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1. Intrauterine exposure to nicotine through maternal vaping disrupts embryonic lung and skeletal development via the Kcnj2 potassium channel

   https://doi.org/10.1016/j.ydbio.2023.06.002  

   Ozekin, Yunus H.; Saal, Maxwell L.; Pineda, Ricardo H.; Moehn, Kayla; Ordonez-Erives, Madison A.; Delgado Figueroa, Maria F.; Frazier, Caleb; Korth, Kamryn M.; Königshoff, Melanie; Bates, Emily A.; et al (September 2023, Developmental Biology)

   Smoking cigarettes during pregnancy is associated with adverse effects on infants including low birth weight, defective lung development, and skeletal abnormalities. Pregnant women are increasingly turning to vaping [use of electronic (e)-cigarettes] as a perceived safer alternative to cigarettes. However, nicotine disrupts fetal development, suggesting that like cigarette smoking, nicotine vaping may be detrimental to the fetus. To test the impact of maternal vaping on fetal lung and skeletal development in mice, pregnant dams were exposed to e-cigarette vapor throughout gestation. At embryonic day (E)18.5, vape exposed litter sizes were reduced and some embryos exhibited growth restriction compared to air exposed controls. Fetal lungs were collected for histology and whole transcriptome sequencing. Maternally nicotine vaped embryos exhibited histological and transcriptional changes consistent with impaired distal lung development. Embryonic lung gene expression changes mimicked transcriptional changes observed in adult mouse lungs exposed to cigarette smoke, suggesting that the developmental defects may be due to direct nicotine exposure. Fetal skeletons were analyzed for craniofacial and long bone lengths. Nicotine directly binds and inhibits the Kcnj2 potassium channel which is important for bone development. The length of the maxilla, palatal shelves, humerus, and femur were reduced in vaped embryos, which was further exacerbated by loss of one copy of the Kcnj2 gene. Nicotine vapor exposed Kcnj2KO/+ embryos also had significantly lower birth weights than unexposed animals of either genotype. Kcnj2 mutants had severely defective lungs with and without vape exposure, suggesting that potassium channels may be broadly involved in mediating the detrimental developmental effects of nicotine vaping. These data indicate that intrauterine nicotine exposure disrupts fetal lung and skeletal development likely through inhibition of Kcnj2. 

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2. Kalata B1 Enhances Temozolomide Toxicity to Glioblastoma Cells

   https://doi.org/10.3390/biomedicines12102216  

   Gerlach, Samantha L; Metcalf, James S; Dunlop, Rachael A; Banack, Sandra Anne; Her, Cheenou; Krishnan, Viswanathan V; Göransson, Ulf; Gunasekera, Sunithi; Slazak, Blazej; Cox, Paul Alan (October 2024, Biomedicines)

   Glioblastoma (GBM) is the most aggressive cancer originating in the brain, but unfortunately combination treatments with resection, radiation, and chemotherapy are relatively ineffective. Therefore, novel methods of adjuvant therapy are critically needed. Cyclotides are plant-derived circular peptides that chemosensitize drug-resistant breast cancer to doxorubicin. We analyzed naturally occurring and synthetic cyclotides (Cycloviolacin O3, Cycloviolacin O19, natural Kalata B1, synthetic Kalata B1, and Vitri E) alone and in co-exposure treatments with the drug temozolomide (TMZ) in human glioblastoma cells. The cyclotides were identified by UPLC-PDA and HPLC-UV. The synthetic Kalata B1 sequence was verified with orbitrap LC-MS, and structural confirmation was provided by NMR spectroscopy. The cyclotides displayed dose-dependent cytotoxicity (IC50 values 2.4–21.1 µM) both alone and as chemosensitizers of U-87 MG and T 98 cells to TMZ. In fact, a 16-fold lower concentration of TMZ (100 µM) was needed for significant cytotoxicity in U-87 MG cells co-exposed to synthetic Kalata B (0.5 µM). Similarly, a 15-fold lower concentration of TMZ (75 µM) was required for a significant reduction in cell viability in T 98 cells co-exposed to synthetic Kalata B1 (0.25 µM). Kalata B1 remained stable in human serum stability assays. The data support the assertion that cyclotides may chemosensitize glioblastoma cells to TMZ. 

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3. Effects of Copper on Legionella pneumophila Revealed via Viability Assays and Proteomics

   https://doi.org/10.3390/pathogens13070563  

   Song, Yang; Mena-Aguilar, Didier; Brown, Connor L; Rhoads, William J; Helm, Richard F; Pruden, Amy; Edwards, Marc A (July 2024, Pathogens)

   Cu is an antimicrobial that is commonly applied to premise (i.e., building) plumbing systems for Legionella control, but the precise mechanisms of inactivation are not well defined. Here, we applied a suite of viability assays and mass spectrometry-based proteomics to assess the mechanistic effects of Cu on L. pneumophila. Although a five- to six-log reduction in culturability was observed with 5 mg/L Cu2+ exposure, cell membrane integrity only indicated a <50% reduction. Whole-cell proteomic analysis revealed that AhpD, a protein related to oxidative stress, was elevated in Cu-exposed Legionella relative to culturable cells. Other proteins related to cell membrane synthesis and motility were also higher for the Cu-exposed cells relative to controls without Cu. While the proteins related to primary metabolism decreased for the Cu-exposed cells, no significant differences in the abundance of proteins related to virulence or infectivity were found, which was consistent with the ability of VBNC cells to cause infections. Whereas the cell-membrane integrity assay provided an upper-bound measurement of viability, an amoebae co-culture assay provided a lower-bound limit. The findings have important implications for assessing Legionella risk following its exposure to copper in engineered water systems. 

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4. Euler Transformation of Polyhedral Complexes

   https://doi.org/10.1142/S0218195920500090  

   Gupta, Prashant; Krishnamoorthy, Bala (January 2021, International Journal of Computational Geometry & Applications)

   null (Ed.)

   We propose an Euler transformation that transforms a given [Formula: see text]-dimensional cell complex [Formula: see text] for [Formula: see text] into a new [Formula: see text]-complex [Formula: see text] in which every vertex is part of the same even number of edges. Hence every vertex in the graph [Formula: see text] that is the [Formula: see text]-skeleton of [Formula: see text] has an even degree, which makes [Formula: see text] Eulerian, i.e., it is guaranteed to contain an Eulerian tour. Meshes whose edges admit Eulerian tours are crucial in coverage problems arising in several applications including 3D printing and robotics. For [Formula: see text]-complexes in [Formula: see text] ([Formula: see text]) under mild assumptions (that no two adjacent edges of a [Formula: see text]-cell in [Formula: see text] are boundary edges), we show that the Euler transformed [Formula: see text]-complex [Formula: see text] has a geometric realization in [Formula: see text], and that each vertex in its [Formula: see text]-skeleton has degree [Formula: see text]. We bound the numbers of vertices, edges, and [Formula: see text]-cells in [Formula: see text] as small scalar multiples of the corresponding numbers in [Formula: see text]. We prove corresponding results for [Formula: see text]-complexes in [Formula: see text] under an additional assumption that the degree of a vertex in each [Formula: see text]-cell containing it is [Formula: see text]. In this setting, every vertex in [Formula: see text] is shown to have a degree of [Formula: see text]. We also present bounds on parameters measuring geometric quality (aspect ratios, minimum edge length, and maximum angle of cells) of [Formula: see text] in terms of the corresponding parameters of [Formula: see text] for [Formula: see text]. Finally, we illustrate a direct application of the proposed Euler transformation in additive manufacturing. 

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5. The Beneficial Regulation of Extracellular Matrix and Heat Shock Proteins, and the Inhibition of Cellular Oxidative Stress Eects and Inflammatory Cytokines by 1-alpha, 25 dihydroxyvitaminD3 in Non-Irradiated and Ultraviolet Radiated Dermal Fibroblasts

   Philips, Neena; Ding, Xinxing; Kandalai, Pranathi; Marte, Ilonka; Krawczyk, Hunter; Richardson, Richard (August 2019, Cosmetics)

   null (Ed.)

   Intrinsic skin aging and photoaging, from exposure to ultraviolet (UV) radiation, are associated with altered regulation of genes associated with the extracellular matrix (ECM) and inflammation, as well as cellular damage from oxidative stress. The regulatory properties of 1-alpha, 25dihydroxyvitamin D3 (vitamin D) include endocrine, ECM regulation, cell differentiation, photoprotection, and anti-inflammation. The goal of this research was to identify the beneficial effects of vitamin D in preventing intrinsic skin aging and photoaging, through its direct effects as well as its effects on the ECM, associated heat shock proteins (HSP-47, and -70), cellular oxidative stress effects, and inflammatory cytokines [interleukin (IL)-1 and IL-8] in non-irradiated, UVA-radiated, UVB-radiated dermal fibroblasts. With regard to the ECM, vitamin D stimulated type I collagen and inhibited cellular elastase activity in non-irradiated fibroblasts; and stimulated type I collagen and HSP-47, and inhibited elastin expression and elastase activity in UVA-radiated dermal fibroblasts. With regard to cellular protection, vitamin D inhibited oxidative damage to DNA, RNA, and lipids in non-irradiated, UVA-radiated and UVB-radiated fibroblasts, and, in addition, increased cell viability of UVB-radiated cells. With regard to anti-inflammation, vitamin D inhibited expression of Il-1 and IL-8 in UVA-radiated fibroblasts, and stimulated HSP-70 in UVA-radiated and UVB-radiated fibroblasts. Overall, vitamin D is predominantly beneficial in preventing UVA-radiation induced photoaging through the differential regulation of the ECM, HSPs, and inflammatory cytokines, and protective effects on the cellular biomolecules. It is also beneficial in preventing UVB-radiation associated photoaging through the stimulation of cell viability and HSP-70, and the inhibition of cellular oxidative damage, and in preventing intrinsic aging through the stimulation of type I collagen and inhibition of cellular oxidative damage. 

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