7 vs 12.6, P = .02; 11.7 vs 13.1, P = .005) and in mini-AQLQ scores at 6 months (55.5 vs 64.2, P = .02). There were significant decreases in asthma-related emergency department visits at 6 months (0.6 vs 0, P less then .001) and in hospitalizations at 4 and 6 months (0.3 vs 0.1, P = .02; 0.3 vs 0, P = .002). Prednisone use decreased at 4 and 6 months (1.2 vs 0.6, P = .01; 1.2 vs 0.3, P less then .001). Conclusions ASTHMAXcel contributes to improved asthma knowledge and outcomes and to decreased health care utilization. ASTHMAXcel is an inexpensive, scalable aid for out-patient asthma management.To investigate the role of oxidative stress-induced DNA damage and mutagenesis in cellular senescence and immortalization, here we profiled spontaneous and methylene blue plus light-induced mutations in the cII gene from lambda phage in transgenic mouse embryonic fibroblasts during the transition from primary culture through senescence and immortalization. Consistent with detection of characteristic oxidized guanine lesions (8-oxodG) in the treated cells, we observed significantly increased relative cII mutant frequency in the treated pre-senescent cells, which was augmented in their immortalized counterparts. The predominant mutation type in the treated pre-senescent cells was GC→TA transversion, whose frequency was intensified in the treated immortalized cells. Conversely, the prevailing mutation type in the treated immortalized cells was AT→CG transversion, with a unique sequence-context specificity, i.e. flanking purines at the 5′ end of the mutated nucleotide. This mutation type was also enriched in the pre-senescent cells, although to a lower extent. selleck products The signature mutation of GC→TA transversions in the treated cells accorded with the well-established translesion synthesis bypass caused by 8-oxodG, and the hallmark AT→CG transversions conformed to the known replication errors due to oxidized guanine nucleosides (8-OHdGTPs). The distinctive features of oxidative stress-induced mutagenesis in the immortalized cells, which were present at attenuated levels, in spontaneously immortalized cells, provide insights into the underlying mechanisms of senescence bypass and immortalization. Our results have important implications for cancer biology because oxidized purines in the nucleoside pool can significantly contribute to genetic instability in DNA mismatch repair-defective human tumors.tRNA-derived small RNAs (tsRNAs) from spermatozoa could act as acquired epigenetic factors and contribute to offspring phenotypes. However, the roles of specific tsRNAs in early embryo development remain to be elucidated. Here, using pigs as a research model, we probed the tsRNA dynamics during spermatogenesis and sperm maturation, and demonstrate the delivery of tsRNAs from semen-derived exosomes to spermatozoa. By microinjection of antisense sequences into in vitro fertilized oocytes and subsequent single-cell RNA-seq of embryos, we identified a specific functional tsRNA group (termed here Gln-TTGs) that participate in the early cleavage of porcine preimplantation embryos, probably by regulating cell cycle-associated genes and retrotransposons. We conclude that specific tsRNAs present in mature spermatozoa play significant roles in preimplantation embryo development.Transmembrane proteins are membrane-anchored proteins whose topologies are important for their functions. These properties enable regulation of certain transmembrane proteins by regulated intramembrane proteolysis (RIP) and regulated alternative translocation (RAT). RIP enables a protein fragment of a transmembrane precursor to function at a new location, and RAT leads to an inverted topology of a transmembrane protein by altering the direction of its translocation across membranes during translation. RIP mediated by Site-1 protease (S1P) and Site-2 protease (S2P) are involved in proteolytic activation of membrane-bound transcription factors. In resting cells, these transcription factors remain in the endoplasmic reticulum (ER) as inactive transmembrane precursors. Upon stimulation by signals within the ER, they are translocated from the ER to the Golgi. There, they are cleaved first by S1P and then by S2P, liberating their N-terminal domains from membranes and enabling them to activate genes in the nucleus. This signaling pathway regulates lipid metabolism, unfolded protein responses, secretion of extracellular matrix proteins, and cell proliferation. Remarkably, ceramide-induced RIP of cAMP response element-binding protein 3-like 1 (CREB3L1) also involves RAT. In resting cells, RIP of CREB3L1 is blocked by transmembrane 4 L6 family member 20 (TM4SF20). Ceramide inverts the orientation of newly synthesized TM4SF20 in membranes through RAT, converting TM4SF20 from an inhibitor to an activator of RIP of CREB3L1. Here, I review recent insights into RIP of membrane-bound transcription factors, focusing on CREB3L1 activation through both RIP and RAT, and discuss current open questions about these two signaling pathways.The cell envelope of Gram-negative bacteria is a multilayered structure essential for bacterial viability; the peptidoglycan cell wall provides shape and osmotic protection to the cell, and the outer membrane serves as a permeability barrier against noxious compounds in the external environment. Assembling the envelope properly and maintaining its integrity is a matter of life and death for bacteria. Our understanding of the mechanisms of envelope assembly and maintenance has increased tremendously over the last two decades. Here, we review the major achievements during this time, giving central stage to the amino acid cysteine, one of the least abundant amino acid residues in proteins, whose unique chemical and physical properties often critically support biological processes. First, we review how cysteines contribute to envelope homeostasis by forming stabilizing disulfides in crucial bacterial assembly factors (LptD, BamA, and FtsN) and stress sensors (RcsF and NlpE). Second, we highlight the emerging role of enzymes that use cysteine residues to catalyze reactions that are necessary for proper envelope assembly, and we also explain how these enzymes are protected from oxidative inactivation. Finally, we suggest future areas of investigation, including a discussion of how cysteine residues could contribute to envelope homeostasis by functioning as redox switches. By highlighting the redox pathways that are active in the envelope of Escherichia coli, we provide a timely overview on the assembly of a cellular compartment that is the hallmark of Gram-negative bacteria.