bluuebunny/crossref_metadata_2025_split huggingface dataset:
AphanoDB: a genomic resource for Aphanomyces pathogens
Authors: Madoui Mohammed-Amine , Gaulin Elodie , Mathé Catherine , San Clemente Hélène , Couloux Arnaud , Wincker Patrick , Dumas Bernard 
Published: February 2008

AbstractBackgroundThe Oomycete genusAphanomycescomprises devastating plant and animal pathogens. However, little is known about the molecular mechanisms underlying pathogenicity ofAphanomycesspecies. In this study, we report on the development of a public database called AphanoDB which is dedicated toAphanomycesgenomic data. As a first step, a large collection of Expressed Sequence Tags was obtained from the legume pathogenA. euteiches, which was then processed and collected into AphanoDB.DescriptionTwo cDNA libraries ofA. euteicheswere created: one from mycelium growing on synthetic medium and one from mycelium grown in contact to root tissues of the model legumeMedicago truncatula. From these libraries, 18,684 expressed sequence tags were obtained and assembled into 7,977 unigenes which were compared to public databases for annotation. Queries on AphanoDB allow the users to retrieve information for each unigene including similarity to known protein sequences, protein domains and Gene Ontology classification. Statistical analysis of EST frequency from the two different growth conditions was also added to the database.ConclusionAphanoDB is a public database with a user-friendly web interface. The sequence report pages are the main web interface which provides all annotation details for each unigene. These interactive sequence report pages are easily available through text, BLAST, Gene Ontology and expression profile search utilities. AphanoDB is available from URL:http://www.polebio.scsv.ups-tlse.fr/aphano/.
All and only CpG containing sequences are enriched in promoters abundantly bound by RNA polymerase II in multiple tissues
Authors: Rozenberg Julian M , Shlyakhtenko Andrey , Glass Kimberly , Rishi Vikas , Myakishev Maxim V , FitzGerald Peter C , Vinson Charles 
Published: February 2008

Abstract

Background
The promoters of housekeeping genes are well-bound by RNA polymerase II (RNAP) in different tissues. Although the promoters of these genes are known to contain CpG islands, the specific DNA sequences that are associated with high RNAP binding to housekeeping promoters has not been described.

Results
ChIP-chip experiments from three mouse tissues, liver, heart ventricles, and primary keratinocytes, indicate that 94% of promoters have similar RNAP binding, ranging from well-bound to poorly-bound in all tissues. Using all 8-base pair long sequences as a test set, we have identified the DNA sequences that are enriched in promoters of housekeeping genes, focusing on those DNA sequences which are preferentially localized in the proximal promoter. We observe a bimodal distribution. Virtually all sequences enriched in promoters with high RNAP binding values contain a CpG dinucleotide. These results suggest that only transcription factor binding sites (TFBS) that contain the CpG dinucleotide are involved in RNAP binding to housekeeping promoters while TFBS that do not contain a CpG are involved in regulated promoter activity. Abundant 8-mers that are preferentially localized in the proximal promoters and exhibit the best enrichment in RNAP bound promoters are all variants of six known CpG-containing TFBS: ETS, NRF-1, BoxA, SP1, CRE, and E-Box. The frequency of these six DNA motifs can predict housekeeping promoters as accurately as the presence of a CpG island, suggesting that they are the structural elements critical for CpG island function. Experimental EMSA results demonstrate that methylation of the CpG in the ETS, NRF-1, and SP1 motifs prevent DNA binding in nuclear extracts in both keratinocytes and liver.

Conclusion
In general, TFBS that do not contain a CpG are involved in regulated gene expression while TFBS that contain a CpG are involved in constitutive gene expression with some CpG containing sequences also involved in inducible and tissue specific gene regulation. These TFBS are not bound when the CpG is methylated. Unmethylated CpG dinucleotides in the TFBS in CpG islands allow the transcription factors to find their binding sites which occur only in promoters, in turn localizing RNAP to promoters.
Geographical variations in the benefit of applying a prioritization system for cataract surgery in different regions of Spain
Authors: Román Rubén , Comas Mercè , Mar Javier , Bernal Enrique , Jiménez-Puente Alberto , Gutiérrez-Moreno Santiago , Castells Xavier ,   the IRYSS Network Modelling Group
Published: February 2008

Abstract

Background
In Spain, there are substantial variations in the utilization of health resources among regions. Because the need for surgery differs in patients with appropriate surgical indication, introducing a prioritization system might be beneficial. Our objective was to assess geographical variations in the impact of applying a prioritization system in patients on the waiting list for cataract surgery in different regions of Spain by using a discrete-event simulation model.

Methods
A discrete-event simulation model to evaluate demand and waiting time for cataract surgery was constructed. The model was reproduced and validated in five regions of Spain and was fed administrative data (population census, surgery rates, waiting list information) and data from research studies (incidence of cataract). The benefit of introducing a prioritization system was contrasted with the usual first-in, first-out (FIFO) discipline. The prioritization system included clinical, functional and social criteria. Priority scores ranged between 0 and 100, with greater values indicating higher priority. The measure of results was the waiting time weighted by the priority score of each patient who had passed through the waiting list. Benefit was calculated as the difference in time weighted by priority score between operating according to waiting time or to priority.

Results
The mean waiting time for patients undergoing surgery according to the FIFO discipline varied from 1.97 months (95% CI 1.85; 2.09) in the Basque Country to 10.02 months (95% CI 9.91; 10.12) in the Canary Islands. When the prioritization system was applied, the mean waiting time was reduced to a minimum of 0.73 months weighted by priority score (95% CI 0.68; 0.78) in the Basque Country and a maximum of 5.63 months (95% CI 5.57; 5.69) in the Canary Islands. The waiting time weighted by priority score saved by the prioritization system varied from 1.12 months (95% CI 1.07; 1.16) in Andalusia to 2.73 months (95% CI 2.67; 2.80) in Aragon.

Conclusion
The prioritization system reduced the impact of the variations found among the regions studied, thus improving equity. Prioritization allocates the available resources within each region more efficiently and reduces the waiting time of patients with greater need. Prioritization was more beneficial than allocating surgery by waiting time alone.
Diacylglycerol kinase ζ inhibits myocardial atrophy and restores cardiac dysfunction in streptozotocin-induced diabetes mellitus
Authors: Bilim Olga , Takeishi Yasuchika , Kitahara Tatsuro , Arimoto Takanori , Niizeki Takeshi , Sasaki Toshiki , Goto Kaoru , Kubota Isao 
Published: February 2008

Abstract

Background
Activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway has been implicated in the pathogenesis of a number of diabetic complications. Diacylglycerol kinase (DGK) converts DAG to phosphatidic acid and acts as an endogenous regulator of PKC activity. Akt/PKB is associated with a downstream insulin signaling, and PKCβ attenuates insulin-stimulated Akt phosphorylation.

Methods and Results
We examined transgenic mice with cardiac-specific overexpression of DGKζ (DGKζ-TG) compared to wild type (WT) mice in streptozotocin-induced (STZ, 150 mg/kg) diabetic and nondiabetic conditions. After 8 weeks, decreases in heart weight and heart weight/body weight ratio in diabetic WT mice were inhibited in DGKζ-TG mice. Echocardiography at 8 weeks after STZ-injection demonstrated that decreases in left ventricular end-diastolic diameter and fractional shortening observed in WT mice were attenuated in DGKζ-TG mice. Thinning of the interventricular septum and the posterior wall in diabetic WT hearts were blocked in DGKζ-TG mice. Reduction of transverse diameter of cardiomyocytes isolated from the left ventricle in diabetic WT mice was attenuated in DGKζ-TG mice. Cardiac fibrosis was much less in diabetic DGKζ-TG than in diabetic WT mice. Western blots showed translocation of PKCβ and δ isoforms to membrane fraction and decreased Akt/PKB phosphorylation in diabetic WT mouse hearts. However in diabetic DGKζ-TG mice, neither translocation of PKC nor changes Akt/PKB phosphorylation was observed.

Conclusion
DGKζ modulates intracellular signaling and improves the course of diabetic cardiomyopathy. These data may suggest that DGKζ is a new therapeutic target to prevent or reverse diabetic cardiomyopathy.
Research to action to address inequities: the experience of the Cape Town Equity Gauge
Authors: Scott Vera , Stern Ruth , Sanders David , Reagon Gavin , Mathews Verona 
Published: February 2008

AbstractBackgroundWhile the importance of promoting equity to achieve health is now recognised, the health gap continues to increase globally between and within countries. The description that follows looks at how the Cape Town Equity Gauge initiative, part of the Global Equity Gauge Alliance (GEGA) is endeavouring to tackle this problem.We give an overview of the first phase of our research in which we did an initial assessment of health status and the socio-economic determinants of health across the subdistrict health structures of Cape Town. We then describe two projects from the second phase of our research in which we move from research to action. The first project, the Equity Tools for Managers Project, engages with health managers to develop two tools to address inequity: an Equity Measurement Tool which quantifies inequity in health service provision in financial terms, and a Equity Resource Allocation Tool which advocates for and guides action to rectify inequity in health service provision. The second project, the Water and Sanitation Project, engages with community structures and other sectors to address the problem of diarrhoea in one of the poorest areas in Cape Town through the establishment of a community forum and a pilot study into the acceptability of dry sanitation toilets.MethodsA participatory approach was adopted. Both quantitative and qualitative methods were used. The first phase, the collection of measurements across the health subdistricts of Cape Town, used quantitative secondary data to demonstrate the inequities. In the Equity Tools for Managers Project further quantitative work was done, supplemented by qualitative policy analysis to study the constraints to implementing equity. The Water and Sanitation Project was primarily qualitative, using in-depth interviews and focus group discussions. These were used to gain an understanding of the impact of the inequities, in this instance, inadequate sanitation provision.ResultsThe studies both demonstrate the value of adopting the GEGA approach of research to action, adopting three pillars of assessment and monitoring; advocacy; and community empowerment. In the Equity Tools for Managers Project study, the participation of managers meant that their support for implementation was increased, although the failure to include nurses and communities in the study was noted as a limitation. The development of a community Water and Sanitation Forum to support the Project had some notable successes, but also experienced some difficulties due to lack of capacity in both the community and the municipality.ConclusionThe two very different, but connected projects, demonstrate the value of adopting the GEGA approach, and the importance of involvement of all stakeholders at all stages. The studies also illustrate the potential of a research institution as informed 'outsiders', in influencing policy and practice.
Monomorphic post-transplant lymphoproliferative disorder of the tongue: case report and review of literature
Authors: Gonzalez-Cuyar Luis F , Tavora Fabio , Burke Allen P , Gocke Christopher D , Zimrin Ann , Sauk John J , Zhao Xiafeng F 
Published: February 2008

Abstract

Background
Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of hematological diseases arising in context of immunosuppression after organ transplantation. PTLD can involve any organ; however, it is extremely rare in oral cavity.

Methods
Using morphologic and immunophenotypic approaches we have studied a case of monomorphic PTLD of the tongue that developed in a patient following unilateral kidney and pancreas transplantation on immunosuppressive therapy. Additionally, cases of PTLD in the oral cavity were reviewed in the English literature.

Results
The neoplasm showed large cell morphology and B-cell phenotype. In situ hybridization for Epstein-Barr virus was positive. Complete remission was obtained after decreasing immunosuppressive therapy. The patient remained in remission at 790 days' follow up.

Conclusion
This rare case increased our awareness of PTLD in the oral cavity of patients following solid organ transplantation and immunosuppressive therapy.
Genetic analysis of the spindle checkpoint genes san-1, mdf-2, bub-3 and the CENP-F homologues hcp-1 and hcp-2 in Caenorhabditis elegans
Authors: Hajeri Vinita A , Stewart Anil M , Moore Landon L , Padilla Pamela A 
Published: February 2008

Abstract

Background
The spindle checkpoint delays the onset of anaphase until all sister chromatids are aligned properly at the metaphase plate. To investigate the role san-1, the MAD3 homologue, has in Caenorhabditis elegans embryos we used RNA interference (RNAi) to identify genes synthetic lethal with the viable san-1(ok1580) deletion mutant.

Results
The san-1(ok1580) animal has low penetrating phenotypes including an increased incidence of males, larvae arrest, slow growth, protruding vulva, and defects in vulva morphogenesis. We found that the viability of san-1(ok1580) embryos is significantly reduced when HCP-1 (CENP-F homologue), MDF-1 (MAD-1 homologue), MDF-2 (MAD-2 homologue) or BUB-3 (predicted BUB-3 homologue) are reduced by RNAi. Interestingly, the viability of san-1(ok1580) embryos is not significantly reduced when the paralog of HCP-1, HCP-2, is reduced. The phenotype of san-1(ok1580);hcp-1(RNAi) embryos includes embryonic and larval lethality, abnormal organ development, and an increase in abnormal chromosome segregation (aberrant mitotic nuclei, anaphase bridging). Several of the san-1(ok1580);hcp-1(RNAi) animals displayed abnormal kinetochore (detected by MPM-2) and microtubule structure. The survival of mdf-2(RNAi);hcp-1(RNAi) embryos but not bub-3(RNAi);hcp-1(RNAi) embryos was also compromised. Finally, we found that san-1(ok1580) and bub-3(RNAi), but not hcp-1(RNAi) embryos, were sensitive to anoxia, suggesting that like SAN-1, BUB-3 has a functional role as a spindle checkpoint protein.

Conclusion
Together, these data suggest that in the C. elegans embryo, HCP-1 interacts with a subset of the spindle checkpoint pathway. Furthermore, the fact that san-1(ok1580);hcp-1(RNAi) animals had a severe viability defect whereas in the san-1(ok1580);hcp-2(RNAi) and san-1(ok1580);hcp-2(ok1757) animals the viability defect was not as severe suggesting that hcp-1 and hcp-2 are not completely redundant.
The E3 ubiquitin ligase skp2 regulates neural differentiation independent from the cell cycle
Authors: Boix-Perales Hector , Horan Ian , Wise Helen , Lin Horng-Ru , Chuang Li-Chiou , Yew P Renee , Philpott Anna 
Published: February 2008

Abstract
Background
The SCFskp2 complex is an E3 ubiquitin ligase that is known to target a number of cell cycle regulators, including cyclin-dependent kinase inhibitors, for proteolysis. While its role in regulation of cell division has been well documented, additional functions in differentiation, including in the nervous system, have not been investigated.

Results
Using Xenopus as a model system, here we demonstrate that skp2 has an additional role in regulation of differentiation of primary neurons, the first neurons to differentiate in the neural plate. Xenopus skp2 shows a dynamic expression pattern in early embryonic neural tissue and depletion of skp2 results in generation of extra primary neurons. In contrast, over-expression of skp2 inhibits neurogenesis in a manner dependent on its ability to act as part of the SCFskp2 complex. Moreover, inhibition of neurogenesis by skp2 occurs upstream of the proneural gene encoding NeuroD and prior to cell cycle exit. We have previously demonstrated that the Xenopus cyclin dependent kinase inhibitor Xic1 is essential for primary neurogenesis at an early stage, and before these cells exit the cell cycle. We show that SCFskp2 degrades Xic1 in embryos and this contributes to the ability of skp2 to regulate neurogenesis.

Conclusion
We conclude that the SCFskp2 complex has functions in the control of neuronal differentiation additional to its role in cell cycle regulation. Thus, it is well placed to be a co-ordinating factor regulating both cell proliferation and cell differentiation directly.
Role of vasopressin in the treatment of anaphylactic shock in a child undergoing surgery for congenital heart disease: a case report
Authors: Di Chiara Luca , Stazi Giulia V , Ricci Zaccaria , Polito Angelo , Morelli Stefano , Giorni Chiara , La Salvia Ondina , Vitale Vincenzo , Rossi Eugenio , Picardo Sergio 
Published: February 2008

Abstract

Introduction
The incidence of anaphylactic reactions during anesthesia is between 1:5000 and 1:25000 and it is one of the few causes of mortality directly related to general anesthesia. The most important requirements in the treatment of this clinical condition are early diagnosis and maintenance of vital organ perfusion. Epinephrine administration is generally considered as the first line treatment of anaphylactic reactions. However, recently, new pharmacological approaches have been described in the treatment of different forms of vasoplegic shock.

Case presentation
We describe the case of a child who was undergoing surgery for ventricular septal defect, with an anaphylactic reaction to heparin that was refractory to epinephrine infusion and was effectively treated by low dose vasopressin infusion.

Conclusion
In case of anaphylactic shock, continuous infusion of low-dose vasopressin might be considered after inadequate response to epinephrine, fluid resuscitation and corticosteroid administration.
Correction of technical bias in clinical microarray data improves concordance with known biological information
Authors: Eklund Aron C , Szallasi Zoltan 
Published: February 2008

AbstractThe performance of gene expression microarrays has been well characterized using controlled reference samples, but the performance on clinical samples remains less clear. We identified sources of technical bias affecting many genes in concert, thus causing spurious correlations in clinical data sets and false associations between genes and clinical variables. We developed a method to correct for technical bias in clinical microarray data, which increased concordance with known biological relationships in multiple data sets.
Absolute Risk Reductions for Local Recurrence After Postoperative Radiotherapy After Sector Resection for Ductal Carcinoma In Situ of the Breast
Authors: Holmberg Lars , Garmo Hans , Granstrand Bengt , Ringberg Anita , Arnesson Lars-Gunnar , Sandelin Kerstin , Karlsson Per , Anderson Harald , Emdin Stefan 
Published: February 2008

Purpose Evaluate the effects of radiotherapy after sector resection for ductal carcinoma in situ of the breast (DCIS) in patient groups as defined by age, size of the lesion, focality, completeness of excision and mode of detection. Patients and Methods A total of 1,067 women in Sweden were randomly assigned to either postoperative radiotherapy (RT) or control from 1987 to 1999, and 1,046 were followed for a mean of 8 years. The main outcome was new ipsilateral breast cancer events and distant metastasis–free survival analyzed according to intention to treat. Results There were 64 ipsilateral events in the RT arm and 141 in the control group corresponding to a risk reduction of 16.0 percentage points at 10 years (95% CI, 10.3% to 21.6%) and a relative risk of 0.40 (95% CI, 0.30 to 0.54). There was no statistically significant difference in distant metastasis–free survival. There was an effect modification by age, yielding a low effect of RT in women younger than 50, but substantial protection in women older than 60 years. The age effect was not confounded by focality, lesion size, completeness of excision, or detection mode. There was no group as defined by our stratification variables that had a low risk without radiotherapy. Conclusion Our results indicate that younger women have a low protective effect of conventional RT after sector resection. Older women benefit substantially. We caution that the age effect was seen in a subgroup analysis. Further search with conventional clinical variables for a low risk group that does not need RT does not seem fruitful.
Cardiac Safety Analysis of Doxorubicin and Cyclophosphamide Followed by Paclitaxel With or Without Trastuzumab in the North Central Cancer Treatment Group N9831 Adjuvant Breast Cancer Trial
Authors: Perez Edith A. , Suman Vera J. , Davidson Nancy E. , Sledge George W. , Kaufman Peter A. , Hudis Clifford A. , Martino Silvana , Gralow Julie R. , Dakhil Shaker R. , Ingle James N. , Winer Eric P. , Gelmon Karen A. , Gersh Bernard J. , Jaffe Allan S. , Rodeheffer Richard J. 
Published: February 2008

Purpose To assess cardiac safety and potential cardiac risk factors associated with trastuzumab in the NCCTG N9831 Intergroup adjuvant breast cancer trial. Patients and Methods Patients with HER2-positive operable breast cancer were randomly assigned to doxorubicin plus cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab then trastuzumab alone (arm C). Left ventricular ejection fraction (LVEF) was evaluated at registration and 3, 6, 9, and 18 to 21 months. Results Of 2,992 patients completing AC, 5.0% had LVEF decreases disallowing trastuzumab (decrease below normal: 2.4%, decrease > 15%: 2.6%). There were 1,944 patients with satisfactory or no LVEF evaluation who proceeded to post-AC therapy. Cardiac events (congestive heart failure [CHF] or cardiac death [CD]): arm A, n = 3 (2 CHF, 1 CD); arm B, n = 19 (18 CHF, 1 CD); arm C, n = 19 (all CHF); 3-year cumulative incidence: 0.3%, 2.8%, and 3.3%, respectively. Cardiac function improved in most CHF cases following trastuzumab discontinuation and cardiac medication. Factors associated with increased risk of a cardiac event in arms B and C: older age (P < .003), prior/current antihypertensive agents (P = .005), and lower registration LVEF (P = .033). Incidence of asymptomatic LVEF decreases requiring holding trastuzumab was 8% to 10%; LVEF recovered and trastuzumab was restarted in approximately 50%. Conclusion The cumulative incidence of post-AC cardiac events at 3 years was higher in the trastuzumab-containing arms versus the control arm, but by less than 4%. Older age, lower registration LVEF, and antihypertensive medications are associated with increased risk of cardiac dysfunction in patients receiving trastuzumab following AC.
Modulation of Cystathionine β-Synthase Activity by Altering Heme Environment
Authors: Ozaki Shin-ichi , Doi Masafumi , Migita Catharina T 
Published: February 2008

Abstract
Human cystathionine β-synthase (CBS) is unique in bearing not only a catalytically important pyridoxal-5′-phosphate (PLP) but also heme. We have observed the alternation of heme environment under the alkaline condition causes the inactivation of CBS. On the basis of crystal structure, we propose that the change in the axial ligation of heme would modulate CBS activity through the interaction with Arg-266.