Opioid-related xylazine toxicity manifesting as myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema.

This article provides a report of a case of organ dysfunction, myonecrosis, rhabdomyolysis, multifocal ischemic cerebral infarcts, and cerebral edema after a patient's use of xylazine and fentanyl. Within the US opioid epidemic, xylazine is emerging as a troubling national sub-story. The prevalence of xylazine within illicitly manufactured opioids and the proportion of opioid-involved overdose deaths with detected xylazine are rising dramatically, the latter increasing 276% between 2019 and 2022.

Loss of p19Arf promotes fibroblast survival during leucine deprivation.

Fibroblasts are quiescent and tumor suppressive in nature but become activated in wound healing and cancer. The response of fibroblasts to cellular stress has not been extensively investigated, however the p53 tumor suppressor has been shown to be activated in fibroblasts during nutrient deprivation. Since the p19 Alternative reading frame (p19Arf) tumor suppressor is a key regulator of p53 activation during oncogenic stress, we investigated the role of p19Arf in fibroblasts during nutrient deprivation.

Deletion of Calcineurin Promotes a Protumorigenic Fibroblast Phenotype.

Fibroblast activation is a crucial step in tumor growth and metastatic progression. Activated fibroblasts remodel the extracellular matrix (ECM) in primary tumor and metastatic microenvironments, exerting both pro- and antitumorigenic effects. However, the intrinsic mechanisms that regulate the activation of fibroblasts are not well-defined.

The calcineurin-NFAT pathway negatively regulates megakaryopoiesis.

The calcium regulated calcineurin-nuclear factor of activated T cells (NFAT) pathway modulates the physiology of numerous cell types, including hematopoietic. Upon activation, calcineurin dephosphorylates NFAT family transcription factors, triggering their nuclear entry and activation or repression of target genes. NFATc1 and c2 isoforms are expressed in megakaryocytes.

An unusual tRNAThr derived from tRNAHis reassigns in yeast mitochondria the CUN codons to threonine.

The standard genetic code is used by most living organisms, yet deviations have been observed in many genomes, suggesting that the genetic code has been evolving. In certain yeast mitochondria, CUN codons are reassigned from leucine to threonine, which requires an unusual tRNA(Thr) with an enlarged 8-nt anticodon loop ( ). To trace its evolutionary origin we performed a comprehensive phylogenetic analysis which revealed that evolved from yeast mitochondrial tRNA(His).

The canonical pathway for selenocysteine insertion is dispensable in Trypanosomes.

The micronutrient selenium is found in proteins as selenocysteine (Sec), the 21st amino acid cotranslationally inserted in response to a UGA codon. In vitro studies in archaea and mouse showed that Sec-tRNA(Sec) formation is a 3-step process starting with serylation of tRNA(Sec) by seryl-tRNA synthetase (SerRS), phosphorylation of serine to form phosphoserine (Sep)-tRNA(Sec) by phosphoseryl-tRNA(Sec) kinase (PSTK), and conversion to Sec-tRNA(Sec) by Sep-tRNA:Sec-tRNA synthase (SepSecS). However, a complete study of eukaryotic selenoprotein synthesis has been lacking.