LaTcOm: a web server for visualizing rare codon clusters in coding sequences

We present LaTcOm, a new web tool, which offers several alternative methods for 'rare codon cluster' (RCC) identification from a single and simple graphical user interface. In the current version, three RCC detection schemes are implemented: the recently described %MinMax algorithm and a simplified sliding window approach, along with a novel modification of a linear-time algorithm for the detection of maximally scoring subsequences tailored to the RCC detection problem. Among a number of user tunable parameters, several codon-based scales relevant for RCC detection are available, including tRNA abundance values from Escherichia coli and several codon usage tables from a selection of genomes. Furthermore, useful scale transformations may be performed upon user request (e.g. linear, sigmoid). Users may choose to visualize RCC positions within the submitted sequences either with graphical representations or in textual form for further processing. AVAILABILITY: LaTcOm is freely available online at the URL http://troodos.biol.ucy.ac.cy/latcom.html.     

Further delineation of novel 1p36 rearrangements by array-CGH analysis: Narrowing the breakpoints and clarifying the "extended" phenotype

High resolution oligonucleotide array Comparative Genome Hybridization technology (array-CGH) has greatly assisted the recognition of the 1p36 contiguous gene deletion syndrome. The 1p36 deletion syndrome is considered to be one of the most common subtelomeric microdeletion syndromes and has an incidence of ~1 in 5000 live births, while respectively the "pure" 1p36 microduplication has not been reported so far. We present seven new patients who were referred for genetic evaluation due to Developmental Delay (DD), Mental Retardation (MR), and distinct dysmorphic features. They all had a wide phenotypic spectrum. In all cases previous standard karyotypes were negative. Array-CGH analysis revealed five patients with interstitial 1p36 microdeletion (four de novo and one maternal) and two patients with de novo reciprocal duplication of different sizes. These were the first reported "pure" 1p36 microduplication cases so far. Three of our patients carrying the 1p36 microdeletion syndrome were also found to have additional pathogenetic aberrations. These findings (del 3q27.1; del 4q21.22-q22.1; del 16p13.3; dup 21q21.2-q21.3; del Xp22.12) might contribute to the patients' severe phenotype, acting as additional modifiers of their clinical manifestations. We review and compare the clinical and array-CGH findings of our patients to previously reported cases with the aim of clearly delineating more accurate genotype-phenotype correlations for the 1p36 syndrome that could allow for a more precise prognosis.     

Induction of discrete apoptotic pathways by bromo-substituted indirubin derivatives in invasive breast cancer cells

Indirubin derivatives gained interest in recent years for their anticancer and antimetastatic properties. The objective of the present study was to evaluate and compare the anticancer properties of the two novel bromo-substituted derivatives 6-bromoindirubin-3'-oxime (6BIO) and 7-bromoindirubin-3'-oxime (7BIO) in five different breast cancer cell lines. Cell viability assays identified that 6BIO and 7BIO are most effective in preventing the proliferation of the MDA-MB-231-TXSA breast cancer cell line from a total of five breast cancer cell lined examined. In addition it was found that the two compounds induce apoptosis via different mechanisms. 6BIO induces caspase-dependent programmed cell death through the intrinsic (mitochondrial) caspase-9 pathway. 7BIO up-regulates p21 and promotes G(2)/M cell cycle arrest which is subsequently followed by the activation of two different apoptotic pathways: (a) a pathway that involves the upregulation of DR4/DR5 and activation of caspase-8 and (b) a caspase independent pathway. In conclusion, this study provides important insights regarding the molecular pathways leading to cell cycle arrest and apoptosis by two indirubin derivatives that can find clinical applications in targeted cancer therapeutics.     

Pelagic-Benthic Coupling and Diagenesis of Nucleic Acids in a Deep-Sea Continental Margin and an Open-Slope System of the Eastern Mediterranean

Downward fluxes of nucleic acids adsorbed onto settling particles play a key role in the supply of organic phosphorus and genetic material to the ocean interior. However, information on pelagic-benthic coupling, diagenesis, and processes controlling nucleic acid preservation in deep-sea sediments is practically nonexistent. In this study, we compared nucleic acid fluxes, sedimentary DNA and RNA concentrations, and the enzymatically hydrolyzable fraction of DNA in a bathyal continental margin (North Aegean Sea) and an open-sea system (South Aegean Sea) of the Eastern Mediterranean. The two systems displayed contrasting patterns of nucleic acid fluxes, which increased significantly with depth in the North Aegean Sea and decreased with depth in the South Aegean Sea. These results suggest that in continental margin and open-ocean systems different processes control the nucleic acid supply to the sea floor. Differences in nucleic acid fluxes were reflected by nucleic acid concentrations in the sediments, which reached extremely high values in the North Aegean Sea. In this system, a large fraction of DNA may be buried, as suggested by the large fraction of DNA resistant to nuclease degradation and by estimates of burial efficiency (ca. eight times higher in the North than in the South Aegean Sea). Overall, the results reported here suggest that the preservation of DNA in deeper sediment layers may be favored in benthic systems characterized by high sedimentation rates.     

Modelling of essential fish habitat based on remote sensing,spatial analysis and GIS

Lake Tanganyika is not the most species-rich of the Great East African Lakes, but comprises the greatest diversity of cichlid fishes in terms of morphology, ecology, and breeding styles. The lake contains a polyphyletic assemblage of cichlid lineages, which evolved from several ancient species that colonized the emerging lake some 9–12 million years ago. Based on morphological characteristics, the Tanganyikan cichlids have been classified into 12, or, more recently, 16 tribes, which are largely supported by molecular data. The radiations of East African cichlids are believed to be driven by complex interactions between extrinsic factors, such as climatic changes and geological processes, and intrinsic biological characteristics of the involved organisms. Diversification within different lineages occurred simultaneously in response to drastic habitat changes such as the establishment of lacustrine deep-water conditions 5–6 MYA and subsequent major lake-level fluctuations. This seems particularly true for the mouthbrooding lineages whereas the substrate breeders underwent a more gradual process of diversification. This review presents an account of the taxonomy and phylogeny of the Lake Tanganyika cichlid species assemblage, its relationship to the African cichlid fauna, key factors leading to the astonishing diversity and discusses recently proposed alternative age estimates for the Lake Tanganyika cichlid species assemblage.     

Phytoestrogens as natural prodrugs in cancer prevention: a novel concept

It has been generally accepted that regular consumption of fresh fruits and vegetables is linked with a relatively low incidence of cancers (e.g. breast, cervix, and colon). A number of plant-derived compounds have been identified that are considered to play a role in cancer prevention. However, at present there is no satisfactory explanation for the cancer preventative properties of the above-mentioned compound groups. The current review is an effort to develop a consistent and unambiguous model that explains how some plant-derived compounds can prevent tumour development. The model is based on recent discoveries in the fields of genomics and drug-metabolism; notably, the discovery that CYP1 genes are highly expressed in developing tumour cells but not in the surrounding tissue, and that a variety of plant-derived compounds are substrates for the CYP1 enzymes. Our hypothesis is that some dietary compounds act as prodrugs, i.e. compounds with little or no biological effect as such, but become pharmaceutically effective when activated. More specifically, we state that the abovementioned prodrugs are only activated in CYP1-expressing cells—i.e. cells in the early stages of tumour development—to be converted into compounds which inhibit cell growth. Thus, the prodrugs selectively kill precancerous cells early in tumour development. The review focuses on the identification of naturally-occurring prodrugs that are activated by the tumour-specific CYP1 enzymes and aims to assess their role in cancer prevention.     

Yale school of public health symposium on lifetime exposures and human health: the exposome; summary and future reflections

The exposome is defined as “the totality of environmental exposures encountered from birth to death” and was developed to address the need for comprehensive environmental exposure assessment to better understand disease etiology. Due to the complexity of the exposome, significant efforts have been made to develop technologies for longitudinal, internal and external exposure monitoring, and bioinformatics to integrate and analyze datasets generated. Our objectives were to bring together leaders in the field of exposomics, at a recent Symposium on “Lifetime Exposures and Human Health: The Exposome,” held at Yale School of Public Health. Our aim was to highlight the most recent technological advancements for measurement of the exposome, bioinformatics development, current limitations, and future needs in environmental health. In the discussions, an emphasis was placed on moving away from a one-chemical one-health outcome model toward a new paradigm of monitoring the totality of exposures that individuals may experience over their lifetime. This is critical to better understand the underlying biological impact on human health, particularly during windows of susceptibility. Recent advancements in metabolomics and bioinformatics are driving the field forward in biomonitoring and understanding the biological impact, and the technological and logistical challenges involved in the analyses were highlighted. In conclusion, further developments and support are needed for large-scale biomonitoring and management of big data, standardization for exposure and data analyses, bioinformatics tools for co-exposure or mixture analyses, and methods for data sharing.     

Assessing the Ecological Integrity of a Major Transboundary Mediterranean River Based on Environmental Habitat Variables and Benthic Macroinvertebrates (Aoos‐Vjose River,Greece‐Albania)

Ecological integrity has become a primary objective in monitoring programs of surface waters according to the European Water Framework Directive. For this reason we propose a scheme for assessing the ecological integrity of a major transboundary river, the Aoos‐Vjose (Greece‐Albania), by analysing the effects of physicochemical, hydromorphological and habitat structure variables on benthic macroinvertebrates. Benthos and water samples were obtained from 17 sites, during high and low flow season. Physical habitat structure was determined using the River Habitat Survey method. In all but one of the surveyed habitats no anthropogenic change was evident. Macrobenthos assemblages were mainly influenced by seasonality and river section, whereas the water quality index was negatively correlated to habitat modification. Consequently, a large part of the river is considered of high ecological integrity and as such it may be used as baseline information for the management of other major rivers in the eastern Mediterranean basin. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Coupling biomolecules to fullerenes through a molecular adapter

A novel biotinylated fullerene has been synthesized to facilitate the attachment of biotin-conjugated proteins to C(60) through the use of streptavidin as a molecular adapter. The strong biotin-streptavidin interaction enables the attachment of fullerenes to streptavidin and, because of the availability of four biotin-binding sites on streptavidin, to biotinylated biomolecules. The feasibility of this approach is demonstrated by using biotinylated alkaline phosphatase. Due to the insolubility of fullerenes in aqueous media, the immobilized enzyme can be eventually recovered by simple centrifugation with no significant loss in activity.