Simultaneous control of spectroscopic and electrochemical properties in functionalised electrochemiluminescent tris(2,2\u27-bipyridine)ruthenium(II) complexes

Using a combination of electrochemical, spectroscopic and computational techniques, we have explored the fundamental properties of a series of ruthenium diimine complexes designed for coupling with other molecules or surfaces for electrochemiluminescence (ECL) sensing applications. With appropriate choice of ligand functionality, it is possible to manipulate emission wavelengths while keeping the redox ability of the complex relatively constant. DFT calculations show that in the case of electron withdrawing substituents such as ester or amide, the excited state is located on the substituted bipyridine ligand whereas in the case of alkyl functionality it is localised on a bipyridine. The factors that dictate annihilation ECL efficiency are interrelated. For example, the same factors that determine ΔG for the annihilation reaction (i.e. the relative energies of the HOMO and LUMO) have a corresponding effect on the energy of the excited state product. As a result, most of the complexes populate the excited state with an efficiency (Φex) of close to 80% despite the relatively wide range of emission maxima. The quantum yield of emission (Φp) and the possibility of competing side reactions are found to be the main determinants of ECL intensity

A fluorescent histone deacetylase (HDAC) inhibitor for cellular imaging

Fluorescence microscopy studies using 4-morpholinoscriptaid (4MS) demonstrated rapid cellular uptake of this scriptaid analogue into the cytoplasm but no nuclear penetration. As 4MS and scriptaid have the same in vitro activity against HDACs and KASUMI-1 cells; 4MS exemplifies a rational approach to subtly modify ‘profluorogenic’ substrates for intracellular studies

What Is a Representative Brain? Neuroscience Meets Population Science

The last decades of neuroscience research have produced immense progress in the methods available to understand brain structure and function. Social, cognitive, clinical, affective, economic, communication, and developmental neurosciences have begun to map the relationships between neuro-psychological processes and behavioral outcomes, yielding a new understanding of human behavior and promising interventions. However, a limitation of this fast moving research is that most findings are based on small samples of convenience. Furthermore, our understanding of individual differences may be distorted by unrepresentative samples, undermining findings regarding brain–behavior mechanisms. These limitations are issues that social demographers, epidemiologists, and other population scientists have tackled, with solutions that can be applied to neuroscience. By contrast, nearly all social science disciplines, including social demography, sociology, political science, economics, communication science, and psychology, make assumptions about processes that involve the brain, but have incorporated neural measures to differing, and often limited, degrees; many still treat the brain as a black box. In this article, we describe and promote a perspective—population neuroscience—that leverages interdisciplinary expertise to (i) emphasize the importance of sampling to more clearly define the relevant populations and sampling strategies needed when using neuroscience methods to address such questions; and (ii) deepen understanding of mechanisms within population science by providing insight regarding underlying neural mechanisms. Doing so will increase our confidence in the generalizability of the findings. We provide examples to illustrate the population neuroscience approach for specific types of research questions and discuss the potential for theoretical and applied advances from this approach across areas

Synthesis of norbornane bisether antibiotics via silver-mediated alkylation

A small series of norbornane bisether diguanidines have been synthesized and evaluated as antibacterial agents. The key transformation-bisalkylation of norbornane diol 6-was not successful using Williamson methodology but has been accomplished using Ag2O mediated alkylation. Further functionalization to incorporate two guanidinium groups gave rise to a series of structurally rigid cationic amphiphiles; several of which (16d, 16g and 16h) exhibited antibiotic activity. For example, compound 16d was active against a broad range of bacteria including Pseudomonas aeruginosa (MIC = 8 µg/mL), Escherichia coli (MIC = 8 µg/mL) and methicillin-resistant Staphylococcus aureus (MIC = 8 µg/mL)

Coassembled nanostructured bioscaffold reduces the expression of proinflammatory cytokines to induce apoptosis in epithelial cancer cells

The local inflammatory environment of the cell promotes the growth of epithelial cancers. Therefore, controlling inflammation locally using a material in a sustained, non-steroidal fashion can effectively kill malignant cells without significant damage to surrounding healthy cells. A promising class of materials for such applications is the nanostructured scaffolds formed by epitope presenting minimalist self-assembled peptides; these are bioactive on a cellular length scale, while presenting as an easily handled hydrogel. Here, we show that the assembly process can distribute an anti-inflammatory polysaccharide, fucoidan, localized to the nanofibers within the scaffold to create a biomaterial for cancer therapy. We show that it supports healthy cells, while inducing apoptosis in cancerous epithelial cells, as demonstrated by the significant down-regulation of gene and protein expression pathways associated with epithelial cancer progression. Our findings highlight an innovative material approach with potential applications in local epithelial cancer immunotherapy and drug delivery

Four plant Dicers mediate viral small RNA biogenesis and DNA virus induced silencing

Like other eukaryotes, plants use DICER-LIKE (DCL) proteins as the central enzymes of RNA silencing, which regulates gene expression and mediates defense against viruses. But why do plants like Arabidopsis express four DCLs, a diversity unmatched by other kingdoms? Here we show that two nuclear DNA viruses (geminivirus CaLCuV and pararetrovirus CaMV) and a cytoplasmic RNA tobamovirus ORMV are differentially targeted by subsets of DCLs. DNA virus-derived small interfering RNAs (siRNAs) of specific size classes (21, 22 and 24 nt) are produced by all four DCLs, including DCL1, known to process microRNA precursors. Specifically, DCL1 generates 21 nt siRNAs from the CaMV leader region. In contrast, RNA virus infection is mainly affected by DCL4. While the four DCLs are partially redundant for CaLCuV-induced mRNA degradation, DCL4 in conjunction with RDR6 and HEN1 specifically facilitates extensive virus-induced silencing in new growth. Additionally, we show that CaMV infection impairs processing of endogenous RDR6-derived double-stranded RNA, while ORMV prevents HEN1-mediated methylation of small RNA duplexes, suggesting two novel viral strategies of silencing suppression. Our work highlights the complexity of virus interaction with host silencing pathways and suggests that DCL multiplicity helps mediate plant responses to diverse viral infections

The impact of changes in stakeholder salience on CSR activities in Russian energy firms: a contribution to the divergence / convergence debate

This empirical paper examines the drivers underpinning changes to socially-responsible behaviours in the Russian energy sector. Responding to recent requests to contextualise CSR research, we focus on the changing set of stakeholders and developments in their saliency as reflected in corporations’ CSR activities. Based on interviews with more than thirty industry professionals, our findings suggest that Russian energy companies’ CSR is strongly stakeholder driven, and organisations adapt their activities according to their dependence on the resources that these salient stakeholders possess. We challenge the proposition that CSR in Russia arises from purely endogenous, historical, paternalism or neo-paternalism. We identify stakeholders that now shape CSR in the Russian energy sector, both endogenous (institutional and contextual forces relevant to the national business system) and exogenous (relating to the organisational field of the energy industry - international by nature). We thereby contribute to the convergence / divergence debate within CSR theory by demonstrating that both national business systems and the organisational field must be taken into account when analysing the forces that shape CSR strategies in any one country

Norbornene-based anion receptors as D-alanine binders

Vancomycin is currently used as last-line therapy against many Gram-positive bacterial pathogens. Herein, we report a series of peptidomimetic norbornene-based anion receptors that were designed as simple vancomycin mimics New hosts were evaluated for their affinity to both acetate and acetyl D-Ala by 1H NMR titration. Modest binding to both anions was observed in DMSO-d6 (Log Ka 1-2 for TBA Acetyl D-Alanine) in the anticipated 1:1 mode of binding

On the use of \u27shortcuts\u27 in the method of continuous variation (Job\u27s method)

The use of modified Job plot methodology provides a quick and easy means for evaluating host-guest stoichiometry and requires less material than the original method. In this short paper, the results of a recent anion recognition study using thiourea-functionalised norbornanes and [n]polynorbornanes are presented. A significant difference between the plots constructed using the original and modified method was observed and, as such, caution is advised when the modified Job\u27s method is solely used for the determination of host-guest stoichiometry