bluuebunny/crossref_metadata_2025 huggingface dataset:
Two tail-anchored protein variants, differing in transmembrane domain length and intracellular sorting, interact differently with lipids
Authors: Ceppi Paolo , Colombo Sara , Francolini Maura , Raimondo Francesca , Borgese Nica , Masserini Massimo
Published: October 2005

C-tail-anchored (TA) proteins often require a transmembrane domain of moderate hydrophobicity to maintain their endoplasmic reticulum residence, but the suggested role of protein-lipid interactions in this phenomenon has not been established. Here, we studied the interaction of TA proteins with lipids by differential scanning calorimetry by using a model system consisting of liposomes embedding either of two forms of cytochrome
b
5
: the endoplasmic reticulum-resident wild-type (b
5
wt) and a mutant thereof (b
5
ext), that contains five extra nonpolar amino acids in its transmembrane domain and, therefore, reaches the plasma membrane. The proteins were incorporated into liposomes of palmitoyl-oleyl-phosphatidylcholine (POPC) or POPC mixed with either distearoyl-phosphatidylserine (DSPS), palmitoyl-oleyl-phosphatidylserine (POPS), distearoyl-phosphatidylcholine (DSPC), or C16-ceramide (CER). POPC liposomes displayed a single thermotropic transition centered at -3.4°C. When present, the second lipid formed a domain within the POPC bilayer, as indicated by the appearance of an additional peak. This peak was centered at temperatures close to 0°C in the case of liposomes containing 10% CER, DSPS, and POPS and at 23°C in the case of DSPC, likely reflecting a higher degree of molecular packing for DSPC domains. In DSPS/POPC, POPS/POPC, or CER/POPC, but not in DSPC/POPC liposomes, the insertion of b
5
wt increased, whereas b
5
ext decreased, the relative contribution to the total enthalpy of the higher temperature, phase-separated component. These results were confirmed with fluorescence measurements by using pyrene-labeled phospholipids. The dissimilar interaction with lipids of these two differently localized TA proteins could have implications for their intracellular sorting.
Evaluation of the functional diffusion map as an early biomarker of time-to-progression and overall survival in high-grade glioma
Authors: Hamstra Daniel A. , Chenevert Thomas L. , Moffat Bradford A. , Johnson Timothy D. , Meyer Charles R. , Mukherji Suresh K. , Quint Douglas J. , Gebarski Stephen S. , Fan Xiaoying , Tsien Christina I. , Lawrence Theodore S. , Junck Larry , Rehemtulla Alnawaz , Ross Brian D.
Published: November 2005

Diffuse malignant gliomas, the most common type of brain tumor, carry a dire prognosis and are poorly responsive to initial treatment. The response to treatment is typically evaluated by measurements obtained from radiographic images several months after the start of treatment; therefore, an early biomarker of tumor response would be useful for making early treatment decisions and for prognostic information. Thirty-four patients with malignant glioma were examined by diffusion MRI before treatment and 3 weeks later. These images were coregistered, and differences in tumor-water diffusion values were calculated as functional diffusion maps (fDM), which were correlated with the radiographic response, time-to-progression (TTP), and overall survival (OS). Changes in fDM at 3 weeks were closely associated with the radiographic response at 10 weeks. The percentage of the tumor undergoing a significant change in the diffusion of water (
V
T
) was different between patients with progressive disease (PD) vs. stable disease (SD) (
P
< 0.001). Patients classified as PD by fDM analysis at 3 weeks were found to have a shorter TTP compared with SD (median TTP, 4.3 vs. 7.3 months;
P
< 0.04). By using fDM, early patient stratification also was correlated with shorter OS in the PD group compared with SD patients (median survival, 8.0 vs. 18.2 months;
P
< 0.01). On the basis of fDM, tumor assessment provided an early biomarker for response, TTP, and OS in patients with malignant glioma. Further evaluation of this technique is warranted to determine whether it may be useful in the individualization of treatment or evaluation of the response in clinical protocols.
Effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viableBifidobacterium animalison the intestinal microflora during the first 4 months of life
Authors: Bakker-Zierikzee Astrid M. , Alles Martine S. , Knol Jan , Kok Frans J. , Tolboom Jules J. M. , Bindels Jacques G.
Published: November 2005

Adding prebiotics or probiotics to infant formula to improve the intestinal flora of formula-fed infants is considered to be a major innovation. Several companies have brought relevant formulations onto the market. However, comparative data on the effects of pre- and probiotics on the intestinal microflora of infants are not available. The present study aimed to compare the effects of infant formula containing a mixture of galacto- and fructo-oligosaccharides or viableBifidobacterium animalison the composition and metabolic activity of the intestinal microflora. Before birth, infants were randomised and double blindly allocated to one of three formulas. The prebiotic (GOS/FOS) group (n19) received regular infant formula supplemented with a mixture of galacto-oligosaccharides and fructo-oligosaccharides (6g/l). The probiotic (Bb-12) group (n19) received the same formula supplemented with 6·0×1010viable cells ofB. animalisper litre. The standard group (n19) received non-supplemented regular formula. A group of sixty-three breast-fed infants was included as a reference group. Faecal samples were taken at postnatal day 5 and 10, and week 4, 8, 12 and 16. Compared with the groups fed Bb-12 and standard formula, the GOS/FOS formula group showed higher faecal acetate ratio (69·7% (sem 2·7), 69·9% (sem 3·9) and 82·2% (sem 5·3);P<0·05) and lactate concentration (11·3 (sem 7·9), 3·1 (sem 2·3) and 34·7 (sem 10·7) mmol/kg faeces) and lower pH (6·6 (sem 0·2), 7·1 (sem 0·2) and 5·6 (sem 0·2);P<0·05) at 16 weeks. Differences in percentage of bifidobacteria between the GOS/FOS (59·2% (sem 7·7)), Bb-12 (52·7% (sem 8·0)) and the standard (51·8% (sem 6·4)) groups were not statistically significant at 16 weeks. Feeding infants GOS/FOS formula resulted in a similar effect on metabolic activity of the flora as in breast-fed infants. In the Bb-12 group, composition and metabolic activity of the flora were more similar to those of the standard group.
A comparative study on the effects of oral amiodarone and trimeprazine, twoin vitroretinyl ester hydrolase inhibitors, on the metabolic availability of vitamin A in rats
Authors: Schindler Rainer , Fielenbach Tanja , Rave Gerhard
Published: November 2005

Amiodarone, an antiarrhythmic drug, and trimeprazine, an antipsychotic drug, are bothin vitroinhibitors of retinyl ester hydrolase. To determine whether these agents have deleterious effects on aspects of vitamin A metabolism, Brown Norway rats (n18) were treated at clinically equivalent doses once daily for 26d with either oral drug. On day 27, a tolerance test was used to determine whether these agents interfered with vitamin absorption. During the first 8d, the plasma retinol level declined in all animals. Between days 12 and 27, it rose to near pre-treatment concentrations in the control and trimeprazine groups and remained relatively constant at low levels (P<0·001) in the amiodarone group. The intestinal absorption of vitamin A was reduced (P<0·05) in the amiodarone group compared with the placebo and trimeprazine groups, which did not differ significantly from each other. At the end of the 4-week treatment period, hepatic retinyl ester hydrolase activity was lower in the drug-dosed rats (P=0·06 for amiodarone) than in the controls. With regard to effects on liver reserves, drug treatment resulted in vitamin A depletion (P<0·019), and distinctive patterns of retinol and its esters were seen in response to dosing. In conclusion, amiodarone and trimeprazine have been shown to influence different aspects of retinoid metabolism, namely absorption, storage and transport. In clinical practice, the routine unmonitored use of these drugs and the suggestion that these agents be taken with meals are not recommended.
A review of the instruments used to assess the quality of life of adult patients with chronic intestinal failure receiving parenteral nutrition at home
Authors: Baxter Janet P. , Fayers Peter M. , McKinlay Alastair W.
Published: November 2005

Home parenteral nutrition is an established method of supporting patients with intestinal failure, but this treatment may be life long and imposes severe restrictions on daily life. Impact on quality of life is an important outcome when considering the management of home parenteral nutrition patients. This paper reviews studies in which the quality of life of patients receiving home parenteral nutrition has been assessed. A systematic search of electronic databases and relevant publications was undertaken to identify generic or treatment-specific questionnaires used with home parenteral nutrition patients. Many of the thirty-four reports discovered were small studies. Nineteen used non-specific generic instruments, eight used non-validated questionnaires, four used a combination of both, and three did not use any formal tool. Few systematic patterns emerged. There are few available data on the quality of life of home parenteral nutrition patients, and there is a need for standardised, scientifically validated, treatment-specific instruments to measure quality of life in this population.
Human gut microbiota does not ferment erythritol
Authors: Arrigoni Eva , Brouns Fred , Amadò Renato
Published: November 2005

Erythritol, a naturally occurring polyol, is gaining attention as a bulk sweetener for human nutrition. Industrially, it is produced from glucose by fermentation. From various studies it is known to be non-cariogenic. Moreover, it is rapidly absorbed in the small intestine and quantitatively excreted in the urine. Only about 10 % enters the colon. Earlier in vitro experiments showed that erythritol remained unfermented for a fermentation period of 12 h. In order to investigate whether fresh human intestinal microbiota is able to adapt its enzyme activities to erythritol, a 24 h lasting fermentation was carried out under well-standardised in vitro conditions. For comparison maltitol, lactulose and blank (faecal inoculum only) were incubated as well. Fermentation patterns were established by following total gas production, hydrogen accumulation, changes in pH value, SCFA production and substrate degradation. Taking all fermentation parameters into account, erythritol turned out to be completely resistant to bacterial attack within 24 h, thus excluding an adaptation within that period. Since under in vivo conditions more easily fermentable substrates enter the colon continuously, it seems very unlikely that erythritol will be fermented in vivo.
High-phosphorus diet stimulates receptor activator of nuclear factor-κB ligand mRNA expression by increasing parathyroid hormone secretion in rats
Authors: Katsumata Shin-ichi , Masuyama Ritsuko , Uehara Mariko , Suzuki Kazuharu
Published: November 2005

The purpose of the present study was to clarify the manner by which the supplementation of high-P diet induces bone loss. Eighteen 4-week-old male Wistar-strain rats were assigned randomly to three groups and fed diets containing three P levels (0·3, 0·9, and 1·5%) for 21d. A lower serum Ca concentration was observed in the rats fed on the 1·5% P diet than in the other two groups. Serum P and parathyroid hormone concentrations and urinary excretion of C-terminal telopeptide of type I collagen were elevated with increasing dietary P levels. Serum osteocalcin concentration was increased in the rats fed on the 1·5% P diet than in the other two groups. Bone formation rate of the lumbar vertebra was significantly increased in the two high-P groups than in the 0·3% P group. Osteoclast number was significantly increased with increasing dietary P levels. Bone mineral content and bone mineral density of the femur and lumbar vertebra and ultimate compression load of the lumbar vertebra were decreased with increasing dietary P levels. Additionally, ultimate bending load of the femur was decreased in the rats fed on the 1·5% P diet than in the other two groups. Receptor activator of NF-κB ligand (RANKL) mRNA expression in the femur was significantly higher with increasing dietary P levels. These results suggest that secondary hyperparathyroidism due to a high-P diet leads to bone loss via an increase in bone turnover. Furthermore, an increase in osteoclast number was caused by increased RANKL mRNA expression.
The importance of dietary composition for efficacy of iron absorption measured in a whole diet that includes rye bread fortified with ferrous fumerate: a radioisotope study in young women
Authors: Tetens Inge , Larsen Tanja M. , Kristensen Mette Bach , Hels Ole , Jensen Mikael , Morberg Cathrine M. , Thomsen Agnete D. , Højgaard Liselotte , Henriksen Marianne
Published: November 2005

Fe absorption is affected by many dietary factors. The objective of the present study was to measure the effects of highv. low content of vitamin C, meat and phytic acid in whole diets with Fe-fortified bread on the efficacy of Fe absorption. Thirty-two healthy women with low Fe stores were randomised to three groups, each of which was given two of six test diets containing either low/high amounts of vitamin C, meat or phytic acid, respectively, in a cross-over design. Each diet was served throughout a 5 d period. Fe-fortified rye bread, extrinsically labelled with59Fe, was given with all main meals. Fe absorption was determined from whole-body counter measurements of59Fe retention. The fractional non-haem Fe absorption (corrected to a 40% standard absorption by measurements from the reference dose) was 1·9%v. 3·4% (P=0·04) for the low/high vitamin C diets, 3·0%v. 3·5% (P=0·58) on the low/high meat diets and 4·9%v. 3·8% (P=0·24) on the low/high phytic acid diet, respectively. The total Fe absorbed (geometric mean with standard error) varied from 0·43 (se 0·11) mg from the diet with lowest bioavailability to 1·09 (se 0·18) mg from the diet with highest bioavailability (P<0·001). The present whole-diet study indicates that diet composition is a strong predictor of Fe absorption. In the diet with a low content of enhancers and a high content of inhibitors, vitamin C improved non-haem Fe absorption. The total Fe absorption varied 2·5-fold after small alterations of the content of enhancers and inhibitors in the diet.
The effect of enzyme treatment on thein vitrofermentation of lucerne incubated with equine faecal inocula
Authors: Murray Jo-Anne M. D. , Longland Annette C. , Moore-Colyer Meriel J. S. , Dunnett Catherine
Published: November 2005

A series of experiments was conducted to determine the effects of a fibrolytic enzyme preparation (enzyme 1; E1) on thein vitrofermentation of lucerne incubated with equine faecal inocula. In experiment 1, high-temperature-dried (HT) lucerne was treated with five levels of E1 (0 to 2·4ml/g DM) and incubated at 50°C for 20h. Samples then received a simulated foregut digestion (SFD) treatment before DM and NSP analysis. In experiment 2, HT lucerne was treated with the same enzyme levels used in experiment 1. Samples were then split into two groups; plus or minus an SFD treatment beforein vitrofermentation using an equine faecal inoculum. In experiment 3, fresh and wilted lucerne were treated with the same levels of E1 as experiments 1 and 2, incubated at 50°C for 20h, then fermentedin vitro. For experiment 4, fresh and wilted lucerne were treated with low levels (0 to 0·008ml/g DM) of E1 before fermentation. E1 significantly (P<0·05) enhanced DM and NSP losses from HT lucerne following SFD treatment compared with the control. High levels of E1 significantly (P<0·05) enhanced the rate, but not extent, of fermentation of HT, wilted and fresh lucerne; however, low levels of E1 were ineffective. At higher application levels, E1 appears to have considerable potential to enhance the nutritive value of lucerne for horses. Information on the fermentation kinetics of the substrates was valuable; all end-point measurements showed no effect of enzyme treatment.
Short-term effect of egg-white hydrolysate products on the arterial blood pressure of hypertensive rats
Authors: Miguel Marta , López-Fandiño Rosina , Ramos Mercedes , Aleixandre Amaya
Published: November 2005

In the present study we evaluate the blood pressure-lowering effect of the following products: the hydrolysate obtained from egg white (EW) by enzymatic treatment with pepsin (HEW), the peptide fraction of HEW with molecular mass lower than 3000 Da (HEW<3000 Da), and three peptide sequences isolated from HEW<3000 Da (Tyr-Ala-Glu-Glu-Arg-Tyr-Pro-Ile-Leu: YAEERYPIL); (Arg-Ala-Asp-His-Pro-Phe-Leu: RADHPFL); and (Ile-Val-Phe (IVF)). These peptides, and also HEW and HEW<3000 Da, had been characterized previously in vitro as potent inhibitors of angiotensin-converting enzyme (ACE). EW and the products mentioned earlier were orally administered by gastric intubation, to 17–20-week-old male spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto (WKY) rats. We measured the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats by the tail cuff method before administration and also 2, 4, 6, 8 and 24h post-administration. Distilled water served as negative control, and we used captopril (50mg/kg) as positive control to carry out similar experiments with a known ACE inhibitor. HEW, HEW<3000 Da and the three peptide sequences decreased SBP and DBP in SHR but they did not modify these variables in WKY rats. The peptide sequences YAEERYPIL, RADHPFL and IVF showed a potency to decrease blood pressure greater than HEW or HEW<3000 Da. The results obtained suggest that the studied products could be used as a functional food with potential therapeutic benefit in the prevention and treatment of hypertension.
Misreporting of energy: prevalence, characteristics of misreporters and influence on observed risk estimates in the Malmö Diet and Cancer cohort
Authors: Mattisson Irene , Wirfält Elisabet , Aronsson Carin Andrén , Wallström Peter , Sonestedt Emily , Gullberg Bo , Berglund Göran
Published: November 2005

The present study investigates the prevalence of misreporting of energy in the Malmö Diet and Cancer cohort, and examines anthropometric, socio-economic and lifestyle characteristics of the misreporters. Further, the influence of excluding misreporters on risk estimates of post-menopausal breast cancer was examined. Information of reported energy intake (EI) was obtained from a modified diet history method. A questionnaire provided information on lifestyle and socio-economic characteristics. Individual physical activity level (PAL) was calculated from self-reported information on physical activity at work, leisure time physical activity and household work, and from estimates of hours of sleeping, self-care and passive time. Energy misreporting was defined as having a ratio of EI to BMR outside the 95% CI limits of the calculated PAL. Logistic regression analysed the risk of being a low-energy reporter or a high-energy reporter. Almost 18% of the women and 12% of the men were classified as low-energy reporters, 2·8% of the women and 3·5% of the men were classified as high-energy reporters. In both genders high BMI, large waist circumference, short education and being a blue-collar worker were significantly associated with low-energy reporting. High-energy reporting was significantly associated with low BMI, living alone and current smoking. The results add support to the practice of energy adjustment as a means to reduce the influence of errors in risk assessment.
The case for strategic international alliances to harness nutritional genomics for public and personal health
Authors: Kaput Jim , Ordovas Jose M. , Ferguson Lynnette , van Ommen Ben , Rodriguez Raymond L. , Allen Lindsay , Ames Bruce N. , Dawson Kevin , German Bruce , Krauss Ronald , Malyj Wasyl , Archer Michael C. , Barnes Stephen , Bartholomew Amelia , Birk Ruth , van Bladeren Peter , Bradford Kent J. , Brown Kenneth H. , Caetano Rosane , Castle David , Chadwick Ruth , Clarke Stephen , Clément Karine , Cooney Craig A. , Corella Dolores , da Cruz Ivana Beatrice Manica , Daniel Hannelore , Duster Troy , Ebbesson Sven O. E. , Elliott Ruan , Fairweather-Tait Susan , Felton Jim , Fenech Michael , Finley John W. , Fogg-Johnson Nancy , Gill-Garrison Rosalynn , Gibney Michael J. , Gillies Peter J. , Gustafsson Jan-Ake , Hartman John L. , He Lin , Hwang Jae-Kwan , Jais Jean-Philippe , Jang Yangsoo , Joost Hans , Junien Claudine , Kanter Mitchell , Kibbe Warren A. , Koletzko Berthold , Korf Bruce R. , Kornman Kenneth , Krempin David W. , Langin Dominique , Lauren Denis R. , Lee Jong Ho , Leveille Gilbert A. , Lin Su-Ju , Mathers John , Mayne Michael , McNabb Warren , Milner John A. , Morgan Peter , Muller Michael , Nikolsky Yuri , van der Ouderaa Frans , Park Taesun , Pensel Norma , Perez-Jimenez Francisco , Poutanen Kaisa , Roberts Matthew , Saris Wim H.M. , Schuster Gertrud , Shelling Andrew N. , Simopoulos Artemis P. , Southon Sue , Tai E. Shyong , Towne Bradford , Trayhurn Paul , Uauy Ricardo , Visek Willard J. , Warden Craig , Weiss Rick , Wiencke John , Winkler Jack , Wolff George L. , Zhao-Wilson Xi , Zucker Jean-Daniel
Published: November 2005

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene–nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient–genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.
Panace@ — a successful open access journal from the STM translation community
Authors: Arroyo Cristina Márquez , Munoa Laura , Navarro Fernando A. , Saladrigas María Verónica , Shashok Karen
Published: November 2005

When members of an email discussion group for Spanish medical translators decided to start a journal for their community, they could not foresee the huge, immediate success the publication was to achieve. All issues of the quarterly journal Panace@ are published online with open access from the day of publication. There are no submittal fees for authors, subscription fees for members of the parent organization, or access fees for users. Here we report how the journal got started and what sustains it. Although questions of long‐term sustainability remain unresolved, the system used to start Panace@ may be worth considering for other small organizations with limited access to institutional or private sources of funding.
Publishing in American legal and social science periodicals: an ethical comparison
Authors: Yacoubian George S.
Published: November 2005

Legal professionals are guided by comprehensive rules of professional conduct. The 2002 American Bar Association Model Rules of Professional Conduct include, for example, guidelines related to attorney competence, conflict of interest, trial publicity and voluntary pro bono service. Despite the commitment to high ethical standards, however, there are no guidelines governing the submission and publication of manuscripts in legal periodicals. In contrast, the peer‐review process in the social sciences operates under informal ethical guidelines. This paper evaluates academic publication procedures and suggests that both the legal profession and the social sciences would benefit from formal rules governing manuscript submission and review.
The Flo8 Transcription Factor Is Essential for Hyphal Development and Virulence inCandida albicans
Authors: Cao Fang , Lane Shelley , Raniga Prashna Pala , Lu Yang , Zhou Zhou , Ramon Karalyn , Chen Jiangye , Liu Haoping
Published: November 2005

The transcription factor Flo8 is essential for filamentous growth in Saccharomyces cerevisiae and is regulated under the cAMP/protein kinase A (PKA) pathway. To determine whether a similar pathway/regulation exists in Candida albicans, we have cloned C. albicans FLO8 by its ability to complement S. cerevisiae flo8. Deleting FLO8 in C. albicans blocked hyphal development and hypha-specific gene expression. The flo8/flo8 mutant is avirulent in a mouse model of systemic infection. Genome-wide transcription profiling of efg1/efg1 and flo8/flo8 using a C. albicans DNA microarray suggests that Flo8 controls subsets of Efg1-regulated genes. Most of these genes are hypha specific, including HGC1 and IHD1. We also show that Flo8 interacts with Efg1 in yeast and hyphal cells by in vivo immunoprecipitation. Similar to efg1/efg1, flo8/flo8 and cdc35/cdc35 show enhanced hyphal growth under an embedded growth condition. Our results suggest that Flo8 may function downstream of the cAMP/PKA pathway, and together with Efg1, regulates the expression of hypha-specific genes and genes that are important for the virulence of C. albicans.
Molecular Interaction Maps of Bioregulatory Networks: A General Rubric for Systems Biology
Authors: Kohn Kurt W. , Aladjem Mirit I. , Weinstein John N. , Pommier Yves
Published: November 2005

A standard for bioregulatory network diagrams is urgently needed in the same way that circuit diagrams are needed in electronics. Several graphical notations have been proposed, but none has become standard. We have prepared many detailed bioregulatory network diagrams using the molecular interaction map (MIM) notation, and we now feel confident that it is suitable as a standard. Here, we describe the MIM notation formally and discuss its merits relative to alternative proposals. We show by simple examples how to denote all of the molecular interactions commonly found in bioregulatory networks. There are two forms of MIM diagrams. “Heuristic” MIMs present the repertoire of interactions possible for molecules that are colocalized in time and place. “Explicit” MIMs define particular models (derived from heuristic MIMs) for computer simulation. We show also how pathways or processes can be highlighted on a canonical heuristic MIM. Drawing a MIM diagram, adhering to the rules of notation, imposes a logical discipline that sharpens one's understanding of the structure and function of a network.
Sequence features of DNA binding sites reveal structural class of associated transcription factor
Authors: Narlikar Leelavati , Hartemink Alexander J.
Published: November 2005

Motivation: A key goal in molecular biology is to understand the mechanisms by which a cell regulates the transcription of its genes. One important aspect of this transcriptional regulation is the binding of transcription factors (TFs) to their specific cis-regulatory counterparts on the DNA. TFs recognize and bind their DNA counterparts according to the structure of their DNA-binding domains (e.g. zinc finger, leucine zipper, homeodomain). The structure of these domains can be used as a basis for grouping TFs into classes. Although the structure of DNA-binding domains varies widely across TFs generally, the TFs within a particular class bind to DNA in a similar fashion, suggesting the existence of class-specific features in the DNA sequences bound by each class of TFs.

Results: In this paper, we apply a sparse Bayesian learning algorithm to identify a small set of class-specific features in the DNA sequences bound by different classes of TFs; the algorithm simultaneously learns a true multi-class classifier that uses these features to predict the DNA-binding domain of the TF that recognizes a particular set of DNA sequences. We train our algorithm on the six largest classes in TRANSFAC, comprising a total of 587 TFs. We learn a six-class classifier for this training set that achieves 87% leave-one-out cross-validation accuracy. We also identify features within cis-regulatory sequences that are highly specific to each class of TF, which has significant implications for how TF binding sites should be modeled for the purpose of motif discovery.

Contact:  lee@cs.duke.edu; amink@cs.duke.edu
A method for predicting disease subtypes in presence of misclassification among training samples using gene expression: application to human breast cancer
Authors: Zhang Wensheng , Rekaya Romdhane , Bertrand Keith
Published: November 2005

Motivation: An accurate diagnostic and prediction will not be achieved unless the disease subtype status for every training sample used in the supervised learning step is accurately known. Such an assumption requires the existence of a perfect tool for disease diagnostic and classification, which is seldom available in the majority of the cases. Thus, the supervised learning step has to be conducted with a statistical model that contemplates and handles potential mislabeling in the input data.

Results: A procedure for handling potential mislabeling among training samples in the prediction of disease subtypes using gene expression data was proposed. A real data-based simulation study about the estrogen receptor status (ER+/ER−) of breast cancer patients was conducted. The results demonstrated that when 1–4 training samples (N = 30) were artificially mislabeled, the proposed method was able not only in correcting the ER status of mislabeled training samples but also more importantly in predicting the ER status of validation samples as well as using ‘true’ training data.

Availability: The programs (in Matlab) used for analysis are publicly available at

Contact:  rrekaya@uga.edu
Intelligent client for integrating bioinformatics services
Authors: Navas-Delgado Ismael , Rojano-Muñoz Maria del Mar , Ramírez Sergio , Pérez Antonio J. , Andrés León Eduardo , Aldana-Montes Jose F. , Trelles Oswaldo
Published: October 2005

Motivation: In addition to existing bioinformatics software, a lot of new tools are being developed world wide to supply services for an ever growing, widely dispersed and heterogeneous collection of biological data. The integration of these resources under a common platform is a challenging task. To this end, several groups are developing integration technologies, in which services are usually registered in some sort of catalogue to allow novel discovering and accessing mechanisms to be implemented. However, each service demands specific interfaces to accommodate their parameters and it is a complicated task linking the different service inputs and outputs to solve a biological problem.

Results: In this work we address the design and implementation of a versatile web client to access BioMOBY compatible services (a system by which a client can interact with multiple sources of biological data regardless of the underlying format or schema) using the service description stored in the BioMOBY catalogue. The automatic interface generator significantly reduces developing time and produces uniform service access mechanisms. The design and proof of concept (for such a client) including the generic interface generator have been developed and implemented in the National Institute for Bioinformatics in Spain.

Availability: The INB (National Institute for Bioinformatics, Spain) platform is available at

Contact:  ots@ac.uma.es

Supplementary information:
Using a calibration experiment to assess gene-specific information: full Bayesian and empirical Bayesian models for two-channel microarray data
Authors: Blangiardo Marta , Toti Simona , Giusti Betti , Abbate Rosanna , Magi Alberto , Poggi Filippo , Rossi Luciana , Torricelli Francesca , Biggeri Annibale
Published: November 2005

Motivation: Microarray studies permit to quantify expression levels on a global scale by measuring transcript abundance of thousands of genes simultaneously. A difficulty when analysing expression measures is how to model variability for the whole set of genes. It is usually unrealistic to assume a common variance for each gene. Several approaches to model gene-specific variances are proposed. We take advantage of calibration experiments, in which the probes hybridized on the two channels come from the same population (self–self experiment). In this case it is possible to estimate the gene-specific variance, to be incorporated in comparative experiments on the same tissue, cellular line or species.

Results: We present two approaches to introduce prior information on gene-specific variability from a calibration experiment: an empirical Bayes model and a full Bayesian hierarchical model. We apply the methods in the analysis of human lipopolysaccharide-stimulated leukocyte experiments.

Availability: The calculations are implemented in WinBugs. The codes are available on request from the authors.

Contact:  m.blangiardo@imperial.ac.uk
Traumatic insemination in the plant bug genusCoridromiusSignoret (Heteroptera: Miridae)
Authors: Tatarnic Nikolai J , Cassis Gerasimos , Hochuli Dieter F
Published: November 2005

In traumatic insemination, males pierce females with hypodermic genitalia and ejaculate into the body cavity rather than into the genital tract. This has resulted in the evolution of female counter-adaptations in the form of paragenitalia to reduce the direct physical costs of mating. While rare in the animal kingdom, traumatic insemination is oddly prevalent in the true bug infraorder Cimicomorpha (Heteroptera), where it occurs in six families and is thought to have arisen twice. Here, we report the discovery of traumatic insemination and elaborate paragenital development in the plant bug genusCoridromius(Miridae), representing a third, independent emergence of traumatic insemination in this infraorder.
Digital particle image velocimetry measurements of the downwash distribution of a desert locustSchistocerca gregaria
Authors: Bomphrey Richard J , Taylor Graham K , Lawson Nicholas J , Thomas Adrian L.R
Published: November 2005

Actuator disc models of insect flight are concerned solely with the rate of momentum transfer to the air that passes through the disc. These simple models assume that an even pressure is applied across the disc, resulting in a uniform downwash distribution. However, a correction factor,k, is often included to correct for the difference in efficiency between the assumed even downwash distribution, and the real downwash distribution. In the absence of any empirical measurements of the downwash distribution behind a real insect, the values ofkused in the literature have been necessarily speculative. Direct measurement of this efficiency factor is now possible, and could be used to compare the relative efficiencies of insect flight across the Class. Here, we use Digital Particle Image Velocimetry to measure the instantaneous downwash distribution, mid-downstroke, of a tethered desert locust (Schistocerca gregaria). By integrating the downwash distribution, we are thereby able to provide the first direct empirical measurement ofkfor an insect. The measured value ofk=1.12 corresponds reasonably well with that predicted by previous theoretical studies.
Identification of prognostic signatures in breast cancer microarray data using Bayesian techniques
Authors: Carrivick L , Rogers S , Clark J , Campbell C , Girolami M , Cooper C
Published: November 2005

We apply a new Bayesian data analysis technique (latent process decomposition) to four recent microarray datasets for breast cancer. Compared to hierarchical cluster analysis, for example, this technique has advantages such as objective assessment of the optimal number of sample or gene clusters in the data, penalization of overcomplex models fitting to noise in the data and a common latent space of explanatory variables for samples and genes. Our analysis provides a clearer insight into these datasets, enabling assignment of patients to one of four principal processes, each with a distinct clinical outcome. One process is indolent and associated with under-expression across a number of genes associated with tumour growth. One process is associated with over expression of
GRB7
and
ERBB2
. The most aggressive process is associated with abnormal expression of transcription factor genes, including members of the
FOX
family of transcription factor genes.
Phase transitions in a slender cylinder composed of an incompressible elastic material. I. Asymptotic model equation
Authors: Dai Hui-Hui , Cai Zongxi
Published: November 2005

We present reasons, both experimental and mathematical, for why it is important to consider the radial deformation (thus the lateral traction-free boundary conditions as well) for phase transitions in a slender elastic cylinder. One of the main purposes of this paper is to derive an asymptotic model equation, which takes into account the radial deformation and satisfies the traction-free boundary conditions up to the right order. This is achieved from the three-dimensional field equations through a novel approach that combines a series expansion and an asymptotic expansion. An alternative approach based on Whitham's approach (well used in fluids) is also given. Then, we present some interesting analytic solutions for an infinite cylinder, including those that seem to describe the structure of a phase boundary, the nucleation process and the merge of two-phase boundaries. In particular, by considering the energy distribution based on the nucleation solution, it is revealed that the nucleation process is one of energy localizations, concentrations and separation.
Countergradient variation in body shape between two populations of Atlantic cod (
Gadus morhua
)
Authors: Marcil Julie , Swain Douglas P , Hutchings Jeffrey A
Published: November 2005

Variation in morphological traits is generally thought to be cogradient, with environmental effects on phenotypic expression reinforcing genetic differences between populations. We compared body shape between two populations of Atlantic cod (
Gadus morhua
). Striking shape differences occurred between juveniles from the two populations when reared in a common laboratory environment. However, no difference in body shape occurred between wild-reared juveniles from the two populations, suggesting that the genetic differences between populations were obscured by opposing effects of the environmental differences experienced in the wild. We suggest that much of the genetic diversity in body shape of fishes may be cryptic, with stabilizing selection for the same optimal phenotype resulting in genetic divergence between populations subject to contrasting environmental influences.
Group living and inbreeding depression in a subsocial spider
Authors: Avilés Leticia , Bukowski Todd C
Published: November 2005

Social spiders are unusual among social organisms in being highly inbred—males and females mature within their natal nest and mate with each other to produce successive generations. Several lines of evidence suggest that in spiders inbred social species originated from outbred subsocial ancestors, a transition expected to have been hindered by inbreeding depression. As a window into this transition, we examined the fitness consequences of artificially imposed inbreeding in the naturally outbred subsocial spider
Anelosimus
cf.
jucundus
. Subsocial spiders alternate periods of solitary and social living and are thought to resemble the ancestral system from which the inbred social species originated. We found that inbreeding depression in this subsocial spider only becomes evident in spiders raised individually following the end of their social phase and that ecological and demographic factors such as eclosion date, number of siblings in the group and mother's persistence are more powerful determinants of fitness during the social phase. A potential explanation for this pattern is that maternal care and group living provide a buffer against inbreeding depression, a possibility that may help explain the repeated origin of inbred social systems in spiders and shed light on the origin of other systems involving regular inbreeding.
Reactive oxygen species and redox-regulation of skeletal muscle adaptations to exercise
Authors: Jackson Malcolm J
Published: November 2005

Skeletal muscle has been shown to generate a complex set of reactive oxygen and nitrogen species (ROS) both at rest and during contractile activity. The primary ROS generated are superoxide and nitric oxide and the pattern and magnitude of their generation is influenced by the nature of the contractile activity. It is increasingly clear that the ROS generated by skeletal muscle play an important role in influencing redox-regulated processes that control, at least some of, the adaptive responses to contractile activity. These processes are also recognized to be modified during ageing and in some disease states, providing the potential that interventions affecting ROS activity may influence muscle function or viability in these situations.
Cloning and Molecular Characterization of the Basic Peroxidase Isoenzyme from Zinnia elegans, an Enzyme Involved in Lignin Biosynthesis
Authors: Gabaldón Carlos , López-Serrano Matías , Pedreño María A. , Barceló A. Ros
Published: October 2005

The major basic peroxidase from Zinnia elegans (ZePrx) suspension cell cultures was purified and cloned, and its properties and organ expression were characterized. The ZePrx was composed of two isoforms with a Mr (determined by matrix-assisted laser-desorption ionization time of flight) of 34,700 (ZePrx34.70) and a Mr of 33,440 (ZePrx33.44). Both isoforms showed absorption maxima at 403 (Soret band), 500, and 640 nm, suggesting that both are high-spin ferric secretory class III peroxidases. Mr differences between them were due to the glycan moieties, and were confirmed from the total similarity of the N-terminal sequences (LSTTFYDTT) and by the 99.9% similarity of the tryptic fragment fingerprints obtained by reverse-phase nano-liquid chromatography. Four full-length cDNAs coding for these peroxidases were cloned. They only differ in the 5′-untranslated region. These differences probably indicate different ways in mRNA transport, stability, and regulation. According to the kcat and apparent KmRH values shown by both peroxidases for the three monolignols, sinapyl alcohol was the best substrate, the endwise polymerization of sinapyl alcohol by both ZePrxs yielding highly polymerized lignins with polymerization degrees ≥87. Western blots using anti-ZePrx34.70 IgGs showed that ZePrx33.44 was expressed in tracheary elements, roots, and hypocotyls, while ZePrx34.70 was only expressed in roots and young hypocotyls. None of the ZePrx isoforms was significantly expressed in either leaves or cotyledons. A neighbor-joining tree constructed for the four full-length cDNAs suggests that the four putative paralogous genes encoding the four cDNAs result from duplication of a previously duplicated ancestral gene, as may be deduced from the conserved nature and conserved position of the introns.
Establishment of the Vernalization-Responsive, Winter-Annual Habit inArabidopsisRequires a Putative Histone H3 Methyl Transferase[W]
Authors: Kim Sang Yeol , He Yuehui , Jacob Yannick , Noh Yoo-Sun , Michaels Scott , Amasino Richard
Published: October 2005

Winter-annual accessions of Arabidopsis thaliana are often characterized by a requirement for exposure to the cold of winter to initiate flowering in the spring. The block to flowering prior to cold exposure is due to high levels of the flowering repressor FLOWERING LOCUS C (FLC). Exposure to cold promotes flowering through a process known as vernalization that epigenetically represses FLC expression. Rapid-cycling accessions typically have low levels of FLC expression and therefore do not require vernalization. A screen for mutants in which a winter-annual Arabidopsis is converted to a rapid-cycling type has identified a putative histone H3 methyl transferase that is required for FLC expression. Lesions in this methyl transferase, EARLY FLOWERING IN SHORT DAYS (EFS), result in reduced levels of histone H3 Lys 4 trimethylation in FLC chromatin. EFS is also required for expression of other genes in the FLC clade, such as MADS AFFECTING FLOWERING2 and FLOWERING LOCUS M. The requirement for EFS to permit expression of several FLC clade genes accounts for the ability of efs lesions to suppress delayed flowering due to the presence of FRIGIDA, autonomous pathway mutations, or growth in noninductive photoperiods. efs mutants exhibit pleiotropic phenotypes, indicating that the role of EFS is not limited to the regulation of flowering time.
Tree leaf chemical characters: selective pressures by folivorous primates and invertebrates
Authors: Burgess Matthew A. , Chapman Colin A.
Published: November 2005

Plants have evolved a variety of chemical means to deter herbivory. Several studies have documented that secondary compounds are strong deterrents to certain herbivores, while others have demonstrated that some herbivores ingest large quantities of these compounds without exhibiting deleterious effects. This inconsistent response suggests that plants have evolved compounds to deter specific herbivores. Based on a study in Kibale National Park, Uganda, we explored how two major groups of herbivores, invertebrates and colobus monkeys, respond to chemical characteristics of leaves: protein, attractive from a nutritional perspective, and alkaloids, saponins and cyanogenic glycosides, which are all plant defences, detering herbivory. The intensity that colobus monkeys fed on leaves of different tree species was determined by observations (1300 h), and invertebrate herbivory was indexed by collecting leaves from 20 species and digitizing tracings to quantifying invertebrate damage. Invertebrate damage to leaves varied among species (1.5–22.5%), but showed no relationship with saponin or protein content, or the presence or absence of alkaloids. Colobine foraging effort did not relate to the saponin and protein of leaf species, nor to the presence or absence of alkaloids. Prunus africana, the only species to test positive for cyanogenic glycosides, was fed on by colobus monkeys for 8.1% of their foraging time, but, as it occurred at low densities, it was the most preferred species. These results can be interpreted in different ways. First, it is possible that inactive compounds are retained because they increase the probability of producing new active compounds. Secondly, the indices used to evaluate compound effects may be inappropriate. For example, monkeys may only be able to tolerate a toxin to a specific threshold in a single feeding session, but our index of foraging effort was averaged over the year. Thirdly, it may be that these compounds play an active role with organisms not considered (e.g. prevent fungal attack). Finally, these compounds may serve some unknown function and selection may operate for that purpose.