At the intersection of globalization and "civilizational originality' : cultural production in Putin's Russia

This special issue originates from a transnational collaboration of scholars in philology, comparative literature, social theory, sociology, anthropology, ethnography, and media studies. The collection strives to advance a research agenda built on the nexus of three intellectual and academic domains: post-Soviet Russian cultural studies', the research paradigm put forward by Cultural Studies, as well as empirical methods developed in sociology. The collection illustrates the importance of expanding the experience of Cultural Studies beyond its established spheres of national investigation, while it also speaks to the necessity to re-evaluate the hegemony of the English-language academic and cultural production on the global scale. The collection offers insights into the gamut of cultural practices and institutional environments in which Russian cultural production happens today. It shows how cultural industries and institutions in Russia are integrated into the global marketplace and transnational communities, while they also draw on and contribute to local lives and experiences by trying to create an autonomous space for symbolic production at personal and collective levels. Through diverse topics, the issue sheds light on the agency, i.e. practitioners and participants, creators and consumers, of Russian cultural production and the neoliberal practices implemented on creative work and cultural administration in Russia today. The Introduction outlines the development of academic studies on Russian cultural practices since 1991; describes main political developments shaping the cultural field in Putin's Russia; and, finally, identifies the Cultural Studies debates the editors of the collection find most productive for investigations of Russia, i.e. the instrumentalization of culture and culture as resource. Relocated in an analysis of a post-socialist society, these conceptualisations seem increasingly problematic in a situation where local and federal policies governing cultural and creative work focus simultaneously on marketization and on nationalism as the main tools of legitimizing the federal government.Peer reviewe

Understanding private law. On the work of Hans Nieuwenhuis, 1944-2015

Hans Nieuwenhuis’ work is difficult to capture in a single sentence. It aims to impart an understanding of private law which, Nieuwenhuis says, requires an awareness of time, space and balance. We measure his work by his own yardstick.Coherent privaatrech

Depletion and activation of microglia impact metabolic connectivity of the mouse brain

AimWe aimed to investigate the impact of microglial activity and microglial FDG uptake on metabolic connectivity, since microglial activation states determine FDG-PET alterations. Metabolic connectivity refers to a concept of interacting metabolic brain regions and receives growing interest in approaching complex cerebral metabolic networks in neurodegenerative diseases. However, underlying sources of metabolic connectivity remain to be elucidated.Materials and methodsWe analyzed metabolic networks measured by interregional correlation coefficients (ICCs) of FDG-PET scans in WT mice and in mice with mutations in progranulin (Grn) or triggering receptor expressed on myeloid cells 2 (Trem2) knockouts ((-/-)) as well as in double mutant Grn(-/-)/Trem2(-/-) mice. We selected those rodent models as they represent opposite microglial signatures with disease associated microglia in Grn(-/-) mice and microglia locked in a homeostatic state in Trem2(-/-) mice;however, both resulting in lower glucose uptake of the brain. The direct influence of microglia on metabolic networks was further determined by microglia depletion using a CSF1R inhibitor in WT mice at two different ages. Within maps of global mean scaled regional FDG uptake, 24 pre-established volumes of interest were applied and assigned to either cortical or subcortical networks. ICCs of all region pairs were calculated and z-transformed prior to group comparisons. FDG uptake of neurons, microglia, and astrocytes was determined in Grn(-/-) and WT mice via assessment of single cell tracer uptake (scRadiotracing).ResultsMicroglia depletion by CSF1R inhibition resulted in a strong decrease of metabolic connectivity defined by decrease of mean cortical ICCs in WT mice at both ages studied (6-7 m;p = 0.0148, 9-10 m;p = 0.0191), when compared to vehicle-treated age-matched WT mice. Grn(-/-), Trem2(-/-) and Grn(-/-)/Trem2(-/-) mice all displayed reduced FDG-PET signals when compared to WT mice. However, when analyzing metabolic networks, a distinct increase of ICCs was observed in Grn(-/-) mice when compared to WT mice in cortical (p < 0.0001) and hippocampal (p < 0.0001) networks. In contrast, Trem2(-/-) mice did not show significant alterations in metabolic connectivity when compared to WT. Furthermore, the increased metabolic connectivity in Grn(-/-) mice was completely suppressed in Grn(-/-)/Trem2(-/-) mice. Grn(-/-) mice exhibited a severe loss of neuronal FDG uptake (- 61%, p < 0.0001) which shifted allocation of cellular brain FDG uptake to microglia (42% in Grn(-/-) vs. 22% in WT).ConclusionsPresence, absence, and activation of microglia have a strong impact on metabolic connectivity of the mouse brain. Enhanced metabolic connectivity is associated with increased microglial FDG allocation

Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution

Various cellular sources hamper interpretation of positron emission tomography (PET) biomarkers in the tumor microenvironment (TME). We developed an approach of immunomagnetic cell sorting after in vivo radiotracer injection (scRadiotracing) with three-dimensional (3D) histology to dissect the cellular allocation of PET signals in the TME. In mice with implanted glioblastoma, translocator protein (TSPO) radiotracer uptake per tumor cell was higher compared to tumor-associated microglia/macrophages (TAMs), validated by protein levels. Translation of in vitro scRadiotracing to patients with glioma immediately after tumor resection confirmed higher single-cell TSPO tracer uptake of tumor cells compared to immune cells. Across species, cellular radiotracer uptake explained the heterogeneity of individual TSPO-PET signals. In consideration of cellular tracer uptake and cell type abundance, tumor cells were the main contributor to TSPO enrichment in glioblastoma;however, proteomics identified potential PET targets highly specific for TAMs. Combining cellular tracer uptake measures with 3D histology facilitates precise allocation of PET signals and serves to validate emerging novel TAM-specific radioligands

A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models

van Lengerich et al. developed a human TREM2 antibody with a transport vehicle (ATV) that improves brain exposure and biodistribution in mouse models. ATV:TREM2 promotes microglial energetic capacity and metabolism via mitochondrial pathways. Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody. In human induced pluripotent stem cell (iPSC)-derived microglia, ATV:TREM2 induced proliferation and improved mitochondrial metabolism. Single-cell RNA sequencing and morphometry revealed that ATV:TREM2 shifted microglia to metabolically responsive states, which were distinct from those induced by amyloid pathology. In an AD mouse model, ATV:TREM2 boosted brain microglial activity and glucose metabolism. Thus, ATV:TREM2 represents a promising approach to improve microglial function and treat brain hypometabolism found in patients with AD