Food and time: dietary plasticity of different sources of a generalist insect herbivore.

Painted lady butterflies (Vanessa cardui L., Nymphalidae) are generalist herbivores and serve as a model system across several fields of biology. While it has been demonstrated that V. cardui caterpillars can develop on different host plants, much of this work has been done on commercially sourced caterpillars, which could limit our understanding of wild V. cardui populations. In this study, we sought to explore possible differences in how commercial and wild V. cardui caterpillars may respond to feeding on different host plants, and subsequently, how their diet impacts immune response and survival. Here, we analyzed performance, survival, and immune response of wild and commercially sourced V. cardui caterpillars over several generations on diets that consisted of either 1 of 4 different host plant species or a mixed diet including all 4 species. Qualitatively, we observed that wild larvae had a better larval performance and hemocyte counts compared to the commercial larvae. The results demonstrate that both wild and commercially sourced caterpillars grew and survived best on the same diet treatments (mallow, narrowleaf plantain, and a mixed diet) during development across generations. Immune responses showed similar patterns across host plants between wild and commercial populations, with individuals showing lowered immune responses on dandelion and lupine and higher ones on mallow, plantain and the mixed diet; although the relative rankings on those 3 diets varied. Survival also demonstrated similar patterns, in that individuals reared on dandelion and lupine had the lowest survival.

Use of an exotic host plant reduces viral burden in a native insect herbivore.

Incorporation of exotic plants into the diets of native herbivores is a common phenomenon, influencing interactions with natural enemies and providing insight into the tritrophic costs and benefits of dietary expansion. We evaluated how use of an exotic plant, Plantago lanceolata, impacted immune performance, development and susceptibility to pathogen infection in the neotropical herbivore Anartia jatrophae (Lepidoptera: Nymphalidae). Caterpillars were reared on P. lanceolata or a native plant, Bacopa monnieri, and experimentally infected with a pathogenic virus, Junonia coenia densovirus. We found that virus-challenged herbivores exhibited higher survival rates and lower viral burdens when reared on P. lanceolata compared to B. monnieri, though immune performance and development time were largely similar on the two plants. These findings reveal that use of an exotic plant can impact the vulnerability of a native herbivore to pathogen infection, suggesting diet-mediated protection against disease as a potential mechanism facilitating the incorporation of novel resources.

HAPPILEE: HAPPE In Low Electrode Electroencephalography, a standardized pre-processing software for lower density recordings.

Lower-density Electroencephalography (EEG) recordings (from 1 to approximately 32 electrodes) are widely-used in research and clinical practice and enable scalable brain function measurement across a variety of settings and populations. Though a number of automated pipelines have recently been proposed to standardize and optimize EEG pre-processing for high-density systems with state-of-the-art methods, few solutions have emerged that are compatible with lower-density systems. However, lower-density data often include long recording times and/or large sample sizes that would benefit from similar standardization and automation with contemporary methods. To address this need, we propose the HAPPE In Low Electrode Electroencephalography (HAPPILEE) pipeline as a standardized, automated pipeline optimized for EEG recordings with lower density channel layouts of any size. HAPPILEE processes task-free (e.g., resting-state) and task-related EEG (including event-related potential data by interfacing with the HAPPE+ER pipeline), from raw files through a series of processing steps including filtering, line noise reduction, bad channel detection, artifact correction from continuous data, segmentation, and bad segment rejection that have all been optimized for lower density data. HAPPILEE also includes post-processing reports of data and pipeline quality metrics to facilitate the evaluation and reporting of data quality and processing-related changes to the data in a standardized manner. Here the HAPPILEE steps and their optimization with both recorded and simulated EEG data are described. HAPPILEE's performance is then compared relative to other artifact correction and rejection strategies. The HAPPILEE pipeline is freely available as part of HAPPE 2.0 software under the terms of the GNU General Public License at: https://github.com/PINE-Lab/HAPPE.

Seasonal Variation in Host Plant Chemistry Drives Sequestration in a Specialist Caterpillar.

Sequestration of plant secondary metabolites by herbivores can vary across both host plant phenology and herbivore ontogeny, but few studies have explored how they concurrently change in the field. We explored variation in iridoid glycoside concentration and composition in white turtlehead, Chelone glabra, as well as sequestration of iridoid glycosides by its specialist herbivore, the Baltimore checkerspot, Euphydryas phaeton, across the development of both herbivore and host plant. In 2012 we sampled plants to describe seasonal variation in the concentrations of two iridoid glycosides, aucubin and catalpol. In 2017, we sampled both host plants and caterpillars over an entire growing season and explored the relationship between plant chemistry and herbivore sequestration. We also compared iridoid glycoside concentrations of plants with and without herbivory to gain insight into whether levels of secondary compounds were impacted by herbivory. We found that total plant iridoid glycosides varied across the season and that total sequestered iridoid glycosides in caterpillars closely mirrored concentration patterns in plants. However, the magnitude of sequestration by caterpillars ranged from 2 to 20 times the concentrations in host plants, with different proportions of aucubin and catalpol. In addition, plants with herbivory had lower iridoid glycoside concentrations than plants without herbivory, although this difference changed over time. These results suggest that while variation in host plant secondary metabolites may be a dominant factor driving sequestration, other ecological factors may mitigate the relationship between host plant chemistry and herbivore sequestration.

NYX-2925 induces metabotropic N-methyl-d-aspartate receptor (NMDAR) signaling that enhances synaptic NMDAR and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor.

N-methyl-d-aspartate receptors (NMDARs) mediate both physiological and pathophysiological processes, although selective ligands lack broad clinical utility. NMDARs are composed of multiple subunits, but N-methyl-d-aspartate receptor subunit 2 (GluN2) is predominately responsible for functional heterogeneity. Specifically, the GluN2A- and GluN2B-containing subtypes are enriched in adult hippocampus and cortex and impact neuronal communication via dynamic trafficking into and out of the synapse. We sought to understand if ((2S, 3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3,4]octan-2-yl) butanamide (NYX-2925), a novel NMDAR modulator, alters synaptic levels of GluN2A- or GluN2B-containing NMDARs. Low-picomolar NYX-2925 increased GluN2B colocalization with the excitatory post-synaptic marker post-synaptic density protein 95 (PSD-95) in rat primary hippocampal neurons within 30 min. Twenty-four hours following oral administration, 1 mg/kg NYX-2925 increased GluN2B in PSD-95-associated complexes ex vivo, and low-picomolar NYX-2925 regulated numerous trafficking pathways in vitro. Because the NYX-2925 concentration that increases synaptic GluN2B was markedly below that which enhances long-term potentiation (mid-nanomolar), we sought to elucidate the basis of this effect. Although NMDAR-dependent, NYX-2925-mediated colocalization of GluN2B with PSD-95 occurred independent of ion flux, as colocalization increased in the presence of either the NMDAR channel blocker (5R,10S)-(-)-5-Methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate or glycine site antagonist 7-chlorokynurenic acid. Moreover, while mid-nanomolar NYX-2925 concentrations, which do not increase synaptic GluN2B, enhanced calcium transients, functional plasticity was only enhanced by picomolar NYX-2925. Thus, NYX-2925 concentrations that increase synaptic GluN2B facilitated the chemical long-term potentiation induced insertion of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluA1 subunit levels. Basal (unstimulated by chemical long-term potentiation) levels of synaptic GluA1 were only increased by mid-nanomolar NYX-2925. These data suggest that NYX-2925 facilitates homeostatic plasticity by initially increasing synaptic GluN2B via metabotropic-like NMDAR signaling. Cover Image for this issue: doi: 10.1111/jnc.14735.

Time-Resolved Fuel Density Profiles of the Stagnation Phase of Indirect-Drive Inertial Confinement Implosions.

The implosion efficiency in inertial confinement fusion depends on the degree of stagnated fuel compression, density uniformity, sphericity, and minimum residual kinetic energy achieved. Compton scattering-mediated 50-200 keV x-ray radiographs of indirect-drive cryogenic implosions at the National Ignition Facility capture the dynamic evolution of the fuel as it goes through peak compression, revealing low-mode 3D nonuniformities and thicker fuel with lower peak density than simulated. By differencing two radiographs taken at different times during the same implosion, we also measure the residual kinetic energy not transferred to the hot spot and quantify its impact on the implosion performance.

Critical Phenological Events Affect Chemical Defense of Plant Tissues: Iridoid Glycosides in a Woody Shrub.

Plants are chemically-complex organisms; each individual contains diverse tissue-types, has the ability to differentially allocate secondary metabolites to these tissues and can change this allocation through time. The interaction of variation in chemical defense of different tissue types and variation in chemical defense through time, however, is rarely examined and has not been studied for iridoid glycoside-producing woody plants. In this study, we quantified allocation of iridoid glycosides (IGs) to the leaves, flowers, fruits, and seeds of 25 individuals of a long-lived shrub (Lonicera x bella Zabel, Caprifoliaceae), at five important phenological timepoints (leaf-out, flowering, fruit appearance, fruit ripening, and fruit dispersal) throughout a growing season. We found that leaves had 2x higher IG concentrations during flowering and fruiting than earlier in the season (after leaf-out), and later in the season (after fruit dispersal). The individual IG driving this increase in leaves during reproduction, secologanin, was also the most abundant IG in semiripe fruits. Flowers and seeds were composed of different proportions of individual IGs than fruits or leaves, but did not change across time and had overall low concentrations of IGs. In L. x bella, phenological events such as flowering and fruiting lead to an increase in leaf chemical defense that is likely to influence interactions with leaf-feeders. Our results stress the importance of considering phenology when sampling plants for the quantification of chemical defenses.

Universal reshaping of arrested colloidal gels via active doping.

Colloids that interact via a short-range attraction serve as the primary building blocks for a broad range of self-assembled materials. However, one of the well-known drawbacks to this strategy is that these building blocks rapidly and readily condense into a metastable colloidal gel. Using computer simulations, we illustrate how the addition of a small fraction of purely repulsive self-propelled colloids, a technique referred to as active doping, can prevent the formation of this metastable gel state and drive the system toward its thermodynamically favored crystalline target structure. The simplicity and robust nature of this strategy offers a systematic and generic pathway to improving the self-assembly of a large number of complex colloidal structures. We discuss in detail the process by which this feat is accomplished and provide quantitative metrics for exploiting it to modulate the self-assembly. We provide evidence for the generic nature of this approach by demonstrating that it remains robust under a number of different anisotropic short-ranged pair interactions in both two and three dimensions. In addition, we report on a novel microphase in mixtures of passive and active colloids. For a broad range of self-propelling velocities, it is possible to stabilize a suspension of fairly monodisperse finite-size crystallites. Surprisingly, this microphase is also insensitive to the underlying pair interaction between building blocks. The active stabilization of these moderately sized monodisperse clusters is quite remarkable and should be of great utility in the design of hierarchical self-assembly strategies. This work further bolsters the notion that active forces can play a pivotal role in directing colloidal self-assembly.

Assessing osseointegration of metallic implants with boronized surface treatment.

BACKGROUND: Modification of endosteal implants through surface treatments have been investigated to improve osseointegration. Boronization has demonstrated favorable mechanical properties, but limited studies have assessed translational, in vivo outcomes. This study investigated the effect of implant surface boronization on bone healing. MATERIAL AND METHODS: Two implant surface roughness profiles (acid etched, machined) in CP titanium (type II) alloy implants were boronized by solid-state diffusion until 10-15µm boron coating was achieved. The surface-treated implants were placed bilaterally into 5 adult sheep ilia for three and six weeks. Four implant groups were tested: boronized machined (BM), boronized acid-etched (BAA), control machined (CM), and control acid-etched (CAA). Osseointegration was quantified by calculating bone to implant contact (BIC) and bone area fraction occupancy (BAFO). RESULTS: Both implant types treated with boronization had BIC values not statistically different from machined control implants at t=3 weeks, and significantly less than acid-etched control (p<0.02). BAFO values were not statistically different for all 3-week groups except machined control (significantly less at p <0.02). BAFO had a significant downward trend from 3 to 6 weeks in both boronized implant types (p<0.03) while both control implant types had significant increases in BIC and BAFO from 3 to 6 weeks. CONCLUSIONS: Non-decalcified histology depicted intramembranous-like healing/remodeling in bone for controls, but an absence of this dynamic process in bone for boronized implants. These findings are inconsistent with in vitro work describing bone regenerative properties of elemental Boron and suggests that effects of boron on in vivo bone healing warrant further investigation.

Active sculpting of colloidal crystals.

The development of colloidal particles that can become self-propelled when exposed to a source of light of a given frequency represents one of the most exciting new developments in the field of active matter. In this paper, we perform numerical simulations to explore several properties of crystalline colloidal aggregates in the presence of such external light fields. We show how permanent gaps of tunable size can be carved into these crystals as a result of a solid-gas transition that occurs above a threshold light intensity. We compare this phenomenon to that occurring in a parent system obtained by replacing self-propulsion with an effective temperature and discuss the main differences between the two setups. Finally, we show how moving the light field across a solid-fluid boundary allows us to transfer or transport the fluid component into or across the solid one. We discuss the dynamics of this process and set limits associated with its performance.

NYX-2925 Is a Novel N-Methyl-d-Aspartate Receptor Modulator that Induces Rapid and Long-Lasting Analgesia in Rat Models of Neuropathic Pain.

NYX-2925 [(2S,3R)-3-hydroxy-2-((R)-5-isobutyryl-1-oxo-2,5-diazaspiro[3.4]octan-2-yl)butanamide] is a novel N-methyl-d-aspartate (NMDA) receptor modulator that is currently being investigated in phase 2 clinical studies for the treatment of painful diabetic peripheral neuropathy and fibromyalgia. Previous studies demonstrated that NYX-2925 is a member of a novel class of NMDA receptor-specific modulators that affect synaptic plasticity processes associated with learning and memory. Studies here examined NYX-2925 administration in rat peripheral chronic constriction nerve injury (CCI) and streptozotocin-induced diabetic mechanical hypersensitivity. Additionally, NYX-2925 was examined in formalin-induced persistent pain model and the tail flick test of acute nociception. Oral administration of NYX-2925 resulted in rapid and long-lasting analgesia in both of the neuropathic pain models and formalin-induced persistent pain, but was ineffective in the tail flick model. The analgesic effects of NYX-2925 were blocked by the systemic administration of NMDA receptor antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid. Microinjection of NYX-2925 into the medial prefrontal cortex of CCI rats resulted in analgesic effects similar to those observed following systemic administration, whereas intrathecal administration of NYX-2925 was ineffective. In CCI animals, NYX-2925 administration reversed deficits seen in a rat model of rough-and-tumble play. Thus, it appears that NYX-2925 may have therapeutic potential for the treatment of neuropathic pain, and the data presented here support the idea that NYX-2925 may act centrally to ameliorate pain and modulate negative affective states associated with chronic neuropathic pain.

Hemiparasites can transmit indirect effects from their host plants to herbivores.

Parasitic plants can serve as critical intermediaries between their hosts and other organisms; however these relationships are not well understood. To investigate the relative importance of plant traits in such interactions, we studied the role of the root hemiparasite, Castilleja levisecta (Orobanchaceae), as a mediator of interactions between the host plants it parasitizes and the lepidopteran herbivore Euphydryas editha (Nymphalidae), whose caterpillars feed on Castilleja and sequester iridoid glycosides from it. We tested whether the hemiparasite's size, leaf N concentration, and iridoid glycoside concentrations were influenced by the identity of its host plant, and then whether these traits influenced outcomes for the herbivore. We found that the hemiparasite's size and leaf N depended on the host it parasitized, and these traits in turn affected outcomes for E. editha. Specifically, Euphydryas editha survival increased with hemiparasite size and caterpillar mass increased with leaf N; caterpillars with greater mass were more likely to survive during diapause. We also found preliminary evidence that host identity influenced iridoid glycoside sequestration by the herbivore. Mean iridoid glycoside concentrations in caterpillars ranged from 1-12% depending on the host being parasitized by Castilleja. This study demonstrates that root parasitism can result in strong indirect effects on higher trophic levels, influencing organisms' survival, growth, and chemical interactions.

First Observation of Cross-Beam Energy Transfer Mitigation for Direct-Drive Inertial Confinement Fusion Implosions Using Wavelength Detuning at the National Ignition Facility.

Cross-beam energy transfer (CBET) results from two-beam energy exchange via seeded stimulated Brillouin scattering, which detrimentally reduces ablation pressure and implosion velocity in direct-drive inertial confinement fusion. Mitigating CBET is demonstrated for the first time in inertial-confinement implosions at the National Ignition Facility by detuning the laser-source wavelengths (±2.3 Å UV) of the interacting beams. We show that, in polar direct-drive, wavelength detuning increases the equatorial region velocity experimentally by 16% and alters the in-flight shell morphology. These experimental observations are consistent with design predictions of radiation-hydrodynamic simulations that indicate a 10% increase in the average ablation pressure.

Dietary Omega-3 Fatty Acids Differentially Impact Acute Ethanol-Responsive Behaviors and Ethanol Consumption in DBA/2J Versus C57BL/6J Mice.

BACKGROUND: Complex interactions between environmental and genetic factors influence the risk of developing alcohol use disorder (AUD) in humans. To date, studies of the impact of environment on AUD risk have primarily focused on psychological characteristics or on the effects of developmental exposure to ethanol (EtOH). We recently observed that modifying levels of the long-chain ω-3 (LC ω-3) fatty acid, eicosapentaenoic acid (EPA), alters acute physiological responses to EtOH in Caenorhabditis elegans. Because mammals derive ω-3 fatty acids from their diet, here we asked if manipulating dietary levels of LC ω-3 fatty acids can affect EtOH-responsive behaviors in mice. METHODS: We used 2 well-characterized inbred mouse strains, C57BL/6J (B6) and DBA/2J (D2), which differ in their responses to EtOH. Age-matched young adult male mice were maintained on isocaloric diets that differed only by being enriched or depleted in LC ω-3 fatty acids. Animals were subsequently tested for acute EtOH sensitivity (locomotor activation and sedation), voluntary consumption, and metabolism. Fat deposition was also determined. RESULTS: We found that dietary levels of LC ω-3s altered EtOH sensitivity and consumption in a genotype-specific manner. Both B6 and D2 animals fed high LC ω-3 diets demonstrated lower EtOH-induced locomotor stimulation than those fed low LC ω-3 diets. EtOH sedation and EtOH metabolism were greater in D2, but not B6 mice on the high LC ω-3 diet. Conversely, LC ω-3 dietary manipulation altered EtOH consumption in B6, but not in D2 mice. B6 mice on a high LC ω-3 diet consumed more EtOH in a 2-bottle choice intermittent access model than B6 mice on a low LC ω-3 diet. CONCLUSIONS: Because EtOH sensitivity is predictive of risk of developing AUD in humans, our data indicate that dietary LC ω-3 levels should be evaluated for their impact on AUD risk in humans. Further, these studies indicate that genetic background can interact with fatty acids in the diet to significantly alter EtOH-responsive behaviors.

Plant and herbivore ontogeny interact to shape the preference, performance and chemical defense of a specialist herbivore.

The amount of damage that herbivorous insects impose on plants varies as a function of plant ontogenetic trajectories in tissue quality and defenses, and the herbivores' own developmental trajectories in body size, mandible shape and detoxification enzymes, among others. However, little is known about how host plant and herbivore ontogeny interact. Using four ontogenetic stages of Plantago lanceolata (Plantaginaceae) and three to five larval stages of the specialist caterpillar Junonia coenia (Nymphalidae), we evaluated how ontogenies in both of these trophic levels shape: (i) caterpillar feeding choice, (ii) performance, and (iii) sequestration of plant allelochemicals. Plant physical (leaf toughness) and chemical (iridoid glycosides) defenses increased, while nutritional quality (water and nitrogen content) decreased, as plants aged. These plant ontogenetic trajectories strongly altered the behavior and physiology of this specialist herbivore, but the magnitude of the response varied with larval stage. In feeding experiments, while first instar larvae showed little preference among plant stages, older larvae significantly preferred juvenile over reproductive stages. In turn, larval consumption increased and digestive efficiency decreased, potentially explaining their decrease in relative growth rate, as larvae and host plant aged, but differences were greater for younger than older caterpillars. Finally, sequestration of plant allelochemicals increased through plant and larval development; however, the major differences due to diet occurred earlier during larval development. Our results highlight that changes in plant ontogeny most strongly influence early herbivore instars, emphasizing the need to consider the developmental stage of both trophic levels to better understand temporal variation in herbivore damage.

Host plant iridoid glycosides mediate herbivore interactions with natural enemies.

Many insect herbivores are dietary specialists capable of sequestering the secondary metabolites produced by their host plants. These defensive compounds have important but complex implications for tritrophic interactions between plants, herbivores, and natural enemies. The sequestration of host plant secondary metabolites defends herbivores from attack by generalist predators, but may also compromise the immune response, making insect herbivores more vulnerable to parasitism. Here, we investigate the role of plant secondary metabolites in mediating interactions between a specialist herbivore and its natural enemies. The host plants are two Penstemon species, Penstemon glaber and Penstemon virgatus, which are chemically defended by iridoid glycosides (IGs). First, we examined how Penstemon iridoid glycoside content influences the sequestration of IGs by a specialist herbivore, Euphydryas anicia. Then, we performed ant bioassays to assess how host plant species influences larval susceptibility to predators and phenoloxidase assays to assess the immunocompetence and potential vulnerability to parasitoids and pathogens. We found that the concentration of IGs sequestered by E. anicia larvae varied with host plant diet. Larvae reared on P. glaber sequestered more IGs than larvae reared on P. virgatus. Yet, ant predators found larvae unpalatable regardless of host plant diet and were also repelled by sugar solutions containing isolated IGs. However, E. anicia larvae reared on P. glaber showed higher levels of phenoloxidase activity than larvae reared on P. virgatus. Our results suggest that the sequestration of some secondary metabolites can effectively protect herbivores from predation, yet may also increase vulnerability to parasitism via decreased immunocompetence.

Host Plant Suitability in a Specialist Herbivore, Euphydryas anicia (Nymphalidae): Preference, Performance and Sequestration.

The checkerspot butterfly, Euphydryas anicia (Nymphalidae), specializes on plants containing iridoid glycosides and has the ability to sequester these compounds from its host plants. This study investigated larval preference, performance, and sequestration of iridoid glycosides in a population of E. anicia at Crescent Meadows, Colorado, USA. Although previous studies showed that other populations in Colorado use the host plant, Castilleja integra (Orobanchaceae), we found no evidence for E. anicia ovipositing or feeding on C. integra at Crescent Meadows. Though C. integra and another host plant, Penstemon glaber (Plantaginaceae), occur at Crescent Meadows, the primary host plant used was P. glaber. To determine why C. integra was not being used at the Crescent Meadows site, we first examined the host plant preference of naïve larvae between P. glaber and C. integra. Then we assessed the growth and survivorship of larvae reared on each plant species. Finally, we quantified the iridoid glycoside concentrations of the two plant species and diapausing caterpillars reared on each host plant. Our results showed that E. anicia larvae prefer P. glaber. Also, larvae survive and grow better when reared on P. glaber than on C. integra. Castilleja integra was found to contain two primary iridoid glycosides, macfadienoside and catalpol, and larvae reared on this plant sequestered both compounds; whereas P. glaber contained only catalpol and larvae reared on this species sequestered catalpol. Thus, although larvae are able to use C. integra in the laboratory, the drivers behind the lack of use at the Crescent Meadows site remain unclear.

Genomewide Association Study of Alcohol Dependence Identifies Risk Loci Altering Ethanol-Response Behaviors in Model Organisms.

BACKGROUND: Alcohol dependence (AD) shows evidence for genetic liability, but genes influencing risk remain largely unidentified. METHODS: We conducted a genomewide association study in 706 related AD cases and 1,748 unscreened population controls from Ireland. We sought replication in 15,496 samples of European descent. We used model organisms (MOs) to assess the role of orthologous genes in ethanol (EtOH)-response behaviors. We tested 1 primate-specific gene for expression differences in case/control postmortem brain tissue. RESULTS: We detected significant association in COL6A3 and suggestive association in 2 previously implicated loci, KLF12 and RYR3. None of these signals are significant in replication. A suggestive signal in the long noncoding RNA LOC339975 is significant in case:control meta-analysis, but not in a population sample. Knockdown of a COL6A3 ortholog in Caenorhabditis elegans reduced EtOH sensitivity. Col6a3 expression correlated with handling-induced convulsions in mice. Loss of function of the KLF12 ortholog in C. elegans impaired development of acute functional tolerance (AFT). Klf12 expression correlated with locomotor activation following EtOH injection in mice. Loss of function of the RYR3 ortholog reduced EtOH sensitivity in C. elegans and rapid tolerance in Drosophila. The ryanodine receptor antagonist dantrolene reduced motivation to self-administer EtOH in rats. Expression of LOC339975 does not differ between cases and controls but is reduced in carriers of the associated rs11726136 allele in nucleus accumbens (NAc). CONCLUSIONS: We detect association between AD and COL6A3, KLF12, RYR3, and LOC339975. Despite nonreplication of COL6A3, KLF12, and RYR3 signals, orthologs of these genes influence behavioral response to EtOH in MOs, suggesting potential involvement in human EtOH response and AD liability. The associated LOC339975 allele may influence gene expression in human NAc. Although the functions of long noncoding RNAs are poorly understood, there is mounting evidence implicating these genes in multiple brain functions and disorders.

The Perennial Penstemon: Variation in Defensive Chemistry Across Years, Populations, and Tissues.

Plants produce a variety of secondary metabolites that function as a defense against their natural enemies. Production of these secondary metabolites is genetically controlled, but is also phenotypically plastic and varies in response to both biotic and abiotic factors. Therefore, plant species may vary widely in their chemical defenses and such variation can be evident at temporal, spatial and tissue levels. Focusing on the chemical defenses of a native Colorado wildflower, Penstemon virgatus, we assessed the variation in iridoid glycoside (IG) content across two non-consecutive growing seasons, six natural populations and three tissue types: leaves, stems and flowers. Our results indicate that P. virgatus plants contain high concentrations of IGs (mean = 23.36% dry weight of leaves) and that IGs were differentially allocated among tissue types. Leaves contained the highest concentration of IGs, which varied quantitatively between sampling years, among plant populations, and plant parts. We also quantified leaf herbivore damage at all six populations but we found very little herbivore damage. Our study indicates that the IG concentrations of P. virgatus plants are both spatially and temporally variable. Furthermore, the high concentrations of secondary metabolites combined with the low levels of damage suggest that these plants are well defended against generalist herbivores.

Localization of Defensive Chemicals in Two Congeneric Butterflies (Euphydryas, Nymphalidae).

Many insect species sequester compounds acquired from their host plants for defense against natural enemies. The distribution of these compounds is likely to affect both their efficacy as defenses, and their costs. In this study we examined the distribution of sequestered iridoid glycosides (IGs) in two congeneric species of nymphalid butterfly, Euphydryas anicia and E. phaeton, and found that the pattern of localization of IGs differed between the two species. Although IG concentrations were quite high in the heads of both species, the relative concentrations in wings and abdomens differed substantially. Euphydryas anicia had relatively high IG concentrations in their abdomens and low IG concentrations in their wings, whereas the reverse was true in E. phaeton. We interpret these results in light of two current hypotheses regarding where sequestered chemicals should be localized: that they should be found in wings, which would allow non-lethal sampling by predators; and that their distribution is constrained by the distribution of tissue types to which sequestered compounds bind. We also offer the third hypothesis, that costs of storage may differ among body parts, and that the localization of compounds may reflect a cost-reduction strategy. Results from E. phaeton were consistent with all three of these non-mutually exclusive hypotheses, whereas results from E. anicia were only consistent with the notion that tissue bias among body parts plays a role in IG distribution. The finding that these two congeneric butterflies exhibit different patterns of IG localization suggests that they have been shaped by different selection regimes.