Contraction of cross-linked actomyosin bundles

Cross-linked actomyosin bundles retract when severed in vivo by laser ablation, or when isolated from the cell and micromanipulated in vitro in the presence of ATP. We identify the time scale for contraction as a viscoelastic time tau, where the viscosity is due to (internal) protein friction. We obtain an estimate of the order of magnitude of the contraction time tau ~ 10-100 s, consistent with available experimental data for circumferential microfilament bundles and stress fibers. Our results are supported by an exactly solvable, hydrodynamic model of a retracting bundle as a cylinder of isotropic, active matter, from which the order of magnitude of the active stress is estimated.Comment: To be published in Physical Biolog

Active Tension Network model suggests an exotic mechanical state realized in epithelial tissues.

Mechanical interactions play a crucial role in epithelial morphogenesis, yet understanding the complex mechanisms through which stress and deformation affect cell behavior remains an open problem. Here we formulate and analyze the Active Tension Network (ATN) model, which assumes that the mechanical balance of cells within a tissue is dominated by cortical tension and introduces tension-dependent active remodeling of the cortex. We find that ATNs exhibit unusual mechanical properties. Specifically, an ATN behaves as a fluid at short times, but at long times supports external tension like a solid. Furthermore, an ATN has an extensively degenerate equilibrium mechanical state associated with a discrete conformal - "isogonal" - deformation of cells. The ATN model predicts a constraint on equilibrium cell geometries, which we demonstrate to approximately hold in certain epithelial tissues. We further show that isogonal modes are observed in the fruit y embryo, accounting for the striking variability of apical areas of ventral cells and helping understand the early phase of gastrulation. Living matter realizes new and exotic mechanical states, the study of which helps to understand biological phenomena

A randomised double-blind placebo-controlled feasibility trial of flavonoid-rich cocoa for fatigue in people with relapsing and remitting multiple sclerosis

The impact of flavonoids on fatigue has not been investigated in Relapsing and Remitting Multiple Sclerosis (RRMS). Objective: To determine the feasibility and estimate the potential effect of flavonoid-rich cocoa on fatigue and fatigability in RRMS. Methods: A randomised double-blind placebo-controlled feasibility study in people recently diagnosed with RRMS and fatigue, throughout the Thames Valley (ISRCTN: 69897291). During a six week intervention participants consumed a high or low flavonoid cocoa beverage daily. Fatigue and fatigability were measured at three visits (weeks 0, 3 and 6). Feasibility and fidelity were assessed through recruitment and retention, adherence and a process evaluation. Results: 40 pwMS (10 men, 30 women, age 44 ± 10 yrs) were randomised and allocated to high (n=19) or low (n=21) flavonoid groups and included in analysis. Missing data was 75%. There was a small effect on fatigue (Neuro-QoL: effect size {ES} 0.04; confidence interval {CI} -0.40-0.48) and a moderate effect on fatigability (six-minute walk test: ES 0.45; CI -0.18 - 1.07). There were seven adverse events (four control, three intervention), only one of which was possibly related and it was resolved. Conclusion: A flavonoid beverage demonstrates the potential to improve fatigue and fatigability in RRMS

Identification of Escherichia coli ygaQ and rpmG as novel mitomycin C resistance factors implicated in DNA repair

Using the ASKA (A Complete Set of E. coli K-12 ORF Archive) library for genome-wide screening of E. coli proteins we identified that expression of ygaQ and rpmG promotemitomycin C resistance (MMCR). YgaQ mediated MMCR was independent of homologous recombination involving RecA or RuvABC, but required UvrD. YgaQ is an uncharacterized protein homologous to a-amylases that we identified to have nuclease activity directed to single stranded DNA of 5’ flaps. Nuclease activity was inactivated by mutation of two amino acid motifs, which also abolished MMCR. RpmG is frequently annotated as a bacterial ribosomal protein, although forms an operon with MutM glycosylase and a putative deubiquitinating enzyme, YicR. RpmG associated MMCR was dependent on MutM. MMCR from RpmG resembles DNA repair phenotypes reported for ‘idiosyncratic ribosomal proteins’ in eukaryotes

OPTIMISE: MS study protocol: a pragmatic, prospective observational study to address the need for, and challenges with, real world pharmacovigilance in multiple sclerosis

IntroductionThe power of ‘real world’ data to improve our understanding of the clinical aspects of multiple sclerosis (MS) is starting to be realised. Disease modifying therapy (DMT) use across the UK is driven by national prescribing guidelines. As such, the UK provides an ideal country in which to gather MS outcomes data. A rigorously conducted observational study with a focus on pharmacovigilance has the potential to provide important data to inform clinicians and patients while testing the reliability of estimates from pivotal trials when applied to patients in the UK.Methods and analysisThe primary aim of this study is to characterise the incidence and compare the risk of serious adverse events in people with MS treated with DMTs. The OPTIMISE:MS database enables electronic data capture and secure data transfer. Selected clinical data, clinical histories and patient-reported outcomes are collected in a harmonised fashion across sites at the time of routine clinical visits. The first patient was recruited to the study on 24 May 2019. As of January 2021, 1615 individuals have baseline data recorded; follow-up data are being captured and will be reported in due course.Ethics and disseminationThis study has ethical permission (London City and East; Ref 19/LO/0064). Potential concerns around data storage and sharing are mitigated by the separation of identifiable data from all other clinical data, and limiting access to any identifiable data. The results of this study will be disseminated via publication. Participants provide consent for anonymised data to be shared for further research use, further enhancing the value of the study.</jats:sec

Intensity modulated radiotherapy (IMRT) in the treatment of children and Adolescents - a single institution's experience and a review of the literature

<p>Abstract</p> <p>Background</p> <p>While IMRT is widely used in treating complex oncological cases in adults, it is not commonly used in pediatric radiation oncology for a variety of reasons. This report evaluates our 9 year experience using stereotactic-guided, inverse planned intensity-modulated radiotherapy (IMRT) in children and adolescents in the context of the current literature.</p> <p>Methods</p> <p>Between 1999 and 2008 thirty-one children and adolescents with a mean age of 14.2 years (1.5 - 20.5) were treated with IMRT in our department. This heterogeneous group of patients consisted of 20 different tumor entities, with Ewing's sarcoma being the largest (5 patients), followed by juvenile nasopharyngeal fibroma, esthesioneuroblastoma and rhabdomyosarcoma (3 patients each). In addition a review of the available literature reporting on technology, quality, toxicity, outcome and concerns of IMRT was performed.</p> <p>Results</p> <p>With IMRT individualized dose distributions and excellent sparing of organs at risk were obtained in the most challenging cases. This was achieved at the cost of an increased volume of normal tissue receiving low radiation doses. Local control was achieved in 21 patients. 5 patients died due to progressive distant metastases. No severe acute or chronic toxicity was observed.</p> <p>Conclusion</p> <p>IMRT in the treatment of children and adolescents is feasible and was applied safely within the last 9 years at our institution. Several reports in literature show the excellent possibilities of IMRT in selective sparing of organs at risk and achieving local control. In selected cases the quality of IMRT plans increases the therapeutic ratio and outweighs the risk of potentially increased rates of secondary malignancies by the augmented low dose exposure.</p

Evaluation of a novel nanocrystalline hydroxyapatite paste Ostim® in comparison to Alpha-BSM® - more bone ingrowth inside the implanted material with Ostim® compared to Alpha BSM®

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to evaluate the performance a newly developed nanocrystalline hydroxyapatite, OSTIM^®following functional implantation in femoral sites in thirty-eight sheep for 1, 2 or 3 months. Ostim^®35 was compared to an established calcium phosphate, Alpha BSM^®.</p> <p>Methods</p> <p>Biomechanical testing, μ-CT analysis, histological and histomorphological analyses were conducted to compare the treatments including evaluation of bone regeneration level, material degradation, implant biomechanical characteristics.</p> <p>Results</p> <p>The micro-computed tomography (μCT) analysis and macroscopic observations showed that Ostim^®seemed to diffuse easily particularly when the defects were created in a cancellous bone area. Alpha BSM^®remained in the defect.</p> <p>The performance of Ostim was good in terms of mechanical properties that were similar to Alpha BSM^®and the histological analysis showed that the bone regeneration was better with Ostim^®than with Alpha BSM^®. The histomorphometric analysis confirmed the qualitative analysis and showed more bone ingrowth inside the implanted material with Ostim^®when compared to Alpha BSM ^®at all time points.</p> <p>Conclusions</p> <p>The successful bone healing with osseous consolidation verifies the importance of the nanocrystalline hydroxyapatite in the treatment of metaphyseal osseous volume defects in the metaphyseal spongiosa.</p

Does Intensity Modulated Radiation Therapy (IMRT) prevent additional toxicity of treating the pelvic lymph nodes compared to treatment of the prostate only?

<p>Abstract</p> <p>Background</p> <p>To evaluate the risk of rectal, bladder and small bowel toxicity in intensity modulated radiation therapy (IMRT) of the prostate only compared to additional irradiation of the pelvic lymphatic region.</p> <p>Methods</p> <p>For ten patients with localized prostate cancer, IMRT plans with a simultaneous integrated boost (SIB) were generated for treatment of the prostate only (plan-PO) and for additional treatment of the pelvic lymph nodes (plan-WP). In plan-PO, doses of 60 Gy and 74 Gy (33 fractions) were prescribed to the seminal vesicles and to the prostate, respectively. Three plans-WP were generated with prescription doses of 46 Gy, 50.4 Gy and 54 Gy to the pelvic target volume; doses to the prostate and seminal vesicles were identical to plan-PO. The risk of rectal, bladder and small bowel toxicity was estimated based on NTCP calculations.</p> <p>Results</p> <p>Doses to the prostate were not significantly different between plan-PO and plan-WP and doses to the pelvic lymph nodes were as planned. Plan-WP resulted in increased doses to the rectum in the low-dose region ≤ 30 Gy, only, no difference was observed in the mid and high-dose region. Normal tissue complication probability (NTCP) for late rectal toxicity ranged between 5% and 8% with no significant difference between plan-PO and plan-WP. NTCP for late bladder toxicity was less than 1% for both plan-PO and plan-WP. The risk of small bowel toxicity was moderately increased for plan-WP.</p> <p>Discussion</p> <p>This retrospective planning study predicted similar risks of rectal, bladder and small bowel toxicity for IMRT treatment of the prostate only and for additional treatment of the pelvic lymph nodes.</p