A proteomic approach to identify endosomal cargoes controlling cancer invasiveness.

We have previously shown that Rab17, a small GTPase associated with epithelial polarity, is specifically suppressed by ERK2 (also known as MAPK1) signalling to promote an invasive phenotype. However, the mechanisms through which Rab17 loss permits invasiveness, and the endosomal cargoes that are responsible for mediating this, are unknown. Using quantitative mass spectrometry-based proteomics, we have found that knockdown of Rab17 leads to a highly selective reduction in the cellular levels of a v-SNARE (Vamp8).

A randomized controlled trial of web-based training to increase activity in children with cerebral palsy.

Aim: To determine the efficacy of web-based training on activity capacity and performance in children with unilateral cerebral palsy (CP).

Method: In a matched-pairs randomized waitlist controlled trial, independently ambulant children and adolescents with unilateral CP were allocated to receive 30 minutes of training (intervention) 6 days per week, or usual care (waitlist control) for 20 weeks. Activity capacity was assessed using maximal repetitions of functional strength tasks and 6-minute walk test (6MWT); performance using 4-day ActiGraph GT3X+ accelerometer records at baseline and 20 weeks.

Habitual physical activity of independently ambulant children and adolescents with cerebral palsy: are they doing enough?

Background: Despite the health benefits of regular physical activity, children with cerebral palsy (CP) are thought to participate in reduced levels of physical activity.

Objective: The study objective was to assess physical activity and determine the proportion adhering to the recommended 60 minutes of moderate-to-vigorous physical activity (MVPA) daily in independently ambulant children and adolescents with unilateral CP.

Design: This was a cross-sectional study.

Characteristics associated with physical activity among independently ambulant children and adolescents with unilateral cerebral palsy.

Aim: This study aimed to quantify the contribution of physical, personal and environmental characteristics to physical activity among independently ambulant children with unilateral cerebral palsy (CP).

Method: One-hundred and two children with unilateral CP (52 males, 50 females; 52 right hemiplegia; mean age 11y 3mo, range 8-17y [SD 2y 4mo]) classified at Gross Motor Function Classification System (GMFCS) levels I = 44 and II = 58 participated. Physical activity was measured over 4 days using ActiGraph accelerometers recording as activity counts.

CLIC3 controls recycling of late endosomal MT1-MMP and dictates invasion and metastasis in breast cancer.

Chloride intracellular channel 3 (CLIC3) drives invasiveness of pancreatic and ovarian cancer by acting in concert with Rab25 to regulate the recycling of α5β1 integrin from late endosomes to the plasma membrane. Here, we show that in two estrogen receptor (ER)-negative breast cancer cell lines, CLIC3 has little influence on integrin recycling, but controls trafficking of the pro-invasive matrix metalloproteinase MT1-MMP (also known as MMP14). In MDA-MB-231 cells, MT1-MMP and CLIC3 are localized primarily to late endosomal/lysosomal compartments located above the plane of adhesion and near the nucleus.

Variability in measuring physical activity in children with cerebral palsy.

Introduction: This study aimed to establish the variability in the measurement of habitual physical activity using the ActiGraph® GT3X+ accelerometer in children with cerebral palsy (CP).

Method: Repeated measures: Independently ambulant children with unilateral CP (n = 30; age, 11 yr 3 months (2 yr 4 months)) completed standardized tasks over two consecutive days, wearing an ActiGraph® GT3X+ accelerometer and HR monitor. Testing protocol comprised 5 min of seated rest (REST), walking at light, moderate, and vigorous pace, and rapid stepping on/off a step.

A systematic review of the clinimetric properties of measures of habitual physical activity in primary school aged children with cerebral palsy.

Regular participation in physical activity is an important determinant of health for children and adolescents with cerebral palsy (CP). However, there is little consensus on the most valid or reliable method to measure physical activity in this population. This study aimed to systematically review the psychometric properties of habitual physical activity (HPA) measures in primary school-aged children with CP.

Move it to improve it (Mitii): study protocol of a randomised controlled trial of a novel web-based multimodal training program for children and adolescents with cerebral palsy.

Introduction: Persons with cerebral palsy require a lifetime of costly and resource intensive interventions which are often limited by equity of access. With increasing burden being placed on health systems, new methods to deliver intensive rehabilitation therapies are needed. Move it to improve it (Mitii) is an internet-based multimodal programme comprising upper-limb and cognitive training with physical activity.

A systematic review of the clinimetric properties of habitual physical activity measures in young children with a motor disability.

Aim. To identify and systematically review the clinimetric properties of habitual physical activity (HPA) measures in young children with a motor disability. Method.

Direct regulation of tRNA and 5S rRNA gene transcription by Polo-like kinase 1.

Polo-like kinase Plk1 controls numerous aspects of cell-cycle progression. We show that it associates with tRNA and 5S rRNA genes and regulates their transcription by RNA polymerase III (pol III) through direct binding and phosphorylation of transcription factor Brf1. During interphase, Plk1 promotes tRNA and 5S rRNA expression by phosphorylating Brf1 directly on serine 450.

Epstein-Barr virus-encoded EBNA1 enhances RNA polymerase III-dependent EBER expression through induction of EBER-associated cellular transcription factors.

Background: Epstein-Barr Virus (EBV)-encoded RNAs (EBERs) are non-polyadenylated RNA molecules transcribed from the EBV genome by RNA polymerase III (pol III). EBERs are the most abundant viral latent gene products, although the precise mechanisms by which EBV is able to achieve such high levels of EBER expression are not fully understood. Previously EBV has been demonstrated to induce transcription factors associated with EBER expression, including pol III transcription factors and ATF-2.