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The literature has evaluated studies of hospice nurses and stress but very few studies have focused on community hospice nurses. This study explored hospice at home nurses’ experiences of caring for palliative and dying patients. Hospice at home nurses working in the community across North West Wales were interviewed and a grounded theory approach was used to categorise the data into the following themes: job satisfaction, stressors, coping strategies, and support. Recommendations arising from the study include encouraging the use of clinical supervision, attendance at multidisciplinary meetings, and the provision of stress-awareness training, and raising awareness of the role of hospice at home nurses in primary care. Implementation of these recommendations might be beneficial for staff wellbeing. Further work would identify whether such recommendations can help to prevent sickness and promote staff retention.

A new series of 2,6,9-trisubstituted purines, characterized by the presence of a common alkynyl substituent at C-2 and a range of different anilino/benzylamino groups at C-6, were synthesized. These compounds were evaluated for their capacity to inhibit cyclin-dependent kinase activity (CDK1−cyclin B) in vitro. Compounds 4e (N-6-p-Cl-benzylamino derivative) and 5e (N-6-m-Cl-anilino derivative) exhibited the strongest inhibitory activity with an IC50 of 60 nM. The structure of compound 4b (N-6-p-methoxybenzylamino derivative) in complex with human CDK2 was determined by X-ray crystallography, revealing the molecular basis of inhibition by this molecule. Subsequent molecular modeling studies allowed us to rationalize the SAR observed for these compounds.

We have prepared phosphorylated cyclin-dependent protein kinase 2 (CDK2) for crystallization using the CDK-activating kinase 1 (CAK1) from Saccharomyces cerevisiae and have grown crystals using microseeding techniques. Phosphorylation of monomeric human CDK2 by CAK1 is more efficient than phosphorylation of the binary CDK2-cyclin A complex. Phosphorylated CDK2 exhibits histone H1 kinase activity corresponding to approximately 0.3% of that observed with the fully activated phosphorylated CDK2-cyclin A complex. Fluorescence measurements have shown that Thr160 phosphorylation increases the affinity of CDK2 for both histone substrate and ATP and decreases its affinity for ADP. By contrast, phosphorylation of CDK2 has a negligible effect on the affinity for cyclin A. The crystal structures of the ATP-bound forms of phosphorylated CDK2 and unphosphorylated CDK2 have been solved at 2.1-A resolution. The structures are similar, with the major difference occurring in the activation segment, which is disordered in phosphorylated CDK2. The greater mobility of the activation segment in phosphorylated CDK2 and the absence of spontaneous crystallization suggest that phosphorylated CDK2 may adopt several different mobile states. The majority of these states are likely to correspond to inactive conformations, but a small fraction of phosphorylated CDK2 may be in an active conformation and hence explain the basal activity observed.