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Rapid nerve conduction in the peripheral nervous system (PNS) is facilitated by the multilamellar myelin sheath encasing many axons of peripheral nerves. Charcot-Marie-Tooth type 1A (CMT1A), and hereditary neuropathy with liability to pressure palsy (HNPP) are common demyelinating inherited peripheral neuropathies and are caused by mutations in the peripheral myelin protein 22 (PMP22) gene. Duplication of PMP22 leads to its overexpression and causes CMT1A, while its deletion results in PMP22 under expression and causes HNPP. Here, we investigated novel targets for modulating the protein level of PMP22 in HNPP. We found that genetic attenuation of the transcriptional coactivator Yap in Schwann cells reduces p-TAZ levels, increased TAZ activity, and increases PMP22 in peripheral nerves. Based on these findings, we ablated Yap alleles in Schwann cells of the Pmp22-haploinsufficient mouse model of HNPP and identified fewer tomacula on morphological assessment and improved nerve conduction in peripheral nerves. These findings suggest YAP modulation may be a new avenue for treatment of HNPP.
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Schwann cells are critical for the proper development and function of the peripheral nervous system (PNS), where they form a collaborative relationship with axons. Past studies highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (Phb2) in vivo results in severe defects in radial sorting and myelination. We show in vivo that Phb2-null Schwann cells cannot effectively proliferate and the transcription factors EGR2 (KROX20), POU3F1 (OCT6), and POU3F2 (BRN2), necessary for proper Schwann cell maturation, are dysregulated. Schwann cell-specific deletion of Jun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the developmental defect seen in mice lacking Schwann cell Phb2. Finally, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on neuronal signals, and thus are potential mediators of PHB2-associated developmental defects. This work develops our understanding of Schwann cell biology, revealing that Phb2 may modulate the timely expression of transcription factors necessary for proper PNS development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.
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Microbial communities are increasingly recognized as crucial for animal health. However, our understanding of how microbial communities are structured across wildlife populations is poor. Mechanisms such as interspecific associations are important in structuring free-living communities, but we still lack an understanding of how important interspecific associations are in structuring gut microbial communities in comparison with other factors such as host characteristics or spatial proximity of hosts. Here, we ask how gut microbial communities are structured in a population of North American moose Alces alces. We identify key microbial interspecific associations within the moose gut and quantify how important they are relative to key host characteristics, such as body condition, for predicting microbial community composition. We sampled gut microbial communities from 55 moose in a population experiencing decline due to a myriad of factors, including pathogens and malnutrition. We examined microbial community dynamics in this population utilizing novel graphical network models that can explicitly incorporate spatial information. We found that interspecific associations were the most important mechanism structuring gut microbial communities in moose and detected both positive and negative associations. Models only accounting for associations between microbes had higher predictive value compared to models including moose sex, evidence of previous pathogen exposure or body condition. Adding spatial information on moose location further strengthened our model and allowed us to predict microbe occurrences with ~90% accuracy. Collectively, our results suggest that microbial interspecific associations coupled with host spatial proximity are vital in shaping gut microbial communities in a large herbivore. In this case, previous pathogen exposure and moose body condition were not as important in predicting gut microbial community composition. The approach applied here can be used to quantify interspecific associations and gain a more nuanced understanding of the spatial and host factors shaping microbial communities in non-model hosts.
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Cervos , Microbiota , Animais , Animais Selvagens , Trato Gastrointestinal , Herbivoria , Estados UnidosRESUMO
Toxoplasma gondii infections are widespread in white-tailed deer (Odocoileus virginianus) but little is known of its prevalence in other cervids in the USA. Moose (Alces alces) is a popular large game animal, hunted for its meat and trophy antlers. Here, we report seroprevalence, isolation, and genetic characterization of T. gondii from moose from Minnesota. Antibodies against T. gondii were detected in 8 of 79 (10%) moose tested by the modified agglutination test (MAT 1:25 or higher). The myocardium of 68 moose was bioassayed individually in mice, irrespective of serological status. T. gondii was detected in three moose (2 adults, 1 3 weeks old). The parasite from 2 adults was further propagated in cell culture. PCR-RFLP genotyping of cell culture derived tachyzoites using 10 genetic markers, SAG1, SAG2 (5' and 3' SAG2, and alt.SAG2), SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1, and Apico revealed two different ToxoDB PCR-RFLP genotypes (#5, designated TgMooseUS1, and #7, TgMooseUS2). The mice inoculated with myocardium of the juvenile moose developed antibodies against T. gondii, and DNA extracted from infected mouse brain was only partially characterized by PCR-RFLP genotyping, which suggests a potential new genotype. Result documented prevalence of T. gondii in moose, and its possible transplacental/transmammary transmission of T. gondii in moose.
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Cervos/parasitologia , Toxoplasma/genética , Toxoplasmose Animal/epidemiologia , Testes de Aglutinação/veterinária , Animais , Animais Recém-Nascidos/parasitologia , Anticorpos Antiprotozoários/sangue , Bioensaio/veterinária , Feminino , Marcadores Genéticos , Genótipo , Coração/parasitologia , Humanos , Transmissão Vertical de Doenças Infecciosas/veterinária , Masculino , Camundongos , Minnesota/epidemiologia , Reação em Cadeia da Polimerase/veterinária , Polimorfismo de Fragmento de Restrição , Estudos Soroepidemiológicos , Toxoplasma/classificação , Toxoplasma/imunologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/parasitologia , Toxoplasmose Animal/transmissãoRESUMO
BACKGROUND: Prey are more vulnerable during migration due to decreased familiarity with their surroundings and spatially concentrated movements. Predators may respond to increased prey vulnerability by shifting their ranges to match prey. Moose (Alces alces) and white-tailed deer (Odocoileus virginianus) are primary gray wolf (Canis lupus) prey and important subsistence species for Indigenous communities. We hypothesized wolves would increase use of ungulate migration corridors during migrations and predicted wolf distributions would overlap primary available prey. METHODS: We examined seasonal gray wolf, moose, and white-tailed deer movements on and near the Grand Portage Indian Reservation, Minnesota, USA. We analyzed GPS collar data during 2012-2021 using Brownian bridge movement models (BBMM) in Migration Mapper and mechanistic range shift analysis (MRSA) to estimate individual- and population-level occurrence distributions and determine the status and timing of range shifts. We estimated proportional overlap of wolf distributions with moose and deer distributions and tested for differences among seasons, prey populations, and wolf sex and pack affiliations. RESULTS: We identified a single migration corridor through which white-tailed deer synchronously departed in April and returned in October-November. Gray wolf distributions overlapped the deer migration corridor similarly year-round, but wolves altered within-range distributions seasonally corresponding to prey distributions. Seasonal wolf distributions had the greatest overlap with deer during fall migration (10 October-28 November) and greatest overlap with moose during summer (3 May-9 October). CONCLUSIONS: Gray wolves did not increase their use of the white-tailed deer migration corridor but altered distributions within their territories in response to seasonal prey distributions. Greater overlap of wolves and white-tailed deer in fall may be due to greater predation success facilitated by asynchronous deer migration movements. Greater summer overlap between wolves and moose may be linked to moose calf vulnerability, American beaver (Castor canadensis) co-occurrence, and reduced deer abundance associated with migration. Our results suggest increases in predation pressure on deer in fall and moose in summer, which can inform Indigenous conservation efforts. We observed seasonal plasticity of wolf distributions suggestive of prey switching; that wolves did not exhibit migratory coupling was likely due to spatial constraints resulting from territoriality.
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AIMS: We investigated the presence of SARS-CoV-2 in free-ranging wildlife populations in Northeastern Minnesota on the Grand Portage Indian Reservation and Isle Royale National Park. METHODS AND RESULTS: One hundred twenty nasal samples were collected from white-tailed deer, moose, grey wolves and black bears monitored for conservation efforts during 2022-2023. Samples were tested for viral RNA by RT-qPCR using the CDC N1/N2 primer set. Our data indicate that no wildlife samples were positive for SARS-CoV-2 RNA. CONCLUSIONS: Continued surveillance is therefore crucial to better understand the changing landscape of zoonotic SARS-CoV-2 in the Upper Midwest.
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Animais Selvagens , COVID-19 , Parques Recreativos , SARS-CoV-2 , Animais , Minnesota/epidemiologia , Animais Selvagens/virologia , SARS-CoV-2/genética , COVID-19/epidemiologia , COVID-19/veterinária , RNA Viral , Cervos/virologiaRESUMO
Fish serve as indicators of exposure to contaminants of emerging concern (CECs)-chemicals such as pharmaceuticals, hormones, and personal care products-which are often designed to impact vertebrates. To investigate fish health and CECs in situ, we evaluated the health of wild fish exposed to CECs in waterbodies across northeastern Minnesota with varying anthropogenic pressures and CEC exposures: waterbodies with no human development along their shorelines, those with development, and those directly receiving treated wastewater effluent. Then, we compared three approaches to evaluate the health of fish exposed to CECs in their natural environment: a refined fish health assessment index, a histopathological index, and high-throughput (ToxCast) in vitro assays. Lastly, we mapped adverse outcome pathways (AOPs) associated with identified ToxCast assays to determine potential impacts across levels of biological organization within the aquatic system. These approaches were applied to subsistence fish collected from the Grand Portage Indian Reservation and 1854 Ceded Territory in 2017 and 2019. Overall, 24 CECs were detected in fish tissues, with all but one of the sites having at least one detection. The combined implementation of these tools revealed that subsistence fish exposed to CECs had histological and macroscopic tissue and organ abnormalities, although a direct causal link could not be established. The health of fish in undeveloped sites was as poor, or sometimes poorer, than fish in developed and wastewater effluent-impacted sites based on gross and histologic tissue lesions. Adverse outcome pathways revealed potential hazardous pathways of individual CECs to fish. A better understanding of how the health of wild fish harvested for consumption is affected by CECs may help prioritize risk management research efforts and can ultimately be used to guide fishery management and public health decisions. Integr Environ Assess Manag 2024;20:846-863. © 2023 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
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Schwann cells are critical for the proper development and function of the peripheral nervous system, where they form a mutually beneficial relationship with axons. Past studies have highlighted that a pair of proteins called the prohibitins play major roles in Schwann cell biology. Prohibitins are ubiquitously expressed and versatile proteins. We have previously shown that while prohibitins play a crucial role in Schwann cell mitochondria for long-term myelin maintenance and axon health, they may also be present at the Schwann cell-axon interface during development. Here, we expand on this work, showing that drug-mediated modulation of prohibitins in vitro disrupts myelination and confirming that Schwann cell-specific ablation of prohibitin 2 (Phb2) in vivo results in early and severe defects in peripheral nerve development. Using a proteomic approach in vitro, we identify a pool of candidate PHB2 interactors that change their interaction with PHB2 depending on the presence of axonal signals. Furthermore, we show in vivo that loss of Phb2 in mouse Schwann cells causes ineffective proliferation and dysregulation of transcription factors EGR2 (KROX20), POU3F1 (OCT6) and POU3F2 (BRN2) that are necessary for proper Schwann cell maturation. Schwann cell-specific deletion of Jun, a transcription factor associated with negative regulation of myelination, confers partial rescue of the development defect seen in mice lacking Schwann cell Phb2. This work develops our understanding of Schwann cell biology, revealing that Phb2 may directly or indirectly modulate the timely expression of transcription factors necessary for proper peripheral nervous system development, and proposing candidates that may play a role in PHB2-mediated integration of axon signals in the Schwann cell.
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Our understanding of wildlife multihost pathogen transmission systems is often incomplete due to the difficulty of observing contact between hosts. Understanding these interactions can be critical for preventing disease-induced wildlife declines. The proliferation of high-throughput sequencing technologies provides new opportunities to better explore these cryptic interactions. Parelaphostrongylus tenuis, a multihost parasite, is a leading cause of death in some moose (Alces alces) populations threatened by local extinction in the midwestern and northeastern US and southeastern Canada. Moose contract P. tenuis by consuming infected gastropod intermediate hosts, but little is known about which gastropod species moose consume. To gain more insight, we used a genetic metabarcoding approach on 258 georeferenced and temporally stratified moose fecal samples collected May-October 2017-20 from a declining population in the north-central US. We detected moose consumption of three species of gastropods across five positive samples. Two of these (Punctum minutissimum and Helisoma sp.) have been minimally investigated for the ability to host P. tenuis, while one (Zonitoides arboreus) is a well-documented host. Moose consumption of gastropods documented herein occurred in June and September. Our findings prove that moose consume gastropod species known to become infected by P. tenuis and demonstrate that fecal metabarcoding can provide novel insight on interactions between hosts of a multispecies pathogen transmission system. After determining and improving test sensitivity, these methods may also be extended to document important interactions in other multihost disease systems.
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Cervos , Metastrongyloidea , Animais , Código de Barras de DNA Taxonômico/veterinária , Animais Selvagens , DNA , Cervos/parasitologia , Fezes/parasitologiaRESUMO
Wolves (Canis lupus) can exert top-down pressure and shape ecological communities through the predation of ungulates and beavers (Castor spp.). Therefore, understanding wolf foraging is critical to estimating their ecosystem-level effects. Specifically, if wolves are consumers that optimize tradeoffs between the cost and benefits of prey acquisition, changes in these factors may lead to prey-switching or negative-density dependent selection with potential consequences for community stability. For wolves, factors affecting cost and benefits include prey vulnerability, risk, reward, and availability, which can vary temporally. We described the wolf diet by the frequency of occurrence and percent biomass and characterized the diet using prey remains found in wolf scats on Isle Royale National Park, Michigan, USA, during May-October 2019 and 2020. We used logistic regression to estimate prey consumption over time. We predicted prey with temporal variation in cost (availability and/or vulnerability) such as adult moose (Alces alces), calf moose, and beaver (Castor canadensis) to vary in wolf diets. We analyzed 206 scats and identified 62% of remains as beaver, 26% as moose, and 12% as other species (birds, smaller mammals, and wolves). Adult moose were more likely to occur in wolf scats in May when moose are in poor condition following winter. The occurrence of moose calves peaked during June-mid-July following birth but before calf vulnerability declined as they matured. By contrast, beaver occurrence in wolf scat did not change over time, reflecting the importance of low-handling cost prey items for recently introduced lone or paired wolves. Our results demonstrate that the wolf diet is responsive to temporal changes in prey costs. Temporal fluctuation in diet may influence wolves' ecological role if prey respond to increased predation risk by altering foraging or breeding behavior.
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Pregnancy determination is necessary for sound wildlife management and understanding population dynamics. Pregnancy rates are sensitive to environmental and physiological factors and may indicate the overall trajectory of a population. Pregnancy can be assessed through direct methods (rectal palpation, sonography) or indicated using hormonal assays (serum progesterone or pregnancy-specific protein B, fecal progestogen metabolites). A commonly used threshold of 2 ng/ml of progesterone in serum has been used by moose biologists to indicate pregnancy but has not been rigorously investigated. To refine this threshold, we examined the relationship between progesterone concentrations in serum samples and pregnancy in 87 moose (Alces alces; 64 female, 23 male) captured from 2010 to 2020 in the Grand Portage Indian Reservation in northeastern Minnesota, USA. Pregnancy was confirmed via rectal palpation (n = 25), necropsy (n = 2), calf observation (n = 25) or characteristic pre-calving behavior (n = 6), with a total of 58 females determined pregnant and 6 not pregnant; 23 males were included to increase the non-pregnant sample size. Using receiver operating characteristic analysis, we identified an optimal threshold of 1.115 ng/ml with a specificity of 0.97 (95% confidence interval [CI] = 0.90-1.00) and a sensitivity of 0.98 (95% CI = 0.95-1.00). Progesterone concentrations were significantly higher in cases of pregnant versus non-pregnant cows, but we did not detect a difference between single and twin births. We applied our newly refined threshold to calculate annual pregnancy rates for all female moose (n = 133) captured in Grand Portage from 2010 to 2021. Mean pregnancy rate during this period was 91% and ranged annually from 69.2 to 100%. Developing a reliable method for determining pregnancy status via serum progesterone analyses will allow wildlife managers to assess pregnancy rates of moose without devoting substantial time and resources to palpation and calf monitoring.
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Enhanced vegetation index (EVI) data can be used to identify and define the space in which ungulates practice parturition and encounter predation. This study explores the use of EVI data to identify landscapes linked to ungulate parturition and predation events across space, time, and environmental conditions. As a case study, we used the moose population (Alces alces) of northern Minnesota in the USA. Using remotely sensed EVI data rasters and global positioning system collar data, we quantified how vegetation phenology and moose movement shaped the births and predation of 52 moose calves from 2013 to 2020 on or adjacent to the Grand Portage Indian Reservation. The known sources of predation were American black bears (Ursus americanus, n = 22) and gray wolves (Canis lupus, n = 28). Satellite-derived data summarizing seasonal landscape features at the local level revealed that landscape heterogeneity use by moose can help to quantitatively identify landscapes of parturition and predation in space and time across large areas. Vegetation phenology proved to be differentiable between adult moose ranges, sites of cow parturition, and sites of calf predation. Landscape characteristics of each moose group were consistent and tractable based on environment, suggesting that sites of parturition and predation of moose are predictable in space and time. It is possible that moose selected specific landscapes for parturition despite risk of increased predation of their calves, which could be an example of an "ecological trap." This analytical framework can be employed to identify areas for future ungulate research on the impacts of landscape on parturition and predation dynamics.
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Given recent and abrupt declines in the abundance of moose (Alces alces) throughout parts of Minnesota and elsewhere in North America, accurately estimating statewide population trends and demographic parameters is a high priority for their continued management and conservation. Statistical population reconstruction using integrated population models provides a flexible framework for combining information from multiple studies to produce robust estimates of population abundance, recruitment, and survival. We used this framework to combine aerial survey data and survival data from telemetry studies to recreate trends and demographics of moose in northeastern Minnesota, USA, from 2005 to 2020. Statistical population reconstruction confirmed the sharp decline in abundance from an estimated 7,841 (90% CI = 6,702-8,933) in 2009 to 3,386 (90% CI = 2,681-4,243) animals in 2013, but also indicated that abundance has remained relatively stable since then, except for a slight decline to 3,163 (90% CI = 2,403-3,718) in 2020. Subsequent stochastic projection of the population from 2021 to 2030 suggests that this modest decline will continue for the next 10 years. Both annual adult survival and per-capita recruitment (number of calves that survived to 1 year per adult female alive during the previous year) decreased substantially in years 2005 and 2019, from 0.902 (SE = 0.043) to 0.689 (SE = 0.061) and from 0.386 (SE = 0.030) to 0.303 (SE = 0.051), respectively. Sensitivity analysis revealed that moose abundance was more sensitive to fluctuations in adult survival than recruitment; thus, we conclude that the steep decline in 2013 was driven primarily by decreasing adult survival. Our analysis demonstrates the potential utility of using statistical population reconstruction to monitor moose population trends and to identify population declines more quickly. Future studies should focus on providing better estimates of per-capita recruitment, using pregnancy rates and calf survival, which can then be incorporated into reconstruction models to help improve estimates of population change through time.
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Cervos , Animais , Feminino , Minnesota/epidemiologia , América do Norte , GravidezRESUMO
Moose (Alces alces americanus) populations in many areas along the southern extent of the North American moose range, including Minnesota, have experienced decline. Ascertaining neonate health and cause-specific mortality is critical where calf survival is low and understanding underlying causes of population dynamics is important. To investigate moose neonate health and causes of mortality, we studied 43 calves shortly after parturition during 2013-15 and 2018. The observed natural calf mortality rate was 84% by the following January of each calving season. Most natural calf mortalities were caused by black bear (Ursus americanus) or wolf (Canis lupus) predation or associated injuries (71%) but also included stillbirth (16%), orphaning (7%), generalized bacterial infection (3%), and hunter harvest (3%). Neonate health was evaluated in 27 calves by hematology, serum biochemistry profile, and maternally derived immunoglobulin. General health parameters were mostly within an expected range for normal health and adequate maternal immunoglobulin transfer. Importantly, these data contribute to a growing body of literature on moose neonate health and is the first report, to our knowledge, of maternally derived immunity in moose neonates.
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Distribuição Animal , Animais Recém-Nascidos , Cervos , Animais , Infecções Bacterianas/mortalidade , Infecções Bacterianas/veterinária , Feminino , Minnesota , Dinâmica Populacional , Comportamento Predatório , Gravidez , Natimorto , Ursidae , Lobos , Ferimentos e LesõesRESUMO
Echinococcus spp. are zoonotic cestode parasites with a worldwide distribution and a complex, two-host life cycle involving carnivore definitive hosts and small mammal or ungulate intermediate hosts. Surveillance for Echinococcus spp. in the Midwestern United States (USA) is rare. Using a mixed-methods approach, we examined Echinococcus infection risks in wildlife and domestic dogs in four Minnesota Tribal Nations. We hypothesized that the spillover of Echinococcus spp. into domestic dogs would vary with the presence or absence of suspected wildlife host species and certain behaviors associated with domestic dog ownership, like feeding wildlife host carcasses or frequency of veterinary care. Among 83 dogs tested, three (3.6%) were positive for Echinococcus spp. Despite low prevalence, pet owner survey and focus group findings indicated that dogs encounter peri-domestic wildlife most often when they roam freely or consume wildlife carcasses. This study demonstrates a need for further research into spillover potential of endemic zoonotic Echinococcus spp. in the Midwest USA.
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Equinococose , Echinococcus , Animais , Animais Selvagens/parasitologia , Cães , Equinococose/epidemiologia , Equinococose/veterinária , Mamíferos , Minnesota/epidemiologia , PrevalênciaRESUMO
Predators can modulate disease transmission within prey populations by influencing prey demography and behavior. Predator-prey dynamics can involve multiple species in heterogeneous landscapes; however, studies of predation on disease transmission rarely consider the role of landscapes or the transmission among diverse prey species (i.e., spillover). We used high-resolution habitat and movement data to model spillover risk of the brainworm parasite (Parelaphostrongylus tenuis) between two prey species [white-tailed deer (Odocoileus virginianus) and moose (Alces alces)], accounting for predator [gray wolf (Canis lupus)] presence and landscape configuration. Results revealed that spring migratory movements of cervid hosts increased parasite spillover risk from deer to moose, an effect tempered by changes in elevation, land cover, and wolf presence. Wolves induced host-species segregation, a nonlethal mechanism that modulated disease emergence by reducing spatiotemporal overlap between infected and susceptible prey, showing that wildlife disease dynamics may change with landscape disturbance and the loss of large carnivores.
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Contaminants of emerging concern (CECs) include a variety of pharmaceuticals, personal care products, and hormones commonly detected in surface waters. Human activities, such as wastewater treatment and discharge, contribute to the distribution of CECs in water, but other sources and pathways are less frequently examined. This study aimed to identify anthropogenic activities and environmental characteristics associated with the presence of CECs, previously determined to be of high priority for further research and mitigation, in rural inland lakes in northeastern Minnesota, United States. The setting for this study consisted of 21 lakes located within both the Grand Portage Indian Reservation and the 1854 Ceded Territory, where subsistence hunting and fishing are important to the cultural heritage of the indigenous community. We used data pertaining to numbers of buildings, healthcare facilities, wastewater treatment plants, impervious surfaces, and wetlands within defined areas surrounding the lakes as potential predictors of the detection of high priority CECs in water, sediment, and fish. Separate models were run for each contaminant detected in each sample media. We used least absolute shrinkage and selection operator (LASSO) models to account for both predictor selection and parameter estimation for CEC detection. Across contaminants and sample media, the percentage of impervious surface was consistently positively associated with CEC detection. Number of buildings in the surrounding area was often negatively associated with CEC detection, though nonsignificant. Surrounding population, presence of wastewater treatment facilities, and percentage of wetlands in surrounding areas were positively, but inconsistently, associated with CECs, while catchment area and healthcare centers were generally not associated. The results of this study highlight human activities and environmental characteristics associated with CEC presence in a rural area, informing future work regarding specific sources and transport pathways. We also demonstrate the utility of LASSO modeling in the identification of these important relationships.
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Lagos , Poluentes Químicos da Água , Animais , Monitoramento Ambiental , Humanos , Minnesota , Águas Residuárias , Poluentes Químicos da Água/análiseRESUMO
Contaminants of emerging concern (CECs), such as pharmaceuticals, personal care products, and hormones, are frequently found in aquatic ecosystems around the world. Information on sublethal effects from exposure to commonly detected concentrations of CECs is lacking and the limited availability of toxicity data makes it difficult to interpret the biological significance of occurrence data. However, the ability to evaluate the effects of CECs on aquatic ecosystems is growing in importance, as detection frequency increases. The goal of this study was to prioritize the chemical hazards of 117 CECs detected in subsistence species and freshwater ecosystems on the Grand Portage Indian Reservation and adjacent 1854 Ceded Territory in Minnesota, USA. To prioritize CECs for management actions, we adapted Minnesota Pollution Control Agency's Aquatic Toxicity Profiles framework, a tool for the rapid assessment of contaminants to cause adverse effects on aquatic life by incorporating chemical-specific information. This study aimed to 1) perform a rapid-screening assessment and prioritization of detected CECs based on their potential environmental hazard; 2) identify waterbodies in the study region that contain high priority CECs; and 3) inform future monitoring, assessment, and potential remediation in the study region. In water samples alone, 50 CECs were deemed high priority. Twenty-one CECs were high priority among sediment samples and seven CECs were high priority in fish samples. Azithromycin, DEET, diphenhydramine, fluoxetine, miconazole, and verapamil were high priority in all three media. Due to the presence of high priority CECs throughout the study region, we recommend future monitoring of particular CECs based on the prioritization method used here. We present an application of a chemical hazard prioritization process and identify areas where the framework may be adapted to meet the objectives of other management-related assessments.
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Ecossistema , Poluentes Químicos da Água , Animais , Monitoramento Ambiental , Água Doce , Minnesota , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
Rett syndrome (RTT) is a severe, progressive X-linked neurodevelopmental disorder caused by mutations in the transcriptional regulator MECP2 We previously identified aberrant NF-κB pathway upregulation in brains of Mecp2-null mice and demonstrated that genetically attenuating NF-κB rescues some characteristic neuronal RTT phenotypes. These results raised the intriguing question of whether NF-κB pathway inhibitors might provide a therapeutic avenue in RTT. Here, we investigate whether the known NF-κB pathway inhibitor vitamin D ameliorates neuronal phenotypes in Mecp2-mutant mice. Vitamin D deficiency is prevalent among RTT patients, and we find that Mecp2-null mice similarly have significantly reduced 25(OH)D serum levels compared with wild-type littermates. We identify that vitamin D rescues aberrant NF-κB pathway activation and reduced neurite outgrowth of Mecp2 knock-down cortical neurons in vitro Further, dietary supplementation with vitamin D in early symptomatic male Mecp2 hemizygous null and female Mecp2 heterozygous mice ameliorates reduced neocortical dendritic morphology and soma size phenotypes and modestly improves reduced lifespan of Mecp2-nulls. These results elucidate fundamental neurobiology of RTT and provide foundation that NF-κB pathway inhibition might be a therapeutic target for RTT.
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Síndrome de Rett , Animais , Suplementos Nutricionais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Proteína 2 de Ligação a Metil-CpG/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B , Fenótipo , Síndrome de Rett/tratamento farmacológico , Síndrome de Rett/genética , Vitamina DRESUMO
Pharmaceuticals, personal care products, hormones, and other chemicals lacking water quality standards are frequently found in surface water. While evidence is growing that these contaminants of emerging concern (CECs) - those previously unknown, unrecognized, or unregulated - can affect the behavior and reproduction of fish and wildlife, little is known about the distribution of these chemicals in rural, tribal areas. Therefore, we surveyed the presence of CECs in water, sediment, and subsistence fish species across various waterbodies, categorized as undeveloped (i.e., no human development along shorelines), developed (i.e., human development along shorelines), and wastewater effluent-impacted (i.e., contain effluence from wastewater treatment plants), within the Grand Portage Indian Reservation and 1854 Ceded Territory in northeastern Minnesota, U.S.A. Overall, in 28 sites across three years (2016-2018), 117 of the 158 compounds tested were detected in at least one form of medium (i.e., water, sediment, or fish). CECs were detected most frequently at wastewater effluent-impacted sites, with up to 83 chemicals detected in one such lake, while as many as 17 were detected in an undeveloped lake. Although there was no statistically significant difference between the number of CECs present in developed versus undeveloped lakes, a range of 3-17 CECs were detected across these locations. Twenty-two CECs were detected in developed and undeveloped sites that were not detected in wastewater effluent-impacted sites. The detection of CECs in remote, undeveloped locations, where subsistence fish are harvested, raises scientific questions about the safety and security of subsistence foods for indigenous communities. Further investigation is warranted so that science-based solutions to reduce chemical risks to aquatic life and people can be developed locally and be informative for indigenous communities elsewhere.