Whole transcriptome-sequencing and network analysis of CD1c+ human dendritic cells identifies cytokine-secreting subsets linked to type I IFN-negative autoimmunity to the eye

Background: Inflammatory subsets of CD1c+ conventional dendritic cells (CD1c+ DCs) are promoted by type I interferons (IFN), but the molecular basis for CD1c+ DCs involvement in conditions not driven by type I IFNs is unknown. Methods: Our objective was to use RNA-sequencing of blood CD1c+ DCs and high-dimensional flow cytometry of two cohorts of autoimmune uveitis patients and healthy donors to characterize the CD1c+ DCs population of type I IFN-negative autoimmune uveitis. Results: We report that the CD1c+ DCs pool from patients with autoimmune uveitis (n=45) is skewed towards a transcriptional network characterized by surface receptor genes CX3CR1, CCR2, and CD36. We confirmed the association of the transcriptional network with autoimmune uveitis by RNA-sequencing in another case-control cohort (n=35) and demonstrated that this network was governed by NOTCH2-RUNX3 signaling. Unbiased flow cytometry analysis based on the transcriptional network identified blood CD1c+ DC subsets that can be distinguished by CX3CR1 and CD36 surface expression. A CD36+CX3CR1+CD1c+ DC subset within the novel DC3 population was diminished in peripheral blood of patients, while CD1c+ DCs expressing CD36 and CX3CR1 accumulate locally in the inflamed eye. The CD36+CX3CR1+CD1c+ DC subset showed a differential capacity to produce cytokines, including TNF-alpha, IL-6, and VEGF, but not IL-23. Conclusion: These results show that CD1c+ DC subsets defined on the basis of surface expression of CD36 and CX3CR1 are linked to type I IFN-negative human autoimmune uveitis and show a differential capacity to secrete proinflammatory mediators that drive its pathophysiology.

The ‘Feel Good’ Event

Collective forms of affect shape the possibilities for selfhood and the affects engendered in encounters with others. This chapter examines two different types of collective affect shaping community development in Medan, Indonesia. A moral atmosphere of ‘each giving a share’ hangs over and infects programme activities, making volunteers sticky with suspicion and susceptible to arousing cynicism in others. In contrast, the affective practices of volunteers generate a different tone, engendering feelings that reaffirm their actions as making a positive difference in the lives of others. The collision between these forms of collective affect have two implications for power configurations in development. First, collective conditions determine the differential capacity/susceptibility to affect and be affected. Second, the ability to shape collective forms of affect often (but not always) map on to existing social hierarchies.

Compulsion

This chapter examines how the differential capacity to affect and susceptibility to be affected shapes citizens’ access to resources in Dehradun, India. In encounters between municipal councillors and their constituents, affects are engendered that animate, mobilize or compel the former to accede to the demands of the latter, or alternatively, to ignore them. Voters’ capacity to affect in these encounters is not even, with some voters able to demand and receive more than their legal entitlements, while others are unable to secure their basic rights. The capacity to affect is therefore an important, yet overlooked factor in citizens’ ability to gain access to resources and services from the government, or their ‘entitlements’. The uneven force of citizens’ capacity to affect municipal councillors has the potential to reinforce, as well as disrupt existing forms of privilege and disadvantage.

Determination of the Differential Capacity of Lithium-Ion Batteries by the Deconvolution of Electrochemical Impedance Spectra

Electrochemical impedance spectroscopy (EIS) is a powerful tool for investigating electrochemical systems, such as lithium-ion batteries or fuel cells, given its high frequency resolution. The distribution of relaxation times (DRT) method offers a model-free approach for a deeper understanding of EIS data. However, in lithium-ion batteries, the differential capacity caused by diffusion processes is non-negligible and cannot be decomposed by the DRT method, which limits the applicability of the DRT method to lithium-ion batteries. In this study, a joint estimation method with Tikhonov regularization is proposed to estimate the differential capacity and the DRT simultaneously. Moreover, the equivalence of the differential capacity and the incremental capacity is proven. Different types of commercial lithium-ion batteries are tested to validate the joint estimation method and to verify the equivalence. The differential capacity is shown to be a promising approach to the evaluation of the state-of-health (SOH) of lithium-ion batteries based on its equivalence with the incremental capacity.

Candida albicans and non-albicans Isolates from Bloodstream Have Different Capacities to Induce Neutrophil Extracellular Traps

Neutrophils activated with pathogens or their products induce formation of extracellular traps (NETs), but if this constitutes a general response against all pathogenic species in a single genus or intrageneric differences exist remains unknown, yet this is of great importance for the establishment of effective treatments. To determine this, we analyzed neutrophil extracellular traps formation after the stimulation with bloodstream isolates from different Candida species (Candida albicans, C. tropicalis, C. parapsilosis, and C. glabrata), and found that each species has a different capacity to induce DNA extrusion, which is independent of their morphology (yeast or hyphae). We observed that phospholipase producer’s strains and their secretion products were able to induce NETs, a property not observed with phospholipase deficient strains, with exception of some Candida glabrata sensu stricto isolates, which showed no NETs induction although they did show phospholipase production. To further analyze this, we extended our study to include Candida glabrata cryptic species (C. bracarensis and C. nivariensis) and no extracellular traps formation was observed. Here, we contribute to the understanding of how neutrophils initiate NETs, and we found that certain strains may have a differential capacity to trigger these structures, which may explain the high mortality of some isolates.