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Extending the success of cellular immunotherapies against blood cancers to the realm of solid tumors will require improved in vitro models that reveal therapeutic modes of action at the molecular level. Here we describe a system, called BEHAV3D, developed to study the dynamic interactions of immune cells and patient cancer organoids by means of imaging and transcriptomics. We apply BEHAV3D to live-track >150,000 engineered T cells cultured with patient-derived, solid-tumor organoids, identifying a ‘super engager’ behavioral cluster comprising T cells with potent serial killing capacity. Among other T cell concepts we also study cancer metabolome-sensing engineered T cells (TEGs) and detect behavior-specific gene signatures that include a group of 27 genes with no previously described T cell function that are expressed by super engager killer TEGs. We further show that type I interferon can prime resistant organoids for TEG-mediated killing. BEHAV3D is a promising tool for the characterization of behavioral-phenotypic heterogeneity of cellular immunotherapies and may support the optimization of personalized solid-tumor-targeting cell therapies.

Black widow spider dragline silk is one of nature's high-performance biological polymers, exceeding the strength and toughness of most man-made materials including high tensile steel and Kevlar. Major ampullate (Ma), or dragline silk, is primarily comprised of two spidroin proteins (Sp) stored within the Ma gland. In the native gland environment, the MaSp1 and MaSp2 proteins self-associate to form hierarchical 200-300 nm superstructures despite being intrinsically disordered proteins (IDPs). Here, dynamic light scattering (DLS), three-dimensional (3D) triple resonance solution NMR, and diffusion NMR is utilized to probe the MaSp size, molecular structure, and dynamics of these protein pre-assemblies diluted in 4 M urea and identify specific regions of the proteins important for silk protein pre-assembly. 3D NMR indicates that the Gly-Ala-Ala and Ala-Ala-Gly motifs flanking the poly(Ala) runs, which comprise the β-sheet forming domains in fibers, are perturbed by urea, suggesting that these regions may be important for silk protein pre-assembly stabilization.

The ritual murder accusation is one of a series of myths that fall under the label blood libel, and describes the medieval legend that Jews require Christian blood for obscure religious purposes and are capable of committing murder to obtain it. This malicious myth continues to have an explosive afterlife in the public sphere, where Sarah Palin's 2011 gaffe is only the latest reminder of its power to excite controversy. Blood Libel is the first book-length study to analyze the recent historiography of the ritual murder accusation and to consider these debates in the context of intellectual and cultural history as well as methodology. Hannah R. Johnson articulates how ethics shapes methodological decisions in the study of the accusation and how questions about methodology, in turn, pose ethical problems of interpretation and understanding. Examining recent debates over the scholarship of historians such as Gavin Langmuir, Israel Yuval, and Ariel Toaff, Johnson argues that these discussions highlight an ongoing paradigm shift that seeks to reimagine questions of responsibility by deliberately refraining from a discourse of moral judgment and blame in favor of an emphasis on historical contingencies and hostile intergroup dynamics.

Despite advances in three-dimensional (3D) imaging, it remains challenging to profile all the cells within a large 3D tissue, including the morphology and organization of the many cell types present. Here, we introduce eight-color, multispectral, large-scale single-cell resolution 3D (mLSR-3D) imaging and image analysis software for the parallelized, deep learning-based segmentation of large numbers of single cells in tissues, called segmentation analysis by parallelization of 3D datasets (STAPL-3D). Applying the method to pediatric Wilms tumor, we extract molecular, spatial and morphological features of millions of cells and reconstruct the tumor's spatio-phenotypic patterning. In situ population profiling and pseudotime ordering reveals a highly disorganized spatial pattern in Wilms tumor compared to healthy fetal kidney, yet cellular profiles closely resembling human fetal kidney cells could be observed. In addition, we identify previously unreported tumor-specific populations, uniquely characterized by their spatial embedding or morphological attributes. Our results demonstrate the use of combining mLSR-3D and STAPL-3D to generate a comprehensive cellular map of human tumors.

The blood libel is sometimes described as a paradigmatic example of the irrational qualities of antisemitic thinking. Certainly it is difficult to understand the history of this legend without recourse to some theory concerning the psychological operations of antisemitism. This paper reviews a common narrative that has emerged in recent scholarship to account for medieval antisemitism. This explanatory narrative privileges structures of repression, projection, and identity formation as critical to the operation of legends such as the blood libel. This common story of explanation is considered in order to ask what other paths remain to be explored in the discussion of the psychological aspects of antisemitism. .Two scholars, Anthony Bale and Gavin Langmuir, offer possible models for formulating new questions at this difficult confluence of psychology and history.