169,862 research outputs found
PREVENTIVE STRATEGIES TO COUNTERBALANCE FOOD PESTICIDE EFFECT ON EPIGENOME AND GUT MICROBIOTA
No full textFood pesticide residues have been identified in food as well as in people’s urine [1]. Studies on early life exposure to the food pesticide permethrin demonstrate its ability to modulate gene expression, epigenome and gut microbiota leading to long term effects later in life [2-4].
In particular, permethrin pesticide, binding to sodium channels, induces neuron depolarization which modulate DNMTs activities responsible for DNA methylation [5].
Previously, we demonstrated changes in the DNMTs in striatum of animals exposed to permethrin during brain development [2]. Besides, we observed that permethrin is able to decrease global DNA methylation and dopamine level in mothers exposed to food pesticide during early life as well as in their untreated offspring, underlining the intergenerational effect of the food pesticide [6]. Of particular interest is the evidence that permethrin exposure can also promote significantly changes in gut microbiota.
With the aim to propose strategies for prevention, bioactive supplements have been studied and positive nutrigenomic effects able to counterbalance the brain and gut microbiota alterations will be discussed.
References
1. Tang W, Wang D, Wang J, Wu Z, Li L, Huang M, Xu S, Yan D. Pyrethroid pesticide residues in the global environment: An overview. Chemosphere. 2018;191:990-1007.
2. Fedeli D, Montani M, Bordoni L, Galeazzi R, Nasuti C, Correia-Sá L, Domingues VF, Jayant M, Brahmachari V, Massaccesi L, Laudadio E, Gabbianelli R. In vivo and in silico studies to identify mechanisms associated with Nurr1 modulation following early life exposure to permethrin in rats. Neuroscience. 2017 Jan 6;340:411-423.
3. Nasuti C, Brunori G, Eusepi P, Marinelli L, Ciccocioppo R, Gabbianelli R. Early life exposure to permethrin: a progressive animal model of Parkinson's disease.
J Pharmacol Toxicol Methods. 2017;83:80-86.
4. Nasuti C, Coman MM, Olek RA, Fiorini D, Verdenelli MC, Cecchini C, Silvi S, Fedeli D, Gabbianelli R. Changes on fecal microbiota in rats exposed to permethrin during postnatal development.
Environ Sci Pollut Res Int. 2016; 23(11):10930-7.
5. Sharma RP, Tun N, Grayson DR (2008) Depolarization induces downregulation of DNMT1 and DNMT3a in primary cortical cultures. Epigenetics 3:74–80
6. Bordoni L, Nasuti C, Mirto M, Caradonna F, Gabbianelli R. Intergenerational Effect of Early Life Exposure to Permethrin: Changes in Global DNA Methylation and in Nurr1 Gene Expression.
Toxics. 2015;3(4):451-46
Protective effect of glutathione on damage induced by permethrin in a neuronal model of PC12 cells.
No full textObjective: Permethrin, a member of the family of synthetic pyrethroids, can induce oxidative stress and impairment in expression of Nurr1, a transcription factor essential for the maintenance of dopaminergic neurons. These conditions, flanked to low level of glutathione (GSH), are typical in neurons affected by Parkinson Disease (PD). The aim of this study is to evaluate in vitro effects of GSH on a stress dependent parameters (Nurr1) measured in PC12 cells culture treated with permethrin.
Methods: PC12 cells were seeded and treated for 72h with 1uM permethrin and separately co-treated with the pesticide and 32nM glutathione (1). Then, qRT-PCR was performed to evaluate Nurr1 gene expression.
Results: In cells cultures under stress condition, such as those induced by permethrin, Nurr1 gene expression changed, maybe as a compensatory effect to damage. In contrast, when cells were co-treated with glutathione, Nurr1 value was reestablished as the control.
Conclusion: Pesticides, mainly assumed with diet, can modulate gene expression leading to the onset and progression of age-related diseases. Permethrin, in particular, can induce stress in neuronal dopaminergic cells, mimicking PD condition (2). As demonstrated by previous in vivo studies, permethrin exposure can lead to progressive neuronal damage characterized by GSH and Nurr1 deficit (3,4). The present study shows that GSH in vitro can contrast the negative effect induced by permethrin. We can hypothesize that GSH can prevent oxidative stress damage, avoiding cells to overreact by modifying the production of Nurr1. Hence, GSH can act as a preventive agent to cellular damage induced by permethrin.
References
1. Mesner PW, Winters TR, Green SH. (1992). Nerve growth factor withdrawal-induced cell death in neuronal PC12 cells resembles that in sympathetic neurons. J Cell Biol 119:1669–1680.
2. Carloni, M., Nasuti, C., Fedeli, D., Montani. M., Amici, A., Vadhana, M.S.D., Gabbianelli, R., 2013. Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2, Brain Research 1515, 19-28.
3. Falcioni ML, Nasuti C, Bergamini C, Fato R, Lenaz G. ( 2010). The primary role of GSH against nuclear DNA damage of striatum induced by permethrin in rats. Neuroscience 168(1), 2-10.
4. Nasuti C, Falcioni ML, Nwankwo IE, Cantalamessa F, Gabbianelli R. (2008). Effect of permethrin plus antioxidants on locomotor activity and striatum in adolescent rats. Toxicology., 29;251(1-3):45-50
Epigenetics of pesticide-induced neurodegeneration
No full textEarly life represents a key window of plasticity important for the programming of development through the cellular differentiation. During this period exogenous and endogenous factors (ie, nutrition, xenobiotics, stress, hypoxia, infections, hormones, etc.) can induce epigenetic changes leading to the development of diseases in adult age. Transgenerational studies on animal models show that epigenetic changes, such as DNA methylation and histone modifications, may be transferred to next generations.
Early life exposure to permethrin pyrethroid pesticide, during brain development is associated with dopaminergic neuron degeneration leading to the Parkinson-like disease (PD) in an animal model [1-3]. Pyrethroids represent a real risk for population as demonstrated by the detection of pyrethroid metabolites in the urine of world wide population, depending on the their presence in all vegetables and fruits [4-6].
Data from the PD animal model demonstrated that genetic and epigenetic changes are associated to permethrin-induced neurodegeneration [7]. Nurr1, the transcription factor responsible for the development and the maintenance of dopaminergic neurons, was significantly increased in early-life permethrin exposed rats. 33% of their untreated offspring showed the same Nurr1 increase as their parents. Furthermore, both mothers and untreated offspring (F1 generation) demonstrated a decrease in global DNA methylation.
It should be underlined that permethrin can cross the blood brain barrier, storing in the brain after the end of treatment. Furthermore, several sites of binding between Nurr1 and permethrin have been identified by in silico studies highlighting that the direct interaction between permethrin and Nurr1 might be suggested in early-life exposed rats [1]. Epigenetic modifications have been hypothesized to explain the intergenerational effect of Nurr1 in F1 generation.
References
[1] Fedeli D, Montani M, Bordoni L, Galeazzi R, Nasuti C, Correia-Sá L, Domingues VF, Jayant M, Brahmachari V, Massaccesi L, Laudadio E, Gabbianelli R. In vivo and in silico studies to identify mechanisms associated with Nurr1 modulation following early life exposure to permethrin in rats. Neuroscience. 2017, 340, 411.
[2] Nasuti C, Brunori G, Eusepi P, Marinelli L, Ciccocioppo R, Gabbianelli R.Early life exposure to permethrin: a progressive animal model of Parkinson's disease. J Pharmacol Toxicol Methods. 2017, 83, 80.
[3] Carloni M, Nasuti C, Fedeli D, Montani M, Vadhana MS, Amici A, Gabbianelli R. Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2. Brain Res. 2013, 17, 1515.
[4] Marsha K. Morgan. Children’s Exposures to Pyrethroid Insecticides at Home: A Review of Data Collected in Published Exposure Measurement Studies Conducted in the United States. Int J Environ Res Public Health. 2012, 9, 296.
[5] Dana Boyd Barr, Anders O. Olsson, Lee-Yang Wong, Simeon Udunka, Samuel E. Baker, Ralph D. Whitehead, Jr., Melina S. Magsumbol, Bryan L. Williams, Larry L. Needham. Urinary Concentrations of Metabolites of Pyrethroid Insecticides in the General U.S. Population: National Health and Nutrition Examination Survey 1999–2002. Environ Health Perspect. 2010, 118, 742.
[6] W. Li, M.K. Morgan, S.E. Graham, J.M. Starr. Measurement of pyrethroids and their environmental degradation products in fresh fruits and vegetables using a modification of the quick easy cheap effective rugged safe (QuEChERS) method. Talanta 2016, 151, 42.
[7] Bordoni L, Nasuti C, Mirto M, Caradonna F and Gabbianelli R. Intergenerational effect of early life exposure to permethrin: changes in global DNA methylation and in Nurr1 gene expression.
Toxics, 2015, 3(4), 451
Early life permethrin treatment induces in striatum of older rats changes in alpha-synuclein content
No full textObjectives: Many reports have demonstrated the strong relationship between environmental exposure during the first stages of life and the development in adult phase of neurodegenerative disorders. Previous studies performed in rats exposed from postnatal day 6 to 21 to low dose of permethrin (PERM) induced Parkinson-like neurodegeneration characterized in the striatum by a decrease of Nurr1 gene and protein expression, reduced dopamine level, together with its accelerated turnover (1-3). α-Synuclein is a presynaptic neuronal protein that contributes to Parkinson pathogenesis through its aggregation in oligomeric conformations called protofibrils that mediate disruption of cellular homeostasis and neuronal death. The present work aims to analyze in the striatum of early PERM treated rats the -sinuclein content in the adolescent, adult and old rats.
Methods PERM was dissolved in corn oil and administered orally to Wistar rats for 15 days, once a day in the morning from PND6 to PND21. Control rats were treated with vehicle (corn oil 4 ml/kg) on a similar schedule. Rats were sacrificed after 90 days (adolescent age), 180 days (adult age) and 300 days (old age) from the treatment and the striatum collected and kept at -80°C. Tissue lysates were prepared using two different buffers that solubilize -sinuclein in the free and aggregated forms. 40 g of protein were used for western blot analysis, separated using SDS–PAGE (7,5%) and electrophoretically blotted on a nitrocellulose support (Hybond C, Amersham Bioscience, Little Chalfont, UK). -synuclein antibody was purchased by Santa Cruz.
Results -synuclein free resulted more expressed in striatum from adolescent treated rats with respect to control while in samples from adult and old rats we observed an opposite situation with decreased level of -sinuclein in treated respect to their controls. Different oligomeric conformations of the protein were also observed when we analyzed by western blotting the lysate with solubilised aggregated protein. Striatum from adolescent treated rats shows higher expression of protein respect to the control with the formations of oligomers
Conclusions The early life treatment with PERM induces more significant effect on adolescent rats with the increase of -synuclein in both form, free and aggregated. This behavior could be explained with a more effective impairment of dopaminergic system in the first important phase of the life such as adolescence.
References:
1) Carloni M et al. 2012, Exp Gerontol. 47(1):60-66 2) Nasuti C et al.2013, Toxicology 303:162-168 3) Nasuti C et al. 2007, Toxicology 229(3):194-20
Yeast Bioflavoring in Beer: Complexity Decoded and Built up Again
No full textYeast is a powerful bioflavoring platform, suitable to confer special character and complexity to beer aroma. Enhancing yeast bioflavoring represents a chance for the brewing production chain to diversify its product portfolio and to increase environmental sustainability in the era of climate change. In flavor compound metabolism, multiple genes encoding biosynthetic enzymes and the related regulatory factors are still poorly known, but significant advances have been recently made to dissect gene contribution in flavor molecule production. Furthermore, causative mutations responsible for the huge strain diversity in yeast bioflavoring aptitude have been recently disclosed. This review covers the most recent advances in the genetics of yeast bioflavoring, with special regards to higher alcohols, esters, monoterpene alcohols, thiols, and phenolic derivatives of hydroxycinnamic acids. We also critically discussed the most significant strategies to enhance yeast bioflavoring, including bioprospecting for novel Saccharomyces and non-Saccharomyces strains, whole-genome engineering, and metabolic engineering
Permethrin pesticide residues in food mediate progressive neuronal disorder
No full textObjective: Pyrethroids are used in many formulations in agriculture to control insect pests in crops, forestry and horticulture. Environmental exposure results from dietary intake and this is confirmed by the quantification in human urine of the 3-PBA pyrethroid metabolite. The exposure to xenobiotics in the early stages of life, represents the most important component in the etiology of neurodegenerative diseases (1-3). Here, the impact of permethrin administered to rats from 6th to 21st day of life, was studied in adult animals by proteomic analysis of plasma and striatum. The concentration of permethrin and its 3-PBA metabolite were also evaluated.
Methods: GC-MS/SIM and GC-ECD were used to detect 3-PBA and permethrin in urine and striatum samples of rats 24 h and 14 days after the treatment. Two-dimensional electrophoresis followed by LC-MS/MS analysis was used for proteomic analysis.
Results: Permethrin in the brain was found at either 24 h or 14 days after the end of treatment and it was 10 times higher at 14 days; while the 3-PBA levels was higher at 24 h in both brain and urine. In plasma, long chain fatty acid protein transporter resulted significantly decreased on treated animal compared to control group. In striatum, mitochondrial Aspartate aminotransferase and voltage dependent anion channel were down expressed while Malate dehydrogenase, Myelin basic protein and Ubiquitin-60S ribosomal protein L40 resulted completely absent.
Conclusion: Permethrin accumulation in striatum can be responsible for the long term effects reported in striatum leading to down expression of proteins associated with neuronal disorder. Proteomic data can be utilized as biomarkers of neurodegeneration.
References:
1. Carloni, M., Nasuti, C., Fedeli, D., Montani, M., Amici, A., Vadhana, M.S., Gabbianelli, R., 2012. The impact of early life permethrin exposure on development of neurodegeneration in adulthood, Exp Gerontol. 47, 60-66.
2. Carloni, M., Nasuti, C., Fedeli, D., Montani. M., Amici, A., Vadhana, M.S.D., Gabbianelli, R., 2013. Early life permethrin exposure induces long-term brain changes in Nurr1, NF-kB and Nrf-2, Brain Research 1515, 19-28.
3. Fedeli, D., Montani, M., Nasuti, C., Gabbianelli, R., 2014. Early life permethrin treatment induces in striatum of older rats changes in alpha-synuclein content, Journal Nutrigenetics and Nutrigenomics 7, 80
Mitochondrial DNA methylation and copy number predict body composition in a young female population
No full textBackground: Since both genomic and environmental factors are involved in obesity etiology, several studies about the infuence of adiposity on both nuclear DNA and mitochondrial DNA methylation patterns have been carried out. Nevertheless, few evidences exploring the usage of buccal swab samples to study mitochondrial DNA epigenetics can be found in literature. Methods: In this study, mitochondrial DNA from buccal swabs collected from a young Caucasian population (n=69) have been used to examine potential correlation between mitochondrial DNA copy number and methylation with body composition (BMI, WHtR and bioimpedance measurements). Results: A negative correlation between mitochondrial DNA copy number and BMI was measured in females (p=0.028), but not in males. The mean percentage of D-loop methylation is signifcantly higher in overweight than in lean female subjects (p=0.003), and a specifc CpG located in the D-loop shows per se an association with impaired body composition (p=0.004). Body composition impairment is predicted by a combined variable including mtDNA copy number and the D-loop methylation (AUC=0.785; p=0.009). Conclusions: This study corroborates the hypothesis that mitochondrial DNA carries relevant information about body composition. However, wider investigations able to validate the usage of mtDNA methylation from buccal swabs as a biomarker are warrante
An approximate Riemann solver for real gas parabolized Navier-Stokes equations
No full textUnder specific assumptions, parabolized Navier-Stokes equations are a suitable mean to study channel flows. A special case is that of high pressure flow of real gases in cooling channels where large crosswise gradients of thermophysical properties occur. To solve the parabolized Navier-Stokes equations by a space marching approach, the hyperbolicity of the system of governing equations is obtained, even for very low Mach number flow, by recasting equations such that the streamwise pressure gradient is considered as a source term. For this system of equations an approximate Roe's Riemann solver is developed as the core of a Godunov type finite volume algorithm. The properties of the approximated Riemann solver, which is a modification of Roe's Riemann solver for the parabolized Navier-Stokes equations, are presented and discussed with emphasis given to its original features introduced to handle fluids governed by a generic real gas EoS. Sample solutions are obtained for low Mach number high compressible flows of transcritical methane, heated in straight long channels, to prove the solver ability to describe flows dominated by complex thermodynamic phenomena. (C) 2012 Elsevier Inc. All rights reserved
A new tectonic model for the Palaeoproterozoic Kautokeino Greenstone Belt, northern Norway, based on high-resolution airborne magnetic data and field structural analysis and implications for mineral potential
No full textThe Palaeoproterozoic Kautokeino Greenstone Belt (KkGB) is a highly tectonised metasupracrustal belt sandwiched between the gneissic Ráiseatnu
Complex to the west and the metaplutonic Jergul Complex to the east. The KkGB has been interpreted as an Early Proterozoic rift basin inverted
during the Svecofennian orogeny (c. 1.9-1.7 Ga). The structural framework and tectonic development of the KkGB remain poorly investigated and
understood. New airborne magnetic and structural data help to unravel the belt ́s architecture and tectonic evolution, allowing its subdivision into two
tectonic compartments. The eastern part shows NE-SW-trending, weak magnetic anomalies. The western part has pronounced NNW-SSE-trending
anomalies. In the Jergul Complex, to the east of the KkGB, only relatively weak but pervasive NE-SW-trending anomalies are observed, similar to those
in the eastern KkGB. These are locally deflected into NNE-SSW sets of discrete anomalies with a dextral offset. These two anomaly sets in the east
are truncated by a pervasive set of NNW-SSE-trending strong anomalies in the western KkGB. The Jergul and Ráiseatnu Complexes display different
aeromagnetic signatures suggesting that they are different terranes juxtaposed along the KkGB. Field structural analysis supports our interpretation
of the geophysics. The eastern NE-SW-trending KkGB and the Jergul Complex contain flat-lying, west-dipping, NE-SW-trending shear zones
accommodating dip-slip, top-to-the-east thrusting. The western NNW-SSE-trending KkGB is characterised by steeply dipping shear zones with both
dip-slip and strike-slip kinematics. Strike-slip shear zones are predominantly sinistral, but coexisting sinistral and dextral kinematics are commonly
observed together with steeply plunging lineations suggesting a degree of horizontal flattening. The NNW-SSE-trending shear zones, corresponding to
the NNW-SSE-trending magnetic anomalies, form a mega-sinistral array truncating and sinistrally deflecting the earlier thrust structures. The KkGB
is geometrically and kinematically similar to other Archaean-Palaeoproterozoic basement domains in northern Norway. Gold mineralisation at the
Bidjovagge mine is genetically related to deformation along the NNW-SSE-trending ductile shear zone of the western KkGB
Conditions for the occurrence of heat transfer deterioration in light hydrocarbons flows
No full textHeat transfer deterioration could affect heated channel flows of supercritical pressure fluids in a number of technological applications. Aim of the present study is to analyze the phenomenon onset and to investigate its dependence on the pressure, for three light hydrocarbons: methane, ethane and propane. To this goal a parametric numerical analysis is carried out on uniformly heated straight channels varying, for each different species, the inlet reduced pressure and the enforced heat flux. A parabolized Navier-Stokes solver is used to carry out the simulations, together with Helmholtz energy equation of state and accurate models for the transport properties. Results lead to an unambiguous definition of the threshold value for the ratio between heat flux and specific mass flow rate which identifies the boundary for heat transfer deterioration onset. On the basis of this definition, for assigned inlet reduced temperature, a correlation for the threshold parameter in terms of reduced pressure is presented for the considered species. (C) 2013 Elsevier Ltd. All rights reserved
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