Three-dimensional waves of excitation during Dictyostelium morphogenesis

Cells in Dictyostelium slugs follow well-defined patterns of motion. We found that the chemotactic cell response is controlled by a scroll wave of messenger concentration in the highly excitable prestalk zone of the slug that decays in the less-excitable prespore region into planar wave fronts. This phenomenon is investigated by numerical solutions of partial differential equations that couple local nonlinear kinetics and diffusive transport of the chemotactic signal. In the interface of both regions a complex twisted scroll wave is formed that reduces the wave frequency in the prespore zone. The spatio-temporal dynamics of waves and filaments are followed over 33 periods of rotation. These results yield an explanation of collective self-organized cell motion in a multicellular organism

Impact of CONSORT extension for cluster randomised trials on quality of reporting and study methodology : review of random sample of 300 trials, 2000-8

Peer reviewedPublisher PD

Coupled Oscillators with Chemotaxis

A simple coupled oscillator system with chemotaxis is introduced to study morphogenesis of cellular slime molds. The model successfuly explains the migration of pseudoplasmodium which has been experimentally predicted to be lead by cells with higher intrinsic frequencies. Results obtained predict that its velocity attains its maximum value in the interface region between total locking and partial locking and also suggest possible roles played by partial synchrony during multicellular development.Comment: 4 pages, 5 figures, latex using jpsj.sty and epsf.sty, to appear in J. Phys. Soc. Jpn. 67 (1998

Exercise-induced modulation of cardiac lipid content in healthy lean young men

Cardiac lipid accumulation is associated with decreased cardiac function and energy status (PCr/ATP). It has been suggested that elevated plasma fatty acid (FA) concentrations are responsible for the cardiac lipid accumulation. Therefore, the aim of the present study was to investigate if elevating plasma FA concentrations by exercise results in an increased cardiac lipid content, and if this influences cardiac function and energy status. Eleven male subjects (age 25.4 ± 1.1 years, BMI 23.6 ± 0.8 kg/m2) performed a 2-h cycling protocol, once while staying fasted and once while ingesting glucose, to create a state of high versus low plasma FA concentrations, respectively. Cardiac lipid content was measured by proton magnetic resonance spectroscopy (1H-MRS) at baseline, directly after exercise and again 4 h post-exercise, together with systolic function (by multi-slice cine-MRI) and cardiac energy status (by 31P-MRS). Plasma FA concentrations were increased threefold during exercise and ninefold during recovery in the fasted state compared with the glucose-fed state (p < 0.01). Cardiac lipid content was elevated at the end of the fasted test day (from 0.26 ± 0.04 to 0.44 ± 0.04%, p = 0.003), while it did not change with glucose supplementation (from 0.32 ± 0.03 to 0.26 ± 0.05%, p = 0.272). Furthermore, PCr/ATP was decreased by 32% in the high plasma FA state compared with the low FA state (n = 6, p = 0.014). However, in the high FA state, the ejection fraction 4 h post-exercise was higher compared with the low FA state (63 ± 2 vs. 59 ± 2%, p = 0.018). Elevated plasma FA concentrations, induced by exercise in the fasted state, lead to increased cardiac lipid content, but do not acutely hamper systolic function. Although the lower cardiac energy status is in line with a lipotoxic action of cardiac lipid content, a causal relationship cannot be proven

Cluster over individual randomization: are study design choices appropriately justified? Review of a random sample of trials

Taljaard, M., Goldstein, C. E., Giraudeau, B., Nicholls, S. G., Carroll, K., Hey, S. P., … Weijer, C. (2020). Cluster over individual randomization: are study design choices appropriately justified? Review of a random sample of trials. Clinical Trials. Copyright © The Author(s), 2020. DOI: https://doi.org/10.1177/174077451989679

Does clinical equipoise apply to cluster randomized trials in health research?

This article is part of a series of papers examining ethical issues in cluster randomized trials (CRTs) in health research. In the introductory paper in this series, Weijer and colleagues set out six areas of inquiry that must be addressed if the cluster trial is to be set on a firm ethical foundation. This paper addresses the third of the questions posed, namely, does clinical equipoise apply to CRTs in health research? The ethical principle of beneficence is the moral obligation not to harm needlessly and, when possible, to promote the welfare of research subjects. Two related ethical problems have been discussed in the CRT literature. First, are control groups that receive only usual care unduly disadvantaged? Second, when accumulating data suggests the superiority of one intervention in a trial, is there an ethical obligation to act

The UFM1 Pathway Impacts HCMV US2-Mediated Degradation of HLA Class I

To prevent accumulation of misfolded proteins in the endoplasmic reticulum, chaperones perform quality control on newly translated proteins and redirect misfolded proteins to the cytosol for degradation by the ubiquitin-proteasome system. This pathway is called ER-associated protein degradation (ERAD). The human cytomegalovirus protein US2 induces accelerated ERAD of HLA class I molecules to prevent immune recognition of infected cells by CD8(+) T cells. Using US2-mediated HLA-I degradation as a model for ERAD, we performed a genome-wide CRISPR/Cas9 library screen to identify novel cellular factors associated with ERAD. Besides the identification of known players such as TRC8, p97, and UBE2G2, the ubiquitin-fold modifier1 (UFM1) pathway was found to affect degradation of HLA-I. UFMylation is a post-translational modification resembling ubiquitination. Whereas we observe ubiquitination of HLA-I, no UFMylation was detected on HLA-I or several other proteins involved in degradation of HLA-I, suggesting that the UFM1 pathway impacts ERAD in a different manner than ubiquitin. Interference with the UFM1 pathway seems to specifically inhibit the ER-to-cytosol dislocation of HLA-I. In the absence of detectable UFMylation of HLA-I, UFM1 may contribute to US2-mediated HLA-I degradation by misdirecting protein sorting indirectly. Mass spectrometry analysis of US2-expressing cells showed that ribosomal proteins are a major class of proteins undergoing extensive UFMylation; the role of these changes in protein degradation may be indirect and remains to be established

Sensitivity of the Atlantic meridional overturning circulation to South Atlantic freshwater anomalies

The sensitivity of the Atlantic Meridional Overturning Circulation (AMOC) to changes in basin integrated net evaporation is highly dependent on the zonal salinity contrast at the southern border of the Atlantic. Biases in the freshwater budget strongly affect the stability of the AMOC in numerical models. The impact of these biases is investigated, by adding local anomaly patterns in the South Atlantic to the freshwater fluxes at the surface. These anomalies impact the freshwater and salt transport by the different components of the ocean circulation, in particular the basin-scale salt-advection feedback, completely changing the response of the AMOC to arbitrary perturbations. It is found that an appropriate dipole anomaly pattern at the southern border of the Atlantic Ocean can collapse the AMOC entirely even without a further hosing. The results suggest a new view on the stability of the AMOC, controlled by processes in the South Atlantic. <br/