Recommendations from evaluating the implementation of the 'GP Daffodil Standards' to support the provision of palliative and end-of-life care in primary care: a mixed-methods study.

Background: The 'GP Daffodil Standards for Advanced Serious Illness and End of Life Care' was launched by the Royal College of General Practitioners and Marie Curie in 2019 to support improvement of end-of-life care activity in primary care.

Aim: To undertake and independent evaluation of the implementation of the Daffodil Standards.

Method: A multi-method evaluation, informed by Normalisation Process Theory.

Associations between rumination, depression, and distress tolerance during CBT treatment for depression in a tertiary care setting.

Background: Rumination is strongly associated with depressive symptom severity and course. However, changes in rumination during outpatient cognitive behavioral therapy (CBT), and their links to baseline features such as distress tolerance and clinical outcomes, have received limited attention.

Methods: 278 outpatients with depression received group or individual CBT.

Emerging approaches to CDK inhibitor development, a structural perspective.

Aberrant activity of the cyclin-dependent kinase family is frequently noted in a number of diseases identifying them as potential targets for drug development. However, current CDK inhibitors lack specificity owing to the high sequence and structural conservation of the ATP binding cleft across family members, highlighting the necessity of finding novel modes of CDK inhibition. The wealth of structural information regarding CDK assemblies and inhibitor complexes derived from X-ray crystallographic studies has been recently complemented through the use of cryo-electron microscopy.

Mapping Ligand Interactions of Bromodomains BRD4 and ATAD2 with FragLites and PepLites─Halogenated Probes of Druglike and Peptide-like Molecular Interactions.

The development of ligands for biological targets is critically dependent on the identification of sites on proteins that bind molecules with high affinity. A set of compounds, called FragLites, can identify such sites, along with the interactions required to gain affinity, by X-ray crystallography. We demonstrate the utility of FragLites in mapping the binding sites of bromodomain proteins BRD4 and ATAD2 and demonstrate that FragLite mapping is comparable to a full fragment screen in identifying ligand binding sites and key interactions.

Rubisco substitutions predicted to enhance crop performance through carbon uptake modelling.

Improving the performance of the CO2-fixing enzyme Rubisco is among the targets for increasing crop yields. Here, Earth system model (ESM) representations of canopy C3 and C4 photosynthesis were combined with species-specific Rubisco parameters to quantify the consequences of bioengineering foreign Rubiscos into C3 and C4 crops under field conditions. The 'two big leaf' (sunlit/shaded) model for canopy photosynthesis was used together with species-specific Rubisco kinetic parameters including maximum rate (Kcat), Michaelis-Menten constant for CO2 at ambient atmospheric O2 (Kc21%O2), specificity for CO2 to O2 (Sc/o), and associated heat activation (Ha) values.