bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐throughput microscopy must re‐invent the microscope rather than speed up its functions
Authors: Oheim M 
Published: July 2007

Knowledge gained from the revolutions in genomics and proteomics has helped to identify many of the key molecules involved in cellular signalling. Researchers, both in academia and in the pharmaceutical industry, now screen, at a sub‐cellular level, where and when these proteins interact. Fluorescence imaging and molecular labelling combine to provide a powerful tool for real‐time functional biochemistry with molecular resolution. However, they traditionally have been work‐intensive, required trained personnel, and suffered from low through‐put due to sample preparation, loading and handling. The need for speeding up microscopy is apparent from the tremendous complexity of cellular signalling pathways, the inherent biological variability, as well as the possibility that the same molecule plays different roles in different sub‐cellular compartments. Research institutes and companies have teamed up to develop imaging cytometers of ever‐increasing complexity. However, to truly go high‐speed, sub‐cellular imaging must free itself from the rigid framework of current microscopes.British Journal of Pharmacology (2007) 152, 1–4; doi:10.1038/sj.bjp.0707348
Ginsenoside Rb1 inhibits tube‐like structure formation of endothelial cells by regulating pigment epithelium‐derived factor through the oestrogen β receptor
Authors: Leung K W , Cheung L W T , Pon Y L , Wong R N S , Mak N K , Fan T‐PD , Au S C L , Tombran‐Tink J , Wong A S T 
Published: July 2007

Background and purpose:Angiogenesis is a crucial step in tumour growth and metastasis. Ginsenoside‐Rb1 (Rb1), the major active constituent of ginseng, potently inhibits angiogenesis in vivo and in vitro. However, the underlying mechanism remains unknown. We hypothesized that the potent anti‐angiogenic protein, pigment epithelium‐derived factor (PEDF), is involved in regulating the anti‐angiogenic effects of Rb1.Experimental approaches:Rb1‐induced PEDF was determined by real‐time PCR and western blot analysis. The anti‐angiogenic effects of Rb1 were demonstrated using endothelial cell tube formation assay. Competitive ligand‐binding and reporter gene assays were employed to indicate the interaction between Rb1 and the oestrogen receptor (ER).Key results:Rb1 significantly increased the transcription, protein expression and secretion of PEDF. Targeted inhibition of PEDF completely prevented Rb1‐induced inhibition of endothelial tube formation, suggesting that the anti‐angiogenic effect of Rb1 was PEDF specific. Interestingly, the activation of PEDF occurred via a genomic pathway of ERβ. Competitive ligand‐binding assays indicated that Rb1 is a specific agonist of ERβ, but not ERα. Rb1 effectively recruited transcriptional activators and activated an oestrogen‐responsive reporter gene. Furthermore, Rb1‐mediated PEDF activation and the subsequent inhibition of tube formation were blocked by the ER antagonist ICI 182,780 or transfection of ERβ siRNA, indicating ERβ dependence.Conclusions and implications:Here we show for the first time that the Rb1 suppressed the formation of endothelial tube‐like structures through modulation of PEDF via ERβ. These findings demonstrate a novel mechanism of the action of this ginsenoside that may have value in anti‐cancer and anti‐angiogenesis therapy.British Journal of Pharmacology (2007) 152, 207–215; doi:10.1038/sj.bjp.0707359
Neuroprotective and anticonvulsant effects of EGIS‐8332, a non‐competitive AMPA receptor antagonist, in a range of animal models
Authors: Gigler G , Móricz K , ágoston M , Simó A , Albert M , Benedek A , Kapus G , Kertész S , Vegh M , Barkóczy J , Markó B , Szabó G , Matucz É , Gacsályi I , Lévay G , Hársing L G , Szénási G 
Published: July 2007

Background and purpose:Blockade of AMPA (α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid) receptors is a good treatment option for a variety of central nervous system disorders. The present study evaluated the neuroprotective and anticonvulsant effects of EGIS‐8332, a non‐competitive AMPA receptor antagonist, as a potential drug candidate.Experimental approach:AMPA antagonist effects of EGIS‐8332 were measured using patch‐clamp techniques. Neuroprotective and anticonvulsant effects of EGIS‐8332 were evaluated in various experimental models, relative to those of GYKI 53405.Key results:EGIS‐8332 inhibited AMPA currents in rat cerebellar Purkinje cells and inhibited the AMPA‐ and quisqualate‐induced excitotoxicity in primary cultures of telencephalon neurons (IC50=5.1‐9.0 μM),in vitro. Good anticonvulsant actions were obtained in maximal electroshock‐, sound‐ and chemically‐induced seizures (range of ED50=1.4‐14.0 mg kg−1i.p.) in mice. Four days after transient global cerebral ischaemia, EGIS‐8332 decreased neuronal loss in the hippocampal CA1 area in gerbils and rats. EGIS‐8332 dose‐dependently reduced cerebral infarct size after permanent middle cerebral artery occlusion in mice and rats (minimum effective dose=3 mg kg−1i.p.). Side effects of EGIS‐8332 emerged much above its pharmacologically active doses. A tendency for better efficacy of GYKI 53405 than that of EGIS‐8332 was observed in anticonvulsant tests that reached statistical significance in few cases, while the contrary was perceived in cerebral ischaemia tests.Conclusions and implications:EGIS‐8332 seems suitable for further development for the treatment of epilepsy, ischaemia and stroke based on its efficacy in a variety of experimental disease models, and on its low side effect potential.British Journal of Pharmacology(2007)152, 151–160; doi:10.1038/sj.bjp.0707362
α1‐Adrenoceptors are required for normal male sexual function
Authors: Sanbe A , Tanaka Y , Fujiwara Y , Tsumura H , Yamauchi J , Cotecchia S , Koike K , Tsujimoto G , Tanoue A 
Published: July 2007

Background and purpose:α1‐Adrenoceptor antagonists are extensively used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia. Among the side effects, ejaculatory dysfunction occurs more frequently with drugs that are relatively selective for α1A‐adrenoceptors compared with other drugs of this class. This suggests that α1A‐adrenoceptors may contribute to ejaculation. However, this has not been studied at the molecular level.Experimental approach:The physiological contribution of each α1‐adrenoceptor subtype was characterized using α1‐adrenoceptor subtype‐selective knockout (KO) mice (α1A‐, α1B‐ and α1D‐AR KO mice) since the subtype‐specific drugs available are only moderately selective. We analysed the role of α1‐adrenoceptors in the blood pressure and vascular response as well as ejaculation by determining these variables in α1‐adrenoceptor subtype‐selective KO mice and in mice with all their α1‐adrenoceptor subtypes deleted (α1‐AR triple‐KO mice).Key results:The pregnancy rate was reduced by 50% in α1A‐adrenoceptor KO mice, and this reduction was dramatically enhanced in α1‐adrenoceptor triple‐KO mice. Contractile tension of the vas deferens in response to noradrenaline was markedly decreased in α1A‐adrenoceptor KO mice, and this contraction was completely abolished in α1‐adrenoceptor triple‐KO mice. This attenuation of contractility was also observed in the electrically stimulated vas deferens.Conclusions and implications:These results demonstrate that α1‐adrenoceptors, particularly α1A‐adrenoceptors, are required for normal contractility of the vas deferens and consequent sperm ejaculation as well as having a function in fertility.British Journal of Pharmacology (2007) 152, 332–340; doi:10.1038/sj.bjp.0707366; published online 2 July 2007
Staining Proteins in Gels with Silver Nitrate
Authors: Simpson Richard J. 
Published: July 2007

INTRODUCTIONSilver staining is one of the commonly used procedures for visualizing proteins in acrylamide gels. All silver staining methods rely on the reduction of ionic to metallic silver to provide metallic silver images; the selective reduction at gel sites occupied by proteins compared to nonprotein sites is dependent on differences in the oxidation-reduction potentials at these sites. There are two broad methodologies for silver staining. One approach (nondiamine silver nitrate stains) uses silver nitrate as the silvering agent and formaldehyde in alkaline carbonate solution as the developing agent, whereas the other approach (diamine or ammoniacal stains) uses ammoniacal silver as the silvering agent and formaldehyde in dilute citric acid as the developing agent. Although protocols using ammoniacal silver are arguably more sensitive and give darker hues than those based on silver nitrate, they are more prone to negative staining, resulting in hollow or “doughnut” spots, give unacceptable backgrounds with tricine-based gel systems, and are not very robust because of their reliance on the ammonia-silver ratio. Additionally, ammoniacal silver staining is more sensitive for basic proteins but less so for very acidic proteins. This protocol describes a silver nitrate staining approach. Its sensitivity is in the low-nanogram range, which is 50-100 times more sensitive than classical Coomassie Blue staining, ~10 times better than colloidal Coomassie Blue staining, and at least twice as sensitive as the zinc/imidazole negative staining method.
Immunohistochemistry on Cryosections from Embryonic and Adult Zebrafish Eyes
Authors: Uribe Rosa A. , Gross Jeffrey M. 
Published: July 2007

INTRODUCTIONThis protocol describes methods for the fixation, cryosectioning, and immunohistochemical detection of proteins in embryonic and adult zebrafish eyes. The methods described can easily be adapted for use on other zebrafish tissues.
Setting Up a PCR Laboratory
Authors: Mifflin Theodore E. 
Published: July 2007

INTRODUCTIONDevelopment of the polymerase chain reaction (PCR) as a basic component of the molecular biology laboratory has occurred very rapidly from its inception in 1985. As PCR became more widely used, scientists rapidly learned more about it and, as a result, learned that PCR had its strong points and its deficiencies. Very quickly, PCR demonstrated its power to amplify very small amounts (e.g., a single copy) of template nucleic acid and to amplify different nucleic acids (e.g., DNA and RNA). At the same time, laboratory personnel learned that this biochemical reaction had a unique deficiency, namely, a strong susceptibility to contamination from its own product. This article is devoted to establishing a PCR laboratory whose operations will give reliable and contamination-free results.
Phosphoinositide 3‐kinase signalling in lung disease: leucocytes and beyond
Authors: Medina‐Tato David A. , Ward Stephen G. , Watson Malcolm L. 
Published: July 2007

SummaryThe family of lipid kinases termed phosphoinositide‐3‐kinase (PI3K) is known to contribute at multiple levels to innate and adaptive immune responses, and is hence an attractive target for drug discovery in inflammatory and autoimmune disease, including respiratory diseases. The development of isoform‐selective pharmacological inhibitors, targeted gene manipulation and short interfering RNA (siRNA) target validation have facilitated a better understanding of the role that each member of this family of kinases plays in the physiology and pathology of the respiratory system. In this review, we will evaluate the evidence for the roles of specific PI3K isoforms in the lung and airways, and discuss their potential as targets for novel drug therapies.
A survey of school nursing provision in the UK
Authors: Merrell Joy , Carnwell Ros , Williams Anne , Allen Davina , Griffiths Lesley 
Published: July 2007

AbstractTitle.  A survey of school nursing provision in the UK Aim.  This paper is a report of a study to map school nursing provision across the health and education sectors in Wales to identify the number, age, qualifications, terms of employment, location, functions and access to continuing professional development and clinical supervision of school nurses.Background.  School nurses are important in promoting the health of school‐aged children. Increased demands have arisen from changes in patterns of health, illness and lifestyles.Methods.  An interview survey was conducted with a purposive sample of school nursing/health visiting managers from 13 healthcare sector providers, senior personnel officers from 22 Local Education Authorities and 45 head teachers/school nurses from independent schools. Data were collected between March and June 2004 and the overall response rate exceeded 80%.Results.  A total of 249 school nurses were identified: 90% employed by the healthcare sector and 10% by the education sector. An ageing, under‐developed and under‐resourced service was identified. Disparity in practice within and across the sectors was evident, resulting from lack of policy direction regarding the scope and content of school nursing services. Workforce size, age and educational profile pose challenges for service delivery.Conclusion.  Investment in recruitment and education is required if school nurses are to meet increasing demands and fulfil their public health role. The low percentage of school nurses aged under 30 years may reflect lack of a career pathway and understanding of school nursing. The findings enable national and international comparisons in terms of numbers, size of caseload, age, qualifications, terms of employment and activities and functions.
Resilience in the operating room: developing and testing of a resilience model
Authors: Gillespie Brigid M. , Chaboyer Wendy , Wallis Marianne , Grimbeek Peter 
Published: July 2007

AbstractTitle.  Resilience in the operating room: developing and testing of a resilience model Aim.  This paper is a report of a study to examine the relation of perceived competence, collaboration, control, self‐efficacy, hope, coping, age, experience, education and years of employment to resilience in operating room (OR) nurses.Background.  Resilience is viewed as a vital attribute for nurses because it augments adaptation in demanding and volatile clinical environments such as ORs. However, there has been little research into the utility of resilience as a means of dealing with workplace stress, and there is only limited understanding of variables that explain resilience in the context of nursing.Method.  A correlational cross‐sectional survey design was used. Of a national sample of 2860 Australian OR nurses, 1430 were selected by systematic random sampling and invited to complete a questionnaire in 2006. The instrument included scales measuring perceived competence, collaboration, control, self‐efficacy, hope, coping and resilience, and gathered information about the demographic characteristics of respondents.Results.  Two regression models were used to develop a model of resilience. An initial model tested the hypothesis that a set of 12 explanatory variables contributed to resilience in OR nurses. Five variables (hope, self‐efficacy, coping, control and competence) explained resilience at statistically significant levels. Age, experience, education and years of employment did not contribute to resilience at statistically significant levels. The final model explained 60% of the variance. In both models, the strongest explanatory variables were hope, self‐efficacy and coping.Conclusion.  Identification of explanatory variables that contribute to resilience in ORs may assist in implementing strategies that promote these behaviours, and thus retain nurses in this specialty.
Factors associated with term low birthweight in Cardiff, Wales
Authors: Meis Paul J. , Michielutte Robert , Peters Tim J. , Wells H. Bradley , Sands R. Evan , Coles E. C. , Johns K. A. 
Published: July 2007

SummaryThis project was undertaken to examine the associations of a number of risk factors with impaired fetal growth, exemplified by delivery of a low‐birthweight infant at term (TLBW). Utilising a large database of largely homogeneous (white) births in Wales, the Cardiff Births Survey, multivariable analysis by logistic regression examined the relative importance of these risk variables. Significant independent associations with TLBW were found (in decreasing order of magnitude) for low maternal weight, pre‐eclampsia, smoking, short maternal height, late pregnancy bleeding, early pregnancy bleeding, history of a previous stillbirth, primiparity and older maternal age. In this population, risk of TBLW was associated with a number of demographic, medical and social factors. Of these, only smoking is likely to be modified by intervention.
Salt tolerance (STO), a stress‐related protein, has a major role in light signalling
Authors: Indorf Martin , Cordero Julio , Neuhaus Gunther , Rodríguez‐Franco Marta 
Published: July 2007

SummaryThe salt tolerance protein (STO) of Arabidopsis was identified as a protein conferring salt tolerance to yeast cells. In order to uncover its function, we isolated an STO T‐DNA insertion line and generated RNAi and overexpressor Arabidopsis plants. Here we present data on the hypocotyl growth of these lines indicating that STO acts as a negative regulator in phytochrome and blue‐light signalling. Transcription analysis of STO uncovered a light and circadian dependent regulation of gene expression, and analysis of light‐regulated genes revealed that STO is involved in the regulation of CHS expression during de‐etiolation. In addition, we could show that CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1) represses the transcription of STO and contributes to the destabilization of the protein in etiolated seedlings. Microscopic analysis revealed that the STO:eGFP fusion protein is located in the nucleus, accumulates in a light‐dependent manner, and, in transient transformation assays in onion epidermal cells, co‐localizes with COP1 in nuclear and cytoplasmic aggregations. However, the analysis of gain‐ and loss‐of‐function STO mutants in the cop1‐4 background points towards a COP1‐independent role during photomorphogenesis.
The SWI/SNF chromatin‐remodeling gene AtCHR12 mediates temporary growth arrest in Arabidopsis thaliana upon perceiving environmental stress
Authors: Mlynárová Ludmila , Nap Jan‐Peter , Bisseling Ton 
Published: July 2007

SummaryOne of the earliest responses of plants to environmental stress is establishing a temporary growth arrest that allows adaptation to adverse conditions. The response to abiotic stress requires the modulation of gene expression, which may be mediated by the alteration of chromatin structures. This alteration can be accomplished with the help of chromatin‐remodeling enzymes, such as the various SWI/SNF classes of ATPases. Here, we investigate the role of the Arabidopsis SNF2/Brahma‐type AtCHR12 chromatin‐remodeling gene in plant growth and development in reaction to adverse environmental conditions. We show that the AtCHR12 chromatin‐remodeling gene plays a vital role in mediating the temporary growth arrest of Arabidopsis that is induced upon perception of stress. Exposing an AtCHR12 overexpressing mutant to stress conditions leads to growth arrest of normally active primary buds, as well as to reduced growth of the primary stem. In contrast, the AtCHR12 knockout mutant shows less growth arrest than the wild‐type when exposed to moderate stress. Without stress, mutant plants are indistinguishable from the wild‐type, and the growth arrest response seems to depend on the severity of the stress applied. Modulation of AtCHR12 expression correlates with changes in expression of dormancy‐associated genes. This is in agreement with the concept of AtCHR12 participation in priming the plants for the growth arrest response. Our data indicate that AtCHR12‐associated growth arrest differs from DELLA‐mediated growth restraint. This establishes AtCHR12 as a novel gene involved in the response repertoire of plants that permits flexible modulation of growth in adverse and/or otherwise limiting environments.
De novo membranous nephropathy associated with donor‐specific alloantibody
Authors: El Kossi M. , Harmer A. , Goodwin J. , Wagner B. , Shortland J. , Angel C. , McKane W. 
Published: July 2007

Abstract:  Recent evidence suggests that alloantibody may play an aetiological role in the pathogenesis of membranous glomerulopathy in native kidneys. There is an increased awareness of the significance of alloantibody on renal transplant outcome, particularly with the development of more sensitive assays. We describe a kidney transplant patient who developed de novo membranous glomerulopathy (DNMG) with heavy proteinuria in the context of a donor‐specific alloantibody (DSA) directed against HLA DQ7. Proteinuria resolved and kidney function stabilized following treatment with mycophenolate mofetil and an angiotensin receptor blocker. The titre of the DSA fell in parallel with resolution of the proteinuria.This is the first reported case of DNMG after kidney transplantation clearly associated with a DSA. We hypothesize that de novo membranous glomerulopathy may be an atypical manifestation of acute antibody‐mediated damage. Cases of DNMG should be screened for alloantibody and the presence of alloantibody may influence the choice of therapy.
Human NK cell and ADCC reactivity against xenogeneic porcine target cells including fetal porcine islet cells
Authors: Kumagai‐Braesch Makiko , Satake Masahiro , Qian Yunjian , Holgersson Jan , Möller Erna 
Published: July 2007

ABSTRACT:In vitro studies of human NK cell‐mediated cytotoxicity and ADCC against porcine target cells were performed. Stimulation of human PBMC responder cells with either allogeneic or xenogeneic porcine cells led to a marked increase in NK cell reactivity. Maximum reactivity was reached following 3–6 days of in vitro culture. The sensitivity of target cells ranked as follows: K562 > porcine PHA‐induced lymphoblasts > resting porcine PBMC. Limiting dilution analysis showed that allo‐ and xeno‐stimulation in vitro led to differentiation of similar frequencies of effector NK cells. Split culture experiments showed that single NK effector cells were cytotoxic against both K562 and porcine lymphoblasts, demonstrating that individual NK cells lack species specificity. NK effector cell generation stimulated by xenogeneic cells was cyclosporin A (CsA) sensitive and dependent on the presence of autologous responder T lymphocytes, a dependence that was completely reconstituted by the sole addition of human IL‐2. Xenostimulation of enriched CD3+ cells also led to a preferential appearance of CD 16+ or CD56+ lymphoblasts.Natural xenoreactive human anti‐porcine antibodies are mainly of IgM and IgG2 subclasses, but antibodies in xenoimmunised patients reactive against porcine lymphocytes and fetal porcine islet cells were also of IgG1 and IgG3 subclasses. The same subclass distribution was found among antibodies specific for galα1,3 gal epitopes as shown by tests performed with α1,3 galactosyltransferase‐transfected Raji cells (human Burkitt lymphoma cells). Natural antibodies did not mediate ADCC, whereas galα1,3 gal‐specific antibodies in sera from xenoimmunised patients did. Fetal porcine islet cells were sensitive to human NK cell‐mediated cytotoxicity and to ADCC mediated by xenoimmune sera.
Anatomie comparative et chirurgicale du Tendon calcanéen commun des Mammiféres domestiques*
Authors: Pavaux Cl. , Lignereux Y. , Sautet J. Y. 
Published: July 2007

AbstractThe components of the common calcanean tendon were studied by dissection of ten limbs each of eight domestic mammalian species. The tendon of the bovine triceps surae muscle was found to consist of two distinct parts. This led to the suggestion, after examining the topography and trials on patients, to alter the tenotomy procedure (after Götze, 1932) for the treatment of spastic paresis.
Micromorphological Studies on the Stomach of Sheep during Prenatal Life
Authors: El‐Bab M. R. Fath , Schwarz R. , Ali A. M. A. 
Published: July 2007

Abstract17 Merino and Blackface sheep foetuses were used in a study of the development of the ovine foetal stomach. The histogenesis of each compartment of the stomach during the period from the 26th to the 130th day of prenatal life was described.