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Liquid argon time-projection chambers (LArTPCs) have become a prominent tool for experiments in particle physics. Recent years have yielded significant advances in the techniques used to capture the signals generated by these cryogenic detectors. This article summarizes these novel developments for detection of ionization electrons and scintillation photons in LArTPCs. New methods to capture ionization signals address the challenges of scaling traditional techniques to the large scales necessary for future experiments. Pixelated readouts improve signal fidelity and expand the applicability of LArTPCs to higher-rate environments. Methods that leverage amplification in argon enable measurements in the keV regime and below. Techniques to enhance collection of argon scintillation photons improve calorimetry and expand the physics program for very large detectors. Future efforts aim to demonstrate systems for the combined detection of both electrons and photons.

Mast cells (MCs) expressing a distinctive protease phenotype (MCTs) selectively expand within the epithelium of human mucosal tissues during type 2 (T2) inflammation. While [MC.sub.T]s are phenotypically distinct from subepithelial MCs ([MC.sub.TC]s), signals driving human [MC.sub.T] differentiation and this subset's contribution to inflammation remain unexplored. Here, we have identified TGF-[beta] as a key driver of the [MC.sub.T] transcriptome in nasal polyps. We found that short-term TGF-[beta] signaling alters MC cell surface receptor expression and partially recapitulated the in vivo [MC.sub.T] transcriptome, while TGF- [beta] signaling during MC differentiation upregulated a larger number of [MC.sub.T]-associated transcripts. TGF-[beta] inhibited the hallmark [MC.sub.TC] proteases chymase and cathepsin G at both the transcript and protein level, allowing selective in vitro differentiation of [MC.sub.T]s for functional study. We identified discrete differences in effector phenotype between in vitro-derived [MC.sub.T]s and [MC.sub.TC]s, with [MC.sub.T]s exhibiting enhanced proinflammatory lipid mediator generation and a distinct cytokine, chemokine, and growth factor production profile in response to both innate and adaptive stimuli, recapitulating functional features of their tissue-associated counterpart MC subsets. Thus, our findings support a role for TGF-[beta] in promoting human [MC.sub.T] differentiation and identified a discrete contribution of this cell type to T2 inflammation., Introduction Mast cells (MCs) are tissue-resident granulocytes thought to play key roles in type 2 (T2) inflammatory diseases, including asthma and chronic rhinosinusitis (CRS). MCs originate from rare circulating progenitors [...]

"γc" cytokines are a family whose receptors share a "common-gamma-chain" signaling moiety, and play central roles in differentiation, homeostasis, and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines across all immunocyte lineages. The results reveal an unprecedented landscape: broader, with extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere) and essentially no effects unique to any one cytokine. Responses include a major downregulation component and a broad Myc-controlled resetting of biosynthetic and metabolic pathways. Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises were uncovered: IL2 effects in mast cells, shifts between follicular and marginal zone B cells, paradoxical and cell-specific cross-talk between interferon and γc signatures, or an NKT-like program induced by IL21 in CD8+ T cells.

The study published in the journal "Allergy" explores the expression of IL-5 receptors in human sinonasal epithelial cells. The research found that while these cells express IL-5Rα, they lack the CSF2RB co-receptor necessary for IL-5 signaling. This discovery suggests tissue-specific differences in IL-5 responsiveness between upper and lower airway epithelial cells, with implications for respiratory diseases and targeted therapies. The study also highlights potential variations in the efficacy of anti-IL-5 treatments for asthma and chronic rhinosinusitis with nasal polyps. [Extracted from the article]

Severe asthma and sinus disease are consequences of type 2 inflammation (T2I), mediated by interleukin (IL)-33 signaling through its membrane-bound receptor, ST2. Soluble (s)ST2 reduces available IL-33 and limits T2I, but little is known about its regulation. We demonstrate that prostaglandin E 2 (PGE 2) drives production of sST2 to limit features of lung T2I. PGE 2 -deficient mice display diminished sST2. In humans with severe respiratory T2I, urinary PGE 2 metabolites correlate with serum sST2. In mice, PGE 2 enhanced sST2 secretion by mast cells (MCs). Mice lacking MCs, ST2 expression by MCs, or E prostanoid (EP) 2 receptors by MCs showed reduced sST2 lung concentrations and strong T2I. Recombinant sST2 reduced T2I in mice lacking PGE 2 or ST2 expression by MCs back to control levels. PGE 2 deficiency also reversed the hyperinflammatory phenotype in mice lacking ST2 expression by MCs. PGE 2 thus suppresses T2I through MC-derived sST2, explaining the severe T2I observed in low PGE 2 states. [Display omitted] • PGE 2 is necessary to elevate sST2 levels in the lung with type 2 lung inflammation • Intraepithelial mast cells are the principal source of PGE 2 -driven lung sST2 production • Deficiency of mast-cell-derived sST2 exaggerates type 2 lung inflammation • PGE 2 alters the mast cell transcriptome and promotes short Il1rl1 expression Limiting IL-33-driven lung inflammation is a promising means of controlling asthma. Alhallak et al. demonstrate that prostaglandin E 2 modulates airway mucosal mast cells and enhances their production of soluble ST2 (IL-33 receptor) to limit asthma-associated lung inflammation. These findings may also help explain the severity of PGE 2 -low respiratory disease. [ABSTRACT FROM AUTHOR]