In a comfort zone and beyond—Ecological plasticity of key marine mediators

Copepods of the genus Calanus are the key components of zooplankton. Understanding their response to a changing climate is crucial to predict the functioning of future warmer high‐latitude ecosystems. Although specific Calanus species are morphologically very similar, they have different life strategies and roles in ecosystems. In this study, C. finmarchicus and C. glacialis were thoroughly studied with regard to their plasticity in morphology and ecology both in their preferred original water mass (Atlantic vs. Arctic side of the Polar Front) and in suboptimal conditions (due to, e.g., temperature, turbidity, and competition in Hornsund fjord). Our observations show that “at the same place and time,” both species can reach different sizes, take on different pigmentation, be in different states of population development, utilize different reproductive versus lipid accumulation strategies, and thrive on different foods. Size was proven to be a very mutable morphological trait, especially with regard to reduced length of C. glacialis. Both species exhibited pronounced red pigmentation when inhabiting their preferred water mass. In other domains, C. finmarchicus individuals tended to be paler than C. glacialis individuals. Gonad maturation and population development indicated mixed reproductive strategies, although a surprisingly similar population age structure of the two co‐occurring species in the fjord was observed. Lipid accumulation was high and not species‐specific, and its variability was due to diet differences of the populations. According to the stable isotope composition, both species had a more herbivorous diatom‐based diet in their original water masses. While the diet of C. glacialis was rather consistent among the domains studied, C. finmarchicus exhibited much higher variability in its feeding history (based on lipid composition). Our results show that the plasticity of both Calanus species is indeed impressive and may be regulated differently, depending on whether they live in their “comfort zone” or beyond it.     

LigandRNA: computational predictor of RNA–ligand interactions

RNA molecules have recently become attractive as potential drug targets due to the increased awareness of their importance in key biological processes. The increase of the number of experimentally determined RNA 3D structures enabled structure-based searches for small molecules that can specifically bind to defined sites in RNA molecules, thereby blocking or otherwise modulating their function. However, as of yet, computational methods for structure-based docking of small molecule ligands to RNA molecules are not as well established as analogous methods for protein-ligand docking. This motivated us to create LigandRNA, a scoring function for the prediction of RNA–small molecule interactions. Our method employs a grid-based algorithm and a knowledge-based potential derived from ligand-binding sites in the experimentally solved RNA–ligand complexes. As an input, LigandRNA takes an RNA receptor file and a file with ligand poses. As an output, it returns a ranking of the poses according to their score. The predictive power of LigandRNA favorably compares to five other publicly available methods. We found that the combination of LigandRNA and Dock6 into a “meta-predictor” leads to further improvement in the identification of near-native ligand poses. The LigandRNA program is available free of charge as a web server at http://ligandrna.genesilico.pl.     

Canine Mammary Tumours Are Affected by Frequent Copy Number Aberrations,including Amplification of MYC and Loss of PTEN

BackgroundCopy number aberrations frequently occur during the development of many cancers. Such events affect dosage of involved genes and may cause further genomic instability and progression of cancer. In this survey, canine SNP microarrays were used to study 117 canine mammary tumours from 69 dogs.ResultsWe found a high occurrence of copy number aberrations in canine mammary tumours, losses being more frequent than gains. Increased frequency of aberrations and loss of heterozygosity were positively correlated with increased malignancy in terms of histopathological diagnosis. One of the most highly recurrently amplified regions harbored the MYC gene. PTEN was located to a frequently lost region and also homozygously deleted in five tumours. Thus, deregulation of these genes due to copy number aberrations appears to be an important event in canine mammary tumour development. Other potential contributors to canine mammary tumour pathogenesis are COL9A3, INPP5A, CYP2E1 and RB1. The present study also shows that a more detailed analysis of chromosomal aberrations associated with histopathological parameters may aid in identifying specific genes associated with canine mammary tumour progression.ConclusionsThe high frequency of copy number aberrations is a prominent feature of canine mammary tumours as seen in other canine and human cancers. Our findings share several features with corresponding studies in human breast tumours and strengthen the dog as a suitable model organism for this disease.     

IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity

The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV. IPS-1^−/− mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1^−/− mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection. Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection.     

Concentration of <Emphasis Type="Italic">Cupriavidus necator</Emphasis> cells by flocculation and sedimentation

Separation and cells concentration constitute important stages in most biotechnological processes. Particularly, use of flocculation/sedimentation can improve significantly the extraction of biopolymers accumulated by microorganisms and the biodegradation of xenobiotic compounds by cell sludge. In this work the use of tannin and aluminum sulphate (Al₂(SO₄)₃) as flocculating agents for concentration of cells of Cupriavidus necator DSM 545 is evaluated. Cells were grown in broth nutrient medium in Erlenmeyer flasks, submitted to orbital agitation of 160 rpm at 30 °C for 21 h. The optimal concentrations of flocculating agents, as determined with a standard jar test method, were equal to 2,800 mg/L for tannin and 800 mg/L for Al₂(SO₄)₃, allowing for recovery of 95% of the cells in both cases. Obtained flocs presented density and average diameter of 1.03 g/mL ± 0.01 g/mL and 158 μm ± 19 μm for tannin and of 1.05 g/mL ± 0.01 g/mL and 146 μm ± 14 μm for Al₂(SO₄)₃, respectively. Batch settling tests were performed in order to determine the operational capacity of continuous settlers to be used for separation of the investigated flocculent suspensions. Finally, cultivation of cells using flocs as inoculum indicated that the cells remained viable after flocculation with usage of the optimum flocculating agent concentrations.     

Trans fat diet causes decreased brood size and shortened lifespan in Caenorhabditis elegans delta-6-desaturase mutant fat-3

Trans-fatty acids (TFAs) enter the diet through industrial processes and can cause adverse human health effects. The present study was aimed to examine the effects of dietary cis- and trans-fatty acids on the model organism Caenorhabditis elegans. Cis- or trans-18:1n9 triglycerides (25 μM) caused no apparent changes in the numbers of viable progeny of wild-type N2 animals. However, in fat-3 mutants lacking delta-6-desaturase, the trans-isomer caused modest decreases in lifespan and progeny after three generations. Long-chain polyunsaturated fatty acids (PUFA) profiles were significantly altered in fat-3 mutants compared to wild type but were not altered after exposure to dietary cis- or trans-18:1n9. Genome-wide expression analysis of fat-3 mutants revealed hundreds of changes. Several genes involved in fat metabolism (acs-2, fat-7, mdt-15) were significantly increased by cis- or trans-18:1n9 without discrimination between isomers. These results provide support for the hypothesis that dietary trans fats are detrimental to development and aging.