Managing core resources for genomics and proteomics

Recent years have seen an explosive growth in biological data, which is often not published in a conventional sense but rather deposited in a database. This trend and the need for computational analyses of the data make databases essential tools for biological research. Data from a variety of sources, covering a wide range of biological information, are stored in different, often quite specialized, databases. The provision of such databases as useful resources for the scientific community is a demanding task since the data not only have to be stored in a consistent way, but also have to be easily accessible and highly integrated with other databases. Furthermore, it is necessary to provide users with effective tools to search the databases and to analyze the data. At the European Bioinformatics Institute (EBI), we develop and maintain a number of biological databases and provide a variety of bioinformatics tools to facilitate database and similarity searches and data analysis. In this review, we will provide examples of the core resources maintained at the EBI and summarize important issues of database management of such resources.     

Insulin and estrogen receptor ligand influence the FGF-2 activities in MCF-7 breast cancer cells

From the MCF-7 cell line we have developed, a human mammary cancer cell subline with the same karyotype as the mother strain and named MCF-7(SF), able to grow in serum-free chemically defined medium. This cell subline was firstly used to analyze the effect of basic fibroblast growth factor (FGF-2) in estrogen-receptor-positive human breast cancer cells. FGF-2 like estradiol is able to increase cell proliferation and pS2 expression but was also found to inhibit progesterone receptor (PR) expression. The anti-estrogen tamoxifen partly counteracts the effects of FGF-2 and to discriminate between its two main mediators (estrogen receptor vs. anti-estrogen binding site, AEBS) we compare the efficacies of pure anti-estrogen (ICI 182,780) and AEBS ligand (PBPE). It appears that pure anti-estrogen counteracts cell growth and pS2 effects of FGF-2 since AEBS ligand inhibits the cell growth but has no activity on pS2 expression. Secondly, adding insulin (10(-6)M) in the culture medium induces a strong increase in cell proliferation, which then elicits an inhibitory effect of FGF-2 and addition of anti-estrogens, are less efficient to further decrease growth, since the effects of FGF-2 and anti-estrogens on pS2 expression are conserved.     

Delphinidin inhibits endothelial cell proliferation and cell cycle progression through a transient activation of ERK-1/-2

Epidemiological studies have shown that a diet rich in fruits and vegetables might reduce the risk of cardiovascular diseases and protect against cancer by mechanisms that have not been elucidated yet. This study was aimed to define the effect of delphinidin, a vasoactive polyphenol belonging to the class of anthocyanin, on bovine aortic endothelial cells (BAECs) proliferation. Delphinidin inhibited serum- and vascular endothelium growth factor-induced BAECs proliferation. This antiproliferative effect of delphinidin, is triggered by ERK-1/-2 activation, independent of nitric oxide pathway and is correlated with suppression of cell progression by blocking the cell cycle in G(0)/G(1) phase. Furthermore, suppression of cell cycle progression is associated with the modulation of the mitogenic signaling transduction cascade. This includes over-expression of caveolin-1 and p21(WAF1/Cip1) and down-expression of Ras and cyclin D1. In conclusion, the antiproliferative effect of delphinidin may be of importance in preventing both plaque development and stability in atherosclerosis and tumor dissemination in cancer.     

Re-establishment of a normal apoptotic process as a therapeutic approach in B-CLL

Even though the capacity of B-CLL leukemic cells to proliferate has been underestimated until recently, the accumulation of tumor cells in patients mostly results from a defect in the apoptotic program. Several mechanisms can account for this deficient cell death pathway. These include overexpression of anti-apoptotic molecules such as members of the Bcl-2 family, which control the opening of the mitochondrial transition permeability pore, and of the IAP (inhibitors of apoptosis) family, which inhibit the activity of caspases. The latter is also suppressed by nitric oxide (NO) released through an inducible NO synthase present in the leukemic cells. The activity of the receptors with a death domain (Fas, TRAIL) is impaired, thus contributing to the resistance to spontaneous and/or drug-induced apoptosis. Interferons as well as several cytokines and angiogenic factors are also involved in the failure of programmed cell death, either by providing efficient signals for survival (BAFF) or by counteracting the apoptotic process. A better knowledge of the mechanisms of survival and escape from apoptosis of B-CLL cells has led to the proposal of new drugs that selectively interfere at the different steps of these cascades. Their study is complicated by the lack of suitable cell lines and pre-clinical models. Nevertheless, some of these chemotherapeutic agents appear to be promising, provided they are correctly targeted to the leukemic cells.     

Social and health determinants of the efficiency of cotton farmers in Northern Côte d'Ivoire

This article assesses the role of malaria and some social determinants on the agricultural development and more precisely on efficiency in the context of cotton crop in the Korhogo region in the North of C?te d'Ivoire. Data envelopment analyses (DEA) was first applied for the purpose of calculating relative efficiencies in production. A Tobit regression model was then used to explain the variation in the DEA scores and check the hypotheses that the efficiency deviations between farmers can be explained by the disparity of malaria morbidity rate among the farmers and their family, by social cohesiveness and cultural behaviour. Field data were collected by the authors between March 1997 and February 1998 on 700 rural households living in three rice production systems differently exposed to the malaria risk. Two malaria indicators were used for the active (11-55 years old) family members of the farm: Plasmodium falciparum infection rate and high parasite density infection rate. The DEA model was applied on the sub-sample of cotton growers (about one third of the households of the full sample). Results of the different DEA and Tobit models (depending of the production process hypothesis) show that high parasite density infection has a direct and indirect negative effect on efficiency in the cotton crop. They also show that more cotton growers in the village improve efficiency, although villages where cotton is growing more widespread have weaker social cohesion.     

Mechanisms by which maternal antibodies influence infant vaccine responses: review of hypotheses and definition of main determinants

Several mechanisms have been suggested as mediating the inhibitory influence of maternal antibodies (MatAb) on infant responses. This inhibition is B cell determinant-specific, depends on the ratio between MatAb titers at the time of immunization and the dose of vaccine antigen, and leaves infant T cell responses largely unaffected. Neutralization of vaccine replication or FcgammaRIIB-mediated inhibitory signalling to infant B cells would not account for these characteristics. In contrast, determinant-specific masking of B cell epitopes and APC uptake of MatAb:vaccine antigen immune complexes, followed by antigen processing and presentation, explain the pattern of pre-clinical and clinical responses to infant vaccines. This allows the definition of the main determinants of the influence of MatAb on infant immunity.     

Factors associated with positive HIV serostatus among women who use drugs: continued evidence for expanding factors of influence

OBJECTIVE: To identify risk factors associated with positive HIV serostatus among African American women who smoke crack and/or inject drugs and who are not enrolled in drug treatment or another institutional setting. METHODS: Baseline interviews were conducted from June 1998 to June 2000 with 379 heterosexually active women (ages 18 to 59) who had been recruited for potential enrollment into an HIV intervention trial. RESULTS: Adjusted for age and drug using status, women who expressed more difficulty saying no to sex with male partners were more likely to be HIV-positive (adjusted odds ratio [aOR]=3.08, 95% confidence interval [CI] 2.02, 4.83). Similarly, those who indicated greater communication with casual sex partner(s) were less likely to test positive (aOR=0.29, 95% CI 0.10, 0.89). Lower HIV internal control and a history of cuts or burns on lips due to crack smoking were also associated with positive serostatus, and were important confounders in the final multivariate model. A higher level of internal control was associated with a decreased likelihood of positive serostatus, while a history of cuts or burns on the lips was associated with an increased likelihood of HIV antibodies, even after controlling for the amount of oral sex. CONCLUSIONS: A broad array of factors may promote or avert infection with HIV. The degree to which personal attributes and beliefs, and relationship characteristics contribute to the likelihood of infection must continue to be addressed. The importance of oral sex and presence of oral sores and their potential role in transmission was suggested.