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Endophenotypes for alcohol use disorder are well known and may reflect paternal exposure effects passed down to offspring via epigenetic mechanisms. Previously, we showed that paternal alcohol exposure prior to conception attenuates the acquisition of operant alcohol self-administration. We now test whether paternal alcohol exposure alters their offsprings' behavioral responses to alcohol (endophenotypes) and global DNA methylation levels in reward-related brain regions.Adult male rats were exposed to alcohol vapors or air for 6 weeks and mated with alcohol-naïve females 8 weeks later. Adult male and female offspring of the alcohol- and control-sired litters were tested on three behaviors 30 m after gavage with water or alcohol (1.5 g/kg): open field, elevated plus maze, and accelerating rotarod. Global DNA methylation levels in sperm, nucleus accumbens, and prefrontal cortex were examined in male sires and in another group of offspring.Alcohol-sired males showed less anxiety-like behavior in the elevated plus maze that was not affected by alcohol administration. By contrast, alcohol had anxiolytic effects in the open field in male offspring only with no paternal alcohol effect. Neither paternal alcohol exposure nor alcohol administration altered locomotor activity in either sex. Sex-specific effects of paternal alcohol exposure were seen in the rotarod test. Alcohol-sired male offspring showed blunted sensitivity to the alcohol's motor-impairing effects, whereas alcohol-sired female offspring showed enhanced sensitivity. Global DNA methylation was altered in the sperm of alcohol-exposed males, but no changes were seen in their offspring.Paternal alcohol exposure prior to conception has sex- and task-dependent effects on unconditioned behaviors in their offspring.

Microbial production of biopolymers represents a promising, sustainable alternative to current approaches for plastic production. Cyanophycin synthetase 1 (CphA1) produces cyanophycin - an attractive biopolymer consisting of a poly-L-aspartic acid backbone decorated with L-arginine side groups. In this work, a series of CphA1 enzymes from different bacteria were screened for heterologous cyanophycin production in engineeredEscherichia coli, from which it was found that CphA1 fromTatumella morbirosei(TmCphA1) was especially productive.TmCphA1 was capable of supporting up to ~2-fold greater yields of insoluble cyanophycin than any other tested CphA1 enzymes, including 10.8-times more than CphA1 fromSynechocystissp. PCC6308. Finally, using a bench-scale bioreactor, cyanophycin production byTmCphA1-expressingE. colireached up to 1.9 g per liter of culture by 48 h.

Drug addiction is a serious relapsing disease that has high costs to society and to the individual addicts. Treatment of these addictions is still in its nascency, with only a few examples of successful therapies. Therapeutic response depends upon genetic, biological, social, and environmental components. A role for genetic makeup in the response to treatment has been shown for several addiction pharmacotherapies with response to treatment based on individual genetic makeup. In this chapter, we will discuss the role of genetics in pharmacotherapies, specifically for cocaine, alcohol, and opioid dependences. The continued elucidation of the role of genetics should aid in the development of new treatments and increase the efficacy of existing treatments.

Robust systematic approaches for the metabolic engineering of cell factories remain elusive. The available models for predicting phenotypical responses and mechanisms are incomplete, particularly within the context of compound toxicity that can be a significant impediment to achieving high yields of a target product. This study describes a Multi-Omic Based Production Strain Improvement (MOBpsi) strategy that is distinguished by integrated time-resolved systems analyses of fed-batch fermentations. As a case study, MOBpsi was applied to improve the performance of an Escherichia coli cell factory producing the commodity chemical styrene. Styrene can be bio-manufactured from phenylalanine via an engineered pathway comprised of the enzymes phenylalanine ammonia lyase and ferulic acid decarboxylase. The toxicity, hydrophobicity, and volatility of styrene combine to make bio-production challenging. Previous attempts to create styrene tolerant E. coli strains by targeted genetic interventions have met with modest success. Application of MOBpsi identified new potential targets for improving performance, resulting in two host strains (E. coli NST74ΔaaeA and NST74ΔaaeA cpxPo) with increased styrene production. The best performing re-engineered chassis, NST74ΔaaeA cpxPo, produced ∼3 × more styrene and exhibited increased viability in fed-batch fermentations. Thus, this case study demonstrates the utility of MOBpsi as a systematic tool for improving the bio-manufacturing of toxic chemicals.

Over the last decade, the northeast Pacific experienced marine heatwaves that caused devastating marine ecological impacts with socioeconomic implications. Here we use two different attribution methods and show that forcing by elevated greenhouse gases levels has virtually certainly caused the multi-year persistent 2019–2021 marine heatwave. There is less than 1% chance that the 2019–2021 event with ~3 years duration and 1.6 ∘C intensity could have happened in the absence of greenhouse gases forcing. We further discover that the recent marine heatwaves are co-located with a systematically-forced outstanding warming pool, which we attribute to forcing by elevated greenhouse gases levels and the recent industrial aerosol-load decrease. The here-detected Pacific long-term warming pool is associated with a strengthening ridge of high-pressure system, which has recently emerged from the natural variability of climate system, indicating that they will provide favorable conditions over the northeast Pacific for even more severe marine heatwave events in the future.

Over the last decade, the northeast Pacific experienced strong marine heatwaves (MHWs) that produced devastating marine ecological impacts and received major societal concerns. Here, we assess the link between the well-mixed greenhouse gas (GHG) forcing and the occurrence probabilities of the duration and intensity of the North Pacific MHWs. We investigate whether GHG forcing was necessary for the North Pacific MHWs to occur and whether it is a sufficient cause for such events to continue to repeatedly occur in the 21st Century. To begin with, we apply attribution technique on the long-term SST time series, and detect a region of systematically and externally-forced SST increase -- the long-term warming pool -- co-located with the past notably Blob-like SST anomalies. We further show that the anthropogenic signal has recently emerged from the natural variability of SST over the warming pool, which we attribute primarily to increased GHG concentrations, with anthropogenic aerosols playing a secondary role.After we demonstrate that the GHG forcing has a dominant influence on the base climate state in the region, we pursue an event attribution analysis for MHWs on a more localized region. Extreme event attribution analysis reveals that GHG forcing is a necessary, but not sufficient, causation for the multi-year persistent MHW events in the current climate, such as that happened in 2014/2015 and 2019/2020. However, the occurrence of the 2019/2020 (2014/2015) MHW was extremely unlikely in the absence of GHG forcing. Thus, as GHG emissions continue to firmly rise, it is very likely that GHG forcings will become a sufficient cause for events of the magnitude of the 2019/2020 record event.

Over the last decade, the northeast Pacific (NP) experienced strong marine heatwaves (MHWs) that produced devastating marine ecological impacts and received major societal concerns. Here, we assess the link between the well-mixed greenhouse gas (GHG) forcing and the occurrence probabilities of the duration and intensity of the NP MHWs. To begin with, we apply attribution technique on the SST time series, and detect a region of systematically and externally-forced SST increase -- the long-term warming pool -- co-located with the past notably Blob-like SST anomalies. The anthropogenic signal has recently emerged from the natural variability of SST over the warming pool, which we attribute primarily to increased GHG concentrations, with anthropogenic aerosols playing a secondary role. With extreme event attribution technique, we further show that GHG forcing is a necessary, but not a sufficient, causation for the multi-year persistent MHW events in the current climate, such as that happened in 2019/2020 over the warming pool. However, the occurrence of the 2019/2020 MHW was extremely unlikely in the absence of GHG forcing. Thus, as GHG emissions continue to firmly rise, it is very likely that GHG forcings will become a sufficient cause for events of the magnitude of the 2019/2020 record event.

In the Pacific Ocean, off-equatorial Rossby waves (RWs), initiated by atmosphere-ocean interaction, modulate the inter-annual variability of the thermocline. In this study, we explore the resulting potential gain in predictability of central tropical Pacific primary production, which in this region strongly depends on the supply of macronutrients from below the thermocline. We use a decadal prediction system based on the Max Planck Institute Earth system model to demonstrate that for the time period 1998–2014 properly initialized RWs explain an increase in predictability of net primary productivity (NPP) in the off-equatorial central tropical Pacific. We show that, for up to 5 years in advance, predictability of NPP derived from the decadal prediction system is significantly larger than that derived from persistence alone, or an uninitialized historical simulation. The predicted signal can be explained by the following mechanism: off-equatorial RWs are initiated in the eastern Pacific and travel towards the central tropical Pacific on a time scale of 2–6 years. On their arrival the RWs modify the depths of both thermocline and nutricline, which is fundamental to the availability of nutrients in the euphotic layer. Local upwelling transports nutrients from below the nutricline into the euphotic zone, effectively transferring the RW signal to the near-surface ocean. While we show that skillful prediction of central off-equatorial tropical Pacific NPP is possible, we open the door for establishing predictive systems for food web and ecosystem services in that region.

Genetic variation in the serotonin transporter (SLC6A4) has been shown to moderate the acute subjective effects of cocaine. Methylation of the SLC6A4 gene is associated with decreased transcription of the serotonin transporter, leading to increased serotonin in the synapse. In this study, methylation of the SLC6A4 gene was investigated in the moderation of the subjective effects of cocaine. Non-treatment-seeking cocaine-dependent individuals (N = 53) were intravenously administered cocaine (40 mg) and saline in a randomized order. The subjective effects of cocaine were self-reported using a visual analog scale starting prior to the administration of cocaine (−15 min) or saline and up to 20 min after infusion. Participants were evaluated for methylation of the SLC6A4 promoter region and 5-HTTLPR genotype. A series of ANCOVAs for SLC6A4 methylation (high/low) were run for each of ten subjective and three cardiovascular effects controlling for age, sex [utilizing the sex-determining region Y protein (SRY)], and population structure (determined from ancestry informative markers and STRUCTURE software). Participants with SLC6A4 hypermethylation reported greater subjective response to cocaine for ‘depressed’ relative to participants with SLC6A4 hypomethylation (experiment-wise p =.002). These findings indicate that SLC6A4 methylation moderates the ‘depressed’ subjective effect of cocaine in non-treatment-seeking cocaine-dependent participants.