Author Report for: Cai YNo contact information in database for Cai Y
Yi F, An G, Song A, Cheng K, Liu J, Wang C, Wu S, Wang P, Zhu J and Cai Y <11 more author(s)> Yi F, An G, Song A, Cheng K, Liu J, Wang C, Wu S, Wang P, Zhu J, Liang Z, Chang Y, Chu Z, Cai C, Zhang X, Chen A, Xu J, Burritt DJ, Herrera-Estrella L, Tran LP, Li W, Cai Y (- 11) Ref: Plant Physiol, :, 2023 : PubMed ESTHER: Yi_2023_Plant.Physiol__ PubMedSearch: Yi 2023 Plant.Physiol PubMedID: 36718522 Abstract Verticillium wilt caused by Verticillium dahliae is a serious vascular disease in cotton (Gossypium spp.). V. dahliae induces the expression of the CAROTENOID CLEAVAGE DIOXYGENASE 7 (GauCCD7) gene involved in strigolactone (SL) biosynthesis in Gossypium australe, suggesting a role for SLs in Verticillium wilt resistance. We found that the SL analog rac-GR24 enhanced while the SL biosynthesis inhibitor TIS108 decreased cotton resistance to Verticillium wilt. Knock-down of GbCCD7 and GbCCD8b genes in island cotton (Gossypium barbadense) decreased resistance, whereas overexpression of GbCCD8b in upland cotton (Gossypium hirsutum) increased resistance to Verticillium wilt. Additionally, Arabidopsis (Arabidopsis thaliana) SL mutants defective in CCD7 and CCD8 putative orthologs were susceptible, whereas both Arabidopsis GbCCD7- and GbCCD8b-overexpressing plants were more resistant to Verticillium wilt than wild-type (WT) plants. Transcriptome analyses showed that several genes related to the jasmonic acid (JA)- and abscisic acid (ABA)-signaling pathways, such as MYELOCYTOMATOSIS 2 (GbMYC2) and ABA-INSENSITIVE 5, respectively, were up-regulated in the roots of WT cotton plants in responses to rac-GR24 and V. dahliae infection but down-regulated in the roots of both GbCCD7- and GbCCD8b-silenced cotton plants. Furthermore, GbMYC2 suppressed the expression of GbCCD7 and GbCCD8b by binding to their promoters, which might regulate the homeostasis of SLs in cotton through a negative feedback loop. We also found that GbCCD7- and GbCCD8b-silenced cotton plants were impaired in V. dahliae-induced reactive oxygen species (ROS) accumulation. Taken together, our results suggest that SLs positively regulate cotton resistance to Verticillium wilt through crosstalk with the JA and ABA-signaling pathways and by inducing ROS accumulation. Title: Sublethal Effects of Thiamethoxam on Biological Traits and Detoxification Enzyme Activities in the Small Brown Planthopper, Laodelphax striatellus (Falln) Cai Y, Dou T, Gao F, Wang G, Dong Y, Song N, An S, Yin X, Liu X, Ren Y Ref: J Econ Entomol, :, 2022 : PubMed ESTHER: Cai_2022_J.Econ.Entomol__ PubMedSearch: Cai 2022 J.Econ.Entomol PubMedID: 36351784 Abstract The small brown planthopper (Laodelphax striatellus (Falln), Hemiptera: Delphacidae), is an important agricultural pest of rice, and neonicotinoid insecticides are commonly used for controlling L. striatellus. However, the sublethal effects of thiamethoxam on L. striatellus remain relatively unknown. In this study, an age-stage life table procedure was used to evaluate the sublethal effects of thiamethoxam on the biological parameters of L. striatellus. Additionally, activities of carboxylesterase, glutathione S-transferase, and cytochrome P450 monooxygenase in the third instar nymphs were analyzed. The results indicated that the survival time of F0 adults and the fecundity of female adults decreased significantly after the third instar nymphs were treated with sublethal concentrations of thiamethoxam (LC15 0.428 mg/liter and LC30 0.820 mg/liter). The developmental duration, adult preoviposition period, total preoviposition period, and mean generation time of the F1 generation increased significantly, whereas the fecundity of the female adults, intrinsic rate of increase (ri), and finite rate of increase (Lambda) decreased significantly. The oviposition period was significantly shorter for the insects treated with LC30 than for the control insects. Neither sublethal concentrations had significant effects on the adult longevity, net reproduction rate (R0), or gross reproduction rate (GRR) of the F1 generation. The activities of carboxylesterase, glutathione-S-transferase, and cytochrome P450 monooxygenase increased significantly after the thiamethoxam treatments. These results indicate that sublethal concentrations of thiamethoxam can inhibit L. striatellus population growth and enhance detoxification enzyme activities. Title: Design, synthesis, and evaluation of 8-aminoquinoline-melatonin derivatives as effective multifunctional agents for Alzheimer's disease Chen Z, Yu X, Chen L, Xu L, Cai Y, Hou S, Zheng M, Liu F Ref: Ann Transl Med, 10:303, 2022 : PubMed ESTHER: Chen_2022_Ann.Transl.Med_10_303 PubMedSearch: Chen 2022 Ann.Transl.Med 10 303 PubMedID: 35433950 Abstract BACKGROUND: Alzheimer's disease (AD) is thought to be a complex, multifactorial syndrome with many related molecular lesions contributing to its pathogenesis. Thus, multi-target-directed ligands are considered an effective way of treating AD. This study sought to evaluate 8-aminoquinoline-melatonin derivatives as effective multifunctional agents for AD. METHODS: Thioflavin-T fluorescence assays were used to detect the inhibitory potency of 8-aminoquinoline-melatonin hybrids (a1-a5, b1-b5, and c1-c5) on self- and acetylcholinesterase (AChE)-induced amyloid-beta (Abeta) aggregation. The AChE and butyrylcholinesterase (BuChE) inhibitory potency within the compounds was evaluated by Ellman's assays. Methyl thiazolyl tetrazolium (MTT) assays were performed to evaluate the cytotoxicity of the compounds to C17.2 cells. MTT assay was used to detect the cell viability of HT22 cells to evaluate the antioxidant effect of the compounds. Metal chelation property was measured by ultraviolet-visible spectrophotometry. RESULTS: Compounds c3 and c5 had superior inhibitory activity against self-induced Abeta aggregation (with inhibitory rates of 41.4+/-2.1 and 25.5+/-3.2 at 10 microM, respectively) compared to the other compounds. Compounds in the carbamate group (i.e., a4, a5, b4, b5, c4, and c5) showed significant BuChE inhibitory activity and excellent selectivity over AChE. Most of the compounds exhibited low cytotoxicity in the C17.2 cells. Notably, a2, a3, b2, and b3 and series c (c1-c5) exhibited strong protective effects. Additionally, a3 and c1 specifically chelated with copper ions. CONCLUSIONS: Taking all of the promising results together, 8-aminoquinoline-melatonin hybrids can serve as lead molecules in the further development of new multi-functional anti-AD agents. Title: Safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor: a singlecenter, phase I study in healthy young and elderly Chinese subjects Qian H, Yu C, Zhu H, Ding Q, Cai Y, Jing J, Xu X, Guo R, Zhang H and Liu Y <2 more author(s)> Qian H, Yu C, Zhu H, Ding Q, Cai Y, Jing J, Xu X, Guo R, Zhang H, Liu H, Chen X, Liu Y (- 2) Ref: ResearchSquare, :, 2022 : PubMed ESTHER: Qian_2022_ResearchSquare__ PubMedSearch: Qian 2022 ResearchSquare Inhibitor(s) related to this paper: Fluoropezil Abstract https://www.researchsquare.com/article/rs-1744060/latest.pdf Background Acetylcholinesterase (AChE) inhibitors attempt to reduce the breakdown of acetylcholine levels in the brain of patients with Alzheimers disease (AD) by inhibiting the responsible enzyme AChE in the synaptic cleft. This study evaluated the safety, tolerability, and pharmacokinetics of fluoropezil (DC20), a novel AChE inhibitor under development for the treatment of AD in healthy young and elderly Chinese subjects. Methods The study on young subjects were divided into two arms: the multiple ascending-dose (MAD) arm (double-blind, randomized, placebo-controlled, multiple ascending-dose, 2 and 6 mg, N = 24), and the food effect arm (three-period, self-crossover, open-labeled, fasting/standard diet/high-fat diet administration, 4 mg, N = 12). A two-period, self-crossover, open-labeled, single ascending-dose study was designed for elderly subjects (2 and 4 mg, N = 11). Results For young subjects study: In the MAD arm, the accumulation ratios of DC20 in vivo were 2.29 and 2.15, respectively. In the food effect arm, compared with fasting administration, area under the concentrationtime curve from zero to t (AUC0-t) orally after a standard diet and high-fat diet slightly increased by about 19% and 29% and the Tmax were delayed by around 1 hour. For elderly subjects study, Tmax were 1.5 and 1.25 hour, t1/2 were 77.1 and 74.2 hour, respectively. After oral administration of DC20 in healthy young and elderly subjects, no serious adverse events occurred, the most common adverse events associated with the study drug were gastrointestinal reactions. Conclusion We predicted the safety risks of DC20 in the clinical treatment of AD, which were well tolerated by the healthy young and elderly subjects. The elimination of DC20 from the body was slower in elderly subjects than in young subjects. Title: Capsulation of AuNCs with AIE Effect into Metal-Organic Framework for the Marriage of a Fluorescence and Colorimetric Biosensor to Detect Organophosphorus Pesticides Cai Y, Zhu H, Zhou W, Qiu Z, Chen C, Qileng A, Li K, Liu Y Ref: Analytical Chemistry, :, 2021 : PubMed ESTHER: Cai_2021_Anal.Chem__ PubMedSearch: Cai 2021 Anal.Chem PubMedID: 33957044 Abstract Organophosphorus pesticides (OPs) can inhibit the activity of acetylcholinesterase (AChE) to induce neurological diseases. It is significant to exploit a rapid and sensitive strategy to monitor OPs. Here, a metal-organic framework (MOF) acted as a carrier to encapsulate AuNCs, which can limit the molecular motion of AuNCs, trigger the aggregation-induced emission (AIE) effect, and exhibit a strong fluorescence with a fluorescence lifetime and quantum yield of 6.83 micros and 4.63%, respectively. Then, the marriage of fluorescence and colorimetric signals was realized on the basis of the dual function of the enzymolysis product from AChE and choline oxidase (CHO) on AuNCs@ZIF-8. First, it can decompose ZIF-8 to weaken the restraint on AuNCs, and thus the fluorescence receded. Second, it can be used as a substrate for the peroxidase mimics of the released AuNCs to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) and a visible blue appeared. Thus, on the basis of the inhibition of AChE activity by OPs, a fluorescence-colorimetric dual-signal biosensor was established. In addition, colorimetric paper strips were exploited to realize a visual semiquantitative detection, and a smartphone APP was developed to make the visualization results more precise and realize real-time supervision of pesticide contamination. Title: Combined toxicity of micro/nano scale polystyrene plastics and ciprofloxacin to Corbicula fluminea in freshwater sediments Guo X, Cai Y, Ma C, Han L, Yang Z Ref: Sci Total Environ, 789:147887, 2021 : PubMed ESTHER: Guo_2021_Sci.Total.Environ_789_147887 PubMedSearch: Guo 2021 Sci.Total.Environ 789 147887 PubMedID: 34051493 Abstract Plastic pollution has become a global environmental threat, and its potential to affect the bioavailability and toxicity of pharmaceuticals to aquatic organism are of growing concern. However, little is known regarding the combined toxicity of micro/nano-plastics and pharmaceuticals to benthic organisms in sediments. Thus, we employed a freshwater benthic bivalve, Corbicula fluminea (C. fluminea), to investigate the individual and co-toxicity of model plastics, microscopic fluorescent polystyrene (PS) (PS nano-plastic (PS-NP) and PS micro-plastic (PS-MP), 80 nm and 6 microm, respectively) and the common antibiotic ciprofloxacin (CIP) in formulated sediments. Our results suggest that oxidative damage and neurotoxicity were confirmed to occur in C. fluminea in all the treatments. The oxidative damage in the digestive glands reduced the clam ability to scavenge free radicals, causing severe tissue damage to the digestive glands of C. fluminea. Filtration rates of C. fluminea were significantly decreased in a concentration-dependent manner across all the treatments, which might be due to the inhibition of acetylcholinesterase activities. Interactions between CIP and micro/nano-plastic were observed, whereby the presence of PS decreased the toxicity of CIP in the digestive glands but aggravated the C. fluminea siphoning inhibition rate in the nano-plastic co-treatments group; in addition, the CIP toxicity to C. fluminea decreased because that the concentration of free dissolved CIP was lowered by micro/nano-PS. Taken together, the current study could contribute greatly to evaluating the ecological risk of CIP and PS in aquatic environments and sheds light on potential issues of food safety caused by both emerging pollutants. Title: Soluble Epoxide Hydrolase Deletion Attenuated Nicotine-induced Arterial Stiffness via Limiting the Loss of SIRT1 Hu S, Luo J, Fu M, Luo L, Cai Y, Li W, Li Y, Dong R, Yang Y and Xu X <1 more author(s)> Hu S, Luo J, Fu M, Luo L, Cai Y, Li W, Li Y, Dong R, Yang Y, Tu L, Xu X (- 1) Ref: American Journal of Physiology Heart Circ Physiol, :, 2021 : PubMed ESTHER: Hu_2021_Am.J.Physiol.Heart.Circ.Physiol__ PubMedSearch: Hu 2021 Am.J.Physiol.Heart.Circ.Physiol PubMedID: 34142887 Abstract Arterial stiffness, a consequence of smoking, is an underlying risk factor of cardiovascular diseases. Epoxyeicosatrienoic acids (EETs), hydrolyzed by soluble epoxide hydrolase (sEH), have beneficial effects against vascular dysfunction. However, the role of sEH knockout in nicotine-induced arterial stiffness was not characterized. We hypothesized that sEH knockout could prevent nicotine-induced arterial stiffness. In the present study, Ephx2 (the gene encodes sEH enzyme) null (Ephx2(-/-)) mice and wild-type (WT) littermate mice were infused with or without nicotine and administered with or without nicotinamide (NAM, SIRT1 inhibitor) simultaneously for four weeks. Nicotine treatment increased sEH expression and activity in the aortas of WT mice. Nicotine infusion significantly induced vascular remodeling, arterial stiffness, and SIRT1 deactivation in WT mice, which was attenuated in Ephx2(-/-) mice without NAM treatment. However, the arterial protective effects were gone in Ephx2(-/-) mice with NAM treatment. In vitro, 11,12-EET treatment attenuated nicotine-induced MMP2 upregulation via SIRT1-mediated YAP deacetylation. In conclusion, sEH knockout attenuated nicotine-induced arterial stiffness and vascular remodeling via SIRT1-induced YAP deacetylation. Title: Inhibition of soluble epoxide hydrolase alleviates insulin resistance and hypertension via downregulation of SGLT2 in the mouse kidney Luo J, Hu S, Fu M, Luo L, Li Y, Li W, Cai Y, Dong R, Yang Y and Xu X <1 more author(s)> Luo J, Hu S, Fu M, Luo L, Li Y, Li W, Cai Y, Dong R, Yang Y, Tu L, Xu X (- 1) Ref: Journal of Biological Chemistry, :100667, 2021 : PubMed ESTHER: Luo_2021_J.Biol.Chem__100667 PubMedSearch: Luo 2021 J.Biol.Chem 100667 PubMedID: 33864813 Abstract The epoxyeicosatrienoic acid (EET) exerts beneficial effects on insulin resistance and/or hypertension. EETs could be readily converted to less biological active diols by soluble epoxide hydrolase (sEH). However, whether sEH inhibition can ameliorate the comorbidities of insulin resistance and hypertension, and the underlying mechanisms of this relationship, are unclear. In this study, C57BL/6 mice were rendered hypertensive and insulin resistant through a high-fat and high-salt (HF-HS) diet. The sEH inhibitor trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was used to treat mice (1 mg/kg/d) for 8 weeks, followed by analysis of metabolic parameters. The expression of sEH and the sodium-glucose cotransporter 2 (SGLT2) were markedly upregulated in the kidneys of mice fed a HF-HS diet. We found that TPPU administration increased kidney EET levels, improved insulin resistance, and reduced hypertension. Furthermore, TPPU treatment prevented upregulation of SGLT2, and the associated increased urine volume and the excretion of urine glucose and urine sodium. Importantly, TPPU alleviated renal inflammation. In vitro, human renal proximal tubule epithelial cells (HK-2 cells) were used to further investigate the underlying mechanism. We observed that 14,15-EET or sEH knock-down or inhibition prevented the upregulation of SGLT2 upon treatment with palmitic acid or NaCl by inhibiting the IKKalpha/beta/NF-kappaB signaling pathway. In conclusion, sEH inhibition by TPPU alleviated insulin resistance and hypertension induced by a HF-HS diet in mice. The increased urine excretion of glucose and sodium was mediated by decreased renal SGLT2 expression due to inactivation of the IKKalpha/beta/NF-kappaB-induced inflammatory response. Title: Red ginseng has stronger anti-aging effects compared to ginseng possibly due to its regulation of oxidative stress and the gut microbiota Peng X, Hao M, Zhao Y, Cai Y, Chen X, Chen H, Zhang Y, Dong L, Liu X and Luo Y <3 more author(s)> Peng X, Hao M, Zhao Y, Cai Y, Chen X, Chen H, Zhang Y, Dong L, Liu X, Ding C, Liu W, Yang M, Luo Y (- 3) Ref: Phytomedicine, 93:153772, 2021 : PubMed ESTHER: Peng_2021_Phytomedicine_93_153772 PubMedSearch: Peng 2021 Phytomedicine 93 153772 PubMedID: 34753028 Abstract BACKGROUND: Panax ginseng (PG) and red ginseng (RG) are considered to be effective anti-aging treatments. However, evidence of their therapeutic mechanisms and difference in anti-aging effects is lacking. PURPOSE: To explore the potential therapeutic mechanisms of RG and PG in brain damage in D-Gal-induced aging mice, and evaluate the difference in anti-aging effects caused by their compositional differences. METHODS: We first tested the chemical components in PG and RG. In D-Gal aging mouse model, RG and PG (800 mg/kg) were orally administered for 9 weeks. The mice performed the Radial Arm Maze (RAM) behavior test. We collected blood, brain tissue, and fecal samples and performed biochemical analysis, histological examination, western blot, and Illumina MiSeq sequencing analysis. RESULTS: The results of component analysis showed that the total polyphenols and rare ginsenosides were present in RG in 3.2, and 2.2 fold greater concentrations, respectively, compared to PG, while the proportion of non-starch polysaccharides in the crude polysaccharides of RG was 1.94 fold greater than that of PG. In D-Gal-induced aging mice, both PG and RG could prevent the increase in acetylcholinesterase (AChE), and malondialdehyde (MDA) levels, and improved the expression of superoxide dismutase (SOD), and catalase (CAT) in the serum. Meanwhile, both PG and RG could ameliorate brain tissue architecture and behavioral trial. In addition, the D-Gal-induced translocation of nuclear factor-kappaB (NF-kappaB), as well as activation of the pro-apoptotic factors Caspase-3 and the PI3K/Akt pathways were inhibited by PG and RG. Overall, both PG and RG exerted anti-aging effects, with RG stronger than PG. Finally, although both PG and RG regulated the diversity of gut microbes, RG appeared to aggravate the increase in probiotics, such as Bifidobacterium and Akkermania, and the decrease in inflammatory bacteria to a greater extent compared to PG. CONCLUSION: Our results suggest that RG is more conducive to delay the D-Gal-induced aging process than PG, with possible mechanisms including beneficial changes in brain structure, cognitive functions, oxidative stress inhibition, and gut microbiome structure and diversity than PG, These mechanisms may rely on the presence of more total polyphenols, rare ginsenosides and non-starch polysaccharides in RG. Title: Gene Expression, Biochemical Characterization of a sn-1, 3 Extracellular Lipase From Aspergillus niger GZUF36 and Its Model-Structure Analysis Xing S, Zhu R, Cheng K, Cai Y, Hu Y, Li C, Zeng X, Zhu Q, He L Ref: Front Microbiol, 12:633489, 2021 : PubMed ESTHER: Xing_2021_Front.Microbiol_12_633489 PubMedSearch: Xing 2021 Front.Microbiol 12 633489 PubMedID: 33776965 Gene_locus related to this paper: aspng-EXANL1 Abstract In this study, a sn-1, 3 extracellular lipases from Aspergillus niger GZUF36 (PEXANL1) was expressed in Pichia pastoris, characterized, and the predicted structural model was analyzed. The optimized culture conditions of P. pastoris showed that the highest lipase activity of 66.5 +/- 1.4 U/mL (P < 0.05) could be attained with 1% methanol and 96 h induction time. The purified PEXANL1 exhibited the highest activity at pH 4.0 and 40 degreesC temperature, and its original activity remained unaltered in the majority of the organic solvents (20% v/v concentration). Triton X-100, Tween 20, Tween 80, and SDS at a concentration of 0.01% (w/v) enhanced, and all the metal ions tested inhibited activity of purified PEXANL. The results of ultrasound-assisted PEXANL1 catalyzed synthesis of 1,3-diaglycerides showed that the content of 1,3-diglycerides was rapidly increased to 36.90% with 25 min of ultrasound duration (P < 0.05) and later decreased to 19.93% with 35 min of ultrasound duration. The modeled structure of PEXANL1 by comparative modeling showed alpha/beta hydrolase fold. Structural superposition and molecular docking results validated that Ser162, His274, and Asp217 residues of PEXANL1 were involved in the catalysis. Small-angle X-ray scattering analysis indicated the monomer properties of PEXANL1 in solution. The ab initio model of PEXANL1 overlapped with its modeling structure. This work presents a reliable structural model of A. niger lipase based on homology modeling and small-angle X-ray scattering. Besides, the data from this study will benefit the rational design of suitable crystalline lipase variants in the future. Title: Astilbin ameliorates oxidative stress and apoptosis in D-galactose-induced senescence by regulating the PI3K/Akt/m-TOR signaling pathway in the brains of mice Zhang Y, Ding C, Cai Y, Chen X, Zhao Y, Liu X, Zhang J, Sun S, Liu W Ref: Int Immunopharmacol, 99:108035, 2021 : PubMed ESTHER: Zhang_2021_Int.Immunopharmacol_99_108035 PubMedSearch: Zhang 2021 Int.Immunopharmacol 99 108035 PubMedID: 34435579 Abstract An increasing amount of evidence has shown that injection of D-galactose (D-gal) can mimic natural aging that typically is associated with brain injury. Oxidative stress and apoptosis has been shown to play an essential role in aging process. The purpose of this study was to investigate the protective effectsof astilbin (ASB) on D-Gal-induced agingin miceand to further explore the underlying mechanisms. We randomly divided 50 mice into 5 groups.To establish this model of aging, 40micewere intraperitoneally administered D-Gal (500 mg/kg). The mice in the treatmentgroupswere intragastricaly administratedASB at doses of 40 and 80 mg/kg. H&E and TUNEL staining were used to determine the effect of ASB on the number of apoptotic cells in the brain. Furthermore, biochemical indices of serum, oxidative stress factors, and apoptosis factors were determined to clarify the underlying mechanism using reagent test kits and western blotting. The results showed that varying doses of ASB could improve D-Gal-induced histopathological damageand significantly alleviatedthe aging induced by D-Galin mice. ASB remarkably decreased the activities of malondialdehyde (MDA)(p < 0.01)and Acetyl cholinesterase (AChE)(p < 0.05) and markedlyincreased the content of catalase (CAT)(p < 0.01)and superoxide dismutase (SOD)(p < 0.01), respectively. In addition, Western blotting revealed thatASB treatment (40 mg/kg)attenuated the D-gal-induced Bax and Caspase 3 protein expression(p < 0.01) and reversed the increase in Bcl-2protein expressionin brain. Moreover, ASB treatment significantly upregulated the protein expression ofp-PI3K/PI3K and altered the p-Akt/Akt ratio (p < 0.05), while inhibiting the expression of p-m-TOR relative to m-TOR(p < 0.05). Moreover, the expression of P53 tended to decreasein the low ASB treatmentgroup (40 mg/kg), whereas no change was observed in the high ASB treatmentgroup (80 mg/kg). In the intestinal flora, the richness of the normal group and the ASB group was higher than that of the D-Gal group. Heat map analysis also showed that ASB promoted Lactobacillus and other probiotics and also confirmed the advantages of ASB. The observed changes in intestinal flora further verified the efficacy of ASB. Title: Effect of cross-linked enzyme aggregate strategy on characterization of sn-1,3 extracellular lipase from Aspergillus niger GZUF36 Zhu R, Li C, Chen C, Xing S, Cai Y, Zeng X, He L Ref: Applied Microbiology & Biotechnology, :, 2021 : PubMed ESTHER: Zhu_2021_Appl.Microbiol.Biotechnol__ PubMedSearch: Zhu 2021 Appl.Microbiol.Biotechnol PubMedID: 33559718 Abstract The sn-1,3 extracellular lipase from Aspergillus niger GZUF36 (EXANL1) has important potential applications. The cross-linked enzyme aggregate (CLEA) of purified EXANL1 (CLEA-EXANL1) achieved optimum activity recovery (148.5 +/- 0.9%), immobilization yield (100 +/- 0%), and recovered activity (99.7 +/- 0.6%) with 80% tert-butanol as the precipitant, glutaraldehyde (GA) concentration of 30 mM, GA treatment time of 1.5 h, and centrifugal speed of 6000xg. The effect of CLEA strategy on the characterization of EXANL1 was evaluated in this work. CLEA-EXANL1 exhibited a broader optimum pH range (4-6) compared with free EXANL1 (6.5). CLEA-EXANL1 presented optimum activity at 40 degreesC, which was 5 degreesC higher than that of free EXANL1. CLEA strategy decreased the maximum reaction rate and increased the Michaelis-Menten constant of EXANL1 when olive oil emulsion was used as a substrate. Moreover, after 30 days, free EXANL1 lost more than 80.0% of its activity, whereas CLEA-EXANL1 retained more than 90.0% of its activity. CLEA strategy improved the tolerance of EXANL1 in polar organic solvents. Fourier transform infrared spectroscopy results showed that the CLEA technique increased the contents of beta-sheets and beta-turns in EXANL1 and reduced those of alpha-helixes and irregular crimps. CLEA strategy caused no change in the sn-1,3 selectivity of EXANL1. Therefore, EXANL1 in the form of CLEA is a valuable catalyst in the synthesis of 1,3-diacylglycerol. KEY POINTS: Cross-linked enzyme aggregate (CLEA) strategy broadened the optimum pH range of sn-1,3 extracellular lipase from Aspergillus niger GZUF36 (EXANL1). CLEA strategy improved the tolerance of EXANL1 in polar organic solvents. CLEA strategy caused no change in the positional selectivity of EXANL1. Title: Enzyme-Triggered Disassembly of Perylene Monoimide-based Nanoclusters for Activatable and Deep Photodynamic Therapy Cai Y, Ni D, Cheng W, Ji C, Liu Y, Su Z, Chen C, Yin M, Mullen K, Wang Y Ref: Angew Chem Int Ed Engl, :, 2020 : PubMed ESTHER: Cai_2020_Angew.Chem.Int.Ed.Engl__ PubMedSearch: Cai 2020 Angew.Chem.Int.Ed.Engl PubMedID: 32363672 Abstract Photodynamic therapy (PDT) exhibits great potential for cancer therapy, but still suffers from nonspecific photosensitivity and poor penetration of photosensitizer. Here, a smart perylene monoimide-based nanocluster with enzyme-triggered disassembly is reported as an activatable and deeply penetrable photosensitizer. A novel carboxylesterase (CE)-responsive tetrachloroperylene monoimide (P1) was synthesized and assembled with folate-decorated albumins into a nanocluster ( FHP ) with a diameter of ~100 nm. Once P1 is hydrolyzed by the tumor-specific CE, FHP disassembles into ultrasmall nanoparticles (~10 nm), facilitating the deep tumor penetration of FHP . Furthermore, such enzyme-triggered disassembly of FHP leads to enhanced fluorescence intensity (~8-fold) and elevated singlet oxygen generation ability (~4-fold), enabling in situ near-infrared fluorescence imaging and promoted PDT. FHP permits remarkable tumor inhibition in vivo with minimal side effects through imaging-guided, activatable, and deep PDT. This work confirms that this cascaded multifunctional control via enzyme-triggered molecular disassembly is an effective strategy for precise cancer theranostics. Title: Cadmium exposure affects growth performance, energy metabolism, and neuropeptide expression in Carassius auratus gibelio Cai Y, Yin Y, Li Y, Guan L, Zhang P, Qin Y, Wang Y Ref: Fish Physiol Biochem, 46:187, 2020 : PubMed ESTHER: Cai_2020_Fish.Physiol.Biochem_46_187 PubMedSearch: Cai 2020 Fish.Physiol.Biochem 46 187 PubMedID: 31612298 Abstract Cadmium (Cd) is the most abundant heavy metal in aquatic environments and is easily detected on a global scale. Carassius auratus gibelio is a common aquaculture species. The aim of this study was to explore the toxic effects of 1, 2, and 4 mg/L Cd on the energy metabolism, growth performance, and neurological responses of C. gibelio. After 30 days of exposure, Cd concentrations in the liver and brain were significantly increased in Cd-exposed groups. Low-level Cd exposure (1 mg/L) increased weight and length gains, as well as food intake, in the fish. Acetylcholinesterase activity decreased significantly in the Cd-exposed groups. Energy metabolism levels (as reflected by oxygen consumption, ammonia excretion rate, and swimming activity), as well as serum T3 and T4 levels, increased significantly in the fish exposed to 1 mg/L Cd. However, energy metabolism and serum T3/T4 levels decreased significantly in the 4-mg/L Cd group. Neuropeptide gene expression levels in brain were consistent with the observed changes in food intake. In the Cd-exposed groups, the expression levels of neuropeptide Y (NPY), apelin, and metallothionein (MT) increased significantly, while those of pro-opinmelanocortin (POMC), ghrelin, and corticotrophin-releasing factor (CRF) decreased significantly. Our data suggested that in fish, low doses of Cd might increase food intake, as well as weight and length gains, but high doses of Cd might have the opposite effect. These effects might be a result of neurohumoral regulation. Long-term exposure to low doses of Cd might cause weight gain and affect food intake. Title: Genome sequencing of the Australian wild diploid species Gossypium australe highlights disease resistance and delayed gland morphogenesis Cai Y, Cai X, Wang Q, Wang P, Zhang Y, Cai C, Xu Y, Wang K, Zhou Z and Liu F <25 more author(s)> Cai Y, Cai X, Wang Q, Wang P, Zhang Y, Cai C, Xu Y, Wang K, Zhou Z, Wang C, Geng S, Li B, Dong Q, Hou Y, Wang H, Ai P, Liu Z, Yi F, Sun M, An G, Cheng J, Shi Q, Xie Y, Shi X, Chang Y, Huang F, Chen Y, Hong S, Mi L, Sun Q, Zhang L, Zhou B, Peng R, Zhang X, Liu F (- 25) Ref: Plant Biotechnol J, 18:814, 2020 : PubMed ESTHER: Cai_2020_Plant.Biotechnol.J_18_814 PubMedSearch: Cai 2020 Plant.Biotechnol.J 18 814 PubMedID: 31479566 Gene_locus related to this paper: gosra-a0a0d2pzd7 Abstract The diploid wild cotton species Gossypium australe possesses excellent traits including resistance to disease and delayed gland morphogenesis, and has been successfully used for distant breeding programmes to incorporate disease resistance traits into domesticated cotton. Here, we sequenced the G. australe genome by integrating PacBio, Illumina short read, BioNano (DLS) and Hi-C technologies, and acquired a high-quality reference genome with a contig N50 of 1.83 Mb and a scaffold N50 of 143.60 Mb. We found that 73.5% of the G. australe genome is composed of various repeat sequences, differing from those of G. arboreum (85.39%), G. hirsutum (69.86%) and G. barbadense (69.83%). The G. australe genome showed closer collinear relationships with the genome of G. arboreum than G. raimondii and has undergone less extensive genome reorganization than the G. arboreum genome. Selection signature and transcriptomics analyses implicated multiple genes in disease resistance responses, including GauCCD7 and GauCBP1, and experiments revealed induction of both genes by Verticillium dahliae and by the plant hormones strigolactone (GR24), salicylic acid (SA) and methyl jasmonate (MeJA). Experiments using a Verticillium-resistant domesticated G. barbadense cultivar confirmed that knockdown of the homologues of these genes caused a significant reduction in resistance against Verticillium dahliae. Moreover, knockdown of a newly identified gland-associated gene GauGRAS1 caused a glandless phenotype in partial tissues using G. australe. The G. australe genome represents a valuable resource for cotton research and distant relative breeding as well as for understanding the evolutionary history of crop genomes. Title: Characterization of a novel carboxylesterase from Bacillus velezensis SYBC H47 and its application in degradation of phthalate esters Huang L, Meng D, Tian Q, Yang S, Deng H, Guan Z, Cai Y, Liao X Ref: J Biosci Bioeng, 129:588, 2020 : PubMed ESTHER: Huang_2020_J.Biosci.Bioeng_129_588 PubMedSearch: Huang 2020 J.Biosci.Bioeng 129 588 PubMedID: 31761671 Gene_locus related to this paper: baca2-a7z8b1 Abstract Recently, residual plasticizer phthalate esters (PAEs) in the different environments pose a serious health threat to humans and mammals. Biodegradation has been considered a promising and eco-friendly way to eliminate PAEs. In this study, a gene (baces04) encoding the novel PAEs hydrolase, carboxylesterase (BaCEs04), was screened from the genome of Bacillus velezensis SYBC H47 via bioinformatics analysis. Then, baces04 was cloned and expressed in Escherichia coli BL21 (DE3). BaCEs04 belonged to the esterase family VI. It contained a conserved domain (Gly159-His160-Ser161-Leu162-Gly163) and a typical serine hydrolase catalytic site (Ser161-Asp204-His261). The characterization of BaCEs04 showed that the activity was optimal at 60 degrees C and pH 7.5. This enzyme also displayed high resistance to metal ions, organic solvents, and detergents. After treatment with BaCEs04 for 5 h, the degradation ratio of four different 1 mM PAEs, including dimethyl phthalate, diethyl phthalate, dipropyl phthalate, and dibutyl phthalate, was 32.4%, 50.5%, 77.9%, and 86.8%, respectively. The degradation products of four PAEs were identified as their corresponding monoalkyl phthalates. This is the first report that family VI esterase displaying PAE-hydrolysis activity. This study also proved that BaCEs04 could be used as an ideal candidate for the application in bioremediation and industry. Title: A novel feruloyl esterase with high rosmarinic acid hydrolysis activity from Bacillus pumilus W3 Liang W, Xiong T, Wang X, Deng H, Bai Y, Fan TP, Zheng X, Cai Y Ref: Int J Biol Macromol, 161:525, 2020 : PubMed ESTHER: Liang_2020_Int.J.Biol.Macromol_161_525 PubMedSearch: Liang 2020 Int.J.Biol.Macromol 161 525 PubMedID: 32531366 Gene_locus related to this paper: 9baci-BpFae12 Inhibitor(s) related to this paper: Rosmarinic-acid Abstract A novel feruloyl esterase (BpFae12) with rosmarinic acid (RA) hydrolysis activity was isolated from Bacillus pumilus W3 and expressed in Escherichia coli BL21 (DE3). With RA as a substrate, the optimal pH and temperature of BpFae12 were pH 8.0 and 50 degreesC, respectively. The specific enzyme activity was 12.8 U.mg(-1). BpFae12 showed the highest activity and substrate affinity toward RA (V(max) of 13.13 U.mg(-1), K(m) of 0.41 mM). Moreover, it also presented strong hydrolysis performance against chlorogenic acid (190.17 U.mg(-1)). RA was effectively Hydrolyzed into more bioactive caffeic acid and 3,4-dihydroxyphenyllactic acid by BpFae12, which have potential applications in the food industry. Title: Huperzine A inhibits heroin-seeking behaviors induced by cue or heroin priming in rats Ma B, Cai Y, Zhang X, Wang F, Zhuang D, Liu H, Liu Y, Zhou W Ref: Neuroreport, 31:819, 2020 : PubMed ESTHER: Ma_2020_Neuroreport_31_819 PubMedSearch: Ma 2020 Neuroreport 31 819 PubMedID: 32576772 Abstract Cholinergic systems modulate dopaminergic function in brain pathways are thought to mediate heroin addiction. This study investigated whether huperzine A, an acetylcholinesterase inhibitor, has beneficial effects on heroin reward and heroin-seeking behavior. Rats were trained to self-administer heroin (50microg/kg/infusion) under the fixed ratio 1 schedule for 14days and then drug-seeking was extinguished for 10days, after which reinstatement of drug-seeking was induced by conditioned cues or heroin priming. Acute treatment with huperzine A at dose from 0.05 to 0.2mg/kg potently and dose-dependently suppressed the cue- and heroin-induced reinstatement of heroin-seeking behavior following extinction. Huperzine A at these doses failed to alter either heroin rewarding effect or spontaneous locomotion activity. The study demonstrated that acute treatment with huperzine A inhibited heroin-seeking behavior, suggesting that huperzine A may be used as an adjuvant treatment for heroin relapse and addiction. Title: Efficient Cocaine Degradation by Cocaine Esterase-Loaded Red Blood Cells Rossi L, Pierige F, Agostini M, Bigini N, Termopoli V, Cai Y, Zheng F, Zhan CG, Landry DW, Magnani M Ref: Front Physiol, 11:573492, 2020 : PubMed ESTHER: Rossi_2020_Front.Physiol_11_573492 PubMedSearch: Rossi 2020 Front.Physiol 11 573492 PubMedID: 33013487 Abstract Recombinant bacterial cocaine esterase (CocE) represents a potential protein therapeutic for cocaine use disorder treatment. Unfortunately, the native enzyme was highly unstable and the corresponding mutagenized derivatives, RBP-8000 and E196-301, although improving in vitro thermo-stability and in vivo half-life, were a partial solution to the problem. For cocaine use disorder treatment, an efficient cocaine-metabolizing enzyme with a longer residence time in circulation would be needed. We investigated in vitro the possibility of developing red blood cells (RBCs) loaded with RBP-8000 and E196-301 as a biocompatible system to metabolize cocaine for a longer period of time. RBP 8000 stability within human RBCs is limited (approximately 50% residual activity after 1 h at 37degC) and not different as for the free enzyme, while both free and encapsulated E196-301 showed a greater thermo-stability. By reducing cellular glutathione content during the loading procedure, in order to preserve the disulfide bonds opportunely created to stabilize the enzyme dimer structure, it was possible to produce an encapsulated protein maintaining 100% stability at least after 4 h at 37degC. Moreover, E196-301-loaded RBCs were efficiently able to degrade cocaine in a time- and concentration-dependent manner. The same stability results were obtained when murine RBCs were used paving the way to preclinical investigations. Thus, our in vitro data show that E196-301-loaded RBCs could act as efficient bioreactors in degrading cocaine to non-toxic metabolites to be possibly considered in substance-use disorder treatments. This approach should now be investigated in a preclinical model of cocaine use disorder to evaluate if further protein modifications are needed to further improve long term enzyme stability. Title: Dimerization of human butyrylcholinesterase expressed in bacterium for development of a thermally stable bioscavenger of organophosphorus compounds Cai Y, Zhou S, Stewart MJ, Zheng F, Zhan CG Ref: Chemico-Biological Interactions, 310:108756, 2019 : PubMed ESTHER: Cai_2019_Chem.Biol.Interact_13ChEPon_310_108756 PubMedSearch: Cai 2019 Chem.Biol.Interact 13ChEPon 310 108756 PubMedID: 31325422 Abstract Human butyrylcholinesterase (BChE) is a widely distributed plasma enzyme. For decades, numerous research efforts have been directed at engineering BChE as a bioscavenger of organophosphorus insecticides and chemical warfare nerve agents. However, it has been a grand challenge to cost-efficiently produce BChE in large-scale. Recently reported studies have successfully designed a truncated BChE mutant (with amino-acid substitutions on 47 residues that are far away from the catalytic site), denoted as BChE-M47 for convenience, which can be expressed in E. coli without loss of its catalytic activity. In this study, we aimed to dimerize the truncated BChE mutant protein expressed in a prokaryotic system (E. coli) in order to further improve its thermal stability by introducing a pair of cross-subunit disulfide bonds to the BChE-M47 structure. Specifically, the E377C/A516C mutations were designed and introduced to BChE-M47, and the obtained new protein entity, denoted as BChE-M48, with a pair of cross-subunit disulfide bonds indeed exists as a dimer with significantly improved thermostability and unaltered catalytic activity and reactivity compared to BChE-M47. These results provide a new strategy for optimizing protein stability for production in a cost-efficient prokaryotic system. Our enzyme, BChE-M48, has a half-life of almost one week at a 37 degrees C, suggesting that it could be utilized as a highly stable bioscavenger of OP insecticides and chemical warfare nerve agents. Title: Reengineering of Albumin-Fused Cocaine Hydrolase CocH1 (TV-1380) to Prolong Its Biological Half-Life Cai Y, Zhou S, Jin Z, Wei H, Shang L, Deng J, Zhan CG, Zheng F Ref: AAPS J, 22:5, 2019 : PubMed ESTHER: Cai_2019_AAPS.J_22_5 PubMedSearch: Cai 2019 AAPS.J 22 5 PubMedID: 31754920 Abstract Therapeutic treatment of cocaine toxicity or addiction is a grand medical challenge. As a promising therapeutic strategy for treatment of cocaine toxicity and addiction to develop a highly efficient cocaine hydrolase (CocH) capable of accelerating cocaine metabolism to produce physiologically/biologically inactive metabolites, our previously designed A199S/S287G/A328W/Y332G mutant of human butyrylcholinesterase (BChE), known as cocaine hydrolase-1 (CocH1), possesses the desirably high catalytic activity against cocaine. The C-terminus of CocH1, truncated after amino acid #529, was fused to human serum albumin (HSA) to extend the biological half-life. The C-terminal HSA-fused CocH1 (CocH1-HSA), known as Albu-CocH1, Albu-CocH, AlbuBChE, Albu-BChE, or TV-1380 in literature, has shown favorable preclinical and clinical profiles. However, the actual therapeutic value of TV-1380 for cocaine addiction treatment is still limited by the short half-life. In this study, we designed and tested a new type of HSA-fused CocH1 proteins, i.e., N-terminal HSA-fused CocH1, with or without a linker between the HSA and CocH1 domains. It has been demonstrated that the catalytic activity of these new fusion proteins against cocaine is similar to that of TV-1380. However, HSA-CocH1 (without a linker) has a significantly longer biological half-life (t1/2 = 14 +/- 2 h) compared to the corresponding C-terminal HSA-fused CocH1, i.e., CocH1-HSA (TV-1380 with t1/2 = 5-8 h), in rats. Further, the N-terminal HSA-fused CocH1 proteins with a linker have further prolonged biological half-lives: t1/2 = 17 +/- 2 h for both HSA-EAAAK-CocH1 and HSA-PAPAP-CocH1, and t1/2 = 18 +/- 3 h for HSA-(PAPAP)2-CocH1. These N-terminal HSA-fused CocH1 proteins may serve as more promising protein drug candidates for cocaine addiction treatment. Title: Expression and characterisation of feruloyl esterases from Lactobacillus fermentum JN248 and release of ferulic acid from wheat bran Deng H, Jia P, Jiang J, Bai Y, Fan TP, Zheng X, Cai Y Ref: Int J Biol Macromol, 138:272, 2019 : PubMed ESTHER: Deng_2019_Int.J.Biol.Macromol_138_272 PubMedSearch: Deng 2019 Int.J.Biol.Macromol 138 272 PubMedID: 31306699 Abstract Genes encoding six feruloyl esterases (FAEs; lbff0997, lbff0272, lbff1432, lbff1695, lbff1849, lbff0153) from Lactobacillus fermentum JN248 were cloned, overexpressed and characterised. Maximum enzyme activity was observed at 35 degrees C for recombinant FAEs LFFae0997, LFFae0272 and LFFae0153, at 30 degrees C for LFFae1695, and at 40 degrees C for LFFae1432and LFFae1849. For five of the enzymes, optimal activity was observed at pH7.0 or pH8.0, and high thermostability was measured up to 55 degrees C. By contrast, LFFae1432 lost less than 10.0% activity after incubation at 40 degrees C for 2h, and pH stability was highest between pH7.0 and pH9.0. In addition, LFFae1432 was the most robust esterase, with a higher affinity and hydrolytic activity against synthetic esters. The enzymes released ferulic acids (FAs) from de-starched wheat bran (DSWB), and 60.7% of the total alkali-extractable FAs were released when LFFae1432 was added alone, compared with less than 10% for the other enzymes. The amount of FAs released by FAEs increased when combined with xylanase. These FAEs could serve as promising biocatalysts for biodegradation, and LFFae1432 may hold promise for potential industrial applications. Title: Distribution characteristics of sweat gland nerve fibres in normal humans identified by acetylcholinesterase histochemical staining Ling L, Liu Y, Sun Y, Cai Y, Jiang Y, Chen L, He L, Xue J Ref: Clin Neurol Neurosurg, 189:105620, 2019 : PubMed ESTHER: Ling_2019_Clin.Neurol.Neurosurg_189_105620 PubMedSearch: Ling 2019 Clin.Neurol.Neurosurg 189 105620 PubMedID: 31812030 Abstract OBJECTIVE: To quantitatively analyze distribution characteristics of sweat gland nerve fibres (SGNF) in normal Chinese individuals for obtaining a reference for early diagnosis of peripheral neuropathy. PATIENTS AND METHODS: Skin biopsy samples were collected from 192 normal Chinese individuals and divided into six, four and two groups according to anatomic sites, age and gender, respectively. SGNF morphology was observed and SGNF density (SGNFD) was determined. RESULTS: There was a significant difference in SGNFD among different anatomic sites, age and gender. A degressive tendency was observed from proximal to distal anatomic sites. SGNFD was the lowest in subjects in the 21-40-year-old age group, but was the highest in subjects in the >61-year-old age group. Overall, SGNFD fluctuated with age. SGNFD in males was significantly higher than that in females. CONCLUSIONS: Distribution characteristics of SGNF in normal individuals may serve as a reference for early diagnosis of nerve fibre damage. Title: Functional analysis of the GbDWARF14 gene associated with branching development in cotton Wang P, Zhang S, Qiao J, Sun Q, Shi Q, Cai C, Mo J, Chu Z, Yuan Y and Cai Y <3 more author(s)> Wang P, Zhang S, Qiao J, Sun Q, Shi Q, Cai C, Mo J, Chu Z, Yuan Y, Du X, Miao Y, Zhang X, Cai Y (- 3) Ref: PeerJ, 7:e6901, 2019 : PubMed ESTHER: Wang_2019_PeerJ_7_e6901 PubMedSearch: Wang 2019 PeerJ 7 e6901 PubMedID: 31143538 Abstract Plant architecture, including branching pattern, is an important agronomic trait of cotton crops. In recent years, strigolactones (SLs) have been considered important plant hormones that regulate branch development. In some species such as Arabidopsis, DWARF14 is an unconventional receptor that plays an important role in the SL signaling pathway. However, studies on SL receptors in cotton are still lacking. Here, we cloned and analysed the structure of the GbD14 gene in Gossypium barbadense and found that it contains the domains necessary for a SL receptor. The GbD14 gene was expressed primarily in the roots, leaves and vascular bundles, and the GbD14 protein was determined via GFP to localize to the cytoplasm and nucleus. Gene expression analysis revealed that the GbD14 gene not only responded to SL signals but also was differentially expressed between cotton plants whose types of branching differed. In particular, GbD14 was expressed mainly in the axillary buds of normal-branching cotton, while it was expressed the most in the leaves of nulliplex-branch cotton. In cotton, the GbD14 gene can be induced by SL and other plant hormones, such as indoleacetic acid, abscisic acid, and jasmonic acid. Compared with wild-type Arabidopsis, GbD14-overexpressing Arabidopsis responded more rapidly to SL signals. Moreover, we also found that GbD14 can rescue the multi-branched phenotype of Arabidopsis Atd14 mutants. Our results indicate that the function of GbD14 is similar to that of AtD14, and GbD14 may be a receptor for SL in cotton and involved in regulating branch development. This research provides a theoretical basis for a profound understanding of the molecular mechanism of branch development and ideal plant architecture for cotton breeding improvements. Title: Genistein: A Dual Inhibitor of Both Amyloid beta and Human Islet Amylin Peptides Ren B, Liu Y, Zhang Y, Cai Y, Gong X, Chang Y, Xu L, Zheng J Ref: ACS Chem Neurosci, 9:1215, 2018 : PubMed ESTHER: Ren_2018_ACS.Chem.Neurosci_9_1215 PubMedSearch: Ren 2018 ACS.Chem.Neurosci 9 1215 PubMedID: 29432676 Abstract Abnormal misfolding and aggregation of amyloid peptides into amyloid fibrils are common and critical pathological events in many neurodegenerative diseases. Most inhibitors or drugs have been developed to prevent amyloid aggregation of a specific peptide, showing sequence-dependent inhibition mechanisms. It is more challenging to develop or discover inhibitors capable of preventing the aggregation of two or more different amyloid peptides. Genistein, a major phytoestrogen in soybean, has been widely used as an anti-inflammation and cerebrovascular drug due to its antioxidation and antiacetylcholinesterase effects. Herein, we examine the inhibitory effects of genistein on the aggregation of amyloid-beta (Abeta, associated with Alzheimer's disease) and human islet amylin (hIAPP, associated with type 2 diabetes) and Abeta- and hIAPP-induced neurotoxicity using a combination of experimental and computational approaches. Collective experimental results from thioflavin T (ThT), atomic force microscopy (AFM), and circular dichroism (CD) demonstrate that genistein shows strong inhibition ability to prevent the conformational transition of both Abeta and hIAPP monomers to beta-sheet structures, thus reducing final amyloid fibrillization from Abeta and hIAPP monomer aggregation by 40-63%. Further 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH), and large unilamellar vesicle (LUV) assays show that genistein helps to increase cell viability, decrease cell apoptosis, and reduce cell membrane leakage, where the cell protection effect of genistein is likely correlated with its reduced membrane leakage. Comparative molecular dynamics (MD) simulations reveal that genistein prefers to bind the beta-sheet groove, a common structural motif of amyloid fibrils, of both Abeta and hIAPP oligomers to interfere with their self-aggregation. This work for the first time demonstrates genistein as a dual inhibitor of Abeta and hIAPP aggregation. Further structural optimization and refinement of genistein may generate a series of effective sequence-independent inhibitors against the aggregation and toxicity of different amyloid peptides. Title: Interaction of erythromycin and ketoconazole on the neurological, biochemical and behavioral responses in crucian carp Liu J, Cai Y, Lu G, Dan X, Wu D, Yan Z Ref: Environ Toxicol Pharmacol, 55:14, 2017 : PubMed ESTHER: Liu_2017_Environ.Toxicol.Pharmacol_55_14 PubMedSearch: Liu 2017 Environ.Toxicol.Pharmacol 55 14 PubMedID: 28802958 Abstract The presence of pharmaceuticals in the aquatic environment has received great attention due to their potential impacts on public health. The single, as well as the combined toxicities of erythromycin (ERY) and ketoconazole (KCZ) on the bioaccumulation, biochemical and behavioral responses, were examined in crucian carp. This study focused on the uptake of contaminants, acetylcholinesterase (AChE) activity in the brain, swimming and shoaling behavior of fish. After 14days of binary exposure, the addition of KCZ at nominal concentrations of 0.2, 2 and 20mug/L significantly increased the accumulation of ERY in the brain of the fish and the bioconcentration factor of 2.08 was 2.6-fold higher than that calculated from the ERY-alone exposure. The brain AChE activity was significantly inhibited by ERY and KCZ with a significant correlation with respect to the accumulative concentration of the contaminants. The inhibition rates of swimming activity to KCZ were increased with a corresponding increase in the exposure concentration of KCZ in the single exposure. However, this manner was altered by the combined exposure. In addition, shoaling was significantly enhanced by KCZ-alone exposure, which was significantly correlated with the swimming activity. This study indicates that the mixture of the contaminants may cause endocrine disrupting effects and behavior modification especially in fish with known ecological and evolutionary consequences. Title: Concurrent administration of thyroxine and donepezil induces plastic changes in the prefrontal cortex of adult hypothyroid rats Wang F, Wu Z, Zha X, Cai Y, Wu B, Jia X, Zhu D Ref: Mol Med Rep, 16:3233, 2017 : PubMed ESTHER: Wang_2017_Mol.Med.Rep_16_3233 PubMedSearch: Wang 2017 Mol.Med.Rep 16 3233 PubMedID: 28713915 Abstract The aim of the present study was to observe the effects of the concurrent administration of thyroxine (T4) and an acetylcholinesterase (AChE) inhibitor, donepezil (DON), on the hypothyroidisminduced ultrastructural changes of the prefrontal cortex (PFC) in adult rats. The acetylcholine (ACh) content and AChE activity was assessed, as well as the expressions of synaptotagmin1 (syt1) and SNAP25 were analyzed in the rats. Adding 0.05% propylthiouracil to rats' drinking water induced a hypothyroid rat model. The animals were treated with T4 and DON administered separately or in combination from the fifth week. Transmission electron microscope analysis revealed that hypothyroidism induced marked ultrastructural changes, including the neurons, the synapses and the myelin sheath in the PFC. T4 or DON treatment improved the morphologic features of the PFC, and the performance of the T4 combined DON group was the closest to the control group. Moreover, hypothyroidism significantly decreased the content of ACh (29.8%) and activity of AChE (27.8%), which were restored to control values by T4 admi-nistration. In addition, DON treatment restored ACh content to normal. At the protein level, hypothyroidism increased the levels of syt1 and SNAP25 in the PFC, both of which were not restored to control values following T4 administration, while concurrent administration of T4 and DON was able to induce this effect. These results suggested that adultonset hypothyroidism induce morphological, biochemical and molecular alterations in the PFC, combined administration of T4 and DON induce plastic changes in the PFC, different from that of the standard T4 therapy, and that the DON treatment may facilitate the recovery of synaptic protein impairments induced by hypothyroidism. Title: Evaluation and application of constitutive promoters for cutinase production by Saccharomyces cerevisiae Zhang J, Cai Y, Du G, Chen J, Wang M, Kang Z Ref: J Microbiol, 55:538, 2017 : PubMed ESTHER: Zhang_2017_J.Microbiol_55_538 PubMedSearch: Zhang 2017 J.Microbiol 55 538 PubMedID: 28664516 Abstract Cutinase as a promising biocatalyst has been intensively studied and applied in processes targeted for industrial scale. In this work, the cutinase gene tfu from Thermobifida fusca was artificially synthesized according to codon usage bias of Saccharomyces cerevisiae and investigated in Saccharomyces cerevisiae. Using the alpha-factor signal peptide, the T. fusca cutinase was successfully overexpressed and secreted with the GAL1 expression system. To increase the cutinase level and overcome some of the drawbacks of induction, four different strong promoters (ADH1, HXT1, TEF1, and TDH3) were comparatively evaluated for cutinase production. By comparison, promoter TEF1 exhibited an outstanding property and significantly increased the expression level. By fed-batch fermentation with a constant feeding approach, the activity of cutinase was increased to 29.7 U/ml. The result will contribute to apply constitutive promoter TEF1 as a tool for targeted cutinase production in S. cerevisiae cell factory. Title: Discovery of novel feruloyl esterase activity of BioH in Escherichia coli BL21(DE3) Kang L, Bai Y, Cai Y, Zheng X Ref: Biotechnol Lett, 38:1009, 2016 : PubMed ESTHER: Kang_2016_Biotechnol.Lett_38_1009 PubMedSearch: Kang 2016 Biotechnol.Lett 38 1009 PubMedID: 26956238 Abstract OBJECTIVES: To characterize a novel feruloyl esterase from Escherichia coli BL21 DE3. Title: Testosterone Deficiency Induces Changes of the Transcriptomes of Visceral Adipose Tissue in Miniature Pigs Fed a High-Fat and High-Cholesterol Diet Zhang L, Cai Y, Wei S, Ling Y, Zhu L, Li D, Cai Z Ref: Int J Mol Sci, 17:, 2016 : PubMed ESTHER: Zhang_2016_Int.J.Mol.Sci_17_ PubMedSearch: Zhang 2016 Int.J.Mol.Sci 17 PubMedID: 27999286 Abstract Testosterone deficiency causes fat deposition, particularly in visceral fat, and its replacement might reverse fat accumulation, however, the underlying mechanisms of such processes under diet-induced adiposity are largely unknown. To gain insights into the genome-wide role of androgen on visceral adipose tissue (VAT), RNA-Seq was used to investigate testosterone deficiency induced changes of VAT in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT) treatments. The results showed that testosterone deficiency significantly increased VAT deposition and serum leptin concentrations. Moreover, a total of 1732 differentially expressed genes (DEGs) were identified between any two groups. Compared with gene expression profiles in IM and CMT pigs, upregulated genes in CM pigs, i.e., LOC100520753 (CD68), LCN2, EMR1, S100A9, NCF1 (p47phox), and LEP, were mainly involved in inflammatory response, oxidation-reduction process, and lipid metabolic process, while downregulated genes in CM pigs, i.e., ABHD5, SPP1, and GAS6, were focused on cell differentiation and cell adhesion. Taken together, our study demonstrates that testosterone deficiency alters the expression of numerous genes involved in key biological processes of VAT accumulation under HFC diet and provides a novel genome-wide view on the role of androgen on VAT deposition under HFC diet, thus improving our understanding of the molecular mechanisms involved in VAT changes induced by testosterone deficiency. Title: CD26/DPP4 cell-surface expression in bat cells correlates with bat cell susceptibility to Middle East respiratory syndrome coronavirus (MERS-CoV) infection and evolution of persistent infection Cai Y, Yu SQ, Postnikova EN, Mazur S, Bernbaum JG, Burk R, Zhang T, Radoshitzky SR, Muller MA and Kuhn JH <4 more author(s)> Cai Y, Yu SQ, Postnikova EN, Mazur S, Bernbaum JG, Burk R, Zhang T, Radoshitzky SR, Muller MA, Jordan I, Bollinger L, Hensley LE, Jahrling PB, Kuhn JH (- 4) Ref: PLoS ONE, 9:e112060, 2014 : PubMed ESTHER: Cai_2014_PLoS.One_9_e112060 PubMedSearch: Cai 2014 PLoS.One 9 e112060 PubMedID: 25409519 Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors. Title: Effects of thyroxin and donepezil on hippocampal acetylcholine content and syntaxin-1 and munc-18 expression in adult rats with hypothyroidism Wang N, Cai Y, Wang F, Zeng X, Jia X, Tao F, Zhu D Ref: Exp Ther Med, 7:529, 2014 : PubMed ESTHER: Wang_2014_Exp.Ther.Med_7_529 PubMedSearch: Wang 2014 Exp.Ther.Med 7 529 PubMedID: 24520241 Abstract Adult-onset hypothyroidism induces various impairments in hippocampus-dependent cognitive function, in which numerous synaptic proteins and neurotransmitters are involved. Donepezil (DON), an acetylcholinesterase inhibitor, has been shown to be efficient in improving cognitive function. The aim of the present study was to investigate the effects of adult-onset hypothyroidism on the expression levels of the synaptic proteins syntaxin-1 and munc-18, as well as the content of the neurotransmitter acetylcholine (ACh) in the hippocampus. In addition, the study explored the effects of thyroxin (T4) and DON treatment on the altered parameters. The study involved 55 Sprague-Dawley rats that were randomly divided into five groups: Control, hypothyroid (0.05% 6-n-propyl-2-thiouracil; added to the drinking water), hypothyroid treated with T4 (6 mug/100 g body weight once daily; intraperitoneal injection), hypothyroid treated with DON (0.005%; added to the drinking water) and hypothyroid treated with a combination of the two drugs (6 mug/100 g T4 and 0.005% DON). The concentration of ACh was determined in the homogenized hippocampus of each animal by alkaline hydroxylamine colorimetry. The protein levels of syntaxin-1 and munc-18 were determined by immunohistochemistry. The results showed that the content of ACh in the hippocampi of the hypothyroid rats was significantly decreased compared with that in the controls and that T4 monotherapy and DON administration restored the ACh content to normal values. In the hippocampi of the hypothyroid group, munc-18 was expressed at significantly lower levels, while the expression levels of syntaxin-1 were increased compared with the levels in the control group. Treatment with T4 alone restored the expression of syntaxin-1 but failed to normalize munc-18 expression levels. The co-administration of T4 and DON returned the munc-18 levels to normal values. These observations indicate that adult-onset hypothyroidism induces alterations in the levels of munc-18, syntaxin-1 and ACh in the hippocampus. Syntaxin-1 and ACh levels were restored by T4 monotherapy while munc-18 levels were not. In addition, the co-administration of T4 and DON resulted in more effective restoration than either alone. The thyroid hormone has a direct effect on metabolism of hippocampal ACh in adult rats and DON is helpful for treatment of synaptic protein impairment induced by hypothyroidism. Title: Toxicological effects of multi-walled carbon nanotubes adsorbed with nonylphenol on earthworm Eisenia fetida Hu C, Cai Y, Wang W, Cui Y, Li M Ref: Environ Sci Process Impacts, 15:2125, 2013 : PubMed ESTHER: Hu_2013_Environ.Sci.Process.Impacts_15_2125 PubMedSearch: Hu 2013 Environ.Sci.Process.Impacts 15 2125 PubMedID: 24104387 Abstract The high surface area of multi-walled carbon nanotubes (MWCNTs) tends to adsorb a large variety of toxic chemicals, which may enhance the toxicity of both MWCNTs and chemicals to organisms. In order to evaluate the combined toxicity of nonylphenol (NP) and MWCNTs to the earthworm Eisenia fetida in soil, artificial soil systems containing distilled water, 0.1 g kg(-1) MWCNTs, 1 g kg(-1) MWCNTs, 1 g kg(-1) MWCNTs absorbed 5 mg kg(-1) NP, and 10 mg kg(-1) NP alone were prepared and exposed to earthworms for 7 days. Antioxidative responses, and activities of cellulase, Na(+), K(+)-ATPase and acetylcholinesterase (TChE) as well as DNA damage were chosen as toxicological endpoints. The results showed that 1 g kg(-1) MWCNTs adsorbed 5 mg kg(-1) NP from the soil which caused much more adverse effects on the earthworms than each chemical alone, evident from the responses of cellulase, Na(+), K(+)-ATPase and comet assay. This study indicated that MWCNTs facilitated the bioavailability of NP to the earthworm and increased the harmful effects of NP. Title: gamma-secretase binding sites in aged and Alzheimer's disease human cerebrum: the choroid plexus as a putative origin of CSF Abeta Liu F, Xue ZQ, Deng SH, Kun X, Luo XG, Patrylo PR, Rose GM, Cai H, Struble RG and Yan XX <1 more author(s)> Liu F, Xue ZQ, Deng SH, Kun X, Luo XG, Patrylo PR, Rose GM, Cai H, Struble RG, Cai Y, Yan XX (- 1) Ref: European Journal of Neuroscience, 37:1714, 2013 : PubMed ESTHER: Liu_2013_Eur.J.Neurosci_37_1714 PubMedSearch: Liu 2013 Eur.J.Neurosci 37 1714 PubMedID: 23432732 Abstract Deposition of beta -amyloid (Abeta) peptides, cleavage products of beta-amyloid precursor protein (APP) by beta-secretase-1 (BACE1) and gamma-secretase, is a neuropathological hallmark of Alzheimer's disease (AD). gamma-Secretase inhibition is a therapeutical anti-Abeta approach, although changes in the enzyme's activity in AD brain are unclear. Cerebrospinal fluid (CSF) Abeta peptides are thought to derive from brain parenchyma and thus may serve as biomarkers for assessing cerebral amyloidosis and anti-Abeta efficacy. The present study compared active gamma-secretase binding sites with Abeta deposition in aged and AD human cerebrum, and explored the possibility of Abeta production and secretion by the choroid plexus (CP). The specific binding density of [(3) H]-L-685,458, a radiolabeled high-affinity gamma-secretase inhibitor, in the temporal neocortex and hippocampal formation was similar for AD and control cases with similar ages and post-mortem delays. The CP in post-mortem samples exhibited exceptionally high [(3) H]-L-685,458 binding density, with the estimated maximal binding sites (Bmax) reduced in the AD relative to control groups. Surgically resected human CP exhibited APP, BACE1 and presenilin-1 immunoreactivity, and beta-site APP cleavage enzymatic activity. In primary culture, human CP cells also expressed these amyloidogenic proteins and released Abeta40 and Abeta42 into the medium. Overall, our results suggest that gamma-secretase activity appears unaltered in the cerebrum in AD and is not correlated with regional amyloid plaque pathology. The CP appears to be a previously unrecognised non-neuronal contributor to CSF Abeta, probably at reduced levels in AD. Title: BACE1 elevation is involved in amyloid plaque development in the triple transgenic model of Alzheimer's disease: differential Abeta antibody labeling of early-onset axon terminal pathology Cai Y, Zhang XM, Macklin LN, Cai H, Luo XG, Oddo S, LaFerla FM, Struble RG, Rose GM and Yan XX <1 more author(s)> Cai Y, Zhang XM, Macklin LN, Cai H, Luo XG, Oddo S, LaFerla FM, Struble RG, Rose GM, Patrylo PR, Yan XX (- 1) Ref: Neurotox Res, 21:160, 2012 : PubMed ESTHER: Cai_2012_Neurotox.Res_21_160 PubMedSearch: Cai 2012 Neurotox.Res 21 160 PubMedID: 21725719 Abstract beta-amyloid precursor protein (APP) and presenilins mutations cause early-onset familial Alzheimer's disease (FAD). Some FAD-based mouse models produce amyloid plaques, others do not. beta-Amyloid (Abeta) deposition can manifest as compact and diffuse plaques; it is unclear why the same Abeta molecules aggregate in different patterns. Is there a basic cellular process governing Abeta plaque pathogenesis? We showed in some FAD mouse models that compact plaque formation is associated with a progressive axonal pathology inherent with increased expression of beta-secretase (BACE1), the enzyme initiating the amyloidogenic processing of APP. A monoclonal Abeta antibody, 3D6, visualized distinct axon terminal labeling before plaque onset. The present study was set to understand BACE1 and axonal changes relative to diffuse plaque development and to further characterize the novel axonal Abeta antibody immunoreactivity (IR), using triple transgenic AD (3xTg-AD) mice as experimental model. Diffuse-like plaques existed in the forebrain in aged transgenics and were regionally associated with increased BACE1 labeled swollen/sprouting axon terminals. Increased BACE1/3D6 IR at axon terminals occurred in young animals before plaque onset. These axonal elements were also co-labeled by other antibodies targeting the N-terminal and mid-region of Abeta domain and the C-terminal of APP, but not co-labeled by antibodies against the Abeta C-terminal and APP N-terminal. The results suggest that amyloidogenic axonal pathology precedes diffuse plaque formation in the 3xTg-AD mice, and that the early-onset axonal Abeta antibody IR in transgenic models of AD might relate to a cross-reactivity of putative APP beta-carboxyl terminal fragments. Title: Affinity binding-guided fluorescent nanobiosensor for acetylcholinesterase inhibitors via distance modulation between the fluorophore and metallic nanoparticle Zhang Y, Hei T, Cai Y, Gao Q, Zhang Q Ref: Analytical Chemistry, 84:2830, 2012 : PubMed ESTHER: Zhang_2012_Anal.Chem_84_2830 PubMedSearch: Zhang 2012 Anal.Chem 84 2830 PubMedID: 22339669 Abstract The magnitude of fluorescence enhancement was found to depend strongly on the distance between fluorophores and metal nanostructures in metal-enhanced fluorescence (MEF). However, the precise placement of the particle in front of the molecule with nanometer accuracy and distance control is a great challenge. We describe a method using acetylcholinesterase (AChE) to modulate the distance between a gold nanoparticle (AuNP) and the fluorophore 7-hydroxy-9H-(1,3-dichloro-9,9-dimethylacridin-2-one) (DDAO). We found that DDAO is a reversible mixed type-I AChE inhibitor. DDAO binds to the peripheral anionic site and penetrates into the active gorge site of AChE via inhibition kinetics test and molecular docking study. The affinity ligand DDAO bound to AChE which was immobilized onto AuNPs, and its fluorescence was sharply enhanced due to MEF. The fluorescence was reduced by distance variations between the AuNP and DDAO, which resulted from other inhibitors competitively binding with AChE and partly or completely displacing DDAO. Experimental results show that changes in fluorescence intensity are related to the concentration of inhibitors present in the solution. In addition, the nanobiosensor has high sensitivity, with detection limits as low as 0.4 muM for paraoxon and 10 nM for tacrine, and also exhibits different reduction efficiencies for the two types of inhibitor. Thus, instead of an inhibition test, a new type of affinity binding-guided fluorescent nanobiosensor was fabricated to detect AChE inhibitors, determine AChE inhibitor binding mode, and screen more potent AChE inhibitors. The proposed strategy may be applied to other proteins or protein domains via changes in the affinity ligand. Title: beta-Secretase-1 elevation in aged monkey and Alzheimer's disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and beta-amyloid accumulation Cai Y, Xiong K, Zhang XM, Cai H, Luo XG, Feng JC, Clough RW, Struble RG, Patrylo PR and Yan XX <2 more author(s)> Cai Y, Xiong K, Zhang XM, Cai H, Luo XG, Feng JC, Clough RW, Struble RG, Patrylo PR, Chu Y, Kordower JH, Yan XX (- 2) Ref: European Journal of Neuroscience, 32:1223, 2010 : PubMed ESTHER: Cai_2010_Eur.J.Neurosci_32_1223 PubMedSearch: Cai 2010 Eur.J.Neurosci 32 1223 PubMedID: 20726888 Abstract Alzheimer's disease (AD) is the most common dementia-causing disorder in the elderly; it may be related to multiple risk factors, and is characterized pathologically by cerebral hypometabolism, paravascular beta-amyloid peptide (Abeta) plaques, neuritic dystrophy, and intra-neuronal aggregation of phosphorylated tau. To explore potential pathogenic links among some of these lesions, we examined beta-secretase-1 (BACE1) alterations relative to Abeta deposition, neuritic pathology and vascular organization in aged monkey and AD human cerebral cortex. Western blot analyses detected increased levels of BACE1 protein and beta-site-cleavage amyloid precursor protein C-terminal fragments in plaque-bearing human and monkey cortex relative to controls. In immunohistochemistry, locally elevated BACE1 immunoreactivity (IR) occurred in AD but not in control human cortex, with a trend for increased overall density among cases with greater plaque pathology. In double-labeling preparations, BACE1 IR colocalized with immunolabeling for Abeta but not for phosphorylated tau. In perfusion-fixed monkey cortex, locally increased BACE1 IR co-existed with intra-axonal and extracellular Abeta IR among virtually all neuritic plaques, ranging from primitive to typical cored forms. This BACE1 labeling localized to swollen/sprouting axon terminals that might co-express one or another neuronal phenotype markers (GABAergic, glutamatergic, cholinergic, or catecholaminergic). Importantly, these BACE1-labeled dystrophic axons resided near to or in direct contact with blood vessels. These findings suggest that plaque formation in AD or normal aged primates relates to a multisystem axonal pathogenesis that occurs in partnership with a potential vascular or metabolic deficit. The data provide a mechanistic explanation for why senile plaques are present preferentially near the cerebral vasculature. Title: Subunit composition and substrate specificity of a MOF-containing histone acetyltransferase distinct from the male-specific lethal (MSL) complex Cai Y, Jin J, Swanson SK, Cole MD, Choi SH, Florens L, Washburn MP, Conaway JW, Conaway RC Ref: Journal of Biological Chemistry, 285:4268, 2010 : PubMed ESTHER: Cai_2010_J.Biol.Chem_285_4268 PubMedSearch: Cai 2010 J.Biol.Chem 285 4268 PubMedID: 20018852 Gene_locus related to this paper: human-KANSL3 Abstract Human MOF (MYST1), a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs), is the human ortholog of the Drosophila males absent on the first (MOF) protein. MOF is the catalytic subunit of the male-specific lethal (MSL) HAT complex, which plays a key role in dosage compensation in the fly and is responsible for a large fraction of histone H4 lysine 16 (H4K16) acetylation in vivo. MOF was recently reported to be a component of a second HAT complex, designated the non-specific lethal (NSL) complex (Mendjan, S., Taipale, M., Kind, J., Holz, H., Gebhardt, P., Schelder, M., Vermeulen, M., Buscaino, A., Duncan, K., Mueller, J., Wilm, M., Stunnenberg, H. G., Saumweber, H., and Akhtar, A. (2006) Mol. Cell 21, 811-823). Here we report an analysis of the subunit composition and substrate specificity of the NSL complex. Proteomic analyses of complexes purified through multiple candidate subunits reveal that NSL is composed of nine subunits. Two of its subunits, WD repeat domain 5 (WDR5) and host cell factor 1 (HCF1), are shared with members of the MLL/SET family of histone H3 lysine 4 (H3K4) methyltransferase complexes, and a third subunit, MCRS1, is shared with the human INO80 chromatin-remodeling complex. In addition, we show that assembly of the MOF HAT into MSL or NSL complexes controls its substrate specificity. Although MSL-associated MOF acetylates nucleosomal histone H4 almost exclusively on lysine 16, NSL-associated MOF exhibits a relaxed specificity and also acetylates nucleosomal histone H4 on lysines 5 and 8. Title: Functional deprivation promotes amyloid plaque pathogenesis in Tg2576 mouse olfactory bulb and piriform cortex Zhang XM, Xiong K, Cai Y, Cai H, Luo XG, Feng JC, Clough RW, Patrylo PR, Struble RG, Yan XX Ref: European Journal of Neuroscience, 31:710, 2010 : PubMed ESTHER: Zhang_2010_Eur.J.Neurosci_31_710 PubMedSearch: Zhang 2010 Eur.J.Neurosci 31 710 PubMedID: 20384814 Abstract Cerebral hypometabolism and amyloid accumulation are principal neuropathological manifestations of Alzheimer's disease (AD). Whether and how brain/neuronal activity might modulate certain pathological processes of AD are interesting topics of recent clinical and basic research in the field, and may be of potential medical relevance in regard to both the disease etiology and intervention. Using the Tg2576 transgenic mouse model of AD, this study characterized a promotive effect of neuronal hypoactivity associated with functional deprivation on amyloid plaque pathogenesis in the olfactory pathway. Unilateral naris-occlusion caused beta-secretase-1 (BACE1) elevation in neuronal terminals in the deprived relative to the non-deprived bulb and piriform cortex in young adult mice. In parallel with the overall age-related plaque development in the forebrain, locally increased BACE1 immunoreactivity co-occurred with amyloid deposition first in the piriform cortex then within the bulb, more prominent on the deprived relative to the non-deprived side. Biochemical analyses confirmed elevated BACE1 protein levels, enzymatic activity and products in the deprived relative to non-deprived bulbs. Plaque-associated BACE1 immunoreactivity in the bulb and piriform cortex was localized preferentially to swollen/sprouting glutamatergic axonal terminals, with Abeta immunoreactivity occurring inside as well as around these terminals. Together, these findings suggest that functional deprivation or neuronal hypoactivity facilitates amyloid plaque formation in the forebrain in a transgenic model of AD, which operates synergistically with age effect. The data also implicate an intrinsic association of amyloid accumulation and plaque formation with progressive axonal pathology. Title: Doublecortin expression in adult cat and primate cerebral cortex relates to immature neurons that develop into GABAergic subgroups Cai Y, Xiong K, Chu Y, Luo DW, Luo XG, Yuan XY, Struble RG, Clough RW, Spencer DD and Yan XX <3 more author(s)> Cai Y, Xiong K, Chu Y, Luo DW, Luo XG, Yuan XY, Struble RG, Clough RW, Spencer DD, Williamson A, Kordower JH, Patrylo PR, Yan XX (- 3) Ref: Experimental Neurology, 216:342, 2009 : PubMed ESTHER: Cai_2009_Exp.Neurol_216_342 PubMedSearch: Cai 2009 Exp.Neurol 216 342 PubMedID: 19166833 Abstract DCX-immunoreactive (DCX+) cells occur in the piriform cortex in adult mice and rats, but also in the neocortex in adult guinea pigs and rabbits. Here we describe these cells in adult domestic cats and primates. In cats and rhesus monkeys, DCX+ cells existed across the allo- and neocortex, with an overall ventrodorsal high to low gradient at a given frontal plane. Labeled cells formed a cellular band in layers II and upper III, exhibiting dramatic differences in somal size (5-20 microm), shape (unipolar, bipolar, multipolar and irregular), neuritic complexity and labeling intensity. Cell clusters were also seen in this band, and those in the entorhinal cortex extended into deeper layers as chain-like structures. Densitometry revealed a parallel decline of the cells across regions with age in cats. Besides the cellular band, medium-sized cells with weak DCX reactivity resided sparsely in other layers. Throughout the cortex, virtually all DCX+ cells co-expressed polysialylated neural cell adhesion molecule. Medium to large mature-looking DCX+ cells frequently colocalized with neuron-specific nuclear protein and gamma-aminobutyric acid (GABA), and those with a reduced DCX expression also partially co-labeled for glutamic acid decarboxylase, parvalbumin, calbindin, beta-nicotinamide adenine dinucleotide phosphate diaphorase and neuronal nitric oxide synthase. Similar to cats and monkeys, small and larger DCX+ cells were detected in surgically removed human frontal and temporal cortices. These data suggest that immature neurons persist into adulthood in many cortical areas in cats and primates, and that these cells appear to undergo development and differentiation to become functional subgroups of GABAergic interneurons. Title: Doublecortin-expressing cells persist in the associative cerebral cortex and amygdala in aged nonhuman primates Zhang XM, Cai Y, Chu Y, Chen EY, Feng JC, Luo XG, Xiong K, Struble RG, Clough RW and Yan XX <2 more author(s)> Zhang XM, Cai Y, Chu Y, Chen EY, Feng JC, Luo XG, Xiong K, Struble RG, Clough RW, Patrylo PR, Kordower JH, Yan XX (- 2) Ref: Front Neuroanat, 3:17, 2009 : PubMed ESTHER: Zhang_2009_Front.Neuroanat_3_17 PubMedSearch: Zhang 2009 Front.Neuroanat 3 17 PubMedID: 19862344 Abstract A novel population of cells that express typical immature neuronal markers including doublecortin (DCX+) has been recently identified throughout the adult cerebral cortex of relatively large mammals (guinea pig, rabbit, cat, monkey and human). These cells are more common in the associative relative to primary cortical areas and appear to develop into interneurons including type II nitrinergic neurons. Here we further describe these cells in the cerebral cortex and amygdala, in comparison with DCX+ cells in the hippocampal dentate gyrus, in three age groups of rhesus monkeys: young adult (12.3 +/- 0.2 years, n = 3), mid-age (21.2 +/- 1.9 years, n = 3) and aged (31.3 +/- 1.8 years, n = 4). DCX+ cells with a heterogeneous morphology persisted in layers II/III primarily over the associative cortex and amygdala in all groups (including in two old animals with cerebral amyloid pathology), showing a parallel decline in cell density with age across regions. In contrast to the cortex and amygdala, DCX+ cells in the subgranular zone diminished in the mid-age and aged groups. DCX+ cortical cells might arrange as long tangential migratory chains in the mid-age and aged animals, with apparently distorted cell clusters seen in the aged group. Cortical DCX+ cells colocalized commonly with polysialylated neural cell adhesion molecule and partially with neuron-specific nuclear protein and gamma-aminobutyric acid, suggesting a potential differentiation of these cells into interneuron phenotype. These data suggest a life-long role for immature interneuron-like cells in the associative cerebral cortex and amygdala in nonhuman primates. Title: Beta-secretase-1 elevation in transgenic mouse models of Alzheimer's disease is associated with synaptic/axonal pathology and amyloidogenesis: implications for neuritic plaque development Zhang XM, Cai Y, Xiong K, Cai H, Luo XG, Feng JC, Clough RW, Struble RG, Patrylo PR, Yan XX Ref: European Journal of Neuroscience, 30:2271, 2009 : PubMed ESTHER: Zhang_2009_Eur.J.Neurosci_30_2271 PubMedSearch: Zhang 2009 Eur.J.Neurosci 30 2271 PubMedID: 20092570 Abstract The presence of neuritic plaques is a pathological hallmark of Alzheimer's disease (AD). However, the origin of extracellular beta-amyloid peptide (Abeta) deposits and the process of plaque development remain poorly understood. The present study attempted to explore plaque pathogenesis by localizing beta-secretase-1 (BACE1) elevation relative to Abeta accumulation and synaptic/neuritic alterations in the forebrain, using transgenic mice harboring familial AD (FAD) mutations (5XFAD and 2XFAD) as models. In animals with fully developed plaque pathology, locally elevated BACE1 immunoreactivity (IR) coexisted with compact-like Abeta deposition, with BACE1 IR occurring selectively in dystrophic axons of various neuronal phenotypes or origins (GABAergic, glutamatergic, cholinergic or catecholaminergic). Prior to plaque onset, localized BACE1/Abeta IR occurred at swollen presynaptic terminals and fine axonal processes. These BACE1/Abeta-containing axonal elements appeared to undergo a continuing process of sprouting/swelling and dystrophy, during which extracellular Abeta IR emerged and accumulated in surrounding extracellular space. These data suggest that BACE1 elevation and associated Abeta overproduction inside the sprouting/dystrophic axonal terminals coincide with the onset and accumulation of extracellular amyloid deposition during the development of neuritic plaques in transgenic models of AD. Our findings appear to be in harmony with an early hypothesis that axonal pathogenesis plays a key or leading role in plaque formation. Title: [Directed evolution of lipase of Bacillus pumilus YZ02 by error-prone PCR] Huang Y, Cai Y, Yang J, Yan Y Ref: Sheng Wu Gong Cheng Xue Bao, 24:445, 2008 : PubMed ESTHER: Huang_2008_Sheng.Wu.Gong.Cheng.Xue.Bao_24_445 PubMedSearch: Huang 2008 Sheng.Wu.Gong.Cheng.Xue.Bao 24 445 PubMedID: 18589821 Abstract Random mutagenesis on Bacillus pumilus lipase YZ02 gene was conducted by using error-prone PCR strategy. Through two cycles of directed evolution, two optimum mutants BpL1-7 and BpL2-1369 with lipase activity improved 2 folds and 6 folds respectively were screened. The sequence of BpL2-1369 lipase gene showed that four nucleotides substitution, T61C, C147T, A334G and T371A have occurred, and three of them caused amino acid changes. Thus, amine acid Ser21 was changed into Pro21, Arg112 to Gly112, and Leu124 to His124. According to the 3D structure of Bacillus pumilus lipase mimicked by SWISS-MODEL Repository, three mutated amino acids were located at the third amino acid of the first alpha-helix, the turn between the fourth and fifth beta fold, and the first amino acid of the fifth beta fold, respectively. The BpL and BpL2-1369 genes were ligated into pET28a vector, and transferred into E. coli BL21 (DE3). After induced by IPTG the lipases were purified and characterized. The results showed that the specific activity of the evolved lipase was 1.31-fold than that of the wild lipase, and the Km decreased from 8.24 mmol/L to 7.17 mmol/L. The pH stability of the evolved lipase was better than wild lipase when pH>8.0. Title: Genome sequence of the cat pathogen, Chlamydophila felis Azuma Y, Hirakawa H, Yamashita A, Cai Y, Rahman MA, Suzuki H, Mitaku S, Toh H, Goto S and Shirai M <6 more author(s)> Azuma Y, Hirakawa H, Yamashita A, Cai Y, Rahman MA, Suzuki H, Mitaku S, Toh H, Goto S, Murakami T, Sugi K, Hayashi H, Fukushi H, Hattori M, Kuhara S, Shirai M (- 6) Ref: DNA Research, 13:15, 2006 : PubMed ESTHER: Azuma_2006_DNA.Res_13_15 PubMedSearch: Azuma 2006 DNA.Res 13 15 PubMedID: 16766509 Gene_locus related to this paper: chlff-q253e0, chlff-q254l8 Abstract Chlamydophila felis (Chlamydia psittaci feline pneumonitis agent) is a worldwide spread pathogen for pneumonia and conjunctivitis in cats. Herein, we determined the entire genomic DNA sequence of the Japanese C. felis strain Fe/C-56 to understand the mechanism of diseases caused by this pathogen. The C. felis genome is composed of a circular 1,166,239 bp chromosome encoding 1005 protein-coding genes and a 7552 bp circular plasmid. Comparison of C. felis gene contents with other Chlamydia species shows that 795 genes are common in the family Chlamydiaceae species and 47 genes are specific to C. felis. Phylogenetic analysis of the common genes reveals that most of the orthologue sets exhibit a similar divergent pattern but 14 C. felis genes accumulate more mutations, implicating that these genes may be involved in the evolutional adaptation to the C. felis-specific niche. Gene distribution and orthologue analyses reveal that two distinctive regions, i.e. the plasticity zone and frequently gene-translocated regions (FGRs), may play important but different roles for chlamydial genome evolution. The genomic DNA sequence of C. felis provides information for comprehension of diseases and elucidation of the chlamydial evolution. | |||||||
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