Glucose influences endometrial receptivity to embryo implantation through O-GlcNAcylation-mediated regulation of the cytoskeleton.

Phenotypic changes to endometrial epithelial cells underpin receptivity to embryo implantation at the onset of pregnancy but the effect of hyperglycaemia on these processes remains poorly understood. Here we show that physiological levels of glucose (5mM) abolished receptivity in the endometrial epithelial cell line, Ishikawa. However, embryo attachment was supported by 17mM glucose as a result of glucose flux through the hexosamine biosynthetic pathway (HBP) and modulation of cell function via protein O-GlcNAcylation. Pharmacological inhibition of HBP or protein O-GlcNAcylation reduced embryo attachment in co-cultures at 17mM glucose. Mass spectrometry analysis of the O-GlcNAcylated proteome in Ishikawa cells revealed that myosin phosphatase target subunit 1 (MYPT1) is more highly O-GlcNAcylated in 17mM glucose, correlating with loss of its target protein, phospho-myosin light chain 2, from apical cell junctions of polarised epithelium. 2D and 3D morphologic analysis demonstrated that the higher glucose level attenuates epithelial polarity through O-GlcNAcylation. Inhibition of RhoA-associated kinase (ROCK) or myosin II led to reduced polarity and enhanced receptivity in cells cultured in 5mM glucose, consistent with data showing that MYPT1 acts downstream of ROCK signalling. These data implicate regulation of endometrial epithelial polarity through RhoA signaling upstream of actomyosin contractility in the acquisition of endometrial receptivity. Glucose levels impinge on this pathway through O-GlcNAcylation of MYPT1, which may impact endometrial receptivity to an implanting embryo in women with diabetes.

Making practice perfect.

IT IS CRUCIAL to quality assurance that nursing students are given opportunities to evaluate their learning environments ( NHS Education for Scotland 2003 , Quality Assurance Agency for Higher Education 2001 ).

Clinical practice and placement support: supporting learning in practice.

It is the responsibility of Higher Education Institutions (HEI) in partnership with the NHS to prepare nurses and midwives who are equipped to cope with the complex nature of clinical practice. This paper explores how, through partnership working, the School of Nursing and Midwifery (SNM) at the University of Dundee developed a Clinical Practice and Placement Support Unit (CPPSU) whose remit is to support learning in practice. The setting up of this successful unit resulted from the clear identification of three key elements which enables the CPPSU to support learning in practice. These elements are adequate mentor support, developing and monitoring the clinical learning environment and increased collaboration between the HEI and service providers in the allocation of students to appropriate practice placement areas. Each of these will be explored in depth in order to give an overview of how the CPPSU delivers its remit.

The ethics of assisted suicide.

There is continuing national and international debate with reference to autonomy and the right to choose the manner and time of our death. It is now recognised that human life has a natural end and that, as such, it should not be preserved simply because a treatment exists. Three cases are briefly discussed which raise the issue of whether or not we should be permitted by law to choose how and when to die. The ethical principle of autonomy and the influence of religion are considered. Central to the debate about end-of-life choices is the recognition that not all persons can be healed and not all suffering can be relieved.