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The pesticides paraquat (PQ) and maneb (MB) have been described as environmental risk factors for Parkinson’s disease (PD), with mechanisms associated with mitochondrial dysfunction and reactive oxygen species generation. A combined exposure of PQ and MB in murine models and neuroblastoma cells has been utilized to further advance understanding of the PD phenotype. MB acts as a redox modulator through alkylation of protein thiols and has been previously characterized to inhibit complex III of the electron transport chain and uncouple the mitochondrial proton gradient. The purpose of this study was to analyze ATP-linked respiration and glycolysis in human neuroblastoma cells utilizing the Seahorse extracellular flux platform. Employing an acute, subtoxic exposure of MB, this investigation revealed a MB-mediated decrease in mitochondrial oxygen consumption at baseline and maximal respiration, with inhibition of ATP synthesis and coupling efficiency. Additionally, MB-treated cells showed an increase in nonmitochondrial respiration and proton leak. Further investigation into mitochondrial fuel flex revealed an elimination of fuel flexibility across all 3 major substrates, with a decrease in pyruvate capacity as well as glutamine dependency. Analyses of glycolytic function showed a substantial decrease in glycolytic acidification caused by lactic acid export. This inhibition of glycolytic parameters was also observed after titrating the MB dose as low as 6 μM, and appears to be dependent on the dithiocarbamate functional group, with manganese possibly potentiating the effect. Further studies into cellular ATP and NAD levels revealed a drastic decrease in cells treated with MB. In summary, MB significantly impacted both aerobic and anaerobic energy production; therefore, further characterization of MB’s effect on cellular energetics may provide insight into the specificity of PD to dopaminergic neurons.
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Through phenotypic plasticity, bones can change in structure and morphology, in response to physiological and biomechanical influences over the course of individual life. Changes in bones also occur in evolution as functional adaptations to environment. In this study, we report on the evolution of bone mass increase (BMI) that occurred in the postcranium and skull of extinct aquatic sloths. Although non-pathological BMI in postcranial skeleton has been known in aquatic mammals, we here document general BMI in the skull for the first time. We present evidence of thickening of the nasal turbinates, nasal septum, and cribriform plate, and further thickening of the frontals, and infilling of sinus spaces by compact bone in the late and more aquatic species of the extinct sloth Thalassocnus. Systemic bone mass increase occurred among the successively more aquatic species of Thalassocnus, as an evolutionary adaptation to the lineage’s changing environment. The newly documented pachyostotic turbinates appear to have conferred little or no functional advantage and are herein hypothesized as a correlation with or consequence of the systemic BMI among Thalassocnus species. This could in turn be consistent with a genetic accommodation of a physiological adjustment to a change of environment.
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The discernment of populations as management units is a fundamental prerequisite for sustainable exploitation of species. A lack of clear stock boundaries complicates not only the identification of spatial management units, but also the assessment of mixed fisheries by population assignment and mixed stock analysis. Many marine species, such as Pacific cod, are characterized by isolation-by-distance, showing significant differentiation but no clear stock boundaries. Here, we used restriction-site associated DNA (RAD) sequencing to investigate population structure and assess power to genetically assign Pacific cod to putative populations of origin. Samples were collected across the species range in the Eastern Pacific Ocean, from the Salish Sea to the Aleutian Islands. A total of 6,425 putative biallelic single nucleotide polymorphisms were identified from 276 individuals. We found a strong isolation-by-distance signal along coastlines that mirrored previous microsatellite results, and pronounced genetic differentiation between coastal samples and those from the inland waters of the Salish Sea with no evidence for hybridization between these two populations. Individual assignment success based on two methods was high overall (≥ 84%) but decreased from south to north. Assignment to geographic location of origin also was successful, with average distance between capture and assignment location of 220 km. Outlier analyses identified more loci potentially under selection along the coast than between Salish Sea and coast samples, suggesting more diverse adaptation to latitudinal environmental factors than inshore vs offshore environments. Our results confirm previous observations of sharp genetic differentiation of the Salish Sea population and isolation-by-distance along the coast, but also highlight the feasibility of using modern genomic techniques to inform stock boundaries and fisheries management in a low FST marine species.
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Two subspecies of the house mouse, Mus musculus domesticus and Mus musculus musculus, meet in a narrow contact zone across Europe. Mice in the hybrid zone are highly admixed, representing the full range of mixed ancestry from the two subspecies. Given the distinct morphologies of these subspecies, these natural hybrids can be used for genome-wide association mapping at sufficiently high resolution to directly infer candidate genes. We focus here on limb bone length differences, which is of special interest for understanding the evolution of developmentally correlated traits. We used 172 first-generation descendants of wild-caught mice from the hybrid zone to measure the length of stylopod (humerus / femur), zeugopod (ulna / tibia) and autopod (metacarpal / metatarsal) elements in skeletal CT scans. We find phenotypic covariation between limb elements in the hybrids similar to patterns previously described in M. m. domesticus inbred strains, suggesting that the hybrid genotypes do not influence the covariation pattern in a major way. Mapping was performed using 143,592 SNPs and identified several genomic regions associated with length differences in each bone. Each candidate region explains only a small proportion of phenotypic variance, suggesting that bone length is highly polygenic. None of the candidate regions includes the canonical genes known to control embryonic limb development. Instead, we are able to identify candidate genes with known roles in osteoblast differentiation and bone structure determination, as well as recently evolved genes of, as yet, unknown function.
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The evolution of mammalian olfaction is manifested in a remarkable diversity of gene repertoires, neuroanatomy, and skull morphology across living species. Olfactory receptor genes (ORG), which initiate the conversion of odorant molecules into odor perceptions and help an animal resolve the olfactory world, range in number from a mere handful to several thousand genes across species. Within the snout, each of these ORGs is exclusively expressed by a discrete population of olfactory sensory neurons (OSN), suggesting that newly evolved ORGs may be coupled with new OSN populations in the nasal epithelium. Because OSNs axon bundles leave high-fidelity perforations (foramina) in the bone as they traverse the cribriform plate (CP) to reach the brain, we predicted that taxa with larger ORG repertoires would have proportionately expanded footprints in the CP foramina. Previous work found a correlation between ORG number and absolute CP size that disappeared when body size effects were accounted for. Using updated, digital measurement data from high-resolution CT scans and reexamining the relationship between CP and body size, we report a striking linear correlation between relative CP area and number of functional ORGs across species from all mammalian superorders. This correlation suggests strong developmental links in the olfactory pathway between genes, neurons, and skull morphology. Furthermore, because ORG number is linked to olfactory discriminatory function, this correlation supports relative CP size as a viable metric for inferring olfactory capacity across modern and extinct species. By quantifying CP area from a fossil sabertooth cat (Smilodon fatalis) we predicted a likely ORG repertoire for this extinct felid.
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We describe a nearly complete, and thus extremely rare, featherstar (Crinoidea, Comatulida) from Oligocene strata of North Otago/South Canterbury, New Zealand. A detailed analysis of this specimen, as well as newly recovered material and previously described fragmentary remains from nearby contemporaneous sedimentary units, in addition to relevant historical specimens, lead us to conclude that it cannot be placed in any currently established genus. A new genus, Rautangaroa, is proposed to accommodate it. This intact specimen of Rautangaroa aotearoa (Eagle, 2007), new combination, provides rare data on the morphology of arms and cirri. It represents the first example of arm autotomy and regeneration in a fossil featherstar, and thus has bearing on the importance of predation to the evolutionary history of this group.
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Progress in understanding and managing complex systems comprised of decision-making agents, such as cells, organisms, ecosystems, or societies, is—like many scientific endeavors—limited by disciplinary boundaries. These boundaries, however, are moving and can actively be made porous or even disappear. To study this process, we advanced an original bibliometric approach based on network analysis to track and understand the development of the model-based science of agent-based complex systems (ACS). We analyzed research citations between the two communities devoted to ACS research, namely agent-based (ABM) and individual-based modeling (IBM). Both terms refer to the same approach, yet the former is preferred in engineering and social sciences, while the latter prevails in natural sciences. This situation provided a unique case study for grasping how a new concept evolves distinctly across scientific domains and how to foster convergence into a universal scientific approach. The present analysis based on novel hetero-citation metrics revealed the historical development of ABM and IBM, confirmed their past disjointedness, and detected their progressive merger. The separation between these synonymous disciplines had silently opposed the free flow of knowledge among ACS practitioners and has thereby hindered the transfer of methodological advances and the emergence of general systems theories. A surprisingly small number of key publications sparked the ongoing fusion between ABM and IBM research. Beside reviews raising awareness of broad-spectrum issues, generic protocols for model formulation and boundary-transcending inference strategies were critical means of science integration. From the modeling viewpoint, the discovery of the unification of ABM and IBM demonstrates that a wide variety of systems substantiate the premise of ACS research that microscale behaviors of agents and system-level dynamics are inseparably bound.
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Plate tectonics and sediment processes control regional continental shelf topography. We examine the genetic consequences of how glacial-associated sea-level change interacted with variable near-shore topography since the last glaciation. We reconstructed the size and distribution of areas suitable for tidal estuary formation from the Last Glacial Maximum, ~20 thousand years ago, to present from San Francisco, California, USA (~38 °N) to Reforma, Sinaloa, Mexico (~25 °N). We assessed range-wide genetic structure and diversity of three co-distributed tidal estuarine fishes (California Killifish, Shadow Goby, Longjaw Mudsucker) along ~4,600 km using mitochondrial control region and cytB sequence, and 16–20 microsatellite loci from a total of 524 individuals. Results show that glacial-associated sea-level change limited estuarine habitat to few, widely separated refugia at glacial lowstand, and present-day genetic clades were sourced from specific refugia. Habitat increased during postglacial sea-level rise and refugial populations admixed in newly formed habitats. Continental shelves with active tectonics and/or low sediment supply were steep and hosted fewer, smaller refugia with more genetically differentiated populations than on broader shelves. Approximate Bayesian computation favored the refuge-recolonization scenarios from habitat models over isolation by distance and seaway alternatives, indicating isolation at lowstand is a major diversification mechanism among estuarine (and perhaps other) coastal species. Because sea-level change is a global phenomenon, we suggest this top-down physical control of extirpation-isolation-recolonization may be an important driver of genetic diversification in coastal taxa inhabiting other topographically complex coasts globally during the Mid- to Late Pleistocene and deeper timescales.
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Recent studies of the trophic structure of the underwater cave ecosystems in the Yucatán Peninsula have regarded the largest crustacean inhabitant, the blind palaemonid shrimp Creaseria morleyi (Creaser, 1936), as a scavenger and predator without any evidence on the behavior of the shrimp. The predatory behavior of C. morleyi is here described for the first time, verifying its classification as a predator. A variety of prey targets, including the atyid shrimp Typhlatya sp., were used to demonstrate predation and saprophagous feeding behavior in C. morleyi using in vitro and in situ observations. Scanning electron microscope images show the structures of the antennules and antennae that could be responsible for prey detection. Findings show that C. morleyi is capable of hunting a variety of prey, most likely depending on their relative size. Observations on the feeding strategy of C. morleyi suggest any animal within a particular size range is a potential prey, including its own species, which suggests the hypothesis that growth may be favored in early stages of life in order to reach a size refuge from predation. These observations provide information of some of the adaptations necessary for a predator to thrive in an aphotic and oligotrophic environment.
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Background: Populations of herbivorous insects may become genetically differentiated because of local adaptation to different hosts and climates as well as historical processes, and further genetic divergence may occur following the development of reproductive isolation among populations. Here we investigate the population genetic structure of the orchard pest peach fruit moth (PFM) Carposina sasakii (Lepidoptera: Carposinidae) in China, which shows distinct biological differences when characterized from different host plants. Genetic diversity and genetic structure were assessed among populations from seven plant hosts and nine regions using 19 microsatellite loci and a mitochondrial sequence. Results: Strong genetic differentiation was found among geographical populations representing distinct geographical regions, but not in host-associated populations collected from the same area. Mantel tests based on microsatellite loci indicated an association between genetic differentiation and geographical distance, and to a lesser extent environmental differentiation. Approximate Bayesian Computation analyses supported the scenario that PFM likely originated from a southern area and dispersed northwards before the last glacial maximum during the Quaternary. Conclusions: Our analyses suggested a strong impact of geographical barriers and historical events rather than host plants on the genetic structure of the PFM; however, uncharacterized environmental factors and host plants may also play a role. Studies on adaptive shifts in this moth should take into account geographical and historical factors.
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