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Biopharmaceutical products are often produced in Chinese hamster ovary (CHO) cell cultures that are vulnerable to virus infections. Therefore, it is a regulatory requirement that downstream purification steps for biopharmaceuticals can remove viruses from feedstocks. Anion exchange chromatography (AEX) is one of the downstream unit operations that is most frequently used for this purpose and claimed for its capability to remove viruses. However, the impact of various process parameters on virus removal by AEX is still not fully understood. Mechanistic modeling could be a promising way to approach this gap, as these models require comparatively few experiments for calibration. This makes them a valuable tool to improve understanding of viral clearance, especially since virus spiking studies are costly and time consuming. In this study, we present how the virus clearance of a MVM mock virus particle by Q Sepharose FF resin can be described by mechanistic modeling. A lumped kinetic model was combined with a steric mass action model and calibrated at micro scale using three linear gradient experiments and an incremental step elution gradient. The model was subsequently verified for its capability to predict the effect of different sodium chloride concentrations, as well as residence times, on virus clearance and was in good agreement with the LRVs of the verification runs. Overall, models like this could enhance the mechanistic understanding of viral clearance mechanisms and thereby contribute to the development of more efficient and safer biopharmaceutical downstream processes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Glioblastomas are incurable tumors infiltrating the brain. A subpopulation of glioblastoma cells forms a functional and therapy-resistant tumor cell network interconnected by tumor microtubes (TMs). Other subpopulations appear unconnected, and their biological role remains unclear. Here, we demonstrate that whole-brain colonization is fueled by glioblastoma cells that lack connections with other tumor cells and astrocytes yet receive synaptic input from neurons. This subpopulation corresponds to neuronal and neural-progenitor-like tumor cell states, as defined by single-cell transcriptomics, both in mouse models and in the human disease. Tumor cell invasion resembled neuronal migration mechanisms and adopted a Lévy-like movement pattern of probing the environment. Neuronal activity induced complex calcium signals in glioblastoma cells followed by the de novo formation of TMs and increased invasion speed. Collectively, superimposing molecular and functional single-cell data revealed that neuronal mechanisms govern glioblastoma cell invasion on multiple levels. This explains how glioblastoma's dissemination and cellular heterogeneity are closely interlinked., Competing Interests: Declaration of interests F.W. and W.W. report the patent (WO2017020982A1) “Agents for use in the treatment of glioma.” F.W. is co-founder of DC Europa Ltd (a company trading under the name Divide & Conquer) that is developing new medicines for the treatment of glioma. Divide & Conquer also provides research funding to F.W.’s lab under a research collaboration agreement., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The type 2 taste receptors (Tas2rs) comprise a large family of G protein-coupled receptors that recognize compounds bitter to humans and aversive to vertebrates. Tas2rs are expressed in both gustatory and nongustatory tissues, however, identification and functional analyses of T2R-expressing cells have been difficult in most tissues. To overcome these limitations and to be able to manipulate Tas2r-expressing cells in vivo, we used gene-targeting to generate a Tas2r131-specific Cre knock-in mouse strain. We then employed a binary genetic approach to characterize Cre-mediated recombination in these animals and to investigate Tas2r131 expression during postnatal development. We demonstrate that a Cre-activated fluorescent reporter reliably visualizes Tas2r131-cells in gustatory tissue. We show that the onset of Tas2r131 as well as of α-Gustducin expression is initiated at different developmental stages depending on the type of taste bud. Furthermore, the number of Tas2r131- and α-Gustducin-expressing cells increased during postnatal development. Our results demonstrate that the Tas2r131-expressing cells constitute a subpopulation of α-Gustducin positive cells at all stages. We detected Tas2r131-expressing cells in several nongustatory tissues including lung, trachea, ovary, ganglia, and brain. Thus, the Tas2r131-Cre strain will help to dissect the functional role of Tas2r131 cells in both gustatory and nongustatory tissues in the future., (© The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)