A cell-permeable biscyclooctyne as a novel probe for the identification of protein sulfenic acids

Reactive oxygen species act as important second messengers in cell signaling and homeostasis through the oxidation of protein thiols. However, the dynamic nature of protein oxidation and the lack of sensitivity of existing molecular probes have hindered our understanding of such reactions; therefore, new tools are required to address these challenges. We designed a bifunctional variant of the strained bicyclo[6.1.0]nonyne (BCN-E-BCN) that enables the tagging of intracellular protein sulfenic acids for biorthogonal copper-free click chemistry. In validation studies, BCN-E-BCN binds the sulfenylated form of the actin-severing protein cofilin, while mutation of the cognate cysteine residues abrogates its binding. BCN-E-BCN is cell permeable and reacts rapidly with cysteine sulfenic acids in cultured cells. Using different azide-tagged conjugates, we demonstrate that BCN-E-BCN can be used in various applications for the detection of sulfenylated proteins. Remarkably, cycloaddition of an azide-tagged fluorophore to BCN-E-BCN labelled proteins produced in vivo can be visualized by fluorescence microscopy to reveal their subcellular localization. These findings demonstrate a novel and multifaceted approach to the detection and trapping of sulfenic acids

Broadcasting Convolutional Network for Visual Relational Reasoning

In this paper, we propose the Broadcasting Convolutional Network (BCN) that extracts key object features from the global field of an entire input image and recognizes their relationship with local features. BCN is a simple network module that collects effective spatial features, embeds location information and broadcasts them to the entire feature maps. We further introduce the Multi-Relational Network (multiRN) that improves the existing Relation Network (RN) by utilizing the BCN module. In pixel-based relation reasoning problems, with the help of BCN, multiRN extends the concept of `pairwise relations' in conventional RNs to `multiwise relations' by relating each object with multiple objects at once. This yields in O(n) complexity for n objects, which is a vast computational gain from RNs that take O(n^2). Through experiments, multiRN has achieved a state-of-the-art performance on CLEVR dataset, which proves the usability of BCN on relation reasoning problems.Comment: Accepted paper at ECCV 2018. 24 page

The value of a breast care nurse in supporting rural and remote cancer patients in Queensland

The role of the Breast Care Nurse in Queensland's Supporting Rural Women with Breast Cancer Project was evaluated by mixed methodology. Through questionnaire and interview patients provided views about the nurse's role under categories of Awareness, Access, Coordination, Information and Psychosocial, Emotional and Practical support. Of the 51 participants 37 resided in rural and remote areas with 18 living between 100 and 500 miles from specialised breast care services. The BCN met with patients at their regular hospital visits and was available by telephone at any time. There was overwhelming agreement among the participants that the timing of contact, ease of accessibility, information provided and support offered were extremely valuable in making their treatment and recovery easier. The vast majority of participants would recommend hospitals with a BCN to their friends. Members of the multidisciplinary care team provided views on Awareness of the BCN, Influence on Care Management, Communication and Patient Outcomes. They recognised the benefits of the BCN to patients and to coordination and liaison of the team. The findings concur with unpublished Australian reports that demonstrate the success of dedicated Breast Care Nurses. The BCN model of care could be used successfully to support other medical conditions

Introduction of anti-fouling coatings at the surface of supramolecular elastomeric materials:via post-modification of reactive supramolecular additives

Protein repellent coatings have been extensively studied to introduce anti-fouling properties at material surfaces. Here we introduce a covalent anti-fouling coating at the surface of supramolecular ureidopyrimidinone (UPy) based materials introduced via post-modification of reactive UPy-functionalized tetrazine additives incorporated into the supramolecular polymer material. After material formulation, an anti-fouling coating comprised of bicyclononyne (BCN) functionalized poly(ethylene glycol) (PEG) polymers was reacted. This coating was covalently attached to the surface via a highly selective electron-demand Diels-Alder cycloaddition between tetrazine and BCN. The anti-fouling properties of three different BCN-PEG polymers, mono-functional-PEG-BCN, bi-functional-PEG-BCN and star-PEG-BCN, respectively, were systematically studied. The mono-functional-PEG-BCN showed minor reduction in both protein adsorption and cell adhesion, whereas the bi-functional-PEG-BCN and the star-PEG-BCN polymer coating demonstrated complete anti-fouling performance, both towards protein adhesion as well as cell adhesion. Additionally, a bioorthogonal ligation strategy was performed in culture medium in the presence of cells showing a similar behavior for the three anti-fouling coatings, which indicates that this strategy can be applied for post-modification reactions in a complex environment.</p