The relationship between muscle activation and handwriting quality with non-native grip styles.

PURPOSE: This study aimed to explore the differences in muscle activity, handwriting legibility, and consistency when using the 4 primary handwriting grip styles: dynamic quadrupod (DQ), dynamic tripod, lateral quadrupod (LQ) and lateral tripod. STUDY DESIGN AND METHODS: Thirty-four 18-22-year-old participants completed a handwriting legibility test on paper as well as consistency and metrics tests using both surface electromyography and a digital writing tablet. Electromyography was used to measure the activity of 6 muscles associated with handwriting, and the tablet measured stroke duration, length, velocity, and pen pressure. Subjects used each grip style with all protocols and scores were normalized to their native grip. Significance was set at P < .05. RESULTS: Females had a lower range in legibility scores than males by 3.5% ± 1.7% (p = .046, d = 0.713), but grip style did not impact legibility. The upper trapezius (UT) was more active in the lateral tripod and LQ grips compared to DQ by 16.8% ± 5.2% and by 13.8% ± 5.2%, (p = .007, p = .012, respectively, partial η2 = 0.188). The stroke duration was greater in the LQ grip style than dynamic tripod and DQ grip styles (p = .008, p = .023, respectively; partial η2 = 0.123). CONCLUSIONS: Lateral grip styles involve more whole-arm, stabilizing movements while dynamic grip styles require fine dexterous movements. Furthermore, females are likely to be able to employ any grip with minimal effect on legibility. For a patient needing guidance in rehabilitation, understanding the differences in grips could aid selection of the optimum grip style to employ based on their muscular control deficits.

Mechanisms of endocrine resistance in breast cancer: an overview of the proposed roles of noncoding RNA.

Endocrine therapies such as tamoxifen and aromatase inhibitors are the standard treatment options for estrogen receptor-positive breast cancer patients. However, resistance to these agents has become a major clinical obstacle. Potential mechanisms of resistance to endocrine therapies have been identified, often involving enhanced growth factor signaling and changes in the expression or action of the estrogen receptor, but few studies have addressed the role of noncoding RNA (ncRNA). Two important types of ncRNA include microRNA (miRNA) and long noncoding RNA (lncRNA). miRNAs are small RNA molecules that regulate gene expression via translational inhibition or degradation of mRNA transcripts, while lncRNAs are larger RNA molecules that have been shown to play a role in multiple cellular maintenance functions such as protein scaffolding, chromatin looping, and regulation of mRNA stability. Both miRNA and lncRNA have recently impacted the field of breast cancer research as important pieces in the mechanistic puzzle of the genes and pathways involved in breast cancer development and progression. This review serves as an overview of the roles of miRNA and lncRNA in breast cancer progression and the development of endocrine resistance. Ideally, future experiments in the field should include identification of ncRNAs that could be potential therapeutic targets in endocrine-resistant tumors, as well as ncRNA biomarkers that facilitate more tumor-specific treatment options for endocrine-resistant breast cancer patients.

Engineering a trifunctional proline utilization A chimaera by fusing a DNA-binding domain to a bifunctional PutA.

Proline utilization A (PutA) is a bifunctional flavoenzyme with proline dehydrogenase (PRODH) and Δ1-pyrroline-5-carboxylate (P5C) dehydrogenase (P5CDH) domains that catalyses the two-step oxidation of proline to glutamate. Trifunctional PutAs also have an N-terminal ribbon-helix-helix (RHH) DNA-binding domain and moonlight as autogenous transcriptional repressors of the put regulon. A unique property of trifunctional PutA is the ability to switch functions from DNA-bound repressor to membrane-associated enzyme in response to cellular nutritional needs and proline availability. In the present study, we attempt to construct a trifunctional PutA by fusing the RHH domain of Escherichia coli PutA (EcRHH) to the bifunctional Rhodobacter capsulatus PutA (RcPutA) in order to explore the modular design of functional switching in trifunctional PutAs. The EcRHH-RcPutA chimaera retains the catalytic properties of RcPutA while acquiring the oligomeric state, quaternary structure and DNA-binding properties of EcPutA. Furthermore, the EcRHH-RcPutA chimaera exhibits proline-induced lipid association, which is a fundamental characteristic of functional switching. Unexpectedly, RcPutA lipid binding is also activated by proline, which shows for the first time that bifunctional PutAs exhibit a limited form of functional switching. Altogether, these results suggest that the C-terminal domain (CTD), which is conserved by trifunctional PutAs and certain bifunctional PutAs, is essential for functional switching in trifunctional PutAs.