Contractile units in disordered actomyosin bundles arise from F-actin buckling

Bundles of filaments and motors are central to contractility in cells. The classic example is striated muscle, where actomyosin contractility is mediated by highly organized sarcomeres which act as fundamental contractile units. However, many contractile bundles in vivo and in vitro lack sarcomeric organization. Here we propose a model for how contractility can arise in actomyosin bundles without sarcomeric organization and validate its predictions with experiments on a reconstituted system. In the model, internal stresses in frustrated arrangements of motors with diverse velocities cause filaments to buckle, leading to overall shortening. We describe the onset of buckling in the presence of stochastic actin-myosin detachment and predict that buckling-induced contraction occurs in an intermediate range of motor densities. We then calculate the size of the "contractile units" associated with this process. Consistent with these results, our reconstituted actomyosin bundles contract at relatively high motor density, and we observe buckling at the predicted length scale.Comment: 5 pages, 4 figures, Supporting text and movies attache

Sonic Gestures Applied to a Percussive Dialogue in TanGram using Wii Remotes

TanGram, is an original music score composed by Carlos D. Perales for Percussion Quartet and Nintendo Wii Remotes used as a wireless interface for Live Electronics. This paper examines how this composition explores exiting research in interaction and communication between instruments and digital sound processing discourse to produce a unique music mixed-media score, to explore the sonic possibilities of a multi-timbrical instrument with the integration of the visual gestures of an accessible device using processes of real-time gestural mimesis.

Requirements for contractility in disordered cytoskeletal bundles

Actomyosin contractility is essential for biological force generation, and is well understood in highly organized structures such as striated muscle. Additionally, actomyosin bundles devoid of this organization are known to contract both in vivo and in vitro, which cannot be described by standard muscle models. To narrow down the search for possible contraction mechanisms in these systems, we investigate their microscopic symmetries. We show that contractile behavior requires non-identical motors that generate large enough forces to probe the nonlinear elastic behavior of F-actin. This suggests a role for filament buckling in the contraction of these bundles, consistent with recent experimental results on reconstituted actomyosin bundles.Comment: 10 pages, 6 figures; text shortene

Morphine and fentanyl exposure during therapeutic hypothermia does not impair neurodevelopment

Background Hypothermia-treated and intubated infants with moderate or severe hypoxic-ischemic encephalopathy (HIE) usually receive morphine for sedation and analgesia (SA) during therapeutic hypothermia (TH) and endotracheal ventilation. Altered drug pharmacokinetics in this population increases the risk of drug accumulation. Opioids are neurotoxic in preterm infants. In term infants undergoing TH, the long-term effects of morphine exposure are unknown. We examined the effect of opioid administration during TH on neurodevelopmental outcome and time to extubation after sedation ended. Methods In this prospectively collected population-based cohort of 282 infants with HIE treated with TH (2007–2017), the cumulative opioid dose of morphine and equipotent fentanyl (10–60 µg/kg/h) administered during the first week of life was calculated. Clinical outcomes and concomitant medications were also collected. Of 258 survivors, 229 underwent Bayley-3 neurodevelopmental assessments of cognition, language and motor function at 18–24 months. Multivariate stepwise linear regression analysis was used to examine the relation between cumulative opioid dose and Bayley-3 scores. Three severity-groups (mild-moderate-severe) were stratified by early (<6 h) amplitude-integrated electroencephalography (aEEG) patterns. Findings The cumulative dose of opioid administered as SA during TH was median (IQR) 2121 µg/kg (1343, 2741). Time to extubation was independent of SA dose (p > 0.2). There was no significant association between cumulative SA dose and any of the Bayley-3 domains when analysing the entire cohort or any of the aEEG severity groups. Interpretation Higher cumulative opioid doses in TH-treated infants with HIE was not associated with worse Bayley-3 scores at 18–24 months of age. Funding The Bristol cooling program was funded by the Children's Medical Research Charity SPARKS managing donations for our research from the UK and US, the UK Moulton Foundation, the Lærdal Foundation for Acute Medicine in Norway and the Norwegian Research Council (JKG)

The significance of lifeworld and the case of hospice

Questions on what it means to live and die well are raised and discussed in the hospice movement. A phenomenological lifeworld perspective may help professionals to be aware of meaningful and important dimensions in the lives of persons close to death. Lifeworld is not an abstract philosophical term, but rather the opposite. Lifeworld is about everyday, common life in all its aspects. In the writings of Cicely Saunders, known as the founder of the modern hospice movement, facets of lifeworld are presented as important elements in caring for dying patients. Palliative care and palliative medicine today are, in many ways, replacing hospices. This represents not only a change in name, but also in the main focus. Hospice care was originally very much about providing support and comfort for, and interactions with the patients. Improved medical knowledge today means improved symptomatic palliation, but also time and resources spent in other ways than before. Observations from a Nordic hospice ward indicate that seriously ill and dying persons spend much time on their own. Different aspects of lifeworld and intersubjectivity in the dying persons’ room is presented and discussed

Communication skills in children aged 6-8 years, without cerebral palsy cooled for neonatal hypoxic-ischemic encephalopathy

We assessed communication skills of 48 children without cerebral palsy (CP) treated with therapeutic hypothermia (TH) for neonatal hypoxic-ischemic encephalopathy (HIE) (cases) compared to 42 controls at early school-age and examined their association with white matter diffusion properties in both groups and 18-month Bayley-III developmental assessments in cases. Parents completed a Children’s Communication Checklist (CCC-2) yielding a General Communication Composite (GCC), structural and pragmatic language scores and autistic-type behavior score. GCC ≤ 54 and thresholds of structural and pragmatic language score differences defined language impairment. Using tract-based spatial statistics (TBSS), fractional anisotropy (FA) was compared between 31 cases and 35 controls. Compared to controls, cases had lower GCC (p = 0.02), structural (p = 0.03) and pragmatic language score (p = 0.04) and higher language impairments (p = 0.03). GCC correlated with FA in the mid-body of the corpus callosum, the cingulum and the superior longitudinal fasciculus (p < 0.05) in cases. Bayley-III Language Composite correlated with GCC (r = 0.34, p = 0.017), structural (r = 0.34, p = 0.02) and pragmatic (r = 0.32, p = 0.03) language scores and autistic-type behaviors (r = 0.36, p = 0.01)

Nitrogen storage and use of biochemical indices to assess nitrogen deficiency and growth rate in natural plankton populations

Various newly developed indicators of N deficiency, physiological state (approximate growth rate), and N source for growth were measured during five cruises to Dabob Bay, Washington from early spring to summer. Although nitrate and ammonium in the surface layer were depleted early in the spring, the plankton populations never became extremely N deficient, as indicated by high intracellular amino acid/protein ratios. However, growth rates, estimated from protein/DNA or RNA/DNA ratios, were usually low unless nitrate concentrations were high or had recently been high, as indicated by large intracellular nitrate pools or high nitrate reductase activities. High growth rates were observed during the spring bloom or as a result of the sporadic supply of nitrate to the euphotic zone, which was inferred from measurements of biochemical indicators on several cruises after the spring bloom. The sporadic supply of nitrate could account for the lack of N deficiency in these populations and mask diel periodicity in N utilization. These results demonstrate that biochemical indicators can be easily measured in the field and that variations in indicators such as intracellular amino acid/protein, protein/DNA, RNA/DNA ratios, NR activities and intracellular nitrate concentrations are an aid in understanding plankton dynamics

Development of the corpus callosum and cognition after neonatal encephalopathy

Objective: Neonatal imaging studies report corpus callosum abnormalities after neonatal hypoxic–ischaemic encephalopathy (HIE), but corpus callosum development and relation to cognition in childhood are unknown. Using magnetic resonance imaging (MRI), we examined the relationship between corpus callosum size, microstructure and cognitive and motor outcomes at early school-age children cooled for HIE (cases) without cerebral palsy compared to healthy, matched controls. A secondary aim was to examine the impact of HIE-related neonatal brain injury on corpus callosum size, microstructure and growth. Methods: Participants aged 6–8 years underwent MRI, the Movement Assessment Battery for Children Second Edition and Wechsler Intelligence Scale for Children Fourth Edition. Cross-sectional area, volume, fractional anisotropy and radial diffusivity of the corpus callosum and five subdivisions were measured. Multivariable regression was used to assess associations between total motor score, full-scale IQ (FSIQ) and imaging metrics. Results: Adjusting for age, sex and intracranial volume, cases (N = 40) compared to controls (N = 39) demonstrated reduced whole corpus callosum area (β = −26.9, 95% confidence interval [CI] = −53.17, −0.58), volume (β = −138.5, 95% CI = −267.54, −9.56), fractional anisotropy and increased radial diffusivity (P < 0.05) within segments II–V. In cases, segment V area (β = 0.18, 95% CI = 0.004, 0.35), volume (β = 0.04, 95% CI = 0.001, 0.079), whole corpus callosum fractional anisotropy (β = 13.8 95% CI = 0.6, 27.1) and radial diffusivity (β = −11.3, 95% CI = −22.22, −0.42) were associated with FSIQ. Growth of the corpus callosum was restricted in cases with a FSIQ ≤85, and volume was reduced in cases with mild neonatal multifocal injury compared to white matter injury alone. Interpretation: Following neonatal HIE, morphological and microstructural changes in the corpus callosum are associated with reduced cognitive function at early school age