Search results for "Astronomy"
showing 10 items of 11180 documents
Few layer 2D pnictogens catalyze the alkylation of soft nucleophiles with esters
2019
Group 15 elements in zero oxidation state (P, As, Sb and Bi), also called pnictogens, are rarely used in catalysis due to the difficulties associated in preparing well–structured and stable materials. Here, we report on the synthesis of highly exfoliated, few layer 2D phosphorene and antimonene in zero oxidation state, suspended in an ionic liquid, with the native atoms ready to interact with external reagents while avoiding aerobic or aqueous decomposition pathways, and on their use as efficient catalysts for the alkylation of nucleophiles with esters. The few layer pnictogen material circumvents the extremely harsh reaction conditions associated to previous superacid–catalyzed alkylations…
EphrinB2 repression through ZEB2 mediates tumour invasion and anti-angiogenic resistance.
2016
Diffuse invasion of the surrounding brain parenchyma is a major obstacle in the treatment of gliomas with various therapeutics, including anti-angiogenic agents. Here we identify the epi-/genetic and microenvironmental downregulation of ephrinB2 as a crucial step that promotes tumour invasion by abrogation of repulsive signals. We demonstrate that ephrinB2 is downregulated in human gliomas as a consequence of promoter hypermethylation and gene deletion. Consistently, genetic deletion of ephrinB2 in a murine high-grade glioma model increases invasion. Importantly, ephrinB2 gene silencing is complemented by a hypoxia-induced transcriptional repression. Mechanistically, hypoxia-inducible facto…
Signalling strength determines proapoptotic functions of STING
2017
Mammalian cells use cytosolic nucleic acid receptors to detect pathogens and other stress signals. In innate immune cells the presence of cytosolic DNA is sensed by the cGAS–STING signalling pathway, which initiates a gene expression programme linked to cellular activation and cytokine production. Whether the outcome of the STING response varies between distinct cell types remains largely unknown. Here we show that T cells exhibit an intensified STING response, which leads to the expression of a distinct set of genes and results in the induction of apoptosis. Of note, this proapoptotic STING response is still functional in cancerous T cells and delivery of small molecule STING agonists prev…
Nanoparticle delivery to metastatic breast cancer cells by nanoengineered mesenchymal stem cells
2017
We created a 3D cell co-culture model by combining nanoengineered mesenchymal stem cells (MSCs) with the metastatic breast cancer cell line MDA-MD-231 and primary breast cancer cell line MCF7 to explore the transfer of quantum dots (QDs) to cancer cells. First, the optimal conditions for high-content QD loading in MSCs were established. Then, QD uptake in breast cancer cells was assessed after 24 h in a 3D co-culture with nanoengineered MSCs. We found that incubation of MSCs with QDs in a serum-free medium provided the best accumulation results. It was found that 24 h post-labelling QDs were eliminated from MSCs. Our results demonstrate that breast cancer cells efficiently uptake QDs that a…
Collective behavior of quorum-sensing run-and-tumble particles in confinement
2016
We study a generic model for quorum-sensing bacteria in circular confinement. Every bacterium produces signaling molecules, the local concentration of which triggers a response when a certain threshold is reached. If this response lowers the motility then an aggregation of bacteria occurs, which differs fundamentally from standard motility-induced phase separation due to the long-ranged nature of the concentration of signal molecules. We analyze this phenomenon analytically and by numerical simulations employing two different protocols leading to stationary cluster and ring morphologies, respectively.
Brain-like large scale cognitive networks and dynamics
2018
A new approach to the study of the brain and its functions known as Human Connectomics has been recently established. Starting from magnetic resonance images (MRI) of brain scans, it is possible to identify the fibers that link brain areas and to build an adjacency matrix that connects these areas, thus creating the brain connectome. The topology of these networks provides a lot of information about the organizational structure of the brain (both structural and functional). Nevertheless this knowledge is rarely used to investigate the possible emerging brain dynamics linked to cognitive functions. In this work, we implement finite state models on neural networks to display the outcoming bra…
Improving risk assessments in conservation ecology
2019
Conservation efforts and management decisions on the living environment of our planet often rely on the results from statistical models. Yet, these models are imperfect and quantification of risk associated with the estimate of management-relevant quantities becomes crucial in providing robust advice. Here we demonstrate that estimates of risk themselves could be substantially biased but by combining data fitting with an extensive simulation–estimation procedure, one can back-calculate the correct values. We apply the method to 627 time series of population abundance across four taxa using the Gompertz state-space model as an example. We find that the risk of large bias in population status…
Contribution of allelic imbalance to colorectal cancer
2018
Point mutations in cancer have been extensively studied but chromosomal gains and losses have been more challenging to interpret due to their unspecific nature. Here we examine high-resolution allelic imbalance (AI) landscape in 1699 colorectal cancers, 256 of which have been whole-genome sequenced (WGSed). The imbalances pinpoint 38 genes as plausible AI targets based on previous knowledge. Unbiased CRISPR-Cas9 knockout and activation screens identified in total 79 genes within AI peaks regulating cell growth. Genetic and functional data implicate loss of TP53 as a sufficient driver of AI. The WGS highlights an influence of copy number aberrations on the rate of detected somatic point muta…
Dynamic coarse-graining fills the gap between atomistic simulations and experimental investigations of mechanical unfolding
2017
We present a dynamic coarse-graining technique that allows to simulate the mechanical unfolding of biomolecules or molecular complexes on experimentally relevant time scales. It is based on Markov state models (MSM), which we construct from molecular dynamics simulations using the pulling coordinate as an order parameter. We obtain a sequence of MSMs as a function of the discretized pulling coordinate, and the pulling process is modeled by switching among the MSMs according to the protocol applied to unfold the complex. This way we cover seven orders of magnitude in pulling speed. In the region of rapid pulling we additionally perform steered molecular dynamics simulations and find excellen…
Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.
2016
During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition…