Induction of fibroblast senescence generates a non-fibrogenic myofibroblast phenotype that differentially impacts on cancer prognosis

Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two

Happy Protest Voters: The Case of Rotterdam 1997–2009

Protest parties are on the rise in several European countries. This development is commonly attributed to a growing dissatisfaction with life and associated with declining quality of life in modern society of the lowest social strata. This explanation is tested in a cross-sectional analysis of voting and life-satisfaction in 63 districts of the city of Rotterdam in the Netherlands, where the share of protest voters increased from 10 % in 1994 to 31 % in 2009. Contrary to this explanation protest voting appeared not to be the most frequent in the least happy districts of Rotterdam, but in the medium happy segment. Also divergent from this explanation was that average happiness in city districts is largely independent of local living conditions, but is rather a matter of personal vulnerability in terms of education, income and health. These results fit alternative explanations in terms of mid

mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype

Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses

Simpson's paradox visualized: The example of the Rosiglitazone meta-analysis

<p>Abstract</p> <p>Background</p> <p>Simpson's paradox is sometimes referred to in the areas of epidemiology and clinical research. It can also be found in meta-analysis of randomized clinical trials. However, though readers are able to recalculate examples from hypothetical as well as real data, they may have problems to easily figure where it emerges from.</p> <p>Method</p> <p>First, two kinds of plots are proposed to illustrate the phenomenon graphically, a scatter plot and a line graph. Subsequently, these can be overlaid, resulting in a overlay plot. The plots are applied to the recent large meta-analysis of adverse effects of rosiglitazone on myocardial infarction and to an example from the literature. A large set of meta-analyses is screened for further examples.</p> <p>Results</p> <p>As noted earlier by others, occurrence of Simpson's paradox in the meta-analytic setting, if present, is associated with imbalance of treatment arm size. This is well illustrated by the proposed plots. The rosiglitazone meta-analysis shows an effect reversion if all trials are pooled. In a sample of 157 meta-analyses, nine showed an effect reversion after pooling, though non-significant in all cases.</p> <p>Conclusion</p> <p>The plots give insight on how the imbalance of trial arm size works as a confounder, thus producing Simpson's paradox. Readers can see why meta-analytic methods must be used and what is wrong with simple pooling.</p

Listeners form average-based representations of individual voice identities.

Models of voice perception propose that identities are encoded relative to an abstracted average or prototype. While there is some evidence for norm-based coding when learning to discriminate different voices, little is known about how the representation of an individual's voice identity is formed through variable exposure to that voice. In two experiments, we show evidence that participants form abstracted representations of individual voice identities based on averages, despite having never been exposed to these averages during learning. We created 3 perceptually distinct voice identities, fully controlling their within-person variability. Listeners first learned to recognise these identities based on ring-shaped distributions located around the perimeter of within-person voice spaces - crucially, these distributions were missing their centres. At test, listeners' accuracy for old/new judgements was higher for stimuli located on an untrained distribution nested around the centre of each ring-shaped distribution compared to stimuli on the trained ring-shaped distribution

Tendencies, variability and persistence of sea surface temperature anomalies

Quantifying global trends and variability in sea surface temperature (SST) is of fundamental importance to understanding changes in the Earth’s climate. One approach to observing SST is via remote sensing. Here we use a 37-year gap-filled, daily-mean analysis of satellite SSTs to quantify SST trends, variability and persistence between 1981-2018. The global mean warming trend is 0.08 K per decade globally, with 95 % of local trends being between -0.1 K and +0.35 K. Excluding perennial sea-ice regions, the mean warming trend is 0.11 K per decade. After removing the long-term trend we calculate the SST power spectra over different time periods. The maximum variance in the SST power spectra in the equatorial Pacific is 1.9 K2 on 1-5 year timescales, dominated by ENSO processes. In western boundary currents characterised by an intense mesoscale activity, SST power on sub-annual timescales dominates, with a maximum variance of 4.9 K2. Persistence timescales tend to be shorter in the summer hemisphere due to the shallower mixed layer. The median short-term persistence length is 11-14 days, found over 71-79 % of the global ocean area, with seasonal variations. The mean global correlation between monthly SST anomalies with a three-month time-lag is 0.35, with statistically significant correlations over 54.0 % of the global oceans, and notably in the northern and equatorial Pacific, and the sub-polar gyre south of Greenland. At six months, the mean global SST anomaly correlation falls to 0.18. The satellite data record enables the detailed characterisation of temporal changes in SST over almost four decades

Endovascular coils as lung tumour markers in real-time tumour tracking stereotactic radiotherapy: preliminary results

To evaluate the use of endovascular coils as markers for respiratory motion correction during high-dose stereotactic radiotherapy with the CyberKnife, an image-guided linear accelerator mounted on a robotic arm. Endovascular platinum embolisation coils were used to mark intrapulmonary lesions. The coils were placed in subsegmental pulmonary artery branches in close proximity to the target tumour. This procedure was attempted in 25 patients who were considered unsuitable candidates for standard transthoracic percutaneous insertion. Vascular coils (n = 87) were succesfully inserted in 23 of 25 patients. Only minor complications were observed: haemoptysis during the procedure (one patient), development of pleural pain and fever on the day of procedure (one patient), and development of small infiltrative changes distal to the vascular coil (five patients). Fifty-seven coils (66% of total inserted number) could be used as tumour markers for delivery of biologically highly effective radiation doses with automated tracking during CyberKnife radiotherapy. Endovascular markers are safe and allow high-dose radiotherapy of lung tumours with CyberKnife, also in patients who are unsuitable candidates for standard transthoracic percutaneous marker insertion