Assessment of Accelerometers for Measuring Upper-Extremity Physical Activity

Objective: The overarching goal of this study was to examine the use of triaxial accelerometers in measuring upper-extremity motions to monitor upper-extremity-exercise compliance. There were multiple questions investigated, but the primary objective was to investigate the correlation between visually observed arm motions and triaxial accelerometer activity counts to establish fundamental activity counts for the upper extremity. Study Design: Cross-sectional, basic research. Setting: Clinical laboratory. Participants: Thirty healthy individuals age 26 ± 6 y, body mass 24 ± 3 kg, and height 1.68 ± 0.09 m volunteered. Intervention: Participants performed 3 series of tasks: activities of daily living (ADLs), rehabilitation exercises, and passive shoulder range of motion at 5 specific velocities on an isokinetic dynamometer while wearing an accelerometer on each wrist. Participants performed exercises with their dominant arm to examine differences between sides. A researcher visually counted all arm motions to correlate counts with physical activity counts provided by the accelerometer. Main Outcome Measure: Physical activity counts derived from the accelerometer and visually observed activity counts recorded from a single investigator. Results: There was a strong positive correlation (r = .93, P \u3c .01) between accelerometer physical activity counts and visual activity counts for all ADLs. Accelerometers activity counts demonstrated side-to-side difference for all ADLs (P \u3c .001) and 5 of the 7 rehabilitation activities (P \u3c .003). All velocities tested on the isokinetic dynamometer were shown to be significantly different from each other (P \u3c .001). Conclusion: There is a linear relationship between arm motions counted visually and the physical activity counts generated by an accelerometer, indicating that arm motions could be potentially accounted for if monitoring arm usage. The accelerometers can detect differences in relatively slow arm-movement velocities, which is critical if attempting to evaluate exercise compliance during early phases of shoulder rehabilitation. These results provide fundamental information that indicates that triaxial accelerometers have the potential to objectively monitor and measure arm activities during rehabilitation and ADLs

Conversation Club: A Promising Practice in Youth Mentoring of Migrants and Refugees

This paper evaluates Conversation Club, a Canadian after-school group mentoring intervention focusing on the expansion of the program across three separate regions of Ontario. The authors use a multiple methods design, including questionnaires (n=101), post-session process data, and qualitative interviews (n=18), to evaluate how Conversation Club impacts members’ feelings of hope, belonging, sense of ethnic identity, and social support. A focus group (n = 7) with program facilitators was also conducted to explore the process of dissemination of the Club across regions. Findings suggest that Conversation Club holds promise for newcomer youth across settings. Quantitative data showed significant change (p <.01) in levels of hope and sense of belonging. Interviews revealed an increased sense of belonging, possibility, and social support, as well as improved confidence in communicating with others. Insights regarding use of the Club manual suggest the importance of integrating Conversation Club values with flexibility in facilitation to incorporate the strengths and opportunities of context across regions. Study limitations, as well as implications for further social work research and dissemination of best practices in services for migrant and refugee youth, are discussed

Stem Cells Have Different Needs for REST

REST is a well known repressor of neuronal gene expression. Genome-wide analysis of REST occupancy in different cell types now reveals new and cell-specific roles for REST in embryonic stem cells

A Genome-Wide Screen for Genetic Variants That Modify the Recruitment of REST to Its Target Genes

Increasing numbers of human diseases are being linked to genetic variants, but our understanding of the mechanistic links leading from DNA sequence to disease phenotype is limited. The majority of disease-causing nucleotide variants fall within the non-protein-coding portion of the genome, making it likely that they act by altering gene regulatory sequences. We hypothesised that SNPs within the binding sites of the transcriptional repressor REST alter the degree of repression of target genes. Given that changes in the effective concentration of REST contribute to several pathologies—various cancers, Huntington's disease, cardiac hypertrophy, vascular smooth muscle proliferation—these SNPs should alter disease-susceptibility in carriers. We devised a strategy to identify SNPs that affect the recruitment of REST to target genes through the alteration of its DNA recognition element, the RE1. A multi-step screen combining genetic, genomic, and experimental filters yielded 56 polymorphic RE1 sequences with robust and statistically significant differences of affinity between alleles. These SNPs have a considerable effect on the the functional recruitment of REST to DNA in a range of in vitro, reporter gene, and in vivo analyses. Furthermore, we observe allele-specific biases in deeply sequenced chromatin immunoprecipitation data, consistent with predicted differenes in RE1 affinity. Amongst the targets of polymorphic RE1 elements are important disease genes including NPPA, PTPRT, and CDH4. Thus, considerable genetic variation exists in the DNA motifs that connect gene regulatory networks. Recently available ChIP–seq data allow the annotation of human genetic polymorphisms with regulatory information to generate prior hypotheses about their disease-causing mechanism

The REST remodeling complex protects genomic integrity during embryonic neurogenesis

The timely transition from neural progenitor to post-mitotic neuron requires down-regulation and loss of the neuronal transcriptional repressor, REST. Here, we have used mice containing a gene trap in the Rest gene, eliminating transcription from all coding exons, to remove REST prematurely from neural progenitors. We find that catastrophic DNA damage occurs during S-phase of the cell cycle, with long-term consequences including abnormal chromosome separation, apoptosis, and smaller brains. Persistent effects are evident by latent appearance of proneural glioblastoma in adult mice deleted additionally for the tumor suppressor p53 protein (p53). A previous line of mice deleted for REST in progenitors by conventional gene targeting does not exhibit these phenotypes, likely due to a remaining C-terminal peptide that still binds chromatin and recruits co-repressors. Our results suggest that REST-mediated chromatin remodeling is required in neural progenitors for proper S-phase dynamics, as part of its well-established role in repressing neuronal genes until terminal differentiation

REST Controls Self-Renewal and Tumorigenic Competence of Human Glioblastoma Cells

The Repressor Element 1 Silencing Transcription factor (REST/NRSF) is a master repressor of neuronal programs in non-neuronal lineages shown to function as a central regulator of developmental programs and stem cell physiology. Aberrant REST function has been associated with a number of pathological conditions. In cancer biology, REST has been shown to play a tumor suppressor activity in epithelial cancers but an oncogenic role in brain childhood malignancies such as neuroblastoma and medulloblastoma. Here we examined REST expression in human glioblastoma multiforme (GBM) specimens and its role in GBM cells carrying self-renewal and tumorigenic competence. We found REST to be expressed in GBM specimens, its presence being particularly enriched in tumor cells in the perivascular compartment. Significantly, REST is highly expressed in self-renewing tumorigenic-competent GBM cells and its knock down strongly reduces their self-renewal in vitro and tumor-initiating capacity in vivo and affects levels of miR-124 and its downstream targets. These results indicate that REST contributes to GBM maintenance by affecting its self-renewing and tumorigenic cellular component and that, hence, a better understanding of these circuitries in these cells might lead to new exploitable therapeutic targets

Control of chromosome stability by the \u3b2-TrCP\u2013REST\u2013Mad2 axis

REST/NRSF (repressor-element-1-silencing transcription factor/ neuron-restrictive silencing factor) negatively regulates the tran- scription of genes containing RE1 sites1,2. REST is expressed in non-neuronal cells and stem/progenitor neuronal cells, in which it inhibits the expression of neuron-specific genes. Overexpression of REST is frequently found in human medulloblastomas and neuroblastomas3\u20137, in which it is thought to maintain the stem character of tumour cells. Neural stem cells forced to express REST and c-Myc fail to differentiate and give rise to tumours in the mouse cerebellum3. Expression of a splice variant of REST that lacks the carboxy terminus has been associated with neuronal tumours and small-cell lung carcinomas8\u201310, and a frameshift mutant (REST-FS), which is also truncated at the C terminus, has oncogenic properties11. Here we show, by using an unbiased screen, that REST is an interactor of the F-box protein b-TrCP. REST is degraded by means of the ubiquitin ligase SCFb-TrCP dur- ing the G2 phase of the cell cycle to allow transcriptional derepres- sion of Mad2, an essential component of the spindle assembly checkpoint. The expression in cultured cells of a stable REST mutant, which is unable to bind b-TrCP, inhibited Mad2 expres- sion and resulted in a phenotype analogous to that observed in Mad21/2 cells. In particular, we observed defects that were con- sistent with faulty activation of the spindle checkpoint, such as shortened mitosis, premature sister-chromatid separation, chro- mosome bridges and mis-segregation in anaphase, tetraploidy, and faster mitotic slippage in the presence of a spindle inhibitor. An indistinguishable phenotype was observed by expressing the oncogenic REST-FS mutant11, which does not bind b-TrCP. Thus, SCFb-TrCP-dependent degradation of REST during G2 permits the optimal activation of the spindle checkpoint, and consequently it is required for the fidelity of mitosis. The high levels of REST or its truncated variants found in certain human tumours may contri- bute to cellular transformation by promoting genomic instability