Biology subjects

Schaeffer, A.

Publications and source records attributed to Schaeffer, A..

4 recordsLinked to original sources

bioRxiv2022

Evaluating microbial contaminations of alternative heating oils

Since 2008, legislative initiatives for climate protection and reduced dependency on fossil resource imports led to the introduction of biofuels as CO2-reduced alternatives in the heating oil sector. In the case of biodiesel, the oil industry or its customers were confronted with accelerated and escalating microbial contaminations during heating oil storage. Since then, other fuel alternatives, like hydrogenated vegetable oils, gas-to-liquid products (GtL), or Oxymethylenether (OME) have been or will be developed and potentially introduced to the market. In this study, we use online monitoring of microbial CO2 production and the simulation of onset of microbial contamination to investigate the contamination potential of fuel alternatives during storage. As reference and blends, fossil heating oils of various refineries, in the course of this from various crude oils, and refinery processes reveal considerable variation in potential microbial activity. Oxymethylene ethers have an antimicrobial effect, while various forms of biodiesel confirm the promotion of microbial activity and diversity. The paraffinic Fischer-Tropsch products and biogenic hydrogenation products demonstrate high resistance to microbial contamination despite allowing microbial diversity. Through an array of analytics, including advanced chromatography coupled mass spectrometry, elemental analysis, and microbial sequencing, we can discuss critical fuel properties that promote or inhibit microbial contaminations. In summary, novel, non-fossil heating oils show different strengths and weaknesses for long-term storage. Designing blends for microbial activity reduced long-term storage might be an option. While being niche products, these fuels will contribute to the rapid reduction of fossil resource use.

microbiology↗

bioRxiv2022

Microtubules self-repair in living cells

Microtubule self-repair has been studied both in vitro and in vivo as an underlying mechanism of microtubule stability. The turnover of tubulin dimers along the microtubule network has challenged the pre-existing dogma that only growing ends are dynamic. However, although there is clear evidence of tubulin incorporation into the shaft of polymerized microtubules in vitro, the possibility of such events taking place in living cells remains uncertain. In this study, we investigated this possibility by microinjecting purified tubulin dimers labeled with a red fluorophore into the cytoplasm of cells expressing GFP-tubulin. We observed the appearance of red dots along pre-existing green microtubule network within minutes. We found that the fluorescence intensities of these red dots were inversely correlated with the green signal, suggesting that the red dimers were incorporated into the microtubules and replaced the pre-existing green dimers. We then characterized the size and spatial frequency of these incorporations as a function of injected tubulin concentration and post-injection delay. The saturation of these measurements contradicted the hypothesis of nonspecific adsorption along microtubules and suggested that the injected dimers incorporated into a finite number of damaged sites. By our low estimate, within a few minutes of the injections, free dimers incorporated into major repair sites every 70 micrometers of microtubules. Finally, we mapped the location of these sites in micropatterned cells and found that they were more concentrated in regions where the actin filament network was less dense and where microtubules exhibited greater lateral fluctuations. These results provide evidences that microtubules do self-repair in living cells, and they provide a quantitative characterization of the temporal and spatial dynamics of this process in PtK2 cells.

cell biology↗

bioRxiv2021

Compensatory CSF2-driven macrophage activation promotes adaptive resistance to CSF1R inhibition in breast-to-brain metastasis

Tumor microenvironment-targeted therapies are emerging as promising treatment options for different cancer types. Tumor-associated macrophages and microglia (TAMs) represent an abundant non-malignant cell type in brain metastases and have been proposed to modulate metastatic colonization and outgrowth. We used an inhibitor of colony stimulating factor 1 receptor (CSF1R) to target TAMs at distinct stages of the metastatic cascade in preclinical breast-to-brain metastasis models and found that CSF1R inhibition leads to anti-tumor responses in prevention and intervention trials. However, in established brain metastases, compensatory CSF2Rb-STAT5-mediated pro-inflammatory TAM activation blunted the ultimate efficacy of CSF1R inhibition by inducing neuro-inflammation gene signatures in association with wound repair responses that fostered tumor recurrence. Consequently, combined blockade of CSF1R and STAT5 signaling led to sustained tumor control, a normalization of microglial activation states and amelioration of neuronal damage.

cancer biology↗

bioRxiv2020

Hematopoietic progenitors polarize in contact with bone marrow stromal cells by engaging CXCR4 receptors.

Hematopoietic stem and progenitor cells (HSPCs) are located in the bone marrow, where they regulate the permanent production and renewal of all blood-cell types. HSPC proliferation and differentiation is locally regulated by their interaction with cells forming specific microenvironments close to the bone matrix or close to blood vessels. However, the cellular mechanisms underlying HSPCs interaction with these cells and their potential impact on HSPC polarity is still poorly understood. Here we modelled the bone-marrow niche using microfluidic technologies in a bone-marrow on a chip device, and evaluated long-duration cell-cell contacts between single HSPCs and stromal cells or endothelial cells in a custom-designed microwell cell-culture system. We found that an HSPC can form a discrete contact site that leads to the extensive polarization of their cytoskeleton architectures. As in the case with immune synapses formed by lymphocytes, the centrosome was located in proximity of the cell-cell contact. The entire microtubule network emanated from the centrosome, and the nucleus was confined to the side opposite of the cell-cell contact. The capacity of the HSPC to polarize appeared specific as it was not observed in contact with skin fibroblasts. The receptors ICAM, VCAM and CXCR4 were identified in the polarizing contact, and were all independently capable of inducing morphological polarization. However, only CXCR4 was independently capable of inducing the polarization of the centrosome-microtubule network. Altogether these results revealed a novel mechanism of HSPC polarization associated with its anchorage to specific cells in the bone-marrow, which might be instrumental in the regulation of their fate.

cell biology↗