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Bars represent the hACE2 Rosetta binding energies upon alanine substitution at the indicated site as a percentage of binding score prior to substitution. This procedure assesses how important is the identity of the native residues by defaulting them to alanine and observing whether this significantly affects binding. The percent loss of hACE2 binding upon substitution to alanine was used as a proxy score for assessing the importance of each RBD residue in binding and subsequent pathogenesis.

The results from the alanine scan study see Fig. This is because they help establish one strong electrostatic contact with Asp30, and three with Gln, Lys, and Gly as listed in Table 1.

The computational alanine scanning results identify the same three residues Phe, Gln, and Asn to be important for hACE2 binding as proposed by Wan et al.

Only twelve residues are involved in strong electrostatic coupling with hACE2 residues, out of which six are hydrogen bonded indicated in Table 1. All three viral RBDs are enriched in tyrosine residues. As many as We have not explored the phylogenetic basis for the presence of tyrosine residues but they do seem to be important for conferring high binding affinity spike and hACE2 for both SARS-CoV-2 and RaTG13, as alluded to by the alanine scan results see Fig.

We use Fig. The SARS-CoV-2 and RaTG13 Tyr and Tyr backbones, even though present in a loop, are mutually stabilized by hydrogen bonding and the side chains are locked in place by a pi-pi aromatic interaction between the phenyl rings. This enables both of these tyrosine side-chains to form a strong electrostatic contact with the Thr27 side-chain of hACE2. Next, we focus on the role of glycine residues see Fig. Interestingly, for all three variants the interaction with the hACE2 residue Lys with glycine residues in the spike protein is the same.

Atomic coordinates of both these complexes were independently, and experimentally confirmed by Song et al. Analysis of the three hACE2 binding interfaces see Fig. Nevertheless, the associated Rosetta binding energy is Up to this point we examined the biophysical characterization of hACE2 binding with the spike protein. Deshotels et al. We allowed all 21 contacting residues of the RBD of the spike protein to simultaneously mutate. We find see also Supplementary Fig. These predictions are largely in agreement with the exhaustive mutagenesis study by Wang et al.

A recent report [25] analyzes that humans can transfer SARS-CoV-2 to domesticated animals such as dogs, cats, ducks, and chickens in varying degrees. However, animal-to-human transmission has not been observed [26]. This is due to the formation of nine electrostatic contacts and one pi-pi stacking.

In all other cases, the Rosetta binding energies of ACE2 with the spike protein were at most We found that feline ACE2 had the closest Our findings qualitatively agree with Qiu et al. Note that Qiu et al. Thus it is difficult to resolve discrepancies as their result shows birds can serve as hosts for SARS-CoV-2 while our binding calculations say otherwise which corroborates experimental data by Mallapaty et al.

Chan et al. We recovered 40 out of 77 binding improving single amino acid substitutions reported by Chan et al. In addition, we computationally predicted eleven double and seven triple amino acid substitutions that lead to improvements in binding interactions by as much as 5.

Multiple lines of computational evidence indicate that the spike RBD binds hACE2 through electrostatic attachment with every fourth residue on the N-terminal alpha-helix starting from Ser19 to Asn53 as the turn of the helix makes these residues solvent accessible. Higher affinity with ACE2 may enable infection of epithelial cell in the upper respiratory track where ACE2 expression is lower in contrast to SARS-CoV that primarily infects epithelial cells in the deeper respiratory track lungs where ACE2 expression is higher [31] , [32] , [33] , [34].

Even though a founder effect cannot be excluded as the reason, increased conformational flexibility [37] of the spike may enhance SARS-CoV-2 ability to access cells. It is clear that binding with ACE2 remains unchanged as neither our computational analysis nor the exhaustive mutagenesis effort by Wang et al.

Zhang et al. Their binding experiments agree with our computational finding that the DG mutation does not cause stronger binding with hACE2. ZDOCK uses pairwise shape-complementarity, electrostatics, and implicit solvation terms in scoring the docked poses.

Implicit solvation treats the water as a dielectric continuum. Subsequently, PyRosetta [41] scripts were written to rank and identify the most stable complexes from each cluster which were then energy-minimized and re-ranked. Finally, the complex which ranked high in stability and binding scores was chosen as the model.

An alanine scan was again performed using PyRosetta scripts, where the computational models of the alanine variants were first generated, energy minimized, and hACE2 binding scores computed. A python script was prepared to execute multiple times the iTasser program [38].

Finally atomic-level backbone and side chain refinement was performed using fragment-guided molecular dynamics simulations FG-MD [45] for 50 ns for each structure.

MD simulations were performed using the Desmond [50] application v2. The initial positioning of the structure in the membrane was obtained from. Then, the membrane-bound structure was prepared using Desmond system builder. The default relaxation protocol of Desmond was performed followed by a 50 ns of production simulation at 1 atm pressure and K temperature, using the NPT ensemble under a periodic boundary condition using particle mesh Ewald.

Time step of 2. RC, and CDM conceived, and designed the study. VSB helped in performing the MD simulations. All three authors wrote the study. Costas D. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. RC thanks Debolina Sarkar for advice on the renin angiotensin system and also editing the paper.

Read article at publisher's site DOI : Int J Mol Sci , 23 3 , 04 Feb Vaccines Basel , 10 2 , 16 Feb One Health , , 24 Nov Emrani J , Hefner EN. Rabbani G , Ahn SN. Int J Biol Macromol , pt a , 18 Oct This data has been text mined from the article, or deposited into data resources. To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation. J Virol , 94 15 :e, 16 Jul Sci Bull Beijing , 66 12 , 19 Jan J Virol , 94 7 :e, 17 Mar Fraguas Bringas C , Booth D.

Access Microbiol , 2 11 :acmi, 08 Sep Nayak SK. Mini Rev Med Chem , 21 6 , 01 Jan Cited by: 3 articles PMID: Front Cell Dev Biol , , 16 Sep Contact us. Europe PMC requires Javascript to function effectively. Recent Activity. Search life-sciences literature 41,, articles, preprints and more Search Advanced search. This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

Search articles by 'Ratul Chowdhury'. Chowdhury R 1 ,. Search articles by 'Veda Sheersh Boorla'. Boorla VS 1 ,. Search articles by 'Costas D Maranas'. Maranas CD 1. Affiliations 3 authors 1. Share this article Share with email Share with twitter Share with linkedin Share with facebook. Abstract SARS-CoV-2 is a novel highly virulent pathogen which gains entry to human cells by binding with the cell surface receptor - angiotensin converting enzyme ACE2.

Free full text. Comput Struct Biotechnol J. Published online Sep PMID: Author information Article notes Copyright and License information Disclaimer.

Maranas: ude. Corresponding author. Copyright notice. This article has been cited by other articles in PMC. Go to:. Open in a separate window. In silico alanine scanning to identify spike residues most important for hACE2 binding Each one of the hACE2 binding residues from the three viral spike RBDs was computationally mutated to alanine one at a time and the resultant hACE2-RBD complexes were energy minimized and scored using the Rosetta energy function.

Presence of tyrosine and glycine residues in the hACE2 binding domains of these spike proteins All three viral RBDs are enriched in tyrosine residues. Competing financial interests The authors declare no competing financial interests. Supplementary data 1: Click here to view. Supplementary data 2: Click here to view. Hoffmann M. Shang J. Wang Q. Asai A. COVID drug discovery using intensive approaches.

Int J Mol Sci. Kuba K. Nat Med. Walls A. Yan R. Science doi: Watanabe Y. Wang Y. Proc Natl Acad Sci. Brielle E. Spinello A. J Phys Chem Lett. Amin M. Starr TN. Wan Y. Receptor recognition by novel coronavirus from Wuhan: an analysis based on decade-long structural studies of SARS. J Virol. Lam S. Research to date has focused primarily on exposure to single pesticides or pesticide classes in isolation; there are little data on the effect of exposure to pesticide mixtures on child and adolescent neurodevelopment.

We observed mostly null associations between pesticide applications and neurobehavioral outcomes. There were some trends of modestly increased internalizing behaviors and attention problems in association with organophosphate insecticide use near the home during the prenatal period. We observed some protective associations with imidacloprid during the prenatal period, particularly in sex-specific analyses.

We found only some subtle associations between some pesticides and neurobehavioral outcomes. This study extends previous work by considering potential exposure to mixtures of pesticides. Prenatal and early-life exposure to organophosphate pesticides has been associated with adverse child neurodevelopment; however, data gaps exist regarding the impact of exposure to mixtures of pesticides.

We employ Bayesian Hierarchical Models to examine associations of agricultural use of neurotoxic pesticides near the home during pregnancy and early childhood and adolescent neurobehavior in the Centers for the Health Assessment of Mothers and Children of Salinas cohort.

This study extends previous work by considering potential exposure to mixtures of pesticides and is the first to examine associations of pesticides with behavior problems measured longitudinally into adolescence and young adulthood. Epidemiologic studies to date have focused primarily on exposure to single pesticides or pesticide classes at a time, which may result in biased measures of association due to copollutant confounding by other pesticides.

These studies have largely relied on urinary biomarkers such as dialkylphosphate DAP metabolites, which are nonspecific, to characterize exposure; less is known about the effects of specific OPs with varying levels of toxicity. Bayesian methods have become increasingly utilized in epidemiologic analyses of chemical mixtures due to their ability to simultaneously model multiple highly correlated exposure variables.

Because many pesticides lack biomarkers or are cost-prohibitive to analyze in biological samples, recent analyses have used geospatial methods to characterize potential exposure to a range of pesticides. In a previous analysis in our cohort, we found that participants living in the areas of highest cumulative pesticide use during the prenatal period had intelligence quotient deficits of approximately 7 points at the age of 7 years compared with those living in areas of the lowest pesticide use.

Here, we investigate associations of agricultural applications of neurotoxic pesticides within 1 km of the home during pregnancy and early childhood with maternal- and self-reported behavioral and emotional problems at ages 16 and 18 years in the CHAMACOS cohort.

This analysis extends previous research by employing BHM to examine associations with specific pesticides while accounting for correlated coexposures.

This is the first study to examine associations of prenatal or early-life pesticide exposure with behavioral or emotional problems measured longitudinally into adolescence and young adulthood.

CHAM1 participants were recruited in community clinics serving predominantly low-income Latino patients in — Of the 1, eligible women, CHAM2 participants were recruited via newspaper and radio announcements advertising a study on the health effects of pesticides and environmental chemicals at local elementary schools, churches, libraries, food banks, and community events.

Mothers of CHAM1 participants were interviewed twice during pregnancy, after delivery, and throughout childhood. CHAM2 mothers completed a comprehensive baseline interview when their children were 9 years old. The total sample size with data on the exposure and outcome for the year analyses was for prenatal and for postnatal; the total for year analyses was for prenatal and for postnatal.

The University of California Berkeley Committee for the Protection of Human Subjects approved all study activities, and we obtained written informed consent from all mothers at all study visits. We obtained youth written assent at the age of 16 years and written consent at the age of 18 years.

We examined maternal- and youth-reported scores for four individual scales hyperactivity, attention problems, depression, and anxiety and the internalizing problems composite scale.

In addition, we examined maternal-reported scores for the externalizing problems composite scale there is no externalizing composite score for the youth-reported BASC-2 Self-Report of Personality. We used the latitude and longitude coordinates from geocoded residential addresses, reported prospectively at all study visits for CHAM1 participants, and reported retrospectively at the 9- and year visits from CHAM2 participants. We estimated the total amount of each pesticide that met these criteria applied within a 1-km radius of each residence.

We selected a 1-km buffer because this distance has been used in previous epidemiologic analyses 4 , 5 and has been shown to be most strongly correlated with concentrations of agricultural pesticides from house-dust samples. We determined the direction of each Public Land Survey System centroid relative to residences and weighted pesticide use in a section according to the percentage of time that the wind blew from that direction for each time period.

All pesticide use estimates were log 2 -tranformed and thus measures of association correspond to a two-fold increase in pesticide use. At each study visit, bilingual study staff administered structured questionnaires to ascertain participant characteristics.

We also included the following predictors of the outcome a priori: maternal depression status at the 9-year assessment categorical: yes vs. Spanish; all youth completed assessments in English. We implemented a two-stage BHM 19 , 33 — 39 to examine exposure—outcome associations with all pesticides included simultaneously.

We specified vague second-stage priors for individual pesticides not included in the Z matrix. For the postnatal analyses, we included a second Z matrix in which we adjusted for the 11 pesticides that were included in the prenatal analyses. We specified models in a Fully Bayesian framework 21 and estimated the posterior distribution of all model parameters via Markov Chain Monte Carlo sampling.

Convergence was assessed graphically using trace plots, autocorrelation plots, and density plots, 41 and statistically using the Geweke test 44 and Gelman—Rubin test statistic. We conducted sex-specific analyses by including an interaction term between each pesticide and child sex in the first stage model. We examined the robustness of our results by conducting sensitivity analyses in which we varied the specification of the Z matrix. In addition to the hierarchical models, we also ran multivariable linear mixed-effects regression models in which we included all exposures simultaneously without specifying a second-stage model.

Correlations coefficients for individual pesticides ranged from 0. Total pesticide use in Monterey County in and and distributions of wind-adjusted agricultural pesticide applications within 1 km of maternal residence during prenatal and postnatal periods a.

We observed largely negligible associations between pesticide use near the home during pregnancy and neurobehavioral outcomes. There were some subtle associations of chlorpyrifos use and increased internalizing behaviors from both maternal- and youth-report.

Notes: k , number of participants with data for at least one time point; n, number of observations from both time points. Higher score for each Behavior Assessment System for Children outcome indicates more symptomatic behavior. Imidacloprid use was also associated with decreased maternal-reported internalizing problems and depression among girls, as well as youth-reported internalizing problems and anxiety among girls.

The most consistent associations we observed for pesticide use during the postnatal period were for glyphosate and maternal- and youth-reported internalizing behaviors. Notes: k , number of participants with data for at least one time point; n , number of observations from both time points. We observed some associations of OP use postnatally and increased externalizing problems, though there were no consistent trends. Results from our sensitivity analyses were robust to variations of the specification of the Z matrix, and our overall interpretations were qualitatively the same data not shown.

Confidence intervals were slightly wider for some pesticides in multivariable linear mixed-effects regression models; however, our overall interpretation of the results was consistent with findings from the hierarchical analyses. We observed mostly null associations of agricultural pesticide use near the home during critical periods of brain development and behavioral and emotional problems at ages 16 and 18 years among participants living in an intensive agricultural region.

We observed some associations of use of the OP chlorpyrifos near the home during pregnancy and use of glyphosate near the home during early childhood with increased internalizing problems; however effect estimates were small. We also observed trends of fewer maternal- and youth-reported internalizing behaviors and attention problems in association with imidacloprid use near the home during pregnancy.

This is the first study to examine longitudinal associations of agricultural pesticide use near the home during pregnancy or early childhood with behavioral problems during adolescence or young adulthood, a critical time for the manifestation of these outcomes. Previous studies examining associations of prenatal or postnatal OP exposure and child neurodevelopment have largely assessed exposure using nonspecific DAP metabolites, limiting inferences regarding associations with specific OP pesticides.

In this analysis, we found associations of agricultural use of chlorpyrifos, a diethyl OP, during pregnancy with increased report of internalizing problems, depression, and anxiety from both mothers and youth; however, effect estimates were quite small. We observed some isolated associations of increased youth-reported attention problems in association with applications of the OPs diazinon and dimethoate during the prenatal period.

In previous analyses in this cohort, prenatal DAPs were associated with higher maternal-reported attention problems and psychometrician-assessed Attention Deficit Hyperactivity Disorder ADHD at the age of 5, but not at the age of 3. Cross-sectional and case—control studies have also found associations between childhood OP exposure and more behavioral and attention problems 55 and higher odds of having an ADHD diagnosis. We observed largely null associations of permethrin use near the home during either pregnancy or early childhood with maternal- or youth-reported behavioral or emotional problems.

This is in contrast with previous studies showing associations of prenatal pyrethroid exposure with child behavior problems. Specifically, longitudinal studies in New York City and France have identified associations of prenatal biomarkers of pyrethroid exposure and more parent-reported behavioral and emotional problems, including internalizing problems, depression, and externalizing problems, among children ages 4—9 years.

While one analysis of — data from the National Health and Nutrition Examination Survey found no association of pyrethroid exposure and parental report of ADHD among children ages 6—15 years, 60 another analysis of National Health and Nutrition Examination Survey participants ages 8—15 years from to found that higher urinary levels of a nonspecific pyrethroid biomarker, 3-phenoxybenzoic acid, were associated with higher odds of an ADHD diagnosis and more hyperactive-impulsive symptoms.

Notably, each of these previous studies assessed exposure using urinary biomarkers, which are a more integrated measure of total pyrethroid exposure than PUR data. Residential pesticide use is one of the biggest risk factors for pyrethroid exposure, 63 which would not be captured with our exposure assessment method. We also observed associations of applications of the neonicotinoid imidacloprid during the prenatal period with fewer maternal- and youth-reported internalizing behaviors and attention problems, particularly among girls.

While neonicotinoids are intended to be highly selective to insects 64 and are thought to have low mammalian toxicity due to a lower affinity for binding to the nicotine acetylcholine receptor, 65 , 66 few epidemiologic studies have examined their impacts on human health and significant data gaps exist. It is possible that we observed null or protective effects for imidacloprid because our exposure assessment method—agricultural pesticide use—did not adequately capture imidacloprid exposure due to the physical properties and mode of application of neonicotinoids.

Neonicotinoids are now the most widely used class of insecticides worldwide and use continues to rise. We observed relatively consistent associations of glyphosate use near the home during the postnatal period across maternal- and youth-reported internalizing problems, depression, and anxiety.

Very few epidemiologic studies have examined neurodevelopmental outcomes associated with glyphosate exposure, though toxicology studies have shown neurotoxic effects such as depressive behavior 74 , 75 and poorer locomotor activity 75 — 78 and recognition memory.

We did not observe consistent trends over prenatal and postnatal analyses. We did observe some consistencies for associations with specific pesticides across maternal and youth report.

For example, effect estimates for internalizing behaviors in association with chlorpyrifos use during pregnancy and glyphosate use during early childhood were similar across maternal and youth report. Previous studies have reported relatively poor agreement between maternal and youth report of adolescent psychopathology, 85 particularly for internalizing behaviors.

Although it is difficult to elucidate potential mechanisms of actions of specific pesticides from epidemiology studies in which humans are exposed to a mixture of pesticides, evidence from animal studies suggests that possible mechanisms may include changes in levels of neurotransmitters, 75 inhibition of axonal growth, 89 , 90 alteration of voltage-gated sodium channel function, 91 — 93 increased oxidative stress, 94 — 96 and damage to or decreased synthesis of brain DNA.

Our study has several strengths and limitations. One of the biggest limitations is that applications of pesticides near the home are not a direct measure of exposure and reliance on PUR data may result in measurement error. Previous analyses suggest that PUR data are correlated with environmental concentrations of OPs, but not pyrethroids, in homes, 27 , and data gaps exist regarding how well reliance on PUR may capture exposure to other pesticides such as neonicotinoids or glyphosate.

The precision of the exposure assessment was likely independent of the outcomes of interest and would thus result in nondifferential misclassification that may have contributed to our mostly null findings. We were also only able to characterize potential exposure to pesticides based on use near the maternal residence, and not in other areas the mothers and children may have spent time during the prenatal and postnatal periods, such as work and childcare.

Additionally, while CHAM1 participants reported their residential address at all study visits, addresses and timing of household moves were reported retrospectively for CHAM2 participants and may be prone to error. Strengths include a well-characterized cohort with rich collection of data, including longitudinal neurobehavioral measures from two reporters i.

While it has been well established that prenatal and, to a lesser extent, postnatal OP pesticide exposure is associated with adverse child neurodevelopment, a number of data gaps exist. Previous studies have examined associations among children followed up to age 12 years, and ours is the first to examine the persistence of pesticide—neurodevelopment associations into adolescence and young adulthood.

Moreover, previous investigations have largely examined single pesticides or pesticide classes in isolation, which may result in bias from copollutant confounding. We employed BHM as a principled approach to examine associations with all pesticides included in a single model, allowing for estimation of mutually adjusted exposure effects that are more stable and interpretable than with other approaches to multiple exposure modeling e.

This is the first study to examine associations of applications of mixtures of neurotoxic pesticides near the home during pregnancy or early childhood, critical periods of brain development, and neurobehavioral outcomes assessed during adolescence or young adulthood.

Adolescence is an important time for the manifestation of these behavioral outcomes 47 and may have important downstream effects on other outcomes, including impaired school performance, juvenile delinquency, increased risk-taking behavior, substance abuse, adult crime, and future psychopathology. Pesticide use trends have shifted drastically since the prenatal and postnatal exposure periods for children in this study; as many OPs are being phased out from residential and agricultural use due to evidence of neurotoxicity to the developing brain, it is increasingly important to study the safety of their replacements.

The other authors have no conflicts to report. Environ Epidemiol. Published online May 5. Carly Hyland , a Patrick T.

Bradshaw , b Robert B. Gunier , a Ana M. Patrick T. Robert B. Ana M. Sharon K. Author information Article notes Copyright and License information Disclaimer. E-mail: ude. Received Nov 24; Accepted Mar Published by Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the Creative Commons Attribution License 4. Associated Data Supplementary Materials eees Background: Studies suggest that exposure to pesticides during pregnancy and early childhood is associated with adverse child neurodevelopment.

Results: We observed mostly null associations between pesticide applications and neurobehavioral outcomes. Conclusions: We found only some subtle associations between some pesticides and neurobehavioral outcomes. What this study adds Prenatal and early-life exposure to organophosphate pesticides has been associated with adverse child neurodevelopment; however, data gaps exist regarding the impact of exposure to mixtures of pesticides.

Covariates At each study visit, bilingual study staff administered structured questionnaires to ascertain participant characteristics. Statistical analysis We implemented a two-stage BHM 19 , 33 — 39 to examine exposure—outcome associations with all pesticides included simultaneously. Sensitivity analyses We examined the robustness of our results by conducting sensitivity analyses in which we varied the specification of the Z matrix. Table 1. Open in a separate window.

Table 2. Associations with pesticide applications during prenatal period We observed largely negligible associations between pesticide use near the home during pregnancy and neurobehavioral outcomes.

Table 3. Table 4. Associations with pesticide applications during the postnatal period The most consistent associations we observed for pesticide use during the postnatal period were for glyphosate and maternal- and youth-reported internalizing behaviors. Table 5. Table 6. Sensitivity analyses Results from our sensitivity analyses were robust to variations of the specification of the Z matrix, and our overall interpretations were qualitatively the same data not shown.

Discussion We observed mostly null associations of agricultural pesticide use near the home during critical periods of brain development and behavioral and emotional problems at ages 16 and 18 years among participants living in an intensive agricultural region. Conclusion This is the first study to examine associations of applications of mixtures of neurotoxic pesticides near the home during pregnancy or early childhood, critical periods of brain development, and neurobehavioral outcomes assessed during adolescence or young adulthood.

Supplementary Material Click here to view. Footnotes Published online 5 May A. References 1. Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children. Environ Health Perspect. Prenatal exposure to organophosphates, paraoxonase 1, and cognitive development in childhood. Seven-year neurodevelopmental scores and prenatal exposure to chlorpyrifos, a common agricultural pesticide.

Prenatal residential proximity to agricultural pesticide use and IQ in 7-year-old children. Association between pesticide profiles used on agricultural fields near maternal residences during pregnancy and IQ at age 7 years. Environ Int. Impact of prenatal chlorpyrifos exposure on neurodevelopment in the first 3 years of life among inner-city children. Urinary 3,5,6-trichloropyridinol TCPY in pregnant women from Mexico City: distribution, temporal variability, and relationship with child attention and hyperactivity.

Int J Hyg Environ Health. Prenatal organophosphate pesticide exposure and traits related to autism spectrum disorders in a population living in proximity to agriculture. Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley.

Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study. Environmental exposure mixtures: questions and methods to address them. Curr Epidemiol Rep. US EPA. Environmental Protection Agency; Pyrethroid epidemiology: a quality-based review. Crit Rev Toxicol. Systemic insecticides neonicotinoids and fipronil : trends, uses, mode of action and metabolites.

Environ Sci Pollut Res Int. Benbrook CM. Trends in glyphosate herbicide use in the United States and globally.

   

 

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Lots of long standing bugs have never been fixed in Logic, but with every update new bugs are introduced. Good luck running a session relying on punching into a track. Zoom settings are having random weird problems. They are all excellent and capable DAWs. However, after using Logic Pro X, it is hard to migrate to any other music software. I find myself able to create music with relative ease that the other DAWs just are not capable of.

The MIDI capabilities alone are second to none in Logic and the ability to compose music in all styles makes it the best of the best. Another huge plus is the constant and free updates Apple provides… updates that are really upgrades in the quality and number of plug-ins and soft instruments built into the program.

Composing music or just recording a band is easy with this software. Whether you are into acoustic, jazz, electronica or rock, this software package is the best there is and gets updated constantly by Apple. Apple takes this software very seriously and I commend them for their excellence. Version However, it does have on issue now with Flex Pitch and Flex Tim.

Total disaster when only trying to use Flex Pitch and not edit the time. When you turn off Flex and Follow, all of your time and pitch corrections disappear. I just want to use flex. Nothing can fix this. I have been looking in Apple Forums and trying to find a solution for about a week now. The artifacts that now happen when using flex are so bad the audio almost becomes unusable. The first will open the "New track dialog. The second will create a duplicate of the selected track with it's channel strip settings.

All you need to do is duplicate the regions if desired. Page content loaded. Aug 15, PM in response to rounik music In response to rounik music. Communities Get Support. Sign in Sign in Sign in corporate. Browse Search. Ask a question. User profile for user: racingheart racingheart.

More Less. Reply I have this question too 19 I have this question too Me too 19 Me too. Helpful answers Drop Down menu. Aug 15, PM in response to racingheart In response to racingheart Duplicate the track. View answer in context. Aug 15, PM in response to racingheart In response to racingheart racingheart wrote: Does that copy all your automation parameters too?

   


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