The ErbB2ΔEx16 splice variant is a major oncogenic driver in breast cancer that promotes a pro-metastatic tumor microenvironment.

Amplification and overexpression of erbB2/neu proto-oncogene is observed in 20-30% human breast cancer and is inversely correlated with the survival of the patient. Despite this, somatic activating mutations within erbB2 in human breast cancers are rare. However, we have previously reported that a splice isoform of erbB2, containing an in-frame deletion of exon 16 (herein referred to as ErbB2ΔEx16), results in oncogenic activation of erbB2 because of constitutive dimerization of the ErbB2 receptor. Here, we demonstrate that the ErbB2ΔEx16 is a major oncogenic driver in breast cancer that constitutively signals from the cell surface. We further show that inducible expression of the ErbB2ΔEx16 variant in mammary gland of transgenic mice results in the rapid development of metastatic multifocal mammary tumors. Genetic and biochemical characterization of the ErbB2ΔEx16-derived mammary tumors exhibit several unique features that distinguish this model from the conventional ErbB2 ones expressing the erbB2 proto-oncogene in mammary epithelium. Unlike the wild-type ErbB2-derived tumors that express luminal keratins, ErbB2ΔEx16-derived tumors exhibit high degree of intratumoral heterogeneity co-expressing both basal and luminal keratins. Consistent with these distinct pathological features, the ErbB2ΔEx16 tumors exhibit distinct signaling and gene expression profiles that correlate with activation of number of key transcription factors implicated in breast cancer metastasis and cancer stem cell renewal

Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II

Lanthionine antibiotics are an important class of naturally-occurring antimicrobial peptides. The best-known, nisin, is a commercial food preservative. However, structural and mechanistic details on nisin/lipid II membrane complexes are currently lacking. Recently, we have developed empirical force-field parameters to model lantibiotics. Docking and molecular dynamics (MD) simulations have been used to study the nisin2:lipid II complex in bacterial membranes, which has been put forward as the building block of nisin/lipid II binary membrane pores. A Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wildtype. Wild-type nisin was also docked onto three different lipid II structures and a stable 2:1 nisin:lipid II complex formed. This complex was inserted into a membrane. Six independent MD simulations revealed key interactions in the complex, specifically the N terminal engagement of nisin with lipid II at the pyrophosphate and C-terminus of the pentapeptide chain. Nisin2 inserts into the membrane and we propose this is the first step in pore formation, mediated by the nisin N-terminus–lipid II pentapeptide hydrogen bond. The lipid II undecaprenyl chain adopted different conformations in the presence of nisin, which may also have implications for pore formation

Securing the Anthropocene? International Policy Experiments in Digital Hacktivism: A Case Study of Jakarta

This article analyses security discourses that are beginning to self-consciously take on board the shift towards the Anthropocene. Firstly, it sets out the developing episteme of the Anthropocene, highlighting the limits of instrumentalist cause-and-effect approaches to security, increasingly becoming displaced by discursive framings of securing as a process, generated through new forms of mediation and agency, capable of grasping inter-relations in a fluid context. This approach is the methodology of hacking: creatively composing and repurposing already existing forms of agency. It elaborates on hacking as a set of experimental practices and imaginaries of securing the Anthropocene, using as a case study the field of digital policy activism with the focus on community empowerment through social-technical assemblages being developed and applied in ‘the City of the Anthropocene’: Jakarta, Indonesia. The article concludes that policy interventions today cannot readily be grasped in modernist frameworks of ‘problem solving’ but should be seen more in terms of evolving and adaptive ‘life hacks’

Lactobacillaceae and Cell Adhesion: Genomic and Functional Screening

The analysis of collections of lactic acid bacteria (LAB) from traditional fermented plant foods in tropical countries may enable the detection of LAB with interesting properties. Binding capacity is often the main criterion used to investigate the probiotic characteristics of bacteria. In this study, we focused on a collection of 163 Lactobacillaceace comprising 156 bacteria isolated from traditional amylaceous fermented foods and seven strains taken from a collection and used as controls. The collection had a series of analyses to assess binding potential for the selection of new probiotic candidates. The presence/absence of 14 genes involved in binding to the gastrointestinal tract was assessed. This enabled the detection of all the housekeeping genes (ef-Tu, eno, gap, groEl and srtA) in the entire collection, of some of the other genes (apf, cnb, fpbA, mapA, mub) in 86% to 100% of LAB, and of the other genes (cbsA, gtf, msa, slpA) in 0% to 8% of LAB. Most of the bacteria isolated from traditional fermented foods exhibited a genetic profile favorable for their binding to the gastrointestinal tract. We selected 30 strains with different genetic profiles to test their binding ability to non-mucus (HT29) and mucus secreting (HT29-MTX) cell lines as well as their ability to degrade mucus. Assays on both lines revealed high variability in binding properties among the LAB, depending on the cell model used. Finally, we investigated if their binding ability was linked to tighter cross-talk between bacteria and eukaryotic cells by measuring the expression of bacterial genes and of the eukaryotic MUC2 gene. Results showed that wild LAB from tropical amylaceous fermented food had a much higher binding capacity than the two LAB currently known to be probiotics. However their adhesion was not linked to any particular genetic equipment

Phytoplankton competition in deep biomass maximum

Resource competition in heterogeneous environments is still an unresolved problem of theoretical ecology. In this article I analyze competition between two phytoplankton species in a deep water column, where the distributions of main resources (light and a limiting nutrient) have opposing gradients and co-limitation by both resources causes a deep biomass maximum. Assuming that the species have a trade-off in resource requirements and the water column is weakly mixed, I apply the invasion threshold analysis (Ryabov and Blasius 2011) to determine relations between environmental conditions and phytoplankton composition. Although species deplete resources in the interior of the water column, the resource levels at the bottom and surface remain high. As a result, the slope of resources gradients becomes a new crucial factor which, rather than the local resource values, determines the outcome of competition. The value of resource gradients nonlinearly depend on the density of consumers. This leads to complex relationships between environmental parameters and species composition. In particular, it is shown that an increase of both the incident light intensity or bottom nutrient concentrations favors the best light competitors, while an increase of the turbulent mixing or background turbidity favors the best nutrient competitors. These results might be important for prediction of species composition in deep ocean.Comment: 13 pages, 7 figures; Theoretical Ecology 201

The emotional movie database (EMDB): a self-report and psychophysiological study

Film clips are an important tool for evoking emotional responses in the laboratory. When compared with other emotionally potent visual stimuli (e.g., pictures), film clips seem to be more effective in eliciting emotions for longer periods of time at both the subjective and physiological levels. The main objective of the present study was to develop a new database of affective film clips without auditory content, based on a dimensional approach to emotional stimuli (valence, arousal and dominance). The study had three different phases: (1) the pre-selection and editing of 52 film clips (2) the self-report rating of these film clips by a sample of 113 participants and (3) psychophysiological assessment [skin conductance level (SCL) and the heart rate (HR)] on 32 volunteers. Film clips from different categories were selected to elicit emotional states from different quadrants of affective space. The results also showed that sustained exposure to the affective film clips resulted in a pattern of a SCL increase and HR deceleration in high arousal conditions (i.e., horror and erotic conditions). The resulting emotional movie database can reliably be used in research requiring the presentation of non-auditory film clips with different ratings of valence, arousal and dominance.Portuguese Foundation for Science and Technology with individual grants (SFRH/BD/41484/2007 and SFRH/BD/64355/2009

Body Mass Index and Employment-Based Health Insurance

<p>Abstract</p> <p>Background</p> <p>Obese workers incur greater health care costs than normal weight workers. Possibly viewed by employers as an increased financial risk, they may be at a disadvantage in procuring employment that provides health insurance. This study aims to evaluate the association between body mass index [BMI, weight in kilograms divided by the square of height in meters] of employees and their likelihood of holding jobs that include employment-based health insurance [EBHI].</p> <p>Methods</p> <p>We used the 2004 Household Components of the nationally representative Medical Expenditure Panel Survey. We utilized logistic regression models with provision of EBHI as the dependent variable in this descriptive analysis. The key independent variable was BMI, with adjustments for the domains of demographics, social-economic status, workplace/job characteristics, and health behavior/status. BMI was classified as normal weight (18.5–24.9), overweight (25.0–29.9), or obese (≥ 30.0). There were 11,833 eligible respondents in the analysis.</p> <p>Results</p> <p>Among employed adults, obese workers [adjusted probability (AP) = 0.62, (0.60, 0.65)] (<it>P </it>= 0.005) were more likely to be employed in jobs with EBHI than their normal weight counterparts [AP = 0.57, (0.55, 0.60)]. Overweight workers were also more likely to hold jobs with EBHI than normal weight workers, but the difference did not reach statistical significance [AP = 0.61 (0.58, 0.63)] (<it>P </it>= 0.052). There were no interaction effects between BMI and gender or age.</p> <p>Conclusion</p> <p>In this nationally representative sample, we detected an association between workers' increasing BMI and their likelihood of being employed in positions that include EBHI. These findings suggest that obese workers are more likely to have EBHI than other workers.</p

Influence of soil on the efficacy of entomopathogenic nematodes in reducing Diabrotica virgifera virgifera in maize

The use of entomopathogenic nematodes is one potential non-chemical approach to control the larvae of the invasive western corn rootworm (Diabrotica virgifera virgifera LeConte, Coleoptera: Chrysomelidae) in Europe. This study investigated the efficacy of Heterorhabditis bacteriophora Poinar (Rhabditida: Heterorhabditidae), Heterorhabditis megidis Poinar, Jackson and Klein (Rh., Heterorhabditidae) and Steinernema feltiae Filipjev (Rh., Steinernematidae) in reducing D. v. virgifera as a function of soil characteristics. A field experiment was repeated four times in southern Hungary using artificially infested maize plants potted into three different soils. Sleeve gauze cages were used to assess the number of emerging adult D. v. virgifera from the treatments and untreated controls. Results indicate that nematodes have the potential to reduce D. v. virgifera larvae in most soils; however, their efficacy can be higher in maize fields with heavy clay or silty clay soils than in sandy soils, which is in contrast to the common assumption that nematodes perform better in sandy soils than in heavy soils