Kawakami, Y. | Search bioRxiv

bioRxiv2018

Stretching combined with repetitive small length changes of the plantar flexor muscles enhances their passive extensibility for longer duration than conventional static stretching, while not compromising strength

Static stretching increases flexibility but can decrease muscle strength, and the method to avoid the latter has been longed for. In this study, a novel stretching modality was developed that provides repetitive small length changes to the plantar flexor muscles undergoing passive static stretching (\"local vibration stretching,\"). We investigated the effects of local vibration stretching on muscle strength, flexibility and its persistence. Plantar flexion strength and maximal ankle joint dorsiflexion angle (dorsiflexion range of motion) were measured for 10 healthy young males before (pre) and immediately after (post) three types of stretching: static stretching, local vibration stretching at 15 Hz, and no intervention (control). The dorsiflexion range of motion was measured also at 15, 30, and 60 min post-stretching. Elongation of the medial gastrocnemius and Achilles tendon was determined by ultrasonography. Plantar flexion strength significantly decreased by 4.3 {+/-} 3.5 % in static stretching but not in local vibration stretching. The dorsiflexion range of motion significantly increased both in static stretching (7.2 {+/-} 8.1 %) and local vibration stretching (11.2 {+/-} 14.6 %) which was accompanied by a significantly larger muscle elongation but not tendon elongation. Elevated dorsiflexion range of motion was maintained until 30 min after the local vibration stretching while it returned to baseline level (pre-intervention) in 15 min after the static stretching. All variables remained unchanged in the control condition. In conclusion, local vibration stretching improves extensibility of the muscle belly without decreasing strength, and the increased flexibility is retained longer than static stretching.

physiology↗

bioRxiv2017

In-depth characterization of the cisplatin mutational signature in a human cell line and in esophageal and liver tumors

Background and aimsCisplatin reacts with DNA, and thereby likely generates a characteristic pattern of somatic mutations, called a mutational signature. Despite widespread use of cisplatin in cancer treatment and its role in contributing to secondary malignancies, its mutational signature has not been delineated. We hypothesize that cisplatins mutational signature can serve as a biomarker to identify cisplatin mutagenesis in suspected secondary malignancies. Knowledge of which tissues are at risk of developing cisplatin-induced secondary malignancies could lead to guidelines for non-invasive monitoring for secondary malignancies after cisplatin chemotherapy.\n\nMethodsWe performed whole genome sequencing of 10 independent clones of cisplatin-exposed MCF-10A and HepG2 cells, and delineated the patterns of single- and dinucleotide mutations in terms of flanking sequence, transcription strand bias, and other characteristics. We used the mSigAct signature presence test and non-negative matrix factorization to search for cisplatin mutagenesis in hepatocellular carcinomas and esophageal adenocarcinomas.\n\nResultsAll clones showed highly consistent patterns of single- and dinucleotide substitutions. The proportion of dinucleotide substitutions was high: 8.1% of single nucleotide substitutions were part of dinucleotide substitutions, presumably due to cisplatins propensity to form intra-and inter-strand crosslinks between purine bases in DNA. We identified likely cisplatin exposure in 9 hepatocellular carcinomas and 3 esophageal adenocarcinomas. All hepatocellular carcinomas for which clinical data were available and all esophageal cancers indeed had histories of cisplatin treatment.\n\nConclusionsWe experimentally delineated the single- and dinucleotide mutational signature of cisplatin. This signature enabled us to detect previous cisplatin exposure in human hepatocellular carcinomas and esophageal adenocarcinomas with high confidence.

cancer biology↗