The Piezo1 mechanosensitive ion channel is abundant on several elements of the central nervous system including astrocytes. It has been already demonstrated that activation of these channels is able to elicit calcium waves on astrocytes, which contributes to the release of gliotransmitters. Astrocyte- and N-methyl-D-aspartate (NMDA) receptor-dependent slow inward currents (SICs) are hallmarks of astrocyte–neuron communication. These currents are triggered by glutamate released as gliotransmitter, which in turn activates neuronal NMDA receptors responsible for this inward current having slower kinetics than any synaptic events. In this project, we aimed to investigate whether Piezo1 activation and inhibition is able to alter spontaneous SIC activity of murine neocortical pyramidal neurons. When the Piezo1 opener Yoda1 was applied, the SIC frequency and the charge transfer by these events in a minute time was significantly increased. These changes were prevented by treating the preparations with the NMDA receptor inhibitor D-AP5. Furthermore, Yoda1 did not alter the spontaneous EPSC frequency and amplitude when SICs were absent. The Piezo1 inhibitor Dooku1 effectively reverted the actions of Yoda1 and decreased the rise time of SICs when applied alone. In conclusion, activation of Piezo1 channels is able to alter astrocyte–neuron communication. Via enhancement of SIC activity, astrocytic Piezo1 channels have the capacity to determine neuronal excitability.

Background and Clinical Significance: Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a relatively novel entity, affecting single or multiple organ systems; it is characterized by aggregates of neoplastic cells of the histiocytic lineage, harboring molecular alterations in the ALK gene and exhibiting excellent response to systemic tyrosine kinase inhibitors. Case presentation: Herein, we present a pediatric case with cutaneous-only involvement: the 6-month-old male patient presented with an elevated, tan-colored lesion on his left forearm. Following surgical excision, histopathological evaluation reported spindle cells with wide eosinophilic cytoplasm and Touton-type giant cells. The tumor cells were positive for CD163, ALK, phosphorylated ERK, and cyclin D1. Fluorescent in situ hybridization revealed ALK rearrangement, whereas, upon next-generation sequencing, a DCTN1::ALK fusion was identified. Conclusion: Our case serves as a great addition to the limited number of cases reported in the literature, and it represents the first published pediatric case with the rare DCTN1::ALK fusion. The novelty of this genetic alteration and the lack of knowledge about its potential effects on the clinical aspects of ALK-positive histiocytosis highlight the importance of ancillary molecular testing, when available.

Childhood obesity may be associated with an accelerated loss of thermogenic adipocytes, increasing the risk of progressive lipid accumulation and metabolic deterioration. Early detection of the loss of thermogenic adipocytes would allow improved intervention to abrogate childhood obesity, yet reliable markers of human thermogenic adipocytes remain limited. We previously identified expression of FAM153A (family with sequence similarity 153 member A) in the developing human adipose tissue. Here, we investigated the expression pattern and potential association of FAM153A with the thermogenic transcriptional program in the adipose tissue of infants, children, and adolescents. We found that adipocyte FAM153A expression was triggered by beta adrenergic receptor stimulation, a key signal of adipocyte thermogenesis. FAM153A protein was confined to preadipocyte and adipocyte nuclei, and FAM153A mRNA expression positively correlated with the mRNA levels of canonical thermogenic adipocyte markers including uncoupling protein 1 (UCP1), myogenic differentiation 1 (MYOD1), type II iodothyronine deiodinase (DIO2), transmembrane protein 26 (TMEM26), Lim Homeobox 8 (LHX8), beta adrenergic receptor 2 (ADRB2), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A). Importantly, FAM153A expression was positively associated not only with the expression of individual thermogenic genes but also with their coordinated co-expression. Collectively, our findings identify FAM153A as a novel mRNA biomarker of human thermogenic adipocytes that serves as a robust indicator of the thermogenic transcriptional network.