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

Behaviour-time budget and functional habitat use of a free-ranging European badger(Meles meles)

BackgroundThe European badger (Meles meles) is involved in the maintenance of bovine tuberculosis infection and onward spread to cattle. However, little is known about how transmission occurs. One possible route could be through direct contact between infected badgers and cattle. It is also possible that indirect contact between cattle and infected badger excretory products such as faeces or urine may occur either on pasture or within and around farm buildings. A better understanding of behaviour patterns in wild badgers may help to develop biosecurity measures to minimise direct and indirect contact between badgers and cattle. However, monitoring the behaviour of free-ranging badgers can be logistically challenging and labour intensive due to their nocturnal and semi-fossorial nature. We trialled a GPS and tri-axial accelerometer-equipped collar on a free-ranging badger to assess its potential value to elucidate behaviour-time budgets and functional habitat use.ResultsDuring the recording period between 16:00 and 08:00 on a single night, resting was the most commonly identified behaviour (67.4%) followed by walking (20.9%), snuffling (9.5%) and trotting (2.3%). When examining accelerometer data associated with each GPS fix and habitat type (occurring 2 min 30 s before and after), walking was the most common behaviour in woodland (40.3%) and arable habitats (53.8%), while snuffling was the most common behaviour in pasture (61.9%). Several nocturnal resting periods were also observed. The total distance travelled was 2.28 km.ConclusionsIn the present report, we demonstrate proof of principle in the application of a combined GPS and accelerometer device to collect detailed quantitative data on wild badger behaviour. Behaviour-time budgets allow us to investigate how badgers allocate energy to different activities and how this might change with disease status. Such information could be useful in the development of measures to reduce opportunities for onward transmission of bovine tuberculosis from badgers to cattle.<br/

Vascular Studies for Nonvascular Surgeons

A patient’s therapeutic plan is guided by a combination of their medical history, vascular test results, and physical examination. Diagnostic tests play an essential role in the detection of vascular disease from both a venous and arterial standpoint. The sooner vascular disease can be identified in an individual, the sooner both physicians and patients can work toward integrating therapies that will prevent or mitigate ulcer formation. Knowledge regarding the proper indications and interpretations of the various vascular studies is critical to the successful management of each patient