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1.
Heliyon ; 8(1): e08774, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35106388

ABSTRACT

Digital camera monitoring has revolutionised survey designs in many fields, as an important source of information. The extended sampling coverage offered by this monitoring scheme makes it preferable compared to other traditional methods of survey. However, data obtained from digital camera monitoring are often highly variable, and characterized by sparse periods of zero counts, interspersed with missing observations due to outages. In practice, missing data of relatively shorter duration are mostly observed and are often imputed using interpolation techniques, ignoring long-term trends leading to inherent estimation biases. In this study, we investigated time series forecasting methods that adequately handle intermittency and produced plausible estimates for imputation and forecasting purposes. The study utilised a yearlong digital camera monitoring data set of hourly counts of powerboat launches at three boat ramps in Western Australia. Several time series forecasting methods were evaluated and the accuracies of their point estimates of forecasts for various lead times in hours of up to one week were assessed using cross-validation techniques. Intermittent demand forecasting techniques, including Croston's method and Syntetos-Boylan Approximation (SBA) models, and count data forecasting methods including autoregressive conditional Poisson (ACP) models, integer-valued moving average (INMA) models, and integer-valued autoregressive (INAR) models were evaluated. ACP and INAR models performed better than intermittent demand forecasting techniques for short forecast horizons and provided some evidence of their sufficiency in predicting the dynamics in recreational boating activities. This result established that, in as much as intermittency may be a key feature for a given dataset, it should not override the systemic characteristics of data in the application of forecasting techniques. Our results provide plausible estimates for short-term missing data and forecasts for monitoring events, with applications in supporting proper tracking of usage of facilities, guiding resource allocations and providing insightful perspectives for management decisions.

2.
Sci Adv ; 5(9): eaaw5978, 2019 09.
Article in English | MEDLINE | ID: mdl-31555728

ABSTRACT

The ability to convert between molecular spin states is of utmost importance in materials chemistry. Förster-type energy transfer is based on dipole-dipole interactions and can therefore theoretically be used to convert between molecular spin states. Here, a molecular dyad that is capable of transferring energy from an excited triplet state to an excited singlet state is presented. The rate of conversion between these states was shown to be 36 times faster than the rate of emission from the isolated triplet state. This dyad provides the first solid proof that Förster-type triplet-to-singlet energy transfer is possible, revealing a method to increase the rate of light extraction from excited triplet states.

3.
Adv Dent Res ; 29(2): 144-156, 2018 03.
Article in English | MEDLINE | ID: mdl-29461108

ABSTRACT

Policy on fluoride intake involves balancing caries against dental fluorosis in populations. The origin of this balance lies with Dean's research on fluoride concentration in water supplies, caries, and fluorosis. Dean identified cut points in the Index of Dental Fluorosis of 0.4 and 0.6 as critical. These equate to 1.3 and 1.6 mg fluoride (F)/L. However, 1.0 mg F/L, initially called a permissible level, was adopted for fluoridation programs. McClure, in 1943, derived an "optimum" fluoride intake based on this permissible concentration. It was not until 1944 that Dean referred to this concentration as the "optimal" concentration. These were critical steps that have informed health authorities through to today. Several countries have derived toxicological estimates of an adequate and an upper level of intake of fluoride as an important nutrient. The US Institute of Medicine (IOM) in 1997 estimated an Adequate Intake (AI) of 0.05 mg F/kg bodyweight (bw)/d and a Tolerable Upper Intake Level (UL) of 0.10 mg F/kg bw/d. These have been widely promulgated. However, a conundrum has existed with estimates of actual fluoride intake that exceed the UL without the expected adverse fluorosis effects being observed. Both the AI and UL need review. Fluoride intake at an individual level should be interpreted to inform more nuanced guidelines for individual behavior. An "optimum" intake should be based on community perceptions of caries and fluorosis, while the ultimate test for fluoride intake is monitoring caries and fluorosis in populations.


Subject(s)
Dental Caries/prevention & control , Drinking Water/standards , Fluoridation/standards , Fluorides/administration & dosage , Drinking Water/chemistry , Fluorosis, Dental/etiology , Fluorosis, Dental/prevention & control , Humans , Public Policy
4.
Microb Ecol ; 76(2): 530-543, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29285550

ABSTRACT

Group-living can promote the evolution of adaptive strategies to prevent and control disease. Fungus-gardening ants must cope with two sets of pathogens, those that afflict the ants themselves and those of their symbiotic fungal gardens. While much research has demonstrated the impact of specialized fungal pathogens that infect ant fungus gardens, most of these studies focused on the so-called higher attine ants, which are thought to coevolve diffusely with two clades of leucocoprinaceous fungi. Relatively few studies have addressed disease ecology of lower Attini, which are thought to occasionally recruit (domesticate) novel leucocoprinaceous fungi from free-living populations; coevolution between lower-attine ants and their fungi is therefore likely weaker (or even absent) than in the higher Attini, which generally have many derived modifications. Toward understanding the disease ecology of lower-attine ants, this study (a) describes the diversity in the microfungal genus Escovopsis that naturally infect fungus gardens of the lower-attine ant Mycocepurus smithii and (b) experimentally determines the relative contributions of Escovopsis strain (a possible garden disease), M. smithii ant genotype, and fungal cultivar lineage to disease susceptibility and colony fitness. In controlled in-vivo infection laboratory experiments, we demonstrate that the susceptibility to Escovopsis infection was an outcome of ant-cultivar-Escovopsis interaction, rather than solely due to ant genotype or fungal cultivar lineage. The role of complex ant-cultivar-Escovopsis interactions suggests that switching M. smithii farmers onto novel fungus types might be a strategy to generate novel ant-fungus combinations resistant to most, but perhaps not all, Escovopsis strains circulating in a local population of this and other lower-attine ants.


Subject(s)
Ants/microbiology , Biological Coevolution , Fungi/pathogenicity , Gardening , Host-Pathogen Interactions/physiology , Symbiosis , Animal Diseases/microbiology , Animals , Disease Resistance/physiology , Ecology , Fungi/classification , Fungi/genetics , Fungi/isolation & purification , Genotype , Hypocreales/classification , Hypocreales/genetics , Hypocreales/isolation & purification , Hypocreales/pathogenicity
5.
Trends Microbiol ; 23(10): 606-617, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26422463

ABSTRACT

Animal and plant microbiomes encompass diverse microbial communities that colonize every accessible host tissue. These microbiomes enhance host functions, contributing to host health and fitness. A novel approach to improve animal and plant fitness is to artificially select upon microbiomes, thus engineering evolved microbiomes with specific effects on host fitness. We call this engineering approach host-mediated microbiome selection, because this method selects upon microbial communities indirectly through the host and leverages host traits that evolved to influence microbiomes. In essence, host phenotypes are used as probes to gauge and manipulate those microbiome functions that impact host fitness. To facilitate research on host-mediated microbiome engineering, we explain and compare the principal methods to impose artificial selection on microbiomes; discuss advantages and potential challenges of each method; offer a skeptical appraisal of each method in light of these potential challenges; and outline experimental strategies to optimize microbiome engineering. Finally, we develop a predictive framework for microbiome engineering that organizes research around principles of artificial selection, quantitative genetics, and microbial community-ecology.


Subject(s)
Microbiota/physiology , Plants/microbiology , Animals , Microbiota/genetics , Soil Microbiology
6.
J Exp Biol ; 217(Pt 14): 2540-7, 2014 Jul 15.
Article in English | MEDLINE | ID: mdl-24803469

ABSTRACT

Fungus-gardening insects are among the most complex organisms because of their extensive co-evolutionary histories with obligate fungal symbionts and other microbes. Some fungus-gardening insect lineages share fungal symbionts with other members of their lineage and thus exhibit diffuse co-evolutionary relationships, while others exhibit little or no symbiont sharing, resulting in host-fungus fidelity. The mechanisms that maintain this symbiont fidelity are currently unknown. Prior work suggested that derived leaf-cutting ants in the genus Atta interact synergistically with leaf-cutter fungi (Attamyces) by exhibiting higher fungal growth rates and enzymatic activities than when growing a fungus from the sister-clade to Attamyces (so-called 'Trachymyces'), grown primarily by the non-leaf cutting Trachymyrmex ants that form, correspondingly, the sister-clade to leaf-cutting ants. To elucidate the enzymatic bases of host-fungus specialization in leaf-cutting ants, we conducted a reciprocal fungus-switch experiment between the ant Atta texana and the ant Trachymyrmex arizonensis and report measured enzymatic activities of switched and sham-switched fungus gardens to digest starch, pectin, xylan, cellulose and casein. Gardens exhibited higher amylase and pectinase activities when A. texana ants cultivated Attamyces compared with Trachymyces fungi, consistent with enzymatic specialization. In contrast, gardens showed comparable amylase and pectinase activities when T. arizonensis cultivated either fungal species. Although gardens of leaf-cutting ants are not known to be significant metabolizers of cellulose, T. arizonensis were able to maintain gardens with significant cellulase activity when growing either fungal species. In contrast to carbohydrate metabolism, protease activity was significantly higher in Attamyces than in Trachymyces, regardless of the ant host. Activity of some enzymes employed by this symbiosis therefore arises from complex interactions between the ant host and the fungal symbiont.


Subject(s)
Ants/enzymology , Fungi/enzymology , Symbiosis/physiology , Amylases/metabolism , Animals , Biological Evolution , Cellulases/metabolism , Fungi/metabolism , Plant Leaves , Polygalacturonase/metabolism , Species Specificity
8.
J Evol Biol ; 26(6): 1353-62, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23639137

ABSTRACT

Partner fidelity through vertical symbiont transmission is thought to be the primary mechanism stabilizing cooperation in the mutualism between fungus-farming (attine) ants and their cultivated fungal symbionts. An alternate or additional mechanism could be adaptive partner or symbiont choice mediating horizontal cultivar transmission or de novo domestication of free-living fungi. Using microsatellite genotyping for the attine ant Mycocepurus smithii and ITS rDNA sequencing for fungal cultivars, we provide the first detailed population genetic analysis of local ant-fungus associations to test for the relative importance of vertical vs. horizontal transmission in a single attine species. M. smithii is the only known asexual attine ant, and it is furthermore exceptional because it cultivates a far greater cultivar diversity than any other attine ant. Cultivar switching could permit the ants to re-acquire cultivars after garden loss, to purge inferior cultivars that are locally mal-adapted or that accumulated deleterious mutations under long-term asexuality. Compared to other attine ants, symbiont choice and local adaptation of ant-fungus combinations may play a more important role than partner-fidelity feedback in the co-evolutionary process of M. smithii and its fungal symbionts.


Subject(s)
Ants/physiology , Biological Evolution , Fungi/physiology , Animals , Ants/genetics , Ants/microbiology , DNA/isolation & purification , Molecular Sequence Data , Symbiosis
9.
Article in English | MEDLINE | ID: mdl-23695564

ABSTRACT

The electron and proton transport mediated by protein-bound cofactors in photosynthesis have been investigated by various methods in order to determine the energetics, the dynamics and the pathway of this process. In purple bacteria, primary photosynthetic charge separation and the build-up of a proton gradient across the periplasmic membrane are catalyzed by the photosynthetic reaction centre (RC). Here, the purification, crystallization and preliminary X-ray analysis of wild-type and L(M196)H-mutant RCs of Rhodobacter sphaeroides are presented, enabling study of the influence of the protein environment of the primary electron donor on the spectral properties and photochemical activity of the RC.


Subject(s)
Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Gene Expression Regulation, Bacterial , Mutation/genetics , Photosynthetic Reaction Center Complex Proteins/chemistry , Photosynthetic Reaction Center Complex Proteins/genetics , Rhodobacter sphaeroides , Bacterial Proteins/isolation & purification , Crystallization , Crystallography, X-Ray , Photosynthetic Reaction Center Complex Proteins/isolation & purification , Rhodobacter sphaeroides/genetics
11.
Int J Adolesc Med Health ; 4(1): 29-34, 2011 May 18.
Article in English | MEDLINE | ID: mdl-22912081
12.
Article in English | MEDLINE | ID: mdl-22312942

ABSTRACT

Despite promising reports of the use of omalizumab as add-on therapy in patients with systemic mastocytosis and recurrent anaphylaxis during specific venom immunotherapy (VIT), unpredicted adverse effects may lead to therapy failure. We present the case of a patient with systemic mastocytosis and Hymenoptera venom allergy who was administered omalizumab as add-on therapy to improve VIT tolerability after repeated severe adverse reactions despite H1/H2-antihistamine prophylaxis. We describe an unexpected discontinuation of omalizumab following successful initiation of VIT in a patient with systemic mastocytosis, with subsequent lack of tolerability of VIT. An interesting aspect of this case is the correlation of basophil activation test results with both clinical tolerability and VIT intolerance.


Subject(s)
Anti-Allergic Agents/adverse effects , Antibodies, Anti-Idiotypic/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Mastocytosis, Systemic/therapy , Animals , Arthropod Venoms/immunology , Desensitization, Immunologic , Humans , Hymenoptera/immunology , Male , Middle Aged , Omalizumab
13.
Int Orthop ; 33(2): 301-13, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19130056

ABSTRACT

Low back pain (LBP) is currently the most prevalent and costly musculoskeletal problem in modern societies. Screening instruments for the identification of prognostic factors in LBP may help to identify patients with an unfavourable outcome. In this systematic review screening instruments published between 1970 and 2007 were identified by a literature search. Nine different instruments were analysed and their different items grouped into ten structures. Finally, the predictive effectiveness of these structures was examined for the dependent variables including "work status", "functional limitation", and "pain". The strongest predictors for "work status" were psychosocial and occupational structures, whereas for "functional limitation" and "pain" psychological structures were dominating. Psychological and occupational factors show a high reliability for the prognosis of patients with LBP. Screening instruments for the identification of prognostic factors in patients with LBP should include these factors as a minimum core set.


Subject(s)
Disability Evaluation , Low Back Pain/diagnosis , Low Back Pain/psychology , Surveys and Questionnaires , Work Capacity Evaluation , Acute Disease , Chronic Disease , Disease Progression , Female , Humans , Low Back Pain/epidemiology , Male , Mass Screening/methods , Pain Measurement , Predictive Value of Tests , Prognosis , Psychology , Risk Factors , Sensitivity and Specificity , Severity of Illness Index , Sick Leave/statistics & numerical data , Sickness Impact Profile
14.
Microb Ecol ; 56(4): 604-14, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18369523

ABSTRACT

Leafcutter ants (Formicidae: tribe Attini) are well-known insects that cultivate basidiomycete fungi (Agaricales: Lepiotaceae) as their principal food. Fungus gardens are monocultures of a single cultivar strain, but they also harbor a diverse assemblage of additional microbes with largely unknown roles in the symbiosis. Cultivar-attacking microfungi in the genus Escovopsis are specialized parasites found only in association with attine gardens. Evolutionary theory predicts that the low genetic diversity in monocultures should render ant gardens susceptible to a wide range of diseases, and additional parasites with roles similar to that of Escovopsis are expected to exist. We profiled the diversity of cultivable microfungi found in 37 nests from ten Acromyrmex species from Southern Brazil and compared this diversity to published surveys. Our study revealed a total of 85 microfungal strains. Fusarium oxysporum and Escovopsis were the predominant species in the surveyed gardens, infecting 40.5% and 27% of the nests, respectively. No specific relationship existed regarding microfungal species and ant-host species, ant substrate preference (dicot versus grass) or nesting habit. Molecular data indicated high genetic diversity among Escovopsis isolates. In contrast to the garden parasite, F. oxysporum strains are not specific parasites of the cultivated fungus because strains isolated from attine gardens have similar counterparts found in the environment. Overall, the survey indicates that saprophytic microfungi are prevalent in South American leafcutter ants. We discuss the antagonistic potential of these microorganisms as "weeds" in the ant-fungus symbiosis.


Subject(s)
Agaricales/growth & development , Ants/microbiology , Symbiosis , Agaricales/classification , Agaricales/genetics , Animals , Genetic Variation , Molecular Sequence Data , Phylogeny
15.
Insect Mol Biol ; 16(6): 777-84, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18093006

ABSTRACT

Nuclear mitochondrial-like sequences (numts) are copies of mitochondrial DNA that have migrated to the genomic DNA. We present the first characterization of numts in ants, these numts being homologues to a mitochondrial DNA fragment containing loci the 3' portion of the cytochrome oxidase I gene, an intergenic spacer, the tRNA leucine gene and the 5' portion of the cytochrome oxidase II gene. All 67 specimens of Atta cephalotes (Hymenoptera: Formicidae: Attini) investigated had these homologues, which are within two monophyletic groups that we called numt1 and numt2. Numt1 and numt2 sequences are less variable than mitochondrial sequences and released from the severe purifying selection constraining the evolution of mitochondrial genes. Their formation probably involved bottlenecks related to two distinct transfer events of ancient and fast evolving mitochondrial DNA fragments to comparative slowly evolving nuclear DNA regions.


Subject(s)
Ants/genetics , DNA, Mitochondrial/genetics , Amino Acid Sequence , Animals , Ants/enzymology , Base Sequence , Cell Nucleus/genetics , DNA/genetics , DNA Primers/genetics , Electron Transport Complex IV/genetics , Genes, Insect , Molecular Sequence Data , Phylogeny , Sequence Homology, Amino Acid
16.
Caries Res ; 41(2): 141-5, 2007.
Article in English | MEDLINE | ID: mdl-17284916

ABSTRACT

Our aim was to investigate the effect of TiF4 solutions on mineral loss on enamel and dentine in vitro. Samples were fluoridated 1 x 5 min per day with 1.64% w/v TiF4 or 2.2% w/v NaF solutions, each with a pH of 1.2, and then subjected to a cyclic de- and remineralization procedure for 5 days. Demineralization was performed for 6 x 10 min per day with citric acid (pH 2.3). In controls no fluoridation was performed. Mineral content was determined by longitudinal microradiography. Enamel mineral loss was markedly reduced by both fluoride solutions, but TiF4 was significantly more effective than NaF: cumulative mineral loss on day 3 was 61.7 +/- 15.0 microm in the NaF and 34.2 +/- 13.1 microm in the TiF4 group (p < or = 0.001) compared with 121.0 +/- 27.0 microm in the control group. Dentine mineral loss ceased after both TiF4 and NaF applications (cumulative mineral loss on day 5 in controls: 61.0 +/- 17.0 microm, in the TiF4 group: 15.4 +/- 13.4 microm and in the NaF group: 21.8 +/- 11.8 microm). Both TiF4 and NaF application reduced mineral loss both on enamel and dentine, which could open new possibilities for a symptomatic therapy of erosions.


Subject(s)
Cariostatic Agents/therapeutic use , Fluorides/therapeutic use , Sodium Fluoride/therapeutic use , Titanium/therapeutic use , Tooth Erosion/drug therapy , Tooth Remineralization/methods , Dental Enamel/pathology , Dentin/pathology , Humans , Hydrogen-Ion Concentration , Linear Models , Statistics, Nonparametric
17.
Mol Ecol ; 16(1): 209-16, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17181732

ABSTRACT

Switching of symbiotic partners pervades most mutualisms, despite mechanisms that appear to enforce partner fidelity. To investigate the interplay of forces binding and dissolving mutualistic pairings, we investigated partner fidelity at the population level in the attine ant-fungal cultivar mutualism. The ants and their cultivars exhibit both broad-scale co-evolution, as well as cultivar switching, with short-term symbiont fidelity maintained by vertical transmission of maternal garden inoculates via dispersing queens and by the elimination of alien cultivar strains. Using microsatellite markers, we genotyped cultivar fungi associated with five co-occurring Panamanian attine ant species, representing the two most derived genera, leaf-cutters Atta and Acromyrmex. Despite the presence of mechanisms apparently ensuring the cotransmission of symbiont genotypes, different species and genera of ants sometimes shared identical fungus garden genotypes, indicating widespread cultivar exchange. The cultivar population was largely unstructured with respect to host ant species, with only 10% of the structure in genetic variance being attributable to partitioning among ant species and genera. Furthermore, despite significant genetic and ecological dissimilarity between Atta and Acromyrmex, generic difference accounted for little, if any, variance in cultivar population structure, suggesting that cultivar exchange dwarfs selective forces that may act to create co-adaptive ant-cultivar combinations. Thus, binding forces that appear to enforce host fidelity are relatively weak and pairwise associations between cultivar lineages and ant species have little opportunity for evolutionary persistence. This implicates that mechanisms other than partner fidelity feedback play important roles in stabilizing the leafcutter ant-fungus mutualism over evolutionary time.


Subject(s)
Ants/microbiology , Biological Evolution , Fungi/genetics , Symbiosis , Animals , Ants/genetics , Fungi/physiology , Genetic Variation , Genotype , Microsatellite Repeats , Phylogeny
18.
Curr Biol ; 16(4): R129-31, 2006 Feb 21.
Article in English | MEDLINE | ID: mdl-16488863

ABSTRACT

A recent analysis of decades of US customs intercepts has revealed which ants had an opportunity to become established in the United States, providing insights into the requisite traits that enable an ant species to become a successful invader.


Subject(s)
Ants , Animals , Commerce , Ecology
19.
Article in English | MEDLINE | ID: mdl-16329649

ABSTRACT

The interleukin (IL)-12 family is composed of three heterodimeric cytokines, IL-12 (p40p35), IL-23 (p40p19), and IL-27 (EBI3p28), and of monomeric and homodimeric p40. This review focuses on the three heterodimeric members of the IL-12 family. The p40 and p40-like (EBI3) subunits have homology to the IL-6R, the other subunits (p35, p19, and p28) are homologous to each other and to members of the IL-6 superfamily. On the basis of their structural similarity, it was expected that the members of the IL-12 family have overlapping pro-inflammatory and immunoregulatory functions. However, it was surprising that they also show very distinct activities. IL- 12 has a central role as a Th1-inducing and -maintaining cytokine, which is essential in cell-mediated immunity in nonviral infections and in tumor control. IL-23 recently emerged as an end-stage effector cytokine responsible for autoimmune chronic inflammation through induction of IL-17 and direct activation of macrophages. Very recently, IL-27 was found to exert not only a pro-inflammatory Thl-enhancing but also a significant anti-inflammatory function.


Subject(s)
Immune System/physiology , Inflammation/immunology , Interleukin-12/metabolism , Animals , Antineoplastic Agents/metabolism , Autoimmune Diseases/immunology , Autoimmunity/physiology , Interleukin-12/chemistry , Interleukin-12/genetics , Multigene Family , Organ Specificity , Receptors, Interleukin/metabolism , Receptors, Interleukin-12 , Signal Transduction/physiology
20.
Science ; 308(5730): 1920-3, 2005 Jun 24.
Article in English | MEDLINE | ID: mdl-15976301

ABSTRACT

The formation of the neuromuscular junction (NMJ) is directed by reciprocal interactions between motor neurons and muscle fibers. Neuregulin (NRG) and Agrin from motor nerve terminals are both implicated. Here, we demonstrate that NMJs can form in the absence of the NRG receptors ErbB2 and ErbB4 in mouse muscle. Postsynaptic differentiation is, however, induced by Agrin. We therefore conclude that NRG signaling to muscle is not required for NMJ formation. The effects of NRG signaling to muscle may be mediated indirectly through Schwann cells.


Subject(s)
ErbB Receptors/physiology , Muscle, Skeletal/innervation , Neuregulins/metabolism , Neuromuscular Junction/physiology , Receptor, ErbB-2/physiology , Signal Transduction , Agrin/physiology , Animals , Animals, Newborn , Cells, Cultured , ErbB Receptors/genetics , Genes, erbB , Genes, erbB-2 , Membrane Potentials , Mice , Motor Endplate/metabolism , Motor Endplate/physiology , Motor Endplate/ultrastructure , Muscle, Skeletal/ultrastructure , Mutation , Neuromuscular Junction/embryology , Neuromuscular Junction/metabolism , Neuromuscular Junction/ultrastructure , Presynaptic Terminals/physiology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, ErbB-2/genetics , Receptor, ErbB-4 , Receptors, Cholinergic/chemistry , Receptors, Cholinergic/genetics , Receptors, Cholinergic/metabolism , Recombination, Genetic , Schwann Cells/physiology , Synaptic Transmission
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