Opposite effects of two zinc(II) dithiocarbamates on NF-kB pathway

Inhibiting nuclear factor-kappaB (NF-kB) activation in anticancer and antiinflammatory therapy is of topical interest. Current research in molecular biology has dramatically advanced in the understanding of the cellular events involved in NF-kB induction. Dithiocarbamates, in particular diethyldithiocarbamate and pyrrolidinedithiocarbamate, have been known and widely used as strong inhibitors of NF-kB signaling pathway for more than ten years. Their activity is frequently thought to be due to chelating of zinc or copper present in serum supplemented in the culture medium. Zinc(II) diethyldithiocarbamate (Et2Zn) and zinc(II) dibenzyldithiocarbamate (Bz2Zn) were prepared by direct synthesis in aqueous millieu. They were structurally characterized by X-ray analysis (solid phase) and mass spectrometry (aqueous conditions). Et2Zn and Bz2Zn both in 20 micromolar concentration were applied to HeLa cells. The status of NF-kB signaling was assessed as nuclear translocation of p65 subunit. Surprisingly, Et2Zn activated NF-kB pathway, while TNF-dependent activation of NF-kB was inhibited by Bz2Zn. Our results are preliminary

Extended functorial field theories and anomalies in quantum field theories

We develop a general framework for the description of anomalies using extended functorial field theories extending previous work by Freed and Monnier. In this framework, anomalies are described by invertible field theories in one dimension higher and anomalous field theories live on their boundaries. We provide precise mathematical definitions for all concepts involved using the language of symmetric monoidal bicategories. In particular, field theories with anomalies will be described by symmetric monoidal transformations. The use of higher categorical concepts is necessary to capture the Hamiltonian picture of anomalies. The relation to the path integral and the Hamiltonian description of anomalies will be explained in detail. Furthermore, we discuss anomaly inflow in detail. We apply the general framework to the parity anomaly in fermionic systems coupled to background gauge and gravitational fields on odd-dimensional spacetimes. We use the extension of the Atiyah-Patodi-Singer index theorem to manifolds with corners due to Loya and Melrose to explicitly construct an extended invertible field theory encoding the anomaly. This allows us to compute explicitly the 2-cocycle of the projective representation of the gauge symmetry on the quantum state space, which is defined in a parity-symmetric way by suitably augmenting the standard chiral fermionic Fock spaces with Lagrangian subspaces of zero modes of the Dirac Hamiltonian that naturally appear in the index theorem. As a second application, we study discrete symmetries of Dijkgraaf-Witten theories and their gauging. Non-abelian group cohomology is used to describe discrete symmetries and we derive concrete conditions for such a symmetry to admit ’t Hooft anomalies in terms of the Lyndon-Hochschild-Serre spectral sequence. We give an explicit realization of a discrete gauge theory with ’t Hooft anomaly as a state on the boundary of a higher-dimensional Dijkgraaf-Witten theory using a relative version of the pushforward construction of Schweigert and Woike.Doctoral Training Grant ST/N509099/1 UK Science and Technology Facilities Council (STFC)

Differential immunomodulatory effects of head and neck cancer-derived exosomes on B cells in the presence of ATP

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy. Tumor-derived exosomes (TEX) have immunoregulatory properties. Adenosine triphosphate (ATP) and its immunosuppressive precursor adenosine (ADO) have been found in cancerous tissue. We investigated the effect of TEX on B cells in the presence of ATP. TEX were isolated from human HNSCC cell line (PCI-13) cultures and co-cultured with peripheral blood B cells of healthy donors, with or without TEX in different concentrations and with or without a low (20 µM) or high (2000 µM) ATP dose. We were able to demonstrate that TEX inhibit B-cell proliferation. The addition of TEX to either ATP concentration showed a decreasing trend in CD39 expression on B cells in a dose-dependent manner. High ATP levels (2000 µM) increased apoptosis and necrosis, and analysis of apoptosis-associated proteins revealed dose-dependent effects of ATP, which were modified by TEX. Altogether, TEX exhibited dual immunomodulatory effects on B cells. TEX were immunosuppressive by inhibiting B-cell proliferation; they were immunostimulatory by downregulating CD39 expression. Furthermore, TEX were able to modulate the expression of pro- and anti-apoptotic proteins. In conclusion, our data indicate that TEX play an important, but complex, role in the tumor microenvironment

Choosy beetles : How host trees and southern boreal forest naturalness may determine dead wood beetle communities

Wood-living beetles make up a large proportion of forest biodiversity and contribute to important ecosystem services, including decomposition. Beetle communities in managed southern boreal forests are less species rich than in natural and near-natural forest stands. In addition, many beetle species rely primarily on specific tree species. Yet, the associations between individual beetle species, forest management category, and tree species are seldom quantified, even for red-listed beetles. We compiled a beetle capture dataset from flight intercept traps placed on Norway spruce (Picea abies), oak (Quercus sp.), and Eurasian aspen (Populus tremulae) trees in 413 sites in mature managed forest, near-natural forest, and clear-cuts in southeastern Norway. We used joint species distribution models to estimate the strength of associations for 368 saproxylic beetle species (including 20 vulnerable, endangered, or critical red-listed species) for each forest management category and tree species. Tree species on which traps were mounted had the largest effect on beetle communities; oaks had the most highly associated beetle species, including most of the red-listed species, followed by Norway spruce and Eurasian aspen. Most beetle species were more likely to be captured in near-natural than in mature managed forest. Our estimated associations were compatible ? for many species ? with categorical classifications found in several existing databases of saproxylic beetle preferences. These quantitative beetle-habitat associations will improve future analyses that have typically relied on categorical classifications. Our results highlight the need to prioritize conservation of near-natural forests and oak trees in Scandinavia to protect the habitat of many red-listed species in particular. Furthermore, we underline the importance of carefully considering the species of trees on which traps are mounted in order to representatively sample beetle communities in forest stands.Peer reviewe

Root gravitropism: quantification, challenges, and solutions

Better understanding of root traits such as root angle and root gravitropism will be crucial for development of crops with improved resource use efficiency. This paper describes a high-throughput, automated image analysis method to trace Arabidopsis (Arabidopsis thaliana) seedling roots grown on agar plates. The method combines a ‘particle-filtering algorithm with a graph-based method’ to trace the centre line of a root and can be adopted for the analysis of several root parameters such as length, curvature, and stimulus from original root traces

Single step electrosynthesis of NiMnGa alloys

An electrochemical synthesis route for NiMnGa alloys is presented. Thin films of NiMnGa were fabricated by single step electrodeposition from aqueous electrolytes using direct current over a range of current densities. By electrolyte tuning, homogeneous films with high Ga and Mn content could be achieved at current densities as high as -400 mA cm-2. Detailed compositional analysis of the alloys showed that growth was homogeneous and oxygen content was minimized. Films plated at very low current densities were found to be nanocrystalline/amorphous. In order to obtain fully crystalline samples, thermal annealing was carried out. Mechanical characterization was assessed by nanoindentation, and the effect of Ga content on mechanical properties was investigated

Using the Sustainability Monitoring and Assessment Routine (SMART) for the Systematic Analysis of Trade-Offs and Synergies between Sustainability Dimensions and Themes at Farm Level

When trying to optimize the sustainability performance of farms and farming systems, a consideration of trade-offs and synergies between different themes and dimensions is required. The aim of this paper is to perform a systematic analysis of trade-offs and synergies across all dimensions and themes. To achieve this aim we used the Sustainability Monitoring and Assessment Routine (SMART)-Farm Tool which operationalizes the Sustainability Assessment of Food and Agriculture Systems (SAFA) Guidelines by defining science-based indicator sets and assessment procedures. It identifies the degree of goal achievement with respect to the 58 themes defined in the SAFA Guidelines using an impact matrix that defines 327 indicators and 1769 relations between sustainability themes and indicators. We illustrate how the SMART-Farm Tool can be successfully applied to assess the sustainability performance of farms of different types and in different geographic regions. Our analysis revealed important synergies between themes within a sustainability dimension and across dimensions. We found major trade-offs within the environmental dimension and between the environmental and economic dimension. The trade-offs within the environmental dimension were even larger than the trade-offs with other dimensions. The study also underlines the importance of the governance dimension with regard to achieving a good level of performance in the other dimensions

Endoglin and squamous cell carcinomas

Despite the fact that the role of endoglin on endothelial cells has been extensively described, its expression and biological role on (epithelial) cancer cells is still debatable. Especially its function on squamous cell carcinoma (SCC) cells is largely unknown. Therefore, we investigated SCC endoglin expression and function in three types of SCCs; head and neck (HNSCC), esophageal (ESCC) and vulvar (VSCC) cancers. Endoglin expression was evaluated in tumor specimens and 14 patient-derived cell lines. Next to being expressed on angiogenic endothelial cells, endoglin is selectively expressed by individual SCC cells in tumor nests. Patient derived HNSCC, ESCC and VSCC cell lines express varying levels of endoglin with high interpatient variation. To assess the function of endoglin in signaling of TGF-β ligands, endoglin was overexpressed or knocked out or the signaling was blocked using TRC105, an endoglin neutralizing antibody. The endoglin ligand BMP-9 induced strong phosphorylation of SMAD1 independent of expression of the type-I receptor ALK1. Interestingly, we observed that endoglin overexpression leads to strongly increased soluble endoglin levels, which in turn decreases BMP-9 signaling. On the functional level, endoglin, both in a ligand dependent and independent manner, did not influence proliferation or migration of the SCC cells. In conclusion, these data show endoglin expression on individual cells in the tumor nests in SCCs and a role for (soluble) endoglin in paracrine signaling, without directly affecting proliferation or migration in an autocrine manner.</p

Functional structure of European forest beetle communities is enhanced by rare species

Biodiverse communities have been shown to sustain high levels of multifunctionality and thus a loss of species likely negatively impacts ecosystem functions. For most taxa, however, roles of individual species are poorly known. Rare species, often most likely to go extinct, may have unique traits and functional roles. Alternatively, rare species may be functionally redundant, such that their loss would not disrupt ecosystem functions. We quantified the functional role of rare species by using captures of wood-living (saproxylic) beetle species, combined with recent databases of morphological and ecological traits, from three regions in central and northern Europe. Using a rarity index based on species' local abundance, geographic range, and habitat breadth, we used local and regional species removal simulations to examine the contributions of both the rarest and the most common beetle species to three measures of community functional structure: functional richness, functional specialization, and functional originality. Both regionally and locally, all three measures declined more rapidly when rare species were removed than under common (or random) species removal scenarios. These consistent patterns across scales and among forest types give evidence that rare species provide unique functional contributions, and their loss may disproportionately impact ecosystem functions. This implies that conservation measures targeting rare and endangered species, such as preserving intact forests with dead wood and mature trees, can provide broader ecosystem-level benefits. Experimental research linking functional structure to ecosystem processes should be prioritized to increase understanding of the functional consequences of species loss and to develop more effective conservation strategies

Traits mediate niches and co-occurrences of forest beetles in ways that differ among bioclimatic regions

Aim The aim of this study was to investigate the role of traits in beetle community assembly and test for consistency in these effects among several bioclimatic regions. We asked (1) whether traits predicted species' responses to environmental gradients (i.e. their niches), (2) whether these same traits could predict co-occurrence patterns and (3) how consistent were niches and the role of traits among study regions. Location Boreal forests in Norway and Finland, temperate forests in Germany. Taxon Wood-living (saproxylic) beetles. Methods We compiled capture records of 468 wood-living beetle species from the three regions, along with nine morphological and ecological species traits. Eight climatic and forest covariates were also collected. We used Bayesian hierarchical joint species distribution models to estimate the influence of traits and phylogeny on species' niches. We also tested for correlations between species associations and trait similarity. Finally, we compared species niches and the effects of traits among study regions. Results Traits explained some of the variability in species' niches, but their effects differed among study regions. However, substantial phylogenetic signal in species niches implies that unmeasured but phylogenetically structured traits have a stronger effect. Degree of trait similarity was correlated with species associations but depended idiosyncratically on the trait and region. Species niches were much more consistent-widespread taxa often responded similarly to an environmental gradient in each region. Main conclusions The inconsistent effects of traits among regions limit their current use in understanding beetle community assembly. Phylogenetic signal in niches, however, implies that better predictive traits can eventually be identified. Consistency of species niches among regions means niches may remain relatively stable under future climate and land use changes; this lends credibility to predictive distribution models based on future climate projections but may imply that species' scope for short-term adaptation is limited.Peer reviewe