Assessing the dynamics and macromolecular interactions of the intrinsically disordered protein YY1.

YY1 is a ubiquitously expressed, intrinsically disordered transcription factor involved in neural development. The oligomeric state of YY1 varies depending on the environment. These structural changes may alter its DNA binding ability and hence its transcriptional activity. Just as YY1's oligomeric state can impact its role in transcription, so does its interaction with other proteins such as FOXP2. The aim of this work is to study the structure and dynamics of YY1 so as to determine the influence of oligomerisation and associations with FOXP2 on its DNA binding mechanism. The results confirm that YY1 is primarily a disordered protein, but it does consist of certain specific structured regions. We observed that YY1 quaternary structure is a heterogenous mixture of oligomers, the overall size of which is dependent on ionic strength. Both YY1 oligomerisation and its dynamic behaviour are further subject to changes upon DNA binding, whereby increases in DNA concentration result in a decrease in the size of YY1 oligomers. YY1 and the FOXP2 forkhead domain were found to interact with each other both in isolation and in the presence of YY1-specific DNA. The heterogeneous, dynamic multimerisation of YY1 identified in this work is, therefore likely to be important for its ability to make heterologous associations with other proteins such as FOXP2. The interactions that YY1 makes with itself, FOXP2 and DNA form part of an intricate mechanism of transcriptional regulation by YY1, which is vital for appropriate neural development.

The influence of various regions of the FOXP2 sequence on its structure and DNA-binding function.

FOX proteins are a superfamily of transcription factors which share a DNA-binding domain referred to as the forkhead domain. Our focus is on the FOXP subfamily members, which are involved in language and cognition amongst other things. The FOXP proteins contain a conserved zinc finger and a leucine zipper motif in addition to the forkhead domain. The remainder of the sequence is predicted to be unstructured and includes an acidic C-terminal tail. In the present study, we aim to investigate how both the structured and unstructured regions of the sequence cooperate so as to enable FOXP proteins to perform their function. We do this by studying the effect of these regions on both oligomerisation and DNA binding. Structurally, the FOXP proteins appear to be comparatively globular with a high proportion of helical structure. The proteins multimerise via the leucine zipper, and the stability of the multimers is controlled by the unstructured interlinking sequence including the acid rich tail. FOXP2 is more compact than FOXP1, has a greater propensity to form higher order oligomers, and binds DNA with stronger affinity. We conclude that while the forkhead domain is necessary for DNA binding, the affinity of the binding event is attributable to the leucine zipper, and the unstructured regions play a significant role in the specificity of binding. The acid rich tail forms specific contacts with the forkhead domain which may influence oligomerisation and DNA binding, and therefore the acid rich tail may play an important regulatory role in FOXP transcription.

Move on up: Fingertip forces and felt heaviness are modulated by the goal of the lift.

When we interact with objects, we usually do so for a purpose. It is well known that the specific goal of an action can have a substantial effect on initial reach kinematics. No research, however, has examined the effect that the goal of a lift can have on the fingertip forces and perception of object weight when picking up an object to move it. Here, we report a study in which participants were asked to move objects laterally to a higher platform, to a lower platform, or to a platform of the same height. The objects were rated, on average, as feeling heavier after they were moved to a higher platform than after they were moved to a lower platform or to a platform of the same height. Furthermore, participants gripped and lifted with more force, and used higher rates of force, when moving objects to a higher platform compared with moving it to a platform of the same height. These findings suggest that the goal of movement in the context of object interaction may affect how heavy an object feels and the way in which it is lifted.

A mixed-method evaluation of a New Zealand based midwifery education development unit.

The Midwifery Development Education Service was established in the Birthing Unit at Middlemore Hospital in South Auckland New Zealand in 2007. The service is unique in the New Zealand midwifery context for the way it operates as a collaboration between the education and health provider to optimise the clinical learning experience of student midwives. This paper reports on the evaluation of the Midwifery Development Education Service that was undertaken in 2015. The evaluation captured the views and experience of students and midwives who had been involved with, or had worked alongside, the service. A mixed-method approach was adopted for the evaluation study, comprising of an anonymous on-line survey, qualitative interviews and focus group discussion. Considerable satisfaction with the service was identified. This article draws attention to participants' perceptions of the service as supporting student midwives; the significance of quality time in the provision of the clinical midwifery education; the situating of the service at a unique vantage point (overseeing the needs of the university and the hospital) and its impact upon the learning culture of education within the unit. A potential tension is also identified between the provision of a supportive learning environment and the assessment of student performance.