The Oncogenic Lipid Sphingosine-1-Phosphate Impedes the Phagocytosis of Tumor Cells by M1 Macrophages in Diffuse Large B Cell Lymphoma

Simple Summary: Diffuse large B cell lymphoma (DLBCL), the most common form of non-Hodgkin lymphoma, is clinically aggressive and associated with poor patient outcomes. Antagonists of the small oncogenic lipid sphingosine-1-phosphate (S1P) are already in the clinic and have been suggested to have therapeutic potential in DLBCL. We have studied the impact of S1P signaling on the recruitment of macrophages and their phagocytic functions following the treatment of DLBCL cells with CD20-targeting antibodies. We have shown that tumor-derived S1P is a major chemoattractant for monocytes and macrophages, both in vitro and in animal models of DLBCL, an effect mediated by the S1P receptor S1PR1. However, S1P also robustly inhibited the phagocytosis of antibody-treated tumor cells by M1 macrophages. Future experiments could be directed toward investigating the therapeutic effects of blocking S1P–S1PR1 signaling in combination with chemotherapy and CD20-targeting antibodies. Abstract: Background: A total of 30–40% of diffuse large B cell lymphoma (DLBCL) patients will either not respond to the standard therapy or their disease will recur. The first-line treatment for DLBCL is rituximab and combination chemotherapy. This treatment involves the chemotherapy-induced recruitment of tumor-associated macrophages that recognize and kill rituximab-opsonized DLBCL cells. However, we lack insights into the factors responsible for the recruitment and functionality of macrophages in DLBCL tumors. Methods: We have studied the effects of the immunomodulatory lipid sphingosine-1-phosphate (S1P) on macrophage activity in DLBCL, both in vitro and in animal models. Results: We show that tumor-derived S1P mediates the chemoattraction of both monocytes and macrophages in vitro and in animal models, an effect that is dependent upon the S1P receptor S1PR1. However, S1P inhibited M1 macrophage-mediated phagocytosis of DLBCL tumor cells opsonized with the CD20 monoclonal antibodies rituximab and ofatumumab, an effect that could be reversed by an S1PR1 inhibitor. Conclusions: Our data show that S1P signaling can modulate macrophage recruitment and tumor cell killing by anti-CD20 monoclonal antibodies in DLBCL. The administration of S1PR1 inhibitors could enhance the phagocytosis of tumor cells and improve outcomes for patients

Modelling dynamical 3D electron diffraction intensities. I. A scattering cluster algorithm

Three‐dimensional electron diffraction (3D‐ED) is a powerful technique for crystallographic characterization of nanometre‐sized crystals that are too small for X‐ray diffraction. For accurate crystal structure refinement, however, it is important that the Bragg diffracted intensities are treated dynamically. Bloch wave simulations are often used in 3D‐ED, but can be computationally expensive for large unit cell crystals due to the large number of diffracted beams. Proposed here is an alternative method, the `scattering cluster algorithm' (SCA), that replaces the eigen‐decomposition operation in Bloch waves with a simpler matrix multiplication. The underlying principle of SCA is that the intensity of a given Bragg reflection is largely determined by intensity transfer (i.e. `scattering') from a cluster of neighbouring diffracted beams. However, the penalty for using matrix multiplication is that the sample must be divided into a series of thin slices and the diffracted beams calculated iteratively, similar to the multislice approach. Therefore, SCA is more suitable for thin specimens. The accuracy and speed of SCA are demonstrated on tri‐isopropyl silane (TIPS) pentacene and rubrene, two exemplar organic materials with large unit cells

Byblos During the Chalcolithic Period

Evidence for domestic settlement during the Chalcolithic is scant at Byblos, in contrast to the remarkable number of richly adorned jar burials attributed to the period (Artin, this volume). The Chalcolithic as defined by Levantine archaeologists is a period covering at least 800 years. We know structures, presumably representing domestic settlement, exist across the site, with the excavator (Maurice Dunand) recognising several phases. Due to the uneven quality of the excavations it is impossible to determine which structures were contemporary and which existed hundreds of years apart. Crucially, it is also difficult to understand the relationship of the burials to these structures (Artin 2010 and 2014; Dunand 1973). Still, the Chalcolithic represents an important transitional phase in the history of site, warranting an exploration of the available evidence from Byblos and the wider region

A Design Methodology for Sensing-Ready Concentric Rings-Based Chipless RFID Tags With Effective Spectrum Use and High Coding Capacity

This paper introduces an innovative strategy for the development of sensing-ready concentric rings-based chipless radio frequency identification (CRFID) tags. Our approach is marked by the novel use of exponentially increasing spacing, a significant departure from the conventional uniform spacing method. This innovative design results in an impressive 88.2% improvement in tag data encoding capacity compared to traditional designs. Importantly, our design framework not only advances the current state of CRFID tag technology but also methodically lays the foundation for future integration of high-resolution sensing capabilities. This is achieved by strategically utilizing the innermost ring as a prospective sensing site, complemented by the implementation of nulls for data encoding achieved through the addition of an extra ring at the tag’s outermost edge. Notably, all these features represent advancements that have not been demonstrated in previously published concentric rings-based CRFID tags. To empirically validate our methodology, we have developed and tested 18-bit example tags optimized for operation within the ultrawideband (UWB) spectrum, covering a range from 3.1 to 10.6 GHz. The radar cross-section (RCS) response of these tags exhibits well-distributed resonances, culminating in a high encoding capacity of 17.65 bits/λ2/GHz. Preliminary results using capacitors connected to the innermost ring underscore the future sensing potential of our tags, setting the stage for more advanced sensing implementations in subsequent research

A conceptual model of individuals’ decision to engage in global mobility: integrating self-determination theory and theory of planned behavior

PurposeCompanies target globally mobile workers and face the war for talent, while individuals are more reluctant to engage in global mobility. This scenario led us to propose a model to understand the individuals' decision process to engage in global mobility.Design/methodology/approachBuilding on the self-determination theory, the theory of planned behavior and the literature on decisions for global mobility, the authors propose mechanisms through which psychological variables and assignments' factual and perceived contextual aspects (directly or indirectly) explain the decision to engage or not in global mobility.FindingsThis study offers a conceptual model with the authors' novel propositions to explain individuals' decision to engage in global mobility.Originality/valueThe model provides a more comprehensive explanation of the individuals' decision-making process to engage in global mobility than previous models and potentially yields more effective organizational practices to attract both well-established and emerging phenomena of globally mobile workers

Conceptual and Measurement Issues in Assessing Democratic Backsliding

During the past decade, analyses drawing on several democracy measures have shown a global trend of democratic retrenchment. While these democracy measures use radically different methodologies, most partially or fully rely on subjective judgments to produce estimates of the level of democracy within states. Such projects continuously grapple with balancing conceptual coverage with the potential for bias (Munck and Verkuilen 2002; Przeworski et al. 2000). Little and Meng (L&M) (2023) reintroduce this debate, arguing that “objective” measures of democracy show little evidence of recent global democratic backsliding.1 By extension, they posit that time-varying expert bias drives the appearance of democratic retrenchment in measures that incorporate expert judgments. In this article, we engage with (1) broader debates on democracy measurement and democratic backsliding, and (2) L&M’s specific data and conclusions

The Art of Peace Formation. Arts-based Social Movements, Opportunities and Blockages

This edited collection explores the relationship between the arts, political agency, and peace formation. Developing the concept of artpeace, the book investigates to what extent local art projects have played a role in broader national peace projects, or, alternatively, what factors have blocked artists from translating their social imaginaries into political change in contexts of war and violence. The collection brings together peace and conflict scholarship and arts-based studies of social movements in conflict-affected societies to examine the proposition that the arts may offer an opportunity to shape peace processes in emancipatory ways, whilst examining the blockages that, at times, prevent them from making a tangible difference to the variations of peace being designed

Problematizing Hongkonger Political Subjectivity: The Struggle for, and over, Democracy

In this chapter we explore changing and competing political subjectivities in Hong Kong from a critical feminist and decolonial perspective. We theorize political subjectivity as both collective and individual, as arising from particular historical and political junctures but also, importantly, through social relationships. We argue that political subjectivity must be understood in terms of the multiple processes through which it emerges and evolves in the interplay between history, politics, culture and interpersonal relationships. In so doing we advance an approach to political subjectivity as contextual and relational. While our discussion is based on the specific conditions facing Hong Kong activists, our mode of analysis may offer insights into other socio-political contexts

Mitophagy in plants: Emerging regulators of mitochondrial targeting for selective autophagy

The degradation and turnover of mitochondria is fundamental to Eukaryotes and is a key homeostatic mechanism for maintaining functional mitochondrial populations. Autophagy is an important pathway by which mitochondria are degraded, involving their sequestration into membrane‐bound autophagosomes and targeting to lytic endosomal compartments (the lysosome in animals, the vacuole in plants and yeast). Selective targeting of mitochondria for autophagy, also known as mitophagy, distinguishes mitochondria from other cell components for degradation and is necessary for the regulation of mitochondria‐specific cell processes. In mammals and yeast, mitophagy has been well characterised and is regulated by numerous pathways with diverse and important functions in the regulation of cell homeostasis, metabolism and responses to specific stresses. In contrast, we are only just beginning to understand the importance and functions of mitophagy in plants, chiefly as the proteins that target mitochondria for autophagy in plants are only recently emerging. Here, we discuss the current progress of our understanding of mitophagy in plants, the importance of mitophagy for plant life and the regulatory autophagy proteins involved in mitochondrial degradation. In particular, we will discuss the recent emergence of mitophagy receptor proteins that selectively target mitochondria for autophagy, and discuss the missing links in our knowledge of mitophagy‐regulatory proteins in plants compared to animals and yeast