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Data from: Morph-specific artificial selection reveals a constraint on the evolution of polyphenisms
Theory predicts that the evolution of polyphenic variation is facilitated where morphs are genetically uncoupled and free to evolve towards their phenotypic optima. However, the assumption that developmentally plastic morphs can evolve independently has not been tested directly. Using morph-specific artificial selection, we investigated correlated evolution between the sexes and male morphs of the bulb mite Rhizoglyphus echinopus. Large 'fighter' males have a thick and sharply terminating pair of legs used to kill rival males, while small 'scrambler' males have unmodified legs, and search for unguarded females, avoiding fights. We selected on the relative leg width of only the fighter male morph, tracked the evolutionary responses in fighters and the correlated evolutionary responses in scramblers and females that were untouched by direct selection. Fighters diverged in relative leg thickness after six generations; assaying scramblers and females at the ninth generation we observed correlated responses in relative leg width in both. Our results represent strong evidence for the evolution of intraspecific phenotypic diversity despite correlated evolution between morphs and sexes, challenging the idea that male morphs are genetically uncoupled and free to independen- tly respond to selection. We, therefore, question the perceived necessity for genetic independence in traits with extreme phenotypic plasticity.
Data from: Selection for population specific adaptation has shaped patterns of variation in the photoperiod pathway genes in Arabidopsis lyrata during post glacial colonization
Spatially varying selection can lead to population-specific adaptation, which is often recognized at the phenotypic level; however, the genetic evidence is weaker in many groups of organisms. In plants, environmental shifts that occur due to colonization of a novel environment may require adaptive changes in the timing of growth and flowering, which are often governed by location-specific environmental cues such as day length. We studied locally varying selection in 19 flowering time loci in nine populations of the perennial herb Arabidopsis lyrata, which has a wide but patchy distribution in temperate and boreal regions of the northern hemisphere. The populations differ in their recent population demographic and colonization histories and current environmental conditions, especially in the growing season length. We searched for population-specific molecular signatures of directional selection by comparing a set of candidate flowering time loci with a genomic reference set within each population using multiple approaches and contrasted the patterns of different populations. The candidate loci possessed approximately 20 % of the diversity of the reference loci. On average the flowering time loci had more rare alleles (a smaller Tajima's D) and an excess of highly differentiated sites relative to the reference, suggesting positive selection. The strongest signal of selection was detected in photoperiodic pathway loci in the colonizing populations of Northwestern Europe, whereas no evidence of positive selection was detected in the Central European populations. These findings emphasized the population-specific nature of selection and suggested that photoperiodic adaptation was important during post-glacial colonization of the species.
Data from: Sex-specific selection on plant architecture through 'budget' and 'direct' effects in experimental populations of a wind-pollinated herb
Sexual selection may contribute to the evolution of plant sexual dimorphism by favoring architecture traits that improve pollen dispersal to mates in males. In both sexes, larger individuals may be favored if large size allows the allocation of more resources to gamete production (a 'budget' effect of size). In wind-pollinated plants, large size may also benefit males if it allows them to liberate pollen from greater heights, fostering its dispersal (a 'direct' effect of size). To assess these effects and their implications for trait selection, we measured selection gradients on plant morphology in both males and females, as well as pollen production and dispersal in males, of the wind-pollinated dioecious herb Mercurialis annua. In two separate experimental common gardens established at different densities, selection strongly favored plants dispersing their pollen further. Selection for pollen production was observed in the high-density garden only and was weak. In addition, male morphologies associated with increased mean pollen dispersal differed between the two gardens as elongated branches were favored in the high-density garden while shorter plants with longer peduncles bearing inflorescences were advantaged the low-density garden. Larger females were selected in both gardens. Our results point to the importance of selection on male traits that affect pollen dispersal, and to a lesser extent pollen production.
Data from: A Drosophila female pheromone elicits species-specific long-range attraction via an olfactory channel with dual specificity for sex and food
Background: Mate finding and recognition in animals evolves during niche adaptation and involves social signals and habitat cues. Drosophila melanogaster and related species are known to be attracted to fermenting fruit for feeding and egg-laying, which poses the question of whether species-specific fly odours contribute to long-range premating communication. Results: We have discovered an olfactory channel in D. melanogaster with a dual affinity to sex and food odorants. Female flies release a pheromone, (Z)-4-undecenal (Z4-11Al), that elicits flight attraction in both sexes. Its biosynthetic precursor is the cuticular hydrocarbon (Z,Z)-7,11-heptacosadiene (7,11-HD), which is known to afford reproductive isolation between the sibling species D. melanogaster and D. simulans during courtship. Twin olfactory receptors, Or69aB and Or69aA, are tuned to Z4-11Al and food odorants, respectively. They are co-expressed in the same olfactory sensory neurons, and feed into a neural circuit mediating species-specific, long-range communication; however, the close relative D. simulans, which shares food resources with D. melanogaster, does not respond to Z4-11Al. Conclusion: The Or69aA and Or69aB isoforms have adopted dual olfactory traits. The underlying gene yields a collaboration between natural and sexual selection, which has the potential to drive speciation.
Data from: Maternal pathogen exposure causes diet- and pathogen-specific transgenerational costs
Transgenerational effects, whereby the environment experienced by a parent leads to an altered offspring phenotype, have now been described in a variety of taxa. In invertebrates, much of the research on these effects has concentrated on the role of parental exposure to pathogens or immune elicitors in determining offspring immune investment or disease resistance. To date, however, studies of transgenerational effects in invertebrates have generally been restricted to single infections or immune elicitors in ideal laboratory environments. Animals in field situations will commonly experience sub-optimal environments and co-infection by multiple species of parasites and pathogens, leading to increased relative costs of immune investment and changing fitness benefits from offspring responses to the parental environment. Here we investigate a more ecologically realistic scenario involving both multiple infections and resource limitation, using the Indian meal moth Plodia interpunctella as a model host, challenged with the entomopathogenic bacterium Bacillus thuringiensis and fungus Beauveria bassiana. Mothers were exposed to low doses of one or both pathogens, or a control. Offspring from each family were reared on either good- or poor-quality food and then exposed to one or both pathogens. Maternal exposure to pathogens led to reduced pathogen resistance in offspring, depending on the combination of maternal and offspring pathogen-specific infections and resource limitation in the offspring generation. Much research to date has focussed on trans-generational immune priming, in which parental exposure to pathogens or immune elicitors leads to upregulated immune reactivity in their offspring. The lack of any such effects in our system suggests that the production of less resistant offspring following parental exposure to pathogens might be an important alternative, driven by costs of resistance rather than adaptive benefits.
Data from: Specificity of oral immune priming in the red flour beetle Tribolium castaneum
Immune specificity is the degree to which a host's immune system discriminates among various pathogens or antigenic variants. Vertebrate immune memory is highly specific due to antibody responses. On the other hand, some invertebrates show immune priming, i.e. improved survival after secondary exposure to a previously encountered pathogen. Until now, specificity of priming has only been demonstrated via the septic infection route or when live pathogens were used for priming. Therefore, we tested for specificity in the oral priming route in the red flour beetle, Tribolium castaneum. For priming, we used pathogen-free supernatants derived from three different strains of the entomopathogen, Bacillus thuringiensis, which express different Cry toxin variants known for their toxicity against this beetle. Subsequent exposure to the infective spores showed that oral priming was specific for two naturally occurring strains, while a third engineered strain did not induce any priming effect. Our data demonstrate that oral immune priming with a non-infectious bacterial agent can be specific, but the priming effect is not universal across all bacterial strains.
Data from: Perinatal lead (Pb) exposure results in sex-specific effects on food intake, fat, weight, and insulin response across the murine life-course
Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance. Data analyses were stratified by sex and adjusted for litter effects. Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both). In females, horizontal activity differed significantly from controls (p = 0.02) over the life-course. Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01). Body weight was significantly increased in males at the medium and high exposures (p = 0.001 and p = 0.006). Total body fat differed among exposed females and males (p<0.0001 and p<0.0001, respectively). Insulin response was significantly increased in medium exposure males (p<0.05). Perinatal Pb exposure at blood lead levels between 4.1 µg/dL and 32 µg/dL is associated with increased food intake, body weight, total body fat, energy expenditure, activity, and insulin response in mice. Physiological effects of developmental Pb exposure persist and vary according to sex and age.
Data from: Evolution of male age-specific reproduction under differential risks and causes of death: males pay the cost of high female fitness
Classic theories of ageing evolution predict that increased extrinsic mortality due to an environmental hazard selects for increased early reproduction, rapid ageing and short intrinsic lifespan. Conversely, emerging theory maintains that when ageing increases susceptibility to an environmental hazard, increased mortality due to this hazard can select against ageing in physiological condition and prolong intrinsic lifespan. However, evolution of slow ageing under high-condition-dependent mortality is expected to result from reallocation of resources to different traits and such reallocation may be hampered by sex-specific trade-offs. Because same life-history trait values often have different fitness consequences in males and females, sexually antagonistic selection can preserve genetic variance for lifespan and ageing. We previously showed that increased condition-dependent mortality caused by heat shock leads to evolution of long-life, decelerated late-life mortality in both sexes and increased female fecundity in the nematode, Caenorhabditis remanei. Here, we used these cryopreserved lines to show that males evolving under heat shock suffered from reduced early-life and net reproduction, while mortality rate had no effect. Our results suggest that heat-shock resistance and associated long-life trade-off with male, but not female, reproduction and therefore sexually antagonistic selection contributes to maintenance of genetic variation for lifespan and fitness in this population.
Data from: Viral infection causes sex-specific changes in fruit fly social aggregation behaviour
Host behavioural changes following infection are common and could be important determinants of host behavioural competence to transmit pathogens. Identifying potential sources of variation in sickness behaviours is therefore central to our understanding of disease transmission. Here, we test how group social aggregation and individual locomotor activity vary between different genotypes of male and female fruit flies (Drosophila melanogaster) following septic infection with Drosophila C Virus. We find genetic-based variation in both locomotor activity and social aggregation but we did not detect an effect of DCV infection on fly activity or sleep patterns within the initial days following infection. However, DCV infection caused sex-specific effects on social aggregation, as male flies in most genetic backgrounds increased the distance to their nearest neighbour when infected. We discuss possible causes for these differences in the context of individual variation in immunity and their potential consequences for disease transmission.
Data from: Chlamydomonas genome resource for laboratory strains reveals a mosaic of sequence variation, identifies true strain histories, and enables strain-specific studies
Chlamydomonas reinhardtii is a widely used reference organism in studies of photosynthesis, cilia, and biofuels. Most research in this field uses a few dozen standard laboratory strains that are reported to share a common ancestry, but exhibit substantial phenotypic differences. In order to facilitate ongoing Chlamydomonas research and explain the phenotypic variation, we mapped the genetic diversity within these strains using whole-genome resequencing. We identified 524,640 single nucleotide variants and 4812 structural variants among 39 commonly used laboratory strains. Nearly all (98.2%) of the total observed genetic diversity was attributable to the presence of two, previously unrecognized, alternate haplotypes that are distributed in a mosaic pattern among the extant laboratory strains. We propose that these two haplotypes are the remnants of an ancestral cross between two strains with ∼2% relative divergence. These haplotype patterns create a fingerprint for each strain that facilitates the positive identification of that strain and reveals its relatedness to other strains. The presence of these alternate haplotype regions affects phenotype scoring and gene expression measurements. Here, we present a rich set of genetic differences as a community resource to allow researchers to more accurately conduct and interpret their experiments with Chlamydomonas.
Data from: Sex-specific density-dependent secretion of glucocorticoids in lizards: insights from laboratory and field experiments
Negative density feedbacks have been extensively described in animal species and involve both consumptive (i.e. trophic interactions) and non-consumptive (i.e. social interactions) mechanisms. Glucocorticoids are a major component of the physiological stress response and homeostasis, and therefore make a good candidate for proximate determinants of negative density feedbacks. Here, we combined laboratory and field experiments with enclosed populations to investigate the relationship between density, social stress and plasma corticosterone levels in the common lizard Zootoca vivipara. This species exhibits strong negative density feedbacks that affect females more than males, and its life history is sensitive to experimentally-induced chronic elevation of corticosterone plasma levels. We found that prolonged crowding in the laboratory can trigger a chronic secretion of corticosterone independent from food restriction. In the field experiments, corticosterone levels of females were not affected by population density. Corticosterone levels of males increased with population density but only during the late activity season in a first field experiment where we manipulated density. They also increased with density during the mating season but only in populations with a female-biased sex ratio in a second field experiment where we crossed manipulated density and adult sex ratio. Altogether, our results provide limited evidence for a role of basal corticosterone secretion in density feedbacks in this species. Context and density-dependent effects in males may arise from changes in behavior caused by competition for resources, male–male competition, and mating.
Data from: Molecular signatures of lineage-specific adaptive evolution in a unique sea basin: the example of an anadromous goby Leucopsarion petersii
Climate changes on various time scales often shape genetic novelty and adaptive variation in many biotas. We explored molecular signatures of directional selection in populations of the ice goby Leucopsarion petersii inhabiting a unique sea basin, the Sea of Japan, where a wide variety of environments existed in the Pleistocene in relation to shifts in sea level by repeated glaciations. This species consisted of two historically allopatric lineages, the Japan Sea (JS) and Pacific Ocean (PO) lineages, and these have lived under contrasting marine environments that are expected to have imposed different selection regimes caused by past climatic and current oceanographic factors. We applied a limited genome-scan approach using seven candidate genes for phenotypic differences between two lineages in combination with 100 anonymous microsatellite loci. Neuropeptide Y (NPY) gene, which is an important regulator of food intake and potent orexigenic agent, and three anonymous microsatellites were identified as robust outliers, that is, candidate loci potentially under directional selection, by multiple divergence- and diversity-based outlier tests in comparisons focused on multiple populations of the JS vs. PO lineages. For these outlier loci, populations of the JS lineage had putative signals of selective sweeps. Additionally, real-time quantitative PCR analysis using fish reared in a common environment showed a higher expression level for NPY gene in the JS lineage. Thus, this study succeeded in identifying candidate genomic regions under selection across populations of the JS lineage and provided evidence for lineage-specific adaptive evolution in this unique sea basin.
Data from: Heat hardening capacity in Drosophila melanogaster is life stage specific and juveniles show the highest plasticity
Variations in stress resistance and adaptive plastic responses during ontogeny have rarely been addressed, despite the possibility that differences between life stages can affect species' range margins and thermal tolerance. Here, we assessed the thermal sensitivity and hardening capacity of Drosophila melanogaster across developmental stages from larval to the adult stage. We observed strong differences between life stages in heat resistance, with adults being most heat resistant followed by puparia, pupae and larvae. The impact of heat hardening (1 h at 35°C) on heat resistance changed during ontogeny, with the highest positive effect of hardening observed in puparia and pupae and the lowest in adults. These results suggest that immobile life stages (puparia and pupae) have evolved high plasticity in upper thermal limits whereas adults and larvae rely more on behavioural responses to heat stress allowing them to escape from extreme high temperatures. While most studies on the plasticity of heat resistance in ectotherms have focused on the adult life stage, our findings emphasize the crucial importance of juvenile life stages of arthropods in understanding the thermal biology and life stage-specific physiological responses to variable and stressful high temperatures. Failure to acknowledge this complication might lead to biased estimates of species' ability to cope with environmental changes, such as climate change.
Data from: In silico site-directed mutagenesis informs species-specific predictions of chemical susceptibility derived from the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool
Chemical hazard assessment requires extrapolation of information from model organisms to all species of concern. The Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was developed as a rapid, cost effective method to aid cross-species extrapolation of susceptibility to chemicals acting on specific protein targets through evaluation of protein structural similarities and differences. The greatest resolution for extrapolation of chemical susceptibility across species involves comparisons of individual amino acid residues at key positions involved in protein-chemical interactions. However, a lack of understanding of whether specific amino acid substitutions among species at key positions in proteins affect interaction with chemicals made manual interpretation of alignments time consuming and potentially inconsistent. Therefore, this study used in silico site-directed mutagenesis coupled with docking simulations of computational models for acetylcholinesterase (AChE) and ecdysone receptor (EcR) to investigate how specific amino acid substitutions impact protein-chemical interaction. This study found that computationally derived substitutions in identities of key amino acids caused no change in protein-chemical interaction if residues share the same side chain functional properties and have comparable molecular dimensions, while differences in these characteristics can change protein-chemical interaction. These findings were considered in the development of capabilities for automatically generated species-specific predictions of chemical susceptibility in SeqAPASS. These predictions for AChE and EcR were shown to agree with SeqAPASS predictions comparing the primary sequence and functional domain sequence of proteins for more than 90 % of the investigated species, but also identified dramatic species-specific differences in chemical susceptibility that align with results from standard toxicity tests. These results provide a compelling line-of-evidence for use of SeqAPASS in deriving screening level, species-specific, susceptibility predictions across broad taxonomic groups for application to human and ecological hazard assessment.
Data from: Sex-specific gene expression in the mouse nucleus accumbens before and after cocaine exposure
Females are more sensitive than males to the addictive effects of cocaine and are more likely to relapse. The nucleus accumbens has a well-established major role in the response to cocaine, and sex-specific differential expression of key transcripts at baseline and after cocaine withdrawal could underlie some of these differences. To address this hypothesis, four groups of mice (cycling females, ovariectomized females treated with estradiol or placebo and males) were evaluated for open field activity following 7 daily injections of saline or cocaine. Sensitization to the locomotor effects of cocaine was most pronounced in ovariectomized mice receiving estradiol, was greater in cycling females than in males, and failed to occur in ovariectomized/placebo mice. After a 28-day period of withdrawal, RNA prepared from the nucleus accumbens of individual cocaine or saline injected mice was subjected to RNASeq analysis. Expression of a substantial fraction of the transcripts expressed in the nucleus accumbens (~3%) differed in cycling female mice when compared to male mice, was altered by ovariectomy or was responsive to estradiol treatment. The transcripts differentially expressed in the nucleus accumbens of cycling female mice withdrawn from cocaine for 28-days exhibited substantial overlap with those differentially expressed in the nucleus accumbens of male mice withdrawn for 7-days. A small set of transcripts were similarly affected by cocaine in placebo or estradiol treated ovariectomized mice. Transcripts differentially expressed after 28-days of withdrawal encoded neprilysin, which degrades enkephalin and other neuropeptides, G protein coupled receptors and secreted proteins such as Wnt2, Fst and Igfbp4.
Data from: Trophic consequences of introduced species: comparative impacts of increased inter-specific versus intra-specific competitive interactions
1. Invasive species can cause substantial ecological impacts on native biodiversity. Whilst ecological theory attempts to explain the processes involved in the trophic integration of invaders into native food webs and their competitive impacts on resident species, results are equivocal. In addition, quantifying the relative strength of impacts from non-native species (inter-specific competition) versus the release of native conspecifics (intra-specific competition) is important but rarely completed. 2. Two model non-native fishes, the globally invasive Cyprinus carpio and Carassius auratus, and the model native fish Tinca tinca, were used in a pond experiment to test how increased intra- and inter-specific competition influenced trophic niches and somatic growth rates. This was complemented by samples collected from three natural fish communities where the model fishes were present. The isotopic niche, calculated using stable isotope data, represented the trophic niche. 3. The pond experiment used additive and substitutive treatments to quantify the trophic niche variation that resulted from intra- and inter-specific competitive interactions. Although the trophic niche sizes of the model species were not significantly altered by any competitive treatment, they all resulted in patterns of inter-specific niche divergence. Increased inter-specific competition caused the trophic niche of T. tinca to shift to a significantly higher trophic position, whereas intra-specific competition caused its position to shift towards elevated δ13C. These patterns were independent of impacts on fish growth rates, which were only significantly altered when inter-specific competition was elevated. 4. In the natural fish communities, patterns of trophic niche partitioning between the model fishes was evident, with no niche sharing. Comparison of these results with those of the experiment revealed the most similar results between the two approaches were for the niche partitioning between sympatric T. tinca and C. carpio. 5. These results indicate that trophic niche divergence facilitates the integration of introduced species into food webs, but there are differences in how this manifests between introductions that increase inter- and intra-specific competition. In entirety, these results suggest that the initial ecological response to an introduction appears to be a trophic re-organisation of the food web that minimises the trophic interactions between competing species.
Data from: Adaptive contraction of diet breadth affects sexual maturation and specific nutrient consumption in an extreme generalist omnivore
Animals balance their intake of specific nutrients, but little is known about how they do so when foraging in an environment with toxic resources and whether toxic foods promote adaptations that affect life history traits. In German cockroach (Blattella germanica) populations, glucose aversion has evolved in response to glucose-containing insecticidal baits. We restricted newly eclosed glucose averse (GA) and wild type (WT) female cockroaches to nutritionally defined diets varying in protein-to-carbohydrate (P:C) ratio (3:1, 1:1, or 1:3) or gave them free choice of the 3:1 and 1:3 diets, with either glucose or fructose as the sole carbohydrate source. We measured consumption of each diet over six days and then dissected the females to measure the length of basal oocytes in their ovaries. Our results showed significantly lower consumption by GA compared to WT cockroaches when restricted to glucose-containing diets, but also lower fructose intake by GA compared to WT cockroaches when restricted to high fructose diets or given choice of fructose-containing diets. Protein intake was regulated tightly regardless of carbohydrate intake, except by GA cockroaches restricted to glucose-containing diets. Oocyte growth was completely suppressed in GA females restricted to glucose-containing diets, but also significantly slower in GA than in WT females restricted to fructose-containing diets. Our findings suggest that GA cockroaches have adapted to reduced diet breadth through endocrine adjustments which reduce requirements for energetic fuels. Our study illustrates how an evolutionary change in the chemosensory system may affect the evolution of other traits that govern animal life histories.
Data from: Offspring provisioning explains clone specific maternal age effects on life history and lifespan in the water flea, Daphnia pulex
Genetic inheritance underpins evolutionary theories of aging, but the role that nongenetic inheritance plays is unclear. Parental age reduces the life span of offspring in a diverse array of taxa but has not been explained from an evolutionary perspective. We quantified the effect that maternal age had on the growth and maturation decisions, life history, rates of senescence, and life span of offspring from three Daphnia pulex clones collected from different populations. We then used those data to test general hypotheses proposed to explain maternal age effects on offspring life span. Three generations of breeding from young or old mothers produced dramatic differences in the life histories of fourth-generation offspring, including significant reductions in life span. The magnitude of the effect differed between clones, which suggests that genetic and nongenetic factors ultimately underpin trait inheritance and shape patterns of aging. Older parents did not transmit a senescent state to their offspring. Instead, offspring from older ancestors had increased early-life reproductive effort, which resulted in an earlier onset of reproductive senescence, and an increased rate of actuarial senescence, which shortened their life span. Our results provide a clear example of the need to consider multiple inheritance mechanisms when studying trait evolution.
Data from: Slow and temperature-mediated pathogen adaptation to a non-specific fungicide in agricultural ecosystem
The spread of antimicrobial resistance and global change in air temperature represent two major phenomena that are exerting a disastrous impact on natural and social issues but investigation of the interaction between these phenomena in an evolutionary context is limited. In this study, a statistical genetic approach was used to investigate the evolution of antimicrobial resistance in agricultural ecosystem and its association with local air temperature. We found no resistance to mancozeb, a non-specific fungicide widely used in agriculture for more than half a century, in 215 Alternaria alternata isolates sampled from geographic locations along a climatic gradient and cropping system representing diverse ecotypes in China, consistent with low resistance risk in many non-specific fungicides. Genetic variance accounts for ~35% of phenotypic variation while genotype-environment interaction is negligible, suggesting that heritability plays a more important role in the evolution of resistance to mancozeb in plant pathogens than phenotypic plasticity. We also found that tolerance to mancozeb in agricultural ecosystem is under constraining selection and significantly associated with local air temperature, possibly resulting from a pleiotropic effect of tolerance with thermal and other ecological adaptations. The implication of these results for fungicide and other antimicrobial management in the context of global warming is discussed.
Data from: Agonist-specific voltage-dependent gating of lysosomal Two-Pore Na + Channels
Mammalian Two-Pore-Channels (TPC1, 2; TPCN1, TPCN2) are ubiquitously-expressed cation channels in the endosomes and lysosomes that regulate luminal pH homeostasis, membrane trafficking, and Ebola viral infection. Lysosomal patch-clamp studies and high-resolution structural determinations have demonstrated that TPCs are Na+-selective channels activated by lysosome-localized PI(3,5)P2. Whereas the channel activity of TPC1 is strongly dependent on membrane voltage, TPC2 lacks such voltage dependence despite the presence of several positively-charged amino acid (AA) residues in the presumed "S4 voltage-sensing" domains. By performing a Ca2+-imaging-based high-throughput screening followed by lysosomal electrophysiology, here we identified a class of tri-cyclic anti-depressants (TCAs) as small-molecule agonists of TPC channels. TCAs activate both TPC1 and TPC2 in a voltage-dependent manner, so we refer to them as Lysosomal Na+ channel Voltage-dependent Activators (LyNa-VAs). We also identified another compound which, like PI(3,5)P2, activates TPC2 independent of voltage, suggesting the existence of agonist-specific gating mechanisms. Our identification of small-molecule TPC agonists should facilitate the studies of the cell biological roles of TPCs, and can also readily explain the reported effects of TCAs in the modulation of autophagy and lysosomal function.
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.