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"Weiss, M"
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Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface
During tumor progression, cancer cells come into contact with various non-tumor cell types, but it is unclear how tumors adapt to these new environments. Here, we integrate spatially resolved transcriptomics, single-cell RNA-seq, and single-nucleus RNA-seq to characterize tumor-microenvironment interactions at the tumor boundary. Using a zebrafish model of melanoma, we identify a distinct “interface” cell state where the tumor contacts neighboring tissues. This interface is composed of specialized tumor and microenvironment cells that upregulate a common set of cilia genes, and cilia proteins are enriched only where the tumor contacts the microenvironment. Cilia gene expression is regulated by ETS-family transcription factors, which normally act to suppress cilia genes outside of the interface. A cilia-enriched interface is conserved in human patient samples, suggesting it is a conserved feature of human melanoma. Our results demonstrate the power of spatially resolved transcriptomics in uncovering mechanisms that allow tumors to adapt to new environments.
During tumor progression, cancer cells contact different neighboring cell types, but it is unclear how these interactions affect cancer cell behavior. Here, the authors use spatially resolved transcriptomics and single-cell RNA-seq to study the role of cilia at the tumormicroenvironment interface.
Journal Article
The promise and peril of targeting cell metabolism for cancer therapy
A major challenge of cancer immunotherapy is the potential for undesirable effects on bystander cells and tumor-associated immune cells. Fundamentally, we need to understand what effect targeting tumor metabolism has upon the metabolism and phenotype of tumor-associated leukocytes, whose function can be critical for effective cancer therapeutic strategies. Undesirable effects of cancer therapeutics are a major reason for drug-associated toxicity, which confounds drug dosing and efficacy. As with any chemotherapeutic agent, drugs targeting tumor metabolism will exert potent effects on host stromal cells and tumor-associated leukocytes. Any drug targeting glycolysis, for example, could metabolically starve tumor-infiltrating T cells, inhibit their effector function and enable tumor progression. The targeting of oxidative phosphorylation in tumors will have complex effects on the polarization and function of tumor-associated macrophages. In short, we need to improve our understanding of tumor and immune cell metabolism and devise ways to specifically target tumors without compromising necessary host metabolism. Exploiting cell-specific metabolic pathways to directly target tumor cells may minimize detrimental effects on tumor-associated leukocytes.
Journal Article
Tits polygons
We introduce the notion of a Tits polygon, a generalization of the notion of a Moufang polygon, and show that Tits polygons arise in
a natural way from certain configurations of parabolic subgroups in an arbitrary spherical buildings satisfying the Moufang condition.
We establish numerous basic properties of Tits polygons and characterize a large class of Tits hexagons in terms of Jordan algebras. We
apply this classification to give a “rank
eBook
Abstraction and Detail in Experimental Design
Political scientists designing experiments often face the question of how abstract or detailed their experimental stimuli should be. Typically, this question is framed in terms of trade-offs relating to experimental control and generalizability: the more context introduced into studies, the less control, and the more difficulty generalizing the results. Yet, we have reason to question this trade-off, and there is relatively little systematic evidence to rely on when calibrating the degree of abstraction in studies. We make two contributions. First, we provide a theoretical framework that identifies and considers the consequences of three dimensions of abstraction in experimental design: situational hypotheticality, actor identity, and contextual detail. Second, we replicate and extend three survey experiments, varying these levels of abstraction. We find no evidence that situational hypotheticality substantively changes results in any of our studies, but do find that increased contextual detail dampens treatment effects, and that the salience of actor identities moderates results in our endorsement experiment.
Journal Article
Descent in Buildings (AM-190)
Descent in Buildings begins with the resolution of a major open question about the local structure of Bruhat-Tits buildings. The authors then put their algebraic solution into a geometric context by developing a general fixed point theory for groups acting on buildings of arbitrary type, giving necessary and sufficient conditions for the residues fixed by a group to form a kind of subbuilding or \"form\" of the original building. At the center of this theory is the notion of a Tits index, a combinatorial version of the notion of an index in the relative theory of algebraic groups. These results are combined at the end to show that every exceptional Bruhat-Tits building arises as a form of a \"residually pseudo-split\" Bruhat-Tits building. The book concludes with a display of the Tits indices associated with each of these exceptional forms.This is the third and final volume of a trilogy that began with Richard Weiss' The Structure of Spherical Buildings and The Structure of Affine Buildings.
eBook