Analysis of postures for handwriting on touch screens without using tools.

The act of handwriting affected the evolutionary development of humans and still impacts the motor cognition of individuals. However, the ubiquitous use of digital technologies has drastically decreased the number of times we really need to pick a pen up and write on paper. Nonetheless, the positive cognitive impact of handwriting is widely recognized, and a possible way to merge the benefits of handwriting and digital writing is to use suitable tools to write over touchscreens or graphics tablets. In this manuscript, we focus on the possibility of using the hand itself as a writing tool. A novel hand posture named FingerPen is introduced, and can be seen as a grasp performed by the hand on the index finger. A comparison with the most common posture that people tend to assume (i.e. index finger-only exploitation) is carried out by means of a biomechanical model. A conducted user study shows that the FingerPen is appreciated by users and leads to accurate writing traits.

MEK drives BRAF activation through allosteric control of KSR proteins.

RAF family kinases have prominent roles in cancer. Their activation is dependent on dimerization of their kinase domains, which has emerged as a hindrance for drug development. In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK). Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. Although GTP-bound RAS can modulate the dimerization of RAF isoforms by engaging their RAS-binding domains, KSR1 and KSR2 lack an RAS-binding domain and therefore the regulatory principles underlying their dimerization with other RAF family members remain unknown. Here we show that the selective heterodimerization of BRAF with KSR1 is specified by direct contacts between the amino-terminal regulatory regions of each protein, comprising in part a novel domain called BRS in BRAF and the coiled-coil-sterile α motif (CC-SAM) domain in KSR1. We also discovered that MEK binding to the kinase domain of KSR1 asymmetrically drives BRAF-KSR1 heterodimerization, resulting in the concomitant stimulation of BRAF catalytic activity towards free MEK molecules. These findings demonstrate that KSR-MEK complexes allosterically activate BRAF through the action of N-terminal regulatory region and kinase domain contacts and challenge the accepted role of KSR as a scaffold for MEK recruitment to RAF.