Genomic Hallmarks of Genes Involved in Chromosomal Translocations in Hematological Cancer

Reciprocal chromosomal translocations (RCTs) leading to the formation of fusion genes are important drivers of hematological cancers. Although the general requirements for breakage and fusion are fairly well understood, quantitative support for a general mechanism of RCT formation is still lacking. The aim of this paper is to analyze available high-throughput datasets with computational and robust statistical methods, in order to identify genomic hallmarks of translocation partner genes (TPGs). Our results show that fusion genes are generally overexpressed due to increased promoter activity of 5′ TPGs and to more stable 3′-UTR regions of 3′ TPGs. Furthermore, expression profiling of 5′ TPGs and of interaction partners of 3′ TPGs indicates that these features can help to explain tissue specificity of hematological translocations. Analysis of protein domains retained in fusion proteins shows that the co-occurrence of specific domain combinations is non-random and that distinct functional classes of fusion proteins tend to be associated with different components of the gene fusion network. This indicates that the configuration of fusion proteins plays an important role in determining which 5′ and 3′ TPGs will combine in specific fusion genes. It is generally accepted that chromosomal proximity in the nucleus can explain the specific pairing of 5′ and 3′ TPGS and the recurrence of hematological translocations. Using recently available data for chromosomal contact probabilities (Hi-C) we show that TPGs are preferentially located in early replicated regions and occupy distinct clusters in the nucleus. However, our data suggest that, in general, nuclear position of TPGs in hematological cancers explains neither TPG pairing nor clinical frequency. Taken together, our results support a model in which genomic features related to regulation of expression and replication timing determine the set of candidate genes more likely to be translocated in hematological tissues, with functional constraints being responsible for specific gene combinations.     

Flavonoids from Erythroxylon argentinum

Quercetin 3-rutinoside, quercetin 3-α-l-rhamnoside, 7,4′-dimethylquercetin 3-rutinoside and the novel glycoside 7,4′-dimethylquercetin 3-rutinoside-5-glucoside have been identified from aerial parts of Erythroxylon argentinum.     

Evaluating the influence of off-shore cage aquaculture on the benthic ecosystem in Alghero Bay (Sardinia,Italy) using AMBI and M-AMBI

The impact of an off-shore fish farm in Alghero Bay (northwest Sardinia, Italy) on the benthic ecosystem was investigated in 2007 and 2008. In addition to studying the chemical and physical characteristics of the area (i.e., currents and sediment analyses), some biological analyses were also performed. The AZTI's Marine Biotic Index (AMBI) and the multivariate AMBI (M-AMBI) were calculated, which are being used in assessing the ecological status of benthic communities within the European Water Framework Directive (WFD). Clear impact gradients were detected according to both methods; they are related to farm production, prevailing currents, and characteristics of the area (i.e., water depth and distance to the cages). The site affected most was detected within 84 m from the cages; the area that no longer showed effects was over 907 m from the cages. The gradient is shown by decreasing AMBI values and percentage of opportunistic species and increasing richness, diversity, and the presence of sensitive species. This study highlights the importance of setting reference conditions for different areas when calculating M-AMBI. These reference conditions correspond to those in undisturbed sites in the opposite direction of the prevailing currents within the area.     

Response of a native,herbivorous snail to the introduced seaweed <Emphasis Type="Italic">Sargassum muticum</Emphasis>

The role of native consumers in mediating biological invasions is poorly understood. In theory, there are reasons to expect both strong and weak effects of native consumers on non-native species. However, non-native ranges may include multiple regions or even continents, each with its own suite of consumers and invader–consumer interactions may play out differently in different places and times. In this Washington State (USA) study we found that the common herbivorous snail Lacuna vincta was 2–9 times more abundant on the non-native seaweed Sargassum muticum, compared to native kelps. Choice feeding trials with fresh tissue and artificial foods both suggest that S. muticum is a preferred food for Lacuna vincta. Lab experiments indicated that L. vincta did not experience diminished predation by two common predators on Sargassum muticum compared to native kelp hosts. Our results suggest that Sargassum experiences considerable herbivory by Lacuna vincta in our study region, a conclusion that is consistent with previous work and our own field observations. In our system, L. vincta and S. muticum have been coexisting in the same habitats for at least 50 years and available data suggest that it acquired a preference for S. muticum more than 30 years after the initial invasion. Comparison of our results to recent work on Sargassum–herbivore interactions in Europe suggests that the response of native consumer communities to S. muticum varies both within and among regions. Geographic and temporal variation in the response of native consumers are likely to be hallmarks of many large-scale invasions.     

Discordant patterns of introgression across a narrow hybrid zone between two cryptic lineages of an Iberian endemic newt

The study of natural hybrid zones can illuminate aspects of lineage divergence and speciation in morphologically cryptic taxa. We studied a hybrid zone between two highly divergent but morphologically similar lineages (south‐western and south‐eastern) of the Iberian endemic Bosca's newt (Lissotriton boscai) in SW Iberia with a multilocus dataset (microsatellites, nuclear and mitochondrial genes). STRUCTURE and NEWHYBRIDS analyses retrieved few admixed individuals, which classified as backcrosses involving parental individuals of the south‐western lineage. Our results show asymmetric introgression of mtDNA beyond the contact from this lineage into the south‐eastern lineage. Analysis of nongeographic introgression patterns revealed asymmetries in the direction of introgression, but except for mtDNA, we did not find evidence for nonconcordant introgression patterns across nuclear loci. Analysis of a 150‐km transect across the hybrid zone showed broadly coincident cline widths (ca. 3.2–27.9 km), and concordant cline centres across all markers, except for mtDNA that is displaced ca. 60 km northward. Results from ecological niche modelling show that the hybrid zone is in a climatically homogenous area with suitable habitat for the species, suggesting that contact between the two lineages is unlikely to occur further south as their distributions are currently separated by an extensive area of unfavourable habitat. Taken together, our findings suggest the genetic structure of this hybrid zone results from the interplay of historical (biogeographic) and population‐level processes. The narrowness and coincidence of genetic clines can be explained by weak selection against hybrids and reflect a degree of reproductive isolation that is consistent with cryptic speciation.