumption on overall dietary quality in Irish children and teenagers
Authors: Joyce T. , Gibney M. J. 
Published: July 2008

AbstractBackground  There is concern that added sugar may dilute micronutrients and displace nutrient dense foods from the diet.Methods  The data for this analysis was based on the National Children’s Food Survey and National Teen Food Survey, which used 7‐day food diaries to collect food and beverage intake data in representative samples of Irish children (5–12 years, n = 594) and teenagers (13–17 years, n = 441) respectively.Results  High consumption of added sugars was associated with a decrease in the micronutrient density of the diet and increased prevalence of dietary inadequacies in children and teenagers. The decrease in micronutrient density was significant for several micronutrients, including magnesium (P < 0.001), calcium (P < 0.01 children; P < 0.001 teenagers), zinc (P < 0.05) and vitamins B12 (P < 0.01 children; P < 0.001 teenagers) and C (P < 0.05). There was wide variation in the micronutrients for which prevalence of dietary inadequacies increased depending on gender and population group.Conclusions  Clinical data are required before conclusions can be made on whether micronutrient dilution is a concern in Ireland. A change in the consumption of several foods across level of added sugar intake may explain the decrease in the intake of several micronutrients and the decrease in the compliance with macronutrient recommendations in high consumers of added sugars in children and teenagers.
Leaf nitrogen remobilisation for plant development and grain filling
Authors: Masclaux‐Daubresse C. , Reisdorf‐Cren M. , Orsel M. 
Published: July 2008

AbstractA major challenge of modern agriculture is to reduce the excessive input of fertilisers and, at the same time, to improve grain quality without affecting yield. One way to achieve this goal is to improve plant nitrogen economy through manipulating nitrogen recycling, and especially nitrogen remobilisation, from senescing plant organs. In this review, the contribution of nitrogen remobilisation efficiency (NRE) to global nitrogen use efficiency (NUE), and tools dedicated to the determination of NRE are described. An overall examination of the physiological, metabolic and genetic aspects of nitrogen remobilisation is presented.
Natural developmental variations in leaf and plant senescence in Arabidopsis thaliana
Authors: Balazadeh S. , Parlitz S. , Mueller‐Roeber B. , Meyer R. C. 
Published: July 2008

AbstractLeaf senescence is a developmentally regulated process that contributes to nutrient redistribution during reproductive growth and finally leads to tissue death. Manipulating leaf senescence through breeding or genetic engineering may help to improve important agronomic traits, such as crop yield and the storage life of harvested organs. Here, we studied natural variations in the regulation of plant senescence among 16 Arabidopsis thaliana accessions. Chlorophyll content and the proportion of yellow leaves were used as indicator parameters to determine leaf and plant senescence respectively. Our study indicated significant genotype effects on the onset and development of senescence. We selected three late‐ and five early‐senescence accessions for further physiological studies. The relationship between leaf and plant senescence was accession‐dependent. There was a significant correlation between plant senescence and the total number of leaves, siliques and plant bolting age. We monitored expression of two senescence marker genes, SAG12 and WRKY53, to evaluate progression of senescence. Our data revealed that chlorophyll content does not fully reflect leaf age, because even fully green leaves had already commenced senescence at the molecular level. Integrating senescence parameters, such as the proportion of senescent leaves, at the whole plant level provided a better indication of the molecular status of the plant than single leaf senescence parameters.
Investigation of QTL regions on Chromosome 17 for genes associated with meat color in the pig
Authors: Fan B. , Glenn K.L. , Geiger B. , Mileham A. , Rothschild M.F. 
Published: July 2008

SummaryPrevious studies have uncovered several significant quantitative trait loci (QTL) relevant to meat colour traits mapped at the end of SSC17 in the pig. Furthermore, results released from the porcine genome sequencing project have identified genes underlying the entire QTL regions and can further contribute to mining the region for likely causative genes. Ten protein coding genes or novel transcripts located within the QTL regions were screened for single nucleotide polymorphisms (SNPs). Linkage mapping and association studies were carried out in the ISU Berkshire × Yorkshire (B × Y) pig resource family. The total length of the new SSC17 linkage map was 126.6 cM and additional markers including endothelin 3 (EDN3) and phosphatase and actin regulator 3 (PHACTR3) genes were assigned at positions 119.4 cM and 122.9 cM, respectively. A new QTL peak was noted at approximately 120 cM, close to the EDN3 gene, and for some colour traits QTL exceeded the 5% chromosome‐wise significance threshold. The association analyses in the B × Y family showed that the EDN3 BslI and PHACTR3 PstI polymorphisms were strongly associated with the subjective colour score and objective colour reflectance measures in the loin, as well as average drip loss percentage and pH value. The RNPC1 DpnII and CTCFL HpyCH4III polymorphisms were associated with some meat colour traits. No significant association between CBLN4, TFAP2C, and four novel transcripts and meat colour traits were detected. The association analyses conducted in one commercial pig line found that both EDN3 BslI and PHACTR3 PstI polymorphisms were associated with meat colour reflectance traits such as centre loin hue angle and Minolta Lightness score. The present findings suggested that the EDN3 and PHACTR3 genes might have potential effects on meat colour in pigs, and molecular mechanisms of their functions are worth exploring.
Internal Control of Hurricane Intensity Variability: The Dual Nature of Potential Vorticity Mixing
Authors: Rozoff Christopher M. , Kossin James P. , Schubert Wayne H. , Mulero Pedro J. 
Published: July 2008

Abstract
In hurricane eyewalls, the vertical stretching effect tends to produce an annular ring of high vorticity. Idealized, unforced nondivergent barotropic model results have suggested such rings of vorticity are often barotropically unstable, leading to strong asymmetric mixing events where vorticity is mixed inward into a more stable configuration. Such mixing events most often result in weakened maximum winds. The manner in which forcing modifies these unforced simulations remains an open question.
In the current study, a forced, two-dimensional barotropic model is used to systematically study the sensitivity of vorticity rings to ring geometry and spatially and temporally varying forcing. The simulations reveal an internal mechanism that interrupts the intensification process resulting from vorticity generation in the hurricane eyewall. This internal control mechanism is due to vorticity mixing in the region of the eye and eyewall and can manifest itself in two antithetical forms—as a transient “intensification brake” during symmetric intensification or as an enhancer of intensification through efficient transport of vorticity from the eyewall, where it is generated, to the eye.
Composite Life Cycle of Maritime Tropical Mesoscale Convective Systems in Scatterometer and Microwave Satellite Observations
Authors: Mapes Brian , Milliff Ralph , Morzel Jan 
Published: July 2008

Abstract
This study examines scatterometer-observed surface wind divergence and vorticity, along with precipitable water (PW), across the life cycle of tropical maritime mesoscale convective systems (MCSs) as resolved in 0.5° data. Simple composites were constructed around first appearances of cold (&lt;210 K) cloud tops in infrared (IR) data at 3-hourly resolution. Many thousands of such events from the tropical Indo-Pacific in 2000 were used. Composites of subpopulations were also constructed by subdividing the dataset according to IR event size and duration, as well as by prevailing values of PW and vorticity at a 5° scale.
The composite MCS life cycle here spans about a day and covers a few hundred kilometers, with a remarkable sameness across subpopulations. Surface wind convergence and PW buildup lead cold cloud appearance by many hours. Afterward there are many hours of divergence, indicative of downdrafts. Contrary to motivating hypotheses, the strength of this divergence relative to convergence is scarcely different in humid and dry subpopulation composites. Normalized time series of composite vorticity show an evolution that seems consistent with vortex stretching by this convergence–divergence cycle, with peak vorticity near the end of the period of convergence (3 h prior to cold cloud appearance). In rotating conditions, the common 1-day MCS life cycle is superposed on large-scale mean vorticity and convergence, approximately in proportion, which appear to be well scale-separated (covering the whole of the 48-h and 5°–10° averages) and are as strong as or stronger than the MCS signature.
Causes of Late Twentieth-Century Trends in New Zealand Precipitation
Authors: Ummenhofer Caroline C. , Sen Gupta Alexander , England Matthew H. 
Published: July 2008

Abstract
Late twentieth-century trends in New Zealand precipitation are examined using observations and reanalysis data for the period 1979–2006. One of the aims of this study is to investigate the link between these trends and recent changes in the large-scale atmospheric circulation in the Southern Hemisphere. The contributions from changes in Southern Hemisphere climate modes, particularly the El Niño–Southern Oscillation (ENSO) and the southern annular mode (SAM), are quantified for the austral summer season, December–February (DJF). Increasingly drier conditions over much of New Zealand can be partially explained by the SAM and ENSO. Especially over wide parts of the North Island and western regions of the South Island, the SAM potentially contributes up to 80% and 20%–50% to the overall decline in DJF precipitation, respectively. Over the North Island, the contribution of the SAM and ENSO to precipitation trends is of the same sign. In contrast, over the southwest of the South Island the two climate modes act in the opposite sense, though the effect of the SAM seems to dominate there during austral summer. The leading modes of variability in summertime precipitation over New Zealand are linked to the large-scale atmospheric circulation. The two dominant modes, explaining 64% and 9% of the overall DJF precipitation variability respectively, can be understood as local manifestations of the large-scale climate variability associated with the SAM and ENSO.