Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc

The mechanisms of boronate ester formation and fluorescent turn-on in ortho-aminomethylphenylboronic acids

ortho-Aminomethylphenylboronic acids are used in receptors for carbohydrates and various other compounds containing vicinal diols. The presence of the o-aminomethyl group enhances the affinity towards diols at neutral pH, and the manner in which this group plays this role has been a topic of debate. Further, the aminomethyl group is believed to be involved in the turn-on of the emission properties of appended fluorophores upon diol binding. In this treatise, a uniform picture emerges for the role of this group: it primarily acts as an electron-withdrawing group that lowers the pK(a) of the neighbouring boronic acid thereby facilitating diol binding at neutral pH. The amine appears to play no role in the modulation of the fluorescence of appended fluorophores in the protic-solvent-inserted form of the boronic acid/boronate ester. Instead, fluorescence turn-on can be consistently tied to vibrational-coupled excited-state relaxation (a loose-bolt effect). Overall, this Review unifies and discusses the existing data as of 2019 whilst also highlighting why o-aminomethyl groups are so widely used, and the role they play in carbohydrate sensing using phenylboronic acids

23-tól 30-ig Prolongálva! - Előadások kezdete 5 órától folytatólag

Szöveges plakát, melyet széles sávokban szecesziós keret határol. A mozi "Carmen" felirata egy szalagon olvasható. Fölötte filmtekercs kanyarog. A keretet sűrű növényi ornamentika, virágok és levelek alkotják. Színek: mustársárga, sötétkék és fekete, fehér

Implementation between text and work—a qualitative study of a readmission prevention program targeting elderly patients

Abstract Background Numerous studies emphasize the importance of context in implementation. Successful implementation across the health care system depends on conditions and requirements that are often presented to health professionals through text-based materials and might present contradictory expectations to the work of health professionals. In this study, we operationalize institutional context as the text-based material, which from the perspective of health professionals, influence health care work. Via the case of a readmission prevention program for elderly patients, we examine the experiences of health professionals that work with implementation, concerning the contradictions that arise between the demands imposed by program implementation and their everyday work routines, and the role of text-based materials in these contradictions. Method We conducted five focus group interviews among health professionals working at different locations in a single administrative region of Denmark. The 24 health professionals in our study included hospital physicians, hospital nurses, medical secretaries, municipal care managers, registered municipal nurses, and general practitioners. All focus group interviews were transcribed verbatim. Inspired by institutional ethnography, we look into text-based materials, such as written guidelines, if health professionals indicate they are important. Results The health professionals experience that specific demands of the readmission prevention program come into conflict with the existing demands and daily work routines. Professional resistance to control and the existing digital communication tools create tensions with a program requirement for standardized enrollment of patients to the program. In addition, the striving for autonomy among health professionals and the high level of mono-professional working routines create tension with the program requirements for an additional amount of interdisciplinary work. The different demands are widely mediated by text-based materials such as the existing digital communication tools and the instructions on how to use them, and the official agreement of the role and assignment for Danish GPs. Conclusion Successful implementation of the prevention program is affected by various tensions between the program demands and the existing health care work. Text-based materials mediate the different demands of the institutional context in to health care work and influence the process of implementation

SDSS J211852.96−073227.5: The first non-local, interacting, late-type intermediate Seyfert galaxy with relativistic jets

It has been often suggested that a tangible relation exists between relativistic jets in active galactic nuclei (AGN) and the morphology of their host galaxies. In particular, relativistic jets may commonly be related to merging events. Here we present for the first time a detailed spectroscopic and morphological analysis of a Seyfert galaxy, SDSS J211852.96−073227.5, at z = 0.26. This source has previously been classified as a gamma-ray emitting narrow-line Seyfert 1 galaxy. We re-observed it with the 6.5 m Clay Telescope and these new, high-quality spectroscopic data have revealed that it is actually an intermediate-type Seyfert galaxy. Furthermore, the results of modelling the Ks-band near-infrared images obtained with the 6.5 m Baade Telescope indicate that the AGN is hosted by a late-type galaxy in an interacting system, strengthening the suggested connection between galaxy interactions and relativistic jets