ARID1A mutations protect follicular lymphoma from FAS-dependent immune surveillance by reducing RUNX3/ETS1-driven FAS-expression.

The cell death receptor FAS and its ligand (FASLG) play crucial roles in the selection of B cells during the germinal center (GC) reaction. Failure to eliminate potentially harmful B cells via FAS can lead to lymphoproliferation and the development of B cell malignancies. The classic form of follicular lymphoma (FL) is a prototypic GC-derived B cell malignancy, characterized by the t(14;18)(q32;q21)IGH::BCL2 translocation and overexpression of antiapoptotic BCL2.

An integrated approach identifies the molecular underpinnings of murine anterior visceral endoderm migration.

The anterior visceral endoderm (AVE) differs from the surrounding visceral endoderm (VE) in its migratory behavior and ability to restrict primitive streak formation to the opposite side of the mouse embryo. To characterize the molecular bases for the unique properties of the AVE, we combined single-cell RNA sequencing of the VE prior to and during AVE migration with phosphoproteomics, high-resolution live-imaging, and short-term lineage labeling and intervention. This identified the transient nature of the AVE with attenuation of "anteriorizing" gene expression as cells migrate and the emergence of heterogeneities in transcriptional states relative to the AVE's position.

Combined proteomics and CRISPR‒Cas9 screens in PDX identify ADAM10 as essential for leukemia in vivo.

Background: Acute leukemias represent deadly malignancies that require better treatment. As a challenge, treatment is counteracted by a microenvironment protecting dormant leukemia stem cells.

Methods: To identify responsible surface proteins, we performed deep proteome profiling on minute numbers of dormant patient-derived xenograft (PDX) leukemia stem cells isolated from mice.

'The Machine Takes Our Jobs Away': The problem of technological unemployment in the work of Chicago sociologist William F. Ogburn.

This paper examines the Chicago sociologist William F. Ogburn's (1886-1959) views about technological unemployment, which were intimately connected to his analysis of the social impacts of technological developments and resulting social problems due to cultural lag. We trace the development of his views as seen through his well-known 1922 book, Social Change with Respect to Culture and Original Nature, his important contributions to the President's Research Committee on Social Trends (1933), and his lesser-known pamphlets designed for a broader audience-Living with Machines (1933), You and Machines (1934), and Machines and Tomorrow's World (1938).

Brief homogeneous TCR signals instruct common iNKT progenitors whose effector diversification is characterized by subsequent cytokine signaling.

Innate-like T cell populations expressing conserved TCRs play critical roles in immunity through diverse developmentally acquired effector functions. Focusing on the prototypical lineage of invariant natural killer T (iNKT) cells, we sought to dissect the mechanisms and timing of fate decisions and functional effector differentiation. Utilizing induced expression of the semi-invariant NKT cell TCR on double positive thymocytes, an initially highly synchronous wave of iNKT cell development was triggered by brief homogeneous TCR signaling.

CHIP and hips: clonal hematopoiesis is common in patients undergoing hip arthroplasty and is associated with autoimmune disease.

Clonal hematopoiesis (CH) is an age-related condition predisposing to blood cancer and cardiovascular disease (CVD). Murine models demonstrate CH-mediated altered immune function and proinflammation. Low-grade inflammation has been implicated in the pathogenesis of osteoarthritis (OA), the main indication for total hip arthroplasty (THA).

COMUNET: a tool to explore and visualize intercellular communication.

Motivation: Intercellular communication plays an essential role in multicellular organisms and several algorithms to analyze it from single-cell transcriptional data have been recently published, but the results are often hard to visualize and interpret.

Results: We developed Cell cOmmunication exploration with MUltiplex NETworks (COMUNET), a tool that streamlines the interpretation of the results from cell-cell communication analyses. COMUNET uses multiplex networks to represent and cluster all potential communication patterns between cell types.

Nuclear factor of activated T-cells, NFATC1, governs FLT3-driven hematopoietic stem cell transformation and a poor prognosis in AML.

Background: Acute myeloid leukemia (AML) patients with a high allelic burden of an internal tandem duplication (ITD)-mutated FMS-like Tyrosine Kinase-3 (FLT3) have a dismal outcome. FLT3 triggers the proliferation of the quiescent hematopoietic stem cell (HSC) pool but fails to directly transform HSCs. While the inflammatory transcription factor nuclear factor of activated T-cells 2 (NFAT2, NFATC1) is overexpressed in AML, it is unknown whether it plays a role in FLT3-induced HSC transformation.

NFATc1 as a therapeutic target in FLT3-ITD-positive AML.

Internal tandem duplications (ITD) in the Fms-related tyrosine kinase 3 receptor (FLT3) are associated with a dismal prognosis in acute myeloid leukemia (AML). FLT3 inhibitors such as sorafenib may improve outcome, but only few patients display long-term responses, prompting the search for underlying resistance mechanisms and therapeutic strategies to overcome them. Here we identified that the nuclear factor of activated T cells, NFATc1, is frequently overexpressed in FLT3-ITD-positive (FLT3-ITD+) AML.

Rapid evolution of virus sequences in intrinsically disordered protein regions.

Nodamura Virus (NoV) is a nodavirus originally isolated from insects that can replicate in a wide variety of hosts, including mammals. Because of their simplicity and ability to replicate in many diverse hosts, NoV, and the Nodaviridae in general, provide a unique window into the evolution of viruses and host-virus interactions. Here we show that the C-terminus of the viral polymerase exhibits extreme structural and evolutionary flexibility.

Senator Fred Harris's National Social Science Foundation proposal: Reconsidering federal science policy, natural science-social science relations, and American liberalism during the 1960s.

During the 1960s, a growing contingent of left-leaning voices claimed that the social sciences suffered mistreatment and undue constraints within the natural science-dominated federal science establishment. According to these critics, the entrenched scientific pecking order in Washington had an unreasonable commitment to the unity of the sciences, which reinforced unacceptable inequalities between the social and the natural sciences. The most important political figure who advanced this critique, together with a substantial legislative proposal for reform, was the Oklahoma Democratic Senator Fred Harris.

Riding natural scientists' coattails onto the endless frontier: the SSRC and the quest for scientific legitimacy.

This article proposes that the postwar National Science Foundation (NSF) debate constituted a critical, transitional episode in American social science and partisan politics. I show that by responding to powerful conservative critics in the scientific and political communities, the Social Science Research Council's (SSRC's) leading scholars (re)asserted a contested scientistic strategy-to advance the social sciences by following the natural sciences. Further, I reconstruct a wider and longer framework of analysis in order to recover central challenges to the scientistic strategy raised by prominent liberal scholars who rejected the associated commitments to value neutrality and disinterested professionalism.

A survey of fumonisins, deoxynivalenol, zearalenone and aflatoxins contamination in corn-based food products in Argentina.

The presence of mycotoxins in corn-based foods available in Argentina was determined in order to make a preliminary exposure assessment. Thirty-eight samples [corn meal ('polenta') and corn flakes] of different local brands were analysed for zearalenone, deoxynivalenol and aflatoxins by TLC and fumonisins (FB1, FB2 and FB3) by HPLC. None of the 38 samples contained any detectable amount of aflatoxins (< 2 micrograms/kg), zearalenone (< 50 micrograms/kg) and deoxynivalenol (< 50 micrograms/kg).