Mutagenicity of the mycotoxin diacetoxyscirpenol on somatic and germ cells of mice

Genotoxicity of diacetoxyscirpenol (DAS) was studied on laboratory mice after intraperitoneal injection with single and repeated doses. DAS was administrated at three different dose levels (0.5, 0.75, and 1.0 mg/kg body weight). The study was conducted on both somatic and germ cells additional to the sperm morphology analysis. DAS treatment resulted in a significant reduction (P<0.01) in mitotic activity at all levels of doses tested, confirming that DAS is a potent protein and DNA synthesis inhibitor. At somatic cells (bone marrow) both structural and numerical chromosome abnormalities were observed. Single dose treatment showed significant abnormalities only with high dose treatment. In contrast, at repeated dose similar abnormalities were also observed with some significance but no systematic relation between the administrated dose and abnormalities ratio could be settled. In germ cells (testicles), structural and numerical abnormalities were also observed. In general, the frequencies of scored abnormalities at germ cells were lower than that the somatic cells. Sperm count test revealed a decrease in the number of released sperm after toxin treatment. Abnormalities of sperm shape (head and tail) were observed, confirming the positive correlation between cytogenetic damage and sperm abnormality. The results also proved that DAS is a very toxic mycotoxin, in addition to inducing chromosomal abnormalities, it causes a severe inhibition of DNA synthesis which subsequently affects the cell cycle and cell division. A good system for good harvesting practice and good food technology can lower the risk for the consumers.     

Gendered perceptions on infant feeding in Eastern Uganda: continued need for exclusive breastfeeding support

Background

In resource-poor settings, HIV positive mothers are recommended to choose between 'Exclusive breastfeeding' (EBF) or 'Exclusive replacement feeding' (ERF). Acceptability, Feasibility, Affordability, Sustainability and Safety (AFASS) has been the World Health Organization (WHO)'s a priori criteria for ERF the last ten years. 'AFASS' has become a mere acronym among many workers in the field of prevention of mother-to-child transmission of HIV, PMTCT. Thereby, non-breastfeeding has been suggested irrespective of social norms. EBF for the first half of infancy is associated with huge health benefits for children in areas where infant mortality is high. But, even if EBF has been recommended for a decade, few mothers are practicing it. We set out to understand fathers' and mothers' infant feeding perceptions and the degree to which EBF and ERF were 'AFASS.'

Methods

Eight focus groups with 81 informants provided information for inductive content analysis. Four groups were held by men among men and four groups by women among women in Mbale District, Eastern Uganda.

Results

Two study questions emerged: How are the different feeding options understood and accepted? And, what are men's and women's responsibilities related to infant feeding? A mother's commitment to breastfeed and the husband's commitment to provide for the family came out strongly. Not breastfeeding a newborn was seen as dangerous and as unacceptable, except in cases of maternal illness. Men argued that not breastfeeding could entail sanctions by kin or in court. But, in general, both men and women regarded EBF as 'not enough' or even 'harmful.' Among men, not giving supplements to breast milk was associated with poverty and men's failure as providers. Women emphasised lack of time, exhaustion, poverty and hunger as factors for limited breast milk production. Although women had attended antenatal teaching they expressed a need to know more. Most men felt left out from health education.

Conclusion

Breastfeeding was the expected way to feed the baby, but even with existing knowledge among mothers, EBF was generally perceived as impossible. ERF was overall negatively sanctioned. Greater culture-sensitivity in programs promoting safer infant feeding in general and in HIV-contexts in particular is urgently needed, and male involvement is imperative.

Trial Registration

The study was part of formative studies for the ongoing study PROMISE EBF registered at http://clinicaltrials.gov (NCT00397150).     

Molecular cytogenetic characterization of pancreas cancer cell lines reveals high complexity chromosomal alterations

Karyotype analysis can provide clues to significant genes involved in the genesis and growth of pancreas cancer. The genome of pancreas cancer is complex, and G-band analysis cannot resolve many of the karyotypic abnormalities seen. We studied the karyotypes of 15 recently established cell lines using molecular cytogenetic tools. Comparative genomic hybridization (CGH) analysis of all 15 lines identified genomic gains of 3q, 8q, 11q, 17q, and chromosome 20 in nine or more cell lines. CGH confirmed frequent loss of chromosome 18, 17p, 6q, and 8p. 14/15 cell lines demonstrated loss of chromosome 18q, either by loss of a copy of chromosome 18 (n = 5), all of 18q (n = 7) or portions of 18q (n = 2). Multicolor FISH (Spectral Karyotyping, or SKY) of 11 lines identified many complex structural chromosomal aberrations. 93 structurally abnormal chromosomes were evaluated, for which SKY added new information to 67. Several potentially site-specific recurrent rearrangements were observed. Chromosome region 18q11.2 was recurrently involved in nine cell lines, including formation of derivative chromosomes 18 from a t(18;22) (three cell lines), t(17;18) (two cell lines), and t(12;18), t(15;18), t(18;20), and ins(6;18) (one cell line each). To further define the breakpoints involved on chromosome 18, YACs from the 18q11.2 region, spanning approximately 8 Mb, were used to perform targeted FISH analyses of these lines. We found significant heterogeneity in the breakpoints despite their G-band similarity, including multiple independent regions of loss proximal to the already identified loss of DPC4 at 18q21.     

Pattern matching through Chaos Game Representation: bridging numerical and discrete data structures for biological sequence analysis

Background

Chaos Game Representation (CGR) is an iterated function that bijectively maps discrete sequences into a continuous domain. As a result, discrete sequences can be object of statistical and topological analyses otherwise reserved to numerical systems. Characteristically, CGR coordinates of substrings sharing an L-long suffix will be located within 2 ^-L distance of each other. In the two decades since its original proposal, CGR has been generalized beyond its original focus on genomic sequences and has been successfully applied to a wide range of problems in bioinformatics. This report explores the possibility that it can be further extended to approach algorithms that rely on discrete, graph-based representations.

Results

The exploratory analysis described here consisted of selecting foundational string problems and refactoring them using CGR-based algorithms. We found that CGR can take the role of suffix trees and emulate sophisticated string algorithms, efficiently solving exact and approximate string matching problems such as finding all palindromes and tandem repeats, and matching with mismatches. The common feature of these problems is that they use longest common extension (LCE) queries as subtasks of their procedures, which we show to have a constant time solution with CGR. Additionally, we show that CGR can be used as a rolling hash function within the Rabin-Karp algorithm.

Conclusions

The analysis of biological sequences relies on algorithmic foundations facing mounting challenges, both logistic (performance) and analytical (lack of unifying mathematical framework). CGR is found to provide the latter and to promise the former: graph-based data structures for sequence analysis operations are entailed by numerical-based data structures produced by CGR maps, providing a unifying analytical framework for a diversity of pattern matching problems.     

Atlas – a data warehouse for integrative bioinformatics

Background  

We present a biological data warehouse called Atlas that locally stores and integrates biological sequences, molecular interactions, homology information, functional annotations of genes, and biological ontologies. The goal of the system is to provide data, as well as a software infrastructure for bioinformatics research and development.