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. Sirivarasai, Jintana; Kaojarern, Sming; Yoovathaworn, Krongtong; Sura, Thanyachai 2007-07-20 Paraoxonase ( PON1) plays an important role in mechanism of organophosphorus compound (OP) toxicity, as seen both in vitro and in vivo studies. Polymorphisms of PON1 gene at coding and promoter regions have also been to affect on the hydrolytic activity and PON1 level. The objectives of this study were to determine PON1 polymorphism and activity in an OP-exposed population and the effects on inhibition of cholinesterase activity. The studied population consisted of control (n=30) and exposed groups (n=90). All enzyme activities (AChE, BuChE, paraoxonase, arylesterase and diazonase) were measured once for control group and two periods of exposure for exposed group.
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Three polymorphisms of PON1 (Q192R, L55M and T-108C) were identified only in the exposed subjects. The results demonstrated that AChE activity in both high (345.5 microkat/gHb) and low exposure periods (496.9 microkat/gHb) of the exposed group were significantly different from control group (649.7 microkat/gHb, pQRRR, LLLM and -108CC-108CT-108TT, but this was not found for those of arylesterase and diazonase activities. Q192R and L55M as well as Q192R and T-108C also presented substantial linkage disequilibrium. Further analysis was performed with haplotypes and various enzyme activities. AChE activity was not affected by haplotypes. Individuals with '211' haplotype showed significantly higher paraoxonase activity and BuChE activity than other haplotypes but not in diazonase activity.
In conclusion, PON1 gene exhibited a wide variation in enzyme activities both within and between genotypes which implied insights of a potentially difference in sensitivity to OP toxicity. Mccarthy, Bruce G.; Peroutka, Stephen J. 1988-01-01 Radioligand binding studies were used to analyze muscarinic cholinergic receptor subtypes in human cortex and pons. Muscarinic cholinergic receptors were labeled by H-3-quinuclidinyl benzilate (H-3-QNB).
Scopolamine was equipotent in both brain regions and did not discriminate subtypes of H-3-QNB binding. By contrast, the M1 selective antagonist pirenzepine was approximately 33-fold more potent in human cortex than pons.
Carbachol, a putative M2 selective agonist, was more than 100-fold more potent in human pons than cortex. These results demonstrate that the human pons contains a relatively large proportion of carbachol-sensitive muscarinic cholinergic receptors. Drugs targeted to this subpopulation of muscarinic cholinergic receptors may prove to be effective anti-motion sickness agents with less side effects than scopolamine. Rosenblat, M; Elias, A; Volkova, N; Aviram, M 2013-04-01 In the current study, we analysed free radicals scavenging activity of monocytes-macrophages in the absence or presence of antioxidants such as polyphenols or paraoxonase 1 ( PON1). THP-1 human monocytic cell line, murine J774A.1 macrophages, as well as human primary monocytes have the capability to scavenge free radicals, as measured by the 1-diphenyl-2-picryl-hydrazyl (DPPH) assay. This effect (which could be attributed to the cell's membrane) was cell number and incubation time dependent. Upon incubation of J774A.1 macrophages with acetylated LDL (Ac-LDL), with VLDL, or with the radical generator, AAPH, the cells' lipid peroxides content, and paraoxonase 2 ( PON2) activity were significantly increased.
While non-treated cells decreased DPPH absorbance by 65%, the Ac-LDL-, VLDL- or AAPH-treated cells, decreased it by only 33%, 30%, or 45%, respectively. We next analysed the effect of J774A.1 macrophage enrichment with antioxidants, such as polyphenols or PON1 on the cells' free radicals scavenging activity. Non-treated cells decreased DPPH absorbance by 50%, whereas vitamin E-, punicalagin- or PJ-treated cells significantly further decreased it, by 75%.
Similarly, in PON1-treated cells DPPH absorbance was further decreased by 63%, in association with 23% increment in PON1 catalytic activity. In cells under oxidative stress treated with AAPH-, or with oxidized LDL, PON1 activity was decreased by 31% or 40%, as compared to the activity observed in PON1 incubated with non-treated cells. We conclude that monocytes-macrophages possess free radicals scavenging activity, which is decreased under atherogenic conditions, and increased upon cell enrichment with potent antioxidants such as nutritional polyphenols, or PON1. Kieser, Karen J.; Baer, Christina E.; Barczak, Amy K.; Meniche, Xavier; Chao, Michael C.; Rego, E. Hesper; Sassetti, Christopher M.; Fortune, Sarah M.; Rubin, Eric J. 2015-01-01 Cell growth and division are required for the progression of bacterial infections. Most rod-shaped bacteria grow by inserting new cell wall along their mid-section.
However, mycobacteria, including the human pathogen Mycobacterium tuberculosis, produce new cell wall material at their poles. How mycobacteria control this different mode of growth is incompletely understood. Here we find that PonA1, a penicillin binding protein (PBP) capable of transglycosylation and transpeptidation of cell wall peptidoglycan (PG), is a major governor of polar growth in mycobacteria. PonA1 is required for growth of Mycobacterium smegmatis and is critical for M.
Tuberculosis during infection. In both cases, PonA1’s catalytic activities are both required for normal cell length, though loss of transglycosylase activity has a more pronounced effect than transpeptidation. Mutations that alter the amount or the activity of PonA1 result in abnormal formation of cell poles and changes in cell length. Moreover, altered PonA1 activity results in dramatic differences in antibiotic susceptibility, suggesting that a balance between the two enzymatic activities of PonA1 is critical for survival. We also find that phosphorylation of a cytoplasmic region of PonA1 is required for normal activity.
Mutations in a critical phosphorylated residue affect transglycosylase activity and result in abnormal rates of cell elongation. Together, our data indicate that PonA1 is a central determinant of polar growth in mycobacteria, and its governance of cell elongation is required for robust cell fitness during both host-induced and antibiotic stress. PMID:26114871. Bounafaa, Abdelghani; Berrougui, Hicham; Ghalim, Noreddine; Nasser, Boubker; Bagri, Abdallah; Moujahid, Abderrahmane; Ikhlef, Souad; Camponova, Pamela; Yamoul, Najoua; Simo, Olivier Kamtchueng; Essamadi, Abdelkhalid; Khalil, Abdelouahed 2015-01-01 The purpose of the present study was to investigate the distribution of PON1 Q192R and L55M polymorphisms and activities in a North African population and to determine their association with cardiovascular complications. The prevalence of the QQ, QR, RR, LL, LM, and MM genotypes in the study population was 55.4%, 34.09%, 9.83%, 41.97%, 48.20%, and 9.83% respectively. The Q, R, L, and M alleles had a gene frequency of 0.755, 0.245, 0.67, and 0.33, respectively.
The PON1 192 RR genotype was significantly more prevalent among ACS patients than among healthy subjects. There was a 4.33-fold increase in the risk of ACS in subjects presenting the PON1 192 RR genotype compared to those with the QQ genotype (OR=4.33; 95% CI=1.27–17.7). There was a significantly different distribution of PON1 L55M in the ACS patient groups (UA, STEMI, NSTEMI). Moreover, individuals presenting the PON1 55MM genotype present a higher risk for ACS than those with LL genotype (OR=3.69; 95% CI=1.61–11.80). Paraoxonase activities were significantly lower in coronary patients than in healthy subjects. The decrease in PON1 activity was inversely correlated with the number of concomitant risk factors for CVD (r=0.57, p420 nm) at 16 K F(2) P(O)N reacts with molecular nitrogen and some of the azide is regenerated. UV irradiation (lambda=255 nm) of F(2) P(O)N (X(3)A') induced a Curtius-type rearrangement, but instead of a 1,3-fluorine shift, nitrogen migration to give F(2) PON is proposed to be the first step of the photoisomerization of F(2) P(O)N into F(2)PNO (difluoronitrosophosphine).
Formation of novel F(2)PNO was confirmed with (15)N- and (18)O-enriched isotopomers by IR spectroscopy and DFT calculations. Theoretical calculations predict a rather long P-N bond of 1.922 A B3LYP/6-311+G(3df) and low bond-dissociation energy of 76.3 kJ mol(-1) (CBS-QB3) for F(2)PNO. Otocka-Kmiecik, Aneta; Lewandowski, Marek; Szkudlarek, Urszula; Nowak, Dariusz; Orlowska-Majdak, Monika 2014-01-01 The aim of the study was to compare the effect of maximal exercise (ME) on paraoxonase ( PON) and arylesterase (ARE) activity depending on lifestyle in respect to physical activity. The study was performed on 46 young men divided into two groups: sedentary (S) and physically active (PA). All participants performed ME on a treadmill. PON1 activities, FRAP, uric acid, bilirubin, TBARS, and lipid profile were determined in their blood before, at the bout of, and after ME. No significant differences in PON1 activities were found between S and PA subjects at baseline.
Nearly all biochemicals increased at ME in both groups. Both PON and ARE activity increased at the bout of ME in PA subjects and only ARE activity in S subjects. ARE/HDL-C ratio increased at the bout of ME in PA and S subjects.
The difference in PON1 activity response to ME between study groups may be a result of adaptation of PA subjects to regular physical activity. We suggest that PON1 activity may be a marker of antioxidant protection at ME and an indicator of adaptation to exercise. PMID:25379522.
Gonzalez, V.; Huen, K.; Venkat, S.; Pratt, K.; Xiang, P.; Harley, K.G.; Kogut, K.; Trujillo, C.M.; Bradman, A.; Eskenazi, B.; Holland, N.T. 2014-01-01 Exposure to organophosphate and carbamate pesticides can lead to neurotoxic effects through inhibition of cholinesterase enzymes. The paraoxonase ( PON1) enzyme can detoxify oxon derivatives of some organophosphates. Lower PON1, acetylcholinesterase, and butyrylcholinesterase activities have been reported in newborns relative to adults, suggesting increased susceptibility to organophosphate exposure in young children.
We determined PON1, acetylcholinesterase, and butyrylcholinesterase activities in Mexican-American mothers and their 9-year-old children (n=202 pairs) living in an agricultural community in California. We used paired t-tests to compare enzymatic activities among mothers and their children and analysis of variance to determine which factors are associated with enzyme activities. Substrate-specific PON1 activities were slightly lower in children than their mothers; however, these differences were not statistically significant. We observed significantly lower acetylcholinesterase but higher butyrylcholinesterase levels in children compared to their mothers. Mean butyrylcholinesterase levels were strongly associated with child obesity status (BMI Z scores 95%).
We observed highly significant correlations among mother-child pairs for each of the enzymatic activities analyzed; however, PON1 activities did not correlate with acetylcholinesterase or butyrylcholinesterase activities. Our findings suggest that by age nine, PON1 activities approach adult levels and host factors including sex and obesity may affect key enzymes involved in pesticide metabolism. PMID:22760442. Otocka-Kmiecik, Aneta; Lewandowski, Marek; Szkudlarek, Urszula; Nowak, Dariusz; Orlowska-Majdak, Monika 2014-01-01 The aim of the study was to compare the effect of maximal exercise (ME) on paraoxonase ( PON) and arylesterase (ARE) activity depending on lifestyle in respect to physical activity.
The study was performed on 46 young men divided into two groups: sedentary (S) and physically active (PA). All participants performed ME on a treadmill. PON1 activities, FRAP, uric acid, bilirubin, TBARS, and lipid profile were determined in their blood before, at the bout of, and after ME. No significant differences in PON1 activities were found between S and PA subjects at baseline. Nearly all biochemicals increased at ME in both groups. Both PON and ARE activity increased at the bout of ME in PA subjects and only ARE activity in S subjects. ARE/HDL-C ratio increased at the bout of ME in PA and S subjects.
The difference in PON1 activity response to ME between study groups may be a result of adaptation of PA subjects to regular physical activity. We suggest that PON1 activity may be a marker of antioxidant protection at ME and an indicator of adaptation to exercise.
Zhu, Min; Zhong, Wen-De; Zhang, Zhenrong; Luan, Feng 2013-11-01 We propose and demonstrate an improved survivable and energy-saving WDM- PON with colorless ONUs. It incorporates both energy-saving and self-healing operations. A simple effective energy-saving scheme is proposed by including an energy-saving control unit in the OLT and a control unit at each ONU. The energy-saving scheme realizes both dozing and sleep (offline) modes, which greatly improves the energy-saving efficiency for WDM- PONs.
An intelligent protection switching scheme is designed in the OLT, which can distinguish if an ONU is in dozing/sleep (offline) state or a fiber is faulty. Moreover, by monitoring the optical power of each channel on both working and protection paths, the OLT can know the connection status of every fiber path, thus facilitating an effective protection switching and a faster failure recovery. The improved WDM- PON architecture not only significantly reduces energy consumption, but also performs self-healing operation in practical operation scenarios. The scheme feasibility is experimentally verified with 10 Gbit/s downstream and 1.25 Gbit/s upstream transmissions.
We also examine the energy-saving efficiency of our proposed energy-saving scheme by simulation, which reveals that energy saving mainly arises from the dozing mode, not from the sleep mode when the ONU is in the online state. Zare, Sajjad; Ghaffarpour Rahbar, Akbar 2015-01-01 With the expansion of PON networks as Long-Reach PON (LR- PON) networks, the problem of degrading the efficiency of centralized bandwidth allocation algorithms threatens this network due to high propagation delay. This is because these algorithms are based on bandwidth negotiation messages frequently exchanged between the optical line terminal (OLT) in the Central Office and optical network units (ONUs) near the users, which become seriously delayed when the network is extended. To solve this problem, some decentralized algorithms are proposed based on bandwidth negotiation messages frequently exchanged between the Remote Node (RN)/Local Exchange (LX) and ONUs near the users. The network has a relatively high delay since there are relatively large distances between RN/LX and ONUs, and therefore, control messages should travel twice between ONUs and RN/LX in order to go from one ONU to another ONU. In this paper, we propose a novel framework, called ONU Turning with Adaptive Cycle Times (OTACT), that uses Power Line Communication (PLC) to connect two adjacent ONUs. Since there is a large population density in urban areas, ONUs are closer to each other.
Thus, the efficiency of the proposed method is high. We investigate the performance of the proposed scheme in contrast with other decentralized schemes under the worst case conditions. Simulation results show that the average upstream packet delay can be decreased under the proposed scheme. Bindhaiq, Salem; Zulkifli, Nadiatulhuda; Supa'at, Abusahmah M.; Idrus, Sevia M.; Salleh, M. 2017-11-01 Time and wavelength division multiplexed passive optical network (TWDM- PON) trend is considered as the most extraordinary trend of the next generation solution to accommodate exponential traffic growth for converged new services. In this paper, we briefly review recent progress on TWDM- PON system through the use of low cost directly modulated lasers (DMLs) transmission for various line rate transmissions to date.
Furthermore, through simulation, we propose and evaluate a cost effective way to upgrade TWDM- PON up to a symmetric capacity of 128 Gb/s using fiber Bragg gratings (FBGs) in optical line terminal (OLT) as a paramount dispersion manager in high speed light-wave systems in both upstream and downstream directions. A low cost and potential chirpless directed modulated grating laser (DMGL) is employed for downstream link and DML with a single delay-interferometer (DI) is employed for upstream link. After illustrating the demonstrated system architecture and configuration, we present the results and analysis to prove the system feasibility. The results show that a successful transmission is achieved over 40 km single mode fiber with a power budget of 33.7 dB, which could support 1:256 splitting ratio.
Xiong, Yu; Sun, Peng; Liu, Chuanbo; Guan, Jianjun 2017-01-01 Time and wavelength division multiplexed passive optical network (TWDM- PON) is considered to be a primary solution for next-generation passive optical network stage 2 (NG- PON2). Due to the feature of multi-wavelength transmission of TWDM- PON, some of the transmitters/receivers at the optical line terminal (OLT) could be shut down to reduce the energy consumption.
Therefore, a novel scheme called traffic-aware energy saving scheme with modularization supporting is proposed. Through establishing the modular energy consumption model of OLT, the wavelength transmitters/receivers at OLT could be switched on or shut down adaptively depending on sensing the status of network traffic load, thus the energy consumption of OLT will be effectively reduced. Furthermore, exploring the technology of optical network unit (ONU) modularization, each module of ONU could be switched to sleep or active mode independently in order to reduce the energy consumption of ONU.
Simultaneously, the polling sequence of ONU could be changed dynamically via sensing the packet arrival time. In order to guarantee the delay performance of network traffic, the sub-cycle division strategy is designed to transmit the real-time traffic preferentially. Finally, simulation results verify that the proposed scheme is able to reduce the energy consumption of the network while maintaining the traffic delay performance.