bluuebunny/crossref_metadata_2025 huggingface dataset:
Intact signal peptide of CD18, the β-subunit of β2-integrins, renders ruminants susceptible toMannheimia haemolyticaleukotoxin
Authors: Shanthalingam Sudarvili , Srikumaran Subramaniam
Published: August 2009

Signal peptides of membrane proteins are cleaved by endoplasmic reticulum-resident signal peptidase, and thus, are not present on mature membrane proteins. Here, we report that, contrary to the paradigm, the signal peptide of ruminant CD18, the β-subunit of β2-integrins, is not cleaved. Intriguingly, the intact signal peptide of CD18 is responsible for the susceptibility of ruminant leukocytes toMannheimia(Pasteurella)haemolyticaleukotoxin (Lkt). Inhibition of Lkt-induced cytolysis of ruminant leukocytes by CD18 peptide analogs revealed that the Lkt-binding site is formed by amino acids 5–17 of CD18, which, surprisingly, comprise most of the signal sequence. Flow cytometric analysis of ruminant leukocytes indicated the presence of the signal peptide on mature CD18 molecules expressed on the cell surface. Analysis of transfectants expressing CD18 containing the FLAG epitope at the putative cleavage site confirmed that the signal peptide of bovine CD18 is not cleaved. Analysis of the signal sequence of CD18 of eight ruminants and five nonruminants revealed that the signal sequence of CD18 of ruminants contains “cleavage-inhibiting” Q, whereas that of nonruminants contains “cleavage-conducive” G at position −5 relative to the cleavage site. Site-directed mutagenesis of Q to G at position −5 of the signal peptide of bovine CD18 resulted in the cleavage of the signal peptide and abrogation of cytolysis of transfectants expressing bovine CD18 carrying the Q(−5)G mutation. We propose that engineering cattle and other ruminants to contain this mutation would provide a novel technology to render them less susceptible to pneumonic pasteurellosis and concomitant economic losses.
The effect of second‐line surgery on reproductive performance of women with recurrent endometriosis: A systematic review
Authors: VERCELLINI PAOLO , SOMIGLIANA EDGARDO , VIGANÒ PAOLA , DE MATTEIS SARA , BARBARA GIUSSY , FEDELE LUIGI
Published: August 2009

Estimates of endometriosis recurrence after primary surgery are around 10% per annum during the first postoperative quinquennium. The aim of this study was to define the effect of reoperation in women seeking conception. A MEDLINE and PubMed search was conducted to identify English language studies published in the last 30 years evaluating reproductive performance after second‐line surgery. Repeat surgery for recurrent endometriosis and identification of women seeking pregnancy were selected. Two authors abstracted data on standardized forms. The initial literature screening yielded 41 citations, but 19 were excluded because no data on reoperation were described, seven as no original figures were included, three because analyses were performed on the same cohort, and one because extremely skewed data were reported. A total of 313 patients who sought pregnancy after repetitive surgery for recurrent endometriosis were found, 139 in six non‐comparative studies, and 174 in five retrospective comparative studies. Overall, pregnancy was achieved in 81 women (26%; 95% confidence interval (CI), 21–31%), without significant difference between the laparotomy (27%) and laparoscopy (25%) approach. Three studies compared pregnancy rate after second‐line (28/124; 23%) and primary surgery (236/577; 41%; common odds ratio (OR), 0.44; 95% CI, 0.28–0.68%), and two compared the probability of conception after in‐vitro fertilization (IVF) (14/27; 30%) and repetitive surgery (10/50; 20%; common OR, 1.51; 95% CI, 0.58–3.91%). Conclusions. The probability of conception after repeat surgery for recurrent endometriosis appeared limited and reduced compared with that after primary surgery. The results of IVF were not inferior to those of reoperation.
A synthesis of studies searching for school factors: Implications for theory and research
Authors: Kyriakides Leonidas , Creemers Bert , Antoniou Panayiotis , Demetriou Demetris
Published: August 2009

This paper reports the results of a meta‐analysis in which the dynamic model of educational effectiveness is used as a framework to search for school factors associated with student achievement. The methods and results of a synthesis of 67 studies are presented. Findings reveal that effective schools are able to develop policies and take actions in order to improve their teaching practice and learning environment. Factors excluded from the dynamic model were found to be only weakly associated with outcomes. Implications for research on school effectiveness and for improvement of practice are drawn. It is illustrated that this approach of conducting meta‐analysis helps us interpret the findings by providing support to the validity of the dynamic model and suggestions for its further development.
Schooling effects on degree performance: A comparison of the predictive validity of aptitude testing and secondary school grades at Oxford University
Authors: Ogg Tom , Zimdars Anna , Heath Anthony
Published: August 2009

This article examines the cause of school type effects upon gaining a first class degree at Oxford University, whereby for a given level of secondary school performance, private school students perform less well at degree level. We compare the predictive power of an aptitude test and secondary school grades (GCSEs) for final examination performance, using data from the Oxford Admissions Study. Both metrics are predictive of final degree performance but the school effects are only statistically robust for arts students. Private school students perform less well in final examinations relative to their GCSE results when compared with state school students, but they do not under perform relative to their aptitude test scores or in gross terms. It is therefore argued that teaching effects, associated with private school students, distort secondary school grades as an indicator of academic potential in higher education when compared to state school students.
A method for visualizing CellML models
Authors: Wimalaratne S. M. , Halstead M. D. B. , Lloyd C. M. , Cooling M. T. , Crampin E. J. , Nielsen P. F.
Published: August 2009

Motivation: The Physiome Project was established in 1997 to develop tools to facilitate international collaboration in the physiological sciences and the sharing of biological models and experimental data. The CellML language was developed to represent and exchange mathematical models of biological processes. CellML models can be very complicated, making it difficult to interpret the underlying physical and biological concepts and relationships captured/described in the mathematical model.

Results: To address this issue a set of ontologies was developed to explicitly annotate the biophysical concepts represented in the CellML models. This article presents a framework that combines a visual language, together with CellML ontologies, to support the visualization of the underlying physical and biological concepts described by the mathematical model and also their relationships with the CellML model. Automated CellML model visualization assists in the interpretation of model concepts and facilitates model communication and exchange between different communities.

Contact:  sarala.dissanayake@auckland.ac.nz

Supplementary information:  Supplementary data are available at Bioinformatics online.
A new taxonomy-based protein fold recognition approach based on autocross-covariance transformation
Authors: Dong Qiwen , Zhou Shuigeng , Guan Jihong
Published: August 2009

Motivation: Fold recognition is an important step in protein structure and function prediction. Traditional sequence comparison methods fail to identify reliable homologies with low sequence identity, while the taxonomic methods are effective alternatives, but their prediction accuracies are around 70%, which are still relatively low for practical usage.

Results: In this study, a simple and powerful method is presented for taxonomic fold recognition, which combines support vector machine (SVM) with autocross-covariance (ACC) transformation. The evolutionary information represented in the form of position-specific score matrices is converted into a series of fixed-length vectors by ACC transformation and these vectors are then input to a SVM classifier for fold recognition. The sequence-order effect can be effectively captured by this scheme. Experiments are performed on the widely used D-B dataset and the corresponding extended dataset, respectively. The proposed method, called ACCFold, gets an overall accuracy of 70.1% on the D-B dataset, which is higher than major existing taxonomic methods by 2–14%. Furthermore, the method achieves an overall accuracy of 87.6% on the extended dataset, which surpasses major existing taxonomic methods by 9–17%. Additionally, our method obtains an overall accuracy of 80.9% for 86-folds and 77.2% for 199-folds. These results demonstrate that the ACCFold method provides the state-of-the-art performance for taxonomic fold recognition.

Availability: The source code for ACC transformation is freely available at http://www.iipl.fudan.edu.cn/demo/accpkg.html.

Contact:  sgzhou@fudan.edu.cn

Supplementary information:  Supplementary data are available at Bioinformatics online.
integrOmics: an R package to unravel relationships between two omics datasets
Authors: Lê Cao Kim-Anh , González Ignacio , Déjean Sébastien
Published: August 2009

Motivation: With the availability of many ‘omics’ data, such as transcriptomics, proteomics or metabolomics, the integrative or joint analysis of multiple datasets from different technology platforms is becoming crucial to unravel the relationships between different biological functional levels. However, the development of such an analysis is a major computational and technical challenge as most approaches suffer from high data dimensionality. New methodologies need to be developed and validated.

Results:  integrOmics efficiently performs integrative analyses of two types of ‘omics’ variables that are measured on the same samples. It includes a regularized version of canonical correlation analysis to enlighten correlations between two datasets, and a sparse version of partial least squares (PLS) regression that includes simultaneous variable selection in both datasets. The usefulness of both approaches has been demonstrated previously and successfully applied in various integrative studies.

Availability:  integrOmics is freely available from http://CRAN.R-project.org/ or from the web site companion (http://math.univ-toulouse.fr/biostat) that provides full documentation and tutorials.

Contact:  k.lecao@uq.edu.au

Supplementary information:  Supplementary data are available at Bioinformatics online.
Cytotoxic Effects of Bangladeshi Medicinal Plant Extracts
Authors: Uddin Shaikh J. , Grice I. Darren , Tiralongo Evelin
Published: August 2009

To investigate the cytotoxic effect of some Bangladeshi medicinal plant extracts, 16 Bangladeshi medicinal plants were successively extracted with n‐hexane, dichloromethane, methanol and water. The methanolic and aqueous extracts were screened for cytotoxic activity against healthy mouse fibroblasts (NIH3T3) and three human cancer‐cell lines (gastric: AGS; colon: HT‐29; and breast: MDA‐MB‐435S) using the MTT assay. Two methanolic extracts (Hygrophila auriculata and Hibiscus tiliaceous) and one aqueous extract (Limnophila indica) showed no toxicity against healthy mouse fibroblasts, but selective cytotoxicity against breast cancer cells (IC50 1.1–1.6 mg mL−1). Seven methanolic extracts from L. indica, Clerodendron inerme, Cynometra ramiflora, Xylocarpus moluccensis, Argemone mexicana, Ammannia baccifera and Acrostichum aureum and four aqueous extracts from Hygrophila auriculata, Bruguiera gymnorrhiza, X. moluccensis and Aegiceras corniculatum showed low toxicity (IC50 > 2.5 mg mL−1) against mouse fibroblasts but selective cytotoxicity (IC50 0.2–2.3 mg mL−1) against different cancer cell lines. The methanolic extract of Blumea lacera showed the highest cytotoxicity (IC50 0.01–0.08 mg mL−1) against all tested cell lines among all extracts tested in this study. For some of the plants their traditional use as anticancer treatments correlates with the cytotoxic results, whereas for others so far unknown cytotoxic activities were identified.
TheColletotrichum orbiculare ssd1Mutant EnhancesNicotiana benthamianaBasal Resistance by Activating a Mitogen-Activated Protein Kinase Pathway
Authors: Tanaka Shigeyuki , Ishihama Nobuaki , Yoshioka Hirofumi , Huser Aurélie , O'Connell Richard , Tsuji Gento , Tsuge Seiji , Kubo Yasuyuki
Published: August 2009

Plant basal resistance is activated by virulent pathogens in susceptible host plants. A Colletotrichum orbiculare fungal mutant defective in the SSD1 gene, which regulates cell wall composition, is restricted by host basal resistance responses. Here, we identified the Nicotiana benthamiana signaling pathway involved in basal resistance by silencing the defense-related genes required for restricting the growth of the C. orbiculare mutant. Only silencing of MAP Kinase Kinase2 or of both Salicylic Acid Induced Protein Kinase (SIPK) and Wound Induced Protein Kinase (WIPK), two mitogen-activated protein (MAP) kinases, allowed the mutant to infect and produce necrotic lesions similar to those of the wild type on inoculated leaves. The fungal mutant penetrated host cells to produce infection hyphae at a higher frequency in SIPK WIPK-silenced plants than in nonsilenced plants, without inducing host cellular defense responses. Immunocomplex kinase assays revealed that SIPK and WIPK were more active in leaves inoculated with mutant fungus than with the wild type, suggesting that induced resistance correlates with MAP kinase activity. Infiltration of heat-inactivated mutant conidia induced both SIPK and WIPK more strongly than did those of the wild type, while conidial exudates of the wild type did not suppress MAP kinase induction by mutant conidia. Therefore, activation of a specific MAP kinase pathway by fungal cell surface components determines the effective level of basal plant resistance.
ArabidopsisCortical Microtubules Are Initiated along, as Well as Branching from, Existing Microtubules
Authors: Chan Jordi , Sambade Adrian , Calder Grant , Lloyd Clive
Published: August 2009

The principles by which cortical microtubules self-organize into a global template hold important implications for cell wall patterning. Microtubules move along bundles of microtubules, and neighboring bundles tend to form mobile domains that flow in a common direction. The bundles themselves move slowly and for longer than the individual microtubules, with domains describing slow rotary patterns. Despite this tendency for colinearity, microtubules have been seen to branch off extant microtubules at ∼45°. To examine this paradoxical behavior, we investigated whether some microtubules may be born on and grow along extant microtubule(s). The plus-end markers Arabidopsis thaliana end binding protein 1a, AtEB1a-GFP, and Arabidopsis SPIRAL1, SPR1-GFP, allowed microtubules of known polarity to be distinguished from underlying microtubules. This showed that the majority of microtubules do branch but in a direction heavily biased toward the plus end of the mother microtubule: few grow backward, consistent with the common polarity of domains. However, we also found that a significant proportion of emergent comets do follow the axes of extant microtubules, both at sites of apparent microtubule nucleation and at cross-over points. These phenomena help explain the persistence of bundles and counterbalance the tendency to branch.
Down‐regulation of pescadillo inhibits proliferation and tumorigenicity of breast cancer cells
Authors: Li Jun , Yu Liang , Zhang Huizhong , Wu Jueheng , Yuan Jie , Li Xiaoxi , Li Mengfeng
Published: August 2009

Pescadillo, which has been found to be involved in the process of ribosomal biogenesis, has been demonstrated to play a role in embryonic development, DNA replication, and gene transcription. While deregulation of ribosomal biogenesis was also found to contribute to carcinogenesis, and proteins that regulate ribosomal biogenesis are commonly overexpressed in primary tumors, little is known about the clinical significance and biological function of pescadillo in human breast cancer. In the current study, we found that the expression of pescadillo was markedly up‐regulated in human breast cancer cells and tissues at both mRNA and protein levels. Immunohistochemical analysis revealed that pescadillo expression in clinical stage I–IV primary breast cancer tissues was statistically significantly higher than that in normal breast tissues (P < 0.05). Furthermore, we demonstrated that knockdown pescadillo with RNAis inhibited cell proliferation and the colony‐forming ability of the cells. Anchorage‐independent growth ability assay indicated that ablation of pescadillo led to the reduction of breast cancer cells tumorigenicity in vitro. Moreover, depletion of endogenous pescadillo resulted in decreased expression of cell cycle protein cyclin D1 and up‐regulation of cyclin‐dependent kinase inhibitor p27Kip1, as well as attenuated protein kinase B (Akt)/glycogen synthase kinase 3 beta (GSK‐3β) signaling. Taken together, our results suggest that pescadillo might play a role in promoting the proliferation and carcinogenesis of human breast cancer, and thereby might be a potential target for human breast cancer treatment. (Cancer Sci 2009; 100: 2255–2260)
Uncomplicated peptic ulcer in the UK: trends from 1997 to 2005
Authors: CAI S. , GARCÍA RODRÍGUEZ L. A. , MASSÓ‐GONZÁLEZ E. L. , HERNÁNDEZ‐DÍAZ S.
Published: August 2009

Background  Few studies have examined the incidence of uncomplicated peptic ulcer or the trends in factors affecting its incidence.

Aim  To estimate the incidence rate of uncomplicated peptic ulcer in the UK from 1997 to 2005 and report temporal changes in the main known preventive and risk factors.

Methods  Population‐based cohort study of 1 049 689 patients enrolled in The Health Improvement Network in the UK. We estimated the incidence rate of uncomplicated peptic ulcer and evaluated temporal trends in demographic characteristics and prescription patterns for various anti‐inflammatory and gastroprotective agents.

Results  Overall uncomplicated peptic ulcer incidence was 0.75 cases per 1000 persons‐years, declining from 1.1 to 0.52 cases per 1000 person‐years between 1997 and 2005. Distributions of age, gender and alcohol habits were similar in 1997 and 2005. The proportion of documented Helicobacter pylori‐negative cases increased from 5% to 12%. Monthly prevalence of subjects with prescriptions for traditional non‐aspirin NSAIDs changed from 7.7% to 6.8%, Coxibs from 0% to 0.7%, and proton pump inhibitors (PPIs) from 2.4% to 7.4%. The proportion of subjects on prescription NSAIDs on PPIs increased continuously over time.

Conclusion  A reduction in H. pylori‐related peptic ulcers, changing patterns in NSAID use and increasing PPI use may have contributed to a decline in uncomplicated peptic ulcer incidence in the UK.
Predictors of gastroduodenal erosions in patients taking low‐dose aspirin
Authors: HART J. , HAWKEY C. J. , LANAS A. , NAESDAL J. , TALLEY N. J. , THOMSON A. B. R. , YEOMANS N. D.
Published: August 2009

Background  Gastroduodenal ulcers are common in patients taking low‐dose aspirin. However, the factors predisposing to mucosal erosions, the precursor lesions, are not well known.

Aims  To examine the potential risk factors for the development of erosions in patients chronically taking low‐dose aspirin.

Methods  Patients included were taking aspirin 75–325 mg daily for >28 days. Exclusion criteria included use of nonsteroidal anti‐inflammatory and ulcer‐healing drugs. Demographic data were collected at baseline, prior to endoscopy to determine the frequency and number of erosions and Helicobacter pylori status. In those without ulcer or other exclusions, endoscopy was repeated at 3 months.

Results  Fewer patients had gastric erosions if they were H. pylori +ve (48.5% vs. 66.4% in H. pylori−ve patients at baseline, P = 0.17; 40.0% vs. 64.1% at 3 months, P = 0.029). If gastric erosions were present, they were also less numerous in H. pylori +ve patients (3.61 ± 0.83 vs. 4.90 ± 0.53 at baseline, P = 0.026; 2.17 ± 0.68 vs. 5.68 ± 0.86 at 3 months, P = 0.029). There was a trend (0.1 > P > 0.05) for more gastric erosions in those taking >100 mg/day aspirin. Males had more duodenal erosions at baseline (25.2% vs. 7.5%, P = 0.016). Patient age did not affect the presence or number of erosions. H. Pylori was not significantly associated with duodenal erosion numbers.

Conclusions  Helicobacter pylori infection may partially protect against low‐dose aspirin‐induced gastric erosions; damage to the stomach appears weakly dose‐related; and older age does not increase the risk of erosions.
Sensitization profiles in birch pollen‐allergic patients with and without oral allergy syndrome to apple: lessons from multiplexed component‐resolved allergy diagnosis
Authors: Ebo D. G. , Bridts C. H. , Verweij M. M. , De Knop K. J. , Hagendorens M. M. , De Clerck L. S. , Stevens W. J.
Published: August 2009

Background
Component‐resolved diagnosis (CRD) using microarray technology has recently been introduced into the field of clinical allergology.

Objective
To further validate the use of CRD by microarray technology in allergy diagnosis.

Methods
Thiry‐seven patients allergic to birch pollen were included. The discriminative value of apple‐specific IgE (sIgE), recombinant Mal d 1 (rMal d 1) sIgE, apple skin prick test and rMal d 1 on the microarray was assessed between patients with a birch‐related oral allergy syndrome to apple (OAS+, n=20) and healthy control individuals (HC, n=8) without a history of inhalant allergies or apple‐induced OAS. An additional comparative analysis was carried out with individuals allergic to birch pollen allergy without OAS (OAS−; n=17).

Results
rMal d 1 coupled to the microarray constitutes a discriminative marker between OAS+ and HC with a sensitivity 95% and a specificity of 100%. However, in parallel with the traditional sIgE assay, 15 out of 17 OAS− individuals (88%) also displayed IgE reactivity to rMal d 1 coupled to the microarray. OAS− individuals are more frequently sensitized to mite (about three to four times), cat and dog dander (about two to three times) and grass pollen (about 1.5 times) as compared with OAS+ patients.

Conclusion
At first glance, CRD by microarray seems to be a reliable instrument in the diagnosis of apple‐mediated OAS in birch pollen allergy. However, for discriminating between sensitization and a real allergy, micro‐arrayed rMal d 1 offers no advantage over conventional quantification of rMal d 1 sIgE. Most interestingly, within a single run, birch pollen‐allergic patients without OAS to apple were shown to display a broader sensitization to classical inhalant allergens than birch pollen‐allergic patients with an apple‐related OAS.

Cite this as: D. G. Ebo, C. H. Bridts, M. M. Verweij, K. J. De Knop, M. M. Hagendorens, L. S. De Clerck and W. J. Stevens, Clinical & Experimental Allergy, 2010 (40) 339– 347.
Minimal persistent inflammation in allergic rhinitis: implications for current treatment strategies
Authors: Canonica G W , Compalati E
Published: August 2009

Patients with allergic rhinitis have traditionally been placed into ‘seasonal’ and ‘perennial’ categories, which do not account for the subclinical inflammatory state that exists in many patients. In subjects with seasonal and perennial allergic rhinitis, even subthreshold doses of allergen have been found to cause inflammatory cell infiltration in the nasal mucosa, including increases in expression of cellular adhesion molecules, nasal and conjunctival eosinophilia, and other markers of inflammation, which do not result in overt allergy symptoms. This state – which has been termed ‘minimal persistent inflammation’– may contribute to hyperreactivity and increased susceptibility to development of clinical symptoms as well as common co-morbidities of allergic rhinitis, such as asthma. Treating overt allergy symptoms as well as this underlying inflammatory state requires agents that have well-established clinical efficacy, convenient administration, potent anti-inflammatory effects and proven long-term safety, so that long-term continuous administration is feasible. Of the three major classes of commonly used allergic rhinitis medications – intranasal corticosteroids, anti-histamines, and anti-leukotrienes – intranasal corticosteroids appear to represent the most reasonable therapeutic option in patients who would benefit from continuous inhibition of persistent inflammation.
Competitive adsorption between phosphate and carboxylic acids: quantitative effects and molecular mechanisms
Authors: Lindegren M. , Persson P.
Published: August 2009

The competitive adsorption at the water‐goethite interface between phosphate and a carboxylic acid, either oxalate, citrate, 1,2,3,4‐butanetetracarboxylic acid (BTCA), mellitate or Suwannee River Standard Fulvic Acid 1S101F (FA), was investigated over a wide pH range (3–9) by means of batch experiments and attenuated total reflectance Fourier transform infrared (ATR‐FTIR) spectroscopy. The quantitative results from the competitive adsorption measurements show that the efficiency of the organic acids in competing with phosphate was in the order oxalate < citrate < BTCA ≅ FA < mellitate. Oxalate showed no detectable effect, whereas the effect in the mellitate system was strong, and the aggregative results indicate that an increasing number of carboxylic groups favours competitive ability towards phosphate. The infrared spectroscopic results show conclusively that competition for goethite surface sites between carboxylic acids and phosphate is not a ligand‐exchange reaction between inner‐sphere surface complexes. Instead, ligands capable of multiple H‐bonding interactions are required to out‐compete and desorb surface complexes of phosphate. The fact that partially protonated organic acids are the most efficient emphasizes the importance of both H‐accepting carboxylate groups and H‐donating carboxylic acid groups for the competitive effect.
Characteristics of students assigned to technology‐based instruction
Authors: Ross John A. , Sibbald Tim , Bruce Catherine D.
Published: August 2009

Previous research has examined factors influencing teacher decisions to integrate technology using between‐teacher designs. This study used a within‐teacher design to compare students who were assigned multi‐media learning objects for learning fractions with students taught by the same teachers who were not assigned to the technology. There were two conditions: (1) teachers were asked to limit the number of assigned students to 25% of their class (N = 375 grade 7–10 students) and (2) teachers could assign as many students as they wanted (N = 149 grade 7 students). In the constrained decision setting, students assigned to the technology were more likely than students not assigned to score lower on a fractions achievement test, have dysfunctional attitudes towards mathematics learning, have low self‐efficacy, exert low effort, and be male. In the unconstrained decision setting, 70% of students were assigned the technology and the only statistically significant predictor was prior achievement. Teachers' criteria were congruent with research identifying correlates of mathematics achievement and comfort with technology.
Ultrastructural characterization of apoptotic granulosa cells in caprine ovary
Authors: SHARMA R.K. , BHARDWAJ J.K.
Published: August 2009

The unique phenomenon of cell proliferation and apoptosis is encountered in the ovarian follicles undergoing early stages of atresia. The aim of this study was to verify the morphological variations in these two physiologically distinct processes operating in antral follicles of caprine ovaries using histological and ultrastructural techniques. Histologically the degenerating granulosa cells were characterized by condensed cytoplasm, and nucleus fragmentation in hazy cytosol. The pyknotic nuclei of degenerating cells stained darkly with haematoxylin and giemsa while the cytoplasm was eosinophilic. Under electron microscopy, apoptosis was marked by asymmetrical shrinkage, vacuolization of cytoplasm, swollen and vacuolated mitochondria, increased irregularity and/or fragmentation of nucleus, chromatin condensation and finally, production of membrane enclosed nuclear fragments containing intracellular material, the apoptotic bodies. The parallel use of these two methods on caprine ovaries has enabled us to analyse the decline in the frequency of granulosa cells during follicular atresia due to apoptosis.
Computation of a tetrahedral mesh for striated muscle deformation simulation
Authors: ZAHER A.R. , WEICHERT F. , BRAMSIEPE N. , LANDES C.A. , AWAD S. , SHAMAA A. , WAGNER M.
Published: August 2009

Competing concepts exist regarding surgery for instance of the cleft lip and palate to date. Morphology‐based simulations at histological scale may one day be used to help the surgeon predict the possible outcome of a variety of approaches. It however can be a challenge to generate volume meshes that are applicable to the mathematical modelling of three‐dimensional spatial modifications. Computation of surface meshes may be considered less delicate. The aim of this study is to design and evaluate a novel algorithm that supports finite element methods. Images of histological serial sections of a striated muscle were segmented. Results of the three‐dimensional reconstruction of multiple layers of the polygonal segmentation data characterized the hull of the muscle. The corresponding surface mesh was then converted into a tetrahedral mesh to generate volume. This was achieved by mapping multiple template types onto neighbouring intersection polygons. Muscle contraction was subsequently simulated by mesh deformation. The technique successfully generated volumes and was able to provide data on contraction directions. The mesh supported a novel approach to simulate representations of contraction. However, several drawbacks were evident. Mathematical modelling of scenarios with more than one striated muscle will require considerable modification of the currently presented approach. Future studies need to then evaluate the applicability of volume meshes to represent arrays of three‐dimensional biological objects. Surface mesh based mathematical modelling of cleft lip and palate surgery and its results are therefore not yet in reach.
Antipsychotic‐induced hyperprolactinaemia in patients with schizophrenia: considerations in relation to bone mineral density
Authors: STUBBS B.
Published: August 2009

Accessible summary

Schizophrenia affects about 1% of the world's population and such patients are at risk of a variety of physical health conditions, including diabetes, coronary heart disease, hypertensions and osteoporosis.

Osteoporosis secondary to antipsychotic medication‐induced hyperprolactinaemia (i.e. raised prolactin levels) has received little attention, when compared with metabolic syndrome for instance.

A recent study established that schizophrenia and prolactin‐raising antipsychotic medication are directly associated with hip fractures. This is important and concerning as osteoporotic fractures are associated with much morbidity and mortality.

This paper reviews the literature on antipsychotic‐induced hyperprolactinaemia and its subsequent effects on bone mineral density.

Schizophrenia affects about 1% of the world's population. Those with schizophrenia are at elevated risk of a variety of physical health conditions, including diabetes, coronary heart disease, hypertension and osteoporosis. Osteoporosis secondary to antipsychotic‐induced hyperprolactinaemia (i.e. raised prolactin levels) has received little attention, when compared with reports on metabolic syndrome for instance. A recent study established that schizophrenia and prolactin‐raising antipsychotic medication is directly associated with hip fractures. This is important and concerning as osteoporotic fractures are associated with much morbidity and mortality. This paper reviews the literature on antipsychotic‐induced hyperprolactinaemia and its subsequent effects on bone mineral density.
The halophilic alkalithermophile Natranaerobius thermophilus adapts to multiple environmental extremes using a large repertoire of Na+(K+)/H+ antiporters
Authors: Mesbah Noha M. , Cook Gregory M. , Wiegel Juergen
Published: August 2009

Natranaerobius thermophilus is an unusual extremophile because it is halophilic, alkaliphilic and thermophilic, growing optimally at 3.5 M Na+, pH55°C 9.5 and 53°C. Mechanisms enabling this tripartite lifestyle are essential for understanding how microorganisms grow under inhospitable conditions, but remain unknown, particularly in extremophiles growing under multiple extremes. We report on the response of N. thermophilus to external pH at high salt and elevated temperature and identify mechanisms responsible for this adaptation. N. thermophilus exhibited cytoplasm acidification, maintaining an unanticipated transmembrane pH gradient of 1 unit over the entire extracellular pH range for growth. N. thermophilus uses two distinct mechanisms for cytoplasm acidification. At extracellular pH values at and below the optimum, N. thermophilus utilizes at least eight electrogenic Na+(K+)/H+ antiporters for cytoplasm acidification. Characterization of these antiporters in antiporter‐deficient Escherichia coli KNabc showed overlapping pH profiles (pH 7.8–10.0) and Na+ concentrations for activity (K0.5 values 1.0–4.4 mM), properties that correlate with intracellular conditions of N. thermophilus. As the extracellular pH increases beyond the optimum, electrogenic antiport activity ceases, and cytoplasm acidification is achieved by energy‐independent physiochemical effects (cytoplasmic buffering) potentially mediated by an acidic proteome. The combination of these strategies allows N. thermophilus to grow over a range of extracellular pH and Na+ concentrations and protect biomolecules under multiple extreme conditions.
Effects of Lipopolysaccharide on the Induction of Mixed Chimerism in Cyclophosphamide‐Induced Tolerance
Authors: Onzuka T. , Tomita Y. , Shimizu I. , Okano S. , Yamada H. , Yoshikai Y. , Tominaga R.
Published: August 2009

Cyclophosphamide (CP)‐induced tolerance is a mixed chimerism‐based tolerance and is one of the strategies used to induce transplant tolerance. Toll‐like receptor (TLR) agonists are reportedly able to abrogate the induction of tolerance by activating alloreactive T cells, or by inhibiting Treg cells. However, little is known about the effect of the immune response mediated by TLR on mixed chimerism‐based tolerance protocols. In this study, we evaluated the influence of lipopolysaccharide (LPS), which is best known as an TLR4 agonist, on CP‐induced tolerance. BALB/c (H‐2d) mice received a conditioning regimen consisting of 108 donor DBA/2 (H‐2d) spleen cells (SC) on day 0 and 200 mg/kg CP on day 2. A single dose of 20 μg LPS was injected on day −2, 0, 7, or 35. Our results showed that LPS infusion at any time point resulted in chronic rejection of donor skin grafts and the abrogation of mixed chimerism in 33–60% of recipients. We found a correlation between skin graft acceptance and higher levels of mixed chimerism. Flow cytometric analysis revealed that donor‐reactive T cells were permanently eliminated, regardless of LPS infusion. In conclusion, LPS‐infusion had little influence on the immune response of donor‐reactive T cells, but had a significant effect on the induction and maintenance of mixed chimerism in CP‐induced tolerance.
Identification of novel proteins in isolated polyphosphate vacuoles in the primitive red alga Cyanidioschyzon merolae
Authors: Yagisawa Fumi , Nishida Keiji , Yoshida Masaki , Ohnuma Mio , Shimada Takashi , Fujiwara Takayuki , Yoshida Yamato , Misumi Osami , Kuroiwa Haruko , Kuroiwa Tsuneyoshi
Published: August 2009

Plant vacuoles are organelles bound by a single membrane, and involved in various functions such as intracellular digestion, metabolite storage, and secretion. To understand their evolution and fundamental mechanisms, characterization of vacuoles in primitive plants would be invaluable. Algal cells often contain polyphosphate‐rich compartments, which are thought to be the counterparts of seed plant vacuoles. Here, we developed a method for isolating these vacuoles from Cyanidioschyzon merolae, and identified their proteins by MALDI TOF‐MS. The vacuoles were of unexpectedly high density, and were highly enriched at the boundary between 62 and 80% w/v iodixanol by density‐gradient ultracentrifugation. The vacuole‐containing fraction was subjected to SDS–PAGE, and a total of 46 proteins were identified, including six lytic enzymes, 13 transporters, six proteins for membrane fusion or vesicle trafficking, five non‐lytic enzymes, 13 proteins of unknown function, and three miscellaneous proteins. Fourteen proteins were homologous to known vacuolar or lysosomal proteins from seed plants, yeasts or mammals, suggesting functional and evolutionary relationships between C. merolae vacuoles and these compartments. The vacuolar localization of four novel proteins, namely CMP249C (metallopeptidase), CMJ260C (prenylated Rab receptor), CMS401C (ABC transporter) and CMT369C (o‐methyltransferase), was confirmed by labeling with specific antibodies or transient expression of hemagglutinin‐tagged proteins. The results presented here provide insights into the proteome of C. merolae vacuoles and shed light on their functions, as well as indicating new features.
3D reconstruction and dynamic modeling of root architecture in situ and its application to crop phosphorus research
Authors: Fang Suqin , Yan Xiaolong , Liao Hong
Published: August 2009

Root architecture plays important roles in plant water and nutrient acquisition. However, accurate modeling of the root system that provides a realistic representation of roots in the soil is limited by a lack of appropriate tools for the non‐destructive and precise measurement of the root system architecture in situ. Here we describe a root growth system in which the roots grow in a solid gel matrix that was used to reconstruct 3D root architecture in situ and dynamically simulate its changes under various nutrient conditions with a high degree of precision. A 3D laser scanner combined with a transparent gel‐based growth system was used to capture 3D images of roots. The root system skeleton was extracted using a skeleton extraction method based on the Hough transformation, and mesh modeling using Ball‐B spline was employed. We successfully used this system to reconstruct rice and soybean root architectures and determine their changes under various phosphorus (P) supply conditions. Our results showed that the 3D root architecture parameters that were dynamically calculated based on the skeletonization and simulation of root systems were significantly correlated with the biomass and P content of rice and soybean based on both the simulation system and previous reports. Therefore, this approach provides a novel technique for the study of crop root growth and its adaptive changes to various environmental conditions.
Species diversity of Leishmania (Viannia) parasites circulating in an endemic area for cutaneous leishmaniasis located in the Atlantic rainforest region of northeastern Brazil
Authors: Brito Maria Edileuza F. , Andrade Maria S. , Mendonça Mitzi G. , Silva Cláudio J. , Almeida Ericka L. , Lima Bruna S. , Félix Simone M. , Abath Frederico G. C. , Da Graça Grazielle C. , Porrozzi Renato , Ishikawa Edna A. , Shaw Jeffrey J. , Cupolillo Elisa , Brandão‐Filho Sinval P.
Published: August 2009

Objectives  To identify the aetiological agents of cutaneous leishmaniasis and to investigate the genetic polymorphism of Leishmania (Viannia) parasites circulating in an area with endemic cutaneous leishmaniasis (CL) in the Atlantic rainforest region of northeastern Brazil.

Methods  Leishmania spp. isolates came from three sources: (i) patients diagnosed clinically and parasitologically with CL based on primary lesions, secondary lesions, clinical recidiva, mucocutaneous leishmaniasis and scars; (ii) sentinel hamsters, sylvatic or synanthropic small rodents; and (iii) the sand fly species Lutzomyia whitmani. Isolates were characterised using monoclonal antibodies, multilocus enzyme electrophoresis (MLEE) and polymerase chain reaction‐restriction fragment length polymorphism of the internal transcribed spacer region rDNA locus.

Results  Seventy‐seven isolates were obtained and characterised. All isolates were identified as Leishmania (Viannia) braziliensis serodeme 1 based on reactivity to monoclonal antibodies. MLEE identified 10 zymodemes circulating in the study region. Most isolates were classified as zymodemes closely related to L. (V.) braziliensis, but five isolates were classified as Leishmania (Viannia) shawi. All but three of the identified zymodemes have so far been observed only in the study region. Enzootic transmission and multiclonal infection were observed.

Conclusions  Our results confirm that transmission cycle complexity and the co‐existence of two or more species in the same area can affect the level of genetic polymorphism in a natural Leishmania population. Although it is not possible to make inferences as to the modes of genetic exchange, one can speculate that some of the zymodemes specific to the region are hybrids of L. (V.) braziliensis and L. (V.) shawi.
Standardized interventions in international health: Procrustes, where are you now?
Authors: Maher Dermot
Published: August 2009

Two opposing views on implementing interventions in international health are represented on the one hand by ‘one size doesn’t fit all’ and on the other by the promotion of standard approaches. Successes in scaling up access to tuberculosis diagnosis and treatment and access to antiretroviral therapy provide examples of the benefits of a standardized approach to disease management. These benefits may be extended to the management of the emerging epidemic of non‐communicable diseases in developing countries. An enthusiastic advocate of standardization, Procrustes (a figure in Greek mythology) went to extreme lengths but his tendencies can be a useful reminder that one size may not fit all, but does fit enough.
Quality of integrated chronic care measured by patient survey: identification, selection and application of most appropriate instruments
Authors: Vrijhoef Hubertus J. M. , Berbee Rieneke , Wagner Edward H. , Steuten Lotte M. G.
Published: August 2009

Objective To identify the most appropriate generic instrument to measure experience and/or satisfaction of people receiving integrated chronic care.

Background Health care is becoming more user‐centred and, as a result, the experience of users of care and evaluation of their experience and/or satisfaction is taken more seriously. It is unclear to what extent existing instruments are appropriate in measuring the experience and/or satisfaction of people using integrated chronic care.

Methods Instruments were identified by means of a systematic literature review. Appropriateness of instruments was analysed on seven criteria. The two most promising instruments were translated into Dutch, if necessary, and administered to a convenience sample of 109 people with a chronic illness. Data derived from respondents were analysed statistically. Focus‐group interviews were conducted to assess the semantic and technical equivalence as well as opinions of people about the applicability and relevance of the translated instruments.

Results From 37 instruments identified, the Patients’ Assessment of Care for chronIc Conditions (PACIC) and the short form of the Patient Satisfaction Questionnaire III (PSQ‐18) were selected as most promising instruments. Both instruments produced similar median scores across people with different chronic conditions. The overall PACIC and its subscales and the overall PSQ‐18 were highly internally consistent, but not the PSQ‐18 subscales. Overall, the PACIC demonstrated better psychometric characteristics. PACIC and PSQ‐18 scores were found to be moderately correlated. Whereas more respondents preferred the PSQ‐18, focus‐group participants regarded the PACIC to be more applicable and relevant. The technical and semantic equivalence of both instruments were sufficient.

Conclusions Because of its psychometric characteristics, perceived applicability and relevance, the PACIC is the most appropriate instrument to measure the experience of people receiving integrated chronic care.
Développement sous‐cortical d'un ravageur des pins: Pissodes notatus F. (Col., Curculionidae)
Authors: Alauzet C.
Published: August 2009

On the subcortical development of the pine pest, Pissodes notatus F. (Col., Curculionidae). II. Evidence of a facultative diapause

The underbark development of P. notatus during winter was regulated by two main factors resulting in its dormancy: on the one hand, a thermic quiescence which stopped the growth of every stage, and, on the other hand, a facultative diapause involving the fourth larval stage. This diapause occurred only on the brood of adults which laid eggs during a decreasing daylength, and when the larvae of which were submitted to low temperatures during a sufficiently long period. Ecological consequences of these characteristics are discussed.

Zur subkortikalen Entwicklung des Kiefernschädlings Pissodes notatus F. (Col., Curculionidae). II. Nachweis einer fakultativen Diapause

Die Entwicklung von P. notatus unter der Rinde während des Winters wurde durch zwei Hauptfaktoren reguliert, die in einer Dormanz resultierten: eine thermische Quieszenz, die das Wachstum in jedem Larvenstadium stoppt sowie eine fakultative Diapause während des vierten Larvenstadiums. Diese Diapause tritt nur bei der Brut solcher Adulten auf, die ihre Eier während abnehmender Tägeslänge ablegten und die daraus schlüpfenden Larven ausreichend lange einer niedrigen Temperatur ausgesetzt waren. öml;kologische Konsequenzen dieser Kriterien werden diskutiert.
Response in Ips typographus to logging waste odours and synthetic pheromones
Authors: Austarå Ø. , Bakke A. , Midtgaard F.
Published: August 2009

Of two separately performed experiments, the one indicated a primary attraction of Ips typo‐graphus to cut Norway spruce branches with green foliage of winter felled healthy, mature trees.

In the other experiment, the presence of foliated spruce branches at drainpipe traps loaded with synthetic pheromones significantly increased the beetle catches.

Lockwirkung von Schlagabraum und syntbetischen Pheromonen auf Ips typograpbus

Bei zwei unabhängig voneinander durchgeführten Experimenten ergab das erstere, daß abge‐schnittene, benadelte Äste von im Winter gefällten, gesunden Fichten Primäranlockung auf den Buchdrucker, I. typograpbus, ausüben. Im anderen Versuch wurde durch benadelte Fichtenäste in unmittelbarer Nähe von mit synthetischen Pheromonen bestückten Rohrfallen, die Anzahl gefangener Käfer signifikant erhöht.