John Edward Casida - Bibliography from JOHN EDWARD CASIDA. 22 December 1929 — 30 June 2018

John Edward Casida's research in pesticide toxicology led to more effective agricultural chemicals that are far safer for human and environmental health. He used pesticides as probes for his fundamental studies of metabolism and mode of action, resulting in great insight into biological chemistry and the underlying mechanisms of regulatory biology, ranging from voltage-gated sodium channels, through the ryanodine receptor and calcium regulation, the gamma-aminobutyric acid (GABA)-gated chloride channel, to the nicotinic acetylcholine receptors. These discoveries, among many others, have had a profound impact on pharmacology and toxicology. His research career started with the introduction of DDT into agricultural practice and continued to assist in the development of many pesticides that dominate the market today. John Casida trained multiple generations of toxicologists who obtained leading positions in government, industry and academics. He spent many of his formative years in Madison, Wisconsin, where he entered the University of Wisconsin, received his BS, MS and PhD and then joined the faculty to become a full professor six years later. He then moved to the Entomology Department at the University of California, Berkeley where he remained active in teaching and research until his death. He loved laboratory science and this, coupled with insatiable curiosity and a gift for finding the unexpected, led to papers from his laboratory sparkling with creativity. He similarly loved teaching at all levels and had just finished grading the final examination in his toxicology class at the time of his passing. John won numerous national and international awards and is widely viewed as the premiere pesticide toxicologist

Recombinant Arthromyces ramosus Peroxidase Has Similar Substrate Specificity Profiles as, but a Catalytic Efficiency up to 11-Fold Higher than, Horseradish Peroxidase

Fungal peroxidases are valuable enzymes. Arthromyces ramosus peroxidase (ARP) and horseradish peroxidase (HRP) share a conserved catalytic site. Both native ARP and recombinant ARP (rARP) were not commercially available. The substrate specificity and kinetic parameters of rARP and HRP were not well compared, particularly relevent to structure–activity relationship. In this work, rARP expressed by Komagataella phaffii had a production yield of 6.2 mg/L, up to 155-fold higher than ARP and other recombinant peroxidases, and a specific activity of 3240 units/mg toward 2,2′-azino-bis­(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), up to 29-fold higher than HRP and other peroxidases. The Michaelis constant (Km) and first-order rate constant (kcat) of rARP showed 10-fold substrate affinity and consequently 6-fold catalytic efficiency of HRP toward ABTS. Under optimal conditions, rARP shared similar substrate specificity profiles as commercial HRP; the second-order rate constants (kapp) of rARP showed 2–11-fold catalytic efficiency of HRP toward well-known peroxidase substrates. rARP’s higher catalytic efficiency was also in agreement with the shorter binding distance of H/N-His56 in rARP/substrate in comparison to that of HRP/substrate, as illustrated by docking simulation. The rARP had similar substrate specificity profiles as, but higher specific activity and catalytic efficiency than, HRP, which merits its further structure–functional characterization and applications

Anti-Neuroinflammatory Effects of a Semi-Synthetic Isoorientin-Based Glycogen Synthase Kinase-3β Inhibitor in Lipopolysaccharide-Activated Microglial Cells

Neuroinflammation contributes to the pathogenesis of several neurodegenerative disorders. Glycogen synthase kinase-3β (GSK-3β) regulates the release of proinflammatory cytokines and promotes inflammatory responses in immune cells. Microglia are the resident mononuclear immune cells of the central nervous system. Here, we investigated the anti-neuroinflammatory effects of (2S,3S,4R,5R,6S)-6-(2-(3,4-dimethoxyphenyl)-5,7-dimethoxy-4-oxo-4H-chromen-6-yl)-3,4,5-trihydroxy-N-((S)-1,1,1-trifluoropropan-2-yl)­tetrahydro-2H-pyran-2-carboxamide (TFGF-18), a semisynthetic GSK-3β inhibitor, in lipopolysaccharide (LPS) activation of spontaneously immortalized SIM-A9 microglial cells and of mouse cortical microglia. TFGF-18 at 2.5 μM concentration inhibited LPS-induced production of nitric oxide by 56.3% and the proinflammatory cytokines TNF-α and IL-1β by 28.3 and 59.2% in SIM-A9 cells, respectively, relative to the LPS treatment control group. Pretreatment of mouse primary microglial cells with TFGF-18 at 2.5 μM concentration led to a reduction of 58.7% in TNF-α+ microglial cells at 24 h post-LPS stimulation. The migration of LPS-activated SIM-A9 cells was also reduced by 26.7% with pretreatment of TFGF-18 in a scratch assay. Analyses of signaling pathways demonstrated that TFGF-18 led to the suppression of LPS-induced GSK-3β activation and p65/NF-κB activity. Furthermore, the co-culture of SIM-A9 with SH-SY5Y neuroblastoma cells showed the suppression of TFGF-18 to microglia-mediated neurotoxicity in vitro. The findings indicate strong inhibitory effects of TFGF-18 on LPS-induced microglia activation via regulation of GSK-3β and downstream p65/NF-κB signaling. The results suggest a potential role of TFGF-18 in neuroprotection via its anti-neuroinflammatory effect

Methyl Eugenol Binds Recombinant Gamma-Aminobutyric Acid Receptor-Associated Protein from the Western Flower Thrips <i>Frankliniella occidentalis</i>

The western flower thrips (Frankliniella occidentalis) is a major pest insect in agriculture. However, few insecticides are effective for their control. The recombinant gamma-aminobutyric acid receptor-associated protein (rGABARAP) was examined as a potential target of the monoterpenoids responsible for their insecticidal activities. The insecticidal activity of anethole, linalool, and methyl eugenol (ME) was evaluated in the laboratory. The half-maximum lethal concentration (LC50) of ME against second-instar nymphs of F. occidentalis was 5.5 mg/L using membrane and leaf immersion methods, while that of spinosyn A was 1.0 mg/L. The dissociation constants of ME binding to rGABARAP were 1.30 and 4.22 μmol/L, respectively, according to microscale thermophoresis (MST) and isothermal titration calorimetry (ITC) measurements. A molecular docking study showed interactions between ME and Tyr174 via π–π stacking. The MST and ITC experiments showed loss of specific binding between ME and the rGABARAPY174A mutant. Therefore, Tyr174 is a key amino acid residue of rGABARAP involving ME binding. The results revealed GABARAP as a potential target for the development of monoterpenoid insecticides

Cloning, Expression, and Functional Characterization of Two Highly Efficient Flavonoid-di‑<i>O</i>‑glycosyltransferases ZmUGT84A1 and ZmUGT84A2 from Maize (<i>Zea mays</i> L.)

The maize (Zea mays L.) glycosyltransferase family 1 comprises many uridine diphosphate glycosyltransferase (UGT) members. However, UGT activities and biochemical functions have seldom been revealed. In this study, the genes of two flavonoid di-O-glycosyltransferases ZmUGT84A1 and ZmUGT84A2 were cloned from maize plant and expressed in Escherichia coli. Phylogenetic analysis showed that the two enzymes were homologous to AtUGT84A1 and AtUGT84A3. The two recombinant enzymes showed a high conversion rate of luteolin to its glucosides, mainly 4′,7-di-O-glucoside and minorly 3′,7-di-O-glucoside in two-step glycosylation reactions in vitro. Moreover, the recombinant ZmUGT84A1 and ZmUGT84A2 had a broad substrate spectrum, converting eriodictyol, naringenin, apigenin, quercetin, and kaempferol to monoglucosides and diglucosides. The highly efficient ZmUGT84A1 and ZmUGT84A2 may be used as a tool for the effective synthesis of various flavonoid O-glycosides and as markers for crop breeding to increase O-glycosyl flavonoid content in food

Image2_Putative MicroRNA-mRNA Networks Upon Mdfi Overexpression in C2C12 Cell Differentiation and Muscle Fiber Type Transformation.TIF

Mdfi, an inhibitor of myogenic regulatory factors, is involved in myoblast myogenic development and muscle fiber type transformation. However, the regulatory network of Mdfi regulating myoblasts has not been revealed. In this study, we performed microRNAs (miRNAs)-seq on Mdfi overexpression (Mdfi-OE) and wild-type (WT) C2C12 cells to establish the regulatory networks. Comparative analyses of Mdfi-OE vs. WT identified 66 differentially expressed miRNAs (DEMs). Enrichment analysis of the target genes suggested that DEMs may be involved in myoblast differentiation and muscle fiber type transformation through MAPK, Wnt, PI3K-Akt, mTOR, and calcium signaling pathways. miRNA-mRNA interaction networks were suggested along with ten hub miRNAs and five hub genes. We also identified eight hub miRNAs and eleven hub genes in the networks of muscle fiber type transformation. Hub miRNAs mainly play key regulatory roles in muscle fiber type transformation through the PI3K-Akt, MAPK, cAMP, and calcium signaling pathways. Particularly, the three hub miRNAs (miR-335-3p, miR-494-3p, and miR-709) may be involved in both myogenic differentiation and muscle fiber type transformation. These hub miRNAs and genes might serve as candidate biomarkers for the treatment of muscle- and metabolic-related diseases.</p

Table4_Putative MicroRNA-mRNA Networks Upon Mdfi Overexpression in C2C12 Cell Differentiation and Muscle Fiber Type Transformation.XLSX

Mdfi, an inhibitor of myogenic regulatory factors, is involved in myoblast myogenic development and muscle fiber type transformation. However, the regulatory network of Mdfi regulating myoblasts has not been revealed. In this study, we performed microRNAs (miRNAs)-seq on Mdfi overexpression (Mdfi-OE) and wild-type (WT) C2C12 cells to establish the regulatory networks. Comparative analyses of Mdfi-OE vs. WT identified 66 differentially expressed miRNAs (DEMs). Enrichment analysis of the target genes suggested that DEMs may be involved in myoblast differentiation and muscle fiber type transformation through MAPK, Wnt, PI3K-Akt, mTOR, and calcium signaling pathways. miRNA-mRNA interaction networks were suggested along with ten hub miRNAs and five hub genes. We also identified eight hub miRNAs and eleven hub genes in the networks of muscle fiber type transformation. Hub miRNAs mainly play key regulatory roles in muscle fiber type transformation through the PI3K-Akt, MAPK, cAMP, and calcium signaling pathways. Particularly, the three hub miRNAs (miR-335-3p, miR-494-3p, and miR-709) may be involved in both myogenic differentiation and muscle fiber type transformation. These hub miRNAs and genes might serve as candidate biomarkers for the treatment of muscle- and metabolic-related diseases.</p

Table2_Putative MicroRNA-mRNA Networks Upon Mdfi Overexpression in C2C12 Cell Differentiation and Muscle Fiber Type Transformation.DOCX

Mdfi, an inhibitor of myogenic regulatory factors, is involved in myoblast myogenic development and muscle fiber type transformation. However, the regulatory network of Mdfi regulating myoblasts has not been revealed. In this study, we performed microRNAs (miRNAs)-seq on Mdfi overexpression (Mdfi-OE) and wild-type (WT) C2C12 cells to establish the regulatory networks. Comparative analyses of Mdfi-OE vs. WT identified 66 differentially expressed miRNAs (DEMs). Enrichment analysis of the target genes suggested that DEMs may be involved in myoblast differentiation and muscle fiber type transformation through MAPK, Wnt, PI3K-Akt, mTOR, and calcium signaling pathways. miRNA-mRNA interaction networks were suggested along with ten hub miRNAs and five hub genes. We also identified eight hub miRNAs and eleven hub genes in the networks of muscle fiber type transformation. Hub miRNAs mainly play key regulatory roles in muscle fiber type transformation through the PI3K-Akt, MAPK, cAMP, and calcium signaling pathways. Particularly, the three hub miRNAs (miR-335-3p, miR-494-3p, and miR-709) may be involved in both myogenic differentiation and muscle fiber type transformation. These hub miRNAs and genes might serve as candidate biomarkers for the treatment of muscle- and metabolic-related diseases.</p