A primate virus generates transformed human cells by fusion

A model that explains both the origin and sporadic nature of cancer argues that cancer cells are a chance result of events that cause genomic and epigenetic variability. The prevailing view is that these events are mutations that affect chromosome segregation or stability. However, genomic and epigenetic variability is also triggered by cell fusion, which is often caused by viruses. Yet, cells fused by viruses are considered harmless because they die. We provide evidence that a primate virus uses both viral and exosomal proteins involved in cell fusion to produce transformed proliferating human cells. Although normal cells indeed fail to proliferate after fusion, expression of an oncogene or a mutated tumor suppressor p53 in just one of the fusion partners is sufficient to produce heterogeneous progeny. We also show that this virus can produce viable oncogenically transformed cells by fusing cells that are otherwise destined to die. Therefore, we argue that viruses can contribute to carcinogenesis by fusing cells

Control of Pre-mRNA Splicing by the General Splicing Factors PUF60 and U2AF65

Pre-mRNA splicing is a crucial step in gene expression, and accurate recognition of splice sites is an essential part of this process. Splice sites with weak matches to the consensus sequences are common, though it is not clear how such sites are efficiently utilized. Using an in vitro splicing-complementation approach, we identified PUF60 as a factor that promotes splicing of an intron with a weak 3' splice-site. PUF60 has homology to U2AF(65), a general splicing factor that facilitates 3' splice-site recognition at the early stages of spliceosome assembly. We demonstrate that PUF60 can functionally substitute for U2AF(65)in vitro, but splicing is strongly stimulated by the presence of both proteins. Reduction of either PUF60 or U2AF(65) in cells alters the splicing pattern of endogenous transcripts, consistent with the idea that regulation of PUF60 and U2AF(65) levels can dictate alternative splicing patterns. Our results indicate that recognition of 3' splice sites involves different U2AF-like molecules, and that modulation of these general splicing factors can have profound effects on splicing

High-risk HPV E5-induced cell fusion: a critical initiating event in the early stage of HPV-associated cervical cancer

<p>Abstract</p> <p>Background</p> <p>Cervical cancer is strongly associated with high-risk human papillomavirus (HPV) and viral oncoproteins E5, E6 and E7 can transform cells by various mechanisms. It is proposed that oncogenic virus-induced cell fusion may contribute to oncogenesis if p53 or apoptosis is perturbed simultaneously. Recently, HPV-16 E5 was found to be necessary and sufficient for the formation of tetraploid cells, which are frequently found in precancerous cervical lesions and its formation is strongly associated with HPV state.</p> <p>Presentation of the hypothesis</p> <p>We propose that high-risk HPV E5-induced cell fusion is a critical initiating event in the early stage of HPV-associated cervical cancer.</p> <p>Testing the hypothesis</p> <p>Our hypothesis can be tested by comparing the likelihood for colony formation or tumorigenic ability in nude mice between normal HaCaT cells expressing all three oncogenic proteins and E5-induced bi-nucleated HaCaT cells expressing E6 and E7. Moreover, investigating premature chromosome condensation (PCC) in HPV-positive and negative precancerous cervical cells is another way to assess this hypothesis.</p> <p>Implication of the hypothesis</p> <p>This viewpoint would change our understanding of the mechanisms by which HPV induces cervical cancer. According to this hypothesis, blocking E5-induced cell fusion is a promising way to prevent the progression of cervical cancer. Additionally, establishment of a role of cell fusion in cervical carcinogenesis is of reference value for understanding the pathogenesis of other virus-associated cancers.</p

Abundance, movements and biodiversity of flying predatory insects in crop and non-crop agroecosystems

[EN] Predatory insects are key natural enemies that can highly reduce crops pest damage. However, there is a lack of knowledge about the movements of flying predatory insects in agroecosystems throughout the year. In particular, it is still unclear how these predators move from crop to non-crop habitats, which are the preferred habitats to overwinter and to spread during the spring and if these predators leave or stay after chemical treatments. Here, the Neuroptera, a generalist, highly mobile, flying predator order of insects, was selected as model. We studied the effects of farming management and the efficiency of edge shelterbelts, ground cover vegetation, and fruit trees canopy on holding flying predatory insects in Mediterranean traditional agroecosystems. Seasonal movements and winter effects were also assessed. We evaluated monthly nine fruit agroecosystems, six organic, and three pesticides sprayed, of 0.5-1 ha in eastern Spain during 3 years using two complementary methods, yellow sticky traps and aspirator. Results show surprisingly that the insect abundance was highest in pesticide sprayed systems, with 3.40 insects/sample versus 2.32 insects/sample in organic systems. The biodiversity indices were highest in agroecosystems conducted under organic management, with S of 4.68 and D of 2.34. Shelterbelts showed highest biodiversity indices, S of 3.27 and D of 1.93, among insect habitats. Insect species whose adults were active during the winter preferred fruit trees to spend all year round. However, numerous species moved from fruit trees to shelterbelts to overwinter and dispersed into the orchard during the following spring. The ground cover vegetation showed statistically much lower attractiveness for flying predatory insects than other habitats. Shelterbelts should therefore be the first option in terms of investment in ecological infrastructures enhancing flying predators.Sorribas Mellado, JJ.; González Cavero, S.; Domínguez Gento, A.; Vercher Aznar, R. (2016). Abundance, movements and biodiversity of flying predatory insects in crop and non-crop agroecosystems. Agronomy for Sustainable Development. 36(2). doi:10.1007/s13593-016-0360-3S362Altieri MA, Letourneau DK (1982) Vegetation management and biological control in agroecosystems. Crop Prot 1:405–430. doi: 10.1016/0261-2194(82)90023-0Altieri MA, Schmidt LL (1986) The dynamics of colonizing arthropod communities at the interface of abandoned, organic and commercial apple orchards and adjacent woodland habitats. Agric Ecosyst Environ 16:29–43. doi: 10.1016/0167-8809(86)90073-3Bengtsson J, Ahnström J, Weibull A (2005) The effects of organic agriculture on biodiversity and abundance: a meta-analysis. 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Selective Release of MicroRNA Species from Normal and Malignant Mammary Epithelial Cells

MicroRNAs (miRNAs) in body fluids are candidate diagnostics for a variety of conditions and diseases, including breast cancer. One premise for using extracellular miRNAs to diagnose disease is the notion that the abundance of the miRNAs in body fluids reflects their abundance in the abnormal cells causing the disease. As a result, the search for such diagnostics in body fluids has focused on miRNAs that are abundant in the cells of origin. Here we report that released miRNAs do not necessarily reflect the abundance of miRNA in the cell of origin. We find that release of miRNAs from cells into blood, milk and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. In particular, the bulk of miR-451 and miR-1246 produced by malignant mammary epithelial cells was released, but the majority of these miRNAs produced by non-malignant mammary epithelial cells was retained. Our findings suggest the existence of a cellular selection mechanism for miRNA release and indicate that the extracellular and cellular miRNA profiles differ. This selective release of miRNAs is an important consideration for the identification of circulating miRNAs as biomarkers of disease

Biodiversity and structure of spider communities along a metal pollution gradient

The objective of the study was to determine whether long-term metal pollution affects communities of epigeal spiders (Aranea), studied at three taxonomic levels: species, genera, and families. Biodiversity was defined by three indices: the Hierarchical Richness Index (HRI), Margalef index (DM) and Pielou evenness index (J). In different ways the indices describe taxa richness and the distribution of individuals among taxa. The dominance pattern of the communities was described with four measures: number of dominant species at a site, percentage of dominant species at a site, average dominant species abundance at a site, and the share of the most numerous species (Alopecosa cuneata) at a site. Spiders were collected along a metal pollution gradient in southern Poland, extending ca. 33 km from zinc and lead smelter to an uncontaminated area. The zinc concentration in soil was used as the pollution index.The study revealed a significant effect of metal pollution on spider biodiversity as described by HRI for species (p = 0.039), genera (p = 0.0041) and families (p = 0.0147), and by DM for genera (p = 0.0259) and families (p = 0.0028). HRI correlated negatively with pollution level, while DM correlated positively. This means that although broadly described HRI diversity decreased with increasing pollution level, species richness increased with increasing contamination. Mesophilic meadows were generally richer. Pielou (J) did not show any significant correlations. There were a few evidences for the intermediate disturbance hypothesis: certain indices reached their highest values at moderate pollution levels rather than at the cleanest or most polluted sites

The EFF-1A Cytoplasmic Domain Influences Hypodermal Cell Fusions in C. elegans But Is Not Dependent on 14-3-3 Proteins.

BACKGROUND: Regulatory and biophysical mechanisms of cell-cell fusion are largely unknown despite the fundamental requirement for fused cells in eukaryotic development. Only two cellular fusogens that are not of clear recent viral origin have been identified to date, both in nematodes. One of these, EFF-1, is necessary for most cell fusions in Caenorhabditis elegans. Unregulated EFF-1 expression causes lethality due to ectopic fusion between cells not developmentally programmed to fuse, highlighting the necessity of tight fusogen regulation for proper development. Identifying factors that regulate EFF-1 and its paralog AFF-1 could lead to discovery of molecular mechanisms that control cell fusion upstream of the action of a membrane fusogen. Bioinformatic analysis of the EFF-1A isoform\u27s predicted cytoplasmic domain (endodomain) previously revealed two motifs that have high probabilities of interacting with 14-3-3 proteins when phosphorylated. Mutation of predicted phosphorylation sites within these motifs caused measurable loss of eff-1 gene function in cell fusion in vivo. Moreover, a human 14-3-3 isoform bound to EFF-1::GFP in vitro. We hypothesized that the two 14-3-3 proteins in C. elegans, PAR-5 and FTT-2, may regulate either localization or fusion-inducing activity of EFF-1. METHODOLOGY/PRINCIPAL FINDINGS: Timing of fusion events was slightly but significantly delayed in animals unable to produce full-length EFF-1A. Yet, mutagenesis and live imaging showed that phosphoserines in putative 14-3-3 binding sites are not essential for EFF-1::GFP accumulation at the membrane contact between fusion partner cells. Moreover, although the EFF-1A endodomain was required for normal rates of eff-1-dependent epidermal cell fusions, reduced levels of FTT-2 and PAR-5 did not visibly affect the function of wild-type EFF-1 in the hypodermis. CONCLUSIONS/SIGNIFICANCE: Deletion of the EFF-1A endodomain noticeably affects the timing of hypodermal cell fusions in vivo. However, prohibiting phosphorylation of candidate 14-3-3-binding sites does not impact localization of the fusogen. Hypodermal membrane fusion activity persists when 14-3-3 expression levels are reduced