Reversed Expression of the JAK/STAT Pathway Related Proteins Prolactin Receptor and STAT5a in Normal and Abnormal Breast Epithelial Cells

The JAK/STAT pathway is important for cellular metabolism. One component, STAT5a, is activated in the breast upon prolactin to prolactin receptor (PRLR) binding facilitating the transcription of genes involved in lobule development. STAT5a was previously found to be expressed in most normal breast epithelial cells but not in many in situ or invasive carcinomas except secretory carcinomas which retain STAT5a expression. This report examines the JAK/STAT pathway in the breast through the detection of PRLR and STAT5a. Fifty breast tissues, including benign secretory change, microglandular adenosis, usual and atypical hyperplasia and in situ and invasive ductal carcinoma both usual and secretory, were obtained from the files of the Armed Forces Institute of Pathology. Sections were immunostained with antibodies to PRLR and STAT5a. PRLR was minimally detected on the surface of a few normal breast epithelial cells whereas STAT5a was greatly expressed in over 80% of normal cell nuclei. PRLR was also minimally detected in secretory carcinomas expressing STAT5a. However, the opposite pattern was seen in breast carcinomas lacking STAT5a expression. PRLR was abundantly expressed in these cells. This reversed expression may indicate a JAK/STAT pathway disturbance that could play a role in the initiation or maintenance of an abnormal breast phenotype

RDM+PM Checklist: Towards a Measure of Your Institution’s Preparedness for the Effective Planning of Research Data Management

A review at our institution and a number of other Australian universities was conducted to identify an optimal institutional-wide approach to Research Data Management (RDM). We found, with a few notable exceptions, a lack of clear policies and processes across institutes and no harmonisation in the approaches taken. We identified limited methods in place to cater for the development of Research Data Management Plans (RDMPs) across different disciplines, project types and no identifiable business intelligence (BI) for auditing or oversight. When interviewed, many researchers were not aware of their institution’s RDM policy, whilst others did not understand how it was relevant to their research. It was also discovered that primary materials (PM), which are often directly linked to the effective management of research data, were not well covered. Additionally, it was unclear in understanding who was the data custodian responsible for overall oversight, and there was a lack of clear guidance on the roles and responsibilities of researchers and their supervisors. These findings indicate that institutions are at risk in terms of meeting regulatory requirements and managing data effectively and safely. In this paper, we outline an alternative approach focusing on RDM ‘Planning’ rather than on RDMPs themselves. We developed simple-to-understand guidance for researchers on the redeveloped RDM policy, which was implemented via an online ‘RDM+PM Checklist’ tool that guides researchers and students. Moreover, as it is a structured tool, it provides real-time business intelligence that can be used to measure how compliant the organisation is and ideally identify opportunities for continuous improvement

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Heterobimetallic Au(I)/Y(III) single chain nanoparticles as recyclable homogenous catalysts

Heterobimetallic single chain nanoparticles were synthesized and applied as recyclable homogenous catalysts. A terpolymer containing two orthogonal ligand moieties, phosphines and carboxylates, was obtained via nitroxide-mediated polymerization. Single chain nanoparticle (SCNP) formation is induced by selective metal complexation of Y(III) by the carboxylate functions, while Au(I) is selectively coordinated to phosphine moieties. In contrast to previous work, the two functionalities, SCNP folding and formation of a catalytic center, were distributed over two metals, which critically increases the flexibility of the system. The formation of Au(I)/Y(III)-SCNPs is evidenced by size exclusion chromatography, dynamic light scattering, nuclear magnetic resonance (1H, 31P{1H}) and infrared spectroscopy. Importantly, the activity of the Au(I)/Y(III)-SCNPs as homogenous, yet recyclable catalyst, bridging the gap between homogenous and heterogeneous catalysis, was demonstrated using the hydroamination of aminoalkynes as an example

Wavelength-gated photoreversible polymerization and topology control

We exploit the wavelength dependence of [2 + 2] photocycloadditions and-reversions of styrylpyrene to exert unprecedented control over the photoreversible polymerization and topology of telechelic building blocks. Blue light (λmax = 460 nm) initiates a catalyst-free polymerization yielding high molar mass polymers (Mn = 60 000 g mol-1), which are stable at wavelengths exceeding 430 nm, yet highly responsive to shorter wavelengths. UVB irradiation (λmax = 330 nm) induces a rapid depolymerization affording linear oligomers, whereas violet light (λmax = 410 nm) generates cyclic entities. Thus, different colors of light allow switching between a depolymerization that either proceeds through cyclic or linear topologies. The light-controlled topology formation was evidenced by correlation of mass spectrometry (MS) with size exclusion chromatography (SEC) and ion mobility data. Critically, the color-guided topology control was also possible with ambient laboratory light affording cyclic oligomers, while sunlight activated the linear depolymerization pathway. These findings suggest that light not only induces polymerization and depolymerization but that its color can control the topological outcomes.</p

Two-colour light activated covalent bond formation

We introduce a photochemical bond forming system, where two colours of light are required to trigger covalent bond formation. Specifically, we exploit a visible light cis/trans isomerization of chlorinated azobenzene, which can only undergo reaction with a photochemically generated ketene in its cis state. Detailed photophysical mapping of the reaction efficiencies at a wide range of monochromatic wavelengths revealed the optimum irradiation conditions. Subsequent small molecule and polymer ligation experiments illustrated that only the application of both colours of light affords the reaction product. We further extend the functionality to a photo reversible ketene moiety and translate the concept into material science. The presented reaction system holds promise to be employed as a two-colour resist

It’s in the Fine Print: Erasable Three-Dimensional Laser-Printed Micro- and Nanostructures

3D printing, on all scales, is currently a vibrant topic in scientific and industrial research as it has enormous potential to radically change manufacturing. Owing to the inherent nature of the manufacturing process, 3D printed structures may require additional material to structurally support complex features. Such support material must be removed after printing—sometimes termed subtractive manufacturing—without adversely affecting the remaining structure. An elegant solution is the use of photoresists containing labile bonds that allow for controlled cleavage with specific triggers. Herein, we explore state‐of‐the‐art cleavable photoresists for 3D direct laser writing, as well as their potential to combine additive and subtractive manufacturing in a hybrid technology. We discuss photoresist design, feature resolution, cleavage properties, and current limitations of selected examples. Furthermore, we share our perspective on possible labile bonds, and their corresponding cleavage trigger, which we believe will have a critical impact on future applications and expand the toolbox of available cleavable photoresists

Photo-induced chemistry for the design of oligonucleotide conjugates and surfaces

A photocaged diene is introduced at the 5′-end of oligonucleotides using the H-phosphonate approach. The photoenol-functionalized DNA is subsequently employed for the conjugation to a protein and the spatially controlled immobilization onto surfaces using a light-induced Diels–Alder cycloaddition. Fully functional protein–DNA conjugates and patterned DNA surfaces are obtained under mild irradiation conditions